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

We made a retrospective review of the patients with cancer of the digestive organs who died between January 1, 1975 and December 31, 1985, at Shinshu University Hospital. Of 183 patients with such cancers 15 (8.2%) had hypercalcemia. Hypercalcemia was defined as serum calcium level greater than 11.0 mg/dl on at least two determinations. The incidence of hypercalcemia by site was 5 of 74 (6.8%) liver, 1 of 16 (6.3%) biliary tract, 4 of 33 (12.1%) pancreas, 3 of 15 (20.0%) esophagus, 0 of 37 stomach, 0 of 2 duodenum, 2 of 5 colon, and 0 of 1 rectum carcinomas. There was no sexual or age predisposition to hypercalcemia. Bone scans and/or x-ray results were positive in three of eight, negative in five of eight, and were not evaluated in the remaining seven patients. Of five patients tested, four had low to normal serum parathyroid hormone (PTH) levels, and one had a serum PTH level high by C-terminal assay but normal by N-terminal assay. Serum chloride levels at the late stage of hypercalcemia were less than 102 mEq/L in all patients. Therefore, hyperproduction of PTH was unlikely to be a causative factor for hypercalcemia. Indomethacin was given to four patients with hypercalcemia with no effect on serum calcium levels in any cases. Survival from the diagnosis of hypercalcemia ranged from 2 to 96 days (mean 33 days). We conclude that hypercalcemia is a complication not infrequent at the late stages of cancers of the digestive organs, with the exception of gastric cancer, and a portent of a poor prognosis.
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PMID:Hypercalcemia of cancer in the digestive tract. 355 19

To clarify the role of mitogen-inducible cyclooxygenase (COX-2) in the development of malignant tumors, we investigated the effects of COX-2 inhibitors on the growth of gastric cancer xenografts in nude mice in vivo. MKN45 gastric cancer cells (5 x 10(6) cells/animal) that overexpress COX-2 were inoculated subcutaneously into athymic mice. NS-398, a specific COX-2 inhibitor, or indomethacin, a nonspecific COX-2 inhibitor, was administered orally to animals every day for 20 days. These drugs reduced the tumor volume significantly. Immunohistochemistry using bromodeoxyuridine, nick end labeling, and electron microscopy showed that NS-398 induced apoptosis in cancer cells in a dose-dependent manner and inhibited cancer cell replication slightly. Indomethacin also induced apoptosis and suppressed replication of tumor cells. There was a significant negative correlation between tumor volume and apoptotic cell number within the tumor. These results are consistent with the hypothesis that COX-2 inhibitors suppress growth of gastric cancer xenografts mainly by inducing apoptosis and suppressing replication of the neoplastic cells. It follows that COX-2 plays an important role in the development of gastric cancer.
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PMID:Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice. 969 6

Apoptosis plays a major role in gastrointestinal epithelial cell turnover, ulcerogenesis and tumorigenesis. We have examined apoptosis induction by non-steroidal anti-inflammatory drugs (NSAIDs) in human gastric (AGS) cancer cells and the role of protein kinase C (PKC) and apoptosis-related oncogenes. After treatment with aspirin or indomethacin, cell growth was quantified by MTT assay, and apoptosis was determined by acridine orange staining, DNA fragmentation and flow cytometry. The mRNA and protein of p53, p21waf1/cip1 and c-myc was detected by Northern and Western blotting respectively. The influence of PKC on indomethacin-induced apoptosis was determined by co-incubation of 12-O-tetradecanoylphorbol 13-acetate (TPA). The role of c-myc was determined using its antisense oligonucleotides. The results showed that both aspirin and indomethacin inhibited cell growth and induced apoptosis of AGS cells in a dose- and time-dependent manner, without altering the cell cycle. Indomethacin increased c-myc mRNA and protein, whereas p53 and p21wafl/cip1 were unchanged. Down-regulation of c-myc by its antisense oligonucleotides reduced apoptosis induction by indomethacin. TPA could inhibit indomethacin-induced apoptosis and accumulate cells in G2/M. Overexpression of c-myc was inhibited by TPA and p21waf1/cip1 mRNA increased. In conclusion, NSAIDs induce apoptosis in gastric cancer cells which may be mediated by up-regulation of c-myc proto-oncogene. PKC activation can abrogate the effects of NSAIDs by decreasing c-myc expression.
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PMID:Non-steroidal anti-inflammatory drug-induced apoptosis in gastric cancer cells is blocked by protein kinase C activation through inhibition of c-myc. 1002 4

Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are two well-known important causative factors of gastric damage. While H. pylori increases apoptosis and the proliferation of gastric epithelial cells and is an important factor in peptic ulcer and gastric cancer, NSAIDs induce cell apoptosis and have antineoplastic effects. We investigated the effects of NSAIDs (a nonselective cyclooxygenase [COX] inhibitor [indomethacin] and a selective COX-2 inhibitor [NS-398]) on the apoptosis and proliferation of gastric epithelial cells and gastric inflammation in H. pylori-infected mice. C57BL/6 mice were sacrificed 8 weeks after H. pylori SS1 inoculation. Indomethacin (2 mg/kg) or NS-398 (10 mg/kg) was administered subcutaneously once daily for 10 days before sacrifice. The following were assessed: gastric inflammatory activity, gastric COX protein expression by Western blotting; gastric prostaglandin E(2) levels by enzyme immunoassay, apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, and cell proliferation by Ki67 immunostaining. Compared to the controls, H. pylori infection and/or NSAID treatment increased COX-1 and COX-2 protein expression. Gastric prostaglandin E(2) levels, apoptotic index, cell proliferation index, neutrophil activity, and the degree of chronic inflammation were all increased by H. pylori infection, and these effects were significantly decreased by indomethacin treatment. However, NS-398 treatment after H. pylori infection did not induce a significant reduction, although it did result in a tendency to decrease. These results show that NSAIDs can reverse the increased apoptosis and proliferation of epithelial cells and inflammatory activity in the stomachs of H. pylori-infected mice and that, like COX-2 activation, COX-1 induction contributes to the change of gastric mucosal cell turnover and inflammation induced by H. pylori infection.
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PMID:Effects of nonsteroidal anti-inflammatory drugs on Helicobacter pylori-infected gastric mucosae of mice: apoptosis, cell proliferation, and inflammatory activity. 1144 86

Helicobacter pylori (H. pylori) infection has been recognized to be a causal factor of gastritis, ulcers and gastric cancer in man. Using Mongolian gerbils (M. gerbils), which are suitable for an H. pylori infection animal model, we examined 1) how H. pylori infection, indomethacin and their combination affects the healing of gastric ulcers and whether or not such factors provoke a relapse of healed acetic acid ulcers; and 2) whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes, including gastric adenocarcinoma. 1) H. pylori infection significantly delayed ulcer healing 4 weeks following infection. Indomethacin treatment showed a tendency to delay ulcer healing. Ulcer healing in H. pylori-infected M. gerbils was significantly delayed by indomethacin. H. pylori infection resulted in a relapse of healed ulcers from 1 to 6 months after infection, with a gradual increase in size. Omeprazole markedly prevented the ulcer relapse caused by H. pylori infection. 2) Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole + clarithromycin. Immediately after treatment ended in both the 5 and 9 month groups, it was verified that H. pylori were completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible; and atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the non-treated control group. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that 1) H. pylori infection delayed the healing of preexisting gastric ulcers and resulted in the relapse of healed ulcers, yet indomethacin had little or no effect on ulcer healing or relapse; and 2) early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in M gerbils.
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PMID:[Pharmacological study on the pathological changes of the gastric mucosa in Helicobacter pylori-infected Mongolian gerbils]. 1168 Jan 69

Helicobacter pylori (H. pylori) often play an important role in the pathogenesis of gastritis, peptic ulcer, and probably also gastric cancer. Reactive oxygen species (ROS) produced by this bacterium may be one of the crucial factors whereby oxidative stress can play a role in the pathogenesis of ulcer disease. The aim of this study was to assess ROS activity and glutathione redox status, a principal cellular redox sensor, in H. pylori-associated indomethacin-induced gastric ulcers in rats. Gastric lesion was produced by intragastric administration of indomethacin (7 mg/kg) for three days followed by administration of H. pylori suspension (density 10(9) colony forming units). Animals receiving indomethacin only or followed by administration of H. pylori suspension were sacrificed after 11 and 18 days. ROS activity was assessed by the level of lipid peroxidation (LPO) and the glutathione redox status by the ratio between oxidized and reduced glutathione (GSSG/GSH). Indomethacin did not significantly increase the level of LPO and the GSSG/GSH ratio. When H. pylori suspension was given together with indomethacin the LPO was increased both on days 11 and 18 and GSSG/GSH on day 18. H. pylori, thus, substantially increases glutathione redox ratio and lipid peroxidation in gastric mucosa, which may play an important role in the pathological mechanisms of this bacterium. The findings support the idea that dietary antioxidants could be beneficial in combination therapy for eradication of H. pylori.
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PMID:Helicobacter pylori substantially increases oxidative stress in indomethacin-exposed rat gastric mucosa. 1586 8

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


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