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)

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that are associated with the tumorigenic process. MMPs degrade the extracellular matrix, promoting tumor invasion and metastasis. They also regulate host defense mechanisms and normal cell function; blocking all MMPs may not lead to a positive therapeutic outcome. Most clinical trials of MMP inhibitors (MMPIs) have yielded disappointing results, perhaps due to inappropriate study design or tumor staging, or to lack of selectivity. Positive results have been seen in gastric cancer with marimastat and in Kaposi's sarcoma with metastat. This review summarizes the current status of MMPIs.
 ...
PMID:Matrix metalloproteinase inhibitors. 1475 Oct 86

We have efficiently generated the first monoclonal antibody (MAb) against the human ZNRD1 protein, a transcription-associated protein, consisting of two zinc ribbon domains. Hybridomas were screened by indirect enzyme-linked immunosorbent assay (ELISA) using either purified 6 x His-ZNRD1fusion protein or purified 6 x His-OS-9 fusion protein as a control. One MAb named H6 (IgG(1)), effective in detecting the recombinant and cellular protein, was characterized by ELISA and Western immunoblotting. Thus, it binds to native ZNRD1 protein and should be useful in studies of ZNRD1 protein function and expression. By Western immunoblotting analysis of 16 patients with gastric cancer using the MAb, we found ZNRD1 protein was more overexpressed in incision margin than in carcinoma tissue. The results showed that ZNRD1 might be a novel modifier in gastric carcinogenesis.
 ...
PMID:Preparation and characterization of a novel monoclonal antibody specific to human ZNRD1 protein. 1500 Aug 50

Zinc ribbon domain-containing 1 (ZNRD1), a transcription-associated gene, was recently found to be downregulated in human gastric cancer tissues as compared to the matched adjacent nonneoplastic tissues. In this study, we constructed the siRNA eukaryotic expression vectors of ZNRD1 and transfected them into normal gastric epithelial cells (GES-1). We also introduced the ZNRD1 gene into gastric cancer cells that do (SGC7901) and do not (AGS) express ZNRD1 endogenously. GES-1 cells stably transfected with the ZNRD1-RNAi were found to exhibit significantly quicker proliferation than empty vector transfectants. AGS cells stably transfected with the ZNRD1 cDNA exhibited significantly decreased growth rate as compared to control vector transfectants, whereas SGC7901 cells did not. Furthermore, ZNRD1 suppresses growth of AGS cells in soft agar and tumor formation in athymic nude mice. This study clearly demonstrates that ZNRD1 may play an important role in the control of human gastric cancer development by regulating cell proliferation. These results provide new insights into the function of ZNRD1 and further validate ZNRD1 as a potential therapeutic target in gastric cancer.
 ...
PMID:Suppression of the cell proliferation in stomach cancer cells by the ZNRD1 gene. 1535 50

BACKGROUND: Heptaplatin is a new platinum derivative with anticancer activity against various cancer cell lines, including cisplatin-resistant cancer cell lines (Cancer Chemother Pharmacol 1995; 35: 441). METHODS: Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines has been investigated in connection with metallothionein (MT). Cytotoxicity was determined by an MTT assay. MT mRNA, was determined by RT-PCR assay. Transfection study was carried out to examine the function of MT. RESULTS: Of various gastric cancer cell lines, SNU-638 and SNU-601 showed the highest and lowest levels of MT mRNA, respectively, showing 80-fold difference. The IC50 values of SNU-638 to cisplatin, carboplatin and heptaplatin were 11.2-fold, 5.1-fold and 2.0-fold greater than those of SNU-601, respectively. Heptaplatin was more effective against cisplatin-resistant and MT-transfected gastric cancer sublines than cisplatin or carboplatin was. In addition, heptaplatin attenuated cadmium, but not zinc, induction of MT. CONCLUSION: These results indicate that molecular mechanisms of heptaplatin effective against cisplatin-resistant gastric cancer sublines is at least in part due to the less involvement of MT in heptaplatin resistance as well as its attenuation of MT induction.
 ...
PMID:Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines: less involvement of metallothionein. 1549 73

The over-expression of a new zinc ribbon (ZNRD1) gene has been shown previously to promote a multidrug-resistant phenotype in gastric cancer cells through the up-regulation of permeability-glycoprotein (P-gp). In the present study, siRNA eukaryotic expression vectors of ZNRD1 are constructed and transfected into SGC7901/VCR cells to examine whether or not down-regulation of ZNRD1 increases cell sensitivity towards chemotherapeutic drugs. After transfection, ZNRD1 expression decreased dramatically in ZNRD1 siRNA transfectants compared with that in parental cells and empty vector control cells. Down-regulation of ZNRD1 significantly enhanced the sensitivity of SGC7901/VCR cells to vincristine, adriamycin and etoposide, but not to 5-fluorouracil and cisplatin. Cell capacity to efflux adriamycin decreased markedly in ZNRD1 siRNA transfectants, and correlation between ZNRD1 down-regulation and increased multidrug resistance 1 (MDR1) gene transcriptional activity was observed. These results suggest that the ZNRD1 siRNA constructs down-regulate the expression of ZNRD1 effectively and reverse the resistant phenotype of gastric cancer cells. Furthermore, ZNRD1 might influence transcription of the MDR1 gene and thus play an important role in multidrug resistance in gastric carcinoma.
 ...
PMID:Reversal of multidrug resistance of gastric cancer cells by down-regulation of ZNRD1 with ZNRD1 siRNA. 1564 14

The KLF6 is a zinc-finger tumor suppressor that is frequently mutated in several human cancers and broadly involved in differentiation and development, growth-related signal transduction, cell proliferation, apoptosis, and angiogenesis. To determine whether genetic alterations of KLF6 gene are involved in the development and/or progression of gastric cancer, we have screened a set of 80 sporadic gastric cancers for mutations and allele loss of the KLF6 gene. Four missense mutations, S155R, P172 T, S180L, and R198 K, were detected in transactivation domain of the KLF6 gene and one of them had biallelic mutations with somatic mutation of one allele and loss of the remaining allele. All of the cases with mutation were of advanced intestinal-type gastric cancer with lymph node metastasis. In addition, 16 (43.2%) of 37 informative cases showed allelic loss at KLF6 locus. Interestingly, allelic loss was also frequent in intestinal-type gastric cancer. Therefore, our data suggest that genetic alterations of KLF6 gene might play an important role in the development or progression of sporadic gastric cancers.
 ...
PMID:Genetic alterations of the KLF6 gene in gastric cancer. 1582 33

We examined associations among dietary heme iron as a possible pro-oxidant, dietary zinc as a possible antioxidant, and the incidence of upper digestive tract cancer; 34,708 postmenopausal women, aged 55-69 years at baseline who completed a food frequency questionnaire, were followed 16 years. There were 75 upper digestive tract cancer cases (52 gastric cancer and 23 esophageal cancer). When heme iron and zinc were mutually adjusted, in dose-response manners, heme iron intake was positively associated with the risk of upper digestive tract cancer, while zinc intake was inversely associated with risk. After adjusting for age, total energy intake, cigarette smoking and alcohol consumption, relative risks for quintiles of heme iron intake were 1.0, 1.53, 2.15, 3.05 and 2.83 (p for trend = 0.06) and corresponding relative risks for zinc intake were 1.0, 0.86, 0.42, 0.37 and 0.13 (p for trend < 0.01). Additional adjustment for body mass index, physical activity, hormone replacement therapy, multivitamin intake and intake of saturated fat, vitamin C, vitamin E and folate did not change the results. Higher intake of heme iron is associated with higher risk, while higher intake of zinc is associated with lower, risk of upper digestive tract cancer.
 ...
PMID:Heme iron, zinc and upper digestive tract cancer: the Iowa Women's Health Study. 1592 82

The Testin (TES) gene was previously identified as a putative human tumor suppressor gene at 7q31.2, a region that is frequently deleted in hematopoietic malignancies, as well as in epithelial tumors. To determine whether TES acts as a tumor suppressor in vivo, we generated a Tes knockout mouse and then used it in an established model of carcinogen-induced gastric cancer. In mice a zinc-deficient (ZD) diet enhances cellular proliferation in the forestomach and susceptibility to N-nitrosomethylbenzylamine (NMBA)-induced carcinogenesis. Five-week-old Tes wild-type (+/+), heterozygous (+/-), and homozygous (-/-) mice were divided into four groups: mice fed a zinc-sufficient diet (ZS); mice fed a ZD diet; ZS fed plus NMBA-treated mice (ZS+NMBA), and ZD fed plus NMBA-treated mice (ZD+NMBA). After 4 weeks, the ZS+NMBA and ZD+NMBA groups were treated with three intragastric doses of NMBA. Animals were killed 8 weeks after NMBA administration: 25% of +/+ mice developed benign lesions; 88% of +/- showed multiple papillomas, atypical glandular metaplasia, and squamous cell carcinomasl; and 81% of -/- mice displayed very large papillomas, squamous cell carcinomas, and adenocarcinomas. A statistically significant difference in tumor incidence was found between +/- versus +/+ and -/- versus +/+ (P < 0.0001). These data suggest that Tes functions as a tumor suppressor gene in vivo.
 ...
PMID:Knockout mice reveal a tumor suppressor function for Testin. 1603 68

This study aimed to retrospectively investigate the predictive factors for pancreatic fistula following pancreaticosplenectomy. Pancreatic fistula is a major lethal complication of pancreaticosplenectomy. However, predictive factors for this condition have not yet been established. Between April 1992 and March 2000, 147 patients with advanced gastric cancer that was located predominantly in the upper third of the stomach were enrolled in this study. Predictive factors for pancreatic fistula were investigated using univariate and multivariate analyses. Pancreatic fistula, as defined according to our criteria, was observed in 73 (49.7%) patients. In the univariate analysis, age, body mass index, serum zinc level, hyperlipidemia, and comorbid disease all significantly affected the incidence of pancreatic fistula. In the multivariate analysis, body mass index, hyperlipidemia, and comorbid disease independently predicted the occurrence of pancreatic fistula. By contrast, the experience of the operating surgeon had no significant effect on the frequency of this condition. Our results suggest that pancreaticosplenectomy, the surgical merit of which is not apparent, should be avoided whenever possible. If this operative procedure must be used (e.g., in patients with extensive tumor presence), careful manipulation and appropriate drainage are essential, particularly in cases showing predictive factors of pancreatic fistula.
 ...
PMID:Predictive factors for pancreatic fistula after pancreaticosplenectomy for advanced gastric cancer in the upper third of the stomach. 1636 3

In this study, levels of lipid peroxidation and antioxidant enzyme activities were investigated in the erythrocytes of patients with oesophageal and gastric cancers. Erythrocytes were obtained from 17 patients with oesophageal cancer, 37 patients with gastric cancer and 20 healthy controls. Levels of malondialdehyde (MDA), a lipid peroxidation marker, and activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GPx) were determined using spectrophotometric methods. MDA levels and CuZn-SOD activity were significantly higher and GPx and CAT activities significantly lower in patients with oesophageal and gastric cancer than in controls. There were no statistically significant differences in the parameters measured in relation to disease stage in either patient group. These results indicate significant changes in the antioxidant defence system in patients with oesophageal and gastric cancer. It is postulated that this may lead to enhanced action of oxygen radicals, resulting in lipid peroxidation.
 ...
PMID:Antioxidant enzyme activities and lipid peroxidation levels in erythrocytes of patients with oesophageal and gastric cancer. 1674 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>