AIM: To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functi...AIM: To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functional promyelocytic leukemia protein (PML). METHODS: The role of p53 and PML in regulating cy-totoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in two pairs of isogenic human hepatoma cell lines with different p53 status. Further-more,H-1 PV infection was combined with cytostatic drug treatment. RESULTS: While the HCC cells with different p53 status studied were all susceptible to H-1 PV-induced apoptosis,the cytotoxicity of H-1 PV was morepronounced in p53-negative than in p53-positive cells. Apoptosis rates in p53-negative cell lines treated by genotoxic drugs were further enhanced by a treatment with H-1 PV. In flow cytometric analyses,H-1 PV infection resulted in a reduction of the mitochondrial transmembrane potential. In addition,H-1 PV cells showed a significant increase in PML expression. Knocking down PML expression resulted in a striking reduction of the level of H-1 PV infected tumor cell death. CONCLUSION: H-1 PV is a suitable agent to circumvent the resistance of p53-negative HCC cells to genotoxic agents,and it enhances the apoptotic process which is dependent on functional PML. Thus,H-1 PV and its oncolytic vector derivatives may be considered as therapeutic options for HCC,particularly for p53-negative tumors.展开更多
To understand the relationship between expression of P53 protein and HPV16/18 infection in laryngeal papillomas, PCR and immunohistochemical tech-niques were used to examine the paraffin-embedded tissue samples of lar...To understand the relationship between expression of P53 protein and HPV16/18 infection in laryngeal papillomas, PCR and immunohistochemical tech-niques were used to examine the paraffin-embedded tissue samples of laryngeal pa-pillomas from 35 subjects. HPV 16/18-DNA was found in 24 cases of laryngeal papillomas (68. 8 %). Overexpression of P53 protein was detected in 19 cases (54. 3 % ). Both HPV16/18-DNA and overexpression of P53 protein were demon-strated in 12 cases of laryngeal papillomas (34. 3 % ). Our results suggest that HPV16/l8 infection and P53 gene mutation are associated with pathogenesis of la-ryngeal papillomas. The relation between HPV infection and P53 mutation in tis-sues of laryngeal papillomas remains to be clarified.展开更多
基金Grants from the German Cancer Aid (Deutsche Krebshilfe) No.10-2183/102322local university research grants,MAIFOR program,No.9728053 and 9728275
文摘AIM: To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functional promyelocytic leukemia protein (PML). METHODS: The role of p53 and PML in regulating cy-totoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in two pairs of isogenic human hepatoma cell lines with different p53 status. Further-more,H-1 PV infection was combined with cytostatic drug treatment. RESULTS: While the HCC cells with different p53 status studied were all susceptible to H-1 PV-induced apoptosis,the cytotoxicity of H-1 PV was morepronounced in p53-negative than in p53-positive cells. Apoptosis rates in p53-negative cell lines treated by genotoxic drugs were further enhanced by a treatment with H-1 PV. In flow cytometric analyses,H-1 PV infection resulted in a reduction of the mitochondrial transmembrane potential. In addition,H-1 PV cells showed a significant increase in PML expression. Knocking down PML expression resulted in a striking reduction of the level of H-1 PV infected tumor cell death. CONCLUSION: H-1 PV is a suitable agent to circumvent the resistance of p53-negative HCC cells to genotoxic agents,and it enhances the apoptotic process which is dependent on functional PML. Thus,H-1 PV and its oncolytic vector derivatives may be considered as therapeutic options for HCC,particularly for p53-negative tumors.
文摘To understand the relationship between expression of P53 protein and HPV16/18 infection in laryngeal papillomas, PCR and immunohistochemical tech-niques were used to examine the paraffin-embedded tissue samples of laryngeal pa-pillomas from 35 subjects. HPV 16/18-DNA was found in 24 cases of laryngeal papillomas (68. 8 %). Overexpression of P53 protein was detected in 19 cases (54. 3 % ). Both HPV16/18-DNA and overexpression of P53 protein were demon-strated in 12 cases of laryngeal papillomas (34. 3 % ). Our results suggest that HPV16/l8 infection and P53 gene mutation are associated with pathogenesis of la-ryngeal papillomas. The relation between HPV infection and P53 mutation in tis-sues of laryngeal papillomas remains to be clarified.
