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)

Identifying an effective therapeutic target is pivotal in the treatment of gastric cancer. In this study, we investigated the expression of p75 neurotrophin receptor (p75NTR) in gastric cancer and the impact of its alteration on tumor growth. p75NTR expression was absent or significantly decreased in 212 cases of gastric cancers compared with the normal gastric mucosa (P < .05). Moreover, p75NTR expression was also lost or significantly decreased in various human gastric cancer cell lines. p75NTR inhibited in vitro growth activities and caused dramatic attenuation of tumor growth in animal models by induction of cell cycle arrest. Upregulation of p75NTR led to downregulation of cyclin A, cyclin D1, cyclin E, cyclin-dependent kinase 2, p-Rb, and PCNA, but to upregulation of Rb and p27 expressions. Conversely, downregulating p75NTR with specific siRNA yielded inverse results. The rescue of tumor cells from cell cycle progression by a death domain-deleted dominant-negative antagonist of p75NTR (Deltap75NTR) showed that the death domain transduced antiproliferative activity in a ligand-independent manner and further demonstrated the inhibitive effect of p75NTR on growth in gastric cancer. Therefore, we provided evidence that p75NTR was a potential tumor suppressor and may be used as a therapeutic target for gastric cancer.
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PMID:p75 neurotrophin receptor suppresses the proliferation of human gastric cancer cells. 1760 29

Pterostilbene, an active constituent of blueberries, is known to possess anti-inflammatory activity and also induces apoptosis in various types of cancer cells. Here, the effects of pterostilbene on cell viability in human gastric carcinoma AGS cells were investigated. This study demonstrated that pterostilbene was able to inhibit cell proliferation and induce apoptosis in a concentration- and time-dependent manner. Pterostilbene-induced cell death was characterized with changes in nuclear morphology, DNA fragmentation, and cell morphology. The molecular mechanism of pterostilbene-induced apoptosis was also investigated. The results show the caspase-2, -3, -8, and -9 are all activated by pterostilbene, together with cleavage of the downstream caspase-3 target DNA fragmentation factor (DFF-45) and poly(ADP-riobse) polymerase. Moreover, the results indicate that the Bcl-family of proteins, the mitochondrial pathway, and activation of the caspase cascade are responsible for pterostilbene-induced apoptosis. Pterostilbene markedly enhanced the expression of growth arrest DNA damage-inducible gene 45 and 153 (GADD45 and GADD153) in a time-dependent manner. Flow cytometric analysis indicated that pterostilbene blocked cell cycle progression at G1 phase in a dose- and time-dependent manner. Pterostilbene increased the p53, p21, p27, and p16 proteins and decreased levels of cyclin A, cyclin E, cyclin-dependent kinase 2 (Cdk2), Cdk4, and Cdk6, but the expression of cyclin D1 was not affected. Over a 24 h exposure to pterostilbene, the degree of phosphorylation of Rb was decreased after 6 h. In summary, pterostilbene induced apoptosis in AGS cells through activating the caspase cascade via the mitochondrial and Fas/FasL pathway, GADD expression, and by modifying cell cycle progress and changes in several cycle-regulating proteins. The induction of apoptosis by pterostilbene may provide a pivotal mechanism of the antitumor effects and for treatment of human gastric cancer.
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PMID:Pterostilbene induces apoptosis and cell cycle arrest in human gastric carcinoma cells. 1769 82

Altered signaling pathways or deregulated transcription factors represent an important category of molecular events leading to aberrant gene regulation in gastric cancer, among which the role of WNT/beta-catenin pathway remains unclear. LRH-1 is a critical transcription factor in controlling cell proliferation via crosstalk with the beta-catenin signaling pathway. In order to gain a knowledge of the expression of hLRH-1v1 and hLRH-1 in gastric cancer, a Q-PCR analysis was carried out. Our results showed that in about 50 and 47.6% of 42 tested patients with gastric cancer, the mRNA expression of hLRH-1v1 and hLRH-1 was significantly upregulated, as compared with self-paired normal control, respectively. Besides, overexpression of hLRH-1 was shown to promote the proliferation of gastric adenocarcinoma cell SGC-7901 via induction of cyclin E1. Taken together, our present study demonstrated for the first time the increased expression of hLRH-1v1 and hLRH-1 in human gastric cancer, an alteration which may implicate in tumorigenesis.
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PMID:Increased expression of hLRH-1 in human gastric cancer and its implication in tumorigenesis. 1795 62

The immunohistochemical expression of phosphorylated (activated) Akt (pAkt) in 50 advanced gastric carcinomas has been analyzed and the results correlated with age, sex, location in the stomach, histotype, stage, survival, mitotic and apoptotic index, some cell cycle regulators (cyclin D1, cyclin E, p34/cdc2, p27/kip1), and cell proliferation. There was a statistically significant direct correlation between pAkt expression (both cytoplasmatic and nuclear) and depth of infiltration of the tumor, number of infiltrated lymph nodes and p34/cdc2 expression, and between prevalently nuclear pAkt and cyclin D1 and cyclin E. Conversely, there was a significant inverse correlation between nuclear pAkt and apoptotic index and between cytoplasmatic and nuclear pAkt and patient survival. No correlation was found between pAkt and sex, age, tumor location, histotype, mitotic index, and cell proliferation. These findings suggest that pAkt may be considered an indicator of tumor progression and patient survival in gastric cancer.
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PMID:Activated Akt as an indicator of prognosis in gastric cancer. 1884 91

Understanding hub genes involved in gastric cancer (GC) metastasis could lead to effective approaches to diagnose and treat cancer metastasis. In this study, 272 differentially expressed genes between synchronous liver metastasis and the paired GC were selected from microarray assays. KEGG pathway analysis indicated that of 13 enriched pathways, 8 were involved in cancer metastasis. Literature-based annotations showed that the differentially expressed genes significantly enriched known metastasis-related genes. With the use of protein-protein interaction network, we found a subnetwork significantly enriching the metastasis-related genes and hubs. Unannotated hubs in this subnetwork were predicted to be novel metastasis-associated genes. Nine hubs in this subnetwork were validated by using quantitative RT-PCR, and 4 hubs were further validated by immunohistochemistry. NR4A2 was significantly down-regulated in synchronous liver metastasis compared with the paired GC at both transcriptional and translational levels. NR4A2 immunostaining was apparent in the mesenchymal cells of pathologically normal gastric mucosa and in the epithelial cells of primary GC. HSP90AA1 was not only up-regulated in the metastatic GC compared with primary GC at both transcriptional and translational levels, but also up-regulated in primary GC compared with the normal mucosa at the translational level. NR4A2, NR3C1, ARF3, XAB2, and alternatively spliced variants of NR4A2, SP8 and SP-novel, were significantly down-regulated, whereas CCNE1 significantly up-regulated, in primary GC compared with the normal gastric mucosa. Conclusively, NR4A2 and HSP90AA1 stand out as promising diagnostic markers and therapeutic targets for liver metastasis of GC. CCNE1 and NR3C1 indicate primary GC, rather than distant metastasis.
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PMID:Identification of novel hub genes associated with liver metastasis of gastric cancer. 1956 46

Our previous works revealed that human ribosomal protein S13 (RPS13) was up-regulated in multidrug-resistant gastric cancer cells and overexpression of RPS13 could protect gastric cancer cells from drug-induced apoptosis. The present study was designed to explore the role of RPS13 in tumorigenesis and development of gastric cancer. The expression of RPS13 in gastric cancer tissues and normal gastric mucosa was evaluated by immunohistochemical staining and Western blot analysis. It was found RPS13 was expressed at a higher level in gastric cancer tissues than that in normal gastric mucosa. RPS13 was then genetically overexpressed in gastric cancer cells or knocked down by RNA interference. It was demonstrated that up-regulation of RPS13 accelerated the growth, enhanced in vitro colony forming and soft agar cologenic ability and promoted in vivo tumour formation potential of gastric cancer cells. Meanwhile, down-regulation of RPS13 in gastric cancer cells resulted in complete opposite effects. Moreover, overexpression of RPS13 could promote G1 to S phase transition whereas knocking down of RPS13 led to G1 arrest of gastric cancer cells. It was further demonstrated that RPS13 down-regulated p27(kip1) expression and CDK2 kinase activity but did not change the expression of cyclin D, cyclin E, CDK2, CDK4 and p16(INK4A). Taken together, these data indicate that RPS13 could promote the growth and cell cycle progression of gastric cancer cells at least through inhibiting p27(kip1) expression.
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PMID:Human ribosomal protein S13 promotes gastric cancer growth through down-regulating p27(Kip1). 1991 38

The enhancer of zeste homolog 2 (EZH2), a member of the polycomb group of proteins, plays an important role in cell proliferation and cell cycle regulation. EZH2 is overexpressed in aggressive forms of prostate, breast, bladder, and endometrial cancers. However, the role of EZH2 expression in gastric cancer has not been fully determined. This study was conducted to investigate the correlation between EZH2 and cell cycle-related molecules, and the clinical value of EZH2 expression in gastric cancer. We analyzed EZH2 expression using Western blotting in AGS, MKN-28, SNU-16, SNU-484, SNU-601, and SNU-638 gastric cancer cell lines. After transfection of EZH2 siRNA into MKN-28 cells, the change in cell cycle-related molecules was assessed by Western blot analysis. Expression of EZH2, Ki-67, and p53 was determined by immunohistochemical staining of tissue microarrays from specimens of 137 cases of resected gastric cancer. We found high expressions of EZH2 in all of the tested gastric cancer cell lines. RNA interference of EZH2 induced upregulation of p53 and HDAC1 and downregulation of cyclin D1 and cyclin E. High EZH2 expression was observed in 60.6% of gastric cancers and in 6.7% of non-neoplastic gastric tissues (p < 0.01); 40.1% were positive for p53 in gastric cancers. High EZH2 expression was correlated with Ki-67 and p53 expressions and was significantly associated with distant metastases and non-signet ring cells. Our results suggest that high EZH2 expression is associated with tumor cell proliferation and metastasis in gastric cancer.
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PMID:Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasis in gastric cancer. 2013 85

Our previous study revealed that human ribosomal protein L6 (RPL6) was upregulated in multidrug-resistant gastric cancer cells and over-expression of RPL6 could protect gastric cancer cells from drug-induced apoptosis. The present study was designed to explore the role of RPL6 in tumorigenesis and development of gastric cancer. The expression of RPL6 in gastric cancer tissues and normal gastric mucosa was evaluated by immunohistochemical staining. It was found RPL6 was expressed at a higher level in gastric cancer tissues than that in normal gastric mucosa. RPL6 was then genetically overexpressed or knocked down in human immortalized gastric mucosa epithelial GES cells. It was demonstrated that upregulation of RPL6 accelerated the growth and enhanced in vitro colony forming ability of GES cells whereas downregulation of RPL6 showed adverse effects. Moreover, over-expression of RPL6 could promote G1 to S phase transition of GES cells. It was further evidenced that upregulation of RPL6 resulted in elevated cyclin E expression while downregulation of RPL6 caused decreased cyclin E expression in GES cells. Taken together, these data indicated that RPL6 was overexpressed in human gastric cancer and its over-expression could promote cell growth and cell cycle progression at least through upregulating cyclin E expression.
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PMID:Ribosomal protein L6 promotes growth and cell cycle progression through upregulating cyclin E in gastric cancer cells. 2017 Nov 75

Tumor cell growth is influenced by the cellular microenvironment including the presence of immune cells and blood vessels. Currently, no transplantable gastric cancer syngeneic animal models exist; therefore, we set out to establish a mouse gastric carcinoma cell line, which was named mouse gastric carcinoma cell line 3I (MGCC3I), from forestomach carcinoma developed in benzo[a]pyrene-treated ICR mice. MGCC3I cells showed epithelial-like morphology, multinuclear giant cell formation, and retained an intestinal phenotype, which are similar to human gastric cancer carcinoma cells. The expression of gastric cancer markers MUC1, MUC2, and MUC5AC, and oncogenes c-myc, c-met, cyclin E1, and cancer stem cell marker CD44 was determined in MGCC3I cells. MGCC3I cells formed poorly differentiated stomach tumors following orthotopic implantation into the stomachs of syngeneic ICR mice. Histone deacetylase inhibitors are recognized as a new class of anticancer drugs. The immunological therapeutic effects of the histone deacetylase inhibitors sodium butyrate and valproic acid were evaluated in this new animal tumor model. Sodium butyrate inhibited MGCC3I stomach tumor formation in animal models. Increased tumor infiltration by CD8 T cells and neutrophils was observed in mice treated with sodium butyrate or valproic acid. Depletion of CD8 T cells significantly attenuated tumor regression mediated by histone deacetylase inhibitors, which is correlated with enhancement of the MHC class I pathway in MGCC3I cells. Taken together, we have successfully established an orthotopic transplantable gastric tumor animal model and demonstrated its usefulness in revealing the role of CD8 T cells in the therapeutic effects of sodium butyrate.
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PMID:Establishment of an orthotopic transplantable gastric cancer animal model for studying the immunological effects of new cancer therapeutic modules. 2073 21

For gastric cancers, the antineoplastic activity of cannabinoids has been investigated in only a few reports and knowledge regarding the mechanisms involved is limited. We have reported previously that treatment of gastric cancer cells with a cannabinoid agonist significantly decreased cell proliferation and induced apoptosis. Here, we evaluated the effects of cannabinoids on various cellular mediators involved in cell cycle arrest in gastric cancer cells. AGS and MKN-1 cell lines were used as human gastric cancer cells and WIN 55,212-2 as a cannabinoid agonist. Cell cycles were analyzed by flow cytometry and western blotting. Treatment with WIN 55,212-2 arrested the cell cycle in the G0/G1 phase. WIN 55,212-2 also upregulated phospho-ERK1/2, induced Kip1/p27 and Cip1/WAF1/p21 expression, decreased cyclin D1 and cyclin E expression, decreased Cdk 2, Cdk 4, and Cdk 6 expression levels, and decreased phospho-Rb and E2F-1 expression. ERK inhibitor decreased the proportion of G0/G1 phase which was induced by WIN 55,212-2. Inhibition of pAKT led to cell cycle arrest in gastric cancer cells. Cell cycle arrest preceded apoptotic response. Thus, this cannabinoid agonist can reduce gastric cancer cell proliferation via G1 phase cell cycle arrest, which is mediated via activation of the MAPK pathway and inhibition of pAKT.
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PMID:Antiproliferative mechanism of a cannabinoid agonist by cell cycle arrest in human gastric cancer cells. 2131 37


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