Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastrointestinal tumors are among the most common cancers in the world. Palliative chemotherapy is widely used to treat patients with advanced or metastatic disease. The mainstay of chemotherapy for colorectal cancer is 5-fluorouracil (5-FU) modulated by leucovorin (LV), alone or in combination with oxaliplatin or irinotecan (CPT-11). Gemcitabine is currently the standard of care in patients with pancreatic cancer. There is no standard in gastric cancer, although cisplatin, 5-FU, and the anthracyclines are the most common drugs used. Pemetrexed, a new-generation antifolate antimetabolite, has demonstrated a 15% to 17% response rate in metastatic colorectal cancer, similar to those of other single agents in previously untreated patients. In patients with advanced pancreatic cancer, pemetrexed achieved a 6% response rate and a 28% 1-year survival rate, which is comparable to single-agent gemcitabine. Preliminary results in gastric cancer are encouraging. The generally mild side effect profile of pemetrexed, especially with folate supplementation and dexamethasone premedication, and the synergy between pemetrexed and drugs frequently used in gastrointestinal cancers, such as irinotecan, oxaliplatin, and gemcitabine, suggest that further clinical studies are indicated to determine the role of pemetrexed in the treatment of colorectal, pancreatic, and gastric cancers.
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PMID:Pemetrexed in patients with gastrointestinal carcinoma. 1202 92

Gastric cancer is a major clinical challenge, with poor overall prognosis and limited life expectancy for patients with advanced disease. Even with surgery and other modalities, palliation is often difficult. Improvement of response rates has evolved with the development of standard regimens and those incorporating newer chemotherapy agents, such as oral fluoropyrimidines, the taxanes, camptothecins, novel platinums (eg, oxaliplatin [Eloxatin]), and antifolates (eg, pemetrexed [Alimta]). Ongoing trials with these regimens aim toward improving survival, as well as improving the safety profile. It is hoped that in conjunction with molecular research in the pathogenesis of gastric cancer and development of targeted therapies in this disease, these trial data might lead to the evolution of treatment strategies that could prove effective.
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PMID:Pemetrexed in gastric cancer. 1565 38

Pemetrexed is a newly developed multitargeted antifolate with promising clinical activity in many solid tumors including gastric cancer. The aim of the present study was to evaluate the cytotoxicity of pemetrexed and its mode of interaction with cisplatin in gastric cancer cell lines, and to identify genes associated with sensitivity to pemetrexed. The cytotoxic activity of pemetrexed was assessed by tetrazolium-based colorimetric assay (MTT assay) and the interaction between pemetrexed and cisplatin was evaluated by the isobologram method. Western immunoblotting and real time RT-PCR analysis of thymidylate synthase (TS), folylpoly-gamma-glutamate synthetase (FPGS) and reduced folate carrier (RFC1) were performed in order to determine whether sensitivity to pemetrexed would be predictable by protein or mRNA expression levels. Pemetrexed was more cytotoxic than 5-fluorouracil, with IC50 between 17 and 310 nM in most of the gastric cancer cell lines examined and the pemetrexed/cisplatin combination resulted in additive or synergistic interaction. The protein expressions of TS, FPGS, and RFC1 were significantly associated with IC50 for 5-fluorouracil, but no such association was found for pemetrexed chemosensitivity. The mRNA expressions of RFC1, FPGS and other target and resistance related genes revealed no significant association with pemetrexed sensitivity. In conclusion, pemetrexed is active against gastric cancer cell lines and the pemetrexed/cisplatin combination showed a synergistic or additive interaction, supporting its clinical use in gastric cancer. Drug sensitivity toward pemetrexed could not be predicted by the expressions of TS, RFC1, or FPGS and we suggest that it is determined by interactions between multiple genes.
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PMID:Cytotoxic effects of pemetrexed in gastric cancer cells. 1595 60