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)

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

Gastric cancer is an aggressive cancer with poor prognosis. Identification of precise prognostic marker and effective therapeutic target is important in the treatment of gastric cancer. TIP30, a newly identified tumor suppressor, appears to be involved in multiple functions including tumorigenic suppression, apoptosis induction and diminishing angiogenic properties. Here, the level of TIP30 expression was determined in gastric cancer, and the impact of its alteration on cancer biology and clinical outcome was investigated. We found that TIP30 protein was absent or reduced in gastric cancer cell lines. There was also a loss or substantial decrease of TIP30 expression in 106 cases of gastric tumors as compared with that in normal gastric mucosa (p<0.05), which was significantly associated with inferior survival duration. In a Cox proportional hazards model, TIP30 expression independently predicted better survival (p<0.05). We also restored TIP30 protein expression in human gastric cancer-derived cells AGS and MKN28 lacking endogenous TIP30 protein to study the effects of TIP30 expression on cell proliferation, cell kinetics, tumorigenicity and metastasis in BALB/c nude mice and found that adenoviral-mediated restoration of TIP30 expression led to downregulation of cyclin D1, Bcl-2, Bcl-xl, but to upregulation of p27, Bax, p53, caspase 3 and 9 expression, cell cycle G0/G1 arrest and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Taken together, the present work revealed a novel function of TIP30, which can possibly be used as an independent prognostic factor and a potential therapeutic target for gastric cancer.
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PMID:Reduction of TIP30 correlates with poor prognosis of gastric cancer patients and its restoration drastically inhibits tumor growth and metastasis. 1897 34

We have examined 1400 gastric biopsy specimens using classic morphological and immunohistochemical methods. Immunohistochemistry was performed using monoclonal antibodies against CD-20, CD-3, Bcl-2, EMA, CD-30 and Ki-67. A total of 105 cases were diagnosed as MALT lymphoma. We have analyzed age and epidemiological characteristics of these MALT lymphomas. Based on the received data we have concluded that MALT lymphomas are not rare entity in Georgia, particularly, this lymphomas consists 9, 0% of a total gastric cancer cases and 80% of B-lymphomas. In Georgia, as well as in the other countries of the world, MALT lymphomas are most common (80%) at the age of 55-56, with the difference that male population are most frequently diagnosed with this type of lymphomas than females.
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PMID:[Age and epidemiological characteristics of malt lymphomas in Georgia]. 1899 58

To elucidate the mechanism of resistance to 5-fluorouracil (5-FU) in human gastric cancer cells, we established a cell line MKN45/F2R, which acquired 5-FU resistance as a result of continuous exposure to increasing dosages of 5-FU over a year. The cell line showed 157-fold elevated 5-FU resistance compared to the MKN45 human gastric cancer parental cell line. Furthermore, the cells acquired crossresistance to paclitaxel and docetaxel. To identify the mechanism of 5-FU resistance, the expressions of 5-FU metabolic enzymes were examined. Although protein expression and activity of thymidylate synthase and dihydropyrimidine dehydrogenase did not change, orotate phosphoribosyl-transferase (OPRT) protein expression and activity significantly decreased in the 5-FU resistant MKN45/F2R cells. Interestingly, expression of proteins related to taxane resistance including P-glycoprotein, class III beta-tubulin and Bcl-2 increased in MKN45/F2R cells. OPRT-knockout MKN45 parent cells using small interfering RNA demonstrated 15.8-fold increased resistance to 5-FU compared to the control cells. However, resistance to paclitaxel and docetaxel was not observed. These results strongly indicate that decreased activity of OPRT plays an important role in the acquired resistance of gastric cancer cells towards 5-FU; however, it does not play a direct role in paclitaxel and docetaxel resistance. Further studies are now underway to identify genes related to crossresistance to these chemotherapeutic agents.
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PMID:Decreased orotate phosphoribosyltransferase activity produces 5-fluorouracil resistance in a human gastric cancer cell line. 1902 Jul 40

The effects and potential molecular mechanisms underlying carbon dioxide (CO(2)) pneumoperitoneum on gastric cancer cell apoptosis are not fully understood. In this study, we assessed the effects of CO(2) pneumoperitoneum on the apoptosis of MKN-45 gastric cancer cells. Additionally, we investigated the role of HIF-1alpha in CO(2) pneumoperitoneum-induced apoptosis of gastric cancer cells. MKN-45 cells were cultured in CO(2) or air pneumoperitoneum at 0, 12 and 15 mmHg pressures for 4 h. We observed a change in cells morphology and increasing apoptotic ratios in MKN-45 cells when they were put into a 15 mmHg CO(2) pneumoperitoneum environment. However, there was no significant difference between the 0, 12 mmHg CO(2) pneumoperitoneum and the control groups. Exposure to 15 mmHg CO(2) pneumoperitoneum significantly enhanced the expression levels of HIF-1alpha and Bax, while it attenuated Bcl-2 expression levels. When we inhibited HIF-1alpha by small interfering RNA (siRNA), we found that the apoptotic ratio of MKN-45 cells decreased in 15 mmHg CO(2) pneumoperitoneum. This treatment markedly elevated Bcl-2 levels and decreased Bax expression. These data suggest that CO(2) pneumoperitoneum may accelerate the apoptosis of MKN-45 cells at higher pressures. HIF-1alpha is a crucial factor that affects gastric cancer cell apoptosis by downregulating the Bcl-2/Bax ratio.
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PMID:Effects of HIF-1alpha on human gastric cancer cell apoptosis at different CO(2) pressures. 1904 82

The aim of the present study is to evaluate the influence of Helicobacter pylori on Bax and Bcl-2 mRNA and protein levels in patients with chronic gastritis and gastric cancer. The study included 217 patients, of which 26 were uninfected; 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by PCR, and the expression values were determined by quantitative real-time PCR and immunohistochemistry. Our data showed that the up-regulationary effects of H. pylori infection on the pro-apoptotic gene, Bax, were stronger than its induction of Bcl-2; this effect may increase apoptosis in patients with chronic gastritis. In patients with gastric cancer, the up-regulation of the anti-apoptotic gene, Bcl-2, counteracted the pro-apoptotic effects of Bax, leading to a deregulation of apoptosis-associated gene expression, favoring cell proliferation. Thus, the disturbance in Bax and Bcl-2 balance, induced by H. pylori, might be important in gastric cancer development.
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PMID:Effects of Helicobacter pylori infection on the expressions of Bax and Bcl-2 in patients with chronic gastritis and gastric cancer. 1916 45

Cancers in the gastrointestinal system account for a large proportion of malignancies and cancer-related deaths with gastric cancer and colorectal cancer being the most common ones. For those patients in whom surgical resection is not possible, other therapeutic approaches are necessary. Disordered apoptosis has been linked to cancer development and treatment resistance. Apoptosis occurs via extrinsic or intrinsic signaling each triggered and regulated by many different molecular pathways. In recent years, the selective induction of apoptosis in tumor cells has been increasingly recognized as a promising approach for cancer therapy. A detailed understanding of the molecular pathways involved in the regulation of apoptosis is essential for developing novel effective therapeutic approaches. Apoptosis can be induced by many different approaches including activating cell surface death receptors (for example, Fas, TRAIL and TNF receptors), inhibiting cell survival signaling (such as EGFR, MAPK and PI3K), altering apoptosis threshold by modulating pro-apoptotic and anti-apoptotic members of the Bcl-2 family, down-regulating anti-apoptosis proteins (such as XIAP, survivin and c-IAP2), and using other pro-apoptotic agents. In this review, the authors reviewed the currently reported apoptosis-targeting approaches in gastrointestinal cancers.
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PMID:Targeting apoptosis as an approach for gastrointestinal cancer therapy. 1927 96

Bufalin is the active ingredient of the Chinese medicine Chan Su, and it has been reported that bufalin induces apoptosis in some human leukemia and solid cancer cell lines. The exact mechanism of bufalin-induced apoptosis is, however, still not clear. In this study, we demonstrated that bufalin inhibited the proliferation of gastric cancer MGC803 cells in a dose-dependent and time-dependent manner. At a low concentration (20 nmol/l), bufalin induced M-phase cell cycle arrest, whereas at a high concentration (80 nmol/l) it induced apoptosis in MGC803 cells. Bufalin increased the Bax/Bcl-2 ratio and activated caspase-3 during the apoptotic process of MGC803 cells. It should be noted that bufalin transiently activated the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and then inhibited it completely, and upregulated the Casitas B-lineage lymphoma (Cbl) family of ubiquitin ligases, upstream modulators of PI3K. A combination of bufalin and LY294002, a PI3K-specific inhibitor, enhanced apoptosis, but PD98059, an extracellular-regulated protein kinase-specific inhibitor, had no significant effect on bufalin-induced apoptosis. These results suggested that the PI3K/Akt pathway might play a key role in bufalin-induced apoptosis in gastric cancer MGC803 cells.
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PMID:PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells. 1934 1

This study examined the mechanism by which the gastric cancer cells lead to early peritoneal metastasis. HMrSV5 cells, a human peritoneal mesothelial cell line, were co-incubated with the supernatants of gastric cancer cells. Morphological changes of HMrSV5 cells were observed. The cell damage was quantitatively determined by MTT assay. The apoptosis of HMrSV5 cells was observed under transmission electron microscope. Acridine orange/ethidium bromide-stained condensed nuclei was detected by fluorescent microscopy and flow cytometry. The expressions of Bcl-2 and Bax was immunochemically evaluated. The results showed that conspicuous morphological changes of apoptosis were observed in HMrSV5 cells 24 h after treatment with the supernatants of gastric cancer cells. The supernatants could induce apoptosis of HMrSV5 cells in a time-dependent manner. The supernatants could up-regulate the expression of Bax and suppress that of Bcl-2 in HMrSV5 cells. These findings demonstrated that gastric cancer cells can induce the apoptosis of HPMCs through supernatants in the early peritoneal metastasis. The abnormal expressions of Bcl-2 and Bax may contribute to the apoptosis. Anti-apoptosis drugs promise to be adjuvant chemotherapeutic agents in the treatment of peritoneal metastasis of gastric cancer.
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PMID:Destruction of gastric cancer cells to mesothelial cells by apoptosis in the early peritoneal metastasis. 1939 97

The radiosensitizing effects of luteolin were studied in the gastric cancer cell line SGC-7901. SGC-7901 cells were treated with luteolin or/and irradiation, and radiosensitizing effects were assessed by colony-forming assay with cells and nude mice. In order to study the underlying mechanism, the levels of apoptosis-related proteins, the activities of caspase-3 and -9, and the production of PGE2 were measured. The results showed that luteolin could enhance irradiation-induced colonogenic inhibition and the activities of Caspase-3 and -9. The remarkable down-regulation of Bcl-2 and release of cytochrome C were also observed. In addition, significantly reduced production of PGE(2) was observed in luteolin plus radiation treatment by ELISA, as well as decreased expression levels of VEGF and HIF-1 alpha. Finally, luteolin significantly enhances the radioresponse of human tumors transplanted into nude mice. Our results indicate that luteolin may be a promising radiosensitizer for use in the treatment of gastric cancer.
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PMID:Radiosensitization effect of luteolin on human gastric cancer SGC-7901 cells. 1958 87


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