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)

Previous studies have demonstrated that interleukin-24 [IL-24; originally called melanoma differentiation associated gene-7 (mda-7)] as a novel tumor suppressor gene has tumor-suppressive activity against a broad spectrum of human cancers. However, the therapeutic effect of the recombinant human IL-24 (rhIL-24) protein purified from prokaryotic cells on gastric cancer has not been reported. In this study, we purified soluble rhIL-24 using Q-Sepharose column after the denaturing and renaturing process from the protein of Escherichia coli BL21 transfected with pET-21a(+)-hIL-24 vector and treated by isopropyl-beta-D-1-thiogalactopyranoside (IPTG) for enhanced expression of transgene rhIL-24. We demonstrated that rhIL-24 was capable of inducing in vitro apoptosis of SGC7901 gastric cancer cells and activating peripheral blood mononuclear cellsto secrete cytokines such as IL-6, TNF-alpha, and IFN-gamma. We also showed that rhIL-24 was able to inhibit formation of blood capillaries on chicken embryonic allantois and in vivo tumor angiogenesis leading to suppressing SGC7901 gastric cancer cell growth in vitro and in vivo possibly due to its downregulation of Bcl-2/Bax ratio, VEGF (vascular endothelial growth factor), and CD34. Therefore, our results indicate that rhIL-24 has potent suppressive effect on human SGC7901 gastric carcinoma cell line and warrant its further investigation for therapeutic application against gastric cancer.
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PMID:Recombinant human interleukin-24 suppresses gastric carcinoma cell growth in vitro and in vivo. 1991 46

Gastric cancer is a serious public health cancer and causes nearly 1 million deaths a year worldwide. Th1 cells play critical roles in orchestrating the adaptive immune responses against gastric cancer. T-bet, a member of the T-box family of transcription factors, is the Th1 master regulator and up-regulated during Th1 differentiation. Polymorphisms have also been shown to exist in T-bet. Some reports indicated that some tumours were associated with the drift of Th1 and Th2. In the present work, we investigated the drift of Th1/Th2 by detecting the expression levels of T-bet, IFN-gamma, IL-4, and GATA-3 in peripheral blood mononuclear cell of gastric cancer patients by real-time PCR, explored the relationship between the polymorphism of T-bet gene and drift of Th1/Th2 by gene sequence, western blot, and gene transfection. Our results indicated that a predominant Th2 phenotype was existence. T-bet gene mutations may be associated with Th2-dominated condition in gastric cancers.
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PMID:The mutations of Th1 cell-specific T-box transcription factor may be associated with a predominant Th2 phenotype in gastric cancers. 2019 34

Antibody-targeted superantigen has been developed into a new strategy to treat many malignant tumors. In this study, for specific targeting to gastric cancer cell, superantigen SEB (Staphylococcal Enterotoxin B) was genetically fused to the single-chain variable fragment of gastric carcinoma-associated antibody MG7(MG7-scFv) that recognizes the MG7 antigen frequently expressed in gastric cancer cell. The recombinant MG7-scFv/SEB fusion proteins are expressed in E. coli as inclusion bodies, and the purified MG7-scFv/SEB retains high binding affinity with gastric cancer cell SGC-7901 (positive MG7 antigen expression). When incubated with effector cell-peripheral blood mononuclear cells (PBMCs), MG7-scFv/SEB could effectively inhibit the proliferation and induce apoptosis of SGC-7901. After being treated with MG7-scFv/SEB, PBMCs remarkably increased the production of Th1 cytokines (IFN-gamma, IL-2), and slightly increased the production of Th2 cytokines (IL-4, IL-10) in vitro. It was observed that gastric-tumor-bearing rats administrated with MG7-scFv/SEB showed more inflammatory cell infiltration, more significant tumor inhibition, and longer survival time than those of rats treated with SEB or NS (Normal Saline). The data indicated that MG7-scFv/SEB fusion protein could specifically target gastric cancer cell, enhance the activity of T cells and induce tumor cell apoptosis to exert the antitumor effect on gastric cancer.
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PMID:Construction and characterization of a novel fusion protein MG7-scFv/SEB against gastric cancer. 2033 32

Gastric adenocarcinoma develops as a consequence of chronic inflammation of the stomach lining that is caused by persistent infection with the bacterium Helicobacter pylori. Gastric carcinogenesis progresses through a sequence of preneoplastic lesions that manifest histologically as atrophic gastritis, intestinal metaplasia, and dysplasia. We show here in several preclinical models of Helicobacter-induced atrophic gastritis, epithelial hyperplasia, and metaplasia that the inhibition of ADP ribosylation by the small-molecule inhibitor PJ34 not only prevents the formation of gastric cancer precursor lesions, but also efficiently reverses preexisting lesions. PJ34 exerts its chemopreventive and therapeutic effects by impairing Helicobacter-specific T-cell priming and T(H)1 polarization in the gut-draining mesenteric lymph nodes. The subsequent infiltration of pathogenic T cells into the gastric mucosa and the ensuing gastric T cell-driven immunopathology are prevented efficiently by PJ34. Our data indicate that PJ34 directly suppresses T-cell effector functions by blocking the IFN-gamma production of mesenteric lymph node T cells ex vivo. Upon exposure to PJ34, purified T cells failed to synthesize ADP-ribose polymers and to activate the transcription of genes encoding IFN-gamma, interleukin 2, and the interleukin 2 receptor alpha chain in response to stimuli such as CD3/CD28 cross-linking or phorbol 12-myristate 13-acetate/ionomycin. The immunosuppressive and chemoprotective effects of PJ34 therefore result from impaired T-cell activation and T(H)1 polarization, and lead to the protection from preneoplastic gastric immunopathology. In conclusion, ADP-ribosylating enzymes constitute novel targets for the treatment of Helicobacter-associated gastric lesions predisposing infected individuals to gastric cancer and may also hold promise for the treatment of other T cell-driven chronic inflammatory conditions and autoimmune pathologies.
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PMID:Inhibition of ADP ribosylation prevents and cures helicobacter-induced gastric preneoplasia. 2063 4

In select Helicobacter pylori-infected populations with low gastric cancer, nematode coinfections are common and both helicobacter gastritis and filariasis are modeled in gerbils. We evaluated gastritis, worm counts, tissue cytokine gene expression levels and Th1/Th2-associated antibody responses in H. pylori and Brugia pahangi mono- and coinfected gerbils. H. pylori-associated gastritis indices were significantly lower 21 weeks post-infection in coinfected gerbils (p < or = 0.05) and were inversely proportional to worm counts (r(2) = -0.62, p < 0.003). Additionally, IFN-gamma, IL-1 beta, CXCL1, IL-4 and IL-10 mRNA levels in the gastric antrum reflected a significant host response to gastric H. pylori and as well as systemic filariasis (p < or = 0.05). Despite increasing worm burden (p < 0.05), gastritis progressed in coinfected gerbils (p < 0.03) becoming equivalent to H. pylori-infected gerbils at 42 weeks (p = 0.7). Pro- and anti-inflammatory mediator mRNA levels were notably downregulated in B. pahangi infected gerbils below uninfected control values, suggesting hyporesponsiveness to B. pahangi. Consistent with an increasing Th1 response to H. pylori, IgG2a (p < 0.01), IL-1 beta (p = 0.04) and CXCL1 (p = 0.006) responses significantly increased and IL-4 (p = 0.05) and IL-10 (p = 0.04) were decreased in coinfected gerbils at 42 weeks. Initial systemic responses to B. pahangi resulted in attenuated gastritis in coinfected gerbils, but subsequent filarid-associated hyporesponsiveness appears to have promoted H. pylori gastritis.
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PMID:Brugia filariasis differentially modulates persistent Helicobacter pylori gastritis in the gerbil model. 2068 94

Gastric cancer is the second most frequent cause of cancer-related death worldwide. Combined surgery and chemo/radiotherapy give only a limited 5-year survival rate. Alternative therapeutic strategies such as immunotherapy are needed to improve this survival rate. Macrophages are functionally plastic cells. Type 1 macrophages (M1) inhibit, whereas type 2 macrophages (M2) promote, tumor growth. In this study, we examined the effects of in vitro repolarized tumor macrophages on gastric tumor growth in vivo. We demonstrated that peritoneal macrophages isolated from mouse forestomach carcinoma (MFC) tumor-bearing mice (TPM) displayed a M2 functional phenotype as indicated by a characteristic cytokine production profile and expression pattern of inducible nitric oxide synthase (iNOS) and arginase (Arg) of M2 macrophages. Treatment of TPM with type 1 cytokine IL-12 and IFN-gamma repolarized TPM toward the M1 phenotype as confirmed by a cytokine production profile and expression pattern of iNOS and Arg of typical M1 macrophages. Repolarized TPM significantly inhibits the growth of MFC tumors implanted subcutaneously compared to peritoneal macrophage (PM) isolated from normal animals, TPM, or M2 macrophages. Our study supports in vitro repolarization of macrophages as a potential immunotherapeutic strategy for gastric cancer.
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PMID:In vitro repolarized tumor macrophages inhibit gastric tumor growth. 2387 67


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