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 incidence of gastric cancer is higher in men than women. Epidemiological studies suggest that female hormones reduce gastric cancer risk. We examined the effect of ovarian-dependent female hormones on Helicobacter pylori-induced gastric cancer in hypergastrinemic INS-GAS mice. Male and female sexually intact or ovariectomized (OVX) mice were inoculated with H.pylori SS1 or vehicle-only at 10 weeks of age, and tissues were evaluated at 16 or 28 weeks post-infection (WPI). A subset of OVX females were supplemented with 17beta-estradiol (E2), beginning at 16 WPI. Stomachs were evaluated by histopathology, Ki-67 proliferation index, H.pylori quantitative culture and quantitative polymerase chain reaction for messenger RNA expression of inducible nitric oxide synthase (iNOS) and inflammatory cytokines. Infected OVX females developed significantly more severe gastritis (P < 0.05) than infected intact females at both time points. E2 treatment in infected OVX females attenuated the severity of gastritis. Gastrointestinal intraepithelial neoplasia (GIN) developed in 42% of infected males and 10% of infected OVX females by 28 WPI, whereas infected intact females and E2-treated OVX females did not develop GIN. Infected OVX females showed significantly increased iNOS expression and epithelial cell proliferation when compared with intact, infected females. Likewise, interferon-gamma, tumor necrosis factor-alpha and interleukin-1beta (IL-1beta) expression in infected OVX females were significantly increased at 28 WPI when compared with intact counterparts. E2 treatment in infected OVX females significantly decreased IL-1beta expression, increased IL-10 expression and reduced epithelial cell proliferation. These results demonstrate a protective effect of E2 in H.pylori-induced gastric cancer in a mouse model.
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PMID:Protective role of 17 beta -estradiol against the development of Helicobacter pylori-induced gastric cancer in INS-GAS mice. 1772 78

Gastrointestinal ailments evoke changes in the hypothalamic-pituitary-adrenal (HPA) axis and modulation of hepatic protein synthesis. We examined the catabolic effect of certain primary gastrointestinal diseases and surgery on the concentration of insulin-like growth factor I (IGF-I). Blood samples from patients with gastric cancer (GC), cholecystitis (CC), or inguinal hernia (IH) were taken before and after surgery. The concentrations of IGF-I, IGF binding protein-1 (IGFBP-1), insulin, cortisol, and glucose were determined. In GC patients the concentration of IGF-I was reduced and the concentrations of IGFBP-1 and cortisol were elevated preoperatively; after surgery, IGFBP-1 normalized. In CC patients the concentration of IGF-I was low and the concentration of IGFBP-1 was high before cholecystectomy; after surgery IGFBP-1 returned to normal and the concentration of cortisol increased. In IH patients the concentration of IGF-I was low and the concentrations of IGFBP-1 and cortisol were high before surgery; after laparotomy IGFBP-1 returned to normal. The metabolic changes were present in all analyzed patient groups, regardless of the severity of disease and nutrition. The concentration of IGF-I was reduced before surgery and remained reduced after, recommending IGF-I as a metabolic marker in both pre and postoperative examination of patients.
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PMID:Insulin-like growth factor I (IGF-I) as a sensitive biomarker of catabolism in patients with gastrointestinal diseases. 1784 15

Gastric cancer (GC) is a common and complex disease caused by multifactors. The aim of our study was to investigate the association of the common polymorphisms detected in insulin-like growth factor (IGF)-II, IGF-1 receptor, insulin-like growth factor binding protein 1 (IGFBP1), insulin (INS) and tyrosine hydroxylase (TH) with susceptibility to GC in a northwestern Chinese population. One hundred and fifty-four GC patients and 166 healthy controls were investigated in our study. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of CC and CT genotypes of TH were significantly higher in GC patients than in controls, as the odds ratios were 3.03 (95%CI 1.438-6.362, P=0.003) and 1.97 (95%CI 1.218-3.167, P=0.005), respectively. No association was found between the polymorphisms of IGF-II ApaI, insulin-like growth factor-1 receptor MnlI, IGFBP1 Bgl II and INS-23HphI and the development of GC. The presence of CC and CT genotypes of TH was associated with a significantly increased risk of GC. But the polymorphisms of other genes detected did not indicate an increased risk of GC in the investigated population.
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PMID:Association of gastric cancer with tyrosine hydroxylase gene polymorphism in a northwestern Chinese population. 1797 51

Neoplasia was established in 5.4% out of 15,813 patients with diabetes mellitus registered at the City Population-Based Cancer Register and Territorial Diabetic Center, St. Petersburg. Gender-unrelated decreasing order of tumor sites was as follows: breast, skin, uterus, colon and stomach. Broncho-pulmonary and gastric cancer incidence in male patients with diabetes was higher than in females (3.5 and 2.2 times, respectively). The relationship was reversed with thyroid cancer and skin melanoma (4.4 and 2.3 times, respectively). In patients with type 1 diabetes mellitus (10.3%), the cancer incidence pattern differed significantly from that in the whole diabetes-associated cohort of cancer patients: the former tended to involve such sites as pancreas, urinary bladder, stomach, cervix uteri, lung and skin. Data on age at diagnosis of cancer or diabetes, insulin therapy intensity and body mass were evaluated. The value of timely screening for both cancer and diabetes mellitus in such cohorts was confirmed.
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PMID:[Registry-based analysis of cancer and diabetes combination: prevalence and features]. 1819 8

Insulin-like growth factors (IGFs) and their receptors play a crucial role in regulating cell proliferation, differentiation, and apoptosis. Insulin-like growth factor-binding protein-3 is the most abundant insulin-like growth factor receptor in the serum and binds the majority of insulin-like growth factors. Studies reported that circulating level of insulin-like growth factor-binding protein-3 was modulated by functional genetic variants of insulin-like growth factor-binding protein-3 and, therefore, maybe associated with the risk of gastric cancer. In this case-control study of 576 gastric cancer cases and 647 cancer-free control participants in a high-risk Chinese population, we tested the hypothesis that functional polymorphisms A-202C and Gly32Ala of insulinlike growth factor-binding protein-3 are associated with risk of gastric cancer. We found that the variant 32Ala allele was associated with a significantly increased risk of gastric cancer (adjusted odds ratio=1.84, 95% confidence interval=1.45-2.33 for 32Gly/Ala and odds ratio=2.39, 95% confidence interval=1.47-3.90 for 32Ala/Ala, respectively), compared with the wild-type homozygote 32Gly/Gly. Although the A-202C variant was not significantly associated with gastric cancer risk in the single locus analysis, we found a significant locus-locus interaction between insulin-like growth factor-binding protein-3 A-202C and Gly32Ala loci on gastric cancer risk (Pint<0.001). These findings suggest that functional variants of insulin-like growth factor-binding protein-3 might be important markers for gastric cancer susceptibility and further studies are warranted to characterize the functional relevance of the locus-locus interaction of this gene.
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PMID:The role of IGFBP3 functional polymorphisms in the risk of gastric cancer in a high-risk Chinese population. 1828 64

A 69-year-old woman had been treated with insulin for diabetes over the last 8 years. Distal gastrectomy (D2) was undertaken for StageIV stomach cancer. CA19-9 showed marked increases after surgery, but returned to normal after administering S-1. After 12 cycles, the treatment was discontinued due to hepatic disorders, and the clinical course was monitored. Weekly paclitaxel therapy was initiated as second-line therapy when CA19-9 rose again to 467 U/mL. Marked efficacy was noted after completion of one cycle. A total of 23 cycles were conducted. CA19-9 returned to normal, and the patient remains recurrence-free. In the treatment with paclitaxel, pre-treatment with dexamethasone (20 mg each time) is made to prevent hypersensitivity reactions. Since the total dose becomes too large in weekly treatment, however, treatment was initiated at 12 mg in our patient, and the dose was reduced stepwise to 8 mg, 4 mg and 2 mg. At the same time, the dose of insulin at bedtime and before breakfast the following morning was increased in increments of 2 units. This made it possible to maintain good control of blood glucose levels and minimize changes in HbA1c. This experience suggests that the dosage regimen needs refinements in diabetic patients such as a reduction in the dose of steroids and increases in the dose of insulin in long-term treatment.
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PMID:[A case of effective weekly paclitaxel administration for advanced gastric cancer associated with diabetes mellitus -about the control of blood glucose when dexamethasone for prophylaxis against paclitaxel-associated hypersensitivity reactions to the diabetic has been administered]. 1840 35

Helicobacter pylori infection results in chronic gastritis, which may progress to gastric cancer. In this study, we investigated the efficacy of H. pylori eradication in preventing the progression of gastritis to gastric cancer in H. pylori-infected transgenic INS-GAS mice. H. pylori infection induced severe dysplasia and gastric cancer classified as high-grade and low-grade gastrointestinal intraepithelial neoplasia (GIN) in INS-GAS mice at 28 weeks postinfection (WPI). H. pylori eradication therapy using omeprazole, metronidazole, and clarithromycin was administered p.o. at 8, 12, or 22 WPI. Compared with untreated infected mice, H. pylori eradication at 8, 12, and 22 WPI significantly reduced the severity of dysplasia (P < 0.01). Moreover, H. pylori eradication at 8 WPI completely prevented the development of GIN (P < 0.001). Although not as effective as early antimicrobial treatment, prevention of progression to high-grade GIN was achieved by H. pylori eradication at 12 and 22 WPI (P < 0.05). Consistent with reduced gastric pathology, H. pylori eradication at all time points significantly down-regulated gastric Interferon-gamma, tumor necrosis factor-alpha, inducible nitric oxide synthase, and Reg 1 mRNA levels (P < 0.05) and reduced epithelial proliferation in the corpus (P < 0.01) compared with untreated infected mice. We concluded that H. pylori eradication prevented gastric cancer to the greatest extent when antibiotics are given at an early point of infection, but that eradication therapy given at a later time point delayed the development of severe dysplastic lesions.
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PMID:Helicobacter pylori eradication prevents progression of gastric cancer in hypergastrinemic INS-GAS mice. 1844 Oct 88

Chronic gastritis induced by Helicobacter pylori is the strongest known risk factor for peptic ulceration and distal gastric cancer, and adherence of H. pylori to gastric epithelial cells is critical for induction of inflammation. One H. pylori constituent that increases disease risk is the cag pathogenicity island, which encodes a secretion system that translocates bacterial effector molecules into host cells. Decay-accelerating factor (DAF) is a cellular receptor for H. pylori and a mediator of the inflammatory response to this pathogen. H. pylori induces DAF expression in human gastric epithelial cells; therefore, we sought to define the mechanism by which H. pylori up-regulates DAF and to extend these findings into a murine model of H. pylori-induced injury. Co-culture of MKN28 gastric epithelial cells with the wild-type H. pylori cag(+) strain J166 induced transcriptional expression of DAF, which was attenuated by disruption of a structural component of the cag secretion system (cagE). H. pylori-induced expression of DAF was dependent upon activation of the p38 mitogen-activated protein kinase pathway but not NF-kappaB. Hypergastrinemic INS-GAS mice infected with wild-type H. pylori demonstrated significantly increased DAF expression in gastric epithelium versus uninfected controls or mice infected with an H. pylori cagE(-) isogenic mutant strain. These results indicate that H. pylori cag(+) strains induce up-regulation of a cognate cellular receptor in vitro and in vivo in a cag-dependent manner, representing the first evidence of regulation of an H. pylori host receptor by the cag pathogenicity island.
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PMID:Regulation of the Helicobacter pylori cellular receptor decay-accelerating factor. 1857 24

Adiponectin is secreted by adipocytes and is a key hormone responsible for insulin sensitization. Recent studies have shown that plasma adiponectin is decreased in patients with breast, endometrial and gastric cancer. However, the effect of adiponectin on colorectal carcinogenesis is controversial. It is now well known that the adiponectin receptor exists in two isoforms, adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). We examined the expression of the adiponectin receptors on normal colon mucosa and colon cancer tissues in a human study using real-time RT-PCR, Western blotting and immunohistochemical staining. Adiponectin receptors, AdipoR1/AdipoR2, were expressed in normal colon epithelial and colon cancer cells. Furthermore, laser microdissection was performed to confirm our results. These results suggest that adiponectin may exert some effects on normal colon epithelium or colon cancer cells directly through adiponectin receptors. Further studies are required to elucidate the function of the AdipoRs activated by adiponectin and the downstream mechanisms of AdipoRs in colon cancer cells.
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PMID:Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue. 1869 95

Acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt) phosphorylates and regulates the function of many cellular proteins involved in processes such as metabolism, apoptosis and proliferation. However, the precise mechanisms by which Akt promotes cell survival and inhibits apoptosis have been characterized in part only. TR3, an orphan receptor, functions as a transcription factor that can both positively or negatively regulate gene expression. We have reported previously that the translocation of TR3 from the nucleus to the mitochondria can elicit a proapoptotic effect in gastric cancer cells. In our present study, we demonstrate that Akt phosphorylates cytoplasmic TR3 through its physical interaction with the N-terminus of TR3. When coexpressed with Akt, TR3 mitochondrial targeting was blocked and this protein adopted a diffuse expression pattern in the cytoplasm. Moreover, Akt displayed an ability to disrupt the interaction of TR3 with Bcl-2, which is thought to be a critical requirement for mitochondrial TR3 to elicit apoptosis. Consistently, insulin was also found to induce the phosphorylation of TR3 and abolish 12-O-tetradecanoylphorbol-13-acetate-induced mitochondrial localization, which was dependent upon the activation of the phophatidylinositol-3-OH-kinase-Akt signaling pathway. Taken together, our current data demonstrate a unique role for Akt in inhibiting TR3 functions that are not related to transcriptional activity but that correlate with the regulation of its mitochondrial association. This may represent a novel signal pathway by which Akt exerts its antiapoptotic effects in gastric cancer cells, i.e. by regulating the phosphorylation and redistribution of orphan receptors.
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PMID:Akt phosphorylates the TR3 orphan receptor and blocks its targeting to the mitochondria. 1871 40


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