Reference Detail

Ref Type Journal Article
PMID (15494073)
Authors Choi CH, Cha YJ, An CS, Kim KJ, Kim KC, Moon SP, Lee ZH, Min YD
Title Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines: less involvement of metallothionein.
Journal Cancer cell international
Vol 4
Issue 1
Date 2004 Oct 19
URL
Abstract Text BACKGROUND: Heptaplatin is a new platinum derivative with anticancer activity against various cancer cell lines, including cisplatin-resistant cancer cell lines (Cancer Chemother Pharmacol 1995; 35: 441). METHODS: Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines has been investigated in connection with metallothionein (MT). Cytotoxicity was determined by an MTT assay. MT mRNA, was determined by RT-PCR assay. Transfection study was carried out to examine the function of MT. RESULTS: Of various gastric cancer cell lines, SNU-638 and SNU-601 showed the highest and lowest levels of MT mRNA, respectively, showing 80-fold difference. The IC50 values of SNU-638 to cisplatin, carboplatin and heptaplatin were 11.2-fold, 5.1-fold and 2.0-fold greater than those of SNU-601, respectively. Heptaplatin was more effective against cisplatin-resistant and MT-transfected gastric cancer sublines than cisplatin or carboplatin was. In addition, heptaplatin attenuated cadmium, but not zinc, induction of MT. CONCLUSION: These results indicate that molecular mechanisms of heptaplatin effective against cisplatin-resistant gastric cancer sublines is at least in part due to the less involvement of MT in heptaplatin resistance as well as its attenuation of MT induction.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MET F1200L MET Y1230H stomach cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) treated with Xalkori (crizotinib) in culture for several months developed resistance and was found to co-harbor MET Y1230H and MET F1200L(PMID: 28765324). 28765324 15494073
MET Y1230C stomach cancer resistant Capmatinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) treated with Capmatinib (INC280) in culture for several months developed resistance and was found to harbor MET Y1230C (PMID: 28765324). 15494073 28765324
MET Y1230C stomach cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a Capmatinib (INC280)-resistant gastric cancer cell line (PMID: 15494073) harboring MET Y1230C also demonstrated resistance when treated with Xalkori (crizotinib) (PMID: 28765324). 15494073 28765324
MET F1200L MET Y1230H stomach cancer resistant Capmatinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) co-harboring MET Y1230H and MET F1200L demonstrated resistance when treated with Capmatinib (INC280) in culture (PMID: 28765324). 28765324 15494073
MET F1200L MET Y1230H stomach cancer sensitive Glesatinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) co-harboring MET Y1230H and MET F1200L was sensitive to treatment with Glesatinib (MGCD265), demonstrating cell growth inhibition in culture (PMID: 28765324). 28765324 15494073
MET Y1230C stomach cancer sensitive Glesatinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) harboring MET Y1230C was sensitive to treatment with Glesatinib (MGCD265), demonstrating cell growth inhibition in culture (PMID: 28765324). 28765324 15494073