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)

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

One hundred and thirty three gastric cancer cases were investigated immunohistochemically to clarify the biological role of survivin in gastric cancer cells using a commercially available anti-survivin antibody (SURV11A). Five gastric cancer cell lines were employed to assess localization of survivin by reverse-transcription-polymerase chain reaction (RT-PCR) Southern blotting, Western blotting and immunofluorescence, signals being found in both nucleus and cytoplasm. Survivin nuclear staining of gastric cancer cells was evident in 109 of 133 cases (82.0%) and associated with a favorable prognosis, being an independent prognosticator on multivariate analysis. Survivin nuclear positivity also correlated with younger age and lower incidence of vessel cancer invasion. In contrast, survivin cytoplasmic positivity was noted in 117 cases (88.0%) and did not correlate with any factor of progression or prognosis. The results indicate that survivin is present in the majority of gastric cancer cells but a nuclear localization may play an important physiological role in hindering tumor progression.
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PMID:Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. 1116 14

Survivin is a member of the inhibitor of apoptosis protein (IAP) family. The expression of survivin has not been reported in differentiated normal tissues, but it has been observed in many cancerous tissues. Recent studies have revealed that survivin may correlate with the chemo-radio resistance of certain malignant cells. In the present study, the correlation between the occurrence of apoptosis and the level of expression of survivin messenger RNA (mRNA) was investigated in a gastric cancer cell line (MKN-45) and in patients with advanced gastric cancer during cisplatin (CDDP) treatment. In the gastric cancer cell line, the percentage of apoptotic cells (apoptotic index: AI) did not change after 48 h incubation with low-dose CDDP (1 microg/ml), whereas the AI explosively increased between 12 and 24 h treatment with high-dose CDDP (10 microg/ml). Relative levels of expression of survivin mRNA and survivin protein increased after low- and high-dose CDDP treatment. Survivin mRNA was not detected in normal gastric mucosas. Also, in 13 patients with advanced gastric cancer who underwent CDDP-based preoperative chemotherapy, survivin mRNA was detected in only 2 cases (15.4%). Survivin mRNA was observed in the resected tumor specimens of two cases. No significant correlation between survivin mRNA expression and the occurrence of apoptosis in resected tumors or between survivin mRNA expression and patient survival was observed. These findings indicate that survivin may play an important role for the chemoresistance of this cancer cell line. However, the clinical importance of survivin expression remains unclear in patients with gastric cancer.
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PMID:Changes in survivin messenger RNA level during cisplatin treatment in gastric cancer. 1171 83

Survivin is a member of the inhibitor of apoptosis protein (IAP) family. Survivin has been reported to be expressed in many cancers, but not in differentiated normal tissue. Recent studies revealed that survivin correlated with the chemo-resitance of cancer cells. In the present study, the changes in expression levels of survivin messenger RNA (mRNA) and survivin protein in a gastric cancer cell line (MKN-45) during cisplatin (CDDP) treatment were analyzed and compared with the occurrence of apoptotic cell death. Cell growth was inhibited even with a low dose CDDP (0.1 or 1 microg/ml) 1 hr treatment. However, the percentage of apoptotic cells did not change after 48 hr incubation with low dose CDDP. Only with high dose CDDP (10 microg/ml), did the percentage of apoptotic cells explosively increase between 12 and 24 hr treatment. Relative expression levels of survivin mRNA and survivin protein increased after CDDP treatment. The cell expression rates of survivin mRNA after 48 hr treatment with 0.1 and 1 microg/ml of CDDP were 2 to 6 fold higher than that of the survivin mRNA of untreated cells. Also, the relative cell expression level of survivin protein after 24 hr treatment with 0.1 or 1 microg/ml of CDDP was 3 to 6.5 fold higher than that of the survivin protein of untreated cells. These results indicate that survivin expression may correlate with the chemo-resistance of malignant cells.
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PMID:Expression of survivin mRNA and protein in gastric cancer cell line (MKN-45) during cisplatin treatment. 1177 2

Survivin was recently described as an apoptosis inhibitor. Its pathogenic role in gastric cancer is largely unknown. Expression of survivin in gastric cancer and non-cancer first-degree relatives, and its association with apoptosis and cyclo-oxygenase-2 expression was investigated. Fifty gastric cancer, 30 non-cancer first-degree relatives, 20 normal controls and five gastric cancer cell lines were studied. Survivin and cyclo-oxygenase-2 were evaluated by reverse transcriptase-polymerase chain reaction, immunohistochemistry and Western blot. Survivin expression was absent from normal gastric mucosa. All five cancer cell lines and 34 out of 50 (68%) human gastric cancer tissues expressed survivin mRNA. Survivin expression was less frequent (22%; P<0.001) in adjacent non-tumour gastric tissues. Immunohistochemistry and Western blot obtained similar findings. Gastric cancers with survivin expression displayed significantly reduced apoptosis (P=0.02), and associated with cyclo-oxygenase-2 overexpression at both mRNA (P=0.001) and protein levels (P=0.041). Moreover, survivin mRNA was detected in the gastric mucosa of eight (27%) non-cancer relatives. Expression in non-cancer patients showed positive correlation with H. pylori infection (P=0.004). This demonstrates the frequent expression of survivin in gastric cancer and in first-degree relatives. Co-expression of survivin and cyclo-oxygenase-2 may suggest multiple pathways contributing to the inhibition of apoptosis in gastric cancer.
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PMID:Increased expression of survivin in gastric cancer patients and in first degree relatives. 1208 63

We investigated the effect of expression of survivin, an apoptosis inhibiting protein, on cellular proliferation and apoptosis in gastric cancer and assessed its relation to the pathological characteristics of gastric cancer. Resected gastric cancer specimens from 42 patients (intestinal type; 21 cases and diffuse type; 21 cases) were evaluated. There were no significant differences in the clinicopathologic factors between the two groups. Survivin mRNA expression was measured using real-time reverse transcription-polymerase chain reaction, and survivin protein expression was evaluated by immunohistochemical staining. The Ki-67 index was adopted for cell proliferation scoring, and the ss-DNA positive rate as an apoptotic index. The survivin mRNA expression inversely correlated with the apoptotic index (p<0.05). Survivin mRNA expression (p<0.001) and survivin protein expression (p<0.001) were significantly higher in the diffuse type than the intestinal type. In conclusion, gastric cancer avoids cellular death by survivin expression and this tendency was more conspicuous in diffuse type gastric cancer.
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PMID:Effect of survivin on cell proliferation and apoptosis in gastric cancer. 1237 22

Gastric cancer is one of the most common malignant tumors of the gastrointestinal tract. However, the molecular pathways involved in the regulation of gastric carcinogenesis are not completely elucidated. In the last decade, basic cancer research has been focused on the deregulation of apoptosis as a central event in the process of carcinogenesis. Caspase-3 and survivin are regulators of apoptosis and have been implicated in the development of gastric cancer. The aim of the present study was to compare the expression of mRNA and protein for survivin and caspase-3 in the gastric cancer and in the cancer margin with that in normal human gastric mucosa. Fifteen patients with advanced gastric cancer (all H. pylori-positive) and 15 matched control subjects with normal gastric mucosa were included in this study. The biospy specimens for histology and for molecular analyses were taken from gastric tumor, tumor surrounding gastric mucosa and in normal patients from the mucosa of antrum and corpus. Survivin mRNA expression was very weak, but detectable, in the normal gastric mucosa. However, at the protein level, no expression for survivin was detected in the normal gastric mucosa. In the biopsy specimens from tumor and surrounding gastric mucosa, a significant increase in survivin mRNA and protein expression was observed. The expression of survivin was higher in the tumor than in the tumor margin. The mRNA and protein expression of caspase-3 was detected in the gastric mucosa of normal subjects. In gastric cancer only the expression of procaspase-3 was observed, while the expression of active caspase-3 was completely undetectable. In the gastric mucosa surrounding gastric cancer, no gene and protein expression for caspase-3 was detected. We conclude that the changes in the level of caspase-3 and survivin play an important role in the transformation from normal gastric mucosa to gastric career.
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PMID:Expression of survivin and caspase-3 in gastric cancer. 1264 1

Cyclooxygenase-2 (COX-2) expression and certain growth hormones, such as gastrin, have been related to gastric carcinogenesis, but little is known about the factors that enhance this COX-2 expression and whether specific blockade of this enzyme has any influence on tumor growth and progression. Our objective was to determine the influence of a specific COX-2 inhibitor, rofecoxib (Vioxx), on serum and tumor levels of gastrin and its precursor, progastrin, as well as on tumor gene expression of COX-2, peroxisome proliferator-activated receptor gamma (PPARgamma), and apoptosis-related proteins (Bax and Bcl-2, caspase-3, and survivin). Twenty-four gastric cancer (GC) patients entered this study and were examined twice, once before and then following a 14-day treatment with Vioxx at a dose of 25 mg twice daily. For comparison, 48 age- and sex-matched healthy controls and 24 similarly matched Helicobacter pylori (Hp)-positive subjects were enrolled and treated with Vioxx as GC patients. Serum levels of anti-Hp and anti-CagA antibodies as well as IL-8 and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA), while serum and tumor contents of progastrin and amidated gastrin were determined by specific RIA. Tumor gene and protein expressions of COX-2, PPARgamma, Bax and Bcl-2, caspase-3, and survivin were determined by RT-PCR and western blot. The overall Hp and CagA seropositivity in 24 GC patients was significantly higher (82% and 47%) than in 48 controls (61% and 22%) but not in 24 Hp-infected subjects (100% and 38%). Serum IL-8 and TNF-alpha values were significantly higher in GC patients than in controls without GC or Hp-infected controls. Median serum progastrin and gastrin levels were found to be significantly higher in GC than in controls without GC and in Hp-positive subjects. Treatment of GC patients with Vioxx resulted in a significant decrease in plasma and tumor contents of both progastrin and gastrin, and this was accompanied by the increment in tumor expression of COX-2, PPARy, Bax, and caspase-3 with a concomitant reduction in Bcl-2 and survivin expression. We conclude that: (1) GC patients show significantly higher Hp and CagA seropositivity than age- and sex-matched controls, but not Hp-positive subjects, indicating that infection with cytotoxic Hp is linked to GC. (2) Serum progastrin and gastrin levels are significantly higher in GC patients than in matched controls, confirming that both gastrins may be implicated in gastric carcinogenesis. (3) GC patients exhibit significantly higher levels of IL-8 and TNF-alpha than non-GC controls and Hp-positive subjects, probably reflecting more widespread gastritis in GC. (4) COX-2, PPARgamma, Bcl-2, and survivin were overexpressed in gastric tumor, but the inhibition of COX-2 activity by Vioxx resulted in a significant reduction in serum and tumor levels of progastrin and gastrin and serum IL-8 and TNF-alpha levels, suggesting that gastrin and proinflammatory cytokines could mediate the up-regulation of COX-2 in gastric cancerogenesis. (5) Vioxx also enhanced expression of COX-2, PPARy, Bax, and caspase-3, while inhibiting the expression of Bcl-2 and survivin, suggesting that COX-2 blockade might be useful in chemoprevention against gastric cancer possibly due to enhancement of the PPARy- and proapoptotic proteins-dependent apoptosis and the reduction in progastrin/gastrin-induced promotion of tumor growth.
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PMID:Influence of COX-2 inhibition by rofecoxib on serum and tumor progastrin and gastrin levels and expression of PPARgamma and apoptosis-related proteins in gastric cancer patients. 1462 49

Survivin plays an important role in cancer development. We aim to show here that suppression of survivin expression or function by antisense and dominant-negative (DN) mutant can inhibit gastric cancer carcinogenesis and angiogenesis in vivo. Plasmid constructs expressing survivin antisense and DN mutant replacing the cysteine residue at amino acid 84 with alanine (Cys84Ala) were prepared and introduced into BCG-823 and MKN-45 gastric cancer cells to establish stable transfectants. We showed that both antisense and DN mutant stable transfectants exhibited abnormal morphology, with decreased cell growth and increased rate of spontaneous apoptosis and mitotic catastrophe. Furthermore, in nude mice xenografts, these cells exhibited decreased de novo gastric tumor formation and reduced development of angiogenesis. Results from these studies strongly suggest that survivin is a promising target for gastric cancer treatment.
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PMID:Suppression of survivin expression inhibits in vivo tumorigenicity and angiogenesis in gastric cancer. 1463 97

Survivin, a member of the inhibitor-of-apoptosis family, inhibits apoptosis by blocking caspase-3 and -7 activation. Gastric cancer, which is among the most intractable of malignant tumors, is known for resistance to various drugs, including cis-diamminedichloroplatinum (CDDP). Since this agent induces apoptosis via caspase-3 activation, survivin may mediate the drug resistance. We investigated survivin messenger RNA (mRNA) expression in gastric cancers and the relationship between expression and sensitivity to CDDP. Expression of the survivin gene was significantly up-regulated in gastric cancers compared to the tissues of normal mucosa, atrophic gastritis, and intestinal metaplasia (P < 0.0001) as assessed by a quantitative reverse transcription-polymerase chain reaction (RT-PCR), and was negatively associated with overall survival of patients who received CDDP-based chemotherapy. To investigate whether survivin is a resistance factor against CDDP-induced apoptosis, we transfected wild-type and dominant-negative mutants of the survivin gene into gastric cancer cells using a lipofection method. Overexpression of survivin protected MKN45 cells from CDDP-induced apoptosis. Expression of the dominant-negative mutant of the survivin gene sensitized NUGC-3 cells to drug-induced apoptosis. These results indicate that survivin may be pivotal in the development of gastric cancer and resistance to CDDP, and therefore controlling expression of the survivin gene may be therapeutically useful.
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PMID:Survivin as a predictor of cis-diamminedichloroplatinum sensitivity in gastric cancer patients. 1472 Mar 26


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