AIM:To investigate the role of hepatopoietin Cn(HPPCn) in apoptosis of hepatocellular carcinoma(HCC)cells and its mechanism. METHODS:Two human HCC cell lines,SMMC7721 and HepG2,were used in this study.Immunostaining, ...AIM:To investigate the role of hepatopoietin Cn(HPPCn) in apoptosis of hepatocellular carcinoma(HCC)cells and its mechanism. METHODS:Two human HCC cell lines,SMMC7721 and HepG2,were used in this study.Immunostaining, Western blotting and enzyme linked immunosorbent assay were conducted to identify the expression of HPPCn and the existence of an autocrine loop of HPPCn/ HPPCn receptor in SMMC7721 and HepG2.Apoptotic cells were detected using fluorescein isothiocyanate (FITC)-conjugated Annexin V and propidium iodide.RESULTS:The HPPCn was highly expressed in human HCC cells and secreted into culture medium(CM). FITC-labeled recombinant human protein(rhHPPCn) could specifically bind to its receptor on HepaG2 cells. Treatment with 400 ng/mL rhHPPCn dramatically increased the viability of HCC-derived cells from 48.1% and 36.9%to 85.6%and 88.4%,respectively(P< 0.05).HPPCn silenced by small-interfering RNA reduced the expression and secretion of HPPCn and increased the apoptosis induced by trichostatin A.Additionally, HPPCn could up-regulate the expression of myeloid cell leukemia-1(Mcl-1)in HCC cells via mitogen-activated protein kinase(MAPK)and sphingosine kinase-1. CONCLUSION:HPPCn is a novel hepatic growth factor that can be secreted to CM and suppresses apoptosis of HCC cells by up-regulating Mcl-1 expression.展开更多
To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeutically approach for cholangiocellular cancer treatment.METHODSAs most cholangiocarcinomas are chemotherapy-resista...To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeutically approach for cholangiocellular cancer treatment.METHODSAs most cholangiocarcinomas are chemotherapy-resistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma (CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases (PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators. Here, cells were treated with PLK inhibitor BI6727 (Volasertib), Cisplatin, and in combination of both compounds. Cell viability was assessed by MTT; apoptosis was measured by DAPI staining and caspase-3/-7 assay. Western blot and qRT-PCR were used to measure expression levels of apoptosis-related molecules Bax and Bcl-2.RESULTSThe cell viability in the CCA cell lines KMCH-1 and Mz-Ch-1 was reduced in all treatment conditions compared to vehicle-treated cells. Co-treatment with BI6727 and cisplatin could even enhance the cytotoxic effect of cisplatin single treatment. Thus, co-treatment of cisplatin with BI6727 could slightly enhance the cytotoxic effect of the cisplatin in both cell lines whereas there was evidence of increased apoptosis induction solely in Mz-Ch-1 as compared to KMCH-1. Moreover, PLK inhibition decreases protein levels of Bcl-2; an effect that can be reversed by the proteasomal degradation inhibitor MG-132. In contrast, protein levels of Bax were not found to be altered by PLK inhibition. These findings indicate that cytotoxic effects of Cisplatin in Mz-Ch-1 cells can be enhanced by cotreatment with BI6727.CONCLUSIONIn conclusion, BI6727 treatment can sensitize CCA cells to cisplatin-induced apoptosis with proteasomal Bcl-2 degradation as an additional pro-apoptotic effect.展开更多
AIM: To review the characteristics of hematological malignancies in tropical areas, and to focus on the specific difficulties regarding their management. METHODS: This is a retrospective narrative review of cases of p...AIM: To review the characteristics of hematological malignancies in tropical areas, and to focus on the specific difficulties regarding their management. METHODS: This is a retrospective narrative review of cases of patients with hematological malignancies. All medical files of patients with malignant disease whose treatment was coordinated by the HematoOncology service of the Cayenne Hospital in French Guiana between the 1st of January 2010 and the 31 st of December 2012 were reviewed. Clinical data were extracted from the medical files and included: Demographic data, comorbidities, serological status for human immunodeficiency virus, human T-lymphotropic virus 1(HTLV1), hepatitis B virus and hepatitis C virusinfections, cytology and pathology diagnoses, disease extension, treatment, organization of disease management, and follow-up. The subgroup of patients with hematological malignancies and virus-related malignancies were reviewed. Cases involving patients with Kaposi sarcoma, and information on solid tumor occurrence in virus-infected patients in the whole patient population were included. Since the data were rendered anonymous, no informed consent was obtained from the patients for this retrospective analysis. Data were compiled using EXCEL® software, and the data presentation is descriptive only. The references search was guided by the nature of the data and discussion. RESULTS: In total, the clinical files of 594 patients(pts) were reviewed. Hematological malignancies were observed in 87 patients, and Kaposi sarcoma in 2 patients. In total, 70 patients had a viral infection, and 34 of these also had hematological malignancies. The hematological diagnoses were: Multiple myeloma in 27 pts, lymphoma(L) in 43 pts, myeloproliferative disorders in 17 pts and Kaposi sarcoma in two patients. The spectrum of non-Hodgkin lymphomas(NHL) was: Burkitt L(1 pt), follicular L(5 pts), chronic lymphocytic leukemia(5 pts), high-grade NHL(9 pts), mucosa-associated lymphoid tissue NHL(4 pts), T-cell lymphoma(4 pts), Adul展开更多
基金Supported by(in part)Grants From the National Natural Science Foundation of China,No.30800558 and No.30930041the Chinese Major Special Science&Technology Project for Development of Major New Drugs,No.2009ZX09103-617
文摘AIM:To investigate the role of hepatopoietin Cn(HPPCn) in apoptosis of hepatocellular carcinoma(HCC)cells and its mechanism. METHODS:Two human HCC cell lines,SMMC7721 and HepG2,were used in this study.Immunostaining, Western blotting and enzyme linked immunosorbent assay were conducted to identify the expression of HPPCn and the existence of an autocrine loop of HPPCn/ HPPCn receptor in SMMC7721 and HepG2.Apoptotic cells were detected using fluorescein isothiocyanate (FITC)-conjugated Annexin V and propidium iodide.RESULTS:The HPPCn was highly expressed in human HCC cells and secreted into culture medium(CM). FITC-labeled recombinant human protein(rhHPPCn) could specifically bind to its receptor on HepaG2 cells. Treatment with 400 ng/mL rhHPPCn dramatically increased the viability of HCC-derived cells from 48.1% and 36.9%to 85.6%and 88.4%,respectively(P< 0.05).HPPCn silenced by small-interfering RNA reduced the expression and secretion of HPPCn and increased the apoptosis induced by trichostatin A.Additionally, HPPCn could up-regulate the expression of myeloid cell leukemia-1(Mcl-1)in HCC cells via mitogen-activated protein kinase(MAPK)and sphingosine kinase-1. CONCLUSION:HPPCn is a novel hepatic growth factor that can be secreted to CM and suppresses apoptosis of HCC cells by up-regulating Mcl-1 expression.
基金Supported by DFG/German Research Foundation,No.FI 1630/3-1 and No.IFORES D/107-114400(to CDF)
文摘To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeutically approach for cholangiocellular cancer treatment.METHODSAs most cholangiocarcinomas are chemotherapy-resistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma (CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases (PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators. Here, cells were treated with PLK inhibitor BI6727 (Volasertib), Cisplatin, and in combination of both compounds. Cell viability was assessed by MTT; apoptosis was measured by DAPI staining and caspase-3/-7 assay. Western blot and qRT-PCR were used to measure expression levels of apoptosis-related molecules Bax and Bcl-2.RESULTSThe cell viability in the CCA cell lines KMCH-1 and Mz-Ch-1 was reduced in all treatment conditions compared to vehicle-treated cells. Co-treatment with BI6727 and cisplatin could even enhance the cytotoxic effect of cisplatin single treatment. Thus, co-treatment of cisplatin with BI6727 could slightly enhance the cytotoxic effect of the cisplatin in both cell lines whereas there was evidence of increased apoptosis induction solely in Mz-Ch-1 as compared to KMCH-1. Moreover, PLK inhibition decreases protein levels of Bcl-2; an effect that can be reversed by the proteasomal degradation inhibitor MG-132. In contrast, protein levels of Bax were not found to be altered by PLK inhibition. These findings indicate that cytotoxic effects of Cisplatin in Mz-Ch-1 cells can be enhanced by cotreatment with BI6727.CONCLUSIONIn conclusion, BI6727 treatment can sensitize CCA cells to cisplatin-induced apoptosis with proteasomal Bcl-2 degradation as an additional pro-apoptotic effect.
文摘AIM: To review the characteristics of hematological malignancies in tropical areas, and to focus on the specific difficulties regarding their management. METHODS: This is a retrospective narrative review of cases of patients with hematological malignancies. All medical files of patients with malignant disease whose treatment was coordinated by the HematoOncology service of the Cayenne Hospital in French Guiana between the 1st of January 2010 and the 31 st of December 2012 were reviewed. Clinical data were extracted from the medical files and included: Demographic data, comorbidities, serological status for human immunodeficiency virus, human T-lymphotropic virus 1(HTLV1), hepatitis B virus and hepatitis C virusinfections, cytology and pathology diagnoses, disease extension, treatment, organization of disease management, and follow-up. The subgroup of patients with hematological malignancies and virus-related malignancies were reviewed. Cases involving patients with Kaposi sarcoma, and information on solid tumor occurrence in virus-infected patients in the whole patient population were included. Since the data were rendered anonymous, no informed consent was obtained from the patients for this retrospective analysis. Data were compiled using EXCEL® software, and the data presentation is descriptive only. The references search was guided by the nature of the data and discussion. RESULTS: In total, the clinical files of 594 patients(pts) were reviewed. Hematological malignancies were observed in 87 patients, and Kaposi sarcoma in 2 patients. In total, 70 patients had a viral infection, and 34 of these also had hematological malignancies. The hematological diagnoses were: Multiple myeloma in 27 pts, lymphoma(L) in 43 pts, myeloproliferative disorders in 17 pts and Kaposi sarcoma in two patients. The spectrum of non-Hodgkin lymphomas(NHL) was: Burkitt L(1 pt), follicular L(5 pts), chronic lymphocytic leukemia(5 pts), high-grade NHL(9 pts), mucosa-associated lymphoid tissue NHL(4 pts), T-cell lymphoma(4 pts), Adul
