Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Fas-associated factor 1, FAF1, is a protein, which was first identified as an interaction partner of the death receptor Fas. Not much is known about the function of FAF1, but it has been found that it is able to potentiate Fas-induced apoptosis in cell lines. To clarify the role of FAF1 in human cancer, a number of tumors from different organs were screened for expression of the protein, and it was only found reduced in gastric carcinoma tissue. Thus, 58 human gastric carcinomas were collected, and the expression of FAF1 was analyzed by Western blotting and in a few cases also by immunohistochemistry. The hypothesis was that since FAF1 is able to potentiate apoptosis, it would likely be reduced in the gastric carcinomas in order for them to escape apoptosis. We found that FAF1 was reduced in 50% (29/58) of the gastric carcinomas analyzed as compared to non-neoplastic gastric mucosa from the same patients. 26 of the investigated carcinomas contained signet ring cells, and FAF1 was significantly reduced in 69% of these (p=0.017), whereas it was only reduced in 34% of the carcinomas without signet ring cells. The observed reduction of FAF1 was predominantly caused by proteolytic cleavage of the protein. Additionally, 31 colorectal carcinomas were analyzed for expression of FAF1. Here, FAF1 was only reduced in 16% of the carcinomas when compared to non-neoplastic colorectal mucosa. Our findings support the hypothesis that FAF1 is reduced in gastric carcinomas compared to non-neoplastic tissue, and there was a significant relation between FAF1 reduction and content of signet ring cells in the gastric carcinomas. Also, the reduction of FAF1 is likely to be specific for gastric cancer, which might be due to the fact that signet ring cells are most frequently found in gastric cancers.
 ...
PMID:The pro-apoptotic FAS-associated factor 1 is specifically reduced in human gastric carcinomas. 1296 81

The widespread expression of CD40, a member of the tumor necrosis factor (TNF) receptor (TNFR) superfamily, is likely to account for the central role of CD40 in the regulation of humoral immunity and host defense. Interestingly, the expression of the CD40 in various types of carcinoma cells was often observed and conveys signals regulating diverse cellular responses, ranging from proliferation to growth suppression. Thus, the biologic role of the CD40-CD40L interaction in solid tumors is still controversial. In this study, we investigated the expression and function of the CD40 in gastric carcinoma cells. In 3-4,5 dimethylthiozol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay and Annexin V/propidium iodide staining, CD40 stimulation using a soluble form of CD40 ligand did not affect cell viability, but significantly inhibited Fas-mediated or chemotherapy-mediated apoptosis in three CD40-positive gastric cancer cell lines. Moreover, in migration assay, CD40 stimulation induced an elevation of cell motility in CD40-positive gastric carcinoma cells. Our results show that the CD40 expression on gastric carcinoma makes cells less vulnerable to apoptosis induced by Fas or chemotherapy. These results suggest that the CD40 expression on gastric carcinoma may be associated with cell survival and elevation of cell motility.
 ...
PMID:Stimulation of CD40 inhibits Fas- or chemotherapy-mediated apoptosis and increases cell motility in human gastric carcinoma cells. 1461 43

The death receptors Fas and DR5 are known to be expressed not only in immune cells but also in various tumor cells. The aim of the present study was to determine whether X irradiation enhanced induction of apoptosis in Tp53 wild type and Tp53-mutated tumor cell lines treated with agonists against these death receptors. We showed that 5 Gy of X irradiation significantly up-regulated the expression of death receptors Fas and DR5 on the plasma membrane in gastric cancer cell lines MKN45 and MKN28, lung cancer cell line A549, and prostate cancer cell line DU145, and that subsequent treatments with agonistic molecules for these death receptors, Fas antibody CH11 and TRAIL, increased the formation of active fragment p20 of caspase 3 followed by the induction of apoptosis. This death-receptor-mediated apoptosis was independent of Tp53 status since MKN28 and DU145 were Tp53-mutated. The post-irradiation treatment of the cells with N-acetyl-L-cysteine (NAC) abolished the up-regulation of the expression of Fas and DR5 on the plasma membrane. NAC also attenuated the increase in the formation of p20 and the induction of apoptosis by agonistic molecules. These results suggested that the increase in the induction of apoptosis by combined treatment with X irradiation and CH11 or TRAIL occurred through a change of the intracellular redox state independent of Tp53 status in human carcinoma cell lines.
 ...
PMID:Enhanced induction of apoptosis by combined treatment of human carcinoma cells with X rays and death receptor agonists. 1580 65

Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop chronic and life threatening diseases, as peptic ulcer, gastric cancer, B-cell lymphoma, or autoimmune gastritis. The type of host immune response against H. pylori is crucial for the outcome of the infection. A predominant H. pylori-specific Th1 response, characterized by high IFN-gamma, TNF-alpha, and IL-12 production associates with peptic ulcer, whereas combined secretion of both Th1 and Th2 cytokines are present in uncomplicated gastritis. Gastric T cells from MALT lymphoma exhibit abnormal help for autologous B-cell proliferation and reduced perforin- and Fas-Fas ligand-mediated killing of B cells. In H. pylori-infected patients with autoimmune gastritis cytolytic T cells infiltrating the gastric mucosa cross-recognize different epitopes of H. pylori proteins and H+K+ ATPase autoantigen. These data suggest that peptic ulcer can be regarded as a Th1-driven immunopathological response to some H. pylori antigens, whereas deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support the onset of low-grade B-cell lymphoma. Alternatively, H. pylori infection may lead in some individuals to gastric autoimmunity via molecular mimicry.
 ...
PMID:Helicobacter pylori, T cells and cytokines: the "dangerous liaisons". 1586 4

Helicobacter pylori (Hp) can induce apoptosis of gastric cancer cells. The mechanism of the process still needs further elucidating. This study was aimed to analyse the mechanism through which Hp induce apoptosis in human gastric cancer cell line BGC-823. The extract from VacA(+) and CagA(+) Helicobacter pylori strain NCTC11637 was applied to induce apoptosis. The expression, breakdown, and phosphorylation of proteins were probed by Western blotting with specific antibodies. Apoptosis of the cells was detected by flow cytometry. The results showed that incubating the cells with Hp extract caused the breakdown of both caspase-3 and -1. The breakdown was dose-dependent and correlated with the occurrence of the Hp extract-induced apoptosis. Among the substrates of caspase-3, DNA fragment factor (DFF) was degraded during incubation with Hp extract and a small fragment was released. However, poly(ADP-ribose) polymerase (PARP) did not break down during the incubation. Tyrosine kinase inhibitor Genistein prevented both the break down of caspase-3 and the apoptosis induced by Hp extract. MAPK/ERK inhibitor PD98059 did not prevent the apoptosis induced by Hp extract. The expression and activity of JNK, and the expression of Bcl-2 and Fas proteins did not change during the incubation with Hp extract. The results suggested that Hp extract initiated apoptosis in BGC-823 cells through activating tyrosine kinase, caspase-1, -3, and DFF.
 ...
PMID:Analysis on the mechanism of Helicobacter pylori-induced apoptosis in gastric cancer cell line BGC-823. 1614 14

Escape from normal apoptotic controls is thought to be essential for the development of cancer. During Helicobacter pylori infection, the leading cause of gastric cancer, activation of the Fas antigen (Fas Ag) apoptotic pathway is responsible for early atrophy and tissue loss. As disease progresses, metaplastic and dysplastic glands arise which express Fas Ag but are resistant to apoptosis and are believed to be the precursor cells for adenocarcinoma. In this report, we show that one mechanism of acquired Fas resistance is inhibition of receptor aggregation via a major histocompatibility complex class II (MHCII)-mediated, actin-dependent mechanism. For these studies we used the well-described C57BL/6 mouse model of Helicobacter pylori and Helicobacter felis infection. Under normal conditions, Fas Ag is expressed at low levels, and MHCII expression on gastric mucosal cells is negligible. With infection and inflammation, both receptors are upregulated, and 6.1% of gastric mucosal cells express MHCII in combination with Fas Ag. Using the rat gastric mucosal cell line RGM-1 transfected with murine Fas Ag and MHCIIalphabeta chains, we demonstrate that MHCII prevents Fas receptor aggregation and inhibits Fas-mediated signaling through its effects on the actin cytoskeleton. Depolymerization of actin with cytochalasin D allows receptors to aggregate and restores Fas sensitivity. These findings offer one mechanism by which gastric mucosal cells acquire Fas resistance.
 ...
PMID:Major histocompatibility complex class II inhibits fas antigen-mediated gastric mucosal cell apoptosis through actin-dependent inhibition of receptor aggregation. 1617 2

The initiating molecular events in Helicobacter-induced gastric carcinogenesis are not known. Early in infection, Fas antigen-mediated apoptosis depletes parietal and chief cell populations, leading to architectural distortion. As infection progresses, metaplastic and dysplastic glands appear, which are resistant to Fas-mediated apoptosis. These abnormal lineages precede, and are thought to be the precursor lesions of, gastric cancer. Acquisition of an antiapoptotic phenotype before transformation of cells suggests that loss of Fas sensitivity may be an early required trait for gastric cancer. We reasoned that forced Fas-apoptosis resistance would result in earlier and more aggressive gastric cancer in our mouse model. Fas antigen-deficient (lpr) mice or C57BL/6 wild-type mice were irradiated and reconstituted with C57BL/6 marrow forming partial lpr/wt chimera or wt/wt control mice, extending the life span of the lpr and ensuring a competent immune response to Helicobacter felis infection. Infected lpr/wt mice developed gastric cancer as early as 7 months after infection (compared with 15 months in wt/wt mice). At 10 months (90%) and 15 months (100%), mice developed aggressive invasive lesions. This earlier onset and more aggressive histology strongly argues that Fas-apoptosis resistance is an early and important feature of gastric cancer formation.
 ...
PMID:Overcoming Fas-mediated apoptosis accelerates Helicobacter-induced gastric cancer in mice. 1632 38

Hypergastrinemia in INS-GAS mice leads to accelerated carcinogenesis of the stomach, but the mechanisms have not been well defined. We investigated the possible role of gastrin-induced gastric cell apoptosis in the development of gastric cancer. We examined apoptosis and the expression of Bcl-2 family proteins in INS-GAS mice of different ages, as well as in gastrin-deficient (GAS-KO) mice after gastrin-17 (G-17) infusion. In addition, we studied the effects of the gastrin/cholecystokinin-2 (CCK-2) receptor antagonist YF476 and/or histamine H2 (H-2) receptor antagonist loxtidine on apoptosis and atrophy in INS-GAS mice with or without Helicobacter felis (H. felis) infection. INS-GAS mice had age-associated increases in Bax protein expression and decreases in Bcl-2 protein expression, along with increased glandular and epithelial cell apoptosis. At 8-week gastrin infusions in GAS-KO mice resulted in a similar pattern of altered Bax and Bcl-2 expression, followed by gastric cell apoptosis. H. felis infection of INS-GAS mice led to increased apoptosis and the development of atrophy, whereas treatment with either YF476 and/or loxtidine strongly inhibited both apoptosis and atrophy. In vitro studies with Fas-expressing RGM1 cells showed that gastrin stimulation alone directly induced apoptosis via gastrin/CCK-2 receptor and synergized with FasL stimulation. These results indicate that gastrin can induce apoptosis in gastric epithelial cells and contribute to the development of gastric carcinogenesis.
 ...
PMID:Gastrin-induced apoptosis contributes to carcinogenesis in the stomach. 1689 54

Helicobacter pylori is known to be the cause of most gastric diseases, including both peptic ulcer disease and gastric cancer. In the absence of eradication, infection tends to be lifelong and the immune response ineffective in clearing the bacteria. A number of groups have investigated whether the immune clearance of infection can be achieved through a vaccination strategy, but to date, the results have been inconclusive. In fact, in most cases of natural infection, the host immune response leads to a chronic inflammation within the gastric mucosa that actually promotes the development of atrophy and neoplasia. In most cases, eradication of the organism leads to resolution of inflammation, which in many instances can result in reduction in atrophy and gastric cancer risk. This finding suggests that even at late stages, cancer progression is dependent, to a large extent, on infection/immune response. Work from a number of laboratories has led to the hypothesis that T-cells and the Th1 immune response, governed largely by host genetic factors, are strongly associated with the H. pylori-mediated induction of atrophy and cancer. Interleukin-1beta appears to be a particularly important cytokine that inhibits acid secretion and increases serum gastrin levels, factors strongly associated with cancer induction. The induction by H. pylori of cytokines and chemokines and growth-related genes is mediated by the MAPK and NF-kappaB signaling pathway. Recent studies have shown that NF-kappaB is activated through a NF-kappaB-inducing kinase/p21-activated kinase 1 pathway. H. pylori can also promote cellular apoptosis through a number of mechanisms, the most important of which is upregulation of the Fas/FasL pathway. Finally, understanding of H. pylori pathogenesis has been broadened and deepened by the application of genomics and proteomics to the organism.
 ...
PMID:Helicobacter pylori infection: pathogenesis. 1703 Dec 25

Gastric cancer is a common malignancy in many countries of the world, especially in Asia. Prevention is likely to be the most effective means of not only reducing the incidence but also mortality from this disease. The term 'chemoprevention' has been referred to the prevention of cancer using specific agents to suppress or reverse the carcinogenic process. In recent years, attention has been focused on the anticancer properties of edible plants, an important role in the prevention of disease. Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. The purpose of this study was to examine whether the plant, H. sabdariffa extracts (HSE), affects the apoptosis of AGS cells. Using a set of apoptotic detection assays, they showed that HSE induced cytotoxicity and apoptosis of AGS cells in a concentration-dependent manner but is ineffective in Chang liver cells. The result also revealed increased phosphorylation in p38, JNK and c-Jun, cytochrome c release, and expression of Fas, FasL, Bax, and t-Bid in the HSE-treated AGS cells. We further used MAPK inhibitors to evaluate their effect on the HSE-induced AGS death. The data showed that SB203580 (p38 inhibitor), JNK inhibitor I and II or transfection with the mutant JNK expression vector had strong potential in inhibiting AGS cells apoptosis and related proteins expression. Finally, we suggested that HSE mediated AGS apoptosis via the JNK/p38 signaling cascade. According to these results, HSE could be developed as a chemopreventive agent.
 ...
PMID:Chemopreventive properties of Hibiscus sabdariffa L. on human gastric carcinoma cells through apoptosis induction and JNK/p38 MAPK signaling activation. 1714 51


<< Previous 1 2 3 4 5 6 7 Next >>