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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To further investigate the role of p53 gene inactivation in gastric tumorigenesis, the mutational status of the p53 gene in primary human gastric cancer samples was examined. Reverse transcriptase polymerase chain reaction and subsequent direct sequencing of the p53 gene from gastric cancer samples revealed frequent point mutations of the p53 gene: some of these coincided with those previously identified in gastric cancer cell lines. In addition, both allelic deletion analysis using pYNZ 22 and polymerase chain reaction-restriction fragment length polymorphism analysis demonstrated an allelic deletion of the p53 gene in cancer tissue which contained a point mutation of the p53 gene in the remaining allele. Transfection of the wild-type or mutant p53 genes into gastric cancer cells showed that the wild-type but none of the mutated p53 genes suppressed the colony formation of gastric cancer cells. Furthermore, the incorporation of thymidine into DNA was reduced in cancer cells expressing the wild-type p53 gene. The glutathione S-transferase-wild type p53 fusion protein bound to simian virus 40 large T antigen in COS-1 cell lysate. None of the p53 fusion proteins containing mutations at codons 143, 175, 248, or 273 bound to simian virus 40 large T antigen. By contrast, two different mutant p53 fusion proteins containing mutations specifically observed in gastric cancer bound to simian virus 40 large T antigen. These results indicate that inactivation of the p53 gene through mutations and the allelic deletion may play an important role in gastric tumorigenesis. These mutations may cause a conformational change in the p53 protein resulting in the loss of the suppression by p53 of the growth of gastric cells, partly through disruption of the association of p53 protein with a cellular component.
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PMID:p53 gene mutations in human gastric cancer: wild-type p53 but not mutant p53 suppresses growth of human gastric cancer cells. 132 85

We studied activated mutations of K-ras gene in three forms of colorectal tumors, i.e., 45 specimens of colorectal adenoma (CA), 10 of 'cancer in adenoma' (CIA), and 24 of colorectal cancer (CC), and in 15 of gastric cancer (GC) as controls. Chromosome aberrations were also examined in 7 specimens of CA, 3 of CIA, 8 of CC, and 7 of GC. Mutation of K-ras Codon 12 was observed in 12 (26.7%) of the 45 specimens of CA, 6 (60.0%) of the 10 specimens of CIA, 6 (25.0%) of the 24 specimens of CC, and 1 (6.7%) of the 15 specimens of GC. In CA, its frequency increased with the degree of histological atypism. In CA and CIA, its frequency increased with the increase in short diameter. The most frequent chromosome aberration was the numerical excess of chromosome 7. Numerical deficiencies of chromosomes 17 and 18 or structural abnormalities of 17p+ and 18q+ were noted in 1 specimen each of CA and CIA, and 2 of CC. Thus, aberrations of these two chromosomes were concurrent. 5q--was observed in 1 specimen each of CA and CC. These findings were not contradictory to the multi-step carcinogenesis model of the colorectum based on the hypothesis that carcinogenesis requires activation of an oncogene by mutation accompanied by defects of several genes that might normally inhibit tumorigenesis.
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PMID:Genetic changes in multi-step development of colorectal cancer. 145 86

To understand the molecular mechanism of gastric tumorigenesis, the status of neurofibromatosis type 1 (NF1) gene was analyzed in human gastric cancer cell lines. Although the sequencing of the GTPase activating protein (GAP)-related region of NF1 (NF1-GRD) revealed no apparent mutation, the NF1-GRD transcript (type I) and that containing an additional 63 bp insert in the center of NF1-GRD (type II) were equally expressed in most gastric cancer cells. By contrast, type II was predominantly expressed in normal stomach mucosa. When these two types of NF1-GRD were bacterially expressed and their GAP activities were tested, both types of NF1-GRD similarly stimulated ras GTPase activity. However, arachidonic acid inhibited GAP activities of two types of NF1-GRD to different extents. These results suggest that the increased expression of type I NF1 protein may modulate ras-related signal transduction and it may be related to the control of the gastric cellular proliferation.
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PMID:Expression of two types of neurofibromatosis type 1 gene transcripts in gastric cancers and comparison of GAP activities. 152 Mar 17

Transgenic animal technology has been useful for the direct demonstration of the tumorigenic potential of oncogenes in vivo. Over the past eight years a wide variety of oncogenes and proto-oncogenes from viral and cellular sources have been inserted into the germline of mice with subsequent development of neoplasia. Many of the published reports describe similarities between morphologic features of the transgenic mice tumors and those occurring naturally in humans. We discuss the morphologic features of selected transgenic models carrying viral genes and review their applicability to investigations directed toward understanding cancer in general and specifically gastric cancer, neurofibromatosis and leukemia. Examples of the impact of nutrition, interaction with growth factors and initiation with chemical carcinogens are presented. In one of the models functional similarities to the mechanism of oncogenesis in human T-cell leukemia virus type-1 (HTLV-1) lymphoma may exist with activation of cytokine production and subsequent autocrine stimulation. The transgenic model of proximal gastric cancer demonstrates features similar to those seen in carcinogen-induced neoplasia. These studies underscore the vast potential of transgenic models for inquiry into the genetic and epigenetic basis of human carcinogenesis. However, many features of transgenic cancer models differ from cancer in humans and the specific criteria for judging the value of transgenic models remain unclarified. For example, although the tumors arising in the HTLV-1 Tax transgenic mice show numerous similarities to human neurofibromatosis including development of lesions of the iris, the similarities do not necessarily extend to the molecular involvement of neurofibromatosis-1 (NF-1), a gene with structural and functional homology to GTPase activating proteins. Transgenic experiments of the future will ask questions beyond whether a particular gene is capable of initiating the neoplastic process. The ability to construct systems in vivo with a defined starting point that facilitate further controlled manipulation of events resulting in cancer provide great opportunities to dissect the various molecular pathways involved in such a process. Therefore, gene knockout experiments and disruption of gene function will further enhance our ability to understand the multi-factorial process of tumor development.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Transgenic models of human cancer. 166 87

Point mutations of c-Ki-ras genes were analyzed in 33 samples of human gastrointestinal malignancy. DNA extracted from the frozen tissue was amplified by polymerase chain reaction (PCR) and analyzed by direct sequencing and slot-blot hybridization at codons 12, 13 and 61 of c-Ki-ras. In 7 cases out of 19 colorectal cancers, point mutations were found: 3 cases at codon 12, 1 at codon 13, 2 at codon 61 of c-Ki-ras and one case had double mutations at codon 12 and codon 13. In 11 cases of gastric cancer, 4 showed point mutations: 1 at codon 12 and 3 at codon 13 of c-Ki-ras. In 3 pancreatic carcinomas, 2 had point mutations: one at codon 12 and the other at codon 13 of c-Ki-ras. The results indicate that c-Ki-ras gene point mutations are involved in the tumorigenesis of the human gastrointestinal system.
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PMID:Analysis of ras gene mutations in gastrointestinal cancers. 168 83

Tumors derived from 105 patients with gastric cancer were subcutaneously heterotransplanted into nude mice in order to study their tumorigenicity and malignant behavior. Of the 105 gastric cancers, 45 were successfully transplanted (a 42.9% tumorigenesis rate). The tumorigenesis rate of Borrmann type 1 and 2 cancers (77.8%) was significantly higher than that of type 3 and 4 cancers (34.6%). Also, the tumorigenesis rate of differentiated carcinoma (57.1%) was significantly higher than that of undifferentiated carcinoma (30.9%). Spontaneous metastases from the subcutaneous tumors were observed in 5 of the 37 established tumor lines (13.5%), and macroscopic pulmonary metastases were common with one tumor line (SCK-29). Although most of the subcutaneous gastric cancers showed local expansion without distant metastasis, the same tumor cells implanted into the peritoneal cavity exhibited invasive growth and/or metastasis. Thus, the expression of a metastatic phenotype by human gastric cancer was influenced by the host microenvironment. The SCK-29 tumor line with its high metastatic potential may be useful for studies on the mechanism of blood-borne metastasis.
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PMID:Tumorigenicity, invasion, and metastasis of human gastric cancer in nude mice. 174 58

Point mutations of c-ras genes were analyzed in human gastrointestinal cancers. DNA obtained from the tissues was amplified by polymerase chain reaction and then analyzed by dot blot hybridization assay with oligonucleotide probes to detect mutations at codons 12, 13, and 61 of c-Ki-ras, c-Ha-ras, and c-N-ras. In two of 25 cases of stomach cancer point mutations at codon 13 of c-Ki-ras were found. In colorectal cancer, eight of 30 cases showed mutations: four cases of codon 12 and one case at codon 13 of c-Ki-ras and two cases at codon 61 and one case at codon 13 of c-N-ras. These results may indicate involvement of a wide variety of c-ras gene point mutations, in addition to those at codon 12 of c-Ki-ras, in oncogenesis of human gastrointestinal cancers. In all three mutations of c-Ki-ras at codon 13 which had been seldom found in human cancers, glycine to aspartic acid mutations due to identical G to A transition at the second nucleotide were observed.
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PMID:Glycine to aspartic acid mutations at codon 13 of the c-Ki-ras gene in human gastrointestinal cancers. 240 71

This study evaluated the dose-related trophic effects of glutamine, gastrin, and somatostatin on the in vitro growth of human gastric cancer cells and normal human gastric mucosal cells. Quadruplicate cell cultures were seeded into growth medium with or without glutamine, gastrin, or somatostatin. After 72 hours' incubation, cells were counted and their numbers compared with those of controls. Glutamine and gastrin stimulated the growth of both normal and malignant gastric mucosal cells. Compared with normal cells, the malignant cells responded to these growth factors at lower concentrations. Somatostatin enhanced growth of gastric cancer cells at all concentrations and inhibited growth of normal cells at high concentrations. Further studies on the responsiveness of gastric adenocarcinoma to gastrointestinal tract hormones may elucidate mechanisms of oncogenesis and suggest new therapeutic avenues for patients with gastric cancer.
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PMID:Effects of gastrin, glutamine, and somatostatin on the in vitro growth of normal and malignant human gastric mucosal cells. 286 4

Evidence pertaining to the role of dietary factors in carcinogenesis comes from both epidemiological studies and laboratory experiments. In 1982, the Committee on Diet, Nutrition, and Cancer of the National Research Council conducted a comprehensive evaluation of this evidence. That assessment as well as recent epidemiological and laboratory investigations suggest that a high fat diet is associated with increased susceptibility to cancer of different sites, particularly the breast and colon, and to a lesser extent, the prostate. Current data permit no definitive conclusions about other dietary macroconstituents including cholesterol, total caloric intake, protein, carbohydrates and total dietary fiber. Specific components of fiber, however, may have a protective effect against colon cancer. In epidemiological studies, frequent consumption of certain fruits and vegetables, especially citrus fruits and carotene-rich and cruciferous vegetables, is associated with a lower incidence of cancers at various sites. The specific components responsible for these effects are not clearly identified, although the epidemiological evidence appears to be most consistent for a protective effect of carotene on lung cancer and less so for vitamins A and C and various cancer sites. The laboratory evidence is most consistent for vitamin A deficiency and enhanced tumorigenesis, and for the ability of various nonnutritive components in cruciferous vegetables to block in-vivo carcinogenesis. The data for minerals and carcinogenesis are extremely limited, although preliminary evidence from both epidemiological and laboratory studies suggests that selenium may protect against overall cancer risk. Frequent consumption of cured, pickled, or smoked foods, possibly because they may contain nitrosamines or polycyclic aromatic hydrocarbons, appears to increase the risk of esophageal or stomach cancer, however, the specific causative agents in these foods are not clearly identified. Excessive alcohol consumption among smokers appears to be associated with an elevated risk of cancers of the oral cavity, esophagus, larynx, and respiratory tract. The mechanisms of action of dietary factors on carcinogenesis are poorly understood. The NRC committee, and more recently, the National Cancer Institute and the American Cancer Society have proposed interim dietary guidelines to lower the risk of cancer. These guidelines are consistent with general dietary recommendations proposed by U.S. government agencies for maintenance of good health.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diet, nutrition, and cancer. 301 Mar 79

Mitotic events leading to the loss of the normal allele corresponding to a mutated gene are important for tumorigenesis in rare heritable tumors such as retinoblastoma and Wilms tumor. As reported for both colorectal and breast cancers, some common tumors seem to develop because of the same mitotic events. We examined constitutional and tumor genotypes defined by polymorphic DNA clones in 36 patients with gastric cancer. In 14 cases, constitutional heterozygosity at loci on chromosome 13 had been lost. Loss of alleles was also detected at a locus on chromosome 18 in two cases and at a locus on chromosome 17 in one case. The frequent loss of alleles at loci on chromosome 13 (41%) suggests that elimination of genes on this chromosome may be of importance in the tumorigenesis of human primary gastric cancers.
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PMID:Loss of alleles at loci on chromosome 13 in human primary gastric cancers. 341 Apr 77


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