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Does not hUTP14a promoter form a regulation feedback loop with P53?

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Chinese Journal of Cancer Research 2014年第2期26卷 159-165页

作者： Jingyi Zhang Yafei Guo Xiaojuan Du baocai xing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Hepatic Biliary & Pancreatic Surgery IPeking University Cancer Hospital & Institute Department of Cell Biology Peking University Health Science Center

Objective： We previously found that hUTP14a binds P53 and promotes P53 degradation. However, if hUTP14a is a downstream gene of P53 remains to be determined. This study aimed to identify the promoter of h UTP14a and investigate if h UTP14a is regulated by P53. Methods： The hUTPI4a promoter region was cloned into pGL3-Basic-luciferase reporter plasmid to get pGL3-hUTP14a-luc. The reporter plasmid was transfected into 293T cells and luciferase activity was evaluated by the Dual-Luciferase Reporter Assay System. Putative transcription factors were identified through searching Matlnspector Professional and Algorismica i Genetica databases. Either pGL3-hUTPI4aluc or p21 promoter reporter plasmid was co-transfected with increasing dose of p53 plasmid, and luciferase activity was evaluated. A series of deletion constructs of pGL3-hUTP14a-luc were constructed and minimal promoter region of hUTP14a was determined. Differences of the lnciferase activities between different groups were assessed by statistical analysis. Results： The hUTP14a gene promoter reporter construct was correctly cloned and was demonstrated to possess promoter activity. The transcription of hUTP14a was not regulated by P53. The minimal promoter region of h UTP14a gene is located between -203 to -100 of the transcription initiation site. Conclusion： Unlike other P53-interacting proteins such as MDM2, Pirh2 and Cop I which promote P53 degradation and whose transcriptions are regulated by P53, does not hUTP14a transcription form a regulation feedback loop with P 53.

关键词： hUTP 14a luciferase activity promoter P5 3 transcription factor

Surgical decision-making: can patients benefit?

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Hepatobiliary Surgery and Nutrition 2021年第4期10卷 512-514页

作者： Ming Liu baocai xing Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Hepatopancreatobiliary Surgery Department IPeking University Cancer Hospital&InstituteBeijingChina

What is surgery?It is difficult for us to have time to think about this broad question in our busy,day-to-day *** some“super hospitals”,patient admission and surgical operation have even become an“assembly-line”*** a patient successfully recovers from an operation without any postoperative complications,we may be silently proud of our surgical skills.

关键词： operation surgery Surgical

National guidelines for diagnosis and treatment of pancreatic cancer 2022 in China(English version)

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Chinese Journal of Cancer Research 2022年第3期34卷 238-255页

作者：无 baocai xing Kemin Jin National Health Commission of the People’s Republic of China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Peking University Cancer Hospital&Institute

Contents *** *** techniques and applications 2.1 Risk factors for pancreatic cancer 2.2 Clinical manifestations 2.3 Physical examination 2.4 Radiological examination 2.4.1 Ultrasound 2.4.2 Computed tomography(CT)2.4.3 Magnetic resonance imaging(MRI)and magnetic resonance cholangiopancreatography(MRCP)2.4.4 Positron emission tomography-CT(PET-CT)。

关键词： diagnosis cancer Clinical

结直肠癌肝转移术后预后分析——单中心20年经验分享

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中华转移性肿瘤杂志 2024年第1期7卷 10-17页

作者：王明帅王宏伟包全金克敏王崑邢宝才北京大学肿瘤医院暨北京市肿瘤防治研究所肝胆胰外一科恶性肿瘤发病机制及转化研究教育部重点实验室北京100142

目的分析结直肠癌肝转移(CRLM)手术治疗患者预后及相关影响因素。方法回顾性分析2001年1月至2020年12月在北京大学肿瘤医院行结直肠癌肝转移手术的1 139例患者资料。依据手术时间分为A组(2001年1月至2012年12月, 183例)、B组(2013年1月... 详细信息

目的分析结直肠癌肝转移(CRLM)手术治疗患者预后及相关影响因素。方法回顾性分析2001年1月至2020年12月在北京大学肿瘤医院行结直肠癌肝转移手术的1 139例患者资料。依据手术时间分为A组(2001年1月至2012年12月, 183例)、B组(2013年1月至2020年12月, 956例)。对比两组间生存差异及相关影响因素。结果 A组和B组中位总生存(OS)时间分别为34.3个月(95%CI为27.7个月~41.0个月)和54.7个月(95%CI为48.5个月~60.9个月), 5年OS率分别为31.9%和47.2%;中位无瘤生存(DFS)时间分别为10.1个月(95%CI为8.2~12.1个月)和12.2个月(95%CI为11.1~13.2个月), 5年DFS率分别为16.9%和26.4%。多因素分析提示女性、累积疾病评分2~3分、T3-T4期、N1-N2期、RAS/BRAF基因突变、围手术期未行靶向治疗、肝转移病灶多发、术前病灶最大直径>30 mm、术前癌胚抗原>20 ng/mL、大范围肝切除是较差OS的独立危险因素(均P<0.05)。结论 CRLM是生物学行为较好的一类疾病, 应采取积极治疗态度, 多学科会诊的广泛应用以及多手段联合的治疗策略正逐渐改善CRLM患者预后。未来需要更多手段去判断患者肿瘤生物学行为, 期望进一步改善患者预后。

关键词：结直肠癌肝转移肝切除综合治疗预后

Multi-omics Analysis of Primary Cell Culture Models Reveals Genetic and Epigenetic Basis of Intratumoral Phenotypic Diversity

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Genomics, Proteomics & Bioinformatics 2019年第6期17卷 576-589页

作者： Sixue Liu Zuyu Yang Guanghao Li Chunyan Li Yanting Luo Qiang Gong Xin Wu Tao Li Zhiqian Zhang baocai xing Xiaolan Xu Xuemei Lu CAS Key Laboratory of Genomics and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Invasive Pathogens Laboratory Institute of Environmental Science and ResearchPorirua 5022WellingtonNew Zealand Department of Cell Biology Key Laboratory of Carcinogenesis and Translational ResearchCenter for Molecular and Translational MedicinePeking University Cancer Hospital and InstituteBeijing 100142China Department of Hepatobiliary Surgery I Peking University Cancer Hospital and InstituteBeijing 100142China National Key Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China CAS Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China

Uncovering the functionally essential variations related to tumorigenesis and tumor progression from cancer genomics data is still challenging due to the genetic diversity among patients,and extensive inter-and intra-tumoral heterogeneity at different levels of gene expression regulation,including but not limited to the genomic, epigenomic, and transcriptional levels. To minimize the impact of germline genetic heterogeneities, in this study, we establish multiple primary cultures from the primary and recurrent tumors of a single patient with hepatocellular carcinoma(HCC). Multiomics sequencing was performed for these cultures that encompass the diversity of tumor cells from the same patient. Variations in the genome sequence, epigenetic modification, and gene expression are used to infer the phylogenetic relationships of these cell cultures. We find the discrepancy among the relationships revealed by single nucleotide variations(SNVs) and transcriptional/epigenomic profiles from the cell cultures. We fail to find overlap between sample-specific mutated genes and differentially expressed genes(DEGs), suggesting that most of the heterogeneous SNVs among tumor stages or lineages of the patient are functionally insignificant. Moreover, copy number alterations(CNAs) and DNA methylation variation within gene bodies, rather than promoters, are significantly correlated with gene expression variability among these cell cultures. Pathway analysis of CNA/DNA methylation-related genes indicates that a single cell clone from the recurrent tumor exhibits distinct cellular characteristics and tumorigenicity, and such an observation is further confirmed by cellular experiments both in vitro and in vivo. Our systematic analysis reveals that CNAs and epigenomic changes, rather than SNVs, are more likely to contribute to the phenotypic diversity among subpopulations in the tumor. These findings suggest that new therapeutic strategies targeting gene dosage and epigenetic modification s

关键词： Intra-individual tumor heterogeneity Parallel primary culture Multi-omics Functional phenotypic diversity

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结直肠癌肝转移围手术期化疗

中华胃肠外科杂志 2019年第4期22卷 321-328页

作者：徐达邢宝才北京大学肿瘤医院暨北京市肿瘤防治研究所肝胆胰外一科恶性肿瘤发病机制及转化研究教育部重点实验室100142

结直肠癌肝转移(CRLM)的发病率逐年升高。手术切除是CRLM患者获得长期生存最主要的手段,根治切除后的5年生存率约为50%。在初始就诊时只有20%的患者属于可切除,总体手术切除后复发率超过70%。随着有效化疗药物及靶向药物的出现,围手术... 详细信息

结直肠癌肝转移(CRLM)的发病率逐年升高。手术切除是CRLM患者获得长期生存最主要的手段,根治切除后的5年生存率约为50%。在初始就诊时只有20%的患者属于可切除,总体手术切除后复发率超过70%。随着有效化疗药物及靶向药物的出现,围手术期化疗得到了广泛应用。对于初始可切除肝转移患者,通过围手术期化疗可能有助于降低复发、延长生存。而对于初始不可切除的患者,则可以通过强力的化疗使部分患者转化为可切除并进行根治手术。但是由于CRLM预后影响因素众多,异质性高,很多问题缺乏大样本前瞻性的临床试验证据。因此,围手术期化疗的临床实践仍然存在许多争议,包括单纯化疗是否为可切除肝转移的最佳术前治疗方案、新辅助化疗联合靶向治疗是否优于单纯化疗、哪些人群是化疗联合靶向治疗的获益人群、哪些人群是转化治疗的人群、一线治疗如何选择转化治疗方案等。本文详细阐述了CRLM围手期新辅助化疗、转化治疗和辅助化疗的研究现状,并强调CRLM是一种全身性疾病,在为CRLM患者进行治疗决策时,需要多学科团队协作,结合患者的具体情况进行个体化的诊治。

关键词：结直肠肿瘤转移,肝手术化疗

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重视结直肠癌肝转移生物学行为的评价

中华肝胆外科杂志 2020年第7期26卷 481-484页

作者：邢宝才徐达北京大学肿瘤医院暨北京市肿瘤防治研究所肝胆胰外一科恶性肿瘤发病机制及转化研究教育部重点实验室北京100142

近年来结直肠癌肝转移的发生率逐年升高,手术切除是肝转移患者获得长期生存的重要手段,但是手术切除后复发率达到60%~70%。因此,明确结直肠癌肝转移患者术后复发的高危因素,精准评价肿瘤生物学行为,有助于更好地选择术前治疗方案、局部... 详细信息

近年来结直肠癌肝转移的发生率逐年升高,手术切除是肝转移患者获得长期生存的重要手段,但是手术切除后复发率达到60%~70%。因此,明确结直肠癌肝转移患者术后复发的高危因素,精准评价肿瘤生物学行为,有助于更好地选择术前治疗方案、局部治疗时机以及手术方式,也是提高肝转移患者手术切除后生存获益的关键。本文详细阐述了目前研究比较明确的影响结直肠癌肝转移术后复发和生存的主要因素,包括临床危险评分、术前化疗反应性、基因状态和原发肿瘤位置。

关键词：结直肠肿瘤肝转移外科手术

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结直肠癌肝转移转化治疗的争议与思考

中华肿瘤杂志 2019年第2期41卷 81-85页

作者：徐达邢宝才北京大学肿瘤医院暨北京市肿瘤防治研究所肝胆胰外一科恶性肿瘤发病机制及转化研究教育部重点实验室100142

结直肠癌肝转移(CRLM)的发病率近年来逐渐升高。手术切除是CRLM患者获得长期生存的主要手段,但是只有20%的患者有手术切除的机会。通过有效的转化治疗使初诊时不可切除的CRLM转化为可切除并进行外科手术,患者的5年生存率可超过30%,显著... 详细信息

结直肠癌肝转移(CRLM)的发病率近年来逐渐升高。手术切除是CRLM患者获得长期生存的主要手段,但是只有20%的患者有手术切除的机会。通过有效的转化治疗使初诊时不可切除的CRLM转化为可切除并进行外科手术,患者的5年生存率可超过30%,显著优于接受单纯的姑息治疗。因此对于初诊时不可切除的患者,合理地制订转化治疗策略使初诊时不可切除的CRLM转化为可切除,是提高CRLM患者长期生存的关键,但在临床实践中还存在不少争议。笔者根据自身的经验并结合既往的相关研究,分别从转化治疗的适用人群、转化治疗方案的选择以及化疗后消失病灶的认识与处理3个方面进行了探讨。

关键词：结直肠肿瘤转移,肝药物疗法转化治疗

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结直肠癌肝转移外科治疗策略

中国肿瘤临床 2015年第17期42卷 845-849页

作者：徐达邢宝才北京大学肿瘤医院北京市肿瘤防治研究所肝胆胰外一科恶性肿瘤发病机制及转化研究教育部重点实验室北京市100142

目前手术切除是结直肠癌肝转移(CRLM)唯一具有治愈可能的治疗方式。近年来随着全身化疗及靶向药物的发展、肝动脉灌注化疗的应用,对于CRLM治疗的有效率明显升高,通过手术获益的患者逐渐增多;而如射频消融、二步切除等外科技术的进步,也... 详细信息

目前手术切除是结直肠癌肝转移(CRLM)唯一具有治愈可能的治疗方式。近年来随着全身化疗及靶向药物的发展、肝动脉灌注化疗的应用,对于CRLM治疗的有效率明显升高,通过手术获益的患者逐渐增多;而如射频消融、二步切除等外科技术的进步,也为更多CRLM患者提供了治愈的机会。多学科诊疗模式(MDT)也为更多CRLM患者的个体化诊治创造了机会,使未来CRLM的治疗向更加精准的方向发展。

关键词：结直肠癌肝转移外科手术治疗