Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From work done largely on derived cell lines, it has been suggested that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) might be a therapeutic target for many forms of malignancy. However, use of primary tumor cells, including chronic lymphocytic leukemic (CLL) cells, has shown inherent resistance to TRAIL. Although the molecular basis for this resistance remains unknown, treatment with histone deacetylase inhibitors (HDACi) often sensitizes resistant cells to TRAIL-induced apoptosis. We used structurally diverse HDACi to ascertain which HDAC needs to be inhibited for the sensitization. Inhibition of HDAC class I but not class II is required for sensitization to TRAIL-induced apoptosis of CLL cells and various cell lines. Using different HDACi together with small interfering RNA for HDAC1, HDAC2, HDAC3, and HDAC6, we report that inhibition of HDAC1 and HDAC2 but not HDAC3, HDAC6, and HDAC8 are primarily responsible for sensitization to TRAIL-induced apoptosis. Based on these data and our previous studies, we propose that a clinical trial in CLL is warranted using a combination of a selective HDACi that inhibits HDAC1 and/or HDAC2 together with a form of TRAIL that signals through TRAIL receptor 1.
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PMID:Inhibition of histone deacetylase class I but not class II is critical for the sensitization of leukemic cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. 1681 55

Epigenetic modifications are involved in cancer pathogenesis, and HDACis are considered potential therapeutic agents. We and others have shown the inhibitory activity of EGCG on HDAC1. But little is known about the effect of EGCG as on epigenetic regulation in cancer. Here, we try to demonstrate that EGCG acts as an HDACi downregulated APP expression, which was pathophysiologically upregulated in cancers and exerts a key role in cancer cell growth. We used PC-12 cells, SK-N-SH cells and primary tumor tissues for our analysis. Male 4-week-old athymic nude mice were used for heterotopic tumor growth assay. We employed Western blotting analysis to detect Bcl-2, Bax, APP, caspase-3, caspase-7, HDAC1 and H4Ac. We used AnnexinV-FITC and TUNEL staining for apoptosis detection. Tumor tissues were examined by immunohistochemical staining. We demonstrated that EGCG suppresses the growth of xenografted adrenal pheochromocytoma. Flow cytometry analysis and TUNEL staining showed that EGCG induced the apoptosis. Treatment with EGCG resulted in decrease in Bcl-2 but increase in Bax and activated caspase-3 and caspase-7. HDAC inhibitor EGCG leaded to hyperacetylated histone H4 by immunofluorescence. EGCG decreased APP levels by immunofluorescence staining and Western blot analysis. Silencing specific to HDAC1 leaded to caspase-3 and caspase-7 activation and cleavage. Our results are the first to demonstrate a functional interaction between EGCG and APP in suppression tumor growth, and provide a new epigenetic effects of EGCG on antitumor.
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PMID:(-)-Epigallocatechin-3-gallate induces cancer cell apoptosis via acetylation of amyloid precursor protein. 2545 72

YY1 is a DNA-binding transcription factor and reported to be involved in cancer progression. Histone deacetylase inhibitor (HDACi) could inhibit proliferation and promote apoptosis of Hepatocellular carcinoma (HCC) cells. However, it is unclear about the roles of YY1 in the sensitivity of HCC cells to HDACi. In this study, firstly, we identified two drug-response profiles to HDACi in HCC cell lines, while our results showed that HDAC1 expression was positively correlated with YY1 in HCC cell lines and primary tumor tissues. Secondly, YY1 decreased the sensitivity of HCC cells to HDACi in vitro and in vivo. Furthermore, we found that YY1 promoted HDAC1 expression by binding to its promoter, while HDAC1 in turn up-regulated the expression of YY1. In conclusion, our results showed that YY1 could reduce the sensitivity of HCC cells to HDACi and might be a potential therapeutic target in HCC.
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PMID:YY1 promotes HDAC1 expression and decreases sensitivity of hepatocellular carcinoma cells to HDAC inhibitor. 2848 64

Objective To verify the expressions of genes associated with colorectal cancer with hyperglycemia and evaluate their diagnostic values.Methods Tumor tissues,distal normal intestinal mucosa,and peripheral blood samples were harvested from 109 colorectal cancer patients and peripheral blood samples from 30 diabetes patients and 30 healthy volunteers. The mRNA expressions of glucose regulated protein 78 (GRP78),NADPH oxidase-1 (NOX1),carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5),heat shock protein 60 (HSP60),and histone deacetylase 1(HDAC1) were detected by real-time quantitative polymerase chain reaction. The correlation between the gene expressions and clinicopathological parameters in colorectal cancer patients were analyzed using Pearson's correlation analysis. Diagnostic test accuracy evaluation was used to calculate the sensitivity,specificity,accuracy,predictability,Youden index,and likelihood ratio of serum gene expressions in colorectal cancer patients,and the receiver operating characteristic (ROC) curves were drawn. The area under the ROC curve was calculated to evaluate the diagnostic efficiency of the combined detection of multiple genes.Results The mRNA levels of GRP78 (P=0.001),NOX1 (P=0.022),CEACAM5 (P=0.000),HSP60 (P=0.044),and HDAC1 (P=0.047) were positively correlated with the fasting blood glucose level. The mRNA expressions of NOX1 (P=0.000,P=0.008) and HDAC1 (P=0.000,P=0.037) in tissues and serum were significantly higher in colorectal cancer patients than in patients with normal blood glucose levels. The NOX1 mRNA expression was positively correlated with the diameter of colorectal cancer (P=0.013),and the HDAC1 mRNA expression was significantly correlated with the tumor site (P=0.049),depth of primary tumor invasion (P=0.025),and TNM stage (P=0.042). The areas under the ROC curves of NOX1,CEACAM5,and HDAC1 were 0.931,0.852,and 0.860 respectively (all P=0.000). The specificity,accuracy,and negative predictive value of NOX1,HDAC1 mRNA expression in colorectal cancer patients with hyperglycemia were all above 90%. The diagnostic sensitivity and specificity of the combined detection of NOX1,CEACAM5,and HDAC1 were 98.82% and 99.93%,respectively.Conclusion Combined detection of genes associated with colorectal cancer accompanied by hyperglycemia can improve the diagnostic efficiency of early screening.
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PMID:[Validation and Evaluation of Diagnostic Efficiency of Genes Associated with Colorectal Cancer with Hyperglycemia]. 3060 87