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)

E-cadherin germline missense mutations have been shown to be responsible for significant loss of protein activity. A new cytoplasmic E-cadherin germline missense mutation (V832 M) was recently identified in a hereditary diffuse gastric cancer (HDGC) Japanese family. This E-cadherin mutant was cloned in a Chinese hamster ovary cell model system and functionally characterized, in terms of aggregation and invasion. Cells expressing the germline V832M mutant fail to aggregate and invade into collagen, supporting the pathogenic role of this germline missense mutation in gastric cancer. We also tested the ability of this mutation to activate the TCF-LEF trascriptional activity, in comparison with three other E-cadherin missense mutations (T340A, A634V and A617T), associated to loss of E-cadherin function. All the E-cadherin mutants reduced TCF-LEF activation to a similar extent as the wild-type protein, suggesting that the oncogenic effect of the E-cadherin mutants is unlikely to be transmitted through a beta-catenin-dependent activation of the WNT pathway.
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PMID:The intracellular E-cadherin germline mutation V832 M lacks the ability to mediate cell-cell adhesion and to suppress invasion. 1294 22

Ascorbic acid is one of the important water soluble vitamins. It is essential for collagen, carnitine and neurotransmitters biosynthesis. Most plants and animals synthesize ascorbic acid for their own requirement. However, apes and humans can not synthesize ascorbic acid due to lack of an enzyme gulonolactone oxidase. Hence, ascorbic acid has to be supplemented mainly through fruits, vegetables and tablets. The current US recommended daily allowance (RDA) for ascorbic acid ranges between 100-120 mg/per day for adults. Many health benefits have been attributed to ascorbic acid such as antioxidant, anti-atherogenic, anti-carcinogenic, immunomodulator and prevents cold etc. However, lately the health benefits of ascorbic acid has been the subject of debate and controversies viz., Danger of mega doses of ascorbic acid? Does ascorbic acid act as a antioxidant or pro-oxidant? Does ascorbic acid cause cancer or may interfere with cancer therapy? However, the Panel on dietary antioxidants and related compounds stated that the in vivo data do not clearly show a relationship between excess ascorbic acid intake and kidney stone formation, pro-oxidant effects, excess iron absorption. A number of clinical and epidemiological studies on anti-carcinogenic effects of ascorbic acid in humans did not show any conclusive beneficial effects on various types of cancer except gastric cancer. Recently, a few derivatives of ascorbic acid were tested on cancer cells, among them ascorbic acid esters showed promising anticancer activity compared to ascorbic acid. Ascorbyl stearate was found to inhibit proliferation of human cancer cells by interfering with cell cycle progression, induced apoptosis by modulation of signal transduction pathways. However, more mechanistic and human in vivo studies are needed to understand and elucidate the molecular mechanism underlying the anti-carcinogenic property of ascorbic acid. Thus, though ascorbic acid was discovered in 17th century, the exact role of this vitamin/nutraceutical in human biology and health is still a mystery in view of many beneficial claims and controversies.
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PMID:Vitamin C in human health and disease is still a mystery? An overview. 1449 93

The present study was undertaken to clarify the histochemical and ultrastructural properties and the three-dimensional distribution of the smooth muscle cells (SMCs) located in the lamina propria (LP) of the human gastric mucosa. Standard paraffin sections obtained from stomachs surgically resected for gastric cancer were immunostained for alpha-smooth muscle actin (alpha-SMA), vimentin, desmin, laminin, and type IV collagen. In addition, 100-microm-thick sections were fluorostained for alpha-SMA and CD34, while three-dimensional images were prepared by confocal laser scanning microscope. Ultrastructural studies were carried out using normal gastric biopsy specimens. The results indicated that SMCs in the LP differed between the upper and lower regions, SMCs in the lower LP being fairly typical SMCs, whereas those in the upper LP had apparently lost reactivity for desmin but gained that for vimentin. The basal lamina became sparser, but a fibronexus was occasionally seen in SMCs in the upper LP. Three-dimensional images revealed bundles of SMCs in the upper LP encircling several foveolae to form acinus-like structures and, in the upper LP, SMCs branching into fine fibrils with a brush-like (corpus) or besom-like (i.e., a twiggy "witch's broom") appearance (antrum).
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PMID:Histochemical, ultrastructural, and three-dimensional observation of smooth muscle cells in human gastric mucosa. 1496 14

Apoptosis of the target cells is an important index in the assessment of the efficacy of cancer chemotherapy. We previously established a new experimental technique in which cancer cells are distributed in thin collagen gel as one or two cell layers, and cultured with anti-cancer drugs. The cells are stained with fluorescent Hoechst 33258 (Ho) and photographed, then with hematoxylin and eosin (H&E) and again photographed. The results show that most cell death patterns can be determined by combining observations of Ho and H&E-stained cells without the necessity for judging the apoptosis by electron microscopy. 5-fluorouracil (5-FU) and cisplatin (CDDP) are important anti-cancer drugs in the treatment of a variety of cancers. 5-FU or CDDP alone have shown significant effects in the treatment of gastric and colon cancers, and in addition, it has been shown that the combination of 5-FU plus CDDP (FP) therapy produces synergism greater than 5-FU or CDDP alone in gastrointestinal cancer. In this study, we evaluated the efficacy and toxicity of FP therapy in the gastric cancer cell lines MKN45, MKN28, and KATOIII and the colon cancer cell lines HCT116 and COLO320, and examined the relationship between the response to FP therapy and apoptosis. Additionally, we performed transfection of normal p53 gene into p53 mutant MKN28 cells and analyzed the impact of the p53 gene on a sensitivity test. Wild-type p53 in MKN45, HCT116, and COLO320 cells underwent significantly (p<0.01) more apoptosis than MKN28 and KATOIII cells possessing p53 mutant- and deficient-type, respectively, in FP therapy. Transfection of p53 to MKN28 cells resulted in a significantly (p<0.01) higher apoptotic index. From these results, we conclude that the p53 pathway allows induction of apoptosis in gastrointestinal cancers in FP therapy treatment, and that identification of the p53 type of a patient's cancer can be used to predict the success of FP therapy.
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PMID:Expression of p53 protein as a predictor of the response to 5-fluorouracil and cisplatin chemotherapy in human gastrointestinal cancer cell lines evaluated with apoptosis by use of thin layer collagen gel. 1501 Aug 16

Scirrhous gastric cancer is resistant to chemotherapy in comparison to other types of gastric cancers, and cancer cell-stromal fibroblast interactions play an important role in progression of scirrhous gastric cancer. We examined the effect of cancer cell-stromal fibroblast interactions on the sensitivity of an in vitro scirrhous gastric cancer model to the chemotherapeutic agent 5-FU. The model consisted of a human scirrhous gastric cancer cell line, KATO-III, and a human fibroblast cell line, KMST-6, maintained in collagen gel droplet cultures. KATO-III cell sensitivity to 5-FU was significantly decreased in co-cultures with KMST-6. KMST-6 cell sensitivity to 5-FU was also decreased in co-cultures with KATO-III. The addition of tranilast alone inhibited KMST-6, but not KATO-III, cell proliferation. In combination with 5-FU, tranilast significantly enhanced KATO-III cell sensitivity to 5-FU. These results suggest that (i), scirrhous gastric cancer cell sensitivity to 5-FU is decreased by the interactions between the cancer cells and stromal fibroblasts and (ii), tranilast enhances the sensitivity of scirrhous gastric cancer cell to 5-FU by inhibiting stromal fibroblast proliferation.
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PMID:Sensitivity of scirrhous gastric cancer to 5-fluorouracil and the role of cancer cell-stromal fibroblast interaction. 1520 64

Ascorbic acid, as one of the important water-soluble vitamins, is essential for a range of physiological functions, including the syntheses of collagen, carnitine and neurotransmitters. It is also an important dietary antioxidant against oxidative stress. Current information suggests that vitamin C might be protective against the development of gastric cancer. Chronic infection with Helicobacter pylori is recognized to be a significant cause of gastric adenocarcinoma. Inflammation induced by H. pylori infection in the stomach not only causes significantly enhanced consumption of vitamin C, but also reduces secretion of the vitamin into the gastric lumen. Most of the evidence relating to vitamin C and H. pylori infection derives from clinical studies and experiments directly examining the effect of vitamin C on H. pylori-associated gastric carcinogenesis and remains limited. Furthermore, results from recent studies suggest that vitamin C might also increase the risk of cancer through its pro-oxidant activity and protect against oxidative stress in cancer cells through its antioxidant action. In this article we review recent publications on vitamin C research and assess the potential roles of vitamin C in H. pylori associated gastric carcinogenesis. The possible adverse effects of the vitamin C are also discussed.
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PMID:The roles of vitamin C in Helicobacter pylori associated gastric carcinogenesis. 1590 21

Clinical in vivo and in vitro studies have revealed pronounced gastric cancer activity using the combination of 5-fluorouracil (5-FU) and cisplatin (CDDP). In addition, the combination of 5-fluorouracil plus cisplatin (FP treatment) possesses synergistic cytotoxicity against gastric cancer. Sensitivity of two gastric cancer cell lines to anti-cancer drugs, 5-fluorouracil (5-FU) and/or cisplatinum (CDDP), was evaluated by use of either flow cytometric analysis (FACS) or morphological observation in terms of induction of apoptosis. In morphological observation, a new experimental technique was used in which cancer cells were distributed in thin collagen gel as one or two cell layers, and cultured with anti-cancer drugs. Thereafter, cells were stained with fluorescent Hoechst 33258 (Ho) and photographed, then stained with hematoxylin and eosin (H&E) and photographed again. Cell death patterns were determined by combining observations of Ho- and H&E-stained cells. While combined administration of 5-FU and CDDP did not induce apoptosis of MKN-28 (mutant-type p53), apoptotic cells were markedly observed in the case of MKN45 (wild-type p53). In addition, consecutive administration of CDDP for 3 h and 5-FU for 21 h effectively induced apoptosis of MKN45. These results indicated that the type of p53 expression in cancer cells could be a promising factor in predicting response to FP therapy and the administration of CDDP prior to 5-FU may be more effective in inducing apoptosis of gastric cancer cells with wild-type p53 expression. These data may provide evidence to support the idea that p53 expression is related to multidrug resistance (MDR) in FP therapy of gastric cancer cell lines.
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PMID:The evaluation of gastric cancer sensitivity to 5-FU/CDDP in terms of induction of apoptosis: time- and p53 expression-dependency of anti-cancer drugs. 1607 63

The effect of conjugated linoleic acid (CLA) on peritoneal metastasis was examined by in vitro treatment of cancer cells and mouse peritoneal metastasis models. First, cell growth of MKN28 human gastric cancer cells and Colo320 human colon cancer cells was suppressed by CLA in a dose-dependent manner with an increment in apoptosis. CLA significantly inhibited invasion into type IV collagen-coated membrane of MKN28 and Colo320 cells (p < 0.05). CLA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor (PPAR)-gamma in both cell lines. BALB/c nu-nu mice were inoculated with MKN28 and Colo320 cells into their peritoneal cavity, and administrated with CLA intraperitoneally (weekly, 4 times). CLA treatment did not affect food intake or weight gain of mice. CLA treatment significantly decreased metastatic foci of both cells in the peritoneal cavity (p < 0.005). Survival rate in mice inoculated with MKN28 or Colo320 cells was significantly recovered by CLA treatment (p = 0.0025 and 0.0052, respectively). Protein production in MKN28 and Colo320 cells treated with CLA showed a decrease in epidermal growth factor receptor and transforming growth factor-alpha and an increase in Bax. These findings suggest that CLA inhibits metastasis of human gastric and colon cancer cells.
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PMID:Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal cancer cells. 1610 1

Experimental evidence supports a role for E-cadherin in suppressing invasion, metastasis, and proliferation. Germline mutations of the E-cadherin represent the genetic cause of hereditary diffuse gastric cancer (HDGC). In this type of tumor, isolated cancer cells permeate the basal membrane and paradoxically survive in the gastric wall in the absence of contact with neighbor epithelial cells or with the extracellular matrix. This suggests that upon E-cadherin deregulation, cells acquired resistance to apoptosis. To test this hypothesis, CHO cells stably expressing either wild-type E-cadherin or the HDGC-related germline mutations T340A and V832M were seeded either on a thin layer of collagen type I or on plastic and then subjected to the apoptotic agent taxol. We found that in vitro functional E-cadherin renders cells more sensitive to the effect of taxol. Our results also indicate that this effect is associated to decreased level of the anti-apoptotic bcl-2 protein.
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PMID:Loss of functional E-cadherin renders cells more resistant to the apoptotic agent taxol in vitro. 1611 67

In vitro chemosensitivity test using a collagen-gel method was done on 165 primary gastric cancers. All of 5-FU, CBDCA, CDDP and docetaxel showed a high sensitivity. The effects of per oral (po) administration of TS-1, a combination of po TS-1 and intraperitoneal (ip) administration of CDDP, ip 5-FU and ip docetaxel, were evaluated in athymic mice bearing peritoneal dissemination of a gastric cancer cell line (MKN-45-P that shows a high rate of metastasis to the peritoneal cavity of nude mice). Nude mice were inoculated by ip with 10(7) MKN-45-P cells. No survival benefit was obtained after po administration of TS-1 (12 mg/kg) alone or ip CDDP alone. However, a combination of po TS-1 (8 mg/kg x 10 days, from day 3) and ip CDDP (3.5 mg/kg, day 6 and 13) showed a significant survival improvement than that of po TS-1 or ip CDDP treatment alone. ip administration of 30 mg/kg (3 times/week x 3 weeks) or 15 mg/kg (6 times/week x 3 weeks) of 5-FU significantly improved the survival of mice bearing MKN-45-P. 5-FU concentration of ascites after ip administration of 30 mg/kg of 5-FU was 600-fold higher than po administration of 12 mg/kg of TS-1 at peak level. ip injections of docetaxel of 8 mg/kg, and 2 mg/kg improved the survival of 4 and 1 mice, respectively, and they were tumor-free on day 90. Survival of mice treated with ip injection of CBDCA (100 mg/kg, on day 3, or 50 mg/ kg on day 3 and 10) was significantly better than the control group. These results suggest the potential of po TS-1 + ip CDDP, ip 5-FU, ip docetaxel and ip CBDCA administration for the treatment of peritoneal dissemination of gastric cancer.
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PMID:[Effect of intraperitoneal chemotherapy on experimental peritoneal dissemination of gastric cancer]. 1631 93


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