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)

Common and distinct genetic alterations are involved in the multistep mechanism of gastrointestinal carcinogenesis. Inactivation of the p53 and APC genes, activation of teleomerase and anomalous CD44 expression are common events that serve as a genetic marker for differential diagnosis of cancer. Amplification of cyclin D1 gene is preferentially found in esophageal cancer, whereas cyclin E gene amplification is frequently associated with both gastric and colorectal cancers. Multiple genetic alterations differ depending on the two histological types of gastric cancer. These genetic alterations can be applied in the multistep mechanism of the development and progression of gastrointestinal cancers. By application of these observations in clinical practice, we can facilitate and improve the differential diagnosis on cancer, obtain information on the grade of malignancy, determine patient prognosis, and identify patients at high risk for developing multiple cancers.
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PMID:[Molecular diagnosis of gastrointestinal cancers]. 947 27

Gastric epithelial turnover increase in Helicobacter pylori infection has been demonstrated by interventional and non interventional methods for proliferating cell detection. We have observed a progressive hyperproliferation with the progression of Helicobacter pylori-induced mucosal lesions until the development of intestinal metaplasia. A similar result has been reported in other studies in the succession from normal mucosa to gastric carcinoma even if interventional techniques show less conspicuous differences in comparison to non interventional ones, which give an overestimated picture of proliferation. Later studies show that Helicobacter pylori-related hyperproliferation reverses after eradication. We have observed that this reversibility does not occur in areas of intestinal metaplasia, where the oncoprotein ras p21, involved in early gastric carcinogenesis, is expressed. This finding agrees with that demonstrating that hyperproliferation in intestinal metaplasia or gastric cancer is not affected by Helicobacter pylori. Other oncogenetic changes in intestinal metaplasia (i.e., p53 mutation) may further explain the persistently modified proliferative pattern of the epithelium. Recent studies suggest a lack of reversibility of intestinal metaplasia after Helicobacter pylori eradication, but this problem remains controversial. Our experience suggests that the persistence of the bacterium may increase the extent of this lesion. In conclusion the development of intestinal metaplasia is associated with an impaired regulation of gastric epithelial proliferation. Nevertheless, from the biological point of view, the progression towards carcinoma requires further DNA changes. Moreover, many questions need to be answered in order to establish clear guidelines for the clinical management.
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PMID:Effect of Helicobacter pylori eradication on intestinal metaplasia and gastric epithelium proliferation. 949 59

The p53 gene has been shown to be commonly mutated in various human cancers, and mutant p53 can act as a dominant oncogene. The intact p53 protein is also known to induce the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and is implicated in cell cycle arrest. We investigated p53 gene alterations in gastric adenocarcinoma and esophageal squamous cell carcinoma to elucidate the association of the nuclear accumulation of the p53 protein and/or p21WAF1/CIP1 protein. Abnormalities of the tumor suppressor gene p53 protein and the expression of p21WAF1/CIP1 protein were analyzed by immunohistochemical techniques in 32 cases of gastric adenocarcinoma and 15 cases of esophageal squamous cell carcinoma. Twenty cases of gastric cancer and five cases of esophageal cancer were also analyzed for p53 gene mutation by polymerase chain reaction and direct nucleotide sequencing. Overexpression of p53 protein was found in 13/32 (41%) of gastric cancers and 5/15 (33%) of esophageal cancers. We found immunodetectable p53 in 10/14 cases with mutations and in none of 11 cases without mutations in gastric and esophageal cancers. Hence, immunohistochemical and genetic analyses gave concordant results in 84% of 25 cases, revealing a good correlation between immunostaining of p53 and missense mutation of the p53 gene. p53 immunostaining was not observed in cases with frameshift or splicing mutation. The expression of p21WAF1/CIP1 protein was found in 9/32 (29%) of gastric cancers and 4/15 (27%) of esophageal cancers and in 2/14 (14%) cases with alteration of the p53 gene and in 5/11 (45%) without. These results suggest that abnormalities of p53 may be closely associated with the pathogenesis of gastric adenocarcinoma and esophageal squamous cell carcinoma and that the immunoreactivity of p53 protein is a general indicator of the tumors with altered p53 function. The expression of p21WAF1/CIP1 protein was suppressed in the neoplastic tissues with and without p53 gene alteration.
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PMID:Expression of p53 and p21WAF1/CIP1 proteins in gastric and esophageal cancers: comparison with mutations of the p53 gene. 951 19

Orbital or ocular metastatic tumors may originate from breast cancer. Few studies have been made regarding their histopathological classification. A 71-year-old female noted a tumor in the right orbital region. She had had bilateral breast cancer 2 years before and gastric cancer 5 months before. Histopathology had shown stage II invasive ductal cancer (scirrhus) in the right breast and stage III invasive lobular cancer in the left. Signet-ring cells were present in the breast and gastric cancers. Biopsy of the right lower eyelid showed poorly differentiated adenocarcinoma with signet-ring cells. Indian file pattern, which is specific for invasive lobular cancer, was also present, suggesting that the orbital tumor had metastatized from the left breast cancer. Genetic analysis of the gastric cancer using polymerase chain reaction showed a mutation at exon 8 of the p53 tumor suppressor gene, indicating the cancer to be metastatic. These results led to the conclusion that invasive lobular cancer of the left breast was the primary lesion for the gastric and orbital metastases. This case also illustrates that signet-ring cells, which are usually seen in gastric cancer, may be present in invasive lobular breast cancer and in orbital metastasis.
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PMID:[Orbital and stomach metastasis from invasive lobular breast carcinoma]. 951 61

The presence of serum p53 antibody has been reported to have prognostic significance in patients with breast and ovarian cancers. In order to clarify clinical and prognostic significance of p53 antibody in serum, we measured p53 antibody in patients with gastric cancer. Twenty-five patients with gastric cancer were examined as well as 9 patients with gastric polyp as controls. Eight of 25 patients (32%) with gastric cancer were positive for p53 antibody, while no patients with gastric polyp were positive in gastric polyp group (p < 0.05). The presence of p53 antibody was significantly associated with histology, liver metastasis and stage classification in gastric cancer (p < 0.05, respectively). Presence of liver metastasis, type of histology and presence of p53 antibody are independent prognostic factors (p < 0.05, respectively). The overall survival in patients with p53 antibody was significantly shorter survival than for those without antibody (p < 0.05%). These data suggest that p53 antibody serves as one of the prognostic factors in gastric cancer.
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PMID:Clinical significance of serum P53 antibody in patients with gastric cancer. 952 54

Although scrirrhous cancer has the highest malignant potential among various types of gastric cancer, its pathogenesis is still unclear. The relationship between expression of p53 or vascular endothelial growth factor (VEGF) and clinicopathological variables was investigated by immunohistochemical analysis of archival specimens from 40 patients with scirrhous gastric cancer. Staining for p53 and VEGF was observed in the nuclei and cytoplasm of the tumor cells, respectively. There was no significant association between expression of p53 or VEGF and sex, age, depth of invasion, lymph node metastasis or histological stage. Peritoneal dissemination was the most frequent mode of recurrence, and the depth of tumor invasion was a crucial factor. The recurrence rate was 83.9% (2/9) in patients without serosal invasion. Only 7 out of 40 patients (17.5%) survived without recurrence. Among them, the VEGF-positive rate was 14.3% (1/7), whereas it was 52.6% (10/19) in the patients with recurrence. There was no correlation between p53 and VEGF staining. These findings suggest that the progression of scirrhous gastric cancer may be promoted by VEGF overexpression, which is not upregulated by p53 mutation.
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PMID:Relationship of p53 and vascular endothelial growth factor expression of clinicopathological factors in human scirrhous gastric cancer. 956 47

Tumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived multifunctional cytokine that acts as a cytostatic or cytotoxic agent in many tumor cells. However, the molecular mechanisms by which tumor cells become sensitive to the cytotoxic action of TNF-alpha are not clear. In this study we demonstrated that the cytotoxicity of TNF-alpha markedly increased in c-Myc overexpressing tumor cells. The stomach cancer cell line, SNU-16, in which c-Myc expression is high due to gene amplification, showed programmed cell death detected by DNA fragmentation and morphological changes. An antisense c-myc S-oligonucleotide specifically inhibited the TNF-alpha-induced apoptosis of SNU-16 cells, provided that the oligonucleotide was added 4 h prior to TNF-alpha treatment. Western immunoblot analysis of p53 and Bax showed that in this cell line, TNF-alpha increased the level of these proteins in a time-dependent manner and that this effect lasted for 12 h. Taken together these data indicate that the deregulation of c-Myc plays an important role in sensitizing tumor cells to TNF-alpha. Furthermore, TNF-alpha-induced apoptosis in the SNU-16 cell line showed increased expression of p53 and Bax protein levels following TNF-alpha treatment. Therefore, we suggest that TNF-alpha-induced apoptosis, which is cytotoxic to tumor cells, is coupled with a p53 and Bax apoptotic pathway.
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PMID:Increased susceptibility of the c-Myc overexpressing cell line, SNU-16, to TNF-alpha. 956 90

A novel inhibitor of apoptosis designated survivin has recently been found in many common human cancers but not in normal tissues. A potential distribution of survivin in gastric cancer and its implication for apoptosis inhibition have been investigated. Recombinant survivin expressed in Escherichia coli as a glutathione S-transferase fusion protein was used to raise a novel panel of mouse monoclonal antibodies. In an immunohistochemical analysis of 174 cases of gastric carcinomas (stages I-III), anti-survivin monoclonal antibody 8E2 (IgG1) reacted with 34.5% of cases (60 of 174 cases) with a variable number of tumor cells stained (20-100%). In contrast, no expression of survivin in neighboring normal tissues was observed. When stratified for p53 and bcl-2 expression and apoptotic index, the expression of survivin significantly segregated with p53- and bcl-2-positive cases [56.1 versus 15.2% (P = 0.001) and 69.2 versus 31.6% (P = 0.006), respectively] and with a decreased apoptotic index as compared with that of survivin-negative tumors (0.97 +/- 0.64 versus 0.62 +/- 0.39%, P < 0.001). These data identify a role for survivin in promoting aberrantly increased cell viability in gastric cancer and suggest a potential correlation between accumulated p53 and survivin expression in neoplasia.
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PMID:Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. 958 17

Although reports have suggested the incomplete type of intestinal metaplasia (IM) had a close correlation with carcinoma, considerable data showed no apparent relationship between the particular type of IM and the intestinal type carcinoma. The purpose of this study was to establish a novel classification of IM using brain-type glycogen phosphorylase (BGP) from a carcinogenetic viewpoint. The only isoform expressed in gastric cancer was BGP using polymerase chain reaction analysis. We studied 136 specimens with gastric carcinoma and the adjacent IM using specific anti-BGP antibody with its correlation to subtypes of IM, proliferating cell nuclear antigen-labeling index, and various oncogene products. Brain-type glycogen phosphorylase was expressed in 80.5% of the intestinal type and 18.8% of the diffuse type of carcinoma and in 87.5% and 41.6% in the generative zone of IM adjacent to cancer foci, respectively, whereas no reactivity was observed in the normal gastric mucosa. The proportion of the positivity in the cancer and IM was significantly greater in the intestinal-type carcinoma than in the diffuse type. The expression of BGP in the generative cells of IM had no significant correlation with the conventional type of IM. Intestinal metaplasias with BGP expression were significantly higher in a proliferating state than in those without BGP, and some of them that were coexpressed accumulated p53 in the generative cells. The relationship between IM with BGP in the generative cells and intestinal-type carcinoma was apparently closer than the conventional subtype of IM and gastric cancer. Intestinal-type carcinoma might arise from some of these proliferating cells with BGP.
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PMID:Novel subtyping of intestinal metaplasia in the human stomach: brain-type glycogen phosphorylase expression in the proliferative zone and its relationship with carcinogenesis. 958 90

This study was performed to estimate p53 and Bax overexpression as a predictor of the response to chemotherapy of patients with gastric cancer. The subjects were 20 patients with stage IV gastric cancer and 3 with locally recurrent lesions treated with 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) for 4 weeks. Of the total 23 patients, there were 10 responders: 2 showing complete response (CR) and 8, partial response (PR). Carcinoma biopsy specimens of all were obtained endoscopically with anti-p53 and anti-Bax antibodies. Of the 10 responders, 7 were in the negative p53 staining group, while of the 13 non-responders, 11 were in the positive p53 staining group (p = 0.013). But no correlation was demonstrated between the chemotherapeutic effect and Bax staining alone. Moreover, among the p-53-positive cases, the patients with Bax-negative tumors were all chemoresistant. Therefore, immunohistochemical identification of p-53 and Bax prior to chemotherapy may be a useful predictor for choice of non-responders to chemotherapy.
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PMID:[p53 and Bax protein expression as predictor of chemotherapeutic effect in gastric carcinoma]. 958 42


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