UMLS:C0024623 - FACTA Search

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Query: UMLS:C0024623 (gastric cancer)
36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiologic study has shown the association of nitrosamide compounds with the high incidence of stomach cancer in south China. To study the mechanism of gastric carcinogenesis, we have established an immortalized human gastric epithelial cell line GES-1. GES-1 cells and the normal gastric tissues were treated with different concentrations of MNNG for 24 hours. Point mutation at codon 12 of c-Ha-ras gene was found in cells and tissues (43%) as demonstrated by PCR-RFLP. Rearrangement of c-met gene and amplification of c-erbB2 gene were detected by Southern blot assay on the MNNG treated GES-1 cells. The results indicate that MNNG treatment was intimately associated with the activation of certain oncogenes. H-ras and c-met genes, serving as early targets of carcinogens may play important role in the carcinogenesis of human gastric epithelial cells.
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PMID:[Activation of proto-oncogenes induced by MNNG on primary culture of human gastric epithelium and immortalized human gastric epithelial cell line]. 873 1

Ataxia telangiectasia mutated (ATM) is the gene mutated in the genetic disorder ataxia telangiectasia (AT), the symptoms of which include sensitivity to radiation and an increased risk of cancer. ATM is a kinase involved in activating the appropriate damage-response pathway, leading to either cell-cycle arrest or apoptosis, and is therefore a key checkpoint molecule in regulating cell-cycle response to DNA damage and responsible for maintenance of genome integrity. However, little is known about the association of ATM mutations with human gastric cancer (HGC). In order to determine the mutation and mRNA expression changes of the ATM gene in HGC, we performed analyses by denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and RT-PCR technique on 13 human gastric tumor cell lines and 30 cases of fresh tumor specimens matched normal tissue. We compared the potential effect of the ATM gene mutation and cell behavior including cell-cycle arrest and induction of apoptosis in the tumor cell lines MGC803 and BGC823 with and without ionizing radiation (IR) exposure. Our data show that frequent variations were observed at 10 exons and 2 cDNA fragments which covered 8 other exons of the ATM gene as 5 out of 13 on the cell lines (38.5%) and 2 out of 30 cases in the tissue specimens (6.7%). All point mutations were confirmed as base substitutions (5982T-C; 6620A-G; 8684G-G/A; 9389C-G) and deletions (1079delC) by use of DNA sequencing. Among the mutations, one was reported previously in breast cancer, the other five have not yet been reported. The expression of ATM was significantly lower in five cell lines (MGC803; MKN45; SGC7901; GES and SUN-1) than in two others (BGC823 and RF48). G2/M cell-cycle arrest and apoptosis were observed in ATM-deficient MGC803 cells challenged with IR. A transient up-regulation of p53 occurred 1h post-IR in BGC823 cells but not in MGC803 cells. Our findings suggest that ATM mutations might be a pathogenic factor for an increased risk of gastric cancer, and the dysfunction of ATM may lead to a hypersensitivity to ionizing radiation in gastric cancer cells, possibly by a p53-dependent pathway.
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PMID:Alteration of the ATM gene occurs in gastric cancer cell lines and primary tumors associated with cellular response to DNA damage. 1470 17

Rho GTPases were previously shown to have an important role in cancer development and progression, including cell transformation, proliferation, invasion, metastasis, and angiogenesis. However, there is still little information available on the clinical significance of Rho GTPases expression in human cancer specimens. In the present study, we systemically investigated the mRNA expression levels of seven main members RhoA, RhoB, RhoC, Rac1, Rac2, Rac3, and Cdc42 of Rho family using semi-quantitative reverse transcription-PCR in 53 patients with gastric carcinoma and 7 gastric cancer cell lines. The total and activities of RhoA, Rac1 and Cdc42 in 5 gastric cancer cell lines were also examined. The mean mRNA expression levels of RhoA and Rac1 in gastric cancer tissue specimens were significantly higher than those in the adjacent non-tumorous tissue specimens (p < 0.01). The higher expression of RhoA was significantly correlated with higher TNM stage (p < 0.05) as well as with pooly differentiated histological type (p < 0.05) of gastric carcinoma. The increased expression of Rac1 was related to higher TNM stages of gastric carcinoma (p < 0.05). The expression levels of mRNA, total protein and activities of RhoA and Rac1 in 7 gastric cancer cell lines were all higher than that in gastric mucosal epithelial cell line GES-1. These findings indicate that RhoA and Rac1 may play important roles in the carcinogenesis and progression of gastric carcinoma.
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PMID:Expression of seven main Rho family members in gastric carcinoma. 1497 55

Zinc ribbon domain-containing 1 (ZNRD1), a transcription-associated gene, was recently found to be downregulated in human gastric cancer tissues as compared to the matched adjacent nonneoplastic tissues. In this study, we constructed the siRNA eukaryotic expression vectors of ZNRD1 and transfected them into normal gastric epithelial cells (GES-1). We also introduced the ZNRD1 gene into gastric cancer cells that do (SGC7901) and do not (AGS) express ZNRD1 endogenously. GES-1 cells stably transfected with the ZNRD1-RNAi were found to exhibit significantly quicker proliferation than empty vector transfectants. AGS cells stably transfected with the ZNRD1 cDNA exhibited significantly decreased growth rate as compared to control vector transfectants, whereas SGC7901 cells did not. Furthermore, ZNRD1 suppresses growth of AGS cells in soft agar and tumor formation in athymic nude mice. This study clearly demonstrates that ZNRD1 may play an important role in the control of human gastric cancer development by regulating cell proliferation. These results provide new insights into the function of ZNRD1 and further validate ZNRD1 as a potential therapeutic target in gastric cancer.
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PMID:Suppression of the cell proliferation in stomach cancer cells by the ZNRD1 gene. 1535 50

The Runx3 gene is a member of the runt domain family transcription factors, key regulators of development and differentiation in metazoan. Recently, Runx3 was identified as a tumor suppressor gene. Loss of Runx3 was found to be associated with genesis and progression of gastric cancer. In this study, we transfected the gastric cancer cell line SGC7901 with eukaryotic expression vector of Runx3. In vitro drug sensitivity assay suggested that SGC7901/Runx3 cells were more sensitive to various chemotherapeutic drugs. Blocking Runx3 expression in immortalized stomach mucosal cells (GES-1) or gastric cancer cells (SGC7901) by Runx3-specific small interfering RNA conferred the cells resistance to chemotherapeutic drugs. Flow cytometry examination suggested that expression of Runx3 in gastric cancer cells increased the intracellular accumulation and retention of adriamycin. Semiquantitative RT-PCR and Western blot suggested that Runx3 downregulated expression of Bcl-2, MDR-1 (P-gp) and MRP-1. Binding of Runx3 to promoter sequences of Bcl-2, MDR-1 and MRP-1 gene was detected by eletrophoretic mobility shift assay (EMSA) and supershift EMSA. We cloned the MDR-1 and MRP-1 gene promoters containing Runx binding sites and constructed the luciferase reporter vectors of these 2 promoters. Luciferase reporter assay suggested that Runx3 inhibited the promoter activity of the MDR-1 and MRP-1 promoter in SGC7901 cells. Taken together, our findings suggested that overexpression of Runx3 could sensitize gastric cancer cells to chemotherapeutic drugs by downregulating the Bcl-2, MDR-1 and MRP-1.
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PMID:Tumor suppressor gene Runx3 sensitizes gastric cancer cells to chemotherapeutic drugs by downregulating Bcl-2, MDR-1 and MRP-1. 1575 76

Voltage-gated potassium (Kv) channels have been reported to be involved in the proliferation of many types of cells, including tumor cells. The overexpression of the Kv channels and related channel activity are involved in the neoplastic process. Our previous study has shown the existence of delayed rectifier potassium (I(K)) current in gastric cancer cells SGC7901. However, the expression and function of most delayed rectifier potassium (K(D)) channel subunits in gastric cancer cells are not completely resolved. Here we examine expression of K(D) channel subunits in Kv1-Kv3 families in immortalized gastric epithelial cells GES and various gastric cancer cells (including AGS, KATOIII, MKN28, MKN45, MGC803, SGC7901, SGC7901/ADR and SGC7901/VCR), and their roles in cell proliferation. RT-PCR analysis reveals that all cell lines examined express Kv1.3, Kv1.5, Kv1.6, Kv2.1 and Kv2.2. However, Kv1.2 and Kv3.2 genes are barely detectable in any given cancer cell lines. Kv1.5 protein, high mRNA levels in all cell lines examined, is also expressed in some cancer cells lines and more frequently detected in gastric cancer tissues. Downregulation of the expression of Kv1.5 in SGC7901 with RNA interference significantly inhibited the proliferation and tumorigenicity of SGC7901 cells. Moreover, in Ca(2+)-containing rather than Ca(2+)-free medium, KCl (50mM) stimulated a rapid increase in the concentration of cytosolic calcium in empty vector transfected cells that was blocked by verapamil. Likewise, decrease the expression of Kv1.5 with short interfering RNA also blocked the depolarization-induced influx of Ca(2+). This finding suggests that more than one kind of K(D) channel subunits are expressed in various gastric cancer cell lines. Kv1.5 may be involved in tumor cells proliferation by controlling Ca(2+) entry, and the interference of K(D) channels expression and/or activity could provide a novel strategy to reverse the malignant phenotype of gastric cancer cells.
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PMID:Expression of delayed rectifier potassium channels and their possible roles in proliferation of human gastric cancer cells. 1625 62

Antiangiogenesis therapy has become a hot field in cancer research. Blood vessels of tumor carry specific markers that are usually related to angiogenesis. Study of these heterogeneous molecules in different tumor vessels may be beneficial for promoting antiangiogenic therapy. In this study, we established an in vitro co-culture model of human umbilical vein endothelial cells (HUVECs) and gastric adenocarcinoma cell line SGC7901, screened the peptides binding specifically to the HUVECs co-cultured with gastric cancer cells (Co-HUVECs) using phage display peptides library, and studied the affinity of these peptides to gastric cancer vascular endothelial cells. After four rounds of panning, there was an obvious enrichment for the phages specifically binding to the Co-HUVECs, and the output/input ratio of Co-HUVECs increased about 590-fold (from 0.95x10(-7) to 561.25x10(-7)). Five phage clones (M6, M3, M9, IN12, IN11), which could strongly bind to Co-HUVECs instead of wild-type HUVECs, were characterized by ELISA. In vitro cellular binding assay showed that phage IN11 preferably bound to Co-HUVECs rather than control HUVECs, and the number of the phage IN11 recovered from Co-HUVECs was 5.7- and 16.9-folds, respectively, as much as those from control HUVECs and GES cells. Immunocytochemical and immunohistochemical staining confirmed that phage IN11 could specifically bind to Co-HUVECs as well as vascular endothelial cells in gastric cancer tissue sections. Competitive and inhibitory assay revealed the synthetic peptide GEBP11 (CTKNSYLMC) displayed on phage IN11 could competitively inhibit binding of the phage IN11 to Co-HUVECs. Immunofluorescence microscopy showed that the fluorescence-labeled peptide GEBP11 was located at the membrane and perinuclear cytoplasm of Co-HUVECs. Meanwhile, GEBP11 was found to be able to target the gastric cancer vascular endothelial cells. Therefore, GEBP11 may be a potential candidate for targeted drug delivery in antivascular therapy and diagnosis of gastric cancer.
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PMID:Screening and identification of vascular-endothelial-cell-specific binding peptide in gastric cancer. 1676 42

Upregulated gene 4 (URG4), a novel gene located on 7 chromosome (7p13), was found to contribute to hepatocarcinogenesis. However, the role of URG4 in the gastric carcinogenesis still remains unclear. In the present study, URG4 was found by immunohistochemistry to be upregulated in human gastric cancer tissues compared with matched adjacent nonneoplastic tissues. The proliferating cell nuclear antigen index is higher in gastric cancer tissues with high URG4 expression than in those with low URG4 expression. The growth of GES-1 cells, which are immortalized human gastric epithelial mucosa cells with baseline URG4 expression, was accelerated by URG4 induction. Downregulation of URG4 through URG4 small interfering RNA (siRNA) in SGC7901 and MKN28 cells, which had high endogenous URG4 expression, suppressed cell proliferation in both of these cells. URG4-siRNA also inhibited the proliferation of SGC7901 and MKN28 cells in soft agar and tumor formation in nude mice. Overexpression of URG4 in GES cells upregulated cyclin D1, whereas repression of URG4 in SGC7901 and MKN28 cells downregulated cyclin D1. The data suggested that URG4 played an important role in the development of human gastric cancer by regulating the expression of cyclin D1 and might be used as a potential therapeutic target for gastric cancer.
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PMID:Enhanced cell survival of gastric cancer cells by a novel gene URG4. 1721 16

Rho family members are known to regulate malignant transformation and motility of cancer cells, but the clinicopathological significance of RhoC remains unclear yet in the case of gastric cancer. In this study, we evaluated the protein expression level of RhoC in gastric cancer tissues and cell lines. Results showed that only weak staining of RhoC was detected in 3 of 33 non-tumorous cases by immunohistochemistry. The expression of RhoC was significantly higher in gastric cancer tissues (23/42, 54.8%) than in non-tumorous tissues (p < 0.01). Further analysis demonstrated that RhoC had high specificity (80.0%) in detecting gastric carcinomas with metastatic potential. RhoC was positively expressed in 18 out of 20 metastases (90.0%), even higher than that in primary gastric cancer tissues. Western blot showed that RhoC was up-regulated in five different gastric cancer cell lines but not expressed in SV40-transformed immortal gastric epithelial cell GES-1. Overexpression of RhoC GTPase in GES-1 cells could produce the motile and invasive phenotype but did not alter the monolayer growth rate. To further study the functions of RhoC, we took the powerful siRNA technology to knock down the expression of RhoC in SGC7901 cells. It was shown that down-regulation of RhoC did not affect the proliferation of SGC7901 cells. However, interference of RhoC expression could inhibit migration, invasion, and anchorage-independent growth of SGC7901 cells. In conclusion, RhoC may play a very important role in the metastasis of gastric carcinoma. Therapeutic strategies targeting RhoC and RhoC-mediated pathways may be a novel approach for treating metastasis of gastric cancer.
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PMID:RhoC is essential for the metastasis of gastric cancer. 1754 41

Abelson interactor protein-1 (ABI1) is a promising candidate tumor suppressor, and plays critical roles both in the pathogenesis of BCR-Abl-induced leukemia and in the spread of several solid tumors. The expression of ABI1 and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors, including gastric cancer. In this study, we analyzed the correlation between ABI1 expression and the clinicopathological characteristics, tumor progression, and prognosis of patients with gastric carcinoma. Tissue specimens were from 103 gastric cancer patients who underwent gastrectomy in our hospital between January 2000 and December 2007. Among them 59 tumor tissue samples were matched with normal tissue samples. The expression of ABI1 protein was measured using immunohistochemical staining of paraffin-embedded tissue specimens. Meanwhile, quantitative real-time RT-PCR and Western blotting were used to identify the expression of ABI1 in human gastric normal mucosal cell line (GES-1) and gastric cancer cell lines (N87, AGS). We performed a statistical analysis of the potential correlation between ABI1 expression and the patients' clinicopathological characteristics, 5-year survival, and median survival time. The immunohistochemical staining results of 59 patients showed that ABI1 was expressed in 28.8% (17/59) of gastric cancer tissues, compared to 91.5% (54/59) of normal samples. ABI1 expression in 103 patients was strongly correlated with tumor differentiation, clinical stage, and lymph node status (P < 0.01). The 5-year survival rate was 15.3% in the ABI1-negative group and 63.7% in the ABI1-positive group. Median survival time in the ABI1-negative and ABI1-positive groups was 25.0 months (95% CI: 19.7-30.3) and 74.0 months (95% CI: 54.6-93.3), respectively. There was a significant difference between the two groups (chi(2) = 10.888, P = 0.001). Furthermore, we found that ABI1 expressed lowly in poor differentiated AGS, whereas highly in GES-1 and well-differentiated N87. Downregulation of ABI1 expression in human gastric carcinoma may play a critical role in tumor progression and in determining patient prognosis. ABI1 may be a useful diagnostic or prognostic molecular biomarker, and might be a potential target for therapeutic intervention.
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PMID:Downregulation of ABI1 expression affects the progression and prognosis of human gastric carcinoma. 1955 84

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