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1. Connolly L, Maxwell P: Image analysis of Transwell assays in the assessment of invasion by malignant cell lines. Br J Biomed Sci; 2002;59(1):11-4
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  • [Title] Image analysis of Transwell assays in the assessment of invasion by malignant cell lines.
  • This study aims to determine if layering of extracellular matrix (ECM) can achieve a physiological basement membrane thickness of 8 microm and to assess the use of paraffin wax-embedded Transwell plates coupled with digital image analysis as a means of determining invasion by malignant cell lines.
  • Layers of Matrigel, a sarcoma-derived ECM was built to a concentration of 7.4 microg/mm2 in the upper chamber of a Transwell plate invasion assay.
  • Two cell lines from extrahepatic bile duct adenocarcinoma were tested in serum-free growth medium.
  • Conditioned medium was added to the lower chamber to act as a chemoattractant.
  • [MeSH-major] Adenocarcinoma / pathology. Bile Duct Neoplasms / pathology. Image Processing, Computer-Assisted. Neoplasm Invasiveness / pathology
  • [MeSH-minor] Biomarkers. Collagen. Culture Media, Conditioned. Diffusion Chambers, Culture. Drug Combinations. Extracellular Matrix / pathology. Humans. Keratins / analysis. Laminin / analysis. Proteoglycans. Tumor Cells, Cultured

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  • (PMID = 12000178.001).
  • [ISSN] 0967-4845
  • [Journal-full-title] British journal of biomedical science
  • [ISO-abbreviation] Br. J. Biomed. Sci.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers; 0 / CAM 5.2 antigen; 0 / Culture Media, Conditioned; 0 / Drug Combinations; 0 / Laminin; 0 / Proteoglycans; 119978-18-6 / matrigel; 68238-35-7 / Keratins; 9007-34-5 / Collagen
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2. Toxicology and carcinogenesis studies of benzophenone (CAS No. 119-61-9) in F344/N rats and B6C3F1 mice (feed studies). Natl Toxicol Program Tech Rep Ser; 2006 Feb;(533):1-264
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  • Benzophenone is used as a photoinitiator, a fragrance enhancer, an ultraviolet curing agent, and occasionally as a flavor ingredient; it is also used in the manufacture of insecticides, agricultural chemicals, and hypnotics, antihistamines, and other pharmaceuticals; and it is used as an additive in plastics, coatings, and adhesive formulations.
  • Genetic toxicology studies were conducted in Salmonella typhimurium, mouse bone marrow cells, and mouse peripheral blood erythrocytes.
  • 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were fed diets containing 0, 312, 625, or 1,250 ppm benzophenone (equivalent to average daily doses of approximately 15, 30, and 60 mg benzophenone/kg body weight to males and 15, 30, and 65 mg/kg to females) for 105 weeks.
  • Mean body weights of 1,250 ppm males were markedly less than those of the controls during year 2 of the study, and weights of exposed females were consistently less than controls throughout the study.
  • One 625 ppm female and two 1,250 ppm females had histiocytic sarcomas, and the incidence in the 1,250 ppm group exceeded the range in the historical controls.
  • Liver lesions included significantly increased incidences of hepatocytic centrilobular hypertrophy in all exposed groups of males and females, cystic degeneration in 625 and 1,250 ppm males, and bile duct hyperplasia in all exposed groups of females.
  • Incidences of mammary gland fibroadenoma in females exposed to 625 or 1,250 ppm were lower than expected after adjusting for body weight.
  • 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were fed diets containing 0, 312, 625, or 1,250 ppm benzophenone (equivalent to average daily doses of approximately 40, 80, and 160 mg/kg body weight to males and 35, 70, and 150 mg/kg to females) for 105 weeks.
  • Mean body weights of exposed females were less than vehicle controls.
  • In female mice, the incidences of hepatocellular adenoma in the 625 and 1,250 ppm groups were higher than expected after adjusting for the lower body weights in these groups.
  • All exposed groups of male mice had significant increases in the incidences of multinucleated hepatocytes and chronic active inflammation.
  • The incidence of histiocytic sarcoma in 625 ppm females was significantly increased and exceeded the historical control range.
  • No significant increases in the frequencies of micronucleated polychromatic erythrocytes were seen in bone marrow samples from male mice administered benzophenone three times by intraperitoneal injection.
  • There was equivocal evidence of carcinogenic activity of benzophenone in female F344/N rats based on the marginally increased incidences of mononuclear cell leukemia and histiocytic sarcoma.
  • There was some evidence of carcinogenic activity of benzophenone in female B6C3F1 mice based on increased incidences of histiocytic sarcoma; the incidences of hepatocellular adenoma in female B6C3F1 mice may have been related to benzophenone exposure.
  • [MeSH-major] Benzophenones / toxicity. Neoplasms, Experimental / chemically induced. Photosensitizing Agents / toxicity
  • [MeSH-minor] Animals. Body Weight / drug effects. Carcinogenicity Tests. Dose-Response Relationship, Drug. Female. Histiocytic Disorders, Malignant / chemically induced. Histiocytic Disorders, Malignant / pathology. Kidney Neoplasms / chemically induced. Kidney Neoplasms / pathology. Leukemia / chemically induced. Leukemia / pathology. Liver Neoplasms / chemically induced. Liver Neoplasms / pathology. Longevity / drug effects. Male. Mice. Mice, Inbred C57BL. Mutagenicity Tests. Rats. Rats, Inbred F344. Sarcoma / chemically induced. Sarcoma / pathology. Toxicity Tests, Chronic

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  • (PMID = 16741556.001).
  • [ISSN] 0888-8051
  • [Journal-full-title] National Toxicology Program technical report series
  • [ISO-abbreviation] Natl Toxicol Program Tech Rep Ser
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Benzophenones; 0 / Photosensitizing Agents; 701M4TTV9O / benzophenone
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3. Donald S, Verschoyle RD, Greaves P, Colombo T, Zucchetti M, Falcioni C, Zaffaroni M, D'Incalci M, Manson MM, Jimeno J, Steward WP, Gescher AJ: Dietary agent indole-3-carbinol protects female rats against the hepatotoxicity of the antitumor drug ET-743 (trabectidin) without compromising efficacy in a rat mammary carcinoma. Int J Cancer; 2004 Oct 10;111(6):961-7
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  • [Title] Dietary agent indole-3-carbinol protects female rats against the hepatotoxicity of the antitumor drug ET-743 (trabectidin) without compromising efficacy in a rat mammary carcinoma.
  • ET-743, an experimental antitumor drug with promising activity in sarcoma, breast and ovarian carcinoma, is currently under phase 2 clinical evaluation.
  • It is hepatotoxic in animals and patients.
  • We tested the hypothesis that indole-3-carbinol (I3C), the hydrolysis product of glucosinolates occurring in cruciferous vegetables, may protect against ET-743-induced hepatotoxicity in the female Wistar rat, the animal species with the highest sensitivity toward the adverse hepatic effect of this drug.
  • ET-743 (40 microg/kg i.v.) alone caused an elevation of plasma bilirubin, ALP and AST levels and degeneration and patchy focal necrosis of bile duct epithelial cells.
  • In contrast, a dietary concentration of 0.1% I3C did not protect, nor did dietary diindolylmethane (0.2%), an acid-catalyzed condensation product of I3C.
  • Ingestion by rats of I3C for 6 days prior to ET-743 (40 microg/kg i.v.) decreased plasma but not hepatic concentrations of ET-743 compared to animals that received ET-743 alone.
  • I3C should be investigated as a hepatoprotectant in patients who receive ET-743 therapy.
  • [MeSH-major] Antineoplastic Agents, Alkylating / adverse effects. Antioxidants / pharmacology. Dioxoles / adverse effects. Indoles / pharmacology. Isoquinolines / adverse effects. Liver / drug effects. Liver / pathology
  • [MeSH-minor] Administration, Oral. Animals. Chemoprevention. Diet. Female. Mammary Neoplasms, Animal. Neoplasms, Experimental. Rats. Rats, Wistar. Tetrahydroisoquinolines

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  • (PMID = 15300810.001).
  • [ISSN] 0020-7136
  • [Journal-full-title] International journal of cancer
  • [ISO-abbreviation] Int. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Antioxidants; 0 / Dioxoles; 0 / Indoles; 0 / Isoquinolines; 0 / Tetrahydroisoquinolines; 114899-77-3 / trabectedin; C11E72455F / indole-3-carbinol
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4. Lee JA, Kim TW, Min JH, Byon SJ, Jang SH, Choi SY, Kim HJ: [A case of undifferentiated (embryonal) liver sarcoma mimicking klatskin tumor in an adult]. Korean J Gastroenterol; 2010 Feb;55(2):144-8
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  • [Title] [A case of undifferentiated (embryonal) liver sarcoma mimicking klatskin tumor in an adult].
  • Undifferentiated sarcoma is an uncommon primary malignant tumor of the liver typically occurring in older children.
  • It is also referred to as malignant mesenchymoma, fibromyxosarcoma, or mesenchymal sarcoma.
  • We experienced a case of undifferentiated sarcoma in 72-year-old male.
  • Contrast enhanced liver CT scan revealed a 3.4 cm heterogeneously enhancing, ill-defined, and low attenuated mass in the left liver and subtle intrahepatic duct dilatation.
  • And, in tubogram, there were segmental stenosis and occlusion from the hilum to the proximal common bile duct.
  • The pathologic finding revealed infiltrative growth of atypical cells with rhabdoid features.
  • These tumor cells were positive for vimentin only, and the tumor was consistent with undifferentiated sarcoma of the liver.
  • [MeSH-major] Liver Neoplasms / diagnosis. Sarcoma / diagnosis
  • [MeSH-minor] Aged. Bile Ducts, Intrahepatic / pathology. Diagnosis, Differential. Dilatation, Pathologic. Humans. Klatskin Tumor / diagnosis. Male. Positron-Emission Tomography. Tomography, X-Ray Computed. Tuberculosis / diagnostic imaging. Tuberculosis / drug therapy. Ultrasonography. Vimentin / metabolism


6. Twelves C, Hoekman K, Bowman A, Vermorken JB, Anthoney A, Smyth J, van Kesteren C, Beijnen JH, Uiters J, Wanders J, Gomez J, Guzmán C, Jimeno J, Hanauske A: Phase I and pharmacokinetic study of Yondelis (Ecteinascidin-743; ET-743) administered as an infusion over 1 h or 3 h every 21 days in patients with solid tumours. Eur J Cancer; 2003 Sep;39(13):1842-51
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  • Yondelis (ET-743) is a novel anticancer agent isolated from the marine ascidian Ecteinascidia turbinata.
  • ET-743 possesses potent antitumour activity and a novel mechanism of action at the level of gene transcription.
  • We conducted two sequential phase I dose escalation and pharmacokinetic studies of ET-743 given as a 1- or a 3-h intravenous (i.v.) infusion.
  • Seventy-two adults with metastatic or advanced solid tumours received ET-743 in escalating doses between 50 and 1100 microg/m(2), initially as a 1-h infusion, and later at doses between 1000 and 1800 microg/m(2) as a 3-h infusion every 3 weeks.
  • The maximum tolerated dose (MTD) of ET-743 was 1100 microg/m(2) for the 1-h infusion schedule and 1800 microg/m(2) when given as a 3-h infusion.
  • Transient non-cumulatives grade 3-4 increase in transaminases (not considered DLT) and grades 3-4 nausea and vomiting were frequently observed.
  • One pCR (melanoma), CR (uterine leiomyosarcoma), one PR (colon stromal sarcoma) and a MR (37% tumour shrinkage, gastric stromal sarcoma) were observed.
  • A further 9 patients with colorectal, mesothelioma, bile duct carcinoma and bladder cancer had SD which lasted for six or more treatment cycles.
  • Based on the current trial, the recommended dose of ET-743 for phase II studies is 1650 microg/m(2) given as a 3-h infusion.
  • [MeSH-major] Antineoplastic Agents, Alkylating / pharmacokinetics. Dioxoles / pharmacokinetics. Isoquinolines / pharmacokinetics. Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Cohort Studies. Dose-Response Relationship, Drug. Female. Hematologic Diseases / chemically induced. Humans. Infusions, Intravenous. Male. Maximum Tolerated Dose. Middle Aged. Tetrahydroisoquinolines

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  • (PMID = 12932661.001).
  • [ISSN] 0959-8049
  • [Journal-full-title] European journal of cancer (Oxford, England : 1990)
  • [ISO-abbreviation] Eur. J. Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Dioxoles; 0 / Isoquinolines; 0 / Tetrahydroisoquinolines; 114899-77-3 / trabectedin
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7. Fayette J, Coquard IR, Alberti L, Ranchère D, Boyle H, Blay JY: ET-743: a novel agent with activity in soft tissue sarcomas. Oncologist; 2005 Nov-Dec;10(10):827-32
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  • [Title] ET-743: a novel agent with activity in soft tissue sarcomas.
  • Ecteinascidin-743 (ET-743) is a natural product derived from the marine tunicate Ectenascidia turbinate.
  • ET-743 demonstrated cytotoxic activity at very low concentrations against sarcoma cell lines in pre-clinical studies.
  • In several phase II clinical studies in patients with advanced sarcoma failing conventional doxorubicin- and ifosfamide-based chemotherapy, ET-743 delivered by continuous intravenous 24-hour infusion at a dose of 1,500 microg/m2 every 21 days yielded 8% overall response and 30%-40% stabilization rates for a clinical benefit rate close to 40%.
  • In vivo, ET-743 has a specific toxicity profile, the major toxicity of this product being hepatic, through biliary duct destruction, and hematologic.
  • Finally, due to its original mode of action and the lack of cross-resistance with other chemotherapy agents, ET-743 was tested in a preclinical model in combination with other drugs.
  • [MeSH-major] Dioxoles / therapeutic use. Isoquinolines / therapeutic use. Sarcoma / drug therapy

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  • (PMID = 16314293.001).
  • [ISSN] 1083-7159
  • [Journal-full-title] The oncologist
  • [ISO-abbreviation] Oncologist
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Dioxoles; 0 / Isoquinolines; 0 / Tetrahydroisoquinolines; 114899-77-3 / trabectedin
  • [Number-of-references] 45
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8. Filipski E, Subramanian P, Carrière J, Guettier C, Barbason H, Lévi F: Circadian disruption accelerates liver carcinogenesis in mice. Mutat Res; 2009 Nov-Dec;680(1-2):95-105
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  • The suprachiasmatic nuclei in the hypothalamus coordinate the molecular clocks in most mammalian cells through an array of circadian physiological rhythms including rest-activity, body temperature, feeding patterns and hormonal secretions.
  • As a result, shift work that involves circadian disruption is probably carcinogenic in humans.
  • In experimental models, chronic jet-lag (CJL) suppresses rest-activity and body temperature rhythms and accelerates growth of two transplantable tumors in mice.
  • CJL also suppresses or significantly alters the expression rhythms of clock genes in liver and tumors.
  • Here, we investigate the role of CJL as a tumor promoter in mice exposed to the hepatic carcinogen, diethylnitrosamine (DEN).
  • Rest-activity and body temperature were monitored.
  • In Exp 2, mice on CJL had increased mean plasma levels of aspartate aminotransferase and more liver tumors as compared to LD mice at approximately 10 months (p = 0.005 and 0.028, respectively).
  • The mean diameter of the largest liver tumor was twice as large in CJL vs LD mice (8.5 vs 4.4 mm, p = 0.027).
  • In LD, a single histologic tumor type per liver was observed.
  • In CJL, up to four different types were associated in the same liver (hepatocellular- or cholangio-carcinomas, sarcomas or mixed tumors).
  • DEN itself markedly disrupted the circadian rhythms in rest-activity and body temperature in all the mice.
  • Persistent circadian coordination may further be critical for slowing down and/or reverting cancer development after carcinogen exposure.
  • [MeSH-major] Carcinogens / toxicity. Circadian Rhythm / drug effects. Diethylnitrosamine / toxicity. Liver Neoplasms / chemically induced
  • [MeSH-minor] Alanine Transaminase / blood. Animals. Aspartate Aminotransferases / blood. Bile Duct Neoplasms / chemically induced. Bile Duct Neoplasms / pathology. Bile Ducts, Intrahepatic / drug effects. Bile Ducts, Intrahepatic / pathology. Body Weight / drug effects. Carcinoma, Hepatocellular / chemically induced. Carcinoma, Hepatocellular / pathology. Cholangiocarcinoma / chemically induced. Cholangiocarcinoma / pathology. Dose-Response Relationship, Drug. Injections, Intraperitoneal. Liver / drug effects. Liver / pathology. Male. Mice. Neoplasms, Multiple Primary / chemically induced. Neoplasms, Multiple Primary / pathology. Sarcoma / chemically induced. Sarcoma / pathology. Time Factors

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  • (PMID = 19833225.001).
  • [ISSN] 0027-5107
  • [Journal-full-title] Mutation research
  • [ISO-abbreviation] Mutat. Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Carcinogens; 3IQ78TTX1A / Diethylnitrosamine; EC 2.6.1.1 / Aspartate Aminotransferases; EC 2.6.1.2 / Alanine Transaminase
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9. Brunner TB, Grabenbauer GG, Klein P, Baum U, Papadopoulos T, Bautz W, Hohenberger W, Sauer R: Phase I trial of strictly time-scheduled gemcitabine and cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys; 2003 Jan 1;55(1):144-53
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  • [Title] Phase I trial of strictly time-scheduled gemcitabine and cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer.
  • PURPOSE: Maximal therapeutic gain in xenograft sarcoma and toxicity for jejunal mucosa is time dependent for concurrent gemcitabine and radiotherapy (RT).
  • METHODS AND MATERIALS: Patients with pancreatic cancer (n = 33), periampullary carcinoma (n = 1), or bile duct cancer (n = 2) were treated with 3-day conformal RT with 50.4 Gy (tumor, lymphatics) plus a 5.4-Gy boost.
  • [MeSH-minor] Adult. Aged. Blood Cells / drug effects. Blood Cells / radiation effects. Cisplatin / administration & dosage. Combined Modality Therapy. Digestive System / drug effects. Female. Humans. Male. Maximum Tolerated Dose. Middle Aged. Radiotherapy / adverse effects. Radiotherapy Dosage

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  • (PMID = 12504047.001).
  • [ISSN] 0360-3016
  • [Journal-full-title] International journal of radiation oncology, biology, physics
  • [ISO-abbreviation] Int. J. Radiat. Oncol. Biol. Phys.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0W860991D6 / Deoxycytidine; B76N6SBZ8R / gemcitabine; Q20Q21Q62J / Cisplatin
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10. Fayette J, Coquard IR, Alberti L, Boyle H, Méeus P, Decouvelaere AV, Thiesse P, Sunyach MP, Ranchère D, Blay JY: ET-743: a novel agent with activity in soft-tissue sarcomas. Curr Opin Oncol; 2006 Jul;18(4):347-53
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  • [Title] ET-743: a novel agent with activity in soft-tissue sarcomas.
  • PURPOSE OF REVIEW: ET-743 (ecteinascidin-743, trabectedin, Yondelis) is a natural marine product that has shown clinical activity in sarcoma.
  • Leiomyosarcomas, liposarcomas, and synovial sarcomas may be the more sensitive histotypes.
  • The major toxicities of ET-743 are hepatic--through biliary duct destruction--and hematologic.
  • They are not cumulative and a significant number of patients may receive 12 courses or more.
  • In a randomized Phase II study testing weekly ET-743 with treatment every 3 weeks, an improved progression-free survival rate was observed in the 3-weekly arm; the results of the follow-up Phase III trial should be available at the American Society of Clinical Oncology meeting of 2006.
  • SUMMARY: ET-743 is a novel active drug for sarcoma which yields prolonged disease-free survival in subsets of patients.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Dioxoles / therapeutic use. Sarcoma / drug therapy. Tetrahydroisoquinolines / therapeutic use
  • [MeSH-minor] Clinical Trials as Topic. DNA / chemistry. DNA Repair. Disease-Free Survival. Humans. Models, Chemical. Neoplasm Metastasis. Treatment Outcome

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  • (PMID = 16721129.001).
  • [ISSN] 1040-8746
  • [Journal-full-title] Current opinion in oncology
  • [ISO-abbreviation] Curr Opin Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Dioxoles; 0 / Tetrahydroisoquinolines; 114899-77-3 / trabectedin; 9007-49-2 / DNA
  • [Number-of-references] 62
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11. Ramamoorthy SK, Pandita R, Prakash A, Ramaswamy NV, Al Bahar S: Safety of imatinib in chronic myeloid leukemia in blastic crisis presenting as cholestatic jaundice. Acta Haematol; 2007;118(3):141-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • It can occur due to granulocytic sarcoma compressing the bile ducts in case of acute myeloid leukemia.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Blast Crisis / drug therapy. Jaundice, Obstructive / drug therapy. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Liver Neoplasms / drug therapy. Piperazines / administration & dosage. Pyrimidines / administration & dosage
  • [MeSH-minor] Adult. Benzamides. Diagnosis, Differential. Drug-Related Side Effects and Adverse Reactions. Humans. Imatinib Mesylate. Male






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