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)

Developing an efficient and safe strategy to introduce a therapeutic gene into targeting cells in vivo is a key issue in cancer gene therapy nowadays. Novel non-viral gene carriers, such as nanoparticles, have been shown to be able to deliver DNA into cancer cells efficiently. Suicide gene therapy has been demonstrated to be effective in inhibiting tumor growth, however, the lack of tumor specificity limits its application in clinic. Developing a targeting system for suicide gene is an attractive strategy in cancer gene therapy. In this study, the CMV enhancer and carcinoembryonic antigen (CEA) promoter was fused to a chimeric suicide gene yCDglyTK. This construct was delivered into SGC7901 gastric cancer cells using calcium phosphate nanoparticles (CPNPs). The expression of yCDglyTK in SGC7901 cells was confirmed by RT-PCR and western blot. Immunofluorescence experiments showed that yCDglyTK is only expressed in CEA-positive cancer cells, but not in CEA-negative cells. The expression of yCDglyTK induced cancer cell death following the addition of the prodrug 5-FC, and also elicit "bystander effect" to kill the neighboring cells. Intratumoral injection of CPNP-yCDglyTK complex followed by administration of 5-FC produced marked regression in gastric cancer xenografts. Taken together, our study suggests that the combination of calcium phosphate nanoparticles and suicide gene therapy represents a novel approach for targeting gastric cancer gene therapy.
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PMID:Tissue specific expression of suicide genes delivered by nanoparticles inhibits gastric carcinoma growth. 1722 32

The prediction of peritoneal recurrence in gastric cancer patients is extremely important in preventing an unfavorable prognosis. In this prospective study, we examined the usefulness of the carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) mRNA detection in peritoneal washes as a prophylactic tool for peritoneal recurrence. Peritoneal washes were obtained from 164 patients with gastric carcinoma during a laparotomy. CEA, CK20 and glyceraldehyde-3-phosphate-dehydrogenase mRNA levels in the peritoneal washes were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) using LightCycler. Molecular detection of the CEA and CK20 mRNA in the peritoneal washes by real-time RT-PCR showed a significant correlation with tumor size, histological type, depth of invasion, lymphatic invasion, venous invasion, lymph node metastasis, peritoneal dissemination, stage and cytology. The peritoneal recurrence-free survival and overall survival rates of CEA and CK20 mRNA-positive patients were significantly worse than those of marker gene-negative patients. The CEA and CK20 mRNA levels in the peritoneal washes were a significant independent prognostic factor. In conclusion, our prospective study demonstrates that the detection of CEA and CK20 mRNA by quantitative real-time RT-PCR is a useful tool for identifying patients at high risk of peritoneal recurrence who may need adjuvant chemotherapy.
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PMID:Prospective study of the quantitative carcinoembryonic antigen and cytokeratin 20 mRNA detection in peritoneal washes to predict peritoneal recurrence in gastric carcinoma patients. 1727 49

Combretastatin A4 (CA4) is a drug that targets tumor vasculature to inhibit angiogenesis. Whether CA4 has a direct effect on gastric cancer is not known. We herein investigated the effect of CA4 on growth and metastasis of gastric cancer cells at clinically achievable concentration and explored the associated antitumor mechanisms. Nine human gastric cancer cell lines, including two metastatic gastric cancer cell lines (AGS-GFPM1/2), constitutively expressing green fluorescence protein (GFP) were used. These metastatic AGS-GFPM1/2 cells expressed a higher level of phosphorylated serine 473 on AKT (p-AKT). Our results showed that CA4 (0.02-20 microM) has significant in vitro effects on reducing cell attachment, migration, invasiveness, as well as cell cycle G2/M disturbance on p-AKT-positive gastric cancer cells. In addition, a phosphoinositide 3-kinase inhibitor, LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride], a specific AKT inhibitor, and 0.2 to 20 microM CA4 displayed a similar response profile on p-AKT-positive cells, suggesting that CA4-induced effect was mediated by inhibition of the PI3 kinase/AKT pathway. The results from in vivo GFP monitoring system indicated that CA4 phosphate (CA4-P; 200 mg/kg) significantly inhibited the s.c. and intra-abdominal growth of xenotransplanted AGS-GFPM2 cells in nude mice. Furthermore, CA4-P treatment showed a remarkable ability to inhibit gastric tumor metastasis as well as attenuate p-AKT expression. In conclusion, our study is the first to find that CA4 inhibited AKT activity in human gastric cancer cells. The decreased AKT activity correlated well with the CA4 antitumor growth response and decrease of metastasis. Further investigation on drugs targeting the PI3 kinase-AKT pathway may provide a new approach for the treatment of human gastric cancer.
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PMID:Combretastatin A4-induced differential cytotoxicity and reduced metastatic ability by inhibition of AKT function in human gastric cancer cells. 1764 28

Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lysophospholipid mediators of diverse cellular processes important for cancer progression. S1P is produced by two sphingosine kinases, SphK1 and SphK2. Expression of SphK1 is elevated in many cancers. Here, we report that LPA markedly enhanced SphK1 mRNA and protein in gastric cancer MKN1 cells but had no effect on SphK2. LPA also up-regulated SphK1 expression in other human cancer cells that endogenously express the LPA(1) receptor, such as DLD1 colon cancer cells and MDA-MB-231 breast cancer cells, but not in HT29 colon cancer cells or MDA-MB-453 breast cancer cells, which do not express the LPA(1) receptor. An LPA(1) receptor antagonist or down-regulation of its expression prevented SphK1 and S1P(3) receptor up-regulation by LPA. LPA transactivated the epidermal growth factor receptor (EGFR) in these cells, and the EGFR inhibitor AG1478 attenuated the increased SphK1 and S1P(3) expression induced by LPA. Moreover, down-regulation of SphK1 attenuated LPA-stimulated migration and invasion of MNK1 cells yet had no effect on expression of neovascularizing factors, such as interleukin (IL)-8, IL-6, urokinase-type plasminogen activator (uPA), or uPA receptor induced by LPA. Finally, down-regulation of S1P(3), but not S1P(1), also reduced LPA-stimulated migration and invasion of MKN1 cells. Collectively, our results suggest that SphK1 is a convergence point of multiple cell surface receptors for three different ligands, LPA, EGF, and S1P, which have all been implicated in regulation of motility and invasiveness of cancer cells.
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PMID:Cross-talk between LPA1 and epidermal growth factor receptors mediates up-regulation of sphingosine kinase 1 to promote gastric cancer cell motility and invasion. 1870 80

Paclitaxel(referred to hereinafter as PTX )is used in ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, and endometrial cancer with positive treatment result reports. However, severe allergic reactions such as decreases in blood pressure and impaired breathing occur with relatively high frequency. For the prevention of such allergic reactions, administration of a premedication composed of the three components, dexamethasone sodium phosphate injection, diphenhydramine hydrochloride tablet, and ranitidine hydrochloride injection solution(or injectable famodine), is advised in the appended documentation. Administration is difficult because, among these three components, only diphenhydramine hydrochloride is administered orally and thus must be provided through the internal medicine department. Particularly when this combined dosage is administered as outpatient chemotherapy, the doctor must prescribe diphenhydramine hydrochloride tablets, and the patient must not forget to bring them on the day in which chemotherapy is administered. Also, checks by the medical staff such as pharmacists and nurses are required, complicating the administration of this therapy further. Taking this situation into consideration, our hospital uses a short-time premedication method wherein d-Chlorpheniramine Maleate injections are substituted for diphenhydramine hydrochloride tablets, and the time required for premedication is reduced to 15 minutes. This study investigated the allergic reaction ratio to consider the safety and usefulness of the short-time premedication method used at our hospital. The chemotherapy regimens conducted for the subject patients were 9 cases of PTX+CBDCA, 6 cases of biweekly- PTX, and 5 cases of weekly-PTX. A total of 67 PTX injections were given, 15 of them being first-time administrations. The ratio of allergic/hypersensitivity reactions was 10.0%(2 cases in 20). The short-time premedication method using d-Chlorpheniramine Maleate injections did not display a significant difference from the conventional method used for prevention of allergic and hypersensitivity reactions. Also, since this method of medication proves useful for is easy for the patient, reduces treatment time, is safe, economical, and helps reduce the workload of doctors, pharmacists, and nurses.
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PMID:[Evaluation of short-time premedication with d-chlorpheniramine maleate injection for paclitaxel-induced hypersensitivity reaction]. 1870 46

Most cancer cells predominantly produce energy by glycolysis rather than oxidative phosphorylation via the tricarboxylic acid (TCA) cycle, even in the presence of an adequate oxygen supply (Warburg effect). However, little has been reported regarding the direct measurements of global metabolites in clinical tumor tissues. Here, we applied capillary electrophoresis time-of-flight mass spectrometry, which enables comprehensive and quantitative analysis of charged metabolites, to simultaneously measure their levels in tumor and grossly normal tissues obtained from 16 colon and 12 stomach cancer patients. Quantification of 94 metabolites in colon and 95 metabolites in stomach involved in glycolysis, the pentose phosphate pathway, the TCA and urea cycles, and amino acid and nucleotide metabolisms resulted in the identification of several cancer-specific metabolic traits. Extremely low glucose and high lactate and glycolytic intermediate concentrations were found in both colon and stomach tumor tissues, which indicated enhanced glycolysis and thus confirmed the Warburg effect. Significant accumulation of all amino acids except glutamine in the tumors implied autophagic degradation of proteins and active glutamine breakdown for energy production, i.e., glutaminolysis. In addition, significant organ-specific differences were found in the levels of TCA cycle intermediates, which reflected the dependency of each tissue on aerobic respiration according to oxygen availability. The results uncovered unexpectedly poor nutritional conditions in the actual tumor microenvironment and showed that capillary electrophoresis coupled to mass spectrometry-based metabolomics, which is capable of quantifying the levels of energy metabolites in tissues, could be a powerful tool for the development of novel anticancer agents that target cancer-specific metabolism.
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PMID:Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. 1945 66

Phosphatidylinositol-4-phosphate 5-kinase-like 1 (PIP5KL1), the forth member of phosphatidylinositol-4-phosphate 5-kinases (PIPKs) type I, acts as a scaffold for localization and activation of PIPKs, which mediates numerous cellular processes. However, the role of PIP5KL1 in the development of human cancer is still lacking. We therefore examined the expression of PIP5KL1 in human normal and cancer tissues by tissue microarrays (TMAs). Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence imaging analysis were used to testify the mRNA and protein levels of PIP5KL1 in human gastric cancer cell line (BGC823). The cell proliferation was investigated with 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay. Both wound healing and transwell migration assay were performed to study the cell migration. The phosphorylation of v-akt murine thymoma viral oncogene homolog 1 (AKT1) was determined by western immunoblot analysis. Immunostaining of gastric cancer tissue microarrays revealed a negative correlation between PIP5KL1 overexpression and gastric cancer in situ. Transient transfection PIP5KL1 induced a significant increase expression at both transcriptional and translational levels and consequent robust inhibition of proliferation (P < 0.05) and migration (P < 0.05) of BGC823 cells. Overexpression of PIP5KL1 markedly inhibited (P < 0.05) serum-induced phosphorylation of AKT1. Taken together, these studies indicate a functional negative correlation between elevated levels of PIP5KL1 and the development of human gastric cancer, suggesting that PIP5KL1 overexpression may suppress gastric cancer formation.
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PMID:Overexpression of PIP5KL1 suppresses cell proliferation and migration in human gastric cancer cells. 1968 Jul 87

The present study is the first to evaluate the expression and activity of MnSOD, Cu/ZnSOD and catalase in human gastric samples, since ROS play a significant role in the pathogenesis of different forms of malignancy inducing mutations and various diseases such as gastric cancer. Biopsies and surgical samples from 53 patients (male/female 22/31, mean age 56.5+/-15.8 years) consisted of 15 healthy, 12 autoimmune atrophic gastritis, 10 Helicobacter pylori (HP) infection, 8 HP-negative chronic gastritis (CG) and 8 adenocarcinoma cases. Enzyme activity and expression were evaluated by spectrophotometry and immunoblotting after specific extraction in phosphate buffer. We found that MnSOD activity was increased in adenocarcinoma, CG and HP tissues (p<0.05-0.001), while Cu/ZnSOD was significantly lower in adenocarcinoma and HP tissues (p<0.001) when compared to the healthy control. MnSOD and Cu/ZnSOD were expressed to a significantly higher degree in adenocarcinoma and HP tissues (p<0.05 and <0.001 respectively) and to a significantly lower degree in CG tissues with respect to the healthy patients (p<0.05 and <0.001). A significant decrease in CAT activity in adenocarcinoma and HP tissues was observed (p<0.01 and <0.05). Gastric human neoplasms showed significant changes in antioxidant enzymes, that represent the first line in antioxidant protection against radical attack. The difficulties in correlating the antioxidant enzyme with the neoplasms was related to the complexity of the biochemical pathways that regulate the cellular redox balance. Our results are important in enhancing the understanding of the role that these enzymes play in the promotion/suppression of the carcinogenesis cascade in human gastric mucosa.
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PMID:Implications of antioxidant enzymes in human gastric neoplasms. 1978 4

B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk.
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PMID:Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition. 2005 20

Tumorigenesis requires energy production via aerobic glycolysis (Warburg effect) in malignant tumors. Recent research has demonstrated that the pentose phosphate pathway (PPP) is augmented in some tumors, especially the non-oxidative part of the PPP which is controlled by transketolase (TKT) enzyme reactions. One TKT isoform, transketolase-like protein 1 (TKTL1), is specifically upregulated in different human cancers, and its overexpression predicts poor patient survival. To further define the function of in malignant progression, we employed the small interference RNA (siRNA) technique to knockdown gene expression of TKTL1 in the gastric cancer cell line AGS. We used TKTL1 siRNA to observe the effect of reduced TKTL1 expression on gastric cancer tumorigenesis in a nude mice xenograft model and on proliferation in vitro. Our results showed that the expression of double stranded RNA led to the efficient and specific inhibition of endogenous TKTL1 expression in AGS cells. In addition, the TKT activity was significantly deceased in the TKTL1 siRNA-treated AGS cells. TKTL1 suppression resulted in delayed cell proliferation in vitro. Furthermore, loss of TKTL1 inhibited the growth of AGS tumor xenografts. Altogether, our findings indicate that the specific inhibition of TKTL1 may be important therapeutically.
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PMID:Silencing of TKTL1 by siRNA inhibits proliferation of human gastric cancer cells in vitro and in vivo. 2020 Apr 85


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