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Does in-house availability of multidisciplinary teams increase survival in upper gastrointestinal-cancer?

World Journal of Gastrointestinal oncology 2013年第3期5卷 60-67页

作者： Christian Kersten Milada Cvancarova Svein Mjland Odd Mjland department of oncology Southern Hospital Trust the Centre for Cancer Treatment Department of Oncology Southern Hospital Trust the Section of abdominal Surgery Department of Abdominal Surgery Southern Hospital Trust

AIM: To investigate the effect of the establishment of in-house multidisciplinary team (MDT) availability (iMDTa) on survival in upper gastrointestinal cancer (UGI) patients. METHODS: In 2001, a cancer centre with irradiation and chemotherapy facilities was established in the Norwegian county of West Agder with a change of iMDTa (WA/MDT-Change). "iMDTa"-status was defined according to the availability of the necessary specialists within one institution on one campus, serving the population of one county. We compared survival rates during 2000-2008 for UGI patients living in counties with (MDT-Yes), without (MDT-No), with a mix (MDT-Mix) and WA/MDT-Change. Survival was calculated with Kaplan-Meier method. Cox model was used to uncover differences between counties with different MDT status when adjusted for age, sex and stage. RESULTS: We analyzed 395 patients from WA/MDT-Change and compared their survival to 12 135 UGIpatients from four other Norwegian regions. Median overall survival for UGI patients in WA/MDT-Change increased from 129 to 300 d from 2000-2008, P = 0.001. The regions with the highest level of iMDTa achieved the largest decrease in risk of death for UGI cancers (compared to the county with MDT-Mix: MDT-Yes 11%, P <0.05 and WA/MDT-Change 15%, P < 0.05). Analyzing the different tumour entities separately, patients living in the WA/MDT-Change county reached a statisti-cally significant reduction in the risk of death [hazard ratios (HR)] compared to patients in the county with MDT-Mix for oesophageal and gastric, but not for pan-creatic cancer. HR for the study period 2000-2004 are given first and then for the period 2005-2008: The HR for oesophageal cancers was reduced from [HR = 1.12; 95%CI: 0.75-1.68 to HR = 0.60, 95%CI: 0.38-0.95] and for gastric cancers from [HR = 0.87, 95%CI: 0.66-1.15 to HR = 0.63, 95%CI: 0.43-0.93], but not for pancreatic cancer [HR = 1.04-, 95%CI: 0.83-1.3 for 2000-2004 and HR = 1.01, 95%CI: 0.78-1.3 for 2005-2008]. UGI patients treated during the second study period in the co

关键词： Gastric cancer Gastroesophageal cancer Oesophageal cancer Pancreatic cancer Multidisci-plinary treatment Multidisciplinary team Survival

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Challenges and exploration for immunotherapies targeting cold colorectal cancer

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World Journal of Gastrointestinal oncology 2023年第1期15卷 55-68页

作者： Dan-Dan Li Yuan-Ling Tang Xin Wang Department of Abdominal Oncology/Radiation oncology Cancer CenterWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

In recent years,immune checkpoint inhibitors(ICIs)have made significant breakthroughs in the treatment of various tumors,greatly improving clinical efficacy.As the fifth most common antitumor treatment strategy for patients with solid tumors after surgery,chemotherapy,radiotherapy and targeted therapy,the therapeutic response to ICIs largely depends on the number and spatial distribution of effector T cells that can effectively identify and kill tumor cells,features that are also important when distinguishing malignant tumors from“cold tumors”or“hot tumors”.At present,only a small proportion of colorectal cancer(CRC)patients with deficient mismatch repair(dMMR)or who are microsatellite instability-high(MSI-H)can benefit from ICI treatments because these patients have the characteristics of a“hot tumor”,with a high tumor mutational burden(TMB)and massive immune cell infiltration,making the tumor more easily recognized by the immune system.In contrast,a majority of CRC patients with proficient MMR(pMMR)or who are microsatellite stable(MSS)have a low TMB,lack immune cell infiltration,and have almost no response to immune monotherapy;thus,these tumors are“cold”.The greatest challenge today is how to improve the immunotherapy response of“cold tumor”patients.With the development of clinical research,immunotherapies combined with other treatment strategies(such as targeted therapy,chemotherapy,and radiotherapy)have now become potentially effective clinical strategies and research hotspots.Therefore,the question of how to promote the transformation of“cold tumors”to“hot tumors”and break through the bottleneck of immunotherapy for cold tumors in CRC patients urgently requires consideration.Only by developing an in-depth understanding of the immunotherapy mechanisms of cold CRCs can we screen out the immunotherapy-dominant groups and explore the most suitable treatment options for individuals to improve therapeutic efficacy.

关键词： Colorectal cancer Immune checkpoint inhibitors Cold tumors Immunotherapy mechanism Combination therapy Effector T cells

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癌症患者癌因性疲乏、生活质量和疼痛程度的相关性研究

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International Journal of Nursing Sciences 2023年第1期10卷 111-116页

作者：刘敦翁金森柯熹吴贤毅黄思婷 The School of Nursing Fujian Medical UniversityFuzhouFujianChina department of Critical Care Medicine Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouFujianChina Department of Abdominal Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouFujianChina

目的分析癌症患者疼痛程度、疲劳程度与生活质量之间的关系。方法采用横断面研究设计。应用便利抽样法于2019年5-11月选取两省两所三级甲等医院224例接受化疗且符合入选标准的癌症患者进行调查。采用一般资料调查表、简明疲劳量表(Brief... 详细信息

目的分析癌症患者疼痛程度、疲劳程度与生活质量之间的关系。方法采用横断面研究设计。应用便利抽样法于2019年5-11月选取两省两所三级甲等医院224例接受化疗且符合入选标准的癌症患者进行调查。采用一般资料调查表、简明疲劳量表(Brief Fatigue Inventory,BFI)、疼痛数字评分量表(The Nume-rical Rating Scale,NRS)和由欧洲癌症治疗和研究组织编制的生活质量量表(The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire,EORTCQLQ-C30)收集资料。结果在报告过去24 h最严重的疼痛情况时,85例(37.9%)有轻度疼痛,121例(54.0%)有中度疼痛,18例(8.0%)有重度疼痛。此外,92例(41.1%)患者有轻度疲劳,72例(32.1%)有中度疲劳,60例(26.8%)有重度疲劳。大多数轻度疼痛的患者仅经历轻度疲劳,其生活质量也处于中等水平。中度和重度疼痛患者大多有中度或更高程度的疲劳(r=0.296,P<0.01)和较低的生活质量(r=-0.141,P<0.01)。轻度疼痛患者中,疲劳与生活质量间不存在相关性(r=-0.179,P=0.104)。中、重度疼痛患者的疲劳与生活质量呈负相关(r=-0.537,P<0.01;r=-0.509,P<0.05)。结论中、重度疼痛患者的疲劳症状比轻度疼痛患者更重,生活质量也更低。护士应更关注中重度疼痛患者,探索症状间的相互作用机制,开展症状联合干预,以提高患者生活质量。

关键词：疲乏肿瘤疼痛病人生活质量

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Assessment of circulating tumor DNA in cerebrospinal fluid by whole exome sequencing to detect genomic alterations of glioblastoma

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Chinese Medical Journal 2020年第12期133卷 1415-1421页

作者： Hao Duan Ji-Long Hu Zheng-He Chen Jue-Hui Li Zhen-Qiang He Zhen-Ning Wang Guan-Hua Zhang Xiao-Yu Guo Lun Liang Yong-Gao Mou department of Neurosurgery/Neuro-oncology State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China department of abdominal Surgery oncology Jiangxi Cancer HospitalNanchangJiangxi 330029China

Background:Cerebrospinal fluid(CSF)has been demonstrated as a better source of circulating tumor DNA(ctDNA)than plasma for brain tumors.However,it is unclear whether whole exome sequencing(WES)is qualified for detection of ctDNA in CSF.The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma.Methods:CSFs of ten glioblastoma patients were collected pre-operatively at the department of Neurosurgery,Sun Yat-sen University Cancer Center.ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES.The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared.Results:Due to the ctDNA in CSF was unqualified for exome sequencing for one patient,nine patients were included into the final analysis.More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples(3.56±0.75 vs.2.22±0.32,P=0.097),while the statistical significance was limited by the small sample size.The average mutation frequencies were similar in CSF and tumor tissue samples(74.1%±6.0%vs.73.8%±6.0%,P=0.924).The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone,family 3A(H3F3A)which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES.Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF.Conclusion:Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma,which may provide useful information for the decision of treatment strategy.

关键词： Circulating tumor DNA Cerebrospinal fluid Glioblastoma Mutation Whole exome sequencing

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Targeting RAF dimers in RAS mutant tumors: From biology to clinic

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1895-1923页

作者： Yin H. Tang Q. Xia H. Bi F. Division of abdominal Cancer Department of Medical Oncology Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology West China Hospital Sichuan University Chengdu 610041 China

RAS mutations occur in approximately 30% of tumors worldwide and have a poor prognosis due to limited therapies. Covalent targeting of KRAS G12C has achieved significant success in recent years, but there is still a lack of efficient therapeutic approaches for tumors with non-G12C KRAS mutations. A highly promising approach is to target the MAPK pathway downstream of RAS, with a particular focus on RAF kinases. First-generation RAF inhibitors have been authorized to treat BRAF mutant tumors for over a decade. However, their use in RAS-mutated tumors is not recommended due to the paradoxical ERK activation mainly caused by RAF dimerization. To address the issue of RAF dimerization, type II RAF inhibitors have emerged as leading candidates. Recent clinical studies have shown the initial effectiveness of these agents against RAS mutant tumors. Promisingly, type II RAF inhibitors in combination with MEK or ERK inhibitors have demonstrated impressive efficacy in RAS mutant tumors. This review aims to clarify the importance of RAF dimerization in cellular signaling and resistance to treatment in tumors with RAS mutations, as well as recent progress in therapeutic approaches to address the problem of RAF dimerization in RAS mutant tumors. © 2024 The Authors

关键词： Cancer therapy Drug resistance RAF dimerization RAF inhibitors RAS mutations

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Histone variant H2A.Z facilitates DNA replication

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Science China(Life Sciences) 2020年第5期63卷 788-790页

作者： Lei Qiu Xinyi Zeng Junhong Han Department of Abdominal Oncology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu 610041China

In eukaryotes,DNA wraps around the histone octamer to form nucleosomes,which are further compacted into the chromosome structure.The chromosome contains multiple replication origins that are regulated by both DNA sequ... 详细信息

关键词： structure. H2A.Z DNA

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Major roles of the circadian clock in cancer

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Cancer Biology & Medicine 2023年第1期20卷 1-24页

作者： Chen Huang Chenliang Zhang Yubin Cao Jian Li Feng Bi Department of Abdominal Oncology Cancer Center and Laboratory of Molecular Targeted Therapy in OncologyWest China HospitalSichuan UniversityChengdu 610000China Laboratory of Molecular Targeted Therapy in oncology West China HospitalSichuan UniversityChengdu 610000China department of Gastroenterology West China HospitalSichuan UniversityChengdu 610000China West China School of Medicine Sichuan UniversityChengdu 610000China

Circadian rhythms are natural rhythms that widely exist in all creatures,and regulate the processes and physiological functions of various biochemical reactions.The circadian clock is critical for cancer occurrence and progression.Its function is regulated by metabolic activities,and the expression and transcription of various genes.This review summarizes the composition of the circadian clock;the biological basis for its function;its relationship with,and mechanisms in,cancer;its various functions in different cancers;the effects of anti-tumor treatment;and potential therapeutic targets.Research in this area is expected to advance understanding of circadian locomotor output cycles kaput(CLOCK)and brain and muscle ARNT-like protein 1(BMAL1)in tumor diseases,and contribute to the development of new anti-tumor treatment strategies.

关键词： Circadian clock BMAL1 cancer tumor therapy oncology

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Risk factors associated with postoperative hospital stay after pancreaticoduodenectomy： a retrospective study

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Chinese Medical Journal 2013年第19期126卷 3685-3689页

作者： XIE Yi-bin WANG Cheng-feng ZHAO Dong-bing SHAN Yi BAI Xiao-feng SUN Yue-min CHEN Ying-tai ZHAO Ping TIAN Yan-tao department of abdominal Surgical oncology Cancer HospitalChinese Academy of Medical Sciences Peking Union MedicalCollege Beijing 100021 China

Background Postoperative hospital stay after pancreaticoduodenectomy （PD） is relatively longer than after other gastrointestinal operations.The aim of the current study was to investigate the risk factors associated with prolonged hospital stay after PD.Methods Patients who had PD at the Cancer Hospital of Chinese Academy of Medical Sciences between December 2008 and November 2012 were selected for this retrospective study.Clinical and pathological data were collected and analyzed.The primary outcome was postoperative length of stay.Normal discharge or recovery was defined as a postoperative hospital stay of no more than 10 days; otherwise it was defined as delayed discharge or recovery （including hospital death）.Results Atotal of 152 patients were enrolled in the present study.Postoperative hospital stay was （19.7±7.7） days （range 7-57）.Of the 152 patients,67 were discharged within the normal time and 85 had delayed discharge.Postoperative complications occurred in 62.5% （95/152）,and the mortality rate was 3.29% （5/152）.Multiple regression analysis showed that delayed discharge was significantly associated with postoperative complications （adjusted odds ratio （OR） 10.40,95% confidence interval （CI） 3.58-30.22）,age （adjusted OR 4.09,95% CI 1.16-14.39）,body mass index （BMI）（adjusted OR 4.40,95% CI 1.19-16.23）,surgical procedure （adjusted OR 26.14,95% CI 4.94-153.19）,blood transfusion （adjusted OR 7.68,95% Cl 2.09-28.27）,and fluid input （adjusted OR 3.47,95% CI 1.24-11.57）.Conclusions Postoperative complications increase the time to postoperative hospital discharge.The length of hospital stay after PD is also associated with age,BMI,blood transfusion,surgical procedure,and fluid input.Further studies with more patients are needed in future.

关键词： length of stay pancreaticoduodenectomy postoperative period risk factors

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TanshinoneⅡA improves distribution and anti-tumor efficacy of pegylated liposomal doxorubicin via normalizing the structure and function of tumor vasculature in hepa1-6 hepatoma mice model

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Journal of Traditional Chinese Medicine 2018年第6期38卷 815-822页

作者： Zhang Ying Tie MingHui Bi Feng Wang Ke department of Integrated Traditional Chinese and Western Medicine West China Hospital Sichuan University Department of Abdominal Oncology Cancer Center West China Hospital Sichuan University

OBJECTIVE: To investigate whether the Tandistribution and anti-tumor Ⅱef A could improve the ficacy of Pegylated Liposomal Doxorubicin(PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatoma mice model.METHODS: Hepa1-6 hepatoma-bearing mice were treated with TanⅡA for 14 d. Distribution and anti-tumor efficacy of PLD, and the structure and function of the tumor vasculature were evaluated using various techniques.RESULTS: TanⅡ A significantly reduced the micro-vessel density(MVD). After Tan vascular walls were betteⅡr s A treatment,the tumor tructured, as the increased coverage of the pericytes and the promoted contact of the basement membrane and endothelial cell. Functional tests showed that tumor hypoxia was improved and the exudation amount of Evans blue in the parenchyma of the tumor decreased. In addition, mice treated with TanA had greater PLD penetration distance intratumoⅡrally. Furthermore, combined therapy of Tanibited tumor growth.ⅡA and PLD significantly inhCONCLUSION: This study suggests that Tanasculature andⅡ h A helps normalizing the tumor vas therapeutic potential in increasing the distribution of chemotherapy drug in the tumor.

关键词： Liver neoplasms,experimental TanshinoneⅡA Vascular normalization Pegylated liposomal doxorubicin

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Mechanism of cancer: Oncohistones in action

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Journal of Genetics and Genomics 2018年第5期45卷 227-236页

作者： Lei Qiu Xiaoyan Hu Qian Jing Xinyi Zeng Kui-Ming Chan Junhong Han Department of Abdominal Oncology State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University and Collaborative Innovation Center department of Biomedical Sciences City University of Hong Kong

Oncohistones are histones with high-frequency point mutations that are associated with tumorigenesis. Although each histone variant is encoded by multiple genes, a single mutation in one allele of one gene seems to have a dominant effect over global histone H3 methylation level at the relevant amino acid residue. These oncohistones are highly tumor type specific. For example, H3K27M and H3G34V/R mutations occur only in pediatric brain cancers, whereas H3K36M and H3G34W/L have only been found in pediatric bone tumors. H1 mutations also seem to be exclusively linked to lymphomas. In this review, we discuss the occurrence, frequency and potential functional mechanisms of each oncohistone in tumorigenesis of its relevant cancer. We believe that further investigation into the mechanism regarding their tumor type specificity and cancer-related functions will shed new light on their application in cancer diagnosis and targeted therapy development.

关键词： Oncohistone Histone modification Tumorigenesis Pediatric cancer

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