Valproic acid(VPA) is a histone deacetylase inhibitor that has been an object of interest to clinicians for its promising potency in cancer therapy, as it induces apoptosis and differentiation, and enhances of chemoth...Valproic acid(VPA) is a histone deacetylase inhibitor that has been an object of interest to clinicians for its promising potency in cancer therapy, as it induces apoptosis and differentiation, and enhances of chemotherapy sensitivity. Esophageal squamous cell carcinoma(ESCC) is a malignant disease with growing incidence and low survival rate. Due to limited information on VPA activity in ESCC cells, we aimed to determine effects of VPA on chemotherapy responsiveness and expression of malignant markers in ESCC stem-like cells. Upon coadministration of non-toxic VPA + cisplatin(DDP), paclitaxel and 5-fluorouracil, viability of KYSE30 cells was assessed, and induced apoptosis was evaluated by DAPI staining, DNA laddering and flow cytometry. In addition, real time RT-PCR was performed to study changes in the expression of P21, CD44 and BMI-1 upon treatments. MTT test demonstrated that VPA significantly(P < 0.05) increased toxicity of DDP, which was confirmed by DNA laddering, flow cytometry analysis and significant(P < 0.05) overexpression of P21. Moreover, real time RT-PCR results indicated significant(P < 0.05) down regulation of CD44 and BMI-1 after VPA administration. Present attempt provided evidence, for the first time, that VPA not only improved responsiveness of esophageal stem-like cancer cells to DDP, also negatively regulated cancer stem cells markers in these cells.展开更多
Oral squamous cell carcinoma is a challenging oncology problem.A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined.Using quantitative immunohistochemistry,we examined t...Oral squamous cell carcinoma is a challenging oncology problem.A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined.Using quantitative immunohistochemistry,we examined the expression of vimentin,E-cadherin,and beta-catenin in 83 oral squamous cell carcinoma patients,and the relationships between the expression of these markers and specific clinicopathological features were analysed.The high expression of vimentin was observed in 23 of 43(53%) tumours from patients who eventually developed a recurrent tumour and was associated with recurrence and death(P < 0.001 and < 0.001,respectively).The decreased expression of E-cadherin was observed in 36 of 43(84%) tumours from patients who eventually developed a recurrent tumour and was also associated with recurrence and death(P < 0.001 and < 0.001,respectively).Although no correlation between beta-catenin expression in whole-tumour sections and clinicopathological features was observed,decreased beta-catenin expression at the tumour invasive front was closely associated with recurrence and death(P=0.002 and 0.002,respectively).The expression of vimentin and that of E-cadherin were associated with survival and were independent prognostic factors in univariate and multivariate analyses.Our data show that the overexpression of vimentin was closely associated with recurrence and death in oral squamous cell carcinoma patients.The combination of the upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complexes at the tumour invasive front may provide a useful prognostic marker in oral squamous cell carcinoma.展开更多
基金supported by a grant from Ferdowsi University of Mashhad(31546)
文摘Valproic acid(VPA) is a histone deacetylase inhibitor that has been an object of interest to clinicians for its promising potency in cancer therapy, as it induces apoptosis and differentiation, and enhances of chemotherapy sensitivity. Esophageal squamous cell carcinoma(ESCC) is a malignant disease with growing incidence and low survival rate. Due to limited information on VPA activity in ESCC cells, we aimed to determine effects of VPA on chemotherapy responsiveness and expression of malignant markers in ESCC stem-like cells. Upon coadministration of non-toxic VPA + cisplatin(DDP), paclitaxel and 5-fluorouracil, viability of KYSE30 cells was assessed, and induced apoptosis was evaluated by DAPI staining, DNA laddering and flow cytometry. In addition, real time RT-PCR was performed to study changes in the expression of P21, CD44 and BMI-1 upon treatments. MTT test demonstrated that VPA significantly(P < 0.05) increased toxicity of DDP, which was confirmed by DNA laddering, flow cytometry analysis and significant(P < 0.05) overexpression of P21. Moreover, real time RT-PCR results indicated significant(P < 0.05) down regulation of CD44 and BMI-1 after VPA administration. Present attempt provided evidence, for the first time, that VPA not only improved responsiveness of esophageal stem-like cancer cells to DDP, also negatively regulated cancer stem cells markers in these cells.
文摘Oral squamous cell carcinoma is a challenging oncology problem.A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined.Using quantitative immunohistochemistry,we examined the expression of vimentin,E-cadherin,and beta-catenin in 83 oral squamous cell carcinoma patients,and the relationships between the expression of these markers and specific clinicopathological features were analysed.The high expression of vimentin was observed in 23 of 43(53%) tumours from patients who eventually developed a recurrent tumour and was associated with recurrence and death(P < 0.001 and < 0.001,respectively).The decreased expression of E-cadherin was observed in 36 of 43(84%) tumours from patients who eventually developed a recurrent tumour and was also associated with recurrence and death(P < 0.001 and < 0.001,respectively).Although no correlation between beta-catenin expression in whole-tumour sections and clinicopathological features was observed,decreased beta-catenin expression at the tumour invasive front was closely associated with recurrence and death(P=0.002 and 0.002,respectively).The expression of vimentin and that of E-cadherin were associated with survival and were independent prognostic factors in univariate and multivariate analyses.Our data show that the overexpression of vimentin was closely associated with recurrence and death in oral squamous cell carcinoma patients.The combination of the upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complexes at the tumour invasive front may provide a useful prognostic marker in oral squamous cell carcinoma.
