Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Okadaic acid (OA) is a phycotoxin produced by several types of dinoflagellates causing diarrheic shellfish poisoning (DSP) in humans. Symptoms induced by DSP toxins are mainly gastrointestinal, but the intoxication does not appear to be fatal. Despite this, this toxin presents a potential threat to human health even at concentrations too low to induce acute toxicity, since previous animal studies have shown that OA has very potent tumour promoting activity. However, its concrete action mechanism has not been described yet and the results reported with regard to OA cytotoxicity and genotoxicity are often contradictory. In the present study, the genotoxic and cytotoxic effects of OA on three different types of human cells (peripheral blood leukocytes, HepG2 hepatoma cells, and SHSY5Y neuroblastoma cells) were evaluated. Cells were treated with a range of OA concentrations in the presence and absence of S9 fraction, and MTT test and Comet assay were performed in order to evaluate cytotoxicity and genotoxicity, respectively. The possible effects of OA on DNA repair were also studied by means of the DNA repair competence assay, using bleomycin as DNA damage inductor. Treatment with OA in absence of S9 fraction induced not statistically significant decrease in cell viability and significant increase in DNA damage in all cell types at the highest concentrations investigated. However, only SHSY5Y cells showed OA induced genotoxic and cytotoxic effects in presence of S9 fraction. Furthermore, we found that OA can induce modulations in DNA repair processes when exposure was performed prior to BLM treatment, in co-exposure, or during the subsequent DNA repair process.
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PMID:Assessment of okadaic acid effects on cytotoxicity, DNA damage and DNA repair in human cells. 2062 97

The roles and model of action of the chromatin assembly complex factor-1B (CHAF1B) gene in liver cancer have not been fully elucidated. The CHAF1B gene in human hepatocellular carcinoma cell line HUH-7 was knocked down using a lentivirus and the transfected cells were assayed for migration and invasion abilities and cell cycle arrest using the scratch wound healingand Transwell assays as well as flow cytometry, respectively. Cells transfected with an empty vector were used as the control. The expression of genes was profiled. Models were constructed using CHAF1B-knockdown cells and investigated for tumor growth and pathological changes. Our experiments revealed that the knockdown of the CHAF1 gene reduced the invasion and migration ability of HUH-7 cells. Gene expression profiling revealed that after knockdown, PSMB6, SLC30A7, SMC3, TWF2 and BLM genes had the most marked changes as compared with the control. Western blot and RT-PCR analyses revealed that following the knockdown of the CHAF1B gene, protein and mRNA levels of the PSMB6, SLC30A7 and SMC3 genes were significantly upregulated, while those of the BLM and TWF2 genes were significantly downregulated. In the HUH-7-knockdown cells, there were significantly fewer G0/G1 cells and more S1 cells as compared with the control (36.10 vs. 54.10% and 59.7 vs. 40.8%, respectively), while the number of G2/M cells was similar (4.20 vs. 5.10%). The volumes of the tumors were similar between those injected with the empty vector and control, but were significantly smaller in the knockdown models, suggesting that the knockdown of the CHAF1B gene inhibited tumor growth. H&E staining revealed that tumors were developed in mice in all groups.
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PMID:CHAF1B knockdown blocks migration in a hepatocellular carcinoma model. 2976 68