Background:Chemotherapy toxicity is a serious problem from which non-small cell lung cancer(NSCLC) patients suffer.The mismatch repair(MMR) system is associated with platinum-based chemotherapy toxicity in NSCLC patie...Background:Chemotherapy toxicity is a serious problem from which non-small cell lung cancer(NSCLC) patients suffer.The mismatch repair(MMR) system is associated with platinum-based chemotherapy toxicity in NSCLC patients.In this study,we aimed to investigate the relationship between genetic polymorphisms in the MMR pathway and platinum-based chemotherapy toxicity in NSCLC patients.Methods:A total of 220 Chinese lung cancer patients who received at least two cycles of platinum-based chemotherapy were recruited for this study.Toxicity was evaluated in each patient after two cycles of chemotherapy.A total of 44 single nucleotide polymorphisms were selected to investigate their associations with platinum-based chemotherapy toxicity.Results:MutS homolog 2[MSH2) rs6544991[odds ratio(OR) 2.98,95%confidence interval(CI) 1.20-7.40,P = 0.019]was associated with gastrointestinal toxicity in the dominant model;MSH3 rs6151627(OR 2.38,95%CI 1.23-4.60,P = 0.010),rs6151670(OR 2.05,95%CI 1.07-3.93,P = 0.031),and rs7709909(OR 2.38,95%CI 1.23-4.64,P = 0.010)were associated with hematologic toxicity in the dominant model.Additionally,MSH5 rs805304 was significantly associated with overall toxicity(OR 2.21,95%CI 1.19-4.09,P = 0.012),and M5H5 rs707939 was significantly associated with both overall toxicity(OR 0.42,95%CI 0.23-0.76,P = 0.004) and gastrointestinal toxicity(OR 0.44,95%CI 0.20-0.96,P = 0.038) in the dominant model.Conclusion:Genetic polymorphisms in the MMR pathway are potential clinical markers for predicting chemotherapy toxicity in NSCLC patients.展开更多
Objective： A number of studies have reported the association of ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂ gene polymorphisms with lung cancer risk. However, the results were conflict. To clarify the impact of polymorphisms of ...Objective： A number of studies have reported the association of ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂ gene polymorphisms with lung cancer risk. However, the results were conflict. To clarify the impact of polymorphisms of ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂, on lung cancer risk, a meta-analysis was performed in this study. Methods： The electronic databases PubMed and Embase were retrieved for studies included in this meta-analysis by ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂, ＂lung＂, ＂cancer/neoplasm/tumor/carcinoma＂, ＂polymorphism＂ （An upper date limit of October, 31, 2009）. A meta-analysis was performed to evaluate the relationship among XPA, XPC and XPD polymorphism and lung cancer risks. Results： A total of 31 publications retrieved from Pubmed and Embase included in this study. XPC A939C CC genotype increased lung cancer risk in total population （recessive genetic model： OR=1.23, 95% CI：1.05-1.44; homozygote comparison： OR=1.21,95%CI：1.02-1.43and CC vs. CA contrast： OR=1.25,95%CI：1.06-1.48）, except in Asians. XPD A751C, 751C allele and CC genotype also increased lung cancer risk in total population and in Caucasians （recessive genetic model： Total population： OR=1.20, 95%CI：1.07-1.35）. No significant correlation was found between XPD A751C and lung cancer risk in Asians and African Americans. XPD G312A AA genotype increased lung cancer risk in total population, in Asians and Caucasians（recessive genetic model： Total population： OR=1.20, 95%CI： 1.06-1.36）. No significant association was found between XPA G23A, XPC C499T, XPD C156A and lung cancer risk. Conclusion： Our results suggest that the polymorphisms in XPC and XPD involve in lung cancer risks. XPA polymorphisms is less related to lung cancer risk.展开更多
AIM To validate the feasibility of high resolution computed tomography(HRCT) of the lung prior to computed tomography angiography(CTA) in assessing incidental thoracic findings during endovascular aortic aneurysm repa...AIM To validate the feasibility of high resolution computed tomography(HRCT) of the lung prior to computed tomography angiography(CTA) in assessing incidental thoracic findings during endovascular aortic aneurysm repair(EVAR) planning or follow-up.METHODS We conducted a retrospective study among 181 patients(143 men, mean age 71 years, range 50-94) referred to our centre for CTA EVAR planning or followup. HRCT and CTA were performed before or after 1 or 12 mo respectively to EVAR in all patients. All HRCT examinations were reviewed by two radiologists with 15 and 8 years experience in thoracic imaging. The results were compared with histology, bronchoscopy or follow-up HRCT in 12, 8 and 82 nodules respectively. RESULTS There were a total of 102 suspected nodules in 92 HRCT examinations, with a mean of 1.79 nodules per patient and an average diameter of 9.2 mm(range 4-56 mm). Eightynine out of 181 HRCTs resulted negative for the presence of suspected nodules with a mean smoking history of 10 pack-years(p-y, range 5-18 p-y). Eighty-two out of 102(76.4%) of the nodules met criteria for computed tomography follow-up, to exclude the malignant evolution. Of the remaining 20 nodules, 10 out of 20(50%) nodules, suspected for malignancy, underwent biopsy and then surgical intervention that confirmed the neoplastic nature: 4(20%) adenocarcinomas, 4(20%) squamous cell carcinomas, 1(5%) small cell lung cancer and 1(5%) breast cancer metastasis); 8 out of 20(40%) underwent bronchoscopy(8 pneumonia) and 2 out of 20(10%) underwent biopsy with the diagnosis of sarcoidosis.CONCLUSION HRCT in EVAR planning and follow-up allows to correctly identify patients requiring additional treatments, especially in case of lung cancer.展开更多
Lung cancer is the leading cause of cancer-related deaths worldwide.Recently,advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role th...Lung cancer is the leading cause of cancer-related deaths worldwide.Recently,advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role that cells with stem cell-like properties may have in lung tumorigenesis.Much of this research has focused on the use of the airway repair model to study response to injury.In this review,we discuss the primary evidence of the role that cancer stem cells play in lung cancer development.The implications of a stem cell origin of lung cancer are reviewed,and the importance of ongoing research to identify novel therapeutic and prognostic targets is reiterated.展开更多
Introduction: DNA repair enzymes continuously monitor DNA to correct damaged nucleotide residues generated by exposure to environmental mutagenic and cytotoxic compounds or carcinogens. Our objective was to investigat...Introduction: DNA repair enzymes continuously monitor DNA to correct damaged nucleotide residues generated by exposure to environmental mutagenic and cytotoxic compounds or carcinogens. Our objective was to investigate the association among XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD-ERCC2 (Lys751Gln), APE1 (Asp241Glu), PARP-ADPRT (Val762Ala) DNA repair gene polymorphisms and lung cancer in Turkish population. Materials and Methods: Our patient group consists of 90 patients with lung cancer and the control group had 100 healthy individuals all of those smoking. DNA was extracted using the whole blood samples. PCR- RFLP technique was used to investigate the polymorphisms on target genes. Results: There was no significant difference in the genotype distributions of XPD Lys751Gln, XRCC1 Arg194Trp, XRCC3 Thr241Met, APE1 Asp241Glu between lung cancer patients and controls for each polymorphism (p > 0.05). However, there was a significant difference between the genotype distributions of XRCC1 Arg399Gln, and PARP Val762Ala in patients and the control group (p > 0.05). Discussion: Only the polymorphisms of XRCC1 codon 399 and PARP Val762Ala alleles are associated with the risk of lung cancer. Other genotypes were not related to lung cancer.展开更多
E3 ubiquitin ligases are a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome.Therefore,E3 ubiquitin ligases play an essential role in a...E3 ubiquitin ligases are a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome.Therefore,E3 ubiquitin ligases play an essential role in a variety of biological processes including cell cycle regulation,proliferation and apoptosis.E3 ubiquitin ligases are often found overexpressed in human cancers,including lung cancer,and their deregulation has been shown to contribute to cancer development.However,the lack of specific inhibitors in clinical trials is a major issue in targeting E3 ubiquitin ligases with currently only one E3 ubiquitin ligase inhibitor being tested in the clinical setting.In this review,we focus on E3 ubiquitin ligases that have been found deregulated in lung cancer.Furthermore,we discuss the processes in which they are involved and evaluate them as potential anti-cancer targets.By better understanding the mechanisms by which E3 ubiquitin ligases regulate biological processes and their exact role in carcinogenesis,we can improve the development of specific E3 ubiquitin ligase inhibitors and pave the way for novel treatment strategies for cancer patients.展开更多
基金supported by the National Natural Science Foundation of China(81573463)Hunan Provincial Natural Science Foundation of China (2015JJ1024)
文摘Background:Chemotherapy toxicity is a serious problem from which non-small cell lung cancer(NSCLC) patients suffer.The mismatch repair(MMR) system is associated with platinum-based chemotherapy toxicity in NSCLC patients.In this study,we aimed to investigate the relationship between genetic polymorphisms in the MMR pathway and platinum-based chemotherapy toxicity in NSCLC patients.Methods:A total of 220 Chinese lung cancer patients who received at least two cycles of platinum-based chemotherapy were recruited for this study.Toxicity was evaluated in each patient after two cycles of chemotherapy.A total of 44 single nucleotide polymorphisms were selected to investigate their associations with platinum-based chemotherapy toxicity.Results:MutS homolog 2[MSH2) rs6544991[odds ratio(OR) 2.98,95%confidence interval(CI) 1.20-7.40,P = 0.019]was associated with gastrointestinal toxicity in the dominant model;MSH3 rs6151627(OR 2.38,95%CI 1.23-4.60,P = 0.010),rs6151670(OR 2.05,95%CI 1.07-3.93,P = 0.031),and rs7709909(OR 2.38,95%CI 1.23-4.64,P = 0.010)were associated with hematologic toxicity in the dominant model.Additionally,MSH5 rs805304 was significantly associated with overall toxicity(OR 2.21,95%CI 1.19-4.09,P = 0.012),and M5H5 rs707939 was significantly associated with both overall toxicity(OR 0.42,95%CI 0.23-0.76,P = 0.004) and gastrointestinal toxicity(OR 0.44,95%CI 0.20-0.96,P = 0.038) in the dominant model.Conclusion:Genetic polymorphisms in the MMR pathway are potential clinical markers for predicting chemotherapy toxicity in NSCLC patients.
基金supported by the grants from the National Eleveth-Five-Year Key Task Project of China(No.2006BA102A01)the National "863" High Tech R & D Program of China(No.2006AA02A401)China-Sweden International Scientific and Technological Cooperative Project (No.09ZCZDSF04100)
文摘Objective： A number of studies have reported the association of ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂ gene polymorphisms with lung cancer risk. However, the results were conflict. To clarify the impact of polymorphisms of ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂, on lung cancer risk, a meta-analysis was performed in this study. Methods： The electronic databases PubMed and Embase were retrieved for studies included in this meta-analysis by ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂, ＂lung＂, ＂cancer/neoplasm/tumor/carcinoma＂, ＂polymorphism＂ （An upper date limit of October, 31, 2009）. A meta-analysis was performed to evaluate the relationship among XPA, XPC and XPD polymorphism and lung cancer risks. Results： A total of 31 publications retrieved from Pubmed and Embase included in this study. XPC A939C CC genotype increased lung cancer risk in total population （recessive genetic model： OR=1.23, 95% CI：1.05-1.44; homozygote comparison： OR=1.21,95%CI：1.02-1.43and CC vs. CA contrast： OR=1.25,95%CI：1.06-1.48）, except in Asians. XPD A751C, 751C allele and CC genotype also increased lung cancer risk in total population and in Caucasians （recessive genetic model： Total population： OR=1.20, 95%CI：1.07-1.35）. No significant correlation was found between XPD A751C and lung cancer risk in Asians and African Americans. XPD G312A AA genotype increased lung cancer risk in total population, in Asians and Caucasians（recessive genetic model： Total population： OR=1.20, 95%CI： 1.06-1.36）. No significant association was found between XPA G23A, XPC C499T, XPD C156A and lung cancer risk. Conclusion： Our results suggest that the polymorphisms in XPC and XPD involve in lung cancer risks. XPA polymorphisms is less related to lung cancer risk.
文摘AIM To validate the feasibility of high resolution computed tomography(HRCT) of the lung prior to computed tomography angiography(CTA) in assessing incidental thoracic findings during endovascular aortic aneurysm repair(EVAR) planning or follow-up.METHODS We conducted a retrospective study among 181 patients(143 men, mean age 71 years, range 50-94) referred to our centre for CTA EVAR planning or followup. HRCT and CTA were performed before or after 1 or 12 mo respectively to EVAR in all patients. All HRCT examinations were reviewed by two radiologists with 15 and 8 years experience in thoracic imaging. The results were compared with histology, bronchoscopy or follow-up HRCT in 12, 8 and 82 nodules respectively. RESULTS There were a total of 102 suspected nodules in 92 HRCT examinations, with a mean of 1.79 nodules per patient and an average diameter of 9.2 mm(range 4-56 mm). Eightynine out of 181 HRCTs resulted negative for the presence of suspected nodules with a mean smoking history of 10 pack-years(p-y, range 5-18 p-y). Eighty-two out of 102(76.4%) of the nodules met criteria for computed tomography follow-up, to exclude the malignant evolution. Of the remaining 20 nodules, 10 out of 20(50%) nodules, suspected for malignancy, underwent biopsy and then surgical intervention that confirmed the neoplastic nature: 4(20%) adenocarcinomas, 4(20%) squamous cell carcinomas, 1(5%) small cell lung cancer and 1(5%) breast cancer metastasis); 8 out of 20(40%) underwent bronchoscopy(8 pneumonia) and 2 out of 20(10%) underwent biopsy with the diagnosis of sarcoidosis.CONCLUSION HRCT in EVAR planning and follow-up allows to correctly identify patients requiring additional treatments, especially in case of lung cancer.
文摘Lung cancer is the leading cause of cancer-related deaths worldwide.Recently,advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role that cells with stem cell-like properties may have in lung tumorigenesis.Much of this research has focused on the use of the airway repair model to study response to injury.In this review,we discuss the primary evidence of the role that cancer stem cells play in lung cancer development.The implications of a stem cell origin of lung cancer are reviewed,and the importance of ongoing research to identify novel therapeutic and prognostic targets is reiterated.
文摘Introduction: DNA repair enzymes continuously monitor DNA to correct damaged nucleotide residues generated by exposure to environmental mutagenic and cytotoxic compounds or carcinogens. Our objective was to investigate the association among XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD-ERCC2 (Lys751Gln), APE1 (Asp241Glu), PARP-ADPRT (Val762Ala) DNA repair gene polymorphisms and lung cancer in Turkish population. Materials and Methods: Our patient group consists of 90 patients with lung cancer and the control group had 100 healthy individuals all of those smoking. DNA was extracted using the whole blood samples. PCR- RFLP technique was used to investigate the polymorphisms on target genes. Results: There was no significant difference in the genotype distributions of XPD Lys751Gln, XRCC1 Arg194Trp, XRCC3 Thr241Met, APE1 Asp241Glu between lung cancer patients and controls for each polymorphism (p > 0.05). However, there was a significant difference between the genotype distributions of XRCC1 Arg399Gln, and PARP Val762Ala in patients and the control group (p > 0.05). Discussion: Only the polymorphisms of XRCC1 codon 399 and PARP Val762Ala alleles are associated with the risk of lung cancer. Other genotypes were not related to lung cancer.
文摘E3 ubiquitin ligases are a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome.Therefore,E3 ubiquitin ligases play an essential role in a variety of biological processes including cell cycle regulation,proliferation and apoptosis.E3 ubiquitin ligases are often found overexpressed in human cancers,including lung cancer,and their deregulation has been shown to contribute to cancer development.However,the lack of specific inhibitors in clinical trials is a major issue in targeting E3 ubiquitin ligases with currently only one E3 ubiquitin ligase inhibitor being tested in the clinical setting.In this review,we focus on E3 ubiquitin ligases that have been found deregulated in lung cancer.Furthermore,we discuss the processes in which they are involved and evaluate them as potential anti-cancer targets.By better understanding the mechanisms by which E3 ubiquitin ligases regulate biological processes and their exact role in carcinogenesis,we can improve the development of specific E3 ubiquitin ligase inhibitors and pave the way for novel treatment strategies for cancer patients.
