UNC5H4-induced apoptosis in non-small cell lung cancer is not dependent on p53 status only.

The aim of the present study was to investigate the expression profile and prognostic significance of uncoordinated 5 homolog 4 (UNC5H4) in patients with lung cancer and to evaluate whether UNC5H4 expression may serve as an index for radiosensitivity. UNC5H4 and p53 expression levels were detected by immunohistochemistry, apoptosis was determined by a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and caspase 3 activation was determined by western blotting. The results showed that UNC5H4 expression was largely located in the membrane of the normal bronchial epithelium, but absent in the membranous regions or ectopic cytoplasm of 80/130 (61.5%) non-small cell lung cancer (NSCLC) tissue samples. Abnormal UNC5H4 expression was demonstrated to correlate with the degree of differentiation (P=0.015), TNM staging (P=0.037). Cytoplasmic UNC5H4 expression was shown to correlate negatively with p53 mutant type (mt) expression (r=-0.270; P=0.002) and positively with the apoptotic index (r=0.254; P=0.004). The statistical analyses indicated that the prognosis of patients with normal UNC5H4 expression was improved compared with that of patients with abnormal UNC5H4 expression, however, no significant difference was identified (P=0.125). Exposure of NSCLC tissue samples to X-radiation increased UNC5H4 expression and caspase 3 activity significantly, irrespective of p53 mutation status. In conclusion, these results indicate that X-rays induce apoptosis via the p53 pathway, and when this pathway is compromised, an additional pathway is utilized.

[Hypermethylation of Ras association domain family protein 1A, hypermethylated in cancer 1 and p73 genes in hepatocellular carcinoma].

OBJECTIVE: To evaluate the status of promoter hypermethylation of Ras association domain family protein 1A (RASSF1A), hypermethylated in cancer 1 (HIC1) and p73 genes in hepatocellular carcinoma (HCC) and to explore the correlation with clinicopathological features. METHODS: Forty cases of HCC and their corresponding non-tumor liver tissues, other 2 cases of healthy donor livers were detected using methylation specific polymorphism chain reaction (MSP) method. RESULTS: The frequency of promoter hypermethylation of RASSF1A showed 90.0% and 72.5% in tumor and corresponding non-tumor tissues respectively, and there was significant difference between them (P < 0.05). The frequency of promoter hypermethylation of HIC1 showed 77.5% and 70.0% in tumor and corresponding non-tumor tissues respectively. The frequency of hypermethylation of HIC1 in non-tumor liver tissues showed significant correlation between younger and older patients. The frequency of promoter hypermethylation of p73 showed 5.0% in tumor tissues. However, none of hypermethylation of the gene was detected in corresponding non-tumor liver tissues. There was none of hypermethylation of the three genes showed in two cases of healthy donor livers. CONCLUSION: Promoter hypermethylation of RASSF1A and HIC1 genes are common event in HCC and play an important role in the pathogenesis and may be used to develop novel diagnostic and therapeutic approaches for HCC in the future.

[Experimental study on growth factor in promotion of chondrocytes proliferation].

OBJECTIVE: To study the effect of two cytokines, basic fibrolast growth factor(bFGF) and insulin-like growth factor-I(IGF-I), on cell proliferation in chondrocytes of adult rabbits. METHODS: The primary chondrocytes of adult rabbits were harvested and cultured with bFGF and IGF-I at different concentrations, respectively, as well as with the mixture of the two cytokines; the quantity of cultured chondrocytes was detected by MTT assay at the 24th, 48th and 72nd hours; and the final fold increase of different groups was measured by cell count for the 3rd passage; and the proliferation index of the groups was recorded by flowing cytometer on the 14th day. RESULTS: 1. The cultured chondrocytes with either bFGF, IGF-I or their mixture were significantly more than that of control group at the 24th, 48th and 72th hours (P < 0.01). 2. After the 3rd passage, the final folds of proliferation were significantly higher in the groups with cytokines than in the control group (P < 0.01); and the final fold with the mixture of cytokines was significantly higher than that of both IGF-I and bFGF (P < 0.01). 3. The proliferation index was significantly higher in the groups with cytokines than in the control group (P < 0.01); the proliferation index with the mixture of cytokines was significantly higher than that of both IGF-I and bFGF (P < 0.05); besides, proliferation index was higher when cytokine was applied twice than once (P < 0.05); besides, proliferation index was higher when cytokine was applied twice than once (P < 0.05). CONCLUSION: bFGF and IGF-I could promote chondrocytes proliferation of adult rabbits obviously and they are synergistic in cell proliferation.