Peroxisome proliferator-activated receptors(PPARs) are ligand-dependent nuclear transcription factors and members of the nuclear receptor superfamily.Of the three PPARs identified to date(PPARγ,PPARβ/δ,and PPARα),...Peroxisome proliferator-activated receptors(PPARs) are ligand-dependent nuclear transcription factors and members of the nuclear receptor superfamily.Of the three PPARs identified to date(PPARγ,PPARβ/δ,and PPARα),PPARγ has been studied the most,in part because of the availability of PPARγagonists(also known as PPARγ ligands)and its significant effects on the management of several human diseases including type 2 diabetes,metabolic syndrome,cardiovascular disease and cancers.PPARγ is expressed in many tumors including lung cancer,and its function has been linked to the process of lung cancer development, progression and metastasis.Studies performed in gynogenic and xenograft models of lung cancer showed decreased tumor growth and metastasis in animals treated with PPARγ ligands.Furthermore,data are emerging from retrospective clinical studies that suggest a protective role for PPARγ ligands on the incidence of lung cancer.This review summarizes the research being conducted in this area and focuses on the mechanisms and potential therapeutic effects of PPARγ ligands as a novel anti-lung cancer treatment strategy.展开更多
Balb/c nu/nu mice were inoculated intratracheally with multidrug-resistant human lung cancer cells GLK containing p53 mutation at codon 245 and treated with intratracheal instillation of p53-wt retroviral vector (pDOR...Balb/c nu/nu mice were inoculated intratracheally with multidrug-resistant human lung cancer cells GLK containing p53 mutation at codon 245 and treated with intratracheal instillation of p53-wt retroviral vector (pDOR53W) to increase cell chemosensitivity, and then with intraperitoneal injection of doxorubicin. 30 d after tumor cell inoculation, 75% of the control mice showed macroscopic tumors in the lung. Sole pDOR53W suppressed GLK tumor formation in 68 % of mice; sole doxorubicin 33. 3 % , but the combination of pDOR53W and doxorubicin 88.9%. The exogenous p53 sequence was detected and confirmed in the tumor that grew after treatment with pDOR53W retroviral vector by PCR and Southern blot hybridization with p53 cDNA. These results suggested that di-rect administration of a retroviral vector expressing p53-wt combined with treatment of anticancer agent was an effec-tive therapeutic method for multidrug-resistant human lung cancer.展开更多
Human mutant-type (mt) p53 cDNA was synthesized and cloned from human lung cancer cell line GL containing mt-p53 gene by using polymerase chain reaction (PCR). It was confirmed that the mt-p53 cDNA con-tained the comp...Human mutant-type (mt) p53 cDNA was synthesized and cloned from human lung cancer cell line GL containing mt-p53 gene by using polymerase chain reaction (PCR). It was confirmed that the mt-p53 cDNA con-tained the complete coding sequence of p53 gene but mutated at codon 245 (G→T) and resulted in glycine to cysteine by sequencing analysis. The retroviral vector pD53M of the mt-p53 was constructed and introduced into the drug-sen-sitive human lung cancer cells GAO in which p53 gene did not mutate. The transfected GAO cells strongly expressed mutant-type p53 protein by immunohistochemistry, showing that pD53M vector could steadily express in GAO cells. The drug resistance to several anticancer agents of GAO cells infected by pD53M increased in varying degrees, with the highest increase of 4-fold, in vitro and in vivo. By quantitative PCR and flow cytometry (FCM) analyses, the expression of MDR1 gene and the activity of P-glycoprotein (Pgp) did not increase, the expression of MRP gene and the activity of multidrug resistance-related protein (Mrp) increased slightly. These results indicated that the drug re-sistance associated with mt-p53 gene might be somewhat correlated with MRP/Mrp but not with MDR1/Pgp. It was possible to modify the tumor drug resistance by changing status of p53 gene.展开更多
The human lung cancer has high incidence rate and mortality among the carcinoma. The research on enhancing the efficacy of therapy for lung cancer is significant. A resent research found that as a subunit of ESCRT-III...The human lung cancer has high incidence rate and mortality among the carcinoma. The research on enhancing the efficacy of therapy for lung cancer is significant. A resent research found that as a subunit of ESCRT-III, CHMP4C functioned to retard abscission timing to coordinate midbody resolution and prevent accumulation of DNA damage in the abscission checkpoint through phosphorylated by AuroraB. In the current study, we evaluated the possible mechanism of the effects of CHMP4C inhibition on cell cycle and cell survival in A549 cells. We found that CHMP4C knockdown caused lagging S phase in cell cycle through enhancing the phosphorylation of Rb, raising the expression of cyclin B1-cdc2 and suppressing the activation of cyclin A. Meanwhile, CHMP4Cdeletion depressed cell survival via decreasing cell viability and increasing caspase 3/7 activity. This study may promote new significant reference and advance for the mechanism underlying specific function of CHMP4C as well as further research on enhancing therapy effect on non-small lung cancer.展开更多
MALIGNANT tumor is very harmful to human health, and the mortality is very high. About 50% of the patients with malignancy can be operated on, and the other 50% patients have to be treated with chemotherapy. Because t...MALIGNANT tumor is very harmful to human health, and the mortality is very high. About 50% of the patients with malignancy can be operated on, and the other 50% patients have to be treated with chemotherapy. Because tumors are mostly chemoresistant, chemotherapy for these patients often has no effect. The overexpression of MDR1 gene is very common in hu man malignant tumors, about 50% in previously untreated patients and more than 50% in previously treated patients for whom the tumor is resistant to the previous sensitive展开更多
目的研究HDPR1(human homologue of Dapper)在人非小细胞肺癌的表达,分析其表达与p120ctn和β-catenin表达是否相关,及其与肺癌恶性程度的关系。方法应用免疫组织化学染色检测120例非小细胞肺癌石蜡标本,应用WesternBlot和RT-PCR检测了4...目的研究HDPR1(human homologue of Dapper)在人非小细胞肺癌的表达,分析其表达与p120ctn和β-catenin表达是否相关,及其与肺癌恶性程度的关系。方法应用免疫组织化学染色检测120例非小细胞肺癌石蜡标本,应用WesternBlot和RT-PCR检测了42例新鲜组织标本中HDPR1、β-catenin和pl20ctn表达的关系,分析它们的表达与临床病理因素之间的相关性。结果 HDPR1在正常肺组织中为高表达,而在非小细胞中有68.3%(82/120)为表达下调,其表达下调不仅与肺癌高TNM分期、低分化、淋巴结转移和不良预后显著相关,并且与肺癌组织中p120ctn的表达下调呈正相关,与β-catenin的表达上调呈负相关。42例新鲜肺癌组织中,HDPR1和p120ctn的蛋白和mRNA均较癌旁正常组织显著下调(<0.05,n=42),然而,β-catenin蛋白在肺癌组织中却普遍表达上调(<0.05,n=42)。结论肺癌中HDPR1的表达下调与p120ctn和β-catenin异常表达相关,与患者的临床病理因素和不良预后明显相关。展开更多
基金Supported by The National Institutes of Health CA123104(HanSW) and CA116812(Roman J)
文摘Peroxisome proliferator-activated receptors(PPARs) are ligand-dependent nuclear transcription factors and members of the nuclear receptor superfamily.Of the three PPARs identified to date(PPARγ,PPARβ/δ,and PPARα),PPARγ has been studied the most,in part because of the availability of PPARγagonists(also known as PPARγ ligands)and its significant effects on the management of several human diseases including type 2 diabetes,metabolic syndrome,cardiovascular disease and cancers.PPARγ is expressed in many tumors including lung cancer,and its function has been linked to the process of lung cancer development, progression and metastasis.Studies performed in gynogenic and xenograft models of lung cancer showed decreased tumor growth and metastasis in animals treated with PPARγ ligands.Furthermore,data are emerging from retrospective clinical studies that suggest a protective role for PPARγ ligands on the incidence of lung cancer.This review summarizes the research being conducted in this area and focuses on the mechanisms and potential therapeutic effects of PPARγ ligands as a novel anti-lung cancer treatment strategy.
文摘Balb/c nu/nu mice were inoculated intratracheally with multidrug-resistant human lung cancer cells GLK containing p53 mutation at codon 245 and treated with intratracheal instillation of p53-wt retroviral vector (pDOR53W) to increase cell chemosensitivity, and then with intraperitoneal injection of doxorubicin. 30 d after tumor cell inoculation, 75% of the control mice showed macroscopic tumors in the lung. Sole pDOR53W suppressed GLK tumor formation in 68 % of mice; sole doxorubicin 33. 3 % , but the combination of pDOR53W and doxorubicin 88.9%. The exogenous p53 sequence was detected and confirmed in the tumor that grew after treatment with pDOR53W retroviral vector by PCR and Southern blot hybridization with p53 cDNA. These results suggested that di-rect administration of a retroviral vector expressing p53-wt combined with treatment of anticancer agent was an effec-tive therapeutic method for multidrug-resistant human lung cancer.
文摘Human mutant-type (mt) p53 cDNA was synthesized and cloned from human lung cancer cell line GL containing mt-p53 gene by using polymerase chain reaction (PCR). It was confirmed that the mt-p53 cDNA con-tained the complete coding sequence of p53 gene but mutated at codon 245 (G→T) and resulted in glycine to cysteine by sequencing analysis. The retroviral vector pD53M of the mt-p53 was constructed and introduced into the drug-sen-sitive human lung cancer cells GAO in which p53 gene did not mutate. The transfected GAO cells strongly expressed mutant-type p53 protein by immunohistochemistry, showing that pD53M vector could steadily express in GAO cells. The drug resistance to several anticancer agents of GAO cells infected by pD53M increased in varying degrees, with the highest increase of 4-fold, in vitro and in vivo. By quantitative PCR and flow cytometry (FCM) analyses, the expression of MDR1 gene and the activity of P-glycoprotein (Pgp) did not increase, the expression of MRP gene and the activity of multidrug resistance-related protein (Mrp) increased slightly. These results indicated that the drug re-sistance associated with mt-p53 gene might be somewhat correlated with MRP/Mrp but not with MDR1/Pgp. It was possible to modify the tumor drug resistance by changing status of p53 gene.
文摘The human lung cancer has high incidence rate and mortality among the carcinoma. The research on enhancing the efficacy of therapy for lung cancer is significant. A resent research found that as a subunit of ESCRT-III, CHMP4C functioned to retard abscission timing to coordinate midbody resolution and prevent accumulation of DNA damage in the abscission checkpoint through phosphorylated by AuroraB. In the current study, we evaluated the possible mechanism of the effects of CHMP4C inhibition on cell cycle and cell survival in A549 cells. We found that CHMP4C knockdown caused lagging S phase in cell cycle through enhancing the phosphorylation of Rb, raising the expression of cyclin B1-cdc2 and suppressing the activation of cyclin A. Meanwhile, CHMP4Cdeletion depressed cell survival via decreasing cell viability and increasing caspase 3/7 activity. This study may promote new significant reference and advance for the mechanism underlying specific function of CHMP4C as well as further research on enhancing therapy effect on non-small lung cancer.
文摘MALIGNANT tumor is very harmful to human health, and the mortality is very high. About 50% of the patients with malignancy can be operated on, and the other 50% patients have to be treated with chemotherapy. Because tumors are mostly chemoresistant, chemotherapy for these patients often has no effect. The overexpression of MDR1 gene is very common in hu man malignant tumors, about 50% in previously untreated patients and more than 50% in previously treated patients for whom the tumor is resistant to the previous sensitive
文摘目的研究HDPR1(human homologue of Dapper)在人非小细胞肺癌的表达,分析其表达与p120ctn和β-catenin表达是否相关,及其与肺癌恶性程度的关系。方法应用免疫组织化学染色检测120例非小细胞肺癌石蜡标本,应用WesternBlot和RT-PCR检测了42例新鲜组织标本中HDPR1、β-catenin和pl20ctn表达的关系,分析它们的表达与临床病理因素之间的相关性。结果 HDPR1在正常肺组织中为高表达,而在非小细胞中有68.3%(82/120)为表达下调,其表达下调不仅与肺癌高TNM分期、低分化、淋巴结转移和不良预后显著相关,并且与肺癌组织中p120ctn的表达下调呈正相关,与β-catenin的表达上调呈负相关。42例新鲜肺癌组织中,HDPR1和p120ctn的蛋白和mRNA均较癌旁正常组织显著下调(<0.05,n=42),然而,β-catenin蛋白在肺癌组织中却普遍表达上调(<0.05,n=42)。结论肺癌中HDPR1的表达下调与p120ctn和β-catenin异常表达相关,与患者的临床病理因素和不良预后明显相关。
