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)

The expression of the insulin-responsive glucose transporter (GLUT) 4 was studied in three histologically different human gastric cancer cell lines, MKN28, MKN45, and STSA. RT-PCR demonstrated GLUT1 and GLUT4 mRNA in all three cell lines. MKN28 cells expressed GLUT4 protein more than MKN45 and STSA cells by immunohistochemistry. Insulin stimulation of MKN28 cells resulted in a 22% increase in glucose uptake over that found under basal conditions (0.60 +/- 0.05 fmol/cell per min after insulin stimulation versus 0.53 +/- 0.07 fmol/cell per 3 min at basal). No increase in glucose uptake occurred with insulin stimulation in MKN45 or STSA cells. We conclude that the insulin responsive GLUT4 is expressed in MKN28, MKN45, and STKM1 human gastric cancer cell lines, albeit in different amounts. The greater expression of this transporter in MKN28 cells is likely responsible for the cell's ability to increase glucose uptake with insulin stimulation. However, the role played by GLUT4 in regulating the amount of glucose uptake would not be large in those human gastric cancer cell lines.
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PMID:Glucose uptake in the human gastric cancer cell line, MKN28, is increased by insulin stimulation. 1040 43

The antitumor drug NB-506, which is currently undergoing phase I/II clinical trials, contains a DNA-intercalating indolocarbazole chromophore substituted with a glucose residue. In addition to interacting with DNA, the drug stabilizes the topoisomerase I-DNA covalent complex. To reinforce the DNA binding and anti-topoisomerase I activities of NB-506, an analogue containing a new substituent on the naphthalimide ring F was synthesized. The N-formylamino group of NB-506 has been replaced with a more hydrophilic group, N-bis(hydroxymethyl)methylamino. In this study we show that the incorporation of a longer substituent on the N6 position effectively reinforces both the interaction with DNA and the capacity of the drug to maintain the integrity of the topoisomerase I-DNA covalent complexes. The strength and the mode of binding of the drugs to DNA were studied by complementary biophysical techniques including absorption, fluorescence, and circular and linear dichroism. Various biochemical procedures were applied to investigate the effects on human topoisomerase I using plasmid DNA as well as restriction fragments. The drug binding sites and the positions of the topoisomerase I-mediated cleavage sites were mapped with nucleotide resolution using footprinting and sequencing techniques. Cytotoxicity measurements performed with various human cancer cell lines (HCT-116, DLD-1, MKN-45) indicate that the newly designed drug is 3 to 4 times more toxic to colon and gastric cancer cells than NB-506. Therefore, the results suggest that the antitumor activity of indolocarbazole-based drugs can be enhanced by incorporating DNA and/or topoisomerase I reactive groups. They also support the hypothesis that the substituent on the imide nitrogen on the F ring of NB-506 has direct interaction with the molecular target. The study helps to define the structure-activity relationships in the indolocarbazole series of antitumor agents targeting topoisomerase I.
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PMID:Substitution at the F-ring N-imide of the indolocarbazole antitumor drug NB-506 increases the cytotoxicity, DNA binding, and topoisomerase I inhibition activities. 1042 2

Three galloyl monosaccharides contained in medicinal plants were examined for apoptosis-inducing activity in human histiocytic lymphoma U937 cells. Tetragalloyl glucose (TgG) induced apoptosis as found by chromatin condensation, DNA ladder formation, and inhibition by a caspase inhibitor. Digalloyl hamamelose had moderate activity, while monogalloyl glucose was only marginally active. These findings suggest that the number and disposition of their phenolic groups are important for apoptosis induction. TgG induced apoptosis in human colon and stomach cancer cell lines as well, indicating it is potentially useful as an anti-cancer agent.
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PMID:Apoptosis-inducing activity of galloyl monosaccharides in human histiocytic lymphoma U937 cells. 1076 84

Crude methanol extracts of red and white wines were added to diethyl ether in order to divide them into the anthocyanin fraction (insoluble in diethyl ether) and fractions containing other flavonoids and their derivatives (soluble in diethyl ether). However, the white wine did not contain anthocyanins (all of the methanol extract was soluble in diethyl ether). When HCT-15 cells, derived from human colon cancer or AGS cells, derived from human gastric cancer, were cultured with these fractions, the anthocyanin fraction from the red wine and the non-anthocyanic substances extracted from red and white wines suppressed the growth of the cells, and the suppression rate by the anthocyanin fraction was significantly higher than that of the other fractions. Thin-layer chromatographic analysis revealed mostly delphinidin in the anthocyanin fraction. The other fractions contained mostly flavonoids and their derivatives. The sugars in all fractions were mainly glucose, fucose, and fructose. Flow cytometric study suggested that the anthocyanin fraction blocked mostly S, G2, and M phase, and the non-anthocyanic flavonoids also blocked these phases, although the histographic pattern varied depending on the fractions. Methanol insoluble but water soluble fractions (mostly free sugars) of red and white wines did not show such suppressive effects.
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PMID:Anti-tumor effect of methanol extracts from red and white wines. 1085 37

Increased expression of glucose transporter1 (GLUT1) has been reported in many human cancers. We hypothesized that the degree of GLUT1 might provide a useful biological information in gastric adenocarcinoma. RT-PCR and immunostaining were used to analyze GLUT1 expression in gastric cancer. RT-PCR showed GLUT1 expression was not largely detected in normal gastric tissue but was detected in cancerous gastric tissue of counterpart. By immunohistochemistry, GLUT1 protein was absent in normal gastric epithelium and intestinal metaplasia. 11 of 65 patients with gastric adenocarcinoma had specific GLUT1 immunostaining in a plasma membrane pattern with varied intensities. GLUT1 protein did not show any significant correlation with tumor stage and nodal metastasis (p>0.05 by Mann-Whitney test). However, the positive immunostaining for GLUT1 is associated with intestinal differentiation (p=0.003). Our results suggest that GLUT1 protein is associated with intestinal type of gastric cancer.
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PMID:Glucose transporter 1 (GLUT1) expression is associated with intestinal type of gastric carcinoma. 1098 90

We hypothesized that the tolerance for nutrient deprivation as well as angiogenesis might be an important factor for tumor progression under hypovascular conditions. When normal human fibroblasts were subjected to extreme nutrient starvation by culturing in a medium without serum, glucose, and amino acids, cells died within 24 h. When substituted with liver cancer cell lines HepG2, Hep3B, HLE, and HuH-7, cell death occurred within 36 h. In contrast, four of six pancreas cancer cell lines, PANC-1, AsPC-1, BxPC-1, and KP-3, survived for remarkably longer periods; >50% of the cells survived, even after starvation for 48 h. Among three gastric cancer cell lines, MKN28, MKN45, and MKN74, only the most poorly differentiated MKN45 cells survived >36 h. More than 50% of the cells in colon cancer cell lines SW480, WiDr, and DLD-1 survived after 36 h, and the most undifferentiated SW480 cell line survived longest. We examined the possible involvement of PKB/Akt expression in the survival of various cell lines under nutrient starvation conditions. High expression of PKB/Akt was found to be associated with tolerance for nutrient starvation. When Akt antisense RNA expression vectors were introduced into PANC-1 cells, the tolerance was partially but significantly diminished by vectors for Akt1 and Akt2 but not Akt3. Because elimination of the tolerance might serve as a new strategy for cancer therapy, several compounds were tested for this purpose, and troglitazone, an insulin sensitizer, as well as LY294002, a phosphatidylinositol 3-kinase inhibitor, were found to kill PANC-1 cells only under nutrient starvation conditions.
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PMID:Remarkable tolerance of tumor cells to nutrient deprivation: possible new biochemical target for cancer therapy. 1108 46

Most solid tumors, including gastric cancers, respond poorly to non-surgical treatments which are expected to induce an apoptosis-dependent involution. We hypothesize that the apoptotic machinery in solid tumors is either defective or in a suppressed condition. Overcoming the ineffective induction of apoptosis may improve the responsiveness of solid tumors to non-surgical treatments. Recently, sorbitol, a kind of hexose, has been found to be an effective inducer of apoptosis in HEp-2 cells. Therefore, it is of particular interest to examine the effect of sorbitol-treatment on gastric cancer cells. in the present study, we selected 4 gastric cancer cell lines which have been reported to exhibit different abilities in regard to apoptosis induction, and examined the effect of sorbitol-treatment on apoptosis induction. Within 3 hr after sorbitol-treatment, apoptosis was induced comparably in all cell lines examined. Cell death in MKN-1, MKN-28 or MKN-74 proceeded in a biphasic manner, while cell death in KATO-III was monophasic. The cell death partially depended on caspase activity. Treatments with sorbitol in combination with 12-O-tetradecanoylphorbol-13-acetate (TPA) markedly suppressed the apoptotic cell death, suggesting a role of protein kinase-C-dependent process. To our knowledge, this is the most rapid induction of apoptosis in human gastric cancer cells reported to date.
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PMID:Rapid induction of apoptosis in human gastric cancer cell lines by sorbitol. 1123 46

Vitamin C, a water-soluble glucose derivative, has considerable antioxidant activity in vitro, in part because of its ease of oxidation and because the semidehydroascorbate radical derived from it is of low reactivity. Vitamin C in vivo is an essential cofactor for a range of enzymes involved in diverse metabolic pathways, but much recent literature has focused on its antioxidant effects. Consumption of foods rich in Vitamin C (fruits and vegetables) is associated with decreased risk of cardiovascular disease, of many types of cancer and possibly of neurodegenerative disease, but the extent to which Vitamin C contributes to these effects is uncertain. Data using biomarkers of oxidative damage to DNA bases have given no compelling evidence to date that ascorbate supplements can decrease the levels of oxidative DNA damage in vivo, except perhaps in subjects with very low Vitamin C intakes. Similarly, there is no conclusive evidence from studies of strand breaks, micronuclei, or chromosomal aberrations for a protective effect of Vitamin C. There is limited evidence that supplements of Vitamin C might have beneficial effects in disorders of vascular function, and that diet-derived Vitamin C may decrease gastric cancer incidence in certain populations, but it is not clear whether it is the antioxidant or other properties of ascorbate that are responsible for these two actions.
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PMID:Vitamin C and genomic stability. 1129 51

We examined peripheral insulin sensitivity in 32 patients with cancer (17 with stomach cancer, 7 with colorectal cancer, and 8 with lung cancer) and 6 normal control subjects by the euglycemic hyperinsulinemic glucose clamp technique. The relationships between insulin resistance and tumor factors (type and stage), malnutrition, and inflammatory reaction were evaluated. Insulin sensitivity often was reduced in patients with cancer; however, the amount of glucose metabolized was not related to tumor site or stage. The decreased glucose uptake was negatively correlated with the acute-phase response but was not correlated with body-weight loss, serum albumin, or resting energy expenditure. Our results suggest that insulin resistance in cancer patients was not induced by malnutrition. Although the qualitative presence of tumor might be the major factor inducing insulin resistance, other factors such as inflammatory reactions might be involved in the development of insulin resistance.
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PMID:Insulin resistance in patients with cancer: relationships with tumor site, tumor stage, body-weight loss, acute-phase response, and energy expenditure. 1144 78

In this paper the use of arsenic compounds as anticancer agents in clinical trials and in in vitro investigations is reviewed, including the experience at our institute. Treatment of newly diagnosed and relapsed patients with acute promyelocytic leukemia (APL) with arsenic trioxide (As2O3) has been found to result in complete remission (CR) rates of 85-93% when given by intravenous infusion for 2-3 h at a dose of 10 mg/day diluted in 5% glucose saline solution. Patients exhibit a response in 28-42 days. CR rates after administration of Composite Indigo Naturalis tablets containing arsenic sulfide and of pure tetraarsenic tetrasulfide reached 98% and 84.9%, respectively. At higher concentrations (1-2 microM), arsenic induced apoptosis, while at lower concentrations (0.1-0.5 microM), it triggered cell differentiation in vitro. As2O3-induced apoptosis has been observed in many cancer cell lines, including esophageal carcinoma, gastric cancer, neuroblastoma, lymphoid malignancies, and multiple myeloma. Its effectiveness was confirmed in the treatment of multiple myeloma. Arsenic compounds are effective agents in the treatment of APL and their activity against other types of cancer requires further investigation.
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PMID:Arsenic compounds as anticancer agents. 1158 71


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