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)

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

Recently, the detection of occult cancer cells in peripheral blood has received a great deal of attention regarding the prediction of postoperative cancer recurrence and for novel strategies of adjuvant therapy. The aim of this study was to establish a new molecular diagnostic method of detecting circulating tumor cells. Gastric cancer SGC-7901 cells in 2 ml blood from healthy volunteers were serially diluted. Additional peripheral blood samples were collected from 90 patients and 27 healthy volunteers. Real-time reverse transcription-polymerase chain reaction was used to detect the levels of microRNA-106a (miR-106a) and microRNA-17 (miR-17). Receiver operating characteristics (ROC) curves were constructed. In recovery experiments, a significant correlation between the number of cancer cells and the levels of both miR-106a (r = -0.906, p = 0.037) and miR-17 (r = -0.912, p = 0.031) was found. In preoperative and postoperative patient groups, miR-106a and miR-17 levels were significantly higher than those in controls. The areas under the ROC curve for miR-106a, miR-17, and combination were 0.684 (p = 0.0066), 0.743 (p = 0.0001), and 0.741 (p = 0.0002), respectively. Our results indicate that the detection of miRNA in peripheral blood may be a novel tool for monitoring circulating tumor cells in patients with gastric cancers.
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PMID:Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using microRNA as a marker. 2034 19

The practical application of genistein as a low toxicity chemotherapeutic drug is hindered by many of its in vivo properties. To overcome these obstacles, a new multifunctional drug delivery system is developed, which is based on covalently attaching genistein onto Fe3O4 nanoparticles coated by cross-linked carboxymethylated chitosan (CMCH). The structure of the Fe3O4-CMCH-genistein nano-conjugate was confirmed by transmission electron micrographs (TEM), X-ray diffraction (XRD) and Fourier-transfer infrared (FT-IR) spectroscopy. The nano-conjugate shows good water solubility and superparamagnetic properties with a saturation magnetization of 55.1 emu/g. The effects of free genistein and FeO4-CMCH-genistein nano-conjugate on the proliferation and apoptosis of gastric cancer cell line SGC-7901 were investigated by MTT assay and flow cytometry (FACS). MTT results indicate that the Fe3O4-CMCH-genistein nano-conjugate exhibits a significantly enhanced inhibition effect to the SGC-7901 cancer cells than the free genistein. FACS data suggests that the inhibition on cell proliferation of the nano-conjugate is related with an induced apoptosis process. This drug delivery system is promising for future multifunctional chemotherapeutic application that combines drug release and magnetic hyperthermia therapy.
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PMID:Improving the anti-tumor effect of genistein with a biocompatible superparamagnetic drug delivery system. 2035 29

We sought to investigate the efficacy of arsenic trioxide (As(2)O(3)) against a human gastric cell line implanted in nude mice in vivo, as well as the mechanism involved. The solid tumor model was created in nude mice with the gastric cancer cell line SGC-7901. The animals were randomly divided into three groups. As(2)O(3) was injected into animals in two arsenic-treated groups (2.5 mg/kg and 5 mg/kg), and the same volume of saline solution was injected into the control group. The inhibitory effect was observed in every group. Apoptotic cells and apoptotic bodies were observed by transmission electron microscope; the fraction of apoptotic cells was detected by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) under laser confocal technology. The expression of Fas and FasL was detected by immunohistochemical staining. In nude mice, after treatment with 5 mg/kg and 2.5 mg/kg As(2)O(3), approximately 50% and 30% tumor growth inhibition were observed, respectively (P < 0.05 for both treatment groups). Increase in apoptotic cells and apoptotic bodies appeared in As(2)O(3)-treated tumors compared with the control group. The fluorescence intensity levels of apoptotic cells in tumor were significantly higher in the arsenic-treated groups (P < 0.05 for both treatment groups). The fluorescence intensity level of apoptotic cells in the 5-mg/kg group was higher than that in the 2.5-mg/kg group (P < 0.05). The expression of Fas protein increased in dose- and time-dependent manner after the treatment with As(2)O(3), but that of FasL protein showed no significant difference between control and treated groups. As(2)O(3) did not induce hepatic and renal system injury in the nude mice. As(2)O(3) can inhibit the growth of human gastric cell implanted tumor. We ascribe this to upregulation of Fas, which can induce apoptosis of gastric cells.
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PMID:Antitumor effect and mechanisms of arsenic trioxide on subcutaneously implanted human gastric cancer in nude mice. 2036 23

Vitamin E succinate (RRR-alpha-tocopheryl succinate, VES), an efficient inducer of apoptosis, acts as a potent agent for cancer therapy. However, the mechanism by which VES mediates the effects are not yet fully understood. Here we studied the effect of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) on VES-induced apoptosis of SGC-7901 human gastric cancer cells. VES caused cytological changes typical of apoptosis, increased ER dilation and cytosolic Ca(2+) concentration. And endogenous ER stress markers, GRP78 and GRP94 were transcriptionally and translationally altered. In response to VES, induction of CHOP, activation of caspase-4 and JNK were observed. Furthermore, VES also triggered activation of UPR components, including RNA-dependent protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 6 (ATF6), X-box-binding protein 1 (XBP1), and ATF4 in a concentration- and time-dependent manner. Consequently, our results suggest that VES-induced apoptosis is coupled to ER stress and UPR activation in SGC-7901 human gastric cancer cells.
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PMID:Endoplasmic reticulum stress contributes to vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells. 2043 8

The IRX1 tumor suppressor gene is located on 5p15.33, a cancer susceptibility locus. Loss of heterozygosity of 5p15.33 in gastric cancer was identified in our previous work. In this study, we analyzed the molecular features and function of IRX1. We found that IRX1 expression was lost or reduced in gastric cancer. However, no mutations were identified in IRX1-encoding regions. IRX1 transcription was suppressed by hypermethylation, and the expression of IRX1 mRNA was partially restored in gastric cancer cells after 5-Aza-dC treatment. Restoring IRX1 expression in SGC-7901 and NCI-N87 gastric cancer cells inhibited growth, invasion and tumorigenesis in vitro and in vivo. We identified a number of target genes by global microarray analysis after IRX1 transfection combined with real-time PCR and chromatin immunoprecipitation assay. BDKRB2, an angiogenesis-related gene, HIST2H2BE and FGF7, cell proliferation and invasion-related genes, were identified as direct IRX1 target genes. The hypermethylation of IRX1 was not only detected in primary gastric cancer tissues but also in the peripheral blood of gastric cancer patients, suggesting IRX1 could potentially serve as a biomarker for gastric cancer.
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PMID:Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma. 2044 Feb 64

Hypoxia is a common characteristic feature of solid tumors, and carcinoma cells are known to secrete many growth factors. These growth factors, such as vascular endothelial growth factor (VEGF), play a major role in the regulation of tumor angiogenesis and metastasis. In this study, the effect of gamma-tocotrienol, a natural product commonly found in palm oil and rice bran, on the accumulation of HIF-1alpha protein and the paracrine secretion of VEGF in human gastric adenocarcinoma SGC-7901 cell line induced by cobalt(II) chloride (as a hypoxia mimic) was investigated. These results showed that cobalt(II) chloride induced the high expression of VEGF in SGC-7901 cells at dose of 150 micromol/L for 24h. Both basal level and cobalt(II) chloride-induced HIF-1alpha protein accumulation and VEGF paracrine secretion were inhibited in SGC-7901 cells treated with gamma-tocotrienol at 60 micromol/L treatment for 24 h. U0126, a MEK1/2 inhibitor, decreased the expression of HIF-1alpha protein and the paracrine secretion of VEGF under normoxic and hypoxic conditions. In this study, gamma-tocotrienol also significantly inhibited the hypoxia-stimulated expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2). The mechanism seems to involve in inhibiting hypoxia-mediated activation of p-ERK1/2, it leads to a marked decrease in hypoxia-induced HIF-1alpha protein accumulation and VEGF secretion. These data suggest that HIF-1alpha/VEGF could be a promising target for gamma-tocotrienol in an effective method of chemoprevention and chemotherapy in human gastric cancer.
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PMID:gamma-Tocotrienol modulates the paracrine secretion of VEGF induced by cobalt(II) chloride via ERK signaling pathway in gastric adenocarcinoma SGC-7901 cell line. 2045 89

Gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), as a novel IFN-beta/RA-inducible gene product, was identified as a potential tumor suppressor associated with growth inhibition and cell apoptosis. Recently, it has been reported that the apoptotic effects and apoptosis-related gene induction of GRIM-19 can be attenuated by GW112, indicating that GRIM-19 and GW112 are involved in a common signal transduction pathway. To investigate the signaling mechanisms that link GRIM-19 to GW112 and their functional role in tumor cell invasion and metastasis, we utilized adenovirus-mediated overexpression of GRIM-19 in the gastric cancer SGC-7901 cell line. We observed that enhanced expression of GRIM-19 not only downregulated GW112 but also decreased NF-small ka, CyrillicB binding activity. As a result, we found that tumor cell adhesion, migration, invasion and liver metastasis were inhibited. Additionally, upregulation of GRIM-19 also suppressed secretion of urokinase-type plasminogen activator (u-PA), matrix metalloproteinase (MMP)-2, 9 and vascular endothelial growth factor (VEGF). These results indicate that GRIM-19 acts as an upstream regulator of GW112 to block NF-small ka, CyrillicB binding activity, thereby inhibiting gastric cancer cell migration, invasion and metastasis. We conclude that adenoviral transfer of the GRIM-19 gene may be an efficacious approach to controlling the invasion and metastasis of human gastric cancer.
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PMID:Upregulation of the GRIM-19 gene suppresses invasion and metastasis of human gastric cancer SGC-7901 cell line. 2047 5

Lactoferrin, a protein from bovine milk belonging to the transferring family proteins, contains 2 bound Fe(+3) ions. Recent research has revealed that lactoferrin exhibits not only antimicrobial activity by its high affinity for Fe(+3) but also remarkable anticancer capacity in cancer cell lines. Meanwhile, increasing evidence suggests that aberrant activation of Akt is involved in both normal cells and human cancers and that inhibition of Akt signaling pathway might be a promising strategy for cancer treatment. In the present study, we investigated the effect of the antitumor induced by exposing stomach cancer cell SGC-7901 to lactoferrin for 24 and 48 h. The cell viability was assessed by 3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-di-phenytetrazoliumromide (MTT) assay and apoptosis was quantified by propidium iodide uptake and Annexin V-fluorescein isothiocyanate fluorescent probe label through flow cytometry. Our investigation indicates that inhibitory ratio of 50 microM lactoferrin for proliferation of stomach cancer cell SGC-7901 is much higher than 12.5 and 25 microM, and for the extended treatment time, the concentration of 50 microM has more efficiency than 100 microM lactoferrin. To elucidate a mechanism involved in its antitumor effect, we studied the Akt cell signaling pathway of SGC-7901 while treated by 50 microM of lactoferrin after 0, 24, and 48 h, particularly Akt phosphorylation of 2 individual residues, Ser473 and Thr308, Akt/glycogen synthase kinase-3beta, forkhead in human rhabdomyosarcoma, and nuclear factor-kappaB proteins, respectively, activated by Western blot. The expressions of Akt, phosphorylated Akt Ser473, phosphorylated Akt Thr308, phosphorylated nuclear factor-kappa b p65 Ser536, and Bcl-2 significantly decreased; however, the expressions of phosphorylated glycogen synthase kinase-3beta Ser9, phosphorylated forkhead in human rhabdomyosarcoma Ser256, and phosphorylated caspase-9 Ser196 increased in response to lactoferrin treatment in SGC-7901. These results suggest that lactoferrin inhibits Akt activation and modulates its downstream proteins phosphorylation in apoptosis of SGC-7901 human stomach cancer cells.
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PMID:Apoptosis of stomach cancer cell SGC-7901 and regulation of Akt signaling way induced by bovine lactoferrin. 2049 39

Deregulation of E2F1 activity is characteristic of gastric tumorigenesis, which involves in complex molecular mechanisms. microRNA is one of the post-transcriptional regulators for gene expression. Here, we report a member of miR-331 family, miR-331-3p, which was decreased in some kinds of malignancies. However, the biological function of miR-331-3p on gastric cancer is largely unknown. In this study, we screened the expressing levels of miR-331-3p and E2F1 in gastric cancer cell lines. We transfected precursor or inhibitor of miR-331-3p into gastric cancer cells. As results, miR-331-3p is down-regulated in all gastric cancer cell lines by real-time PCR. Over-expression of miR-331-3p blocked G1/S transition on SGC-7901 and AGS cell lines. Introduction of miR-331-3p dramatically suppressed the ability of colony formation and cell growth in vitro by interfering E2F1 activity. Our data highlight an important role of miR-331-3p in cell cycle control by targeting 3'-UTR of cell cycle-related molecule E2F1. We concluded that miR-331-3p is a potential tumor suppressor in gastric cancer. Restoring miR-331-3p in gastric cancer cells revealed potential application in gastric cancer therapy.
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PMID:miRNA-331-3p directly targets E2F1 and induces growth arrest in human gastric cancer. 2051 Jan 61


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