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)

The combined effects of Mitomycin C (MMC) with alpha-interferon (HLBI) or gamma-interferon (TRP-2), which have become attractive drugs for use as Biological Response Modifiers, were investigated using the human tumor clonogenic assay technique. Tumors in this study were five human tumor xenografts serially transplanted into nude mice (three gastric cancer, two colon cancer). When the survival fraction occurring with the combination was smaller than that obtained by multiplication of the survival fractions occurring with either drug alone, the combined effect was considered to be synergism. Four out of five xenografts (three gastric cancer, one colon cancer) showed synergistic effects for the combination of MMC with alpha-interferon. Although two gastric cancer xenografts showed synergism for the combination of MMC with gamma-interferon, antagonistic effects were observed in one gastric cancer and one colon cancer xenograft.
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PMID:[Assessment of the combined effects of mitomycin C with alpha-interferon or gamma-interferon by the clonogenic assay technique]. 392 7

Prostaglandin E(2) (PGE(2)) plays an important role in protection of the gastric mucosa against various damaging agents and growth-inhibitory activity on tumor cells. However, the precise regulation mechanism of PGE(2) in gastric cancer cells is still unclear. In this study, we isolated a gene, which is regulated by PGE(2) in SNU-1, human gastric adenocarcinoma cells, using differential display RT-PCR (DD RT-PCR) and characterized the function of the gene induced by PGE(2). The full-length cDNA of the gene was cloned by the rapid amplification of cDNA ends method. The 1659 base pair cDNA consists of a 30-nt 5'-noncoding region, an 891-nt open reading frame and a 738-nt 3'noncoding region that includes a poly (A) signal. As a result of protein motif search, we found that it has a conserved thioredoxin-active site, Cys-Gly-Pro-Cys and a Myb-DNA binding domain repeat signature. Thus, we designated this gene product as thioredoxin-related protein-1, TRP-1. TRP-1 was expressed in a lower extent in renal, gastric and colon cancer tissues and is translated into 33 kDa protein in nuclear and cytoplasmic fractions. TRP-1 has a thioredoxin activity, which was detected using the insulin disulfide reduction assay. Another potential role of TRP-1 is repression of B-Myb activity through direct binding to B-Myb, a transcriptional factor induced at G1-S transition. Finally, TRP-1 overexpression inhibits mammalian cell proliferation and specifically predispose to G0/G1 phase arrest. In conclusion, these results imply that TRP-1 is a mammalian thioredoxin and plays as a transcriptional repressor through direct binding to the transcription factor B-Myb.
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PMID:Expression of a thioredoxin-related protein-1 is induced by prostaglandin E(2). 1692 93

The 5-FU plus cisplatin containing regimen like FP, ECF and DCF, is considered to be the most effective treatment for advanced gastric cancer in the United States, Europe, and Korea. In Japan, oral fluoropyrimidine S-1 (TS-1) is currently considered to be the first candidate as the standard drug for advanced gastric cancer. S-1 based combination therapies with other promising drugs like cisplatin, irinotecan and taxanes, are expected to yield good results. Above all, S-1+CDDP therapy showed a high efficacy and expected to be a standard therapy for advanced gastric cancer. Two large phase III studies, JCOG 9912 5-FU vs S-1 vs CPT-11 +CDDP and S-1 vs S-1+CDDP, are now on going to establish an acceptable frontline standard for patients with AGC. We therefore need to develop new agents and combination chemotherapy regimens to achieve a greater survival benefit in AGC.
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PMID:[Clinical development of S-1 (TS-1) for advanced gastric cancer]. 1689 73

Gastric cancer is the second most frequent cancer in the world. Approximately 84% of patients with gastric cancer will have advanced disease and median survival of these patients without chemotherapy is only 3-4 months. "Classical" chemotherapy regimens, mainly CF (cisplatin plus infusional 5FU) and ECF (cisplatin plus infusional 5FU plus Epirubicin) obtain responses in 20-40% of the patients and improve quality of life. Nevertheless, duration of these responses is short with very few complete responses. Median time to tumor progression (TTP) with these regimens is only about 4-5 months and median survival does not exceed 7-10 months. Moreover, benefit seems to be limited to patients with good performance status and treatment toxicity and discomfort are not negligible, specially that of regimens with cisplatin or infusional 5FU. Trying to improve these results, the incorporation of new drugs has been explored. Among the new combinations, the more developed ones are those with Docetaxel (DCF), oxaliplatin (EOX, FLO), Capecitabine (EOX, cisplatin-Xeloda) and irinotecan (ILF). We have final results from Phase III trials that suggest that all these regimens could have a role in the treatment of these patients but survival is still very poor and toxicity remains important. It would be interesting to investigate other new combinations and the incorporation of drugs directed against new therapeutic targets in this setting. It would be of utmost interest that these clinical trials would also explore clinical and molecular prognostic and predictive factors.
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PMID:Chemotherapy of advanced gastric cancer. 1737 98

Gastric cancer is one of the most frequent cause of mortality, survival data are insufficient. Several chemotherapeutic combinations were applied successfully in advanced gastric cancer, following total tumor regression and radical resection, but there are very few cases with total regression after a disease forming carcinosis and causing ascites. In our report, a middle age patient suffering from locally advanced gastric cancer with peritonitis carcinomatosa and ascites was treated with neoadjuvant chemotherapy (DCF: docetaxel, cisplatin, fluorouracil protocol) successfully, as at the restaging examination total tumor regression was found. Ascites and carcinosis disappeared, so we performed radical distal surgical resection. The histological preparation resulted in 100% tumor regression of the specimen. Postoperatively the patient was given adjuvant DCF chemotherapy. The therapeutic modality of cases with advanced gastric cancer, especially with carcinosis must be reassessed, because according to our and some international reports, these patients are also candidates for effective neoadjuvant therapy and curative resection. In our own and in the experience of some others the combinations with taxanes and its derivatives are one of the most effective.
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PMID:[Complete regression after neoadjuvant chemotherapy in locally advanced gastric cancer causing peritonitis carcinomatosa--a case report]. 1743 86

We compare Japanese practice guidelines for gastric cancer with those published from National Comprehensive Cancer Network (NCCN). In surgery, D1 dissection is referred as standard in NCCN, because mortality of D2 dissection was higher than that of D1 (10% vs 4%). However, Japanese investigators show lower mortality rate (0.8%) of D2 dissection, so D2 dissection is referred as standard for stage II/III disease in Japan. Chemoradiotherapy is chosen for residual disease or unresectable disease (M0) in NCCN, but these categories are required D2 dissection or extensive resection in Japan. Because Japanese D2 dissection has better optimized survival rate than chemoradiotherapy,chemoradiotherapy will not be introduced to Japan. In chemotherapy, ECF or taxanes (e.g., DCF) is referred as a prior therapy in NCCN, but 5-FU contain regimen (e.g., FP, LV/5-FU, S-1, or S-1/CDDP) as a prior therapy in Japan. Both ECF and DCF are too toxic regimen for Japanese patient to use. Difference of race seem to be relevant to difference of mortality or toxicities. From the results of ACTS-GC, we think that adjuvant chemotherapy is referred as standard in Japan. Future, results of JCOG 9912 and many other trials will be coming soon, so the guidelines will be changed.
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PMID:[Comparison the standard therapies of gastric cancer in Japan with those in the West]. 1749 40

A multidisciplinary approach is mandatory for patients with gastric cancer. Patients should be managed by an experienced team of physicians. The outcome of patients is related to the experience of the multidisciplinary team. Surgery is the cornerstone of the management of patients with resectable gastric cancer. The standard recommendations for resectable gastric adenocarcinoma are free-margin surgery with at least D1 resection combined to removal of a minimum of 15 lymph nodes. It has been shown that the outcome of patients with resectable gastric cancer can be improved by a strategy of perioperative (pre- and postoperative) chemotherapy or by postoperative chemoradiotherapy. The evidence comes from large randomised phase 3 studies. In the treatment of unresectable, locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma, no chemotherapy combination was accepted as the gold standard. Cisplatin/5-FU (CF) and ECF (epirubicin plus CF) regimens have been investigated widely in clinical studies and were until recently presented as the reference regimens. Despite a relative chemosensitivity of gastric cancer, a low rate of complete response was obtained, the response duration was short and patients' outcomes remained poor. Recently, new options have been introduced in the management of advanced gastric cancer. It has been shown that capecitabine is at least as good as 5-FU and that oxaliplatin at least as good as cisplatin in these combinations. It has also been demonstrated that the addition of docetaxel to CF resulted in statistically significant improved efficacy endpoints (including patient's quality of life), but also in an increased toxicity. The DCF regimen (docetaxel, cisplatin and 5-FU) has become, therefore, a new active option in advanced gastric cancer in selected patients in good condition. Further randomised trials are therefore to be designed to further improve chemotherapy by modifying and optimising the chemotherapy regimens, and investigating novel treatment combinations. The addition of biological agents to the optimal chemotherapy regimen may achieve further improvements in efficacy.
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PMID:Expert opinion on management of gastric and gastro-oesophageal junction adenocarcinoma on behalf of the European Organisation for Research and Treatment of Cancer (EORTC)-gastrointestinal cancer group. 1809 27

Treatment of gastric cancer is improved over the past years, but unanswered questions remain regarding the efficacy of systemic treatments in adjuvant, neoadjuvant and metastatic setting. It has not been definitively demonstrated the efficacy of adjuvant chemotherapy, that should not be adopted as a standard approach to localized gastric cancer. On the contrary, compelling evidence in support of perioperative chemotherapy with ECF regimen has been recently provided by the MAGIC trial, although many criticisms have been moved to this study. For metastatic setting, a recent meta-analysis showed a small, but significant survival benefit for combination vs single agent chemotherapy, and the V-325 trial demonstrated the superiority of a docetaxel containing regimen (DCF) over a doublet (CF). Finally, the results of ongoing clinical trials on a number of new molecular-targeted drugs should confirm their role in gastric cancer.
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PMID:Systemic treatment of gastric cancer. 1882 44

A 31-year-old woman suffering from stomach pain was admitted to our hospital, and diagnosed with unresectable advanced gastric cancer. She was initially treated with combination therapy of S-1 and CDDP, and a partial response was achieved. After two courses of the chemotherapy, however, she complained of dyspnea, and pulmonary carcinomatous lymphangitis was confirmed by computed tomography. As second-line chemo-therapy, we attempted combination therapy with docetaxel, CDDP and S-1(DCS). After one course of the combination therapy, a remarkable response in the pulmonary carcinomatous lymphangitis was achieved. Treatment of patients with advanced gastric cancer associated with pulmonary carcinomatous lymphangitis is quite difficult and there is no scientific evidence to select anti-cancer drugs for these patients. We concluded that DCF could be a useful regimen for patients with gastric cancer associated with pulmonary carcinomatous lymphangitis.
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PMID:[A case of advanced gastric cancer with pulmonary carcinomatous lymphangitis responding remarkably to combination chemotherapy of docetaxel, CDDP and S-1]. 1909 10

A globally accepted standard chemotherapy remains undetermined in gastric cancer, but the recent introduction of active "new-generation agents" such as taxanes, irinotecan (CPT-11), oxaliplatin, S-1, and capecitabine, offers hope for markedly improving patient outcomes. Docetaxel, as well as the other new-generation agents, plays a key role in the development of the new-era chemotherapy, and the incorporation of taxanes has provided several regimens, such as docetaxel/cisplatin/5-fluorouracil (5-FU) (DCF), that could become standard treatment. The DCF regimen is now regarded as a standard treatment option in advanced gastric cancer in selected patients in good condition. Many institutions and cooperative groups continue to study a variety of docetaxel-based combinations with "new-generation cytotoxic agents" in various treatment settings, and recent attention has been focused on the incorporation of biological agents, such as cetuximab, bevacizumab, everolimus, and sunitinib, into docetaxel-containing combinations as another innovative approach. The ongoing clinical trials of a number of new regimens will clarify their clinical benefits in gastric cancer treatment. Along with the development of more active docetaxel combination regimens, the identification of predictive biomarkers for each regimen has been intensively studied recently. This review focuses on docetaxel as a key agent in gastric cancer chemotherapy, and discusses the role of this taxane in current and future treatments for advanced gastric cancer.
Gastric Cancer 2009
PMID:Docetaxel: its role in current and future treatments for advanced gastric cancer. 1989 Jun 92


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