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1. Dhingra S, Li W, Tan D, Zenali M, Zhang H, Brown RE: Cell cycle biology of fibrolamellar hepatocellular carcinoma. Int J Clin Exp Pathol; 2010;3(8):792-7
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  • [Title] Cell cycle biology of fibrolamellar hepatocellular carcinoma.
  • CONTEXT: fibrolamellar hepatocellular carcinoma (FLHCC) has a better prognosis than conventional hepatocellular carcinoma.
  • Nevertheless, FLHCC has a propensity to recur with limited responsiveness to chemotherapy.
  • OBJECTIVE: The purpose of this study was to provide insight into the cell cycle biology of FLHCC, as it relates to FLHCC's relatively indolent nature and lack of chemoresponsiveness.
  • DESIGN: in seven cases of FLHCC, we assessed: 1. immunoexpression of protein analytes indicating cell cycle progression including Ki-67 (G1, S, G2 and M phases) and S-phase kinase-associated protein (Skp) 2 along with the mitotic index (MI); 2.immunoreactivity for cyclin-dependent kinase inhibitors of cell cycle progression from G1 to S phase, p27Kip1 and p16INK4.
  • CONCLUSION: our analysis has revealed that cell cycle arrest in FLHCC occurs in G0G1 phase and is associated with overexpression of the cell cycle regulator, p16INK4 in tumoral cell nuclei compared with non-neoplastic hepatocytes.
  • In conjunction with our previous immunohistochemical demonstration of a constitutively activated nuclear factor (NF)-kappaB pathway and stemness characteristics of FLHCC with limited differentiation, this cell cycle arrest elucidates the biology of FLHCC's indolent nature and relative chemoresistance.
  • [MeSH-major] Carcinoma, Hepatocellular / metabolism. Cell Cycle Proteins / metabolism. Liver Neoplasms / metabolism
  • [MeSH-minor] Adult. Aged, 80 and over. Biomarkers, Tumor / metabolism. Cell Nucleus / metabolism. Cell Nucleus / pathology. Cell Proliferation. Cyclin-Dependent Kinase Inhibitor p16 / metabolism. Female. Humans. Ki-67 Antigen / metabolism. Male. Mitotic Index. Prognosis. Young Adult

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  • (PMID = 21151393.001).
  • [ISSN] 1936-2625
  • [Journal-full-title] International journal of clinical and experimental pathology
  • [ISO-abbreviation] Int J Clin Exp Pathol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Cell Cycle Proteins; 0 / Cyclin-Dependent Kinase Inhibitor p16; 0 / Ki-67 Antigen
  • [Other-IDs] NLM/ PMC2993230
  • [Keywords] NOTNLM ; Cell cycle / chemoresistance / fibrolamellar hepatocellular carcinoma / immunohistochemistry / liver / p16INK4
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2. Katzenstein HM, Krailo MD, Malogolowkin MH, Ortega JA, Qu W, Douglass EC, Feusner JH, Reynolds M, Quinn JJ, Newman K, Finegold MJ, Haas JE, Sensel MG, Castleberry RP, Bowman LC: Fibrolamellar hepatocellular carcinoma in children and adolescents. Cancer; 2003 Apr 15;97(8):2006-12
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  • [Title] Fibrolamellar hepatocellular carcinoma in children and adolescents.
  • BACKGROUND: Children with hepatocellular carcinoma (HCC) were treated on a prospective, randomized trial and were then analyzed to determine whether children with the fibrolamellar (FL) histologic variant of HCC have a more favorable presentation, increased surgical resectability, greater response to therapy, and improved outcome compared with children who have typical HCC.
  • After undergoing initial surgery or biopsy, children with Stage I HCC (n = 8 patients), Stage III HCC (n = 25 patients), and Stage IV HCC (n = 13 patients) were assigned randomly, regardless of histology, to receive treatment either with cisplatin, vincristine, and fluorouracil (n = 20 patients) or with cisplatin and continuous-infusion doxorubicin (n = 26 patients).
  • RESULTS: Ten of 46 patients (22%) had the fibrolamellar variant of HCC (FL-HCC).
  • There was no difference in the number of patients with advanced-stage disease, the incidence of surgical resectability at diagnosis, or the response to treatment between patients with FL-HCC and patients with typical HCC.
  • CONCLUSIONS: Children with FL-HCC do not have a favorable prognosis and do not respond any differently to current therapeutic regimens than patients with typical HCC.
  • The use of novel chemotherapeutic agents and the incorporation of other treatment modalities are indicated to improve the dismal survival of pediatric patients with all histologic variants of advanced-stage HCC.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Hepatocellular / drug therapy. Carcinoma, Hepatocellular / surgery. Liver Neoplasms / drug therapy. Liver Neoplasms / surgery
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Cisplatin / administration & dosage. Cohort Studies. Disease-Free Survival. Doxorubicin / administration & dosage. Female. Fluorouracil / administration & dosage. Hepatoblastoma. Humans. Infant. Infusions, Intravenous. Male. Neoplasm Staging. Prognosis. Prospective Studies. Risk Factors. Time Factors. Treatment Outcome. Vincristine / administration & dosage. alpha-Fetoproteins / analysis

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  • [Copyright] Copyright 2003 American Cancer Society.
  • (PMID = 12673731.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / alpha-Fetoproteins; 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; Q20Q21Q62J / Cisplatin; U3P01618RT / Fluorouracil
  • [Number-of-references] 36
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3. Li W, Tan D, Zenali MJ, Brown RE: Constitutive activation of nuclear factor-kappa B (NF-kB) signaling pathway in fibrolamellar hepatocellular carcinoma. Int J Clin Exp Pathol; 2010;3(3):238-43
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  • [Title] Constitutive activation of nuclear factor-kappa B (NF-kB) signaling pathway in fibrolamellar hepatocellular carcinoma.
  • Fibrolamellar hepatocellular carcinoma (FLHCC) is an aggressive neoplasm due to high frequency of recurrence after surgical resection and resistance to chemotherapy and radiation therapy.
  • Formalin-fixed, paraffin-embedded tissue sections of 8 FLHCC, 10 normal liver tissues (NLT) were evaluated immunohistochemically for the expression of p-NF-kBp65 using phosphospecific antibody directed against phosphorylated (p)-NF-kBp65 (Ser 536).
  • Only high expression of p-NF-kBp65 (Ser 536) in cells with nuclear translocation was considered as constitutive NF-kB activation.
  • High expression of p-NF-kBp65 (Ser 536) was found in 88 % (7/8) of FLHCC tissue.
  • The differences in p-NF-kBp65 nuclear expression between FLHCC tissue and NLT were significant (P < 0.001).
  • The findings suggest that NF-kB activation is involved in the tumorigenesis of FLHCC and may represent novel targets for therapeutic intervention to FLHCC.
  • [MeSH-major] Carcinoma, Hepatocellular / physiopathology. Liver Neoplasms / physiopathology. NF-kappa B / physiology. Signal Transduction / physiology
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Biomarkers, Tumor / metabolism. Biopsy. Case-Control Studies. Cell Nucleus / metabolism. Diagnosis, Differential. Disease Progression. Female. Humans. Male. Middle Aged

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  • (PMID = 20224721.001).
  • [ISSN] 1936-2625
  • [Journal-full-title] International journal of clinical and experimental pathology
  • [ISO-abbreviation] Int J Clin Exp Pathol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / NF-kappa B
  • [Other-IDs] NLM/ PMC2836501
  • [Keywords] NOTNLM ; Fibrolamellar hepatocellular carcinoma / immunohistochemistry / nuclear factor-kappa B
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4. Kanai T, Takabayashi T, Kawano Y, Kuramochi S, Miyazawa N: A case of postoperative recurrence of fibrolamellar hepatocellular carcinoma with increased vitamin B12 binding capacity in a young Japanese female. Jpn J Clin Oncol; 2004 Jun;34(6):346-51
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  • [Title] A case of postoperative recurrence of fibrolamellar hepatocellular carcinoma with increased vitamin B12 binding capacity in a young Japanese female.
  • A 17-year-old Japanese female underwent major hepatic resection for a huge fibrolamellar hepatocellular carcinoma that was compressing the inferior vena cava.
  • The tumor was not exposed at the surgical margin but was very close to it.
  • A recurrent lesion at the surgical margin of the liver and a lymph node metastasis were discovered 9 months postoperatively together with a marked elevation of vitamin B12 binding capacity.
  • Several types of chemotherapy, including intraperitoneal injection of epirubicin, were applied and improved the patient's quality of life somewhat, but the patient died of recurrent disease 34 months after the initial hepatic resection.
  • This is the first report in Japan of fibrolamellar hepatocellular carcinoma with increased vitamin B12 binding capacity as a useful marker.
  • Fibrolamellar hepatocellular carcinomas, if resected, have a better prognosis than ordinary hepatocellular carcinoma in Japan, as well as in Western countries.
  • An aggressive strategy should be chosen, which consists mainly of precise surgical resection and postoperative multimodality therapy, including chemotherapy.
  • [MeSH-major] Carcinoma, Hepatocellular / diagnosis. Liver Neoplasms / diagnosis
  • [MeSH-minor] Adolescent. Hepatectomy. Humans. Lymphatic Metastasis. Neoplasm Recurrence, Local. Postoperative Period. Tomography, X-Ray Computed. Transcobalamins / analysis

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  • (PMID = 15333688.001).
  • [ISSN] 0368-2811
  • [Journal-full-title] Japanese journal of clinical oncology
  • [ISO-abbreviation] Jpn. J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Transcobalamins
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5. Grossman EJ, Millis JM: Liver transplantation for non-hepatocellular carcinoma malignancy: Indications, limitations, and analysis of the current literature. Liver Transpl; 2010 Aug;16(8):930-42
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  • [Title] Liver transplantation for non-hepatocellular carcinoma malignancy: Indications, limitations, and analysis of the current literature.
  • Orthotopic liver transplantation (OLT) is currently incorporated into the treatment regimens for specific nonhepatocellular malignancies.
  • For patients suffering from early-stage, unresectable hilar cholangiocarcinoma (CCA), OLT preceded by neoadjuvant radiotherapy has the potential to readily achieve a tumor-free margin, accomplish a radical resection, and treat underlying primary sclerosing cholangitis when present.
  • Hepatic epithelioid hemangioendothelioma is a rare tumor of vascular origin.
  • There exist subtle differences in the timing of chemotherapy between US and European centers; however, the long-term survival rate after transplantation ranges from 66% to 77%.
  • Fibrolamellar hepatocellular carcinoma is a distinct liver malignancy best treated by surgical resection.
  • In the treatment of either primary or metastatic hepatic sarcomas, unacceptable survival and recurrence rates currently prohibit the use of OLT.
  • [MeSH-major] Liver Neoplasms / therapy. Liver Transplantation / methods
  • [MeSH-minor] Aged. Cholangiocarcinoma / therapy. Hemangioendothelioma / therapy. Hepatoblastoma / therapy. Humans. Immunosuppressive Agents / therapeutic use. Liver / pathology. Medical Oncology / methods. Middle Aged. Neoplasm Metastasis. Neuroendocrine Tumors / therapy. Sarcoma / therapy. Treatment Outcome

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  • [Copyright] (c) 2010 AASLD.
  • (PMID = 20677284.001).
  • [ISSN] 1527-6473
  • [Journal-full-title] Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
  • [ISO-abbreviation] Liver Transpl.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunosuppressive Agents
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6. Kutluk MT, Yalçin B, Büyükpamukçu N, Kale G, Büyükpamukçu M: Fibrolamellar hepatocellular carcinoma with skeletal metastases. Pediatr Hematol Oncol; 2001 Jun;18(4):273-8
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  • [Title] Fibrolamellar hepatocellular carcinoma with skeletal metastases.
  • Skeletal metastases is relatively rare in hepatocellular carcinoma and accounts for 4-16% of extrahepatic metastases.
  • The authors report a 13-year-old girl with fibrolamellar hepatocellular carcinoma, who rejected further systemic chemotherapy following hepatic lobectomy and experienced sternal and vertebral painful metastases nearly 5 years after the operation.
  • The patient received no systemic treatment following metastases and died with widespread disease.
  • Despite metastatic disease, the patient survived 6.5 years following the initial diagnosis.
  • [MeSH-major] Bone Neoplasms / secondary. Carcinoma, Hepatocellular / pathology. Liver Neoplasms / pathology

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  • (PMID = 11400652.001).
  • [ISSN] 0888-0018
  • [Journal-full-title] Pediatric hematology and oncology
  • [ISO-abbreviation] Pediatr Hematol Oncol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
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7. Matsuda M, Yamada T, Gono T, Shimojima Y, Ishii W, Fushimi T, Sakashita K, Koike K, Ikeda S: Serum levels of free light chain before and after chemotherapy in primary systemic AL amyloidosis. Intern Med; 2005 May;44(5):428-33
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  • [Title] Serum levels of free light chain before and after chemotherapy in primary systemic AL amyloidosis.
  • OBJECTIVE: Immunoglobulin-related free light chains (FLCs) in serum have recently become quantitatively detectable using the nephelometric assay in plasma cell disorders, including multiple myeloma and AL amyloidosis.
  • To investigate whether FLCs are useful as a diagnostic and therapeutic marker in Japanese patients with primary systemic AL amyloidosis, we determined these values in serum before and after chemotherapy.
  • PATIENTS AND METHODS: The serum FLC analysis was carried out in 25 patients with primary systemic AL amyloidosis (mean age, 60.1+/-8.4 years).
  • All of the patients were shown to have either ALkappa- or ALlambda-immunoreactive amyloid deposits on biopsied tissues.
  • Thirteen patients were treated with VAD (vincristine, doxorubicin and dexamethasone) alone (n=6) or VAD and subsequent high-dose melphalan followed by autologous stem cell support (n=7), and serum FLCs were serially determined before and after the chemotherapy.
  • RESULTS: Before chemotherapy the amyloidogenic FLC was elevated in serum with or without abnormal e/e ratios in 24 patients, including 5 with undetectable M-protein in both serum and urine on immunofixation.
  • After chemotherapy the amyloidogenic FLC in serum was significantly decreased irrespective of high-dose melphalan (p<0.05), and all the patients with normalized kappa/lambda ratios showed a good prognosis.
  • CONCLUSIONS: With respect to sensitivity and quantification serum FLCs will be a key marker for diagnosis and therapeutic effects in primary systemic AL amyloidosis.
  • The prognosis of patients with this disease may be improved if the kappa/lambda ratio in serum can be normalized by intensive chemotherapy.
  • [MeSH-major] Amyloidosis / blood. Antineoplastic Agents, Alkylating / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Immunoglobulin Light Chains / blood. Melphalan / therapeutic use
  • [MeSH-minor] Adult. Aged. Biomarkers / blood. Biopsy. Dexamethasone / administration & dosage. Dexamethasone / therapeutic use. Dose-Response Relationship, Drug. Doxorubicin / administration & dosage. Doxorubicin / therapeutic use. Female. Humans. Immunoassay. Immunoglobulin kappa-Chains / blood. Immunoglobulin lambda-Chains / blood. Incidence. Infusions, Intravenous. Intestinal Mucosa / metabolism. Intestinal Mucosa / pathology. Japan / epidemiology. Kidney / metabolism. Kidney / pathology. Male. Middle Aged. Myeloma Proteins / metabolism. Nephelometry and Turbidimetry. Peripheral Blood Stem Cell Transplantation. Retrospective Studies. Treatment Outcome. Vincristine / administration & dosage. Vincristine / therapeutic use

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  • [CommentIn] Intern Med. 2005 May;44(5):399-400 [15942079.001]
  • (PMID = 15942088.001).
  • [ISSN] 0918-2918
  • [Journal-full-title] Internal medicine (Tokyo, Japan)
  • [ISO-abbreviation] Intern. Med.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Biomarkers; 0 / Immunoglobulin Light Chains; 0 / Immunoglobulin kappa-Chains; 0 / Immunoglobulin lambda-Chains; 0 / Myeloma Proteins; 0 / multiple myeloma M-proteins; 5J49Q6B70F / Vincristine; 7S5I7G3JQL / Dexamethasone; 80168379AG / Doxorubicin; Q41OR9510P / Melphalan; VAD protocol
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8. Braune C, Fangmann J, Scheumann GF, Klempnauer J: [Multiorgan resection in combination with intraoperative, hyperthermic chemotherapy in recurrent fibrolamellar hepatocellular carcinoma. An individual therapeutic concept for a 21-year-old patient]. Zentralbl Chir; 2001 Apr;126(4):318-21; discussion 322
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  • [Title] [Multiorgan resection in combination with intraoperative, hyperthermic chemotherapy in recurrent fibrolamellar hepatocellular carcinoma. An individual therapeutic concept for a 21-year-old patient].
  • [Transliterated title] Multiviszerale Resektion in Kombination mit intraoperativer, hyperthermer Chemotherapie beim Rezidiv des fibrolamellären, hepatozellulären Karzinoms. Ein individuelles, therapeutisches Konzept bei einem 21jährigen Patienten.
  • The fibrolamellar karzinoma of the liver (FLC) as an uncommon variant of the hepatocellular karzinoma (HCC) is an indolent growing tumor.
  • In its prior manifestation the FLC occurs at the adolescence and young adult stage.
  • Early stage diagnosis and aggressive surgical treatment achieve better long-term results than usual resection of the HCC.
  • Usually the FLC is, caused by its inconspicuous clinical appearance, diagnosed at a stage too advanced for effective surgical treatment.
  • Especially the young patient's age and the remaining therapeutic options for palliative or curative treatment postulate a difficult decision for the surgeon.
  • When a subtotal hepatectomy cannot be performed, total hepatectomy with liver transplantation is a valuable option.
  • Palliative treatment protocols include systemic chemotherapy, ethanol instillation and chemoembolisation.
  • We report the case of a 21-year-old male patient who presented with a recurrent intrahepatic FLC, peritoneal karzinomatosis confined to the right lower abdomen including gastric, splenic, diaphragmatic and colon transversum metastasis 14 months after primary surgery.
  • We selected this patient as a reasonable candidate for an extended resection in trying to offer the optimal therapeutic modality.
  • Furthermore hyperthermic intraperitoneal chemotherapy was carried out the next day.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Carcinoma, Hepatocellular / drug therapy. Carcinoma, Hepatocellular / surgery. Cisplatin / administration & dosage. Hyperthermia, Induced. Liver Neoplasms / drug therapy. Liver Neoplasms / surgery. Neoplasm Recurrence, Local / surgery
  • [MeSH-minor] Adult. Colectomy. Colonic Neoplasms / secondary. Colonic Neoplasms / surgery. Combined Modality Therapy. Follow-Up Studies. Gastrectomy. Hepatectomy. Humans. Infusions, Parenteral. Lymph Node Excision. Male. Omentum / surgery. Peritoneal Neoplasms / secondary. Peritoneal Neoplasms / surgery. Peritoneum / surgery. Postoperative Care. Splenectomy. Splenic Neoplasms / secondary. Splenic Neoplasms / surgery. Stomach Neoplasms / secondary. Stomach Neoplasms / surgery. Time Factors

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  • (PMID = 11370396.001).
  • [ISSN] 0044-409X
  • [Journal-full-title] Zentralblatt für Chirurgie
  • [ISO-abbreviation] Zentralbl Chir
  • [Language] ger
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; Q20Q21Q62J / Cisplatin
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9. Meriggi F, Forni E: [Surgical therapy of hepatic fibrolamellar carcinoma]. Ann Ital Chir; 2007 Jan-Feb;78(1):53-8
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  • [Title] [Surgical therapy of hepatic fibrolamellar carcinoma].
  • [Transliterated title] Il carcinoma epatico fibrolamellare. Considerazioni chirurgiche attuali.
  • Hepatic fibrolamellar carcinoma (FLC) is an uncommon tumour that differs from hepatocellular carcinoma (HCC) in demographics, condition of the affected liver, tumour markers, and prognosis.
  • FLC characteristically manifests as a large hepatic mass in adolescents or young adults with female predominance (mean age 23 years).
  • FLC is usually associated with serum tumour markers such as vitamin B12 binding protein, and neurotensin.
  • FLC is characterized pathologically by cords of tumour cells surrounded by abundant collagenous fibrous tissue arranged in a parallel or lamellar distribution.
  • FLC usually appears on radiologic images as a lobulated heterogeneous mass with a central scar in an otherwise normal liver.
  • The clinical presentation of patients with FLC is variable.
  • Use of percutaneous biopsy (FNAB) is beneficial if there is diagnostic uncertainty about the radiologic diagnosis (US, CT MRI).
  • Although FLC is frequently recurrent, patients have a better prognosis than those with HCC, and aggressive surgical liver resection with extended lymphadenectomy or liver transplantation may be indicated.
  • In inoperable cases, the patient may benefit from chemotherapy, permitting in up to 50% of these cases a curative resection.
  • The case is reported of a 18-year-old man with bilateral gynecomastia secondary to an unknown hepatic fibrolamellar carcinoma producing oestrogens.
  • Serum alpha-fetoprotein was negative; des-gamma-carboxy prothrombin (DCP) level was elevated.
  • By a needle biopsy a fibrolamellar carcinoma was diagnosed.
  • Specimen's histologic examination confirmed the preoperative diagnosis.
  • On April 2000 a probable recurrence within the caudate lobe was discovered by a liver CT scan without evidence of extrahepatic spreading.
  • Specimen's histologic examination showed a metastatic lymph nodal disease (FLC).
  • [MeSH-major] Carcinoma, Hepatocellular / diagnosis. Carcinoma, Hepatocellular / surgery. Hepatectomy. Liver Neoplasms / diagnosis. Liver Neoplasms / surgery
  • [MeSH-minor] Adolescent. Biomarkers / blood. Biomarkers, Tumor / blood. Gynecomastia / etiology. Humans. Lymph Node Excision. Male. Neoplasm Recurrence, Local. Prognosis. Protein Precursors / blood. Prothrombin. Treatment Outcome

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  • (PMID = 17518332.001).
  • [ISSN] 0003-469X
  • [Journal-full-title] Annali italiani di chirurgia
  • [ISO-abbreviation] Ann Ital Chir
  • [Language] ita
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Biomarkers, Tumor; 0 / Protein Precursors; 53230-14-1 / acarboxyprothrombin; 9001-26-7 / Prothrombin
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10. Lachmann HJ, Gallimore R, Gillmore JD, Carr-Smith HD, Bradwell AR, Pepys MB, Hawkins PN: Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol; 2003 Jul;122(1):78-84
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  • [Title] Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy.
  • Monoclonal immunoglobulin light chains are deposited as amyloid fibrils in systemic AL (primary) amyloidosis, but the underlying plasma cell dyscrasias are often difficult to detect or unquantifiable.
  • The relationships between circulating monoclonal light chains, amyloid load and clinical outcome, and the relative efficacies of chemotherapy regimens aimed at suppressing monoclonal immunoglobulin production, have not been determined.
  • Circulating free immunoglobulin light chain (FLC) concentration was measured with a sensitive nephelometric immunoassay in 262 patients with AL amyloidosis, and followed serially in 137 patients who received either high-dose chemotherapy or one of two intermediate-dose cytotoxic regimens.
  • A monoclonal excess of FLC was identified at diagnosis in 98% of patients.
  • Among 86 patients whose abnormal FLC concentration fell by more than 50% following chemotherapy, 5-year survival was 88% compared with only 39% among those whose FLC did not fall by half (P < 0.0001).
  • The magnitude and duration of the FLC responses to intermediate- and high-dose chemotherapy regimens were similar.
  • The FLC assay enabled the circulating fibril precursor protein in AL amyloidosis to be quantified and monitored in most patients.
  • Reduction of the amyloidogenic FLC by more than 50% was associated with substantial survival benefit, regardless of the type of chemotherapy used.
  • Clinical improvement following chemotherapy in AL amyloidosis is delayed, but treatment strategies can be guided by their early effect on serum FLC concentration.
  • [MeSH-major] Amyloid / analysis. Amyloidosis / drug therapy. Immunoglobulin Light Chains / blood
  • [MeSH-minor] Adult. Aged. Antibodies, Monoclonal / blood. Biomarkers / blood. Follow-Up Studies. Humans. Middle Aged. Nephelometry and Turbidimetry / methods. Serum Amyloid P-Component / metabolism. Survival Rate. Treatment Outcome

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  • (PMID = 12823348.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Amyloid; 0 / Antibodies, Monoclonal; 0 / Biomarkers; 0 / Immunoglobulin Light Chains; 0 / Serum Amyloid P-Component; 0 / amyloid protein AL
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11. Cruz O, Laguna A, Vancells M, Krauel L, Medina M, Mora J: Fibrolamellar hepatocellular carcinoma in an infant and literature review. J Pediatr Hematol Oncol; 2008 Dec;30(12):968-71
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  • [Title] Fibrolamellar hepatocellular carcinoma in an infant and literature review.
  • Hepatocellular carcinoma (HCC) is a rare pediatric neoplasm exceptionally reported in infants and fibrolamellar hepatocarcinoma (FLC) a HCC variant.
  • Controversy exists whether FLC has a better prognosis than classic HCC, although recent studies of children and young adults with FLC did not report a better outcome.
  • We present a 4-month-old male infant without any related metabolic or infectious disease who developed a metastatic and multifocal FLC.
  • Induction chemotherapy using cisplatin and Adriamycin resulted in a partial response, however, refractory disease developed and regional metastasis precluded surgical resection.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Hepatocellular / pathology. Liver Neoplasms / pathology
  • [MeSH-minor] Chemotherapy, Adjuvant. Cisplatin / administration & dosage. Doxorubicin / administration & dosage. Fatal Outcome. Humans. Infant. Magnetic Resonance Imaging. Male. Neoplasm Recurrence, Local / diagnosis. Neoplasm Recurrence, Local / drug therapy. Prognosis. Tomography, X-Ray Computed. Treatment Outcome. alpha-Fetoproteins / metabolism

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  • (PMID = 19131794.001).
  • [ISSN] 1536-3678
  • [Journal-full-title] Journal of pediatric hematology/oncology
  • [ISO-abbreviation] J. Pediatr. Hematol. Oncol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / alpha-Fetoproteins; 80168379AG / Doxorubicin; Q20Q21Q62J / Cisplatin
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12. Khoo JJ, Clouston A: Fibrolamellar hepatocellular carcinoma: a case report. Malays J Pathol; 2001 Dec;23(2):115-8
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  • [Title] Fibrolamellar hepatocellular carcinoma: a case report.
  • Computerised tomography showed a nodular mass in the left lobe of the liver.
  • Biopsy of the liver mass led to a histological diagnosis of fibrolamellar hepatocellular carcinoma.
  • In view of extensive tumour involvement, he could not be operated on but was treated with chemotherapy.
  • While this is expected for fibrolamellar hepatocellular carcinoma, the possibility of the tumour having a component of ordinary hepatocellular carcinoma could not be excluded as the tumour was not resected.
  • Fibrolamellar hepatocellular carcinoma is a rare histological subtype of hepatocellular carcinoma, associated with a better prognosis.
  • It affects the younger age group and has no association with cirrhosis, hepatitis B virus infection or exposure to oral contraceptives, all of which are implicated in ordinary hepatocellular carcinoma.
  • Serum alpha-fetoprotein level is usually within normal limits and other laboratory values are not contributory to the diagnosis.
  • The diagnosis is usually suggested by radiographic studies viz.
  • CT scan of the abdomen, which would show an irregular non-homogenous mass in the liver, and confirmed by histological examination.
  • The most characteristic microscopical feature is fibrosis arranged in a lamellar fashion around polygonal and deeply eosinophilic neoplastic hepatocytes.
  • [MeSH-major] Carcinoma, Hepatocellular / pathology. Liver Neoplasms / pathology
  • [MeSH-minor] Child. Humans. Male. Tomography, X-Ray Computed

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  • (PMID = 12166592.001).
  • [ISSN] 0126-8635
  • [Journal-full-title] The Malaysian journal of pathology
  • [ISO-abbreviation] Malays J Pathol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Malaysia
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13. Mukai M, Okada K, Fukumitsu H, Yazawa N, Hoshikawa T, Tajima T, Hirakawa H, Ogoshi K, Makuuchi H: Efficacy of 5-FU/LV plus CPT-11 as first-line adjuvant chemotherapy for stage IIIa colorectal cancer. Oncol Rep; 2009 Sep;22(3):621-9
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  • [Title] Efficacy of 5-FU/LV plus CPT-11 as first-line adjuvant chemotherapy for stage IIIa colorectal cancer.
  • The aim of this study was to retrospectively evaluate the effect of adding CPT-11 to postoperative chemotherapy for stage III colorectal cancer.
  • The clinical outcome was compared between patients receiving 5-FU/LV plus CPT-11 (FLC group) and patients receiving 5-FU/LV alone (FL group).
  • The FLC group (54 patients) had a 3-year relapse-free survival (3Y-RFS) of 68.7%, a 5Y-RFS of 68.7% and a 5Y-OS of 67.1%, while the FL group (40 patients) had a 3Y-RFS of 67.5% (n.s.
  • For stage IIIa patients, the corresponding survival rates were 92.4, 92.4 and 90.9% in the FLC group (29 patients) vs. 64.5% (p=0.024), 61.1% (p=0.018), and 77.1% (n.s.) in the FL group (31 patients).
  • For stage IIIb patients, the rates were 36.6, 36.6 and 24.8% in the FLC group (25 patients) vs. 77.8% (n.s.
  • These results suggest that the 3Y-RFS and 5Y-RFS of patients with stage IIIa colorectal cancer were significantly improved by adjuvant chemotherapy with 5-FU/LV plus CPT-11.
  • [MeSH-major] Colorectal Neoplasms / drug therapy
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Camptothecin / administration & dosage. Camptothecin / analogs & derivatives. Chemotherapy, Adjuvant. Fluorouracil / administration & dosage. Humans. Leucovorin / administration & dosage. Neoplasm Staging

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  • (PMID = 19639213.001).
  • [ISSN] 1021-335X
  • [Journal-full-title] Oncology reports
  • [ISO-abbreviation] Oncol. Rep.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Greece
  • [Chemical-registry-number] 7673326042 / irinotecan; Q573I9DVLP / Leucovorin; U3P01618RT / Fluorouracil; XT3Z54Z28A / Camptothecin
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14. Pardee TS, Zuber J, Lowe SW: Effects of the Flt3 ITD on response to chemotherapy in a murine model of acute myeloid leukemia. J Clin Oncol; 2009 May 20;27(15_suppl):7060

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Effects of the Flt3 ITD on response to chemotherapy in a murine model of acute myeloid leukemia.
  • : 7060 Background: Acute myeloid leukemia (AML) is an aggressive, genetically heterogeneous malignancy.
  • This heterogeneity is thought to underlie the divergent responses to treatment observed and contribute to relapse.
  • The Flt3 receptor tyrosine kinase containing an internal tandem duplication (Flt3 ITD) is a common mutation in AML and associated with a poor prognosis; however, its effect on chemotherapy response is currently unknown.
  • METHODS: Murine AML was generated by retroviral transduction of an MLL-ENL fusion protein into fetal liver cells and subsequent transplantation into syngeneic mice.
  • For competition assays mixtures of infected and uninfected blasts were exposed to chemotherapy for 72 hours.
  • Among the remaining viable cells, percentages of infected blasts were determined by flow cytometry.
  • For in vivo competition assays animals were injected with mixtures of blasts, treated with chemotherapy and percentages of Flt3 ITD positive blasts as well as total leukemic burden in femoral bone marrow was assessed.

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  • (PMID = 27961434.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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15. Mansouri D, Van Nhieu JT, Couanet D, Terrier-Lacombe MJ, Brugières L, Cherqui D, Suciu V, Vielh P: Fibrolamellar hepatocellular carcinoma: a case report with cytological features in a sixteen-year-old girl. Diagn Cytopathol; 2006 Aug;34(8):568-71
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Fibrolamellar hepatocellular carcinoma: a case report with cytological features in a sixteen-year-old girl.
  • We report a case of a 16-yr-old girl with a liver tumor revealed by thrombophlebitis of the left leg.
  • Ultrasound and CAT scan showed a large tumor of the left portion of the liver, measuring 14 cm in diameter.
  • Cytological examination using May-Grünwald Giemsa stain revealed highly cellular smears containing large tumor cells with a round nucleus, prominent nucleoli, and abundant granular basophilic cytoplasm.
  • Cytological features were those of fibrolamellar hepatocellular carcinoma, confirmed by histological examination of the biopsy sample as well as the surgical specimen obtained after wide excision of the lesion following ineffective neoadjuvant chemotherapy.
  • [MeSH-major] Carcinoma, Hepatocellular / diagnosis. Liver Neoplasms / diagnosis
  • [MeSH-minor] Adolescent. Biopsy. Cytodiagnosis. Female. Follow-Up Studies. Humans. Tomography, X-Ray Computed. Treatment Outcome

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  • [Copyright] (c) 2006 Wiley-Liss, Inc.
  • [CommentIn] Diagn Cytopathol. 2007 Jul;35(7):459-62 [17580341.001]
  • (PMID = 16850484.001).
  • [ISSN] 8755-1039
  • [Journal-full-title] Diagnostic cytopathology
  • [ISO-abbreviation] Diagn. Cytopathol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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16. Ichikawa T, Federle MP, Grazioli L, Marsh W: Fibrolamellar hepatocellular carcinoma: pre- and posttherapy evaluation with CT and MR imaging. Radiology; 2000 Oct;217(1):145-51
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Fibrolamellar hepatocellular carcinoma: pre- and posttherapy evaluation with CT and MR imaging.
  • PURPOSE: To determine the features of advanced hepatic and extrahepatic fibrolamellar hepatocellular carcinomas (HCCs) and their effects on immediate surgical management and tumor recurrence.
  • MATERIALS AND METHODS: Thirty-one patients with fibrolamellar HCC underwent pretherapy computed tomography (CT); 11 underwent pretherapy magnetic resonance (MR) imaging.
  • Thirteen (42%) had extrahepatic tumor spread, nine (29%) had distant metastases on pretherapy images, and 20 (65%) had lymphadenopathy.
  • Thirty-two (80%) of 40 patients underwent exploration surgery; curative resection was attempted in 25 (62%), including four patients who underwent liver transplantation.
  • Tumor recurred in all eight of the 17 patients who had extrahepatic disease at pretherapy CT and in four of the seven patients who seemed to have tumor limited to the liver.
  • A combination of repeat tumor resection and adjuvant chemotherapy resulted in prolonged tumor-free survival in some cases.
  • CONCLUSION: Fibrolamellar HCC frequently demonstrates aggressive local invasion and nodal and distant metastases.
  • Aggressive surgical resection may be helpful to control fibrolamellar HCC and to prolong survival in appropriately selected cases.
  • [MeSH-major] Carcinoma, Hepatocellular / pathology. Carcinoma, Hepatocellular / radiography. Liver Neoplasms / pathology. Liver Neoplasms / radiography
  • [MeSH-minor] Adolescent. Adult. Aged. Combined Modality Therapy. Contrast Media. Female. Humans. Magnetic Resonance Imaging. Male. Middle Aged. Neoplasm Recurrence, Local. Tomography, X-Ray Computed. Treatment Outcome

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  • (PMID = 11012437.001).
  • [ISSN] 0033-8419
  • [Journal-full-title] Radiology
  • [ISO-abbreviation] Radiology
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Contrast Media
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17. Pawlik TM, Scoggins CR, Thomas MB, Vauthey JN: Advances in the surgical management of liver malignancies. Cancer J; 2004 Mar-Apr;10(2):74-87
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Advances in the surgical management of liver malignancies.
  • Primary malignancies of the liver include tumors arising from the hepatocytes (hepatocellular carcinoma and the fibrolamellar variant) and the intrahepatic bile ducts (intrahepatic cholangiocarcinoma).
  • Hepatocellular carcinoma is the most common primary cancer of the liver and is a leading cause of death from cancer worldwide.
  • Although it is uncommon in the United States, the incidence of hepatocellular carcinoma is rising.
  • New clinical and pathological staging systems have allowed for the more accurate stratification of patients to more appropriately identify patients for resection, transplantation, and percutaneous ablation therapies.
  • A correlation between liver volume and surgical outcome has recently been demonstrated, with small liver remnant size being associated with increased morbidity.
  • Portal vein embolization has therefore been proposed as one way to induce hypertrophy of the anticipated liver remnant before resection.
  • More recently, systemic chemotherapy and chemoembolization have been investigated as both primary and neoadjuvant therapy.
  • Chemoimmunotherapy with 5-fluorouracil and interferon may be associated with a superior response rate in the fibrolamellar variant of hepatocellular carcinoma.
  • [MeSH-major] Bile Duct Neoplasms / surgery. Bile Ducts, Intrahepatic / surgery. Carcinoma, Hepatocellular / surgery. Cholangiocarcinoma / surgery. Liver Neoplasms / surgery
  • [MeSH-minor] Decision Trees. Humans. Liver Cirrhosis / complications. Neoplasm Staging. Organ Size

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  • (PMID = 15130267.001).
  • [ISSN] 1528-9117
  • [Journal-full-title] Cancer journal (Sudbury, Mass.)
  • [ISO-abbreviation] Cancer J
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 141
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18. Maniaci V, Davidson BR, Rolles K, Dhillon AP, Hackshaw A, Begent RH, Meyer T: Fibrolamellar hepatocellular carcinoma: prolonged survival with multimodality therapy. Eur J Surg Oncol; 2009 Jun;35(6):617-21
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Fibrolamellar hepatocellular carcinoma: prolonged survival with multimodality therapy.
  • AIM: We report the clinical outcome for a series of ten patients with fibrolamellar hepatocellular treated with resection followed by close surveillance and aggressive management of relapse.
  • METHODS: The case notes for all patients treated at this institution since 1982 were reviewed and details of initial stage and management were extracted along with investigations and treatment of relapse.
  • Time to relapse, overall survival and post-relapse survival were analysed.
  • RESULTS: Relapse occurred in all ten cases at a median of 2.2 (95% CI 0.9-2.7) years but, with a combination of re-resection, systemic chemotherapy and radiotherapy, the overall median survival was 9.3 (95% CI 3.0-18.5) years.
  • CONCLUSION: The early detection of relapse combined with multimodality therapy results in prolonged survival.
  • Further improvements in systemic therapy are required to improve the prognosis in this disease.
  • [MeSH-major] Carcinoma, Hepatocellular / therapy. Liver Neoplasms / therapy
  • [MeSH-minor] Adolescent. Adult. Combined Modality Therapy. Female. Hepatectomy. Humans. Lymph Node Excision. Male. Middle Aged. Survival Analysis. Treatment Outcome. Young Adult

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  • (PMID = 19144491.001).
  • [ISSN] 1532-2157
  • [Journal-full-title] European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
  • [ISO-abbreviation] Eur J Surg Oncol
  • [Language] eng
  • [Grant] United Kingdom / Department of Health / /
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
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19. Avila LF, Encinas JL, Leal N, Guinea A, García Miguel P, Jara P, Murcia J, Gamez M, Guinea A, López Santamaría M, Tovar JA: [Liver transplatation for malignant tumors in children]. Cir Pediatr; 2007 Oct;20(4):189-93
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  • [Title] [Liver transplatation for malignant tumors in children].
  • OBJECTIVE: To analyse our results on liver transplantation (LTX) in primitive malignant unresectable liver tumours in children and discussing its controversial indications in order to our experience.
  • They had hepatoblastoma (11) and fibrolamellar hepatocelullar carcinoma (1) without cirrhosis.
  • LTX was considered as primary treatment in 10 patients (PRETEXT IV or any grade if extension to retrohepatic cava vein, 3 hepatic veins or porta vein were assessed) and as rescue therapy after recurrence (1) or persistence of unresectable macroscopic rests (2).
  • One of the patients who underwent a LTX as primary therapy had lung metastases previously resolved with chemotherapy.
  • We used entire liver (5), left lateral segment from cadaveric donor (3), live related donor (3, 2 segments II-III and 1 right liver) and left lateral segment from split (1).
  • All children received chemotherapy prior and post-transplantation following SIOPEL protocol.
  • OUTCOMES ANALYSED: Procedure tolerance, survival, recurrence rate, disease-free period and risk factors for adverse evolution.
  • The boy who presented lung metastases developed new ones one year after LTX that were removed and he actually is free of disease.
  • Tumoral tissue persistence is the only risk factor for an adverse evolution in our series.
  • CONCLUSIONS: LTX is possible therapeutic approach for unresectable malignant liver tumours.
  • It provides better results as a primary treatment than as a rescue one, being these outcomes comparable to those from resectable tumours.
  • [MeSH-major] Carcinoma, Hepatocellular / surgery. Hepatoblastoma / surgery. Liver Neoplasms / surgery. Liver Transplantation

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  • (PMID = 18351237.001).
  • [ISSN] 0214-1221
  • [Journal-full-title] Cirugía pediátrica : organo oficial de la Sociedad Española de Cirugía Pediátrica
  • [ISO-abbreviation] Cir Pediatr
  • [Language] spa
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Spain
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20. Hans CP, Weisenburger DD, Vose JM, Hock LM, Lynch JC, Aoun P, Greiner TC, Chan WC, Bociek RG, Bierman PJ, Armitage JO: A significant diffuse component predicts for inferior survival in grade 3 follicular lymphoma, but cytologic subtypes do not predict survival. Blood; 2003 Mar 15;101(6):2363-7
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  • On the basis of possible biologic differences, the new World Health Organization (WHO) classification of lymphoma suggests further subdivision of FL3 into grades 3a and 3b and states that the percentage of involvement by diffuse large B-cell lymphoma (DLBCL) should also be reported.
  • Therefore, we studied 190 newly diagnosed patients with lymph node-based FL3 who received anthracycline-containing combination chemotherapy.
  • The follicular component was subclassified as grade 3a (FL3a) or grade 3b (FL3b) according to the WHO criteria, or as follicular large cleaved cell type (FLC).
  • The percentage of a diffuse component, if present, was also recorded.
  • Of the 190 cases, there were 107 FL3a (56%), 53 FL3b (28%), and 30 FLC (16%) cases.
  • Diffuse areas were seen in 72 cases (31 FL3a, 28 FL3b, and 13 FLC).
  • There were no significant differences in the clinical characteristics, overall survival, or event-free survival between patients with grades FL3a, FL3b, or FLC.
  • However, those cases with a predominant diffuse component (> 50% diffuse) had a significantly worse overall survival (P =.0037) and event-free survival (P =.012).
  • [MeSH-major] Lymphoma, B-Cell / pathology. Lymphoma, Follicular / mortality. Lymphoma, Follicular / pathology. Lymphoma, Large B-Cell, Diffuse / pathology
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bleomycin / therapeutic use. Cyclophosphamide / therapeutic use. Doxorubicin / therapeutic use. Female. Humans. Male. Middle Aged. Mitoxantrone / therapeutic use. Prednisolone / therapeutic use. Prednisone / therapeutic use. Procarbazine / therapeutic use. Prognosis. Survival Rate. Vincristine / therapeutic use

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  • (PMID = 12424193.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA36727
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 11056-06-7 / Bleomycin; 35S93Y190K / Procarbazine; 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; 9PHQ9Y1OLM / Prednisolone; BZ114NVM5P / Mitoxantrone; VB0R961HZT / Prednisone; CHOP protocol; COP-BLAM protocol; MCOP protocol
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21. Avila LF, Luis AL, Hernandez F, Garcia Miguel P, Jara P, Andres AM, Lopez Santamaría M, Tovar JA: Liver transplantation for malignant tumours in children. Eur J Pediatr Surg; 2006 Dec;16(6):411-4
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  • [Title] Liver transplantation for malignant tumours in children.
  • OBJECTIVE: The object of this study was to analyse our results with liver transplantation (LTX) for primitive malignant unresectable liver tumours in children and to discuss the controversial indications, based on our experience.
  • METHODS/PATIENTS: We report on 12 patients, aged 6 months to 14 years, with hepatic malignant tumours: 11 with hepatoblastoma and 1 with fibrolamellar hepatocelullar carcinoma without cirrhosis.
  • LTX was the primary treatment in 10 patients (PRETEXT IV or any grade, if there was extension to the retrohepatic vena cava, 3 hepatic veins or portal vein) and a rescue therapy after recurrence for 1 and for persistence of unresectable macroscopic residuals in 2 patients.
  • One of the patients who underwent a LTX as primary therapy had lung metastases previously resolved with chemotherapy.
  • We used entire liver (n = 5), left lateral segment from cadaveric donor (n = 3), living related donor (n = 3; 2 segments II-III and 1 right lobe) and left lateral segment from split liver (n = 1).
  • All children received chemotherapy prior and post transplantation following the SIOPEL protocol.
  • We analysed procedure tolerance, survival, recurrence rate, disease-free period and risk factors for adverse evolution.
  • The boy who presented with lung metastases developed new ones one year after LTX that were removed and he is currently free of disease.
  • Tumour tissue persistence was the only risk factor for an adverse clinical course in our series.
  • CONCLUSIONS: LTX is a reasonable therapeutic approach for unresectable malignant liver tumours, providing outcomes comparable to those for resectable tumours.
  • Results obtained with LTX are better when it is used as a primary treatment than when used as a rescue procedure.
  • [MeSH-major] Carcinoma, Hepatocellular / surgery. Hepatoblastoma / surgery. Liver Neoplasms / surgery. Liver Transplantation

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  • (PMID = 17211789.001).
  • [ISSN] 0939-7248
  • [Journal-full-title] European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift für Kinderchirurgie
  • [ISO-abbreviation] Eur J Pediatr Surg
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
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22. Wall WJ: Liver transplantation for hepatic and biliary malignancy. Semin Liver Dis; 2000;20(4):425-36
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  • [Title] Liver transplantation for hepatic and biliary malignancy.
  • The treatment of liver cancer by transplantation has evolved into a process of selecting early stage tumors that have a high likelihood of cure.
  • Carefully selected cirrhotic patients with early hepatocellular cancer (< or = 5 cm. diameter and single; < or = 3 cm. diameter if multiple and 3 or fewer lesions; no vascular invasion) have 5-year actuarial survival rates of approximately 75% after transplantation.
  • Preoperative imaging should be as extensive as necessary to accurately define the characteristics of tumor size, location, and number and exclude signs of extrahepatic involvement.
  • Adjuvant and neoadjuvant chemotherapy became part of treatment protocols in many centers at the same time that more stringent criteria for transplant candidacy were applied to patients with cancer, making it difficult to attribute improved results to the chemotherapy.
  • Nevertheless, neoadjuvant chemoembolization for hepatocellular cancer is logical for patients who may wait long periods before receiving transplants.
  • The fibrolamellar variant of hepatoma is a less aggressive tumor and patients can do well after transplantation, but late recurrences are common.
  • Hepatoblastoma in children can respond very favorably to chemotherapy combined with transplantation.
  • Recent work combining chemotherapy and radiation with transplantation has not had dramatic success at improving cure rates.
  • Patients with metastatic neuroendocrine tumors of the liver can receive good palliation by transplantation, but the majority of patients eventually develop recurrent cancer.
  • [MeSH-major] Biliary Tract Neoplasms / therapy. Carcinoma, Hepatocellular / therapy. Cholangiocarcinoma / therapy. Liver Neoplasms / therapy. Liver Transplantation. Neuroendocrine Tumors / therapy
  • [MeSH-minor] Chemoembolization, Therapeutic. Combined Modality Therapy. Humans. Neoplasm Recurrence, Local. Palliative Care. Patient Selection. Prognosis. Treatment Outcome

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  • (PMID = 11200413.001).
  • [ISSN] 0272-8087
  • [Journal-full-title] Seminars in liver disease
  • [ISO-abbreviation] Semin. Liver Dis.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 95
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23. Mroz RM, Korniluk M, Swidzinska E, Dzieciol J, Czaban J, Panek B, Chyczewska E: Lung mass in a 28-year-old male: a case report of a rare tumor. Eur J Med Res; 2010 Nov 4;15 Suppl 2:95-7
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  • [Title] Lung mass in a 28-year-old male: a case report of a rare tumor.
  • A twenty eight-year-old male presented with a two week history of dyspnea, cough, hemoptysis, chest pain, and fever 38-39°C.
  • He was referred with suspicion of lung tumor to our institution.
  • Using computed tomography (CT), a lesion of diameter of 19.3 x 14.1 x 19.1 cm in the right lung, pleuritis, Th3 osteolysis, and compensatory overinflation of the left lung was seen.
  • Transthoracic fine needle aspiration revealed celullae suspectae probabiliter neoplasmaticae suggesting tumor fusocellularis.
  • USG of the abdomen revealed liver with numerous heterogeneous, solid areas hypo- and hyperechogenic, some of them with features of liquid or the disintegration up to diameter of 74 mm.
  • Subsequent fine needle aspirations of the thorax and liver revealed fibrolamellar hepatocarcinoma and carcinoma adenoides of the lung.
  • Patient underwent chemotherapy with 5-FU/DDP/VCR with no response.
  • This report presents a case of a rare lung metastasis from FL-HCC.
  • [MeSH-major] Liver Neoplasms / pathology. Lung Neoplasms / secondary
  • [MeSH-minor] Adult. Biopsy, Needle. Carcinoma, Hepatocellular / pathology. Humans. Male

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  • (PMID = 21147631.001).
  • [ISSN] 0949-2321
  • [Journal-full-title] European journal of medical research
  • [ISO-abbreviation] Eur. J. Med. Res.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] Fibrolamellar hepatocellular carcinoma
  • [Other-IDs] NLM/ PMC4360372
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24. Czauderna P, Zbrzezniak G, Narozanski W, Korzon M, Wyszomirska M, Stoba C: Preliminary experience with arterial chemoembolization for hepatoblastoma and hepatocellular carcinoma in children. Pediatr Blood Cancer; 2006 Jun;46(7):825-8
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  • [Title] Preliminary experience with arterial chemoembolization for hepatoblastoma and hepatocellular carcinoma in children.
  • The objective of this work was to test feasibility and efficacy of hepatic artery chemoembolization (HACE) in unresectable malignant liver tumors.
  • All had locally advanced tumors, which did not respond to systemic chemotherapy: four, hepatoblastoma (HB) and one, hepatocellular carcinoma (HCC).
  • The procedure was performed one to three times in each patient.
  • In four patients (three, HB, one, fibrolamellar HCC), tumor response was observed, with decrease in the diameter of the mass of 25-33% and fall in the AFP level of 83-99%.
  • Two patients (2 HB) underwent macroscopically complete tumor resection, 1 is alive and well, and 1 died at the end of surgery for an unknown reason (possibly related to cardiotoxicity of earlier systemic chemotherapy).
  • HACE can lead to tumor regression in most cases and may be considered an alternative for patients with unresectable liver tumors who do not respond to primary systemic chemotherapy and are not candidates for liver transplantation for various reasons.
  • [MeSH-major] Carcinoma, Hepatocellular / therapy. Chemoembolization, Therapeutic. Hepatoblastoma / therapy. Liver Neoplasms / therapy

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  • [Copyright] (c) 2005 Wiley-Liss, Inc.
  • (PMID = 16123986.001).
  • [ISSN] 1545-5009
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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25. Hutchison CA, Cook M, Heyne N, Weisel K, Billingham L, Bradwell A, Cockwell P: European trial of free light chain removal by extended haemodialysis in cast nephropathy (EuLITE): a randomised control trial. Trials; 2008;9:55
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  • BACKGROUND: Renal failure is a frequent complication of multiple myeloma and when severe is associated with a greatly increased morbidity and mortality.
  • The principal cause of severe renal failure is cast nephropathy, a direct consequence of high concentrations of monoclonal free light chains (FLCs) in patients' sera.
  • FLC removal by extended haemodialysis, using a high cut-off dialyser, has recently been described as a novel therapeutic option.
  • METHODS: The EUropean trial of free LIght chain removal by exTEnded haemodialysis in cast nephropathy (EuLITE) trial is a prospective, randomised, multicentre, open label clinical trial to investigate the clinical benefits of FLC removal haemodialysis in patients with cast nephropathy, dialysis dependent acute renal failure and de novo multiple myeloma.
  • Participants will be randomised, centrally, upon enrolment, to either trial chemotherapy and FLC removal haemodialysis or trial chemotherapy and standard high flux haemodialysis.
  • Trial chemotherapy consists of bortezomib, doxorubicin and dexamethasone.
  • FLC removal haemodialysis is undertaken with two Gambro HCO 1100 dialysers in series using an intensive treatment schedule.
  • Secondary outcomes are: duration of dialysis, reduction in serum FLC concentrations; myeloma response and survival.
  • HYPOTHESIS: FLC removal haemodialysis will increase the rate of renal recovery in patients with severe renal failure secondary to cast nephropathy in de novo multiple myeloma.

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  • [Cites] Ann Intern Med. 2005 Dec 6;143(11):777-84 [16330788.001]
  • [Cites] Arch Intern Med. 1998 Sep 28;158(17):1889-93 [9759684.001]
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  • (PMID = 18822172.001).
  • [ISSN] 1745-6215
  • [Journal-full-title] Trials
  • [ISO-abbreviation] Trials
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC2564897
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26. Yoshida T, Matsuda M, Katoh N, Tazawa K, Shimojima Y, Gono T, Ishii W, Nakazawa Y, Sakashita K, Koike K, Yamada T, Ikeda S: Long-term follow-up of plasma cells in bone marrow and serum free light chains in primary systemic AL amyloidosis. Intern Med; 2008;47(20):1783-90
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  • [Title] Long-term follow-up of plasma cells in bone marrow and serum free light chains in primary systemic AL amyloidosis.
  • OBJECTIVE: Primary systemic AL amyloidosis arises from immunoglobulin light chains produced by plasma cell dyscrasia.
  • To prospectively investigate the production of M-protein and plasma cells in bone marrow before and after chemotherapy, we performed flow cytometry and analysis of serum free light chains (FLCs).
  • PATIENTS AND METHODS: Fifty-nine patients with primary systemic AL amyloidosis (mean age, 59.9+/-8.8 years) were enrolled in this study, and of these 31 were serially studied before and after chemotherapy.
  • Complete hematological remission was defined as normalization of the FLC kappa/lambda ratio.
  • There was a significantly positive correlation between the serum predominant FLC/serum creatinine ratio and MPC-1(+)CD45(-)CD49e(-) (p<0.05).
  • After chemotherapies, such as high-dose melphalan with autologous stem cell support, 20 of 31 patients with AL amyloidosis achieved complete hematological remission.
  • There were no significant differences in any subtype of plasma cells before treatment between the remission and non-remission groups, but in the former group MPC-1(+)CD45(-)CD49e(-) and MPC-1(-)CD45(+) were significantly decreased and increased after chemotherapy compared with before, respectively.
  • CONCLUSION: Abnormal plasma cells in the bone marrow, particularly the MPC-1(+)CD45(-)CD49e(-) subset, may be important as a follow-up marker before and after chemotherapy in primary systemic AL amyloidosis.
  • These cells maintain low levels as long as no relapse occurs.
  • [MeSH-major] Amyloidosis / blood. Amyloidosis / pathology. Bone Marrow / pathology. Immunoglobulin Light Chains / blood. Plasma Cells / pathology
  • [MeSH-minor] Adult. Aged. Antigens, CD45 / blood. Biomarkers / blood. Case-Control Studies. Chemokine CCL2 / blood. Connectin. Creatinine / blood. Drug Therapy. Female. Follow-Up Studies. Humans. Integrin alpha5 / blood. Longitudinal Studies. Male. Middle Aged. Muscle Proteins / blood. Prognosis. Prospective Studies. Treatment Outcome

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  • (PMID = 18854629.001).
  • [ISSN] 1349-7235
  • [Journal-full-title] Internal medicine (Tokyo, Japan)
  • [ISO-abbreviation] Intern. Med.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Biomarkers; 0 / CCL2 protein, human; 0 / Chemokine CCL2; 0 / Connectin; 0 / Immunoglobulin Light Chains; 0 / Integrin alpha5; 0 / Muscle Proteins; AYI8EX34EU / Creatinine; EC 3.1.3.48 / Antigens, CD45; EC 3.1.3.48 / PTPRC protein, human
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27. Palladini G, Lavatelli F, Russo P, Perlini S, Perfetti V, Bosoni T, Obici L, Bradwell AR, D'Eril GM, Fogari R, Moratti R, Merlini G: Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood; 2006 May 15;107(10):3854-8
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  • [Title] Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL.
  • N-terminal natriuretic peptide type B (NT-proBNP) is a marker of cardiac dysfunction in light chain amyloidosis (AL) and a powerful prognostic determinant.
  • Serum NT-proBNP and circulating free light chains (FLCs) were measured at enrollment and after 3 cycles of chemotherapy in 51 patients with cardiac AL.
  • In patients (n = 22, 43%) in whom FLCs decreased by more than 50% (hematologic response), NT-proBNP concentration decreased by a median of 48%, whereas in the remaining patients it increased by 47% (P = .01).
  • The reduction of NT-proBNP was greater in patients (n = 9) in whom amyloidogenic FLCs disappeared at immunofixation (median 53%), than in the remaining responding patients (median 31%, P = .04).
  • Thirteen of them, in whom NT-proBNP and FLCs did not improve, died after a median of 1.8 months.
  • The decrease of FLCs translates into a simultaneous decrease of NT-proBNP and improved survival.
  • Patients in whom chemotherapy fails to induce such a decrease are at risk of early death.
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Creatinine / blood. Female. Heart Ventricles / pathology. Humans. Male. Middle Aged. Prognosis. Retrospective Studies. Survival Analysis. Treatment Outcome

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  • (PMID = 16434487.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin Light Chains; 0 / Peptide Fragments; 0 / pro-brain natriuretic peptide (1-76); 114471-18-0 / Natriuretic Peptide, Brain; AYI8EX34EU / Creatinine
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28. Hutchison CA, Plant T, Drayson M, Cockwell P, Kountouri M, Basnayake K, Harding S, Bradwell AR, Mead G: Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure. BMC Nephrol; 2008;9:11
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  • [Title] Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure.
  • BACKGROUND: Monoclonal free light chains (FLCs) frequently cause rapidly progressive renal failure in patients with multiple myeloma.
  • Immunoassays which provide quantitative measurement of FLCs in serum, have now been adopted into screening algorithms for multiple myeloma and other lymphoproliferative disorders.
  • The assays indicate monoclonal FLC production by the presence of an abnormal kappa to lambda FLC ratio (reference range 0.26-1.65).
  • Previous work, however, has demonstrated that in patients with renal failure the FLC ratio can be increased above normal with no other evidence of monoclonal proteins suggesting that in this population the range should be extended (reference range 0.37-3.1).
  • METHODS: Sera from 142 patients with new dialysis-dependent renal failure were assessed by serum protein electrophoresis (SPE), FLC immunoassays and immunofixation electrophoresis.
  • The sensitivity and specificity of the FLC ratio's published reference range was compared with the modified renal reference range for identifying patients with multiple myeloma; by receiver operating characteristic curve analysis.
  • RESULTS: Forty one patients had a clinical diagnosis of multiple myeloma; all of these patients had abnormal serum FLC ratios.
  • The modified FLC ratio range increased the specificity of the assays (from 93% to 99%), with no loss of sensitivity.
  • Monoclonal FLCs were identified in the urine from 23 of 24 patients assessed.
  • CONCLUSION: Measurement of serum FLC concentrations and calculation of the serum kappa/lambda ratio is a convenient, sensitive and specific method for identifying monoclonal FLC production in patients with multiple myeloma and acute renal failure.
  • Rapid diagnosis in these patients will allow early initiation of disease specific treatment, such as chemotherapy plus or minus therapies for direct removal of FLCs.
  • [MeSH-major] Immunoglobulin Light Chains / blood. Multiple Myeloma / blood. Multiple Myeloma / diagnosis. Renal Insufficiency / blood. Renal Insufficiency / diagnosis

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  • (PMID = 18808676.001).
  • [ISSN] 1471-2369
  • [Journal-full-title] BMC nephrology
  • [ISO-abbreviation] BMC Nephrol
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Immunoglobulin Light Chains
  • [Other-IDs] NLM/ PMC2564915
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29. Hanf W, Guillaume C, Jolivot A, Chapuis-Cellier C, Guebre-Egziabher F, Fontana A, Fouque D, Juillard L: Prolonged hemodialysis for acute kidney injury in myeloma patients. Clin Nephrol; 2010 Oct;74(4):319-22
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • OBJECTIVE: Cast nephropathy, due to free light chain (FLC) toxicity, is the main cause of acute kidney injury in multiple myeloma, with about 10% of patients requiring dialysis.
  • In these patients, in addition to chemotherapy that prevents FLC production, daily hemodialysis using high cutoff or adsorptive membranes, showed promising results by decreasing quickly toxic serum FLC concentrations.
  • CASE HISTORY: We report here the case of 2 patients presenting with acute kidney injury and high FLC serum concentration and M-components one with IgG Kappa and the other with IgD lambda.
  • Both were treated with bortezomib and dexamethasone and received a 24-h continuous hemodialysis using a high and sharp cutoff (around 35,000 Daltons) polysulfone membrane (ultraflux® HD 1000, Fresenius Medical Care GmbH, Bad Homburg, Germany) with citrate regional anticoagulation using a safe and dedicated device (multi filtrate Ci-Ca®).
  • CONCLUSION: Despite similar range of depuration, serum plasma FLC decreased importantly in the patient with the kappa type who recovered but was unchanged in the lambda type patient who remained under maintenance dialysis.
  • Further studies are needed to confirm this new approach therapy.
  • [MeSH-major] Acute Kidney Injury / therapy. Multiple Myeloma / complications. Renal Dialysis

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  • (PMID = 20875387.001).
  • [ISSN] 0301-0430
  • [Journal-full-title] Clinical nephrology
  • [ISO-abbreviation] Clin. Nephrol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Immunoglobulin Light Chains
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30. Kormelink TG, Tekstra J, Thurlings RM, Boumans MH, Vos K, Tak PP, Bijlsma JW, Lafeber FP, Redegeld FA, van Roon JA: Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity. Ann Rheum Dis; 2010 Dec;69(12):2137-44
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  • [Title] Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity.
  • OBJECTIVES: Immunoglobulin (Ig) free light chains (FLCs) are short-lived B cell products that contribute to inflammation in several experimental disease models.
  • In this study, FLC concentrations in inflamed joints of patients with rheumatoid arthritis (RA) as compared to patients with osteoarthritis were investigated.
  • In addition, the relationship of FLCs and disease activity upon B cell depletion (rituximab) in patients with RA was studied.
  • METHODS: Synovial fluid (SF) and tissue from patients with RA were analysed for local presence of FLCs using ELISA and immunohistochemistry.
  • In addition, FLC concentrations were measured (at baseline, 3 and 6 months after treatment) in 50 patients with RA with active disease who were treated with rituximab.
  • Changes in FLCs were correlated to changes in disease activity and compared to alterations in IgM, IgG, IgA, IgM-rheumatoid factor (RF) and IgG-anti-citrullinated protein antibody (ACPA) concentrations.
  • RESULTS: FLCs were detected in synovial tissue from patients with RA, and high FLC concentrations were found in SF from inflamed joints, which positively correlate with serum FLC concentrations.
  • Serum FLC concentrations significantly correlated with disease activity score using 28 joint counts, erythrocyte sedimentation rate (ESR) and C reactive protein, and changes in FLC correlated with clinical improvement after rituximab treatment.
  • Moreover, effect of treatment on FLC concentrations discriminated clinical responders from non-responders, whereas IgM-RF and IgG-ACPA significantly decreased in both patient groups.
  • CONCLUSIONS: FLCs are abundantly present in inflamed joints and FLC levels correlate with disease activity.
  • The correlation of FLC concentrations and disease activity indicates that FLCs may be relevant biomarkers for treatment response to rituximab in patients with RA and suggests that targeting FLC may be of importance in the therapy of RA.
  • [MeSH-major] Antibodies, Monoclonal, Murine-Derived / therapeutic use. Antirheumatic Agents / therapeutic use. Arthritis, Rheumatoid / drug therapy. Immunoglobulin Light Chains / metabolism
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antigens, CD20 / immunology. Autoantibodies / metabolism. Biomarkers / metabolism. Female. Humans. Immunoglobulins / metabolism. Male. Middle Aged. Osteoarthritis, Knee / immunology. Peptides, Cyclic / immunology. Rheumatoid Factor / metabolism. Rituximab. Synovial Membrane / immunology. Treatment Outcome. Young Adult


31. Borde JP, Link R, Offensperger WB: [kappa-light chain amyloidosis of the liver, a rare cause of liver enzyme elevation]. Dtsch Med Wochenschr; 2008 May;133(21):1116-20
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  • [Title] [kappa-light chain amyloidosis of the liver, a rare cause of liver enzyme elevation].
  • HISTORY AND ADMISSION FINDINGS: A 69-year-old man was admitted to the department of gastroenterology having for months had persistently elevated liver enzymes after discontinuing systemic antimycotic therapy.
  • INVESTIGATIONS: Congo-red staining of the liver biopsy revealed massive sinusoidal amyloidosis of the liver.
  • The free light chain (FLC) test confirmed KLC monoclonal gammopathy with an abnormal free kappa to lambda chain (KLLC) ratio.
  • TREATMENT AND COURSE: Systemic KLC amyloidosis in this patient older than 65 years was given chemotherapy with melaphalan and dexamethasone (M-Dex).
  • After three courses of M-Dex the renal clearance deteriorated and the serum N-terminal probrain natriuretic peptide (T-proBNP) had increased.
  • CONCLUSION: KLC amyloidosis is a rare cause of elevated liver enzymes.
  • The nonspecific symptoms often delay the diagnosis.
  • FLC testing is a helpful tool in identifying monoclonal gammopathies, even when immunoelectrophoretic tests are normals.
  • [MeSH-major] Amyloidosis. Immunoglobulin kappa-Chains / analysis. Liver Diseases
  • [MeSH-minor] Aged. Antineoplastic Agents / therapeutic use. Biopsy. Glucocorticoids / therapeutic use. Humans. Male. Paraproteinemias / immunology

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  • (PMID = 18478504.001).
  • [ISSN] 1439-4413
  • [Journal-full-title] Deutsche medizinische Wochenschrift (1946)
  • [ISO-abbreviation] Dtsch. Med. Wochenschr.
  • [Language] ger
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Glucocorticoids; 0 / Immunoglobulin kappa-Chains
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32. Hasegawa M, Kondo F, Yamamoto K, Murakami K, Tomita M, Nabeshima K, Nakai S, Kato M, Ohashi A, Arai J, Hiki Y, Ishii J, Emi N, Sugiyama S, Yuzawa Y: Evaluation of blood purification and bortezomib plus dexamethasone therapy for the treatment of acute renal failure due to myeloma cast nephropathy. Ther Apher Dial; 2010 Oct;14(5):451-6
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  • [Title] Evaluation of blood purification and bortezomib plus dexamethasone therapy for the treatment of acute renal failure due to myeloma cast nephropathy.
  • Aggressive removal of circulating free light chains (FLC) by blood purification accompanied by chemotherapy is a promising approach for the treatment of acute renal failure due to myeloma cast nephropathy.
  • Plasma exchange has been performed to remove serum FLC; in order to examine an alternative strategy we performed hemodiafiltration using protein-leaking dialyzers for the treatment of dialysis-dependent acute renal failure due to myeloma cast nephropathy.
  • In the first case with κ-light chain cast nephropathy, the pre-treatment serum creatinine was 9.65 mg/dL, and the serum κ-FLC was 27100 mg/L.
  • Chemotherapy was started with high-dose dexamethasone and then switched to bortezomib plus dexamethasone.
  • The mean removal rates of κ-FLC were 45.8% (one plasma volume) and 66.9% (one-and-a-half plasma volumes) by plasma exchange.
  • The removal rates of κ-FLC by hemodiafiltration (66.9%, FB210UHβ; 71.6%, PES210Dα; 75.2%, FXS220) were comparable to those by plasma exchange.
  • In the second case with λ-light chain cast nephropathy, the pre-treatment serum creatinine was 4.14 mg/dL, and the serum λ-FLC was 4140 mg/L.
  • The mean removal rates of λ-FLC were 60.2% (FXS140) and 64.2% (FB210UHβ) by hemodiafiltration.
  • The combination of an intense blood purification regimen and bortezomib plus dexamethasone therapy appears to be an efficient approach to renal recovery.
  • Hemodiafiltration using protein-leaking dialyzers could become an alternative to plasma exchange as a method of removing FLC.
  • [MeSH-major] Acute Kidney Injury / therapy. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Hemodiafiltration / methods. Plasma Exchange / methods
  • [MeSH-minor] Aged. Boronic Acids / administration & dosage. Bortezomib. Combined Modality Therapy. Dexamethasone / administration & dosage. Drug Therapy, Combination. Female. Humans. Immunoglobulin Light Chains / blood. Male. Middle Aged. Multiple Myeloma / complications. Pyrazines / administration & dosage. Treatment Outcome

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  • (PMID = 21175542.001).
  • [ISSN] 1744-9987
  • [Journal-full-title] Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy
  • [ISO-abbreviation] Ther Apher Dial
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Boronic Acids; 0 / Immunoglobulin Light Chains; 0 / Pyrazines; 69G8BD63PP / Bortezomib; 7S5I7G3JQL / Dexamethasone
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33. Machimoto T, Yasuchika K, Komori J, Ishii T, Kamo N, Shimoda M, Konishi S, Saito M, Kohno K, Uemoto S, Ikai I: Improvement of the survival rate by fetal liver cell transplantation in a mice lethal liver failure model. Transplantation; 2007 Nov 27;84(10):1233-9
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  • [Title] Improvement of the survival rate by fetal liver cell transplantation in a mice lethal liver failure model.
  • BACKGROUND: The use of cell transplantation as an alternative therapy for orthotopic liver transplantation has been widely anticipated due to a chronic donor shortage.
  • We previously reported the method used to enrich hepatic progenitor cells (HPCs) forming cell aggregations.
  • In this study, we transplanted HPCs into the liver injury model mice to determine whether HPC transplantation may improve the liver dysfunction.
  • METHODS: We obtained donor cells from E13.5 fetal livers of green fluorescent protein (GFP) transgenic mice.
  • We transplanted GFP-positive fetal liver cells into the transgenic mice which express diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter.
  • Subsequently, we induced selective liver injury to recipient mice by DT administration.
  • We then evaluated the engraftment of the transplanted cells and their effect on survivorship.
  • RESULTS: The low dose of DT induced sublethal liver injury and the high dose of DT was lethal to the liver injury model mice.
  • The transplanted GFP-positive cells were engrafted into the recipient livers and expressed albumin, resembling mature hepatocytes.
  • The survival rate at 25 days after transplantation of the cell-transplanted group (8 of 20; 40.0%) was improved significantly (P=0.0047) in comparison to that of the sham-operated group (0 of 20; 0%).
  • CONCLUSIONS: The transplanted cells were engrafted and repopulated the liver of recipient mice, resulting in the improvement of the survival rate of the liver injury model mice.
  • We therefore propose that HPCs are a desirable cell source for cell transplantation.
  • [MeSH-major] Cell Transplantation / methods. Liver / cytology. Liver / embryology. Liver Failure / therapy

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  • (PMID = 18049107.001).
  • [ISSN] 0041-1337
  • [Journal-full-title] Transplantation
  • [ISO-abbreviation] Transplantation
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Diphtheria Toxin; 0 / Hbegf protein, mouse; 0 / Heparin-binding EGF-like Growth Factor; 0 / Intercellular Signaling Peptides and Proteins; 147336-22-9 / Green Fluorescent Proteins
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34. Begum S, Joshi M, Ek M, Holgersson J, Kleman MI, Sumitran-Holgersson S: Characterization and engraftment of long-term serum-free human fetal liver cell cultures. Cytotherapy; 2010 Apr;12(2):201-11
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Characterization and engraftment of long-term serum-free human fetal liver cell cultures.
  • Fetal liver cells (FLC) are attractive candidate donor cells because of their high proliferative capacity.
  • METHODS: Using cell culture and molecular techniques, we studied the in vitro and in vivo characteristics of FLC grown long-term in serum-free conditions.
  • RESULTS: Serum-free FLC obtained from 6-10-week-old human fetal livers grew as multiple clusters in suspension and could be subcultured for at least six passages.
  • These cells maintained stable hepatocyte phenotypes and gene expression patterns in culture for up to 6 months.
  • When a cluster of these cells in various passages was placed on collagen-coated plates, they formed a monolayer and morphologically resembled hepatocytes.
  • The cells expressed alpha -fetoprotein, cytokeratin (CK) 8, CK18 and CK19 and albumin (ALB).
  • Cells at different passages, when transplanted into nude mice with liver injury, engrafted successfully, as detected by in situ hybridization using a human-specific DNA probe.
  • Colonies of human-specific CK8, CK18, c-Met nuclear antigen (Ag), mitochondrial Ag, hepatocyte-specific Ag and ALB-expressing cells were present in the livers of recipient animals.
  • CONCLUSIONS: Primary human FLC can be kept in culture consistently over a long time period and are potential candidates for cell therapy and in vitro diagnostics.
  • [MeSH-major] Cell Culture Techniques / methods. Culture Media, Serum-Free / pharmacology. Fetus / cytology. Hepatocytes / cytology. Hepatocytes / transplantation. Liver / cytology
  • [MeSH-minor] Animals. Biomarkers / metabolism. Cell Differentiation / drug effects. Cell Proliferation / drug effects. Cell Shape / drug effects. Cells, Cultured. Female. Gene Expression Regulation, Developmental / drug effects. Glass. Humans. Immunohistochemistry. Mice. Mice, Inbred C57BL. Mice, Nude. Organ Specificity / drug effects. Spheroids, Cellular / cytology. Spheroids, Cellular / drug effects. Time Factors


35. Cockwell P, Hutchison CA: Management options for cast nephropathy in multiple myeloma. Curr Opin Nephrol Hypertens; 2010 Nov;19(6):550-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • PURPOSE OF REVIEW: This article reviews the relevance of the following areas to the contemporary management of cast nephropathy in multiple myeloma: immunoassays that quantify immunoglobulin free light chain (FLC), novel chemotherapy agents and high cut-off (protein-permeable) haemodialysis, which are under evaluation in patients with cast nephropathy and multiple myeloma.
  • RECENT FINDINGS: Clonal serum FLC can be measured with high sensitivity and specificity and used to rapidly screen for cast nephropathy.
  • A sustained decrease in serum FLC levels within 3 weeks of starting treatment is associated with renal recovery; novel chemotherapy agents can maximize this early response.
  • Although plasma exchange does not produce clinical benefit, pilot studies of high cut-off haemodialysis show high efficacy for serum FLC removal.
  • A prompt diagnosis and commencement of effective chemotherapy is a critical determinant of renal recovery.
  • A randomized controlled trial of high cut-off haemodialysis in patients with cast nephropathy, who all receive bortezomib-based chemotherapy, is underway.
  • [MeSH-major] Acute Kidney Injury / therapy. Multiple Myeloma / therapy. Renal Dialysis
  • [MeSH-minor] Biomarkers / blood. Humans. Immunoassay. Immunoglobulin Light Chains / blood. Predictive Value of Tests. Treatment Outcome

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  • (PMID = 20827195.001).
  • [ISSN] 1473-6543
  • [Journal-full-title] Current opinion in nephrology and hypertension
  • [ISO-abbreviation] Curr. Opin. Nephrol. Hypertens.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Immunoglobulin Light Chains
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36. Matsuda M: [Clinical significance of measurement of free light chains]. Rinsho Byori; 2010 Apr;58(4):401-4
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Plasma cells usually produce free light chains (FLCs) together with intact immunoglobulins, irrespective of the presence of monoclonality.
  • To easily determine the concentration of FLCs in both serum and urine, a new kit using a latex-enhanced immunoassay (Freelite, Binding Site, UK) has recently become available.
  • According to original data of Binding Site, this kit can precisely show an increase in lambda- and kappa-FLCs in serum as well as abnormal kappa/lambda ratios with high-level sensitivity and specificity for multiple myeloma, including intact immunoglobulin and non-secretory types.
  • Serum FLCs well reflect the disease activity of multiple myeloma, and apparently decrease after chemotherapy.
  • We investigated serum FLCs using this kit in another monoclonal plasma cell disorder, primary systemic AL amyloidosis.
  • Almost all patients showed increases in either lambda- or kappa-FLCs as well as abnormal kappa/lambda ratios, as seen in multiple myeloma.
  • Their prognosis was very poor when the kappa/lambda ratio remained abnormal even after intensive chemotherapy.
  • Serum FLCs may be a useful marker on making a diagnosis, but also in evaluating the clinical efficacy of chemotherapy in monoclonal plasma cell disorders, such as multiple myeloma and primary systemic AL amyloidosis.
  • [MeSH-major] Amyloidosis / diagnosis. Immunoglobulin Light Chains / blood. Multiple Myeloma / diagnosis

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  • (PMID = 20496770.001).
  • [ISSN] 0047-1860
  • [Journal-full-title] Rinsho byori. The Japanese journal of clinical pathology
  • [ISO-abbreviation] Rinsho Byori
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Immunoglobulin Light Chains; 0 / Latex; 0 / Reagent Kits, Diagnostic
  • [Number-of-references] 0
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37. Patt YZ, Hassan MM, Lozano RD, Brown TD, Vauthey JN, Curley SA, Ellis LM: Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma. J Clin Oncol; 2003 Feb 1;21(3):421-7
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  • [Title] Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma.
  • PURPOSE: Because cirrhosis is extremely common in hepatocellular carcinoma (HCC) in the United States, and it precludes the use of several chemotherapy agents, this phase II trial of fluorouracil (FU) and recombinant interferon alfa-2b (rIFNalpha2b) in HCC was launched with the assumption that it could be tolerated by cirrhotics.
  • PATIENTS AND METHODS: Forty-three patients with HCC (34), and fibrolamellar HCC (FLHCC;.
  • nine) were treated with continuous intravenous (IV) FU (200 mg/m2/d x 21 every 28 days) and subcutaneous (SC) rIFNalpha2b (4 million U/m2) three times weekly.
  • Liver cirrhosis was present among 71% of HCC patients but among none of the FLHCC patients.
  • Four HCC patients underwent resection, and two had a histologic CR; one HCC patient with a PR underwent orthotopic liver transplantation.
  • CONCLUSION: Continuous IV FU and thrice-weekly SC rIFNalpha2b are an effective treatment, especially for FLHCC, and may have a neoadjuvant role in this disease.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Hepatocellular / drug therapy. Liver Cirrhosis / complications. Liver Neoplasms / drug therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Drug Administration Schedule. Female. Fluorouracil / administration & dosage. Humans. Infusions, Intravenous. Injections, Subcutaneous. Interferon-alpha / administration & dosage. Liver Transplantation. Male. Middle Aged. Neoadjuvant Therapy. Recombinant Proteins. Survival Analysis

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  • (PMID = 12560429.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Interferon-alpha; 0 / Recombinant Proteins; 99210-65-8 / interferon alfa-2b; U3P01618RT / Fluorouracil
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38. Kühnemund A, Liebisch P, Bauchmüller K, zur Hausen A, Veelken H, Wäsch R, Engelhardt M: 'Light-chain escape-multiple myeloma'-an escape phenomenon from plateau phase: report of the largest patient series using LC-monitoring. J Cancer Res Clin Oncol; 2009 Mar;135(3):477-84
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  • PURPOSE: More intensive and novel therapy options in multiple myeloma (MM) hold the promise to improve treatment outcome.
  • However, disease evolution, induced with long disease duration and extensive pretreatment, has resulted in changes in the biological behaviour of MM and unusual relapse emergence, such as of extramedullary (EM) disease or a shift in secretion from intact immunoglobulin (Ig) to free-light chains (FLCs) only.
  • METHODS: We studied ten patients since 2004, thoroughly assessed relevant patient characteristics, prominent similarities, SFLC-changes, therapy response, mode and speed of progression, and the incidence of light-chain escape (LCE)-MM within our entire myeloma patient cohort.
  • Serum FLCs (SFLCs) were determined via Freelite-assay (Dade-Behringer Nephelometer).
  • RESULTS: This report summarizes the to date largest series of ten patients, whose MM appeared stable, as judged by conventional monitoring of intact Ig levels, but developed severe organ dysfunction as a consequence of initially undetected LC-progression.
  • Median number of anti-MM cycles before LCE occurrence was six, including autologous and/or allogeneic stem cell transplants and novel drugs, predominantly thalidomide, in 4/10.
  • CONCLUSIONS: Our report suggests that early detection of LCE-MM by means of serial SFLC measurements may prevent unnecessary complications, allows to detect unusual relapse manifestations in the era of intensive and biological therapy options and possibly also permits to improve treatment results in LCE-MM.
  • [MeSH-major] Immunoglobulin Light Chains / immunology. Multiple Myeloma / drug therapy. Multiple Myeloma / immunology

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  • (PMID = 18802723.001).
  • [ISSN] 1432-1335
  • [Journal-full-title] Journal of cancer research and clinical oncology
  • [ISO-abbreviation] J. Cancer Res. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Immunoglobulin A; 0 / Immunoglobulin G; 0 / Immunoglobulin Light Chains; 0 / Immunoglobulin kappa-Chains; 0 / Immunoglobulin lambda-Chains
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39. Spreghini E, Maida CM, Tomassetti S, Orlando F, Giannini D, Milici ME, Scalise G, Barchiesi F: Posaconazole against Candida glabrata isolates with various susceptibilities to fluconazole. Antimicrob Agents Chemother; 2008 Jun;52(6):1929-33
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  • We investigated the in vitro activities of posaconazole (POS), fluconazole (FLC), amphotericin B (AMB), and caspofungin (CAS) against four clinical isolates of Candida glabrata with various susceptibilities to FLC (FLC MICs ranging from 1.0 to >64 microg/ml).
  • When FLC MICs increased, so did POS MICs, although we did not observe any isolate with a POS MIC greater than 0.5 mug/ml.
  • Time-kill experiments showed that POS, FLC, and CAS were fungistatic against all isolates, while AMB at eight times the MIC was fungicidal against three out of four isolates of C. glabrata tested.
  • Then, we investigated the activity of POS in an experimental model of disseminated candidiasis using three different isolates of C. glabrata: one susceptible to FLC (S; FLC MICs ranging from 1.0 to 4.0 microg/ml; POS MIC of < or =0.03 microg/ml), one susceptible in a dose-dependent manner (SDD; FLC MICs ranging from 32 to 64 microg/ml; POS MICs ranging from 0.125 to 0.25 microg/ml), and another one resistant to FLC (R; FLC MIC of >64 microg/ml; POS MIC of 0.5 microg/ml).
  • FLC significantly reduced the kidney burden of mice infected with the S strain (P = 0.0070) but not of those infected with the S-DD and R strains.
  • Additionally, the new triazole may be a therapeutic option in those cases where an FLC-resistant isolate is found to retain a relatively low POS MIC.
  • [MeSH-major] Antifungal Agents / pharmacology. Antifungal Agents / therapeutic use. Candida glabrata / drug effects. Candidiasis / drug therapy. Drug Resistance, Fungal. Fluconazole / pharmacology. Triazoles / pharmacology. Triazoles / therapeutic use
  • [MeSH-minor] Animals. Humans. Kidney / microbiology. Male. Mice. Microbial Sensitivity Tests. Treatment Outcome


40. Shen H, An MM, Wang de J, Xu Z, Zhang JD, Gao PH, Cao YY, Cao YB, Jiang YY: Fcr1p inhibits development of fluconazole resistance in Candida albicans by abolishing CDR1 induction. Biol Pharm Bull; 2007 Jan;30(1):68-73
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  • Overexpression of Candida drug resistance 1 (CDR1) gene in Candida albicans (C. albicans), an efflux pump, is one of the major mechanisms contributing to drug resistance. C. albicans for fluconazole resistance 1 protein (Fcr1p) is a member of the family of zinc cluster proteins homologous to Pdr1p and Pdr3p (pleiotropic drug resistance protein) mediating azole resistance in Saccharomyces cerevisiae (S. cerevisiae) by regulating the expression of pleiotropic drug resistance 5 (PDR5) homologous to C. albicans CDR1.
  • Our results showed that Fcr1p inhibited fluconazole (FLC) resistance development in C. albicans through abolishing the induction of CDR1 expression by FLC, and in contrast FLC resistance development was accelerated resulting from the deletion of FCR1.
  • [MeSH-major] Antifungal Agents / pharmacology. Candida albicans / drug effects. Drug Resistance, Fungal. Fluconazole / pharmacology. Fungal Proteins / metabolism. Gene Expression Regulation, Fungal / drug effects. Membrane Transport Proteins / metabolism. Metalloproteins / metabolism
  • [MeSH-minor] Animals. Candidiasis / drug therapy. Candidiasis / microbiology. Female. Fluorescent Dyes / metabolism. Kidney / drug effects. Kidney / microbiology. Mice. Mice, Inbred BALB C. Microbial Sensitivity Tests. Mutation. RNA, Messenger / metabolism. Rhodamines / metabolism. Time Factors

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  • (PMID = 17202662.001).
  • [ISSN] 0918-6158
  • [Journal-full-title] Biological & pharmaceutical bulletin
  • [ISO-abbreviation] Biol. Pharm. Bull.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / CDR1 protein, Candida albicans; 0 / Fluorescent Dyes; 0 / Fungal Proteins; 0 / Membrane Transport Proteins; 0 / Metalloproteins; 0 / RNA, Messenger; 0 / Rhodamines; 8VZV102JFY / Fluconazole; 989-38-8 / rhodamine 6G
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41. Serena C, Pastor FJ, Gilgado F, Mayayo E, Guarro J: Efficacy of micafungin in combination with other drugs in a murine model of disseminated trichosporonosis. Antimicrob Agents Chemother; 2005 Feb;49(2):497-502
Hazardous Substances Data Bank. FLUCONAZOLE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Efficacy of micafungin in combination with other drugs in a murine model of disseminated trichosporonosis.
  • Using a murine model of disseminated infection caused by Trichosporon asahii, we have evaluated the efficacies of amphotericin B (AMB; 1 mg/kg of body weight/day), fluconazole (FLC; 20 mg/kg/twice a day), and micafungin (MFG; 5 mg/kg/twice a day).
  • We tested these drugs alone and in combination (MFG with AMB and MFG with FLC).
  • The combination MFG with FLC was able to reduce significantly the kidney fungal burden in comparison to that achieved with either drug administered alone.
  • [MeSH-major] Antifungal Agents / therapeutic use. Lipoproteins / therapeutic use. Mycoses / drug therapy. Peptides, Cyclic / therapeutic use. Trichosporon
  • [MeSH-minor] Amphotericin B / therapeutic use. Animals. Colony Count, Microbial. Cyclophosphamide / pharmacology. Drug Therapy, Combination. Echinocandins. Fluconazole / therapeutic use. Immunosuppressive Agents / pharmacology. Kidney / microbiology. Lipopeptides. Male. Mice

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  • (PMID = 15673724.001).
  • [ISSN] 0066-4804
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Echinocandins; 0 / Immunosuppressive Agents; 0 / Lipopeptides; 0 / Lipoproteins; 0 / Peptides, Cyclic; 7XU7A7DROE / Amphotericin B; 8N3DW7272P / Cyclophosphamide; 8VZV102JFY / Fluconazole; R10H71BSWG / micafungin
  • [Other-IDs] NLM/ PMC547367
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42. Gate L, Couvreur P, Nguyen-Ba G, Tapiero H: N-methylation of anthracyclines modulates their cytotoxicity and pharmacokinetic in wild type and multidrug resistant cells. Biomed Pharmacother; 2003 Sep;57(7):301-8

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] N-methylation of anthracyclines modulates their cytotoxicity and pharmacokinetic in wild type and multidrug resistant cells.
  • Anthracyclines are the most commonly used classes of anticancer agents in chemotherapy.
  • Development of resistance to these molecules is one of the major reasons for treatment failure.
  • This pump, which is responsible for the multidrug resistance (MDR) phenotype, decreases the toxicity of a wide range of unrelated anticancer drugs by increasing their cellular efflux.
  • In sensitive cells (FLC), reduced cytotoxicity was related to the level of N-methylation; whereas in resistant cells (DOX-RFLC(1) and DOX-RFLC(2)) overexpressing different levels of P-gp, increased N-methylation enhanced anthracycline cytotoxicity.
  • Decreased resistance in DOX-RFLCs was associated with an increased drug accumulation due to a reduced cellular efflux.
  • These results suggest that N-methylation of anthracyclines circumvents resistance by diminishing drug transport by P-gp in MDR-positive cells.
  • [MeSH-major] Anthracyclines / chemistry. Anthracyclines / pharmacokinetics. Antineoplastic Agents / chemistry. Antineoplastic Agents / pharmacokinetics. Leukemia, Erythroblastic, Acute / metabolism
  • [MeSH-minor] Animals. Biological Transport. Cell Division / drug effects. Cell Survival / drug effects. Drug Resistance, Multiple. Drug Resistance, Neoplasm. Methylation. Mice. Multidrug Resistance-Associated Proteins / biosynthesis. P-Glycoprotein / biosynthesis. Structure-Activity Relationship. Tumor Cells, Cultured

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  • (PMID = 14499178.001).
  • [ISSN] 0753-3322
  • [Journal-full-title] Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie
  • [ISO-abbreviation] Biomed. Pharmacother.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Anthracyclines; 0 / Antineoplastic Agents; 0 / Multidrug Resistance-Associated Proteins; 0 / P-Glycoprotein
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43. Mansfield BE, Oltean HN, Oliver BG, Hoot SJ, Leyde SE, Hedstrom L, White TC: Azole drugs are imported by facilitated diffusion in Candida albicans and other pathogenic fungi. PLoS Pathog; 2010 Sep 30;6(9):e1001126
Hazardous Substances Data Bank. FLUCONAZOLE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Azole drugs are imported by facilitated diffusion in Candida albicans and other pathogenic fungi.
  • Despite the wealth of knowledge regarding the mechanisms of action and the mechanisms of resistance to azole antifungals, very little is known about how the azoles are imported into pathogenic fungal cells.
  • Here the in-vitro accumulation and import of Fluconazole (FLC) was examined in the pathogenic fungus, Candida albicans.
  • In energized cells, FLC accumulation correlates inversely with expression of ATP-dependent efflux pumps.
  • In de-energized cells, all strains accumulate FLC, suggesting that FLC import is not ATP-dependent.
  • The kinetics of import in de-energized cells displays saturation kinetics with a K(m) of 0.64 μM and V(max) of 0.0056 pmol/min/10⁸ cells, demonstrating that FLC import proceeds via facilitated diffusion through a transporter rather than passive diffusion.
  • Other azoles inhibit FLC import on a mole/mole basis, suggesting that all azoles utilize the same facilitated diffusion mechanism.
  • Import of FLC by facilitated diffusion is observed in other fungi, including Cryptococcus neoformans, Saccharomyces cerevisiae, and Candida krusei, indicating that the mechanism of transport is conserved among fungal species.
  • FLC import was shown to vary among Candida albicans resistant clinical isolates, suggesting that altered facilitated diffusion may be a previously uncharacterized mechanism of resistance to azole drugs.

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  • (PMID = 20941354.001).
  • [ISSN] 1553-7374
  • [Journal-full-title] PLoS pathogens
  • [ISO-abbreviation] PLoS Pathog.
  • [Language] ENG
  • [Grant] United States / NIDCR NIH HHS / DE / DE14161; United States / NIDCR NIH HHS / DE / DE17078; United States / NIDCR NIH HHS / DE / R01 DE017078; United States / NIDCR NIH HHS / DE / DE11367; United States / NIDCR NIH HHS / DE / R01 DE011367; United States / NIDCR NIH HHS / DE / R01 DE014161
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 8VZV102JFY / Fluconazole; S88TT14065 / Oxygen
  • [Other-IDs] NLM/ PMC2947996
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44. Kawano Y, Nakama T, Hata H, Kimura E, Maruyoshi N, Uchino M, Mitsuya H: Successful treatment with rituximab and thalidomide of POEMS syndrome associated with Waldenstrom macroglobulinemia. J Neurol Sci; 2010 Oct 15;297(1-2):101-4
Hazardous Substances Data Bank. THALIDOMIDE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Successful treatment with rituximab and thalidomide of POEMS syndrome associated with Waldenstrom macroglobulinemia.
  • A POEMS syndrome is a rare disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin abnormalities including hyperpigmentation and hypertrichosis.
  • Here we report a 55-year-old female case of a POEMS syndrome associated with Waldenstrom macroglobulinemia.
  • The patient had bed-bound polyneuropathy, splenomegaly, IgM-λ type monoclonal (M) protein, elevated λ-type free light chain (FLC), infiltration of CD20-positive lymphoplasmacytic cells in bone marrow, edema and hypertrichosis, and was diagnosed to have an 'atypical' POEMS syndrome associated with macroglobulinemia.
  • By eight weeks of the treatment, the ambulation activity of the patient was restored and her polyneuropathy completely disappeared as determined by clinical symptoms and electrophysiological examinations.
  • [MeSH-major] Antibodies, Monoclonal, Murine-Derived / therapeutic use. Immunologic Factors / therapeutic use. POEMS Syndrome / drug therapy. Thalidomide / therapeutic use. Waldenstrom Macroglobulinemia / drug therapy
  • [MeSH-minor] Female. Humans. Lymphocytes / drug effects. Middle Aged. Neural Conduction / drug effects. Rituximab

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  • [Copyright] Copyright 2010 Elsevier B.V. All rights reserved.
  • (PMID = 20673674.001).
  • [ISSN] 1878-5883
  • [Journal-full-title] Journal of the neurological sciences
  • [ISO-abbreviation] J. Neurol. Sci.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Immunologic Factors; 4F4X42SYQ6 / Rituximab; 4Z8R6ORS6L / Thalidomide
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45. Guo XL, Leng P, Yang Y, Yu LG, Lou HX: Plagiochin E, a botanic-derived phenolic compound, reverses fungal resistance to fluconazole relating to the efflux pump. J Appl Microbiol; 2008 Mar;104(3):831-8
Hazardous Substances Data Bank. FLUCONAZOLE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • AIM: In this study, we investigated the effect of plagiochin E (PLE), a botanic-derived phenolic natural product, on reversal of fungal resistance to fluconazole (FLC) in vitro and the related mechanism.
  • METHODS AND RESULTS: A synergistic action of PLE and FLC was observed in the FLC-resistant Candida albicans strains and was evaluated using the fractional inhibited concentration index.
  • The effect of PLE on FLC intracellular uptake was investigated in FLC-resistant C. albicans cells by liquid chromatography-tandem mass spectrometry, and the effect on efflux drug pump was assessed by measuring the efflux of Rhodamine 123 (Rh123).
  • PLE significantly inhibited the efflux, but not the absorption, of Rh123 in FLC-resistant strains in phosphate-buffered saline with 5% glucose.
  • Overexpression of the multidrug-resistance gene CDR1 in FLC-resistant C. albicans isolates was detected, and the introduction of PLE to the cells showed a significant reduction of the CDR1 expression in those FLC-resistant isolates.
  • CONCLUSIONS: These findings indicate that PLE could reverse the fungal resistant to FLC by inhibiting the efflux of FLC from C. albicans, and this effect may be related to the efflux pump.
  • SIGNIFICANCE AND IMPACT OF THE STUDY: These results indicate that the combination of PLE and FLC may provide an approach for the clinical therapy of fungus infection induced by FLC-resistant strains.
  • [MeSH-major] Candida albicans / drug effects. Candidiasis / drug therapy. Drug Resistance, Fungal / drug effects. Fluconazole / therapeutic use. Phenols / therapeutic use. Phytotherapy
  • [MeSH-minor] Antifungal Agents. Biological Transport. Combined Modality Therapy. Gene Expression. Genes, Fungal. Genes, MDR. Rhodamine 123

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  • (PMID = 18194250.001).
  • [ISSN] 1365-2672
  • [Journal-full-title] Journal of applied microbiology
  • [ISO-abbreviation] J. Appl. Microbiol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Phenols; 1N3CZ14C5O / Rhodamine 123; 8VZV102JFY / Fluconazole
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46. Marchetti O, Moreillon P, Entenza JM, Vouillamoz J, Glauser MP, Bille J, Sanglard D: Fungicidal synergism of fluconazole and cyclosporine in Candida albicans is not dependent on multidrug efflux transporters encoded by the CDR1, CDR2, CaMDR1, and FLU1 genes. Antimicrob Agents Chemother; 2003 May;47(5):1565-70
Hazardous Substances Data Bank. FLUCONAZOLE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • The combination of fluconazole (FLC) and cyclosporine (CY) is fungicidal in FLC-susceptible C. albicans (O.
  • The hypothesis that CY might inhibit FLC efflux was investigated by comparing the effect of FLC-CY in FLC-susceptible parent CAF2-1 (FLC MIC, 0.25 mg/liter) and in FLC-hypersusceptible mutant DSY1024 (FLC MIC, 0.03 mg/liter), in which the CDR1, CDR2, CaMDR1, and FLU1 transporter genes have been selectively deleted.
  • We postulated that a loss of the fungicidal effect of FLC-CY in DSY1024 would confirm the roles of these efflux pumps.
  • Time-kill curve studies showed a more potent fungistatic effect of FLC (P = 0.05 at 48 h with an inoculum of 10(3) CFU/ml) and a more rapid fungicidal effect of FLC-CY (P = 0.05 at 24 h with an inoculum of 10(3) CFU/ml) in the FLC-hypersusceptible mutant compared to those in the parent.
  • Rats with experimental endocarditis were treated for 2 or 5 days with high-dose FLC, high-dose CY, or both drugs combined.
  • FLC monotherapy for 5 days was more effective against the hypersusceptible mutant than against the parent.
  • However, the addition of CY to FLC still conferred a therapeutic advantage in animals infected with mutant DSY1024, as indicated by better survival (P = 0.04 versus the results obtained with FLC) and sterilization of valves and kidneys after a very short (2-day) treatment (P = 0.009 and 0.002, respectively, versus the results obtained with FLC).
  • Both in vitro and in vivo experiments consistently showed that the deletion of the four membrane transporters in DSY1024 did not result in loss of the fungicidal effect of FLC-CY.
  • Yet, the accelerated killing in the mutant suggested a "dual-hit" mechanism involving FLC hypersusceptibility due to the efflux pump elimination and fungicidal activity conferred by CY.
  • Thus, inhibition of multidrug efflux transporters encoded by CDR1, CDR2, CaMDR1, and FLU1 genes is not responsible for the fungicidal synergism of FLC-CY.
  • [MeSH-major] ATP-Binding Cassette Transporters / genetics. ATP-Binding Cassette, Sub-Family B, Member 1 / genetics. Antifungal Agents / pharmacology. Candida albicans / drug effects. Cyclosporine / pharmacology. Drug Resistance, Multiple / genetics. Fluconazole / pharmacology. Fungal Proteins / genetics. Membrane Transport Proteins / genetics
  • [MeSH-minor] Drug Synergism. Drug Therapy, Combination. Endocarditis / drug therapy

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  • (PMID = 12709323.001).
  • [ISSN] 0066-4804
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / ATP-Binding Cassette Transporters; 0 / ATP-Binding Cassette, Sub-Family B, Member 1; 0 / Antifungal Agents; 0 / CDR1 protein, Candida albicans; 0 / FLU1 protein, Candida albicans; 0 / Fungal Proteins; 0 / Membrane Transport Proteins; 83HN0GTJ6D / Cyclosporine; 8VZV102JFY / Fluconazole
  • [Other-IDs] NLM/ PMC153326
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47. Shieh JS, Chang LW, Wang MS, Sun WZ, Wang YP, Yang YP: Pain model and fuzzy logic patient-controlled analgesia in shock-wave lithotripsy. Med Biol Eng Comput; 2002 Jan;40(1):128-36
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Pain control in conscious patients was investigated using a push-button, demand-driven supply of drugs.
  • A fuzzy logic patient-controlled analgesia (PCA) algorithm was compared with a conventional algorithm, for alfentanil administration in extracorporeal shock-wave lithotripsy.
  • The conventional PCA algorithm used an initial dose of 0.25mg, a fixed infusion rate of 60 mg h(-1) and a fixed bolus size of 0.2 mg with a 1 min lockout.
  • Twelve patients were treated using conventional PCA, and thirteen were treated with PCA + fuzzy logic control (FLC).
  • PCA + FLC patients consumed 45% less drug.
  • Also, PCA + FLC patients had a mean delivery/demand ratio of 82%, compared with 60% in conventional PCA.
  • When the pain intensity scale was analysed, PCA + FLC patients had acceptable pain intensity at 62%, compared with 44% in conventional PCA.
  • [MeSH-major] Analgesia, Patient-Controlled / methods. Fuzzy Logic. Kidney Calculi / therapy. Lithotripsy
  • [MeSH-minor] Adult. Aged. Alfentanil / administration & dosage. Algorithms. Analgesics, Opioid / administration & dosage. Drug Administration Schedule. Female. Humans. Male. Middle Aged

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  • (PMID = 11954700.001).
  • [ISSN] 0140-0118
  • [Journal-full-title] Medical & biological engineering & computing
  • [ISO-abbreviation] Med Biol Eng Comput
  • [Language] eng
  • [Publication-type] Clinical Trial; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Analgesics, Opioid; 1N74HM2BS7 / Alfentanil
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48. Louie A, Kaw P, Banerjee P, Liu W, Chen G, Miller MH: Impact of the order of initiation of fluconazole and amphotericin B in sequential or combination therapy on killing of Candida albicans in vitro and in a rabbit model of endocarditis and pyelonephritis. Antimicrob Agents Chemother; 2001 Feb;45(2):485-94
Hazardous Substances Data Bank. FLUCONAZOLE .

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  • [Title] Impact of the order of initiation of fluconazole and amphotericin B in sequential or combination therapy on killing of Candida albicans in vitro and in a rabbit model of endocarditis and pyelonephritis.
  • In vitro time-kill studies and a rabbit model of endocarditis and pyelonephritis were used to define the impact that the order of exposure of Candida albicans to fluconazole (FLC) and amphotericin B (AMB), as sequential and combination therapies, had on the susceptibility of C. albicans to AMB and on the outcome.
  • The contribution of FLC-induced resistance to AMB for C. albicans also was assessed.
  • In vitro, AMB monotherapy rapidly killed each of four C. albicans strains; FLC alone was fungistatic.
  • Preincubation of these fungi with FLC for 18 h prior to exposure to AMB decreased their susceptibilities to AMB for 8 to >40 h.
  • Induced resistance to AMB was transient, but the duration of resistance increased with the length of FLC preincubation.
  • Yeast sequentially incubated with FLC followed by AMB plus FLC (FLC-->AMB+FLC) showed fungistatic growth kinetics similar to that of fungi that were exposed to FLC alone.
  • Simultaneous exposure of C. albicans to AMB and FLC [AMB+FLC(simult)] demonstrated activity similar to that with AMB alone for AMB concentrations of > or =1 microg/ml; antagonism was seen using an AMB concentration of 0.5 microg/ml.
  • In vivo, AMB monotherapy and treatment with AMB for 24 h followed by AMB plus FLC (AMB-->AMB+FLC) rapidly sterilized kidneys and cardiac vegetations.
  • AMB+FLC(simult) and FLC-->AMB treatments were slower in clearing fungi from infected tissues.
  • FLC monotherapy and FLC-->AMB+FLC were both fungistatic and were the least active regimens.
  • No adverse interaction was observed between AMB and FLC for the AMB-->FLC regimen.
  • However, FLC-->AMB treatment was slower than AMB alone in clearing fungi from tissues.
  • Thus, our in vitro and in vivo studies both demonstrate that preexposure of C. albicans to FLC reduces fungal susceptibility to AMB.
  • The length of FLC preexposure and whether AMB is subsequently used alone or in combination with FLC determine the duration of induced resistance to AMB.
  • [MeSH-major] Amphotericin B / therapeutic use. Antifungal Agents / therapeutic use. Candida albicans / drug effects. Endocarditis / microbiology. Fluconazole / therapeutic use. Pyelonephritis / microbiology
  • [MeSH-minor] Animals. Area Under Curve. Heart / microbiology. Kidney / microbiology. Kidney Function Tests. Male. Microbial Sensitivity Tests. Rabbits. Time Factors

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  • (PMID = 11158745.001).
  • [ISSN] 0066-4804
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 7XU7A7DROE / Amphotericin B; 8VZV102JFY / Fluconazole
  • [Other-IDs] NLM/ PMC90317
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49. Basnayake K, Cheung CK, Sheaff M, Fuggle W, Kamel D, Nakoinz S, Hutchison CA, Cook M, Stoves J, Bradwell AR, Cockwell P: Differential progression of renal scarring and determinants of late renal recovery in sustained dialysis dependent acute kidney injury secondary to myeloma kidney. J Clin Pathol; 2010 Oct;63(10):884-7
NCI CPTAC Assay Portal. NCI CPTAC Assay Portal .

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  • Renal biopsy typically shows cast formation, direct tubular injury and interstitial inflammation caused by nephrotoxic monoclonal free light chains (FLC).
  • Treatment consisted of chemotherapy and high cut-off dialysis to maximise extracorporeal removal of FLC and reduce renal toxicity.
  • All four patients remained dialysis dependent at 6 weeks, at which time they underwent a further biopsy.
  • Six-week biopsies showed differential changes in chronic damage from no progression, to accelerated progression of scarring from 10% to 42%, despite a rapid and sustained fall in FLC in all patients.
  • CONCLUSIONS: Some FLC clones can promote rapid renal scarring.
  • Early diagnosis and treatment may prove crucial in determining renal recovery.
  • Patients who have not recovered renal function after a period of treatment may be usefully reassessed by repeat biopsy for quantitative analysis of chronic damage and cast numbers.

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  • (PMID = 20876319.001).
  • [ISSN] 1472-4146
  • [Journal-full-title] Journal of clinical pathology
  • [ISO-abbreviation] J. Clin. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
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50. Campbell KJ, Bath ML, Turner ML, Vandenberg CJ, Bouillet P, Metcalf D, Scott CL, Cory S: Elevated Mcl-1 perturbs lymphopoiesis, promotes transformation of hematopoietic stem/progenitor cells, and enhances drug resistance. Blood; 2010 Oct 28;116(17):3197-207
The Lens. Cited by Patents in .

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  • [Title] Elevated Mcl-1 perturbs lymphopoiesis, promotes transformation of hematopoietic stem/progenitor cells, and enhances drug resistance.
  • Their lymphoid and myeloid cells displayed increased resistance to a variety of cytotoxic agents.
  • Myelopoiesis was relatively normal, but lymphopoiesis was clearly perturbed, with excess mature B and T cells accumulating.
  • Rather than the follicular lymphomas typical of vavP-BCL-2 mice, aging vavP-Mcl-1 mice were primarily susceptible to lymphomas having the phenotype of a stem/progenitor cell (11 of 30 tumors) or pre-B cell (12 of 30 tumors).
  • Most vavP-Mcl-1/ Eμ-Myc mice died around birth, and transplantation of blood from bitransgenic E18 embryos into unirradiated mice resulted in stem/progenitor cell tumors.
  • Furthermore, lethally irradiated mice transplanted with E13 fetal liver cells from Mcl-1/Myc bitransgenic mice uniformly died of stem/progenitor cell tumors.
  • Collectively, these results demonstrate that Mcl-1 overexpression renders hematopoietic cells refractory to many cytotoxic insults, perturbs lymphopoiesis and promotes malignant transformation of hematopoietic stem and progenitor cells.

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  • (PMID = 20631380.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA043540; United States / NCI NIH HHS / CA / R01 CA043540-22; United States / NCI NIH HHS / CA / CA43540
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Apoptosis Regulatory Proteins; 0 / Bcl-2-like protein 11; 0 / Mcl1 protein, mouse; 0 / Membrane Proteins; 0 / Myc protein, mouse; 0 / Myeloid Cell Leukemia Sequence 1 Protein; 0 / Proto-Oncogene Proteins; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / Proto-Oncogene Proteins c-myc; 8N3DW7272P / Cyclophosphamide
  • [Other-IDs] NLM/ PMC2995351
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51. González GM, Robledo E, Garza-González E, Elizondo M, González JG: Efficacy of albaconazole against Candida albicans in a vaginitis model. Antimicrob Agents Chemother; 2009 Oct;53(10):4540-1
Hazardous Substances Data Bank. FLUCONAZOLE .

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  • Both ABC and fluconazole (FLC) were effective in reducing the fungal load from vaginas of infected mice; however, ABC demonstrated encouraging activities against an FLC-resistant strain, with trends toward superiority over FLC in some treatment groups.
  • [MeSH-major] Antifungal Agents / pharmacology. Antifungal Agents / therapeutic use. Candida albicans / drug effects. Quinazolines / pharmacology. Quinazolines / therapeutic use. Triazoles / pharmacology. Triazoles / therapeutic use. Vaginitis / drug therapy
  • [MeSH-minor] Administration, Oral. Animals. Female. Fluconazole / pharmacology. Fluconazole / therapeutic use. Mice. Mice, Inbred BALB C

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  • (PMID = 19635949.001).
  • [ISSN] 1098-6596
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Quinazolines; 0 / Triazoles; 0 / albaconazole; 8VZV102JFY / Fluconazole
  • [Other-IDs] NLM/ PMC2764185
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52. Wüst S, van den Brandt J, Tischner D, Kleiman A, Tuckermann JP, Gold R, Lühder F, Reichardt HM: Peripheral T cells are the therapeutic targets of glucocorticoids in experimental autoimmune encephalomyelitis. J Immunol; 2008 Jun 15;180(12):8434-43
Mouse Genome Informatics (MGI). Mouse Genome Informatics (MGI) .

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  • [Title] Peripheral T cells are the therapeutic targets of glucocorticoids in experimental autoimmune encephalomyelitis.
  • High-dose glucocorticoid (GC) therapy is widely used to treat multiple sclerosis (MS), but the underlying mechanisms remain debatable.
  • Heterozygous GR knockout mice were less sensitive to dexamethasone therapy, indicating that the expression level of the receptor determines therapeutic efficacy.
  • Mice reconstituted with homozygous GR knockout fetal liver cells showed an earlier onset of the disease and were largely refractory to GC treatment, indicating that the GR in hematopoietic cells is essential for the beneficial effects of endogenous GCs and dexamethasone.
  • Using cell-type specific GR-deficient mice, we could demonstrate that GCs mainly act on T cells, while modulation of macrophage function was largely dispensable in this context.
  • The therapeutic effects were achieved through induction of apoptosis and down-regulation of cell adhesion molecules in peripheral T(H)17 and bystander T cells, while similar effects were not observed within the spinal cord.
  • In addition, dexamethasone inhibited T cell migration into the CNS, confirming that peripheral but not CNS-residing T lymphocytes are the essential targets of GCs.
  • [MeSH-major] Dexamethasone / therapeutic use. Drug Delivery Systems. Encephalomyelitis, Autoimmune, Experimental / drug therapy. Encephalomyelitis, Autoimmune, Experimental / immunology. T-Lymphocyte Subsets / drug effects. T-Lymphocyte Subsets / immunology
  • [MeSH-minor] Animals. Apoptosis / genetics. Apoptosis / immunology. Blood-Brain Barrier / drug effects. Blood-Brain Barrier / immunology. Cell Movement / drug effects. Cell Movement / immunology. Down-Regulation / drug effects. Down-Regulation / genetics. Down-Regulation / immunology. Female. Glycoproteins / administration & dosage. Glycoproteins / immunology. Intercellular Signaling Peptides and Proteins / biosynthesis. Intercellular Signaling Peptides and Proteins / deficiency. Intercellular Signaling Peptides and Proteins / genetics. Leukocytes / drug effects. Leukocytes / immunology. Leukocytes / pathology. Mice. Mice, Inbred C57BL. Mice, Knockout. Mice, Transgenic. Myelin-Oligodendrocyte Glycoprotein. Peptide Fragments / administration & dosage. Peptide Fragments / immunology. Receptors, Glucocorticoid / deficiency. Receptors, Glucocorticoid / genetics. Receptors, Glucocorticoid / physiology. T-Lymphocytes, Regulatory / drug effects

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  • (PMID = 18523311.001).
  • [ISSN] 0022-1767
  • [Journal-full-title] Journal of immunology (Baltimore, Md. : 1950)
  • [ISO-abbreviation] J. Immunol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Glycoproteins; 0 / Grn protein, mouse; 0 / Intercellular Signaling Peptides and Proteins; 0 / Myelin-Oligodendrocyte Glycoprotein; 0 / Peptide Fragments; 0 / Receptors, Glucocorticoid; 0 / dexamethasone receptor; 0 / myelin oligodendrocyte glycoprotein (35-55); 7S5I7G3JQL / Dexamethasone
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53. Biziuleviciene G, Puidokaite G, Siaurys A, Mauricas M: An anti-inflammatory effect of murine fetal liver cells in BALB/c mouse contact hypersensitivity model. Int Immunopharmacol; 2007 Jun;7(6):744-9
Hazardous Substances Data Bank. 1-FLUORO-2,4-DINITROBENZENE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] An anti-inflammatory effect of murine fetal liver cells in BALB/c mouse contact hypersensitivity model.
  • Anti-inflammatory effects of murine fetal liver (FL) cells were studied using BALB/c mouse contact hypersensitivity (paw edema) model.
  • Immunophenotyping revealed that both murine FL homogenate cells (HC) and FL hematopoietic stem cells (HSC) express CD117 and CD38 surface markers.
  • Single doses of 1x10(6) cells/mouse and 2x10(6) cells/mouse of FL HC as well as of FL HSC, when used separately, all statistically significantly (p<0.05) inhibited paw edema, but the lower dose was more effective and giving results similar to that of prednisolone.
  • The data of cytokine studies showed that TNF-alpha concentration in sera of mice treated with either FL HC or FL HSC at a dose of 1x10(6) cells/mouse was statistically significantly (p<0.001) lower than that of the control mice.
  • A concentration of IL-10 was statistically significantly higher (p<0.01) in mice treated with a dose of 1x10(6) cells/mouse of FL HC but not with the same dose of FL HSC as compared to the control group.
  • Histological examination revealed better effects of a dose of 1x10(6) cells/mouse of FL HC when compared with the same dose of FL HSC as in regard to reduction of edema thickness and cell infiltration.
  • [MeSH-major] Anti-Inflammatory Agents / pharmacology. Dermatitis, Contact / drug therapy. Hematopoietic Stem Cells / immunology. Liver / cytology
  • [MeSH-minor] Animals. Antigens, CD38 / immunology. Dinitrofluorobenzene. Disease Models, Animal. Female. Interleukin-10 / blood. Interleukin-10 / immunology. Mice. Mice, Inbred BALB C. Organ Size / drug effects. Proto-Oncogene Proteins c-kit / immunology. Spleen / drug effects. Spleen / growth & development. Thymus Gland / drug effects. Thymus Gland / growth & development. Tumor Necrosis Factor-alpha / blood. Tumor Necrosis Factor-alpha / immunology

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  • (PMID = 17466908.001).
  • [ISSN] 1567-5769
  • [Journal-full-title] International immunopharmacology
  • [ISO-abbreviation] Int. Immunopharmacol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents; 0 / Tumor Necrosis Factor-alpha; 130068-27-8 / Interleukin-10; D241E059U6 / Dinitrofluorobenzene; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit; EC 3.2.2.5 / Antigens, CD38
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54. Magill SS, Shields C, Sears CL, Choti M, Merz WG: Triazole cross-resistance among Candida spp.: case report, occurrence among bloodstream isolates, and implications for antifungal therapy. J Clin Microbiol; 2006 Feb;44(2):529-35
Hazardous Substances Data Bank. FLUCONAZOLE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Triazole cross-resistance among Candida spp.: case report, occurrence among bloodstream isolates, and implications for antifungal therapy.
  • Fluconazole (FLC) remains a first-line therapy for candidemia; and voriconazole (VRC), an expanded-spectrum triazole, was recently approved for the treatment of candidemia in nonneutropenic patients.
  • In vitro studies have suggested that VRC has potent activity against Candida spp. with reduced susceptibilities to FLC.
  • We present a case report of invasive candidiasis and candidemia due to a Candida glabrata isolate that developed resistance to all currently available triazole antifungals after a course of FLC treatment.
  • FLC MICs were determined for 125 of 153 isolates (81.7%).
  • Thirty of 125 isolates (24%) were resistant or showed reduced susceptibilites to FLC (MICs >/= 16 microg/ml).
  • These data have prompted the introduction of reflexive FLC susceptibility testing of first bloodstream Candida isolates at our institution.
  • The case report and our data also suggest that VRC should be avoided as initial therapy in unstable patients with invasive candidiasis, particularly in the setting of prior azole exposure.

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  • (PMID = 16455909.001).
  • [ISSN] 0095-1137
  • [Journal-full-title] Journal of clinical microbiology
  • [ISO-abbreviation] J. Clin. Microbiol.
  • [Language] ENG
  • [Grant] United States / NIAID NIH HHS / AI / K23 AI053601; United States / NIAID NIH HHS / AI / AI53601
  • [Publication-type] Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Triazoles; 8VZV102JFY / Fluconazole
  • [Other-IDs] NLM/ PMC1392670
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55. Suzuki Inoue K, Inoue O, Ozaki Y: [Identification of the novel platelet activation receptor CLEC-2 and Its pathological and physiological roles]. Rinsho Byori; 2010 Dec;58(12):1193-202
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  • Podoplanin is expressed on the surface of tumor cells and facilitates tumor metastasis by inducing platelet aggregation.
  • We showed that an antibody that blocked the binding between CLEC-2 and podoplanin inhibited tumor metastasis using an experimental lung metastasis model in mice.
  • Podoplanin is also expressed in lymphatic endothelial cells, but the physiological role of the interaction between CLEC-2 and podoplanin in lymphatic endothelial cells has not been elucidated.
  • Moreover, through the transplantation of fetal liver cells from CLEC-2 +/+ or CLEC-2-/- embryos, we were able to demonstrate that CLEC-2 is involved in thrombus stabilization in vitro and in vivo, possibly through homophilic interactions without any apparent increase in the bleeding tendency.
  • These findings revealed that CLEC-2 plays a crucial role in not only tumor metastasis, but also in lymphangiogenesis and thrombus stabilization.
  • We propose that CLEC-2 could be an ideal novel target protein for an anti-platelet drug, which inhibits pathological thrombus formation but not physiological hemostasis, as well as a novel target protein for an anti-metastatic drug.
  • [MeSH-major] Lectins, C-Type / isolation & purification. Lectins, C-Type / physiology. Membrane Glycoproteins / isolation & purification. Membrane Glycoproteins / physiology. Platelet Activation
  • [MeSH-minor] Animals. Antineoplastic Agents. Drug Design. Humans. Ligands. Lymphangiogenesis. Mice. Molecular Targeted Therapy. Neoplasm Metastasis. Neovascularization, Physiologic. Platelet Aggregation. Platelet Aggregation Inhibitors. Thrombosis / etiology

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  • (PMID = 21348239.001).
  • [ISSN] 0047-1860
  • [Journal-full-title] Rinsho byori. The Japanese journal of clinical pathology
  • [ISO-abbreviation] Rinsho Byori
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / CLEC2B protein, human; 0 / Lectins, C-Type; 0 / Ligands; 0 / Membrane Glycoproteins; 0 / PDPN protein, human; 0 / Platelet Aggregation Inhibitors
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56. Ku TS, Palanisamy SK, Lee SA: Susceptibility of Candida albicans biofilms to azithromycin, tigecycline and vancomycin and the interaction between tigecycline and antifungals. Int J Antimicrob Agents; 2010 Nov;36(5):441-6
Hazardous Substances Data Bank. AZITHROMYCIN .

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  • Despite growing data on antimicrobial lock therapy (ALT) in treating bacterial catheter-related bloodstream infections (CR-BSIs), ALT has not been established as a treatment option for CR-BSI caused by Candida albicans.
  • Therefore, TIG was assayed alone and in combination with fluconazole (FLC), amphotericin B (AmB) or caspofungin (CAS).
  • TIG at 2048 μg/mL resulted in a >50% reduction in the growth of planktonic C. albicans cells.
  • Furthermore, addition of 512 μg/mL TIG to FLC at all concentrations tested provided additional reduction in the metabolic activity of mature biofilms.
  • These data indicate that high-dose TIG is highly active in vitro against planktonic cells, forming biofilms and mature biofilms of C. albicans.
  • [MeSH-major] Anti-Infective Agents / pharmacology. Azithromycin / pharmacology. Biofilms / drug effects. Candida albicans / drug effects. Minocycline / analogs & derivatives. Vancomycin / pharmacology
  • [MeSH-minor] Drug Interactions. Humans. Inhibitory Concentration 50

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  • [Copyright] Published by Elsevier B.V.
  • (PMID = 20685088.001).
  • [ISSN] 1872-7913
  • [Journal-full-title] International journal of antimicrobial agents
  • [ISO-abbreviation] Int. J. Antimicrob. Agents
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Anti-Infective Agents; 6Q205EH1VU / Vancomycin; 70JE2N95KR / tigecycline; 83905-01-5 / Azithromycin; FYY3R43WGO / Minocycline
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57. Maceira AM, Prasad SK, Hawkins PN, Roughton M, Pennell DJ: Cardiovascular magnetic resonance and prognosis in cardiac amyloidosis. J Cardiovasc Magn Reson; 2008 Nov 25;10:54
Hazardous Substances Data Bank. GADOPENTETATE DIMEGLUMINE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • BACKGROUND: Cardiac involvement is common in amyloidosis and associated with a variably adverse outcome.
  • All patients underwent biopsy, 2D-echocardiography and Doppler studies, 123I-SAP scintigraphy, serum NT pro BNP assay, and CMR with a T1 mapping method and late gadolinium enhancement (LGE).
  • Intramyocardial T1 gradient was a better predictor of survival than FLC response to chemotherapy (Kaplan Meier analysis P = 0.049) or diastolic function (Kaplan-Meier analysis P = 0.205).
  • [MeSH-minor] Aged. Biomarkers / blood. Biopsy. Echocardiography, Doppler. Female. Humans. Kaplan-Meier Estimate. Longitudinal Studies. Male. Middle Aged. Natriuretic Peptide, Brain / blood. Peptide Fragments / blood. Predictive Value of Tests. Prognosis. Prospective Studies. Risk Assessment. Severity of Illness Index. Time Factors

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  • (PMID = 19032744.001).
  • [ISSN] 1532-429X
  • [Journal-full-title] Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
  • [ISO-abbreviation] J Cardiovasc Magn Reson
  • [Language] eng
  • [Grant] United Kingdom / Medical Research Council / / G7900510
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Contrast Media; 0 / Peptide Fragments; 0 / pro-brain natriuretic peptide (1-76); 114471-18-0 / Natriuretic Peptide, Brain; K2I13DR72L / Gadolinium DTPA
  • [Other-IDs] NLM/ PMC2605441
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58. van der Loo JC, Liu BL, Goldman AI, Buckley SM, Chrudimsky KS: Optimization of gene transfer into primitive human hematopoietic cells of granulocyte-colony stimulating factor-mobilized peripheral blood using low-dose cytokines and comparison of a gibbon ape leukemia virus versus an RD114-pseudotyped retroviral vector. Hum Gene Ther; 2002 Jul 20;13(11):1317-30
NCI CPTC Antibody Characterization Program. NCI CPTC Antibody Characterization Program .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Optimization of gene transfer into primitive human hematopoietic cells of granulocyte-colony stimulating factor-mobilized peripheral blood using low-dose cytokines and comparison of a gibbon ape leukemia virus versus an RD114-pseudotyped retroviral vector.
  • Primitive human hematopoietic cells in granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood (MPB) are more difficult to transduce compared to cells from umbilical cord blood.
  • Based on the hypothesis that MPB cells may require different stimulation for efficient retroviral infection, we compared several culture conditions known to induce cycling of primitive hematopoietic cells.
  • MPB-derived CD34(+) cells were stimulated in the presence or absence of the murine fetal liver cell line AFT024 in trans-wells with G-CSF, stem cell factor (SCF), and thrombopoietin (TPO) (G/S/T; 100 ng/ml) or Flt3-L, SCF, interleukin (IL)-7, and TPO (F/S/7/T; 10-20 ng/ml), and transduced using a GaLV-pseudotyped retroviral vector expressing the enhanced green fluorescence protein (eGFP).
  • Compared to cultures without stroma, the presence of AFT024 increased the number of transduced colony-forming cells (CFC) by 3.5-fold (with G/S/T), long-term culture-initiating cells (LTC-IC) by 4.6-fold (with F/S/7/T), and nonobese diabetic/severe immunodeficiency disease (NOD/SCID)-repopulating cells (SRC) by 6.8-fold (with F/S/7/T).
  • Similar numbers of long-term culture-initiating cells (LTC-IC) and SRC could be transduced using AFT024-conditioned medium (AFT-CM) or a defined medium that had been supplemented with factors identified in AFT-CM.
  • Finally, using our best condition based on transduction with the gibbon ape leukemia virus (GaLV)-pseudotyped vector, we demonstrate a 33-fold higher level of gene transfer (p < 0.001) in SRC using an RD114-pseudotyped vector.
  • In summary, using an optimized protocol with low doses of cytokines, and transduction with an RD114 compared to a GaLV-pseudotyped retroviral vector, the overall number of transduced cells in NOD/SCID mice could be improved 144-fold, with a gene-transfer efficiency in SRC of 16.3% (13.3-19.9; n = 6).
  • [MeSH-major] Cytokines / pharmacology. Genetic Vectors. Hematopoietic Stem Cells. Leukemia Virus, Gibbon Ape / genetics. Retroviridae / genetics. Transduction, Genetic / methods
  • [MeSH-minor] Animals. Antigens, CD34 / drug effects. Antigens, CD34 / immunology. Cell Line. Cell Transformation, Viral. Cells, Cultured. Colony-Forming Units Assay. Culture Media / pharmacology. Culture Media, Conditioned / pharmacology. Fetus. Fibronectins / metabolism. Granulocyte Colony-Stimulating Factor / pharmacology. Green Fluorescent Proteins. Humans. Leukemia Virus, Murine / genetics. Leukemia, Erythroblastic, Acute / pathology. Leukocytes, Mononuclear / cytology. Liver / cytology. Liver / embryology. Luminescent Proteins / metabolism. Mice. Mice, Inbred NOD. Mice, SCID. Recombinant Proteins / metabolism. Tumor Cells, Cultured

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  • (PMID = 12162814.001).
  • [ISSN] 1043-0342
  • [Journal-full-title] Human gene therapy
  • [ISO-abbreviation] Hum. Gene Ther.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / 5 P01-CA65493-05
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD34; 0 / Culture Media; 0 / Culture Media, Conditioned; 0 / Cytokines; 0 / Fibronectins; 0 / Luminescent Proteins; 0 / Recombinant Proteins; 143011-72-7 / Granulocyte Colony-Stimulating Factor; 147336-22-9 / Green Fluorescent Proteins
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59. Goldammer A, Derfler K, Herkner K, Bradwell AR, Hörl WH, Haas M: Influence of plasma immunoglobulin level on antibody synthesis. Blood; 2002 Jul 1;100(1):353-5

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • To assess whether these results are conferrable to antibody-depleted humans, we measured free light chains (flcs) as markers of current antibody synthesis in 8 patients treated with immunoadsorption (IA) therapy.
  • The mean serum flc concentration increased to the preapheresis value within 1 day and remained unchanged thereafter.
  • In conclusion, the lack of increased flc synthesis after IA confirms the absence of a feedback mechanism regulating antibody synthesis.
  • [MeSH-major] Antibody Formation / drug effects. Immunoglobulins / pharmacology
  • [MeSH-minor] Adult. Aged. Autoimmune Diseases / blood. Autoimmune Diseases / drug therapy. Feedback, Physiological / immunology. Female. Humans. Immunoglobulin kappa-Chains / blood. Immunosuppressive Agents / administration & dosage. Male. Middle Aged

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  • [CommentIn] Blood. 2002 Oct 15;100(8):3055-6; author reply 3066 [12382650.001]
  • (PMID = 12070050.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin kappa-Chains; 0 / Immunoglobulins; 0 / Immunosuppressive Agents
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60. Arcement CM, Towbin RB, Meza MP, Gerber DA, Kaye RD, Mazariegos GV, Carr BI, Reyes J: Intrahepatic chemoembolization in unresectable pediatric liver malignancies. Pediatr Radiol; 2000 Nov;30(11):779-85
Hazardous Substances Data Bank. DOXORUBICIN .

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  • [Title] Intrahepatic chemoembolization in unresectable pediatric liver malignancies.
  • OBJECTIVE: To determine the effectiveness of a new multidisciplinary approach using neoadjuvant intrahepatic chemoembolization (IHCE) and liver transplant (OLTx) in patients with unresectable hepatic tumors who have failed systemic chemotherapy.
  • MATERIALS AND METHODS: From November 1989 to April 1998, 14 children (2-15 years old) were treated with 50 courses of intra-arterial chemotherapy.
  • Baseline and post-treatment contrast-enhanced CT and alpha-fetoprotein levels were performed.
  • Seven had hepatoblastoma, and 7 had hepatocellular carcinoma (1 fibrolamellar variant).
  • The procedure was repeated every 3-4 weeks based on hepatic function and patency of the hepatic artery.
  • RESULTS: Six of 14 children received orthotopic liver transplants (31 courses of IHC).
  • Pretransplant, 3 of 6 showed a significant decrease in alpha-fetoprotein, while only 1 demonstrated a significant further reduction in tumor size).
  • Three of 6 patients are disease free at this time.
  • Three of 6 patients died of metastatic tumor 6, 38, and 58 months, respectively post-transplant.
  • One of 14 is currently undergoing treatment, has demonstrated a positive response, and is awaiting OLTx.
  • Four of 14 patients developed an increase in tumor size, developed metastatic disease, and were not transplant candidates.
  • CONCLUSION: The results of intrahepatic chemoembolization are promising and suggest that some children who do not respond to systemic therapy can be eventually cured by a combination of intrahepatic chemoembolization orthotopic liver transplant.
  • Alpha-fetoprotein and cross-sectional imaging appear to be complementary in evaluating tumor response.
  • [MeSH-major] Carcinoma, Hepatocellular / therapy. Chemoembolization, Therapeutic / methods. Hepatoblastoma / therapy. Liver Neoplasms / therapy
  • [MeSH-minor] Adolescent. Antineoplastic Agents / administration & dosage. Child. Child, Preschool. Cisplatin / administration & dosage. Doxorubicin / administration & dosage. Female. Humans. Infusions, Intra-Arterial. Liver Transplantation. Male. Treatment Outcome. alpha-Fetoproteins / metabolism

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  • (PMID = 11100496.001).
  • [ISSN] 0301-0449
  • [Journal-full-title] Pediatric radiology
  • [ISO-abbreviation] Pediatr Radiol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] GERMANY
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / alpha-Fetoproteins; 80168379AG / Doxorubicin; Q20Q21Q62J / Cisplatin
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61. Sun S, Li Y, Guo Q, Shi C, Yu J, Ma L: In vitro interactions between tacrolimus and azoles against Candida albicans determined by different methods. Antimicrob Agents Chemother; 2008 Feb;52(2):409-17
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  • Combination therapy could be of use for the treatment of fungal infections, especially those caused by drug-resistant fungi.
  • The fractional inhibitory concentration index (FICI) is the most commonly used method, but it has several drawbacks in characterizing antifungal drug interaction.
  • In the present study, in vitro interactions between tacrolimus (FK506) and three azoles-fluconazole (FLC), itraconazole (ITR), and voriconazole (VRC)-against Candida albicans were evaluated by the checkerboard microdilution method and time-killing test.
  • Colony counting and colorimetric viable detection methods (2,3-bis {2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2H-tetrazolium hydroxide} [XTT] reduction test) were used for evaluating the combination antifungal effects over time.
  • The positive interactions were also confirmed by the time-killing test.
  • Our findings suggest a potential role for combination therapy with calcineurin pathway inhibitors and azoles to augment activity against resistant C. albicans.
  • [MeSH-major] Azoles / pharmacology. Candida albicans / drug effects. Immunosuppressive Agents / pharmacology. Microbial Sensitivity Tests / methods. Tacrolimus / pharmacology
  • [MeSH-minor] Colony Count, Microbial. Colorimetry. Culture Media. Drug Interactions. Drug Resistance, Fungal. Drug Synergism. Humans. Models, Biological. Spectrophotometry / methods

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  • (PMID = 18056277.001).
  • [ISSN] 0066-4804
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Azoles; 0 / Culture Media; 0 / Immunosuppressive Agents; WM0HAQ4WNM / Tacrolimus
  • [Other-IDs] NLM/ PMC2224779
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62. Ibbini M: A PI-fuzzy logic controller for the regulation of blood glucose level in diabetic patients. J Med Eng Technol; 2006 Mar-Apr;30(2):83-92
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • A fuzzy logic control (FLC) scheme was recently proposed for maintaining blood glucose level in diabetics within acceptable limits, and was shown to be more effective with better transient characteristics than conventional techniques.
  • In fact, FLC is based on human expertise and on desired output characteristics, and hence does not require precise mathematical models.
  • Fuzzy PI and PID controllers behave in a similar fashion to those classical controllers with the obvious advantage that the controller parameters are time dependant on the range of the control variables and consequently, result in a better performance.
  • Moreover, the proposed fuzzy PI controller is shown to be more effective than the previously proposed FLC, especially with respect to the overshoot and settling time.
  • [MeSH-major] Artificial Intelligence. Blood Glucose / metabolism. Diabetes Mellitus, Type 1 / blood. Diabetes Mellitus, Type 1 / drug therapy. Drug Therapy, Computer-Assisted / methods. Fuzzy Logic. Insulin / administration & dosage


63. Pelletier R, Loranger L, Marcotte H, De Carolis E: Voriconazole and fluconazole susceptibility of Candida isolates. J Med Microbiol; 2002 Jun;51(6):479-83
Hazardous Substances Data Bank. FLUCONAZOLE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • An adapted NCCLS M27-A method was used to evaluate the activity of voriconazole (VRC) and fluconazole (FLC) against 295 Candida isolates collected from 189 patients (including isolates from deep sites).
  • Forty-two isolates had reduced susceptibility to FLC (MIC >8 mg/L); 83.3% of these had VRC MICs < or =2 mg/L (9 of 11 C. albicans, 18 of 19 C glabrata, 6 of 6 C. krusei, 2 of 2 C. lusitaniae and 0 of 4 C. tropicalis), including 60% of isolates collected from deep-seated infections.
  • These results suggested that in the era of azole resistance, VRC has a promising antifungal activity for serious infections with Candida spp., including most species with low susceptibility to FLC and uncommonly isolated species.
  • [MeSH-major] Antifungal Agents / pharmacology. Candida / drug effects. Candidiasis / drug therapy. Fluconazole / pharmacology. Pyrimidines / pharmacology. Triazoles / pharmacology
  • [MeSH-minor] Colony Count, Microbial. Drug Resistance, Fungal. Humans. Microbial Sensitivity Tests. Treatment Outcome. Voriconazole

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  • (PMID = 12018654.001).
  • [ISSN] 0022-2615
  • [Journal-full-title] Journal of medical microbiology
  • [ISO-abbreviation] J. Med. Microbiol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Pyrimidines; 0 / Triazoles; 8VZV102JFY / Fluconazole; JFU09I87TR / Voriconazole
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64. Lindton B, Markling L, Ringdén O, Westgren M: In vitro studies of haematopoietic colony-forming capacity of human fetal liver cells at exposure to cytotoxic and immunomodulatory drugs. Fetal Diagn Ther; 2002 Mar-Apr;17(2):104-9
Hazardous Substances Data Bank. BETAMETHASONE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] In vitro studies of haematopoietic colony-forming capacity of human fetal liver cells at exposure to cytotoxic and immunomodulatory drugs.
  • OBJECTIVE: Intrauterine transplantation with haematopoietic stem cells (SC) as a treatment for immunological, haematological and metabolic inherited disorders has not been effective in fetuses with a normal immunological status.
  • Inhibition of the fetal haematopoiesis or immunosuppression might therefore be a therapeutic alternative in fetal SC transplantation.
  • The aim of the present study was to evaluate the effects of drugs that might be considered as therapeutic options in fetal transplantations on the colony-forming capacity of fetal haematopoietic SC.
  • METHODS: Fetal liver cells were incubated with doxorubicin, daunorubicin, antithymocyte-globulin (ATG), OKT-3 (Orthoclone) and betamethasone.
  • The effects of these drugs on colony formation by fetal hematopoietic SC were evaluated.
  • Colony-forming capacity assays were cultured during 10 days after drug incubation on day 1 and evaluated for differences in number of colonies compared to unexposed cells.
  • RESULTS: A significant reduction in fetal liver haematopoietic colony formation of BFU-E, CFU-GM and CFU- GEMM was detected when 0.1 M doxorubicin (p < 0.05) and 0.5 microM daunorubicin (p < 0.05) were added.
  • CONCLUSIONS: The drugs investigated in this in vitro study were capable to different degrees to decrease the colony-forming capacity of fetal haematopoietic progenitor cells.
  • Whether this strategy will become an alternative in fetal SC transplantations is an open question and further studies are required to elucidate the potential use of these drugs in fetal transplantation.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Hematopoiesis. Hematopoietic Stem Cells / cytology. Hematopoietic Stem Cells / drug effects. Liver / drug effects. Liver / embryology
  • [MeSH-minor] Antilymphocyte Serum / pharmacology. Betamethasone / pharmacology. Bone Marrow Cells / drug effects. Colony-Forming Units Assay. Daunorubicin / pharmacology. Doxorubicin / pharmacology. Humans. Immunosuppressive Agents / pharmacology

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  • [Copyright] Copyright 2002 S. Karger AG, Basel
  • (PMID = 11844915.001).
  • [ISSN] 1015-3837
  • [Journal-full-title] Fetal diagnosis and therapy
  • [ISO-abbreviation] Fetal. Diagn. Ther.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Antilymphocyte Serum; 0 / Antineoplastic Agents; 0 / Immunosuppressive Agents; 80168379AG / Doxorubicin; 9842X06Q6M / Betamethasone; ZS7284E0ZP / Daunorubicin
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65. Salama SM, Atwal H, Gandhi A, Simon J, Poglod M, Montaseri H, Khan JK, Furukawa T, Saito H, Nishida K, Higashitani F, Uji T, Unemi N, Daneshtalab M, Micetich RG: In vitro and in vivo activities of syn2836, syn2869, syn2903, and syn2921: new series of triazole antifungal agents. Antimicrob Agents Chemother; 2001 Sep;45(9):2420-6
MedlinePlus Health Information. consumer health - Yeast Infections.

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • The in vitro activities of Syn2869, Syn2836, Syn2903, and Syn2921 against a panel of over 240 recently collected clinical isolates of yeast and molds were determined, and the results were compared with those obtained with fluconazole (FLC), itraconazole (ITC), and amphotericin B (AMB).
  • All compounds were also active against FLC-resistant Candida albicans and other Candida sp. strains.
  • The test compounds produced a fungistatic pattern during the time-kill kinetic studies.
  • The results for Syn2903 were similar to those for FLC, while the other compounds were slightly less effective but had ranges of activities similar to the range of activity of ITC.
  • It was concluded from the data generated for this new series of azole compounds in the studies described above that further pharmacokinetic and toxicologic evaluations are warranted prior to selection of a candidate compound for preclinical testing.
  • [MeSH-major] Antifungal Agents / therapeutic use. Aspergillosis / drug therapy. Candidiasis / drug therapy
  • [MeSH-minor] Animals. Aspergillus / drug effects. Candida albicans / drug effects. Disease Models, Animal. Mice. Microbial Sensitivity Tests. Piperazines / pharmacology. Piperazines / therapeutic use. Treatment Outcome. Triazoles / pharmacology. Triazoles / therapeutic use

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  • (PMID = 11502508.001).
  • [ISSN] 0066-4804
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Piperazines; 0 / SYN 2836; 0 / Syn 2869; 0 / Syn2903; 0 / Syn2921; 0 / Triazoles
  • [Other-IDs] NLM/ PMC90671
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66. Prasad K: Natural products in regression and slowing of progression of atherosclerosis. Curr Pharm Biotechnol; 2010 Dec;11(8):794-800
MedlinePlus Health Information. consumer health - Vitamin E.

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Many natural products, including vitamin E, garlic, purpurogallin, flaxseed and its components [secoisolariciresinol diglucoside (SDG) and flax lignan complex (FLC)] and resveratrol have been reported to suppress hypercholesterolemic atherosclerosis.
  • It is known that all of the drugs that suppress the development of atherosclerosis do not regress and/or slow the progression of atherosclerosis.
  • To be of potential benefit in patients with established atherosclerosis, a drug should produce regression and/or slow the progression of atherosclerosis.
  • In this review, the effects of vitamin E, SDG and FLC in the regression and slowing of progression of hypercholesterolemic atherosclerosis and their mechanisms have been described.
  • FLC does not regress hypercholesterolemic atherosclerosis but slows the progression of hypercholesterolemic atherosclerosis.
  • FLC does not regress but slows the progression of established atherosclerosis.
  • [MeSH-major] Atherosclerosis / drug therapy. Atherosclerosis / metabolism. Biological Products / pharmacology. Butylene Glycols / pharmacology. Glucosides / pharmacology. Oxidative Stress / drug effects. Phytotherapy. Vitamin E / pharmacology
  • [MeSH-minor] Animals. Antioxidants / pharmacology. Disease Progression. Flax. Humans. Hypercholesterolemia / drug therapy. Hypercholesterolemia / metabolism. Lignans / pharmacology

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  • (PMID = 20874684.001).
  • [ISSN] 1873-4316
  • [Journal-full-title] Current pharmaceutical biotechnology
  • [ISO-abbreviation] Curr Pharm Biotechnol
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antioxidants; 0 / Biological Products; 0 / Butylene Glycols; 0 / Glucosides; 0 / Lignans; 1406-18-4 / Vitamin E; 148244-82-0 / secoisolariciresinol diglucoside
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67. Comenzo RL: Managing systemic light-chain amyloidosis. J Natl Compr Canc Netw; 2007 Feb;5(2):179-87
NCI CPTC Antibody Characterization Program. NCI CPTC Antibody Characterization Program .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Immunoglobulin (Ig) light-chain amyloidosis (AL), caused by the monoclonal gammopathy of a plasma cell dyscrasia, is the most common type.
  • A hereditary type is also caused by mutant transthyretin and other proteins.
  • In AL, circulating monoclonal Ig light chains can be measured with the free light-chain (FLC) assay and provide a target for therapy to eliminate the underlying plasma cell dyscrasia while supporting the patient's organ function.
  • Amyloid deposits can be resorbed and organ function restored if the amyloid-forming precursor FLC is eliminated.
  • For patients with limited organ involvement, intravenous melphalan in doses from 100 to 200 mg/m2 with autologous stem cell support (SCT) is an effective approach and, when followed at 3 months post-SCT with adjuvant thalidomide and dexamethasone for persistent plasma cell disease, has a 1-year hematologic response rate of 77%.
  • Monthly oral melphalan and dexamethasone for 1 year can also be effective therapy for patients too sick for SCT (67% response rate).
  • For patients with advanced cardiac involvement, the prognosis remains guarded even with treatment.
  • Drugs effective in multiple myeloma are usually active in AL, depending on side effects.
  • [MeSH-major] Amyloidosis / drug therapy. Melphalan / therapeutic use. Myeloablative Agonists / therapeutic use. Paraproteinemias / drug therapy. Stem Cell Transplantation
  • [MeSH-minor] Combined Modality Therapy. Glucocorticoids / therapeutic use. Humans. Immunoglobulin Light Chains / physiology. Immunosuppressive Agents / therapeutic use. Organ Transplantation

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  • Hazardous Substances Data Bank. MELPHALAN .
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  • (PMID = 17335687.001).
  • [ISSN] 1540-1405
  • [Journal-full-title] Journal of the National Comprehensive Cancer Network : JNCCN
  • [ISO-abbreviation] J Natl Compr Canc Netw
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Glucocorticoids; 0 / Immunoglobulin Light Chains; 0 / Immunosuppressive Agents; 0 / Myeloablative Agonists; Q41OR9510P / Melphalan
  • [Number-of-references] 51
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68. Takahata S, Okutomi T, Ohtsuka K, Hoshiko S, Uchida K, Yamaguchi H: In vitro and in vivo antifungal activities of FX0685, a novel triazole antifungal agent with potent activity against fluconazole-resistant Candida albicans. Med Mycol; 2005 May;43(3):227-33
Hazardous Substances Data Bank. FLUCONAZOLE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • To evaluate the therapeutic potential of FX0685, a new triazole antifungal agent, for the treatment of opportunistic fungal infections, particularly systemic candidiasis and aspergillosis, in vitro and in vivo studies were performed using fluconazole (FLC), itraconazole (ITC) and/or amphotericin B (AMB) as reference drugs.
  • A preliminary in vitro study showed that the antifungal activity of FX0685 against FLC-susceptible Candida albicans, several non-C. albicans Candida species and Cryptococcus neoformans was superior to that of FLC and comparable or superior to those of ITC and AMB, while the anti-Aspergillus fumigatus activity of FX0685 was to varying degrees lower than that of ITC.
  • FX0685 appeared to be comparable to FLC and ITC in the treatment of murine systemic C. albicans and pulmonary A. fumigatus infection, respectively.
  • The biological property of FX0685 was characterized by its potent in vitro and in vivo activity against FLC-resistant C. albicans.
  • Part of this unique property was explained by the finding that it retained potent inhibitory activity against those CYP51 molecules in which amino acid substitutions confer a phenotype of resistance to FLC and some other azole derivatives.
  • All of these results lead to the possibility that FX0685 may be a potential antifungal drug candidate for the treatment of various clinical forms of systemic candidiasis, including those caused by FLC-resistant C. albicans, as well as for the treatment of pulmonary aspergillosis.
  • [MeSH-major] Antifungal Agents / pharmacology. Candida albicans / drug effects. Candidiasis / drug therapy. Fluconazole / pharmacology. Triazoles / pharmacology. Triazoles / therapeutic use
  • [MeSH-minor] Animals. Disease Models, Animal. Drug Evaluation, Preclinical. Drug Resistance, Fungal. Injections, Intravenous. Male. Mice. Mice, Inbred CBA. Mice, Inbred DBA. Microbial Sensitivity Tests. Species Specificity

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  • (PMID = 16010849.001).
  • [ISSN] 1369-3786
  • [Journal-full-title] Medical mycology
  • [ISO-abbreviation] Med. Mycol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Triazoles; 8VZV102JFY / Fluconazole
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69. Barchiesi F, Spreghini E, Baldassarri I, Marigliano A, Arzeni D, Giannini D, Scalise G: Sequential therapy with caspofungin and fluconazole for Candida albicans infection. Antimicrob Agents Chemother; 2004 Oct;48(10):4056-8
Hazardous Substances Data Bank. FLUCONAZOLE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Sequential therapy with caspofungin and fluconazole for Candida albicans infection.
  • A sequential therapy of caspofungin (CAS) and fluconazole (FLC) administration for treatment of Candida albicans infection was investigated.
  • Treatment with CAS followed by FLC was as effective as CAS treatment given alone for the same duration.
  • Our data suggest that switching from CAS to FLC is a potentially explorable therapeutic option for treatment of systemic candidiasis.
  • [MeSH-major] Antifungal Agents / therapeutic use. Candidiasis / drug therapy. Fluconazole / therapeutic use. Peptides, Cyclic / therapeutic use
  • [MeSH-minor] Animals. Candida albicans / drug effects. Colony Count, Microbial. Drug Therapy, Combination. Echinocandins. Humans. Kidney / microbiology. Male. Mice

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  • (PMID = 15388480.001).
  • [ISSN] 0066-4804
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Echinocandins; 0 / Peptides, Cyclic; 8VZV102JFY / Fluconazole; F0XDI6ZL63 / caspofungin
  • [Other-IDs] NLM/ PMC521911
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70. Mauseth R, Wang Y, Dassau E, Kircher R Jr, Matheson D, Zisser H, Jovanovic L, Doyle FJ 3rd: Proposed clinical application for tuning fuzzy logic controller of artificial pancreas utilizing a personalization factor. J Diabetes Sci Technol; 2010 Jul 01;4(4):913-22
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • METHOD: We introduce a method that allows a physician to tune a fuzzy logic controller (FLC) artificial pancreas (AP) for a particular patient.
  • The personalization factor (PF) is a scaling of the dose produced by the FLC and is used to customize the dosing.
  • The proposed method was developed using a database of results from 30 University of Virginia/Padova Metabolic Simulator in silico subjects (10 adults, 10 adolescents, and 10 children).
  • RESULTS: Three examples of a wide variation in diabetes situations are given to illustrate the physician's thought process when initially configuring the AP system for a specific patient.
  • CONCLUSIONS: Fuzzy logic controllers are developed by encoding human expertise into the design of the controller.
  • The FLC methodology allows for the real-time scaling of doses without compromising the integrity of the dosing rules matrix.
  • [MeSH-major] Diabetes Mellitus, Type 1 / drug therapy. Fuzzy Logic. Pancreas, Artificial. Precision Medicine
  • [MeSH-minor] Adolescent. Adult. Aging / physiology. Algorithms. Blood Glucose / analysis. Blood Glucose / metabolism. Child, Preschool. Computer Simulation. Diet, Diabetic. Dietary Carbohydrates / blood. Female. Hemoglobin A, Glycosylated / analysis. Humans. Hypoglycemia / blood. Hypoglycemia / drug therapy. Hypoglycemic Agents / administration & dosage. Hypoglycemic Agents / therapeutic use. Insulin / administration & dosage. Insulin / therapeutic use. Male. Physicians

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  • [Copyright] 2010 Diabetes Technology Society.
  • [Cites] N Engl J Med. 1993 Sep 30;329(14):977-86 [8366922.001]
  • [Cites] J Diabetes Sci Technol. 2009 Jan;3(1):44-55 [19444330.001]
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  • (PMID = 20663457.001).
  • [ISSN] 1932-2968
  • [Journal-full-title] Journal of diabetes science and technology
  • [ISO-abbreviation] J Diabetes Sci Technol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Blood Glucose; 0 / Dietary Carbohydrates; 0 / Hemoglobin A, Glycosylated; 0 / Hypoglycemic Agents; 0 / Insulin
  • [Other-IDs] NLM/ PMC2909525
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71. Petraitis V, Petraitiene R, Kelaher AM, Sarafandi AA, Sein T, Mickiene D, Bacher J, Groll AH, Walsh TJ: Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans. Antimicrob Agents Chemother; 2004 Oct;48(10):3959-67
Hazardous Substances Data Bank. FLUCONAZOLE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • We studied the activity of PLD-118 in escalating dosages against experimental oropharyngeal and esophageal candidiasis (OPEC) caused by fluconazole (FLC)-resistant Candida albicans in immunocompromised rabbits.
  • Antifungal therapy was administered for 7 days.
  • Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v.
  • PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P </= 0.05, P </= 0.01, P </= 0.001, respectively), while FLC had no significant activity.
  • PLD-118 demonstrated nonlinear plasma pharmacokinetics across the investigated dosage range, as was evident from a dose-dependent increase in plasma clearance and a dose-dependent decrease in the area under the plasma concentration-time curve.
  • The biochemical safety profile was similar to that of FLC.
  • In summary, PLD-118 demonstrated dosage-dependent antifungal activity and nonlinear plasma pharmacokinetics in treatment of experimental FLC-resistant oropharyngeal and esophageal candidiasis.
  • [MeSH-major] Antifungal Agents / pharmacology. Candida albicans / drug effects. Candidiasis / microbiology. Cycloleucine / analogs & derivatives. Cycloleucine / therapeutic use. Enzyme Inhibitors / pharmacology. Fluconazole / pharmacology. Isoleucine-tRNA Ligase / antagonists & inhibitors
  • [MeSH-minor] Animals. Area Under Curve. Candidiasis, Oral / microbiology. Drug Resistance, Fungal. Esophageal Diseases / microbiology. Female. Half-Life. Immunosuppression. Rabbits

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  • (PMID = 15388459.001).
  • [ISSN] 0066-4804
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / 2-amino-4-methylenecyclopentane-1-carboxylic acid; 0 / Antifungal Agents; 0 / Enzyme Inhibitors; 0TQU7668EI / Cycloleucine; 8VZV102JFY / Fluconazole; EC 6.1.1.5 / Isoleucine-tRNA Ligase
  • [Other-IDs] NLM/ PMC521932
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72. Miceli MH, Bernardo SM, Lee SA: In vitro analyses of the combination of high-dose doxycycline and antifungal agents against Candida albicans biofilms. Int J Antimicrob Agents; 2009 Oct;34(4):326-32
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • The potential of antifungal agents used as antimicrobial lock therapy (ALT) for the conservative management of catheter-related candidemia has not been fully defined.
  • We sought to determine the antifungal effect of high-dose doxycycline (DOX), alone or in combination with standard concentrations of amphotericin B (AMB), caspofungin (CAS) or fluconazole (FLC), against biofilms formed by Candida albicans in vitro.
  • Regardless of the concentration tested, FLC alone showed minimal activity (mean 22.9% reduction) against the C. albicans biofilm.
  • When DOX 2048 microg/mL was used in combination with FLC, antifungal activity also increased up to 85%, suggesting an additive effect.
  • DOX 128 microg/mL in combination with FLC demonstrated synergy (mean 58.3% reduction).
  • Maximal efficacy against the biofilm was observed with CAS at 8-0.25 microg/mL compared with FLC and AMB alone.
  • These findings suggest that a high-dose DOX-based ALT strategy in combination with traditional antifungal agents may be useful for the treatment of C. albicans biofilms.
  • [MeSH-major] Antifungal Agents / pharmacology. Biofilms / drug effects. Candida albicans / drug effects. Doxycycline / pharmacology
  • [MeSH-minor] Amphotericin B / pharmacology. Dose-Response Relationship, Drug. Drug Interactions. Drug Therapy, Combination. Echinocandins / pharmacology. Fluconazole / pharmacology. Humans. Microbial Sensitivity Tests

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  • (PMID = 19515537.001).
  • [ISSN] 1872-7913
  • [Journal-full-title] International journal of antimicrobial agents
  • [ISO-abbreviation] Int. J. Antimicrob. Agents
  • [Language] eng
  • [Grant] United States / NIAID NIH HHS / AI / T32 AI007538
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Echinocandins; 7XU7A7DROE / Amphotericin B; 8VZV102JFY / Fluconazole; F0XDI6ZL63 / caspofungin; N12000U13O / Doxycycline
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73. Min CK, Lee MJ, Eom KS, Lee S, Lee JW, Min WS, Kim CC, Kim M, Lim J, Kim Y, Han K: Bortezomib in combination with conventional chemotherapeutic agents for multiple myeloma compared with bortezomib alone. Jpn J Clin Oncol; 2007 Dec;37(12):961-8
The Lens. Cited by Patents in .

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  • This study examined whether or not the speed of the response, progression and safety from a combination treatment of bortezomib with common chemotherapeutic drugs is superior to bortezomib monotherapy.
  • METHODS: Fifty-seven patients with relapsed, refractory multiple myeloma (MM) who had received at least two cycles of treatment including bortezomib were enrolled in this study.
  • The monoclonal immunoglobulin (mIg) or free light chain (FLC) concentrations were determined in the sera before and after two cycles of bortezomib treatment.
  • RESULTS: Thirty-one of the 57 patients (54.4%) attained an early objective response (EOR) after the second bortezomib treatment, defined as a >/=50% decrease in the serum mIg or FLC concentration.
  • In patients who received bortezomib combined with chemotherapeutic agents, 19 out of 25 patients (76%) showed an EOR, whereas 12 out of 32 patients (37.5%) given bortezomib monotherapy achieved an EOR after the second cycle of bortezomib treatment (P = 0.004); the median decrease from the baseline in the paraprotein level was 74.6 +/- 5.9 and 39.7 +/- 4.2%, respectively (P = 0.003).
  • A statistically significant elevation of serum lactic dehydrogenase (P = 0.007) and alkaline phosphatase (P = 0.027) from baseline within two cycles of bortezomib treatment was observed in responding patients.
  • With the combination treatment, peripheral neuropathy of >/=Grade II occurred in 12 out of 25 patients (48%) compared with 12 of 32 (37.5%) in those given bortezomib alone (P = 0.589).
  • The median time to progression of disease was similar in the two groups (359 +/- 43.5 versus 365 +/- 103.5, P = 0.688).
  • The multivariate Cox regression model showed that a high serum albumin and low beta2-microglobulin are favorable factors for the progression-free survival following bortezomib treatment.
  • CONCLUSIONS: Bortezomib in combination with common chemotherapeutic agents is more active in the treatment of relapsed, refractory MM than with bortezomib alone.
  • However, more effective post-bortezomib treatment is needed to reduce the rate of disease progression particularly in patients with high tumor burden.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Boronic Acids / therapeutic use. Multiple Myeloma / drug therapy. Pyrazines / therapeutic use

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  • (PMID = 18156171.001).
  • [ISSN] 1465-3621
  • [Journal-full-title] Japanese journal of clinical oncology
  • [ISO-abbreviation] Jpn. J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Comparative Study; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Boronic Acids; 0 / Immunoglobulin Light Chains; 0 / Pyrazines; 69G8BD63PP / Bortezomib; EC 1.1.- / Lactate Dehydrogenases; EC 3.1.3.1 / Alkaline Phosphatase
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74. Huang SJ, Shieh JS, Fu M, Kao MC: Fuzzy logic control for intracranial pressure via continuous propofol sedation in a neurosurgical intensive care unit. Med Eng Phys; 2006 Sep;28(7):639-47
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  • Group A used a conventional rule-based controller (RBC), Group B a fuzzy logic controller (FLC), and Group C a self-organizing fuzzy logic controller (SOFLC).
  • The results indicate that FLC can easily mimic the rule-base of human experts (i.e., neurosurgeons) to achieve stable sedation similar to the RBC group.
  • [MeSH-major] Fuzzy Logic. Hypnotics and Sedatives / administration & dosage. Intracranial Pressure / drug effects. Propofol / administration & dosage
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Algorithms. Biomedical Engineering. Brain Injuries / drug therapy. Brain Injuries / physiopathology. Critical Care. Female. Humans. Male. Middle Aged. Psychomotor Agitation / drug therapy. Psychomotor Agitation / physiopathology

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  • (PMID = 16298542.001).
  • [ISSN] 1350-4533
  • [Journal-full-title] Medical engineering & physics
  • [ISO-abbreviation] Med Eng Phys
  • [Language] eng
  • [Publication-type] Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Hypnotics and Sedatives; YI7VU623SF / Propofol
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75. Groll AH, Ritter J: [Diagnosis and management of fungal infections and pneumocystis pneumonitis in pediatric cancer patients]. Klin Padiatr; 2005 Nov;217 Suppl 1:S37-66
MedlinePlus Health Information. consumer health - Fungal Infections.

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Diagnosis and management of fungal infections and pneumocystis pneumonitis in pediatric cancer patients].
  • [Transliterated title] Diagnose und Therapie von Pilzinfektionen und der Pneumozystis-Pneumonie bei Kindern und Jugendlichen mit neoplastischen Erkrankungen.
  • Invasive fungal infections are important causes of morbidity and mortality in pediatric cancer patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation.
  • This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for diagnosis and treatment of fungal infections including Pneumocystis jiroveci.
  • They are based on specific pediatric pharmacological and regulatory considerations and on the results of clinical trials, case series and expert opinions using the evidence criteria set forth by the Infectious Diseases Society of America (IDSA).
  • Options for initial therapy of uncomplicated candidemia include deoxycholate amphotericin B (DAMB), fluconazole (FLC), liposomal amphotericin B (LAMB), the combination of DAMB plus FLC as well as voriconazole (VCZ) for patients > 11 years.
  • First-line therapy for presumed or proven invasive Aspergillus infections in patients 12 years and older is VCZ with DAMB and LAMB serving as alternatives.
  • Due to the yet lacking evidence for enhanced antifungal efficacy and the ongoing dosage finding of caspofungin (CAS) in pediatric patients, combination therapies (LAMB plus CAS or VCZ plus CAS) should only be considered for fulminant or massive, life threatening infections.
  • In granulocytopenic patients, adjunctive therapy with colony-stimulating factors (G-CSF) is recommended.
  • In patients under immunosuppressive therapy, glucocorticosteroids ought to be reduced or discontinued, if feasible.
  • The combination of DAMB plus flucytosine is the initial treatment of choice of cryptococcal mengoencephalitis, and for treatment of Pneumocystis jiroveci pneumonitis, trimethoprim/sulfamethoxazol or intravenous pentamidine is recommended.
  • Beyond the listed entities, the article provides a brief review on the pharmacokinetics and dosing of antifungal agents in children and adolescents as well as detailed discussions and evidence-based recommendations for empirical antifungal therapy, diagnosis and treatment of superficial fungal infections, of invasive infections by previously rare fungal pathogens and endemic moulds and for adjunctive immunomodulatory and surgical interventions.
  • [MeSH-major] Antifungal Agents / therapeutic use. Antineoplastic Agents / adverse effects. Mycoses / drug therapy. Neoplasms / drug therapy. Neutropenia / chemically induced. Opportunistic Infections / drug therapy. Pneumonia, Pneumocystis / drug therapy
  • [MeSH-minor] Adolescent. Cause of Death. Child. Clinical Trials as Topic. Drug Therapy, Combination. Germany. Humans. Pneumocystis jirovecii. Practice Guidelines as Topic. Survival Analysis

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  • (PMID = 16288352.001).
  • [ISSN] 0300-8630
  • [Journal-full-title] Klinische Pädiatrie
  • [ISO-abbreviation] Klin Padiatr
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Antineoplastic Agents
  • [Number-of-references] 364
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76. Ghannoum MA, Kuhn DM: Voriconazole -- better chances for patients with invasive mycoses. Eur J Med Res; 2002 May 31;7(5):242-56
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Voriconazole (VRC) is a novel triazole antifungal, recently approved in Europe for treatment of serious infections caused by Aspergillus, Fusarium, Scedosporium, and resistant Candida species.
  • Voriconazole has in vitro activity against yeasts and yeast-like fungi similar, or superior to, fluconazole (FLC), itraconazole (ITC) and amphotericin B (AMB).
  • The drug possesses potent fungicidal activity against moulds including Aspergillus, Scedosporium, and Fusarium.
  • Most importantly, well-designed human clinical trials have confirmed the efficacy of VRC in the treatment of candidal esophagitis, IA, and febrile neutropenia.
  • Smaller studies and case reports have shown VRC is useful for salvage therapy of IA, cerebral aspergillosis, Scedosporium, and other fungal infections.
  • [MeSH-major] Antifungal Agents / therapeutic use. Mycoses / drug therapy. Pyrimidines / therapeutic use. Triazoles / therapeutic use
  • [MeSH-minor] Candida / drug effects. Candida / metabolism. Candida / ultrastructure. Candidiasis / drug therapy. Drug Interactions. Drug Resistance, Fungal. Drug Tolerance. Humans. Safety. Voriconazole

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  • (PMID = 12069915.001).
  • [ISSN] 0949-2321
  • [Journal-full-title] European journal of medical research
  • [ISO-abbreviation] Eur. J. Med. Res.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Pyrimidines; 0 / Triazoles; JFU09I87TR / Voriconazole
  • [Number-of-references] 111
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77. Barchiesi F, Schimizzi AM, Caselli F, Novelli A, Fallani S, Giannini D, Arzeni D, Di Cesare S, Di Francesco LF, Fortuna M, Giacometti A, Carle F, Mazzei T, Scalise G: Interactions between triazoles and amphotericin B against Cryptococcus neoformans. Antimicrob Agents Chemother; 2000 Sep;44(9):2435-41
Hazardous Substances Data Bank. FLUCONAZOLE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • The interaction of amphotericin B (AmB) and azole antifungal agents in the treatment of fungal infections is still a controversial issue.
  • A checkerboard titration broth microdilution-based method that adhered to the recommendations of the National Committee for Clinical Laboratory Standards was applied to study the in vitro interactions of AmB with fluconazole (FLC), itraconazole (ITC), and the new investigational triazole SCH 56592 (SCH) against 15 clinical isolates of Cryptococcus neoformans.
  • Synergy, defined as a fractional inhibitory concentration (FIC) index of < or =0.50, was observed for 7% of the isolates in studies of the interactions of both FLC-AmB and ITC-AmB and for 33% of the isolates in studies of the SCH-AmB interactions; additivism (FICs, >0.50 to 1.0) was observed for 67, 73, and 53% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively; indifference (FICs, >1.0 to < or =2.0) was observed for 26, 20, and 14% of the isolates in studies of the FLC-AmB, ITC-AmB, and SCH-AmB interactions, respectively.
  • When synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when they were used in combination.
  • To investigate the effects of FLC-AmB combination therapy in vivo, we established an experimental model of systemic cryptococcosis in BALB/c mice by intravenous injection of cells of C. neoformans 2337, a clinical isolate belonging to serotype D against which the combination of FLC and AmB yielded an additive interaction in vitro.
  • Both survival and tissue burden studies showed that combination therapy was more effective than FLC alone and that combination therapy was at least as effective as AmB given as a single drug.
  • On the other hand, when cells of C. neoformans 2337 were grown in FLC-containing medium, a pronounced increase in resistance to subsequent exposures to AmB was observed.
  • In particular, killing experiments conducted with nonreplicating cells showed that preexposure to FLC abolished the fungicidal activity of the polyene.
  • Rather, when the two drugs were used sequentially for the treatment of systemic murine cryptococcosis, a reciprocal potentiation was often observed.
  • Our study shows that (i) the combination of triazoles and AmB is significantly more active than either drug alone against C. neoformans in vitro and (ii) the concomitant or sequential use of FLC and AmB for the treatment of systemic murine cryptococcosis results in a positive interaction.
  • [MeSH-major] Amphotericin B / pharmacology. Antifungal Agents / pharmacology. Cryptococcus neoformans / drug effects. Triazoles / pharmacology
  • [MeSH-minor] Animals. Cryptococcosis / drug therapy. Cryptococcosis / mortality. Disease Models, Animal. Drug Therapy, Combination. Fluconazole / pharmacology. Fluconazole / therapeutic use. Humans. Itraconazole / pharmacology. Itraconazole / therapeutic use. Male. Mice. Mice, Inbred BALB C. Microbial Sensitivity Tests

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  • (PMID = 10952592.001).
  • [ISSN] 0066-4804
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Triazoles; 304NUG5GF4 / Itraconazole; 6TK1G07BHZ / posaconazole; 7XU7A7DROE / Amphotericin B; 8VZV102JFY / Fluconazole
  • [Other-IDs] NLM/ PMC90082
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78. Jin J, Guo N, Zhang J, Ding Y, Tang X, Liang J, Li L, Deng X, Yu L: The synergy of honokiol and fluconazole against clinical isolates of azole-resistant Candida albicans. Lett Appl Microbiol; 2010 Sep;51(3):351-7
Hazardous Substances Data Bank. FLUCONAZOLE .

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  • AIMS: To evaluate the interaction of fluconazole (FLC) and honokiol (HNK) in vitro and vivo against azole-resistant (azole-R) clinical isolates of Candida albicans.
  • METHODS AND RESULTS: A checkerboard microdilution method was used to study the in vitro interaction of FLC and HNK in 24 azole-R clinical isolates of C. albicans.
  • In vivo antifungal activity was performed to further analyse the interaction between FLC and HNK.
  • In the in vitro study, synergism was observed in all 24 FLC-resistant strains tested as determined by fractional inhibitory concentration index (FICI), and in 22 strains by Delta E models.
  • These positive interactions were also confirmed by using the time-killing test for the selected strain C. albicans YL371, which shows strong susceptible to the combination of HNK and FLC.
  • In the in vivo study, the mice with candidiasis were treated successfully by a combination therapy of HNK with FLC, the results showed a decrease of the colony forming unit in infected and treated animals compared to the controls, at the conditions of the treatment used in this study.
  • CONCLUSIONS: Synergistic activity of HNK and FLC against clinical isolates of FLC-resistant C. albicans was observed in vitro and in vivo.
  • SIGNIFICANCE AND IMPACT OF THE STUDY: This report might provide a potential therapeutic method to overcome the problem of drug-resistance in C. albicans.
  • [MeSH-major] Antifungal Agents / pharmacology. Biphenyl Compounds / pharmacology. Candida albicans / drug effects. Drug Resistance, Fungal. Fluconazole / pharmacology. Lignans / pharmacology
  • [MeSH-minor] Animals. Candidiasis / drug therapy. Candidiasis / microbiology. Colony Count, Microbial. Drug Synergism. Humans. Mice. Microbial Sensitivity Tests. Microbial Viability / drug effects. Treatment Outcome

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  • (PMID = 20681969.001).
  • [ISSN] 1472-765X
  • [Journal-full-title] Letters in applied microbiology
  • [ISO-abbreviation] Lett. Appl. Microbiol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Biphenyl Compounds; 0 / Lignans; 11513CCO0N / honokiol; 8VZV102JFY / Fluconazole
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79. Venkatesh MP, Rong L: Human recombinant lactoferrin acts synergistically with antimicrobials commonly used in neonatal practice against coagulase-negative staphylococci and Candida albicans causing neonatal sepsis. J Med Microbiol; 2008 Sep;57(Pt 9):1113-21
MedlinePlus Health Information. consumer health - Yeast Infections.

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  • MIC50 and MIC90 values of human recombinant lactoferrin (talactoferrin; TLF), vancomycin (VAN) and nafcillin (NAF) against CoNS, and of TLF, amphotericin B (AMB) and fluconazole (FLC) against C. albicans, were evaluated according to established guidelines.
  • Antimicrobial combinations of TLF with NAF or VAN against CoNS, and TLF with AMB or FLC against C. albicans, were evaluated by a checkerboard method with serial twofold dilutions.
  • Synergy was evaluated by the median effects principle, and combination indices and dose reduction indices were reported at 50, 75 and 90% inhibitory effect at several drug-dose ratios.
  • It was found that TLF acted synergistically with NAF and VAN against CoNS, and with AMB and FLC against C. albicans, at multiple dose effects and drug-dose ratios with few exceptions.
  • In synergistic combinations, drug reduction indices indicated a significant reduction in doses of antibiotics, which may be clinically relevant.
  • [MeSH-major] Anti-Bacterial Agents / administration & dosage. Antifungal Agents / administration & dosage. Candidiasis / drug therapy. Lactoferrin / administration & dosage. Sepsis / drug therapy. Staphylococcal Infections / drug therapy
  • [MeSH-minor] Candida albicans / drug effects. Coagulase / metabolism. Drug Synergism. Humans. Infant, Newborn. Microbial Sensitivity Tests. Recombinant Proteins / administration & dosage. Recombinant Proteins / therapeutic use. Staphylococcus / enzymology. Staphylococcus / genetics

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  • (PMID = 18719181.001).
  • [ISSN] 0022-2615
  • [Journal-full-title] Journal of medical microbiology
  • [ISO-abbreviation] J. Med. Microbiol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Anti-Bacterial Agents; 0 / Antifungal Agents; 0 / Coagulase; 0 / Recombinant Proteins; EC 3.4.21.- / Lactoferrin
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80. Holmes AR, Lin YH, Niimi K, Lamping E, Keniya M, Niimi M, Tanabe K, Monk BC, Cannon RD: ABC transporter Cdr1p contributes more than Cdr2p does to fluconazole efflux in fluconazole-resistant Candida albicans clinical isolates. Antimicrob Agents Chemother; 2008 Nov;52(11):3851-62
Hazardous Substances Data Bank. FLUCONAZOLE .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Fluconazole (FLC) remains the antifungal drug of choice for non-life-threatening Candida infections, but drug-resistant strains have been isolated during long-term therapy with azoles.
  • Drug efflux, mediated by plasma membrane transporters, is a major resistance mechanism, and clinically significant resistance in Candida albicans is accompanied by increased transcription of the genes CDR1 and CDR2, encoding plasma membrane ABC-type transporters Cdr1p and Cdr2p.
  • The antibodies and inhibitors were standardized using recombinant Saccharomyces cerevisiae strains that hyper-express either protein in a host strain with a reduced endogenous pump background.
  • In all 18 C. albicans strains, including 13 strains with reduced FLC susceptibilities, Cdr1p was present in greater amounts (2- to 20-fold) than Cdr2p.
  • Compounds that inhibited Cdr1p-mediated function, but had no effect on Cdr2p efflux activity, significantly decreased the resistance to FLC of seven representative C. albicans isolates, whereas three other compounds that inhibited both pumps did not cause increased chemosensitization of these strains to FLC.
  • We conclude that Cdr1p expression makes a greater functional contribution than does Cdr2p to FLC resistance in C. albicans.
  • [MeSH-major] ATP-Binding Cassette Transporters / metabolism. Antifungal Agents / pharmacokinetics. Antifungal Agents / pharmacology. Candida albicans / drug effects. Candida albicans / metabolism. Fluconazole / pharmacokinetics. Fluconazole / pharmacology. Fungal Proteins / metabolism. Membrane Transport Proteins / metabolism
  • [MeSH-minor] Antibodies, Fungal. Biological Transport, Active. Candidiasis / drug therapy. Candidiasis / microbiology. Drug Resistance, Fungal / genetics. Gene Expression. Genes, Fungal. Humans. Recombinant Proteins / genetics. Recombinant Proteins / metabolism. Saccharomyces cerevisiae / genetics. Saccharomyces cerevisiae / metabolism

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  • (PMID = 18710914.001).
  • [ISSN] 1098-6596
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Grant] United States / NIDCR NIH HHS / DE / R01 DE016885; United States / NIDCR NIH HHS / DE / R01DE016885-01-RDC; United States / NIDCR NIH HHS / DE / R21DE015075-RDC
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / ATP-Binding Cassette Transporters; 0 / Antibodies, Fungal; 0 / Antifungal Agents; 0 / CDR1 protein, Candida albicans; 0 / Fungal Proteins; 0 / Membrane Transport Proteins; 0 / Recombinant Proteins; 8VZV102JFY / Fluconazole
  • [Other-IDs] NLM/ PMC2573144
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81. Terrier B, Sène D, Saadoun D, Ghillani-Dalbin P, Thibault V, Delluc A, Piette JC, Cacoub P: Serum-free light chain assessment in hepatitis C virus-related lymphoproliferative disorders. Ann Rheum Dis; 2009 Jan;68(1):89-93
Genetic Alliance. consumer health - Hepatitis.

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • OBJECTIVE: To evaluate the relevance of serum-free light chain (FLC) assessment in hepatitis C virus (HCV)-related lymphoproliferative disorders, including mixed cryoglobulinemia (MC) and B cell non-Hodgkin lymphoma (B-NHL).
  • Clinical and biological data were recorded at the time of the initial evaluation and at the end of follow-up.
  • Serum FLC quantitation was carried out using a serum FLC assay.
  • RESULTS: The mean (SD) serum kappa FLC level was higher in patients with asymptomatic MC (27.9 (8.6) mg/litre), MC vasculitis (36.7 (46.2) mg/litre) and B-NHL (51.3 (78.3) mg/litre) than without MC (21.7 (17.6) mg/litre) (p = 0.047, 0.025 and 0.045, respectively).
  • The mean serum FLC ratio was higher in patients with MC vasculitis (2.08 (2.33)) and B-NHL (3.14 (3.49)) than in patients without MC (1.03 (0.26)) (p = 0.008).
  • The rate of abnormal serum FLC ratio (>1.65) correlated with the severity of HCV-related B cell disorder: 0/17 (0%) without MC, 0/7 (0%) asymptomatic MC, 6/26 (23%) MC vasculitis without B-NHL and 4/9 (44%) B-NHL (p = 0.002).
  • Serum kappa FLC levels and the serum FLC ratio correlated with the cryoglobulin level (r = 0.32, p<0.001 and r = 0.25, p = 0.002, respectively) and the severity of the B cell disorder (r = 0.26, p = 0.045 and r = 0.41, p = 0.001, respectively).
  • Among patients with an abnormal serum FLC ratio at baseline, the FLC ratio correlated with the virological response to HCV treatment.
  • CONCLUSIONS: In patients infected with HCV, an abnormal serum FLC ratio appears to be a very interesting marker, as it is consistently associated with the presence of MC vasculitis and/or B-NHL.
  • After antiviral therapy, the serum FLC ratio could be used as a surrogate marker of the control of the HCV-related lymphoproliferation.
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antiviral Agents / therapeutic use. Biomarkers / blood. Cryoglobulinemia / drug therapy. Cryoglobulinemia / immunology. Cryoglobulinemia / virology. Female. Humans. Lymphoma, B-Cell / drug therapy. Lymphoma, B-Cell / immunology. Lymphoma, B-Cell / virology. Male. Middle Aged. Prospective Studies. Treatment Outcome

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  • (PMID = 18375535.001).
  • [ISSN] 1468-2060
  • [Journal-full-title] Annals of the rheumatic diseases
  • [ISO-abbreviation] Ann. Rheum. Dis.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / Biomarkers; 0 / Immunoglobulin Light Chains
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82. Hutchison CA, Cockwell P, Reid S, Chandler K, Mead GP, Harrison J, Hattersley J, Evans ND, Chappell MJ, Cook M, Goehl H, Storr M, Bradwell AR: Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. J Am Soc Nephrol; 2007 Mar;18(3):886-95
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Of patients with newly diagnosed multiple myeloma, approximately 10% have dialysis-dependent acute renal failure, with cast nephropathy, caused by monoclonal free light chains (FLC).
  • Of these, 80 to 90% require long-term renal replacement therapy.
  • Early treatment by plasma exchange reduces serum FLC concentrations, but randomized, controlled trials have shown no evidence of renal recovery.
  • This outcome can be explained by the low efficiency of the procedure.
  • A model of FLC production, distribution, and metabolism in patients with myeloma indicated that plasma exchange might remove only 25% of the total amount during a 3-wk period.
  • For increasing FLC removal, extended hemodialysis with a protein-leaking dialyzer was used.
  • Model calculations suggested that it might remove 90% of FLC during 3 wk.
  • Serum FLC reduced by 35 to 70% within 2 hr, but reduction rates slowed as extravascular re-equilibration occurred.
  • FLC concentrations rebounded on successive days unless chemotherapy was effective.
  • A total of 1.7 kg of FLC was removed from one patient during 6 wk.
  • Extended hemodialysis with the Gambro HCO 1100 dialyzer allowed continuous, safe removal of FLC in large amounts.
  • [MeSH-major] Acute Kidney Injury / therapy. Immunoglobulin Light Chains / blood. Multiple Myeloma / therapy. Renal Dialysis / methods


83. Matthews RC, Rigg G, Hodgetts S, Carter T, Chapman C, Gregory C, Illidge C, Burnie J: Preclinical assessment of the efficacy of mycograb, a human recombinant antibody against fungal HSP90. Antimicrob Agents Chemother; 2003 Jul;47(7):2208-16
The Lens. Cited by Patents in .

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  • Using in vitro assays developed for efficacy assessment of chemotherapeutic antifungal drugs, Mycograb showed activity against a wide range of yeast species (MICs against Candida albicans [fluconazole [FLC]-sensitive and FLC-resistant strains], Candida krusei, Candida tropicalis, Candida glabrata, and Candida parapsilosis, 128 to 256 microg/ml).
  • Synergy was not evident with FLC, except for FLC-sensitive C. albicans.
  • Murine kinetics showed that Mycograb at 2 mg/kg produced a maximum concentration of drug in serum of 4.7 microg/ml, a half-life at alpha phase of 3.75 min, a half-life at beta phase of 2.34 h, and an area under the concentration-time curve from 0 to t h of 155 microg. min/ml.
  • a reduction (Scheffe's test, P < 0.05) in the mean organ colony count for the FLC-resistant strain of C. albicans (kidney, liver, and spleen), C. krusei (liver and spleen), C. glabrata (liver and spleen), C. tropicalis (kidney), and C. parapsilosis (kidney, liver, and spleen) and (ii).
  • a statistically significant increase in the number of negative biopsy specimens (Fisher's exact test, P < 0.05) for C. glabrata (kidney), C. tropicalis (liver and spleen), and C. parapsilosis (liver).
  • Synergy with AMB, defined as an increase (Fisher's exact test, P < 0.05) in the number of negative biopsy specimens compared with those obtained using AMB alone, occurred with the FLC-resistant strain of C. albicans (kidney), C. krusei (spleen), C. glabrata (spleen), and C. parapsilosis (liver and spleen).
  • [MeSH-major] Antibodies, Fungal / pharmacology. Candida albicans / immunology. Candidiasis / therapy. HSP90 Heat-Shock Proteins / immunology. Recombinant Proteins / pharmacokinetics

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  • (PMID = 12821470.001).
  • [ISSN] 0066-4804
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Fungal; 0 / Antifungal Agents; 0 / Antigens, Fungal; 0 / HSP90 Heat-Shock Proteins; 0 / Recombinant Proteins
  • [Other-IDs] NLM/ PMC161838
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84. Tannuri AC, Tannuri U, Gibelli NE, Romão RL: Surgical treatment of hepatic tumors in children: lessons learned from liver transplantation. J Pediatr Surg; 2009 Nov;44(11):2083-7
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  • [Title] Surgical treatment of hepatic tumors in children: lessons learned from liver transplantation.
  • The objective of the present study was to describe our experience in liver resections, in the light of liver transplantation, emphasizing the indications for surgery, surgical techniques, complications, and results.
  • METHODS: The medical records of 53 children who underwent liver resection for primary or metastatic hepatic tumors were reviewed.
  • After neoadjuvant chemotherapy, tumor resectability was evaluated by another CT scan.
  • Surgery was performed by surgeons competent in liver transplantation.
  • As in liver living donor operation, vascular anomalies were investigated.
  • Hilar structures were dissected very close to liver parenchyma.
  • The hepatic artery and portal vein were dissected and ligated near their entrance to the liver parenchyma to avoid damaging the hilar vessels of the other lobe.
  • RESULTS: Fifty-three children with hepatic tumors underwent surgical treatment, 47 patients underwent liver resections, and in 6 cases, liver transplantation was performed because the tumor was considered unresectable.
  • There were 31 cases of hepatoblastoma, with a 9.6% mortality rate.
  • Ten children presented with other malignant tumors-3 undifferentiated sarcomas, 2 hepatocellular carcinomas, 2 fibrolamellar hepatocellular carcinomas, a rhabdomyosarcoma, an immature ovarian teratoma, and a single neuroblastoma.
  • CONCLUSION: The resection of hepatic tumors in children requires expertise in pediatric surgical practice, and many lessons learned from liver transplantation can be applied to hepatectomies.
  • [MeSH-major] Liver Neoplasms / surgery. Liver Transplantation / methods
  • [MeSH-minor] Age Factors. Blood Loss, Surgical. Carcinoma, Hepatocellular / mortality. Carcinoma, Hepatocellular / surgery. Follow-Up Studies. Hepatectomy / methods. Hepatoblastoma / mortality. Hepatoblastoma / surgery. Humans. Infant. Neoplasm Recurrence, Local / mortality. Neoplasm Recurrence, Local / surgery. Postoperative Complications / etiology. Survival Rate. Tomography, X-Ray Computed. Treatment Outcome

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  • (PMID = 19944212.001).
  • [ISSN] 1531-5037
  • [Journal-full-title] Journal of pediatric surgery
  • [ISO-abbreviation] J. Pediatr. Surg.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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85. Sionov E, Chang YC, Garraffo HM, Kwon-Chung KJ: Heteroresistance to fluconazole in Cryptococcus neoformans is intrinsic and associated with virulence. Antimicrob Agents Chemother; 2009 Jul;53(7):2804-15
Hazardous Substances Data Bank. FLUCONAZOLE .

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  • In 1999, heteroresistance to triazoles was reported in Cryptococcus neoformans strains isolated from an azole therapy failure case of cryptococcosis in an AIDS patient and in a diagnostic strain from a non-AIDS patient.
  • In this study, we analyzed 130 strains of C. neoformans isolated from clinical and environmental sources before 1979, prior to the advent of triazoles, and 16 fluconazole (FLC)-resistant strains isolated from AIDS patients undergoing FLC maintenance therapy during 1990 to 2000.
  • All strains isolated prior to 1979 manifested heteroresistance (subset of a population that grows in the presence of FLC) at concentrations between 4 and 64 microg/ml, and all 16 FLC-resistant AIDS isolates manifested heteroresistance at concentrations between 16 and 128 microg/ml.
  • Upon exposure to stepwise increases in the concentration of FLC, subpopulations that could grow at higher concentrations emerged.
  • Repeated transfer on drug-free media caused the highly resistant subpopulations to revert to the original level of heteroresistance.
  • During FLC treatment of mice infected by strains with low levels of heteroresistance, subpopulations exhibiting higher levels of heteroresistance emerged after a certain period of time.
  • The ABC transporter AFR1, known to efflux FLC, was unrelated to the heteroresistance mechanism.
  • Our study showed that heteroresistance to azole is universal and suggests that heteroresistance contributes to relapse of cryptococcosis during azole maintenance therapy.

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  • (PMID = 19414582.001).
  • [ISSN] 1098-6596
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] ENG
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Azoles; 0 / Fungal Proteins; 8VZV102JFY / Fluconazole
  • [Other-IDs] NLM/ PMC2704677
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86. Krüger WH, Kiefer T, Schüler F, Lotze C, Busemann C, Dölken G: Complete remission and early relapse of refractory plasma cell leukemia after bortezomib induction and consolidation by HLA-mismatched unrelated allogeneic stem cell transplantation. Onkologie; 2007 Apr;30(4):193-5
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  • [Title] Complete remission and early relapse of refractory plasma cell leukemia after bortezomib induction and consolidation by HLA-mismatched unrelated allogeneic stem cell transplantation.
  • BACKGROUND: Chromosomal deletion of q13 (del q13) and plasma cell leukemia predict both a worse prognosis in myeloma.
  • Experiences with bortezomib in plasma cell leukemia prior to allogeneic stem cell transplantation (SCT) have not yet been reported.
  • The myeloma progressed to plasma cell leukemia.
  • Bortezomib was given, free light chain (FLC) excretion decreased, and myeloma cells disappeared from blood and decreased in marrow.
  • FLC excretion increased, and immunosuppression was discontinued.
  • From day +84 on, bortezomib was infused again and FLC excretion decreased rapidly.
  • CONCLUSION: This case gives evidence for an excellent initial response of plasma cell leukemia to bortezomib, however, early relapse after SCT clearly indicates limitations of both bortezomib therapy and allogeneic SCT in high-risk myeloma.
  • In addition, there is need to clarify if graft-versus-myeloma effect is diminished by bortezomib therapy after allogeneic SCT.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Boronic Acids / administration & dosage. Hematopoietic Stem Cell Transplantation. Leukemia, Plasma Cell / drug therapy. Multiple Myeloma / drug therapy. Pyrazines / administration & dosage

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  • (PMID = 17396042.001).
  • [ISSN] 0378-584X
  • [Journal-full-title] Onkologie
  • [ISO-abbreviation] Onkologie
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Boronic Acids; 0 / Immunoglobulin A; 0 / Immunoglobulin Light Chains; 0 / Pyrazines; 69G8BD63PP / Bortezomib
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87. Lopez J, Dauwalder O, Joly P, Dimet I, Bienvenu J, Bernon H: [Interest and limit of a free light chain immunoassay in serum and urine for the diagnosis and the follow-up of monoclonal dysglobulinemia]. Ann Biol Clin (Paris); 2006 May-Jun;64(3):287-97

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Interest and limit of a free light chain immunoassay in serum and urine for the diagnosis and the follow-up of monoclonal dysglobulinemia].
  • [Transliterated title] Intérêt et limites des dosages sériques et urinaires des chaînes légères libres pour le diagnostic et le suivi des dysglobulinémies monoclonales.
  • This work aims to define the interest and the limits of free light chain (FLC) determination in serum and urine for the investigation of monoclonal gammopathies.
  • Based on the study of nine typical cases extracted from laboratory practice, the authors demonstrate the interest of this determination for the diagnosis and the monitoring of FLC and non secretory myelomas.
  • This test is also useful for the evaluation of response to chemotherapy and the early detection of relapses in intact immunoglobulin multiple myelomas.
  • These results are discussed in the light of the literature with a special emphasis on AL amyloidosis and monoclonal gammapathy of undetermined significance (MGUS).
  • [MeSH-major] Immunoglobulin Light Chains / blood. Immunoglobulin Light Chains / urine. Paraproteinemias / diagnosis

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  • (PMID = 16698567.001).
  • [ISSN] 0003-3898
  • [Journal-full-title] Annales de biologie clinique
  • [ISO-abbreviation] Ann. Biol. Clin. (Paris)
  • [Language] fre
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Immunoglobulin Light Chains
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88. Kurt IH, Yavuzer K, Batur MK: Short-term effect of levosimendan on free light chain kappa and lambda levels in patients with decompensated chronic heart failure. Heart Vessels; 2010 Sep;25(5):392-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • To investigate the effects of levosimendan, a positive inotropic agent, on the new heart failure markers immunoglobulin free light chains kappa and lambda (FLC-kappa and FLC-lambda) in decompensated chronic heart failure (HF), 59 patients with New York Heart Association (NYHA) class III-IV HF were enrolled.
  • Patients were randomized into levosimendan (n = 31) and standard HF treatment (n = 29) groups.
  • Serum FLC-kappa and FLC-lambda, brain natriuretic peptide (BNP), and ejection fraction (EF) were measured before treatment and on the 5th day of treatment initiation.
  • FLC-kappa (P < 0.05) and FLC-lambda (P < 0.05) were significantly decreased in the levosimendan group compared to baseline, but no difference in either marker in the standard treatment group was observed.
  • Pre- and post-treatment FLC-kappa/FLC-lambda ratios in both groups were similar, whereas FLC-kappa and FLC-lambda levels and the FLC-kappa/FLC-lambda ratio showed no significant correlation with NYHA class, brain natriuretic peptide (BNP) and ejection fraction (EF) levels; and BNP and EF changes after the treatment.
  • Symptomatic improvement in the levosimendan group according to the NYHA class was significantly better than in the standard treatment group (P = 0.044).
  • In conclusion, levosimendan caused short-term hemodynamic and symptomatic improvements, with a more pronounced decrease in FLC levels in patients with advanced decompensated HF.
  • [MeSH-major] Cardiotonic Agents / therapeutic use. Heart Failure / drug therapy. Hydrazones / therapeutic use. Immunoglobulin kappa-Chains / blood. Immunoglobulin lambda-Chains / blood. Pyridazines / therapeutic use
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Biomarkers / blood. Chronic Disease. Down-Regulation. Female. Humans. Male. Middle Aged. Natriuretic Peptide, Brain / blood. Severity of Illness Index. Stroke Volume / drug effects. Time Factors. Treatment Outcome. Turkey

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  • (PMID = 20676961.001).
  • [ISSN] 1615-2573
  • [Journal-full-title] Heart and vessels
  • [ISO-abbreviation] Heart Vessels
  • [Language] eng
  • [Publication-type] Journal Article; Randomized Controlled Trial
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Cardiotonic Agents; 0 / Hydrazones; 0 / Immunoglobulin kappa-Chains; 0 / Immunoglobulin lambda-Chains; 0 / Pyridazines; 114471-18-0 / Natriuretic Peptide, Brain; 349552KRHK / simendan
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89. Sionov E, Lee H, Chang YC, Kwon-Chung KJ: Cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes. PLoS Pathog; 2010 Apr 01;6(4):e1000848
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  • [Title] Cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes.
  • Fluconazole (FLC), a triazole, is widely used for the maintenance therapy of cryptococcosis.
  • Heteroresistance to FLC, an adaptive mode of azole resistance, was associated with FLC therapy failure cases but the mechanism underlying the resistance was unknown.
  • We used comparative genome hybridization and quantitative real-time PCR in order to show that C. neoformans adapts to high concentrations of FLC by duplication of multiple chromosomes.
  • Formation of disomic chromosomes in response to FLC stress was observed in both serotype A and D strains.
  • Strains that adapted to FLC concentrations higher than their minimal inhibitory concentration (MIC) contained disomies of chromosome 1 and stepwise exposure to even higher drug concentrations induced additional duplications of several other specific chromosomes.
  • The number of disomic chromosomes in each resistant strain directly correlated with the concentration of FLC tolerated by each strain.
  • Upon removal of the drug pressure, strains that had adapted to high concentrations of FLC returned to their original level of susceptibility by initially losing the extra copy of chromosome 1 followed by loss of the extra copies of the remaining disomic chromosomes.
  • The duplication of chromosome 1 was closely associated with two of its resident genes: ERG11, the target of FLC and AFR1, the major transporter of azoles in C. neoformans.
  • This adaptive mechanism in C. neoformans may play an important role in FLC therapy failure of cryptococcosis leading to relapse during azole maintenance therapy.

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  • (PMID = 20368972.001).
  • [ISSN] 1553-7374
  • [Journal-full-title] PLoS pathogens
  • [ISO-abbreviation] PLoS Pathog.
  • [Language] ENG
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / Azoles; 8VZV102JFY / Fluconazole
  • [Other-IDs] NLM/ PMC2848560
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90. Matsumori A, Shimada M, Jie X, Higuchi H, Groot Kormelink T, Redegeld FA: Effects of free immunoglobulin light chains on viral myocarditis. Circ Res; 2010 May 14;106(9):1533-40
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • RATIONALE: In recent work, we have demonstrated a crucial role of mast cells in the development of viral myocarditis.
  • Viral infection could lead to increased synthesis of free immunoglobulin light chains (FLC) and our earlier work showed that FLC can trigger mast cell activation.
  • OBJECTIVE: We studied the possible involvement of FLC in the pathogenesis of viral myocarditis, and therapeutic effects of FLC using an animal model of viral myocarditis.
  • Serum levels and concentrations in the heart of kappa FLC on day 14 in mice inoculated with EMC virus were significantly increased compared with controls.
  • Myocardial viral concentration was significantly inhibited, the area of myocardial lesions was smaller in mice treated with kappa or lambda FLC, and survival of mice given FLC significantly improved.
  • In contrast, an FLC antagonist deteriorated myocarditis. kappa and lambda FLC chains inhibited EMC viral replication in human amnion cells in vitro. lambda FLC significantly increased the gene expression of interleukin-10 in the heart which was previously shown to improve viral myocarditis when given exogenously.
  • FLC also tended to increase the gene expressions of interferon-alpha and -gamma in the heart mice.
  • CONCLUSIONS: FLC have antiviral and antiinflammatory effects and improved viral myocarditis in mice.
  • FLC may be promising agents for the treatment of viral myocarditis.
  • [MeSH-major] Anti-Inflammatory Agents / pharmacology. Antiviral Agents / pharmacology. Cardiovirus Infections / drug therapy. Immunoglobulin Light Chains / pharmacology. Myocarditis / drug therapy. Myocarditis / virology
  • [MeSH-minor] Animals. Disease Models, Animal. Encephalomyocarditis virus / drug effects. Encephalomyocarditis virus / physiology. Humans. Male. Mice. Mice, Inbred DBA. Microbial Sensitivity Tests. Survival Rate. Virus Replication / drug effects


91. Golenkov AK, Mitina TA, Kogarko IN, Liubimova NV, Klinushkina EF, Baryshnikov AIu: [Pharmacodynamic characteristics of velcade efficacy in resistant and recurrent multiple myeloma: determination of free light chains of blood serum immunoglobulins]. Ter Arkh; 2009;81(7):37-41
Hazardous Substances Data Bank. BORTEZOMIB .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • AIM: To ascertain individual sensitivity to velkeid in patients with resistant and recurrent multiple myeloma (MM) by determination of free light chains (FLC) of serum immunoglobulins.
  • MATERIAL AND METHODS: Fourteen patients with MM stage III (Gcappa-5, Glambda-2, Acappa-3, Alambda-1, BJcappa-3) aged 52-75 years with documented resistance to treatment or recurrence received second-line monotherapy with velkeid.
  • The drug was injected intravenously (jet) in a dose 1.3 mg/m2 on the treatment day 1, 4, 8 and 11.
  • Free light chains concentration was examined with antibodies to their latent determinants (Binding Site, UK) on nephelometer (Hitathi-911, Japan) on velkeid treatment day 1, 2, 3, 5, 9 and 12.
  • RESULTS: Nine patients showed lowering of FLC concentration and responded to treatment by Durie criteria.
  • CONCLUSION: Dynamic follow-up of FLC concentration of the tumor clone in resistant and recurrent MM evaluates pharmacodynamics of the drug.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Boronic Acids / therapeutic use. Drug Resistance, Neoplasm / drug effects. Immunoglobulin Light Chains / blood. Multiple Myeloma / drug therapy. Pyrazines / therapeutic use
  • [MeSH-minor] Aged. Bortezomib. Drug Administration Schedule. Humans. Middle Aged. Neoplasm Staging. Predictive Value of Tests. Prognosis. Recurrence

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  • (PMID = 19708571.001).
  • [ISSN] 0040-3660
  • [Journal-full-title] Terapevticheskiĭ arkhiv
  • [ISO-abbreviation] Ter. Arkh.
  • [Language] rus
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Russia (Federation)
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Boronic Acids; 0 / Immunoglobulin Light Chains; 0 / Pyrazines; 69G8BD63PP / Bortezomib
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92. Clemons KV, Sobel RA, Williams PL, Pappagianis D, Stevens DA: Efficacy of intravenous liposomal amphotericin B (AmBisome) against coccidioidal meningitis in rabbits. Antimicrob Agents Chemother; 2002 Aug;46(8):2420-6
Hazardous Substances Data Bank. AMPHOTERICIN B .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • The efficacy of intravenously administered liposomal amphotericin B (AmBisome [AmBi]) for the treatment of experimental coccidioidal meningitis was compared with those of oral fluconazole (FLC) and intravenously administered conventional amphotericin B (AMB).
  • Starting 5 days postinfection, animals received one of the following: 5% dextrose water diluent; AMB given at 1 mg/kg of body weight; AmBi given at 7.5, 15, or 22.5 mg/kg intravenously three times per week for 3 weeks; or oral FLC given at 80 mg/kg for 19 days.
  • One week after the cessation of therapy, all survivors were euthanatized, the numbers of CFU remaining in the spinal cord and brain were determined, and histological analyses were performed.
  • All AmBi-, FLC-, or AMB-treated animals survived and had prolonged lengths of survival compared with those for the controls (P < 0.0001).
  • Treated groups had significantly lower numbers of white blood cells and significantly lower protein concentrations in the cerebrospinal fluid compared with those for the controls (P < 0.01 to 0.0005) and had fewer clinical signs of infection (e.g., weight loss, elevated temperature, and neurological abnormalities including motor abnormalities).
  • The mean histological scores for AmBi-treated rabbits were lower than those for FLC-treated and control rabbits (P < 0.016 and 0.0005, respectively); the scores for AMB-treated animals were lower than those for the controls (P < 0.0005) but were similar to those for FLC-treated rabbits.
  • AmBi-treated animals had 3- to 11-fold lower numbers of CFU than FLC-treated rabbits and 6- to 35-fold lower numbers of CFU than AmB-treated rabbits.
  • Three of eight animals given 15 mg of AmBi per kg had no detectable infection in either tissue, whereas other doses of AmBi or FLC cleared either the brain or the spinal cord of infection in fewer rabbits.
  • In addition, clearance of the infection from both tissues was achieved in none of the rabbits, and neither tissue was cleared of infection in AMB-treated animals.
  • Overall, these data indicate that intravenously administered AmBi is superior to oral FLC or intravenous AMB and that FLC is better than AMB against experimental coccidioidal meningitis.
  • These data indicate that AmBi may offer an improvement in the treatment of coccidioidal meningitis.
  • [MeSH-major] Amphotericin B / therapeutic use. Antifungal Agents / therapeutic use. Coccidioidomycosis / drug therapy. Meningitis / drug therapy

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  • (PMID = 12121913.001).
  • [ISSN] 0066-4804
  • [Journal-full-title] Antimicrobial agents and chemotherapy
  • [ISO-abbreviation] Antimicrob. Agents Chemother.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antifungal Agents; 0 / liposomal amphotericin B; 7XU7A7DROE / Amphotericin B
  • [Other-IDs] NLM/ PMC127346
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