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Journal of Huazhong University of Science and Technology(Medical Sciences) 2016年第6期36卷 828-833页

作者： Jing LI Vang TANG Liu HUANG Qian-qian YU Guang-yuan HU Chao CHEN Peng ZHANG Xiang-lin YUAN Department of oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan430022 China

CHEK1 gene is known to play an important role in tumor progression by cell cycle ***,the association between CHEK1 and the prognosis of esophageal squamous cell carcinoma（ESCC） is *** this study,we explored the association between genetic variants in CHEK1 gene and prognosis of ESCC patients treated with radical resection.A total of 131 thoracic ESCC patients who underwent radical resection were included in this retrospective study and genotyped using the Mass Array *** to the univariate Cox hazard analysis,the GT/TT genotype of CHEK1 rs555752 was shown to be strongly related to a decreased overall survival（OS）（HR=2.560,95% CI：1.415–4.631,P=0.002） and disease-free survival（DFS）（HR=2.160,95% CI：1.258–3.710,P=0.005）.Furthermore,according to the multivariate Cox hazard analysis and multiple testing,patients with the GT/TT genotype of CHEK1 rs555752 had a notably decreased OS（HR=2.735,95% CI：1.468–5.096,P=0.002,Pc=0.006） and DFS（HR=2.282,95% CI：1.292–4.023,P=0.004,Pc=0.012）.In conclusion,genetic variants of the CHEK1 gene are significantly related to OS and DFS of ESCC patients,and may therefore be predictors of the prognosis of thoracic ESCC after surgery.

关键词： esophageal squamous cell carcinoma CHEKI single nucleotide polymorphism prognostic factor overall survival disease-free survival

Long noncoding RNA NALT1-induced gastric cancer invasion and metastasis via NOTCH signaling pathway

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World Journal of Gastroenterology 2019年第44期25卷 6508-6526页

作者： Hai-Yan Piao Shuai Guo Yue Wang Jun Zhang Medical oncology Department of Gastrointestinal Cancer Liaoning Province Cancer Hospital&Institute(Cancer Hospital of China Medical University)Shenyang 110042Liaoning ProvinceChina Gastric Cancer Department Liaoning Province Cancer Hospital&Institute(Cancer Hospital of China Medical University)Shenyang 110042Liaoning ProvinceChina

BACKGROUNDLong noncoding RNAs (lncRNAs) are aberrant and play critical roles in gastriccancer (GC) progression and metastasis. Searching for coexpressed lncRNAclusters or representative biomarkers related to malignant phenotypes of GC mayhelp to elucidate the mechanism of tumor development and predict the prognosisof *** investigate the prognostic value of NOTCH1 associated with lncRNA in T cellacute lymphoblastic leukemia 1 (NALT1) in GC and the mechanism of itsinvolvement in GC invasion and *** sequencing and corresponding clinical data were downloaded from TheCancer Genome Atlas database. The significance module was studied byweighted gene coexpression network analysis. A total of 336 clinical sampleswere included in the study. Gene silencing, reverse transcription polymerasechain reaction, western blotting, scrape motility assay, and Transwell migrationassay were used to assess the function of *** the transcriptome level, 3339 differentially expressed lncRNAs were *** gene coexpression network analysis was used to obtain 15 lncRNAclusters and observe their coexpression. Pearson’s correlation showed that blue module was correlated with tumor grade and survival. NALT1 was the hublncRNAof blue module and was an independent risk factor for GC ***1 was overexpressed in GC and its expression was closely related toinvasion and metastasis. The mechanism may involve NALT1 regulation ofNOTCH1, which is associated with lncRNA in T cell acute lymphoblasticleukemia, through cis regulation, thereby affecting the expression of the NOTCHsignaling ***1 is overexpressed and promotes invasion and metastasis of GC. Themechanism may be related to regulation of NOTCH1 by NALT1 and its effect onNOTCH signaling pathway expression.

关键词： Gastric cancer Weighted gene coexpression network analysis NALT1 NOTCH1 Cancer survival

阿帕替尼在转移性结直肠癌三线治疗的疗效及疗效预测分析

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阿帕替尼在转移性结直肠癌三线治疗的疗效及疗效预测分析

作者：杨冬阳南方医科大学

学位级别：硕士

结直肠癌(CRC)是全球第三大常见的恶性肿瘤,现阶段转移性结直肠癌的治疗已有很大进步,中位生存期达近3年,部分患者在二线治疗失败后,仍可进行三线治疗。抗肿瘤血管生成药物已成为转移性结直肠癌治疗的重要手段,该类药物治疗虽有获益,因... 详细信息

结直肠癌(CRC)是全球第三大常见的恶性肿瘤,现阶段转移性结直肠癌的治疗已有很大进步,中位生存期达近3年,部分患者在二线治疗失败后,仍可进行三线治疗。抗肿瘤血管生成药物已成为转移性结直肠癌治疗的重要手段,该类药物治疗虽有获益,因其缺乏特异生物学标志物,无法预测疗效,使得疗效受限,寻找疗效预测因素显得尤为重要。因肠癌三线治疗推荐的抗血管类药瑞戈非尼2017年才在国内上市及价格、医保报销等因素使应用受限,且当时国内无三线抗血管小分子酪氨酸激酶抑制剂药物的现状。我们需要探寻新的治疗药物或新的适应证来使二线化疗失败后仍可治疗的转移性结直肠癌患者获得更好的治疗,并探索可能的预测抗血管药物疗效因素。阿帕替尼是一种小分子血管内皮生长因子受体-2(VEGFR-2)酪氨酸激酶抑制剂(TKI),2014年已被批准用于晚期胃癌或食管胃交界腺癌的治疗。在肠癌有限的研究中亦提示阿帕替尼在转移性结直肠癌有潜在疗效获益及可控的毒性。因此,本研究对标准二线治疗失败的转移性结直肠癌患者,应用阿帕替尼片三线治疗,回顾性分析阿帕替尼在转移性结直肠癌三线治疗的疗效、安全性及可能影响疗效预测的因素,为临床治疗提供数据参考。方法:收集我院2015年10月至2018年3月诊断转移性结直肠癌标准二线治疗失败或不可耐受患者,接受阿帕替尼三线治疗的30例患者的临床资料,患者口服阿帕替尼片500 mg每天一次,28天为一个周期,分析评价阿帕替尼治疗的疗效、安全性和疗效预测因素。结果:1、30例阿帕替尼治疗的患者中位PFS 4.3月,中位OS为8.1月,1年生存率为26.1%,2年生存率为8.7%。客观缓解率(ORR)为16.7%,疾病控制率(DCR)60%,部分缓解(PR)为5例,占16.7%,疾病稳定(SD)13例占43.3%,疾病进展(PD)12例,占40%。2、大部分不良事件如高血压、蛋白尿、手足综合征、转氨酶升高、疲劳、贫血、血小板减少、白细胞减少、口腔黏膜炎等严重程度为Ⅰ或Ⅱ度。3例Ⅲ-Ⅳ度高血压(10%),2例Ⅲ-Ⅳ度蛋白尿(6.6%),3例Ⅲ-Ⅳ度手足综合征(10%)。3、阿帕替尼治疗的PFS与CEA(≤25ng/ml VS>25ng/ml)、CerB2(++～+++VS-～+)、Ki67(≤50%VS>50%)有统计学差异(P50%的患者疗效有延长趋势,提示CEA、CerB2、Ki67潜在疗效预测价值。

关键词：转移性结直肠癌三线治疗阿帕替尼疗效预测疗效安全性

Local definitive intensity-modulated radiation therapy recommended for patients initially diagnosed with nasopharyngeal carcinoma with distant metastasis after an effective systemic chemotherapy

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oncology and Translational Medicine 2018年第6期4卷 234-237页

作者： Lei Zhou Dongbo Liu Cancer Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Objective The aim of the study was to propose a hypothesis that local definitive intensity-modulated radiation therapy(IMRT) should be recommended for initially diagnosed metastatic nasopharyngeal carcinoma(NPC) and demonstrate its *** Recently published papers on local definitive radiotherapy for initially diagnosed metastatic NPC were reviewed to propose a *** Several studies revealed the survival benefits of adding local definitive radiotherapy to the systemic chemotherapy in patients initially diagnosed with metastatic *** We suggested that local definitive IMRT should be recommended in patients initially diagnosed with NPC with distant metastasis after an effective systemic chemotherapy, which may possibly prolong their survival time and potentially treat the disease.

关键词： nasopharyngeal carcinoma(NPC) metastasis intensity-modulated radiation therapy(IMRT)

ETV2 mediates endothelial transdifferentiation of glioblastoma

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Signal Transduction and Targeted Therapy 2018年第1期3卷 291-301页

作者： Chengjian Zhao Gustavo AGomez Yuwei Zhao Yu Yang Dan Cao Jing Lu Hanshuo Yang Shuo Lin Department of Molecular Cell and Developmental BiologyUniversity of California-Los AngelesLos AngelesCA 90095USA Blood research Laboratory Chengdu Blood CenterSichuanChina State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapySichuanChina

Glioblastoma multiforme(GBM)is characterized by extensive endothelial *** studies suggest that a subpopulation of endothelial cells originates via vasculogenesis by the transdifferentiation of GBM tumor cells into endothelial cells(endotransdifferentiation).The molecular mechanism underlying this process remains poorly ***,we show that the expression of ETS variant 2(ETV2),a master regulator of endothelial cell development,is highly correlated with *** studies demonstrate that ETV2 is sufficient and necessary for the transdifferentiation of a subpopulation of CD133+/Nestin+GBM/neural stem cells to an endothelial *** studies of ChIP-Seq with gain-of-function RNA-Seq data sets suggest that ETV2,in addition to activating vascular genes,represses proneural genes to direct *** endotransdifferentiation by ETV2 is VEGF-A independent,it likely accounts for the observed resistance of GBM tumor cells to antiangiogenesis *** characterization of the regulatory networks mediated by ETV2 in endo-transdifferentiation of GBM tumor cells should lead to the identification of more effective therapeutic targets for GBM.

关键词： CD133 trans ETV

The Metabolic Basis of Tumor Growth and Metastasis

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Journal of Nutritional oncology 2017年第1期2卷 22-27页

作者： Hai Yang Zhang Qiu Mo Zhang Jia Yi Han Tao Ning Guo Guang Ying Yi Ba Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin’s Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin 300060 China

Increasing research suggests that cancer is a metabolic *** tumor development,cancer cells increase their biosynthetic and bioenergetic demands to maintain tumor cell proliferation and *** focus of research on this topic has been on the metabolism of the primary tumor,while metabolic adjustments during primary tumor growth/progression and metastatic processes have not been extensively *** current evidence indicates that the metabolism during tumor development is ***,emerging data suggest that,once the tumor cells leave their primary sites,they may show different metabolic features distinct from the primary tumor,enabling them to successfully survive and *** this review,we summarize how this metabolic flexibility occurs during the growth of the primary tumor and the metastatic process,and also explore how metabolic adaptation is influenced by the microenvironments of the tumor *** hope that this review will provide inspiration and guidance for future research on tumor metabolism.

关键词： Tumor Growth Metastasis Metabolism Adaptation

Bioinformatics Analysis of miRNA-related Signaling Pathways in Non-small Cell Lung Cancer

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Journal of Nutritional oncology 2017年第2期2卷 91-102页

作者： Ming Bai Hai Yang Zhang Hai Ou Yang Tao Ning Xin Yi Wang Shao Hua Ge Shuang Li Guo Guang Ying Yi Ba Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China

The morbidity of lung cancer has increased rapidly in recent ***-small cell lung cancer(NSCLC)accounts for 80%-85% of total lung cancer *** molecular mechanism associated with NSCLC remains ***(miRNAs)play an important role at the post-transcriptional ***-associated pathways targeted by NSCLC-related miRNAs(NSCLC-miRNAs)have not been fully *** a previous study,we have demonstrated 10 miRNAs are overexpressed in NSCLC and can be used as biomarkers for NSCLC *** the present study,we found that five of the 10 miRNAs were downregulated in several common *** analyzed the protein classes,molecular functions,biological functions,and signaling pathways targeted by the 5 NSCLC-related miRNAs and four main canonical pathways,identifying potential new targets for future clinical applications.

关键词： NSCLC microRNA Pathway Bioinformatic analysis Network