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1. Engebraaten O, Hjortland GO, Juell S, Hirschberg H, Fodstad O: Intratumoral immunotoxin treatment of human malignant brain tumors in immunodeficient animals. Int J Cancer; 2002 Feb 20;97(6):846-52
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  • [Title] Intratumoral immunotoxin treatment of human malignant brain tumors in immunodeficient animals.
  • Treatment of malignant brain tumors remains a clinical challenge.
  • New treatment modalities are under investigation and among these are intratumoral infusion of immunotoxins that bind to specific cell surface molecules on the malignant cells.
  • We have compared the efficacy of the 425.3-PE immunotoxin (which targets the epidermal growth factor [EGF] receptor) with the well-known immunotoxin Tfn-CRM107 (which targets the transferrin receptor), for the treatment of subcutaneous and intracranial human gliomas in nude animals.
  • Bolus intratumoral administration of 1 microg Tfn-CRM107 or 425.3-PE into sc U87Mg tumors in nude mice reduced the tumor volume to 29 and 79%, respectively, of that in the control group 18 days after start of treatment.
  • Higher doses of Tfn-CRM107 were toxic to the animals, whereas 425.3-PE was tolerated, with a dose-response relationship of up to 8 microg, a dose that reduced the tumor volume to 2% of control.
  • In nude rats, treatment of intracerebral U87Mg tumors with Tfn-CRM107 proved ineffective and doses above 10 ng/animal were toxic to tumor-bearing rats.
  • Direct interstitial infusion of immunotoxins into such tumors reduced the number of animals with detectable tumors at autopsy after 3 months, from 8/9 in the control animals to 4/6 and 2/6 in animals treated with Tfn-CRM107 and 425.3-PE, respectively.
  • [MeSH-major] ADP Ribose Transferases. Bacterial Toxins / therapeutic use. Brain Neoplasms / drug therapy. Exotoxins / immunology. Glioblastoma / drug therapy. Immunotoxins / therapeutic use. Transferrin / therapeutic use. Virulence Factors
  • [MeSH-minor] Animals. Antibodies, Monoclonal / immunology. Biopsy. Cell Division. Flow Cytometry. Humans. Immunoconjugates. Mice. Mice, Nude. Neoplasm Proteins / biosynthesis. Rats. Rats, Nude. Receptor, Epidermal Growth Factor / immunology. Survival Rate. Transplantation, Heterologous. Tumor Cells, Cultured

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  • [Copyright] Copyright 2001 Wiley-Liss, Inc.
  • (PMID = 11857366.001).
  • [ISSN] 0020-7136
  • [Journal-full-title] International journal of cancer
  • [ISO-abbreviation] Int. J. Cancer
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Bacterial Toxins; 0 / Exotoxins; 0 / Immunoconjugates; 0 / Immunotoxins; 0 / Neoplasm Proteins; 0 / Tf-CRM107; 0 / Transferrin; 0 / Virulence Factors; EC 2.4.2.- / ADP Ribose Transferases; EC 2.4.2.31 / toxA protein, Pseudomonas aeruginosa; EC 2.7.10.1 / Receptor, Epidermal Growth Factor
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2. Sampson JH, Raghavan R, Brady ML, Provenzale JM, Herndon JE 2nd, Croteau D, Friedman AH, Reardon DA, Coleman RE, Wong T, Bigner DD, Pastan I, Rodríguez-Ponce MI, Tanner P, Puri R, Pedain C: Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions. Neuro Oncol; 2007 Jul;9(3):343-53
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  • [Title] Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions.
  • Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain.
  • Despite the promise of CED, clinical trials have demonstrated that target-tissue anatomy and patient-specific physiology play a major role in drug distribution using this technique.
  • In this study, we retrospectively tested the ability of a software algorithm using MR diffusion tensor imaging to predict patient-specific drug distributions by CED.
  • A tumor-targeted cytotoxin, cintredekin besudotox (interleukin 13-PE38QQR), was coinfused with iodine 123-labeled human serum albumin (123I-HSA), in patients with recurrent malignant gliomas.
  • The spatial distribution of 123I-HSA was then compared to a drug distribution simulation provided by the software algorithm.
  • The algorithm had a high sensitivity (71.4%) and specificity (100%) for identifying the high proportion (7 of 14) of catheter trajectories that failed to deliver drug into the desired anatomical region (p = 0.021).
  • Routine use of this algorithm, and its further developments, should improve prospective selection of catheter trajectories, and thereby improve the efficacy of drugs delivered by this promising technique.

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  • (PMID = 17435179.001).
  • [ISSN] 1522-8517
  • [Journal-full-title] Neuro-oncology
  • [ISO-abbreviation] Neuro-oncology
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P50 CA108786; United States / NINDS NIH HHS / NS / P50 NS020023; United States / NCI NIH HHS / CA / 5P50-CA108786; United States / NCRR NIH HHS / RR / K23 RR016065; United States / NCRR NIH HHS / RR / K23 RR16065; United States / NCRR NIH HHS / RR / S10 RR15697; United States / Intramural NIH HHS / / ; United States / NCI NIH HHS / CA / R01 CA097611; United States / NINDS NIH HHS / NS / 2P50-NS20023
  • [Publication-type] Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Exotoxins; 0 / IL13-PE38QQR; 0 / Interleukin-13
  • [Other-IDs] NLM/ PMC1907410
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3. Yalçin B, Kremer LC, Caron HN, van Dalen EC: High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma. Cochrane Database Syst Rev; 2010;(5):CD006301
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  • [Title] High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma.
  • BACKGROUND: Despite the development of new treatment options, the prognosis of high-risk neuroblastoma patients is still poor; more than half of patients experience disease recurrence.
  • High-dose chemotherapy and haematopoietic stem cell rescue (i.e. myeloablative therapy) might improve survival.
  • OBJECTIVES: To compare the effectiveness of myeloablative therapy with conventional therapy in children with high-risk neuroblastoma.
  • SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effectiveness of myeloablative therapy with conventional therapy in high-risk neuroblastoma patients.
  • The meta-analysis of event-free survival showed a significant difference in favour of the myeloablative therapy group (HR 0.78; 95% CI 0.67 to 0.90), as did the meta-analysis of overall survival (HR 0.74; 95% CI 0.57 to 0.98).
  • The meta-analysis of secondary malignant disease and treatment-related death did not show a significant difference between the treatment groups.
  • In one study a significant difference in favour of the conventional therapy group was identified for renal effects, interstitial pneumonitis and veno-occlusive disease, whereas for serious infections and sepsis no significant difference between the treatment groups was identified.
  • AUTHORS' CONCLUSIONS: Based on the currently available evidence, myeloablative therapy seems to be a good treatment option for children with high-risk neuroblastoma.
  • It results in higher survival rates than conventional therapy, although possible higher levels of adverse effects should be kept in mind.
  • A definitive conclusion regarding the effect of myeloablative therapy in different subgroups is not possible.
  • This systematic review only allows a conclusion on the concept of myeloablative therapy; no conclusions can be made regarding the best treatment strategy.
  • Future trials on the use of myeloablative therapy for high-risk neuroblastoma should focus on identifying the most optimal induction and/or myeloablative regimen.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Hematopoietic Stem Cell Transplantation / methods. Neuroblastoma / drug therapy
  • [MeSH-minor] Age Factors. Bone Marrow / drug effects. Child. Child, Preschool. Disease-Free Survival. Humans. Infant. Neoplasm Recurrence, Local. Prognosis. Randomized Controlled Trials as Topic

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  • [UpdateIn] Cochrane Database Syst Rev. 2013;8:CD006301 [23970444.001]
  • (PMID = 20464740.001).
  • [ISSN] 1469-493X
  • [Journal-full-title] The Cochrane database of systematic reviews
  • [ISO-abbreviation] Cochrane Database Syst Rev
  • [Language] eng
  • [Publication-type] Journal Article; Meta-Analysis; Review
  • [Publication-country] England
  • [Number-of-references] 75
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4. Shitara K, Munakata M, Ishiguro A, Kudo T, Okada R, Tomioka R, Mitobe S, Yokoyama S, Sakata Y: [Colonic perforation in a patient treated with combination chemotherapy for recurrent ovarian clear cell adenocarcinoma]. Gan To Kagaku Ryoho; 2006 Oct;33(10):1497-1500
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  • [Title] [Colonic perforation in a patient treated with combination chemotherapy for recurrent ovarian clear cell adenocarcinoma].
  • BACKGROUND: Colonic perforation due to colitis is a known and reported side effect of chemotherapy.
  • CASE REPORT: A 53-year-old woman was treated with combination chemotherapy of irinotecan plus cisplatin for a recurrent ovarian clear cell adenocarcinoma.
  • Steroid was also used for suspected interstitial pneumonia.
  • After two cycles of treatment, she developed a colonic perforation.
  • Oral intake could be restarted for a while, but she died from tumor progression one and a half months after the diagnosis of perforation.
  • [MeSH-major] Adenocarcinoma, Clear Cell / drug therapy. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cecal Diseases / etiology. Intestinal Perforation / etiology. Neoplasm Recurrence, Local / drug therapy. Ovarian Neoplasms / drug therapy
  • [MeSH-minor] Camptothecin / administration & dosage. Camptothecin / analogs & derivatives. Cisplatin / administration & dosage. Colonoscopy. Drainage. Drug Administration Schedule. Fatal Outcome. Female. Humans. Lung Neoplasms / secondary. Middle Aged. Pleural Effusion, Malignant / etiology

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  • (PMID = 17033246.001).
  • [ISSN] 0385-0684
  • [Journal-full-title] Gan to kagaku ryoho. Cancer & chemotherapy
  • [ISO-abbreviation] Gan To Kagaku Ryoho
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 7673326042 / irinotecan; Q20Q21Q62J / Cisplatin; XT3Z54Z28A / Camptothecin
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5. Suminoe A, Matsuzaki A, Koga Y, Kusuhara K, Hara T: Human herpesvirus 6 (HHV-6)-associated pleurisy after unrelated cord blood transplantation in children with chemotherapy-resistant malignant Lymphoma. J Pediatr Hematol Oncol; 2007 Oct;29(10):709-12
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Human herpesvirus 6 (HHV-6)-associated pleurisy after unrelated cord blood transplantation in children with chemotherapy-resistant malignant Lymphoma.
  • Two children, 5 and 10 years of age, received unrelated cord blood transplantation (CBT) for malignant lymphoma.
  • Both of them suffered from pleurisy with and without interstitial pneumonitis after transplantation.
  • By the quantitative real-time polymerase chain reaction, human herpesvirus 6 (HHV-6) variant B DNA was detected in pleural effusion.
  • This is the first report of HHV-6-associated pleurisy after hematopoietic stem cell transplantation.
  • HHV-6-associated pleurisy should be considered as a complication after hematopoietic stem cell transplantation even in the absence of pneumonitis.
  • Quantitative polymerase chain reaction is a useful tool for rapid detection of viral DNA, which may facilitate precise diagnosis and appropriate treatment.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cord Blood Stem Cell Transplantation / adverse effects. Drug Resistance, Neoplasm. Herpesvirus 6, Human / isolation & purification. Lymphoma / drug therapy. Pleurisy / virology. Roseolovirus Infections / virology

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  • (PMID = 17921853.001).
  • [ISSN] 1077-4114
  • [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 / DNA, Viral
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6. Bhat GM, Lone MI, Alsolami S, Iqbal QM: Recurrent malignant Leydig cell tumor of testis: a case report with review of literature. Gulf J Oncolog; 2010 Jan;(7):42-5
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  • [Title] Recurrent malignant Leydig cell tumor of testis: a case report with review of literature.
  • Malignant Testicular Leydig Cell tumors (leydigomas) are extremely rare to occur and mostly carry a bad prognosis.
  • Here we describe the disease course of a middle aged patient with recurrent / metastatic Leydig cell tumor of testes, who needed repeated oncosurgical intervention and chemotherapy.
  • [MeSH-major] Leydig Cell Tumor / secondary. Neoplasm Recurrence, Local / pathology. Testicular Neoplasms / pathology

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  • (PMID = 20164008.001).
  • [ISSN] 2078-2101
  • [Journal-full-title] The Gulf journal of oncology
  • [ISO-abbreviation] Gulf J Oncolog
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Kuwait
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7. Iwamoto I, Yanazume S, Fujino T, Yoshioka T, Douchi T: Leydig cell tumor in an elderly patient with complete androgen insensitivity syndrome. Gynecol Oncol; 2005 Mar;96(3):870-2
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  • [Title] Leydig cell tumor in an elderly patient with complete androgen insensitivity syndrome.
  • Testicular tumors often develop in patients with AIS, Sertoli cell tumor and seminoma being the most common types.
  • Leydig cell tumor in AIS is extremely rare.
  • CASE: A large abdominal tumor developed in a 73-year-old female patient.
  • The patient underwent the extirpation of bilateral gonads including the tumor, pelvic lymph nodes, omentum and appendix vermiformis.
  • The pathological diagnosis was malignant Leydig cell tumor of the left testis.
  • There was no adjuvant radiation or chemotherapy performed.
  • CONCLUSION: We reported an extremely rare case of malignant Leydig cell tumor developing in an elderly AIS patient.
  • [MeSH-major] Androgen-Insensitivity Syndrome / complications. Leydig Cell Tumor / complications. Ovarian Neoplasms / complications


8. Nakamura S, Kimura S, Kashima M, Shichijo K, Yoshida S, Harada E, Matsushita T, Oshima Y, Tamaki Y, Horiuchi N, Takeichi T, Fujimoto H, Masuda K, Iwasaka N, Shinomiya S: [A case of peritonitis carcinomatosa from goblet cell carcinoid of the appendix treated by intraperitoneal paclitaxel and systemic S-1 chemotherapy]. Gan To Kagaku Ryoho; 2008 Dec;35(13):2425-8
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  • [Title] [A case of peritonitis carcinomatosa from goblet cell carcinoid of the appendix treated by intraperitoneal paclitaxel and systemic S-1 chemotherapy].
  • Goblet cell carcinoid of the appendix is a rare neoplasm and clinically tends to take a malignant course.
  • But appropriate chemotherapy for inoperable cases with peritoneal dissemination is not established.
  • A 77-year-old woman with a past history of appendectomy was admitted to our hospital complaining of abdominal fullness.
  • Abdominal computed tomography showed massive ascites and slight contrast enhancement of appendix.
  • A tumor was found by colonoscopic examination at the orifice of vermiform and was diagnosed pathologically as goblet cell carcinoid of the appendix.
  • We performed intraperitoneal paclitaxel(PTX)administration at 70 mg/m(2) week without any resection of the tumor.
  • Ascites were reduced immediately, but drug-induced interstitial pneumonia occurred due to PTX.
  • After steroid therapy, we switched to systemic S-1 therapy.
  • For about one year, her tumor was controlled but became worse thirteen months after diagnosis and died.
  • It is thought that intraabdominal paclitaxel administration and systemic S-1 therapy can be one of appropriate forms of chemotherapy for inoperable peritoneal carcinomatosis from goblet cell carcinoid of appendix.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoid Tumor / drug therapy. Carcinoid Tumor / pathology. Oxonic Acid / therapeutic use. Paclitaxel / therapeutic use. Peritonitis / drug therapy. Peritonitis / pathology. Tegafur / therapeutic use
  • [MeSH-minor] Aged. Colonic Neoplasms / complications. Colonic Neoplasms / drug therapy. Colonic Neoplasms / pathology. Colonic Neoplasms / surgery. Colonoscopy. Drug Combinations. Female. Humans. Injections, Intraperitoneal. Tomography, X-Ray Computed. Treatment Failure

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  • (PMID = 19098416.001).
  • [ISSN] 0385-0684
  • [Journal-full-title] Gan to kagaku ryoho. Cancer & chemotherapy
  • [ISO-abbreviation] Gan To Kagaku Ryoho
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Drug Combinations; 150863-82-4 / S 1 (combination); 1548R74NSZ / Tegafur; 5VT6420TIG / Oxonic Acid; P88XT4IS4D / Paclitaxel
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9. Froehner M, Beuthien-Baumann B, Dittert DD, Schuler U, Wirth MP: Lack of efficacy of imatinib in a patient with metastatic Leydig cell tumor. Cancer Chemother Pharmacol; 2006 Nov;58(5):716-8
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  • [Title] Lack of efficacy of imatinib in a patient with metastatic Leydig cell tumor.
  • Imatinib is a tyrosine kinase inhibitor with activity in gastrointestinal stromal tumor and a variety of other solid and hematological malignancies.
  • Studies in vitro and in a mouse model suggested that the imatinib might also be active in malignant Leydig cell tumor.
  • We report on the--to our knowledge--first treatment experiment with imatinib in a patient with metastatic Leydig cell tumor.
  • Unfortunately, the tumor progressed during treatment.
  • [MeSH-major] Leydig Cell Tumor / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use. Testicular Neoplasms / drug therapy
  • [MeSH-minor] Aged. Antineoplastic Agents / pharmacology. Antineoplastic Agents / therapeutic use. Benzamides. Disease Progression. Enzyme Inhibitors / pharmacology. Enzyme Inhibitors / therapeutic use. Humans. Imatinib Mesylate. Male. Protein-Tyrosine Kinases / antagonists & inhibitors. Treatment Failure

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  • (PMID = 16450163.001).
  • [ISSN] 0344-5704
  • [Journal-full-title] Cancer chemotherapy and pharmacology
  • [ISO-abbreviation] Cancer Chemother. Pharmacol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Enzyme Inhibitors; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases
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10. Jain SH, Sadow PM, Nosé V, Dluhy RG: A patient with ectopic cortisol production derived from malignant testicular masses. Nat Clin Pract Endocrinol Metab; 2008 Dec;4(12):695-700
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  • [Title] A patient with ectopic cortisol production derived from malignant testicular masses.
  • DIAGNOSIS: Cushing syndrome was diagnosed on the basis of a markedly elevated 24-hour urine free cortisol level and classic cushingoid features.
  • Nevertheless, the possibility of a malignant Leydig cell tumor with ectopic cortisol production could not be excluded.
  • Despite initial success with this regimen, the patient died as a result of tumor progression and complications of poorly controlled hypercortisolism.
  • [MeSH-major] Adrenal Rest Tumor / complications. Cushing Syndrome / diagnosis. Cushing Syndrome / drug therapy. Hydrocortisone / blood. Testicular Neoplasms / complications
  • [MeSH-minor] Adrenocortical Carcinoma / blood. Adrenocortical Carcinoma / diagnosis. Adrenocortical Carcinoma / pathology. Adrenocorticotropic Hormone / blood. Aged. Humans. Male. Metyrapone / therapeutic use. Mitotane / therapeutic use

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  • (PMID = 18941436.001).
  • [ISSN] 1745-8374
  • [Journal-full-title] Nature clinical practice. Endocrinology & metabolism
  • [ISO-abbreviation] Nat Clin Pract Endocrinol Metab
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 78E4J5IB5J / Mitotane; 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone; ZS9KD92H6V / Metyrapone
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11. Tirilomis T, Zenker D, Mirzaie M, Dalichau H: Pulmonary Langerhans' cell histiocytosis (histiocytosis X) following metastasizing malignant melanoma. Swiss Med Wkly; 2002 Jun 1;132(21-22):285-7
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  • [Title] Pulmonary Langerhans' cell histiocytosis (histiocytosis X) following metastasizing malignant melanoma.
  • BACKGROUND: Pulmonary Langerhans' cell histiocytosis (histiocytosis X) is an uncommon, diffuse interstitial lung disease of unknown cause, mostly presenting in young smokers.
  • Association of pulmonary Langerhans' cell histiocytosis with a malignant neoplasm is rare.
  • CASE DESCRIPTION AND RESULTS: We present and discuss the case of a 48-year-old man (ex-smoker) with metastasising malignant melanoma.
  • A few months after chemotherapy and a modified Whipple procedure for retroduodenal metastasis of a malignant melanoma, computer tomographic scans revealed intrapulmonary "ring-shaped structures".
  • Endobronchial biopsies and bronchioalveolar lavage showed no evidence of neoplasm or inflammation.
  • Open-lung biopsy was performed and revealed pulmonary Langerhans' cell histiocytosis.
  • CONCLUSION: To our knowledge this is the first reported case of pulmonary Langerhans' cell histiocytosis in association with malignant melanoma.
  • Chemotherapy for malignant melanoma may be related to the development of pulmonary Langerhans' cell histiocytosis.
  • [MeSH-major] Histiocytosis, Langerhans-Cell / complications. Melanoma / complications
  • [MeSH-minor] Humans. Male. Middle Aged. Neoplasm Metastasis. Tomography, X-Ray Computed

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  • (PMID = 12362286.001).
  • [ISSN] 1424-7860
  • [Journal-full-title] Swiss medical weekly
  • [ISO-abbreviation] Swiss Med Wkly
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Switzerland
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12. Tange Y, Kondo A, Egorin MJ, Mania-Farnell B, Daneriallis GM, Nakazaki H, Sredni ST, Rajaram V, Goldman S, Soares MB, Tomita T: Interstitial continuous infusion therapy in a malignant glioma model in rats. Childs Nerv Syst; 2009 Jun;25(6):655-62
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  • [Title] Interstitial continuous infusion therapy in a malignant glioma model in rats.
  • PURPOSE: Local direct delivery of chemotherapeutic agents for the treatment of brain tumors is an area of focus in the development of new therapeutic paradigms.
  • These techniques need improvement, especially in terms of drug retention in brain tissue.
  • MATERIALS AND METHODS: In this study, we used a rat glioma model to examine carboplatin distribution, as measured by platinum penetration, after delivery via interstitial continuous (i.c.) infusion.
  • We also examined rat survival times in response to carboplatin and oxaliplatin. I.C. infusion, a modified version of convection-enhanced delivery (CED) for local drug delivery, uses low volume (1 microl per hour) continuous infusion directly into the tumor.
  • RESULTS: I.C. infusion produced a nearly 360-fold higher concentration of platinum in tumor tissue and significantly prolonged rodent survival time compared to intraperitoneal (i.p.) infusion.
  • CONCLUSIONS: We showed i.c. infusion allows for circumvention of the blood-brain barrier, focused drug distribution, and sustained drug delivery.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Brain Neoplasms / drug therapy. Carboplatin / administration & dosage. Glioma / drug therapy
  • [MeSH-minor] Animals. Blood-Brain Barrier / drug effects. Brain / drug effects. Brain / metabolism. Brain / pathology. Catheterization. Cell Line, Tumor. Corpus Striatum / drug effects. Disease Models, Animal. Kaplan-Meier Estimate. Male. Neoplasm Transplantation. Organoplatinum Compounds / administration & dosage. Organoplatinum Compounds / pharmacokinetics. Platinum / metabolism. Rats. Rats, Inbred F344. Treatment Outcome

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  • (PMID = 19212774.001).
  • [ISSN] 1433-0350
  • [Journal-full-title] Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
  • [ISO-abbreviation] Childs Nerv Syst
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Organoplatinum Compounds; 04ZR38536J / oxaliplatin; 49DFR088MY / Platinum; BG3F62OND5 / Carboplatin
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13. de la Roza G, Naqvi A, Clark K: Gastrointestinal stromal tumors presenting as a prostatic mass. Can J Urol; 2009 Feb;16(1):4502-6
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  • Gastrointestinal stromal tumors (GISTs) are a rare and heterogeneous group of spindle cell neoplasms that have also been reported outside of gastrointestinal (GI) tract.
  • These tumors are characterized by somatic mutations of c-KIT (CD117), a proto-oncogene that encodes a receptor tyrosine kinase normally expressed in the interstitial cell of Cajal that control the GI smooth muscle peristalsis, and an exquisite sensitivity to the action of the tyrokinase inhibitor imatinib mesylate (STI571; Gleevec).
  • We report two cases of gastrointestinal stromal tumor identified on prostatic biopsies, where a primary prostatic sarcoma was considered in the differential diagnosis.
  • In one of the cases, there was extensive local disease involving prostate, rectum, and pelvic wall, as well as metastatic disease that quickly lead to the patient's death despite aggressive treatment with imatinib mesylate and conventional chemotherapy.
  • In the other case, the tumor was mostly confined to the rectum but also focally extended into the prostate capsule.
  • In both cases, tissue samples from prostate and the rectum showed a malignant spindle cell neoplasm, which was positive for CD117 (c-kit).
  • Given their unique clinical management, gastrointestinal stromal tumors should be considered in the differential diagnosis of spindle cell lesions on prostatic needle biopsies and CD117 should be added to the immunohistochemical panel in the work-up of such lesions to avoid misinterpreting them as primary prostatic neoplasms.

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  • (PMID = 19222892.001).
  • [ISSN] 1195-9479
  • [Journal-full-title] The Canadian journal of urology
  • [ISO-abbreviation] Can J Urol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Canada
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14. Demetri GD: Identification and treatment of chemoresistant inoperable or metastatic GIST: experience with the selective tyrosine kinase inhibitor imatinib mesylate (STI571). Eur J Cancer; 2002 Sep;38 Suppl 5:S52-9
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  • [Title] Identification and treatment of chemoresistant inoperable or metastatic GIST: experience with the selective tyrosine kinase inhibitor imatinib mesylate (STI571).
  • GIST has been shown to share immunohistochemical, ultrastructural and histogenic similarities with the interstitial cells of Cajal.
  • Both GIST and the interstitial cells of Cajal express KIT, the receptor tyrosine kinase that is the protein product of the c-kit proto-oncogene.
  • Sequencing of c-kit complementary DNA from human GIST cells has demonstrated a high frequency of mutations that lead to constitutive activation of the KIT tyrosine kinase in the absence of stimulation by its physiologic ligand (stem cell factor).
  • Historically, malignant GIST has been highly refractory to conventional cytotoxic therapy.
  • Signal transduction inhibition as cancer therapy was first tested successfully with imatinib mesylate (formerly known as STI571), a selective small-molecule tyrosine kinase inhibitor, with the initial target being blockade of Bcr-Abl, the oncogene with tyrosine kinase activity responsible for the pathogenesis of chronic myelogenous leukemia (CML).
  • The first GIST patient to receive imatinib exhibited dramatic benefit despite far-advanced metastatic disease that was previously refractory to all chemotherapy.
  • The results from these studies have established imatinib as an effective new therapeutic alternative for the majority of patients with advanced GIST, a solid tumor for which no prior chemotherapy has ever shown antitumor efficacy.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Enzyme Inhibitors / therapeutic use. Gastrointestinal Neoplasms / drug therapy. Neoplasms, Connective Tissue / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use. Stromal Cells
  • [MeSH-minor] Benzamides. Drug Resistance, Neoplasm. Humans. Imatinib Mesylate. Neoplasm Proteins / antagonists & inhibitors. Neoplasm Recurrence, Local / prevention & control. Protein-Tyrosine Kinases / antagonists & inhibitors. Proto-Oncogene Proteins c-kit. Receptor Protein-Tyrosine Kinases. Tomography, Emission-Computed

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  • (PMID = 12528773.001).
  • [ISSN] 0959-8049
  • [Journal-full-title] European journal of cancer (Oxford, England : 1990)
  • [ISO-abbreviation] Eur. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Enzyme Inhibitors; 0 / Neoplasm Proteins; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases; EC 2.7.10.1 / Proto-Oncogene Proteins c-kit; EC 2.7.10.1 / Receptor Protein-Tyrosine Kinases
  • [Number-of-references] 28
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15. De Vleeschouwer S, Van Calenbergh F, Demaerel P, Flamen P, Rutkowski S, Kaempgen E, Wolff JE, Plets C, Sciot R, Van Gool SW: Transient local response and persistent tumor control in a child with recurrent malignant glioma: treatment with combination therapy including dendritic cell therapy. Case report. J Neurosurg; 2004 May;100(5 Suppl Pediatrics):492-7
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  • [Title] Transient local response and persistent tumor control in a child with recurrent malignant glioma: treatment with combination therapy including dendritic cell therapy. Case report.
  • Treatment of malignant glioma is difficult and discouraging.
  • Even after resection and maximal adjuvant therapy, the prognosis remains poor.
  • The authors sought a novel form of treatment, such as stimulating the patient's own immune response against the tumor, and developed a protocol of tumor vaccination in which autologous dendritic cells (DCs) were used in patients with recurrent malignant glioma.
  • Ten years later, a Grade III recurrence was discovered and treated with subtotal resection, interstitial radiation, six courses of oral temozolomide, and 12 courses of oral VP 16.
  • At the end of the chemotherapy cycle, a new rapidly growing recurrence was diagnosed.
  • The efficacy of immunization was checked by a positive delayed-type hypersensitivity skin reaction after the second injection.
  • Simultaneously, positron emission tomography imaging revealed a transient increase of metabolic activity around the resection cavity, but the metabolic uptake ratio remained below 1.8.
  • This case report illustrates the potential of vaccination with DCs loaded with crude tumor homogenate as adjuvant therapy to induce prolonged tumor control of malignant glioma and the objective noninvasively monitored immune response against infiltrating tumor cells.
  • [MeSH-major] Astrocytoma / therapy. Brain Neoplasms / therapy. Cancer Vaccines / immunology. Dendritic Cells / immunology. Immunotherapy, Active / methods
  • [MeSH-minor] Child, Preschool. Combined Modality Therapy. Female. Humans. Neoplasm Recurrence, Local. Photomicrography

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  • (PMID = 15287461.001).
  • [ISSN] 0022-3085
  • [Journal-full-title] Journal of neurosurgery
  • [ISO-abbreviation] J. Neurosurg.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Cancer Vaccines
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16. Harding J, Burtness B: Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody. Drugs Today (Barc); 2005 Feb;41(2):107-27
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  • Dimerization results in activation of intracellular tyrosine kinase, protein phosphorylation and stimulation of various cell signaling pathways that mediate gene transcription and cell cycle progression.
  • In addition, expression of the EGFR by malignant cells is associated with poor prognosis and resistance to therapy.
  • Binding of the antibody to the EGFR prevents stimulation of the receptor by endogenous ligands and results in inhibition of cell proliferation, enhanced apoptosis, and reduced angiogenesis, invasiveness and metastasis.
  • The EGFR is a prime target for new anticancer therapy, and other agents in development include small molecular tyrosine kinase inhibitors and antisense therapies.
  • Preclinical studies have demonstrated that cetuximab reduces chemotherapy and radiotherapy resistance in human tumor cell lines in vitro and in nude mice bearing xenografts of human tumors.
  • In clinical and preclinical studies cetuximab has been shown to induce response to treatment when used in combination with chemotherapy in patients previously refractory to chemotherapy.
  • Based on these studies, cetuximab can be added to regimens using docetaxel, cisplatin, carboplatin, irinotecan, paclitaxel and fluorouracil and may add to treatment efficacy.
  • The most commonly reported adverse event associated with cetuximab treatment is an acneiform rash that occurs in 70-80% of patients treated with cetuximab.
  • The rash is rarely dose- or treatment-limiting, and may diminish in intensity with continued exposure to cetuximab.
  • Improvement may be seen after treatment with topical antibiotic preparations, topical steroids or topical retinoids.
  • The rash resolves fully after discontinuation of cetuximab treatment.
  • In fact, analysis of four phase II clinical trials of cetuximab in combination with chemotherapy in patients with colorectal cancer, squamous cell carcinoma of the head and neck, or pancreatic cancer showed that development of the acneiform rash was significantly correlated with response to treatment; grade 3 rash may be especially predictive of response.
  • Serious cetuximab-related toxicities include hypersensitivity, infusion reactions and interstitial lung disease.
  • Other phase II and III studies show significant response to treatment in variable proportions of patients with squamous cell carcinoma of the head and neck, non-small cell lung cancer and pancreatic cancer when cetuximab is used first or second line in combination with chemotherapy.
  • Thus, cetuximab is emerging as a very promising new therapy to be used in conjunction with existing therapies for the treatment of a spectrum of solid tumors.
  • [MeSH-major] Antibodies, Monoclonal / pharmacology. Antibodies, Monoclonal / therapeutic use. Antineoplastic Agents / pharmacology. Antineoplastic Agents / therapeutic use. Neoplasms / drug therapy. Receptor, Epidermal Growth Factor / immunology
  • [MeSH-minor] Animals. Antibodies, Monoclonal, Humanized. Antibody Specificity. Apoptosis / drug effects. Area Under Curve. Cell Proliferation / drug effects. Cetuximab. Chemotherapy, Adjuvant. Clinical Trials as Topic. Drug Resistance, Neoplasm. Half-Life. Humans. Neovascularization, Pathologic / drug therapy. Radiation Tolerance

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  • [Copyright] Copyright 2005 Prous Science. All rights reserved.
  • (PMID = 15821783.001).
  • [ISSN] 1699-3993
  • [Journal-full-title] Drugs of today (Barcelona, Spain : 1998)
  • [ISO-abbreviation] Drugs Today
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Spain
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antineoplastic Agents; EC 2.7.10.1 / Receptor, Epidermal Growth Factor; PQX0D8J21J / Cetuximab
  • [Number-of-references] 87
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17. He MX, Zhu MH, Zhang YM, Fu QG, Wu LL: [Solitary plasmacytoma of spine: a clinical, radiologic and pathologic study of 13 cases]. Zhonghua Bing Li Xue Za Zhi; 2009 May;38(5):307-11
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  • METHODS: The clinical, radiologic and pathologic features, as well as treatment and follow-up data, of 13 solitary plasmacytoma of spine cases were retrieved and analyzed.
  • Histologic examination showed diffuse infiltration by malignant cells.
  • In well-differentiated plasmacytomas, the tumor cells resembled normal plasma cells.
  • The interstitial stroma was scanty and contained plenty of vessels, sometimes with formation of blood lakes.
  • Immunohistochemical study showed that the tumor cells were positive for CD79a and negative for CD20.
  • Plasma cell marker PC was expressed in all cases, while IgG was positive in 5 cases, IgM in 1 case, MUM1 in 10 cases and CD138 in 8 cases.
  • All cases were operated, with adjuvant chemotherapy and radiotherapy given.
  • CONCLUSIONS: Correlation of clinical, radiologic and pathologic features is important in diagnosis of solitary plasmacytoma of spine.
  • Early detection by radiologic examination, local surgical resection, post-operative chemoradiotherapy and long-term follow-up are prudent for successful management of this condition.
  • [MeSH-minor] Adult. Aged. Antigens, CD79 / metabolism. Chemotherapy, Adjuvant. Diagnosis, Differential. Female. Follow-Up Studies. Humans. Lymphoma, Large B-Cell, Diffuse / pathology. Magnetic Resonance Imaging. Male. Middle Aged. Neoplasm Recurrence, Local. Osteosarcoma / pathology. Radiotherapy, Adjuvant. Tomography, X-Ray Computed

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  • (PMID = 19575872.001).
  • [ISSN] 0529-5807
  • [Journal-full-title] Zhonghua bing li xue za zhi = Chinese journal of pathology
  • [ISO-abbreviation] Zhonghua Bing Li Xue Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antigens, CD79; 0 / CD79A protein, human
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18. Rainov NG, Kramm CM: Vector delivery methods and targeting strategies for gene therapy of brain tumors. Curr Gene Ther; 2001 Nov;1(4):367-83
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  • [Title] Vector delivery methods and targeting strategies for gene therapy of brain tumors.
  • Efficient virus and non-virus vector systems for gene transfer to tumor cells have been developed and tested in cell culture and in animal experiments.
  • With some of the earliest and most comprehensively evaluated vectors, such as retroviruses, advanced clinical trials were performed in tumor patients.
  • Malignant primary brain tumors (gliomas) have been chosen for the first clinical studies on novel gene therapy approaches because these tumors are non-metastatic and develop on the largely postmitotic background of normal glial and neuronal tissue.
  • However, the human cancer gene therapy studies performed so far were not as successful as preclinical animal experiments.
  • Furthermore, the clinical studies did not address major limiting factors for in vivo gene therapy, such as insufficient gene transfer rates to the tumor with the used local delivery modalities, and the resulting inability of a particular transgene-prodrug system to confer permanently eradicating cytotoxicity to the whole neoplasm.
  • Critical evaluation of gene transfer and therapy studies has led to the conclusion that, even using identical vectors, the anatomical route of vector administration can dramatically affect both the efficiency of tumor transduction and its spatial distribution, as well as the extent of intratumoral and intracerebral transgene expression.
  • This review concentrates on different physical methods for vector delivery to malignant primary brain tumors in experimental or clinical settings: stereotactic or direct intratumoral injection or convection-enhanced bulk-flow interstitial delivery; intrathecal and intraventricular injection; and intravascular infusion with or without modification of the blood-tumor-barrier.
  • The advantages and drawbacks of the different modes and delivery routes of in vivo vector application, and the possibilities for tumor targeting by modifications of the native tropism of virus vectors or by using tissue-specific or inducible transgene expression are summarized.
  • [MeSH-major] Brain Neoplasms / therapy. Gene Targeting. Genetic Therapy / methods. Genetic Vectors / administration & dosage
  • [MeSH-minor] Animals. Blood-Brain Barrier / drug effects. Humans

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  • (PMID = 12109063.001).
  • [ISSN] 1566-5232
  • [Journal-full-title] Current gene therapy
  • [ISO-abbreviation] Curr Gene Ther
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Netherlands
  • [Number-of-references] 206
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19. Pollack VA, Alvarez E, Tse KF, Torgov MY, Xie S, Shenoy SG, MacDougall JR, Arrol S, Zhong H, Gerwien RW, Hahne WF, Senter PD, Jeffers ME, Lichenstein HS, LaRochelle WJ: Treatment parameters modulating regression of human melanoma xenografts by an antibody-drug conjugate (CR011-vcMMAE) targeting GPNMB. Cancer Chemother Pharmacol; 2007 Aug;60(3):423-35
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  • [Title] Treatment parameters modulating regression of human melanoma xenografts by an antibody-drug conjugate (CR011-vcMMAE) targeting GPNMB.
  • PURPOSE: To investigate the pharmacological properties of the CR011-vcMMAE fully human antibody-drug conjugate (ADC), such as dose titrations, quantitation of the time (days) to complete regression, pharmacokinetics, and schedule dependency.
  • Our prior study characterized a fully human antibody to GPNMB covalently linked to monomethylauristatin E, CR011-vcMMAE, and further demonstrated cell surface staining of melanoma lines susceptible to the immunoconjugate's cytotoxicity (Clin Cancer Res 2005; 12(4): 1373-1382).
  • METHODS: The human SK-MEL-2 and SK-MEL-5 melanoma xenografts were used in athymic mice to assess anti-tumor efficacy.
  • After s.c. implantation, tumors became established (60-100 mg), and treatment commenced by i.v. injection of the immunoconjugate or vinblastine or paclitaxel.
  • Short-term anti-tumor effects (inhibition of tumor growth) and long-term effects (complete regression) were observed.
  • RESULTS: CR011-vcMMAE induced regression of established human SK-MEL-2 and SK-MEL-5 xenografts at doses from 1.25 to 80 mg/kg treatment when administered intravenously every 4 days (4 treatments); strikingly, regressions were not associated with re-growth during the observation period (200 days).
  • The disappearance rate of implants was dose dependent (minimum time, 18.5 days).
  • A low volume of distribution suggested that CR011-vcMMAE was confined to blood and interstitial fluid.
  • CR011-vcMMAE could be delivered by either a single bolus dose or by intermittent dosing (i.e., every 1, 2, 4, 8, or 16 days) with no discernible differences in the proportion of tumor-free survivors, indicating a lack of schedule dependency.
  • The antibody-drug conjugate produced complete regressions, but the equivalent doses of free monomethylauristatin E or unconjugated antibody did not show anti-tumor effects.
  • In addition, decreases in plasma tumor-derived human interleukin-8 coincided with tumor nodule disappearance.
  • CONCLUSIONS: Short-term anti-tumor effects and long-term effects (complete regression) were observed with CR011-vcMMAE, but not with the reference agents.
  • These results suggest that CR011-vcMMAE may provide therapeutic benefit in malignant melanoma.
  • [MeSH-major] Immunotoxins / therapeutic use. Melanoma / drug therapy. Membrane Glycoproteins / drug effects
  • [MeSH-minor] Adult. Animals. Cell Line, Tumor. Disease Models, Animal. Female. Humans. Male. Mice. Mice, Nude. Middle Aged. Neoplasm Metastasis / drug therapy. Transplantation, Heterologous

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  • (PMID = 17541593.001).
  • [ISSN] 0344-5704
  • [Journal-full-title] Cancer chemotherapy and pharmacology
  • [ISO-abbreviation] Cancer Chemother. Pharmacol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / GPNMB protein, human; 0 / Immunotoxins; 0 / Membrane Glycoproteins
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20. Halimi JM, Azizi M, Bobrie G, Bouché O, Deray G, des Guetz G, Lecomte T, Levy B, Mourad JJ, Nochy D, Oudard S, Rieu P, Sahali D: [Vascular and renal effects of anti-angiogenic therapy]. Nephrol Ther; 2008 Dec;4(7):602-15
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  • [Title] [Vascular and renal effects of anti-angiogenic therapy].
  • [Transliterated title] Effets vasculaires et rénaux des médicaments anti-angiogéniques: recommandations françaises pour la pratique (SN, SFHTA, APNET, FFCD).
  • Angiogenesis inhibitor drugs (bevacizumab, sunitinib, sorafénib...) are now widely used for treatment of cancers, including colorectal, advanced renal cell and hepatocellular carcinomas, breast cancer).
  • Vascular and renal side-effects of these drugs are not well known.
  • Arterial pressure can usually be controlled with anti-hypertensive medications, and treatment with angiogenesis inhibitors can be continued in most cases; however, serious hypertension-induced side effects were reported included malignant hypertension, stroke and reversible posterior leucoencephalopathy.
  • Renal damage is infrequently reported: usually reversible mild or moderate proteinuria and in some rare cases nephritic syndrome, acute renal dysfunction, proliferative or collapsing glomerulonephritis, interstitial nephritis and thrombotic microangiopathy.
  • (1) before the first administration of angiogenesis inhibitors: acute IV or oral antihypertensive medications should not be administered in a patient regardless of arterial pressure levels with postponing the administration because of hypertension is not recommended;.
  • (2) initial work-up should include ambulatory measurement of arterial pressure (by the general practitioner or by the patient using home blood pressure (three times in the morning and in the evening during three consecutive days) with a validated (cf: http://afssaps.sante.fr/) upper arm device: ideally, this device should be financed and provided by the pharmaceutical companies marketing the angiogenesis inhibitor drugs.
  • (3) urine dipstick (and quantification if positive) and estimated glomerular filtration rate (using abbreviated MDRD rather than Cockcroft-Gault formula) must be performed before treatment and regularly during follow-up;.
  • (4) therapeutic management must be done in accordance with national or international guidelines (in France: http://www.has-sante.fr/);.
  • [MeSH-major] Angiogenesis Inhibitors / therapeutic use. Colorectal Neoplasms / drug therapy. Kidney / pathology
  • [MeSH-minor] Antibodies, Monoclonal / adverse effects. Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Humanized. Antineoplastic Agents / adverse effects. Antineoplastic Agents / therapeutic use. Benzenesulfonates / adverse effects. Benzenesulfonates / therapeutic use. Bevacizumab. Glomerular Filtration Rate / drug effects. Glomerulonephritis / chemically induced. Humans. Indoles / adverse effects. Indoles / therapeutic use. Neoplasm Metastasis / drug therapy. Niacinamide / analogs & derivatives. Phenylurea Compounds. Practice Guidelines as Topic. Proteinuria / chemically induced. Pyridines / adverse effects. Pyridines / therapeutic use. Pyrroles / adverse effects. Pyrroles / therapeutic use. Vascular Endothelial Growth Factor A / drug effects. Vascular Endothelial Growth Factor A / physiology

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  • (PMID = 19027389.001).
  • [ISSN] 1769-7255
  • [Journal-full-title] Néphrologie & thérapeutique
  • [ISO-abbreviation] Nephrol. Ther.
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Angiogenesis Inhibitors; 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antineoplastic Agents; 0 / Benzenesulfonates; 0 / Indoles; 0 / Phenylurea Compounds; 0 / Pyridines; 0 / Pyrroles; 0 / Vascular Endothelial Growth Factor A; 0 / sunitinib; 25X51I8RD4 / Niacinamide; 2S9ZZM9Q9V / Bevacizumab; 9ZOQ3TZI87 / sorafenib
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