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KRAS Exon 3 and PTEN Exon 7 Mutations in Small-cell Lung Cancer

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Current Medical Science 2019年第3期39卷 379-384页

作者： Lei LEI Zhi-ming JIANG Cheng-hui LI Hong-yang LU zhejiang key laboratory of diagnosis & treatment technology on thoracic oncology (Lung and Esophagus) Zhejiang Cancer Hospital Hangzhou 310022China Department of Medical oncology Zhejiang Cancer Hospital Hangzhou 310022China

Small cell lung cancer (SCLC) is recognized as one of the most aggressive and fatal malignant tumors. No significant improvement has been made to prolong the survival of SCLC patients. This study aimed to examine the mutation status of K-Ras (KRAS) and phosphatase and tensin homolog (PTEN) in SCLC patients in order to identify potential therapeutic targets for SCLC. Nineteen primary SCLC tumor specimens were enrolled in the study. Direct sequencing was perfonned to detect the mutations of KRAS exon 3 and PTEN exon 7 in the specimens. Kaplan- Meier and Cox regression analysis was performed to determine the overall survival (OS) of these SCLC patients. KRAS exon 3 mutation was found in 4 (21%) SCLC patients, and PTEN exon 7 mutation in only 1 (5%) SCLC patient. Kaplan Meier analysis showed that clinical stage and brain metastasis were significantly associated with OS (both P0.05). Cox proportional hazards regression model indicated that extensive stage of disease was the only independent negative prognostic factor for OS in SCLC patients. In conclusion, KRAS exon 3 and PTEN exon 7 mutations had no significant impact on OS of SCLC patients. Further study is still necessary to validate the molecular profiles of SCLC.

关键词： gene Ras small cell lung carcinoma prognosis

Helicobacter pylori infection and esophageal cancer risk:An updated meta-analysis

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World Journal of Gastroenterology 2013年第36期19卷 6098-6107页

作者： Fa-Jun Xie Yi-Ping Zhang Qiu-Qing Zheng Hong-Chuan Jin Fa-Liang Wang Ming Chen Lan Shao De-Hong Zou Xin-Min Yu Wei-Min Mao Department of Medical oncology Zhejiang Cancer Hospital zhejiang key laboratory of diagnosis and treatment technology on thoracic oncology (Lung and Esophagus) laboratory of Cancer Biology Sir Runrun Shaw Hospital Medical School of Zhejiang University

AIM:To clarify the association between Helicobacter pylori(***)infection and the risk of esophageal carcinoma through a meta-analysis of published ***:Studies which reported the association between *** infection and esophageal cancer published up to June 2013 were *** odds ratios(ORs)and corresponding 95%CIs of *** on esophageal cancer with respect to health control groups were *** were extracted independently by two investigators and discrepancies were resolved by discussion with a third *** statistical software,STATA(version 12.0),was applied to investigate heterogeneity among individual studies and to summarize the studies.A meta-analysis was performed using a fixed-effect or random-effect method,depending on the absence or presence of significant ***:No significant association between *** infection and esophageal squamous cell carcinoma(ESCC)risk was found in the pooled overall population(OR=0.97,95%CI:0.76-1.24).However,significant associations between *** infection and ESCC risk were found in Eastern subjects(OR=0.66,95%CI:0.43-0.89).Similarly,cytotoxin-associated gene-A(CagA)positive strains of infection may decrease the risk of ESCC in Eastern subjects(OR=0.77,95%CI:0.65-0.92),however,these associations were not statistically significant in Western subjects(OR=1.26,95%CI:0.97-1.63).For esophageal adenocarcinoma(EAC)the summary OR for *** infection and CagA positive strains of infection were 0.59(95%CI:0.51-0.68)and 0.56(95%CI:0.45-0.70),***:*** infection is associated with a decreased risk of ESCC in Eastern populations and a decreased risk of EAC in the overall population.

关键词： Helicobacter pylori Esophageal carcinoma Cancer risk Meta-analysis

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

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Journal of zhejiang University-Science B(Biomedicine & Biotechnology) 2013年第3期14卷 207-215页

作者： Wei HONG Kai WANG Yi-ping ZHANG Jun-yan KOU Dan HONG Dan SU Wei-min MAO Xin-min YU Fa-jun XIE Xiao-jian WANG Department of Medical oncology Zhejiang Cancer Hospital zhejiang key laboratory of the diagnosis and treatment technology on thoracic oncology Department of Respiratory Medicine the Second Affiliated HospitalSchool of MedicineZhejiang University Department of Medical oncology Hangzhou Cancer Hospital Institute of Immunology School of MedicineZhejiang University

Objective： The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase （MTHFR） C677T excision repair cross-complementation group 1 （ERCC1） genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer （NSCLC）. Methods： A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regi- mens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 Cl18T were genotyped using the TaqMan methods. Results： The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype （TT or CT）（41.2% versus 19.1%, P=0.01 ）. Median time to progression （TTP） of patients with MTHFR CC genotype was longer than that of patients with variant genotype （7.6 months versus 5.0 months, P=0.003）. No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions： Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.

关键词： Non-small cell lung cancer Single nucleotide polymorphism Methylenetetrahydrofolate reductase Gemcitabine Excision repair cross-complementation group 1

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Paclitaxel-etoposide-carboplatin/cisplatin versus etoposidecarboplatin/cisplatin as first-line treatment for combined small-cell lung cancer: a retrospective analysis of 62 cases

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Cancer Biology & Medicine 2015年第2期12卷 117-125页

作者： Yue-Ya Li Chan Zhou Deng-Xia Yang Jing Wang Zhu-Jun Liu Xin-Yue Wang Kai Li Department of thoracic oncology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Lung Cancer Diagnosis and Treatment Center

Objective: To compare the efficacy and adverse effects of paclitaxel-etoposide-carboplatin/cisplatin(TEP/TCE) regimen with those of etoposide-carboplatin/cisplatin(EP/CE) regimen as first-line treatment for combined small-cell lung cancer(CSCLC).Methods: A retrospective study was conducted on 62 CSCLC patients who were treated at Tianjin Medical University Cancer Institute and Hospital from July 2000 to April 2013 and administered with TEP/TCE regimen(n=19) or EP/CE regimen(n=43) as first-line CSCLC treatment. All patients received more than two cycles of chemotherapy, and the response was evaluated every two cycles. The primary endpoint was overall survival(OS), and the secondary endpoints were progression-free survival(PFS), objective response rate(ORR), disease control rate(DCR), and adverse effects. Results: ORR between the TEP/TCE and EP/CE groups showed a statistical difference(90% vs. 53%, P=0.033). Both groups failed to reach a statistical difference in DCR(100% vs. 86%, P=0.212). The median PFS and OS of the TEP/TCE group were slightly longer than those of the EP/CE group, although both groups failed to reach a statistical difference(10.5 vs. 8.9 months, P=0.484; 24.0 vs. 17.5 months, P=0.457). However, stratified analysis indicated that the PFS of patients with stages III and IV CSCLC showed marginally significant difference between the TEP/TCE and EP/CE groups(19.5 vs. 7.6 months; P=0.071). Both rates of grade IV bone marrow depression and termination of chemotherapy in the TEP/TCE group were significantly higher than those in the EP/CE group(26.3% vs. 7.0%, P=0.036; 31.6% vs. 14.7%, P=0.004). Conclusion: The TEP/TCE regimen may not be preferred for CSCLC, and this three-drug regimen requires further exploration and research. To date, the EP/CE regimen remains the standard treatment for CSCLC patients.

关键词： Small cell lung carcinoma (SCLC) chemotherapy CE regimen adverse effects survival analysis prognosis

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Diet high in branched-chain amino acid promotes PDAC development by USP1-mediated BCAT2 stabilization

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National Science Review 2022年第5期9卷 119-128页

作者： Jin-Tao Li Kai-Yue Li Ying Su Yuan Shen Ming-Zhu Lei Fan Zhang Miao Yin Zheng-Jun Chen Wen-Yu Wen Wei-Guo Hu Dan Su Jia Qu Qun-Ying Lei Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Cancer Institutes Key Laboratory of Breast Cancer in ShanghaiShanghai Key Laboratory of Medical EpigeneticsInternational Co-Laboratory of Medical Epigenetics and MetabolismMinistry of Science and Technology Shanghai Medical College Fudan University State key laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell ScienceChinese Academy of Sciences Cancer Research Institute Zhejiang Cancer Hospital and Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology of Zhejiang Province Department of oncology Shanghai Medical College Fudan University State key laboratory of Medical Neurobiology Fudan University

BCAT2-mediated branched-chain amino acid(BCAA) catabolism is critical for pancreatic ductal adenocarcinoma(PDAC) development,especially at an early ***,whether a high-BCAA diet promotes PDAC development in vivo,and the underlying mechanism of BCAT2 upregulation,remain ***,we find that a high-BCAA diet promotes pancreatic intraepithelial neoplasia(PanIN)progression in LSL-KrasG12 D/+; Pdx1-Cre(KC) ***,we screened with an available deubiquitylase library which contains 31 members of USP family and identified that USP1 deubiquitylates BCAT2 at the K229 ***,BCAA increases USP1 protein at the translational level via the GCN2-eIF2α pathway both in vitro and in *** importantly,USP1 inhibition recedes cell proliferation and clone formation in PDAC cells and attenuates pancreas tumor growth in an orthotopic transplanted mice ***,a positive correlation between USP1 and BCAT2 is found in KC;LSL-KrasG12D/+;p53flox/+;Pdx1-Cre mice and clinical ***,a therapeutic targeting USP1-BCAT2-BCAA metabolic axis could be considered as a rational strategy for treatment of PDAC and precisive dietary intervention of BCAA has potentially translational significance.

关键词： USP1 deubiquitylation BCAT2 PanIN PDAC

A Meta-Analysis of Randomized Controlled Trials Comparing Early to Late Concurrent thoracic Radiotherapy with Etoposide and Cisplatin/Carboplatin Chemotherapy for Limited-Disease Small Cell Lung Cancer

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A Meta-Analysis of Randomized Controlled Trials Comparing Ea...

2013年苏、浙两省抗癌协会肿瘤标志物研究新进展学术年会暨国家级继续教育培训班

作者： Hongyang Lu Luo Fang Xiaojia Wang Jufen Cai Weimin Mao zhejiang key laboratory of diagnosis and treatment technology on thoracic oncology(Lung and Esophagus) Zhejiang Cancer Hospital

Purpose:To clear the optimal time of concurrent thoracic radiotherapy(TRT) with etoposide and cisplatin/carboplatin(EP/EC) chemotherapy for limited-disease small cell lung cancer(LD SCLC). Methods:Randomized controlled trials were identified according to MEDLINE,the Cochrane Central Register of Controlled Trials,EMBASE,and so on comparing early to late concurrent TRT with EP/EC chemotherapy for LD *** thoracic radiotherapy(ERT) was defined as beginning radiation within 30 days after the start of chemotherapy. Results:There are three eligible randomized controlled *** significance difference in objective response was detected between early concurrent TRT and late concurrent TRT(RR:1.01,95%CI 0.86-1.18,P=0.90).Similar result was detected in 1-,2-,3-,and 5-year survival rates between early concurrent TRT and late concurrent TRT(RR:1.06,95%CI 0.88-1.27,P=0.56;RR:1.15,95%CI 0.77-1.71, P=0.49;RR:0.90,95%CI 0.66-1.22,P=0.49;RR:1.18,95%CI 0.64-2.16,P=0.60). Total grade 3-4 adverse events including anemia,leucopenia,neutropenia, thrombocytopenia,nausea and vomiting,infection,esophageal toxicity,pulmonary toxicity,alopecia and hemorrhage in early concurrent TRT were significantly higher than that in late concurrent TRT(RR:1.21,95%CI 1.03-1.43,P=0.02). Conclusion:The result of our work indicates that survival rate of LD-SCLC with late concurrent TRT combined EP/EC chemotherapy is similar with early concurrent TRT, while grade 3-4 adverse events were less.

关键词： Small cell lung cancer Timing radiotherapy Limited stage Meta-analysis

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A Meta-Analysis of Randomized Controlled Trials Comparing Ea...

Chemotherapy and EGFR-tyrosine Kinase Inhibitors in The treatment of Non-small Cell Lung Cancer with Brain Metastases:A Survival Analysis of 210 Patients

抗肿瘤药物研究新进展与肿瘤个性化药物治疗论坛

作者： Hongyang Lu Luo Fang Xiaojia Wang Jvfen Cai Weimin Mao zhejiang key laboratory of diagnosis and treatment technology on thoracic oncology(Lung and Esophagus) Zhejiang Cancer Hospital

[Purpose]-To clear the optimal time of concurrent thoracic radiotherapy(TRT) with etoposide and cisplatin/carboplatin(EP/EC) chemotherapy for limited-disease small cell lung cancer (LD SCLC). [Materials and methods]-Randomized controlled trials were identified according to MEDLINE,the Cochrane Central Register of Controlled Trials,EMBASE,and so on comparing early to late concurrent TRT with EP/EC chemotherapy for LD *** thoracic radiotherapy(ERT) was defined as beginning radiation within 30 days after the start of *** are three eligible randomized controlled trials. [Results]- No significance difference in objective response was detected between early concurrent TRT and late concurrent TRT(RR:1.01,95%CI 0.86-1.18,P=0.90).Similar result was detected in 1-,2-,3- and 5-year survival rates between early concurrent TRT and late concurrent TRT(RR:1.06,95%CI 0.88-1.27,P=0.56;RR:1.15,95%CI 0.77- 1.71,P=0.49;RR:0.90,95%CI 0.66-1.22,P=0.49;RR:1.18,95%CI 0.64-2.16,P= 0.60).Total grade 3-4 adverse events including anemia,leucopenia,neutropenia, thrombocytopenia,nausea and vomiting,infection,esophageal toxicity,pulmonary toxicity, alopecia and hemorrhage in early concurrent TRT were significantly higher than that in late concurrent TRT(RR:1.21,95%CI 1.03-1.43,P=0.02). [Conclusion]-The result of our work indicates that survival rate of LD-SCLC with late concurrent TRT combined EP/EC chemotherapy is similar with early concurrent TRT, while grade 3-4 adverse events were less.

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Chemotherapy and EGFR-tyrosine Kinase Inhibitors in The Trea...

Screening of Potential Biomarkers for Gastric Cancer with Diagnostic Value Using Label-free Global Proteome Analysis

抗肿瘤药物研究新进展与肿瘤个性化药物治疗论坛

作者： FAN Yun HUANG Zhi-yu FANG Luo MIU Lu-lu LIN Neng-ming GONG Lei YU Hai-feng YANG Hai-yan zhejiang key laboratory of diagnosis & treatment technology on thoracic oncology(esophagus lung)Zhejiang Cancer Hospital

[Purpose]Chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKIs) treatments remain under dispute for patients with brain metastases from non-small cell lung cancer(NSCLC).[Methods]We retrospectively studied the outcomes of solely localized treatments or localized treatments in combination with chemotherapy and/or EGFR-TKIs medications for 210 NSCLC patients with brain *** effects of treatment modality,Karnofsky performance status(KPS),age, primary tumor histology,number of brain metastases and other factors on survival were analyzed and the robustness of two prognostic indices(the RPA and GPA models) were evaluated.[Results]The median survival time(MST) for patients with systemic medication and localized treatments was higher than that with localized treatments alone (11.0 vs 3.0 months,P=0.000).Within the systemic medication group,the MST was significantly higher for EGFR-TKI than that for chemotherapy treatments(12.0 vs 9.0 months,P=0.002).The MST of patients with mutated EGFR gene was 20 months vs 8 months for patients with the EGFR wild type gene in the EGFR-TKI *** MST with pemetrexed medication was significantly higher than that with other chemotherapies (13.0 vs 7.0 months,P=0.006).In a multivariate analysis,prognosis was significantly correlated with treatment modality(P=0.000),KPS(P=0.000),number of brain metastases(P=0.001) and tumor histological type(P=0.007).In the Graded Prognostic Assessment(GPA) model,the survival curves of subgroups showed clear separations. [Conclusions]NSCLC patients with brain metastases had a longer survival benefit from chemotherapies,especially pemetrexed and/or TKIs along with localized treatments and the GPA index is a robust model for prognostic evaluation.

关键词： non-small cell lung cancer chemotherapy EGFR tyrosine kinase inhibitor brain metastasis

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Genomics, Proteomics & Bioinformatics 2020年第6期18卷 679-695页

作者： Yongxi Song Jun Wang Jingxu Sun Xiaowan Chen Jinxin Shi Zhonghua Wu Dehao Yu Fei Zhang Zhenning Wang Department of Surgical oncology and General Surgery Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsMinistry of EducationThe First Affiliated Hospital of China Medical UniversityShenyang 110001China

Gastric cancer(GC)is known as a top malignant type of tumors *** the recent decrease in mortality rates,the prognosis remains ***,it is necessary to find novel biomarkers with early diagnostic value for *** this study,we present a large-scale proteomic analysis of 30 GC tissues and 30 matched healthy tissues using label-free global proteome *** results identified 537 differentially expressed proteins,including 280 upregulated and 257 downregulated *** ingenuity pathway analysis(IPA)results indicated that the sirtuin signaling pathway was the most activated pathway in GC tissues whereas oxidative phosphorylation was the most ***,the most activated molecular function was cellular movement,including tissue invasion by tumor cell *** on IPA results,15 hub proteins were *** the receiver operating characteristic curve,most of hub proteins showed a high diagnostic power in distinguishing between tumors and healthy controls.A four-protein(ATP5B-ATP5O-NDUFB4-NDUFB8)diagnostic signature was built using a random forest *** area under the curve(AUC)values of this model were 0.996 and 0.886 for the training and testing sets,respectively,suggesting that the four-protein signature has a high diagnostic *** signature was further tested with independent datasets using plasma enzyme-linked immune sorbent assays,resulting in an AUC value of 0.778 for distinguishing GC tissues from healthy controls,and using immunohistochemical tissue microarray analysis,resulting in an AUC value of *** conclusion,this study identifies potential biomarkers and improves our understanding of the pathogenesis,providing novel therapeutic targets for GC.

关键词： Gastric cancer Proteomics Label-free Bioinformatics diagnosis

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