Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytotoxicity of gamma-hexachlorcyclohexane (gamma-HCC) was evaluated in HL-60 cells. Gamma-HCC dose-dependently induced cytotoxicity of HL-60 with an IC50 value of 60+/-5 microM. The gamma-HCC treated cells showed some characteristic changes of apoptosis, including blebbing of the membrane, condensation of the nuclear chromatin, vacuolation of cytoplasm and internucleosomal DNA fragmentation. Gamma-HCC induced DNA fragmentation of HL-60 cells in a dose-, time- and Ca2+-dependent manner. The DNA fragmentation induced was inhibited by intracellular Ca2+ chelator, calmodulin antagonist and Ca2+ sensitive endonuclease inhibitor. Gamma-HCC caused a steady increase in the cytosolic free Ca+ concentration due to release from intracellular stores. Neither the DNA fragmentation nor the increase of intracellular Ca2+ induced by gamma-HCC was inhibited by the removal of extracellular Ca2+. These data suggested that the cytotoxicity of gamma-HCC in HL-60 cells is mediated by the increase of intracellular Ca2+ concentration and the activation of Ca2+-dependent endonuclease, which triggers apoptosis in a Ca2+ and calmodulin-dependent manner.
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PMID:Mediation of gamma-hexachlorocyclohexane-induced DNA fragmentation in HL-60 cells through intracellular Ca2+ release pathway. 967 59

Liver cancer is a lethal disease that is associated with poor prognosis. In order to identify the functionally important genes associated with liver cancer that may reveal novel therapeutic avenues, we performed integrated analysis to profile miRNA and mRNA expression levels for liver tumors compared to normal samples in The Cancer Genome Atlas (TCGA) database. We identified 405 differentially expressed genes and 233 differentially expressed miRNAs in tumor samples compared with controls. In addition, we also performed the pathway analysis and found that mitogen-activated protein kinases (MAPKs) and G-protein coupled receptor (GPCR) pathway were two of the top significant pathway nodes dysregulated in liver cancer. Furthermore, by examining these signaling networks, we discovered that FOS (Fos proto-oncogene, AP-1 transcription factor subunit), LAMC2 (laminin subunit gamma 2), and CALML3 (calmodulin like 3) were the most significant gene nodes with high degrees involved in liver cancer. The expression and disease prediction accuracy of FOS, LAMC2, CALML3, and their interacting miRNAs were further performed using a HCC cohort. Finally, we investigated the prognostic significance of FOS in another HCC cohort. Patients with higher FOS expression displayed significantly shorter time to recurrence (TTR) and overall survival (OS) compared with patients with lower expression. Collectively, our study demonstrates that FOS is a potential prognostic marker for liver cancer that may reveal a novel therapeutic avenue in this lethal disease.
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PMID:Identification of FOS as a Candidate Risk Gene for Liver Cancer by Integrated Bioinformatic Analysis. 3228 Jun 95