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The evolution of cancer genomic medicine in Japan and the role of the National cancer center Japan

cancer Biology & medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National cancer center research Institute Tokyo 104-0045Japan Department of Laboratory medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National cancer center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression

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Signal Transduction and Targeted Therapy 2024年第1期9卷 279-294页

作者： Liping Chen Shihao Zhu Tianyuan Liu Xuan Zhao Tao Xiang Xiao Hu Chen Wu Dongxin Lin Department of Etiology and Carcinogenesis National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of cancer genomic Biology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Collaborative Innovation center for cancer Personalized medicine Nanjing Medical UniversityNanjing 211166China CAMS Oxford Institute Chinese Academy of Medical SciencesBeijing 100006China Sun Yat-sen University cancer center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

Epithelial-mesenchymal transition(EMT)and proliferation play important roles in epithelial cancer formation and progression,but what molecules and how they trigger EMT is largely *** we performed spatial transcriptomic and functional analyses on samples of multistage esophageal squamous-cell carcinoma(ESCC)from mice and humans to decipher these critical *** investigating spatiotemporal gene expression patterns and cell–cell interactions,we demonstrated that the aberrant epithelial cell interaction via EFNB1-EPHB4 triggers EMT and cell cycle mediated by downstream SRC/ERK/AKT *** aberrant epithelial cell interaction occurs within the basal layer at early precancerous lesions,which expands to the whole epithelial layer and strengthens along the cancer development and *** analysis revealed that the aberrant EFNB1-EPHB4 interaction is caused by overexpressedΔNP63 due to TP53 mutation,the culprit in human ESCC *** results shed new light on the role of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in EMT and cell proliferation in epithelial cancer formation.

关键词： esophageal TP53 squamous

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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of Cellular&Molecular research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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Perioperative complication incidence and risk factors for retroperitoneal neuroblastoma in children:analysis of 571 patients

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World Journal of Pediatrics 2024年第3期20卷 250-258页

作者： Min He Jia-Bin Cai Xuan Wu Yin-Bing Tang Jin-Yan Wang Jun-Qin Mao Ji-Jun Chen Li-Feng Zhang Zhong-Hai Guan Jie-Ni Xiong Wan-Xin Peng Jin-Hu Wang Ting Tao Pediatric cancer research center National Clinical Research Center for Child HealthHangzhouChina Department of Surgical Oncology Children's HospitalZhejiang University School of MedicineHangzhouChina cancer center Zhejiang UniversityNo.3333 Binsheng RodeHangzhouChina

Background Surgery plays an important role in the treatment of *** complications may impact the course of neuroblastoma *** date,comprehensive analyses of complications and risk factors have been *** Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and *** data collected included clinical characteristics,operative details,operative complications and postopera-tive *** factors for perioperative complications of retroperitoneal neuroblastoma were *** A total of 571 patients were enrolled in this *** complications were observed in 255(44.7%)*** leakage(28.4%),diarrhea(13.5%),and injury(vascular,nerve and organ;7.5%)were the most frequent *** were three operation-related deaths(0.53%):massive hemorrhage(n=1),biliary tract perforation(n=1)and intestinal necrosis(n=1).The presence of image-defined risk factors(IDRFs)[odds ratio(OR)=2.09,P<0.01],high stage of the International Neuroblastoma Risk Group staging system(INRGSS)(OR=0.454,P=0.04),retroperitoneal lymph node metastasis(OR=2.433,P=0.026),superior mesenteric artery encasement(OR=3.346,P=0.003),and inferior mesenteric artery encasement(OR=2.218,P=0.019)were identified as independent risk factors for perioperative *** Despite the high incidence of perioperative complications,the associated mortality rate was quite ***-perative complications of retroperitoneal neuroblastoma were associated with IDRFs,INRGSS,retroperitoneal lymph node metastasis and vascular *** with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma.

关键词： Complication Neuroblastoma Risk factors Surgery

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The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells

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research 2024年第2期2023卷 373-387页

作者： Di Wu Yi Sun cancer Institute(Key Laboratory of cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China cancer center of Zhejiang University Hangzhou 310029China Zhejang Provincial Clinical research center for cancer Zhejang ProvinceChina Key Laboratory of Molecular Biology in Medical Sciences Zhejang ProvinceChina research center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

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Global, regional, and national burden of early-onset gastric cancer

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cancer Biology & medicine 2024年第8期21卷 667-678页

作者： Nuopei Tan Hongliang Wu Maomao Cao Fan Yang Xinxin Yan Siyi He Mengdi Cao Shaoli Zhang Yi Teng Qianru Li Jiachen Wang Changfa Xia Wanqing Chen Department of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Anesthesiology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

Objective: The burden of gastric cancer(GC) across different age groups needs updating. We determined the GC global, regional, and national burden profiles and changes in incidence for 3 sequential 5-year intervals from 2003 to ***: The latest incidence and mortality estimates of GC from 185 countries and regions were extracted from the GLOBOCAN 2022 database. The 5-year interval age-standardised incidence rates(ASIRs) were evaluated using cancer registry data from volumes X±XII of the cancer Incidence in Five Continents(CI5). Correlation analysis was used to evaluate the relationship between ASIR or the age-standardised mortality rate(ASMR) and the Human Development Index(HDI).Results: There was an estimated global 968,000 new GC cases and 660,000 deaths in 2022, with male predominance. GC ASIRs and ASMRs were 9.2 and 6.1 per 100,000 persons, respectively. East Asia had the highest burden, with 53.8% of cases and 48.2% of deaths among all geographic regions. There was a significant correlation between ASIR and HDI. Over three 5-year intervals from 2003 to 2017, the incidence of GC notably decreased in most countries but peaked at 2008±2012 in New Zealand, Turkey, and South Africa. Several countries in Europe, Oceania, and America suggest an increasingly concerning trend among younger individuals, especially ***: GC is a significant health issue, especially among males and in geographic regions with an HDI, such as eastern Asia. While the incidence of GC is decreasing in many countries due to prevention efforts and improved treatments, a rising trend persists among younger individuals. Comprehensive prevention strategies tailored to different age patterns are clearly needed.

关键词： GLOBOCAN Gastric cancer cancer burden incidence mortality

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cancer statistics for young adults aged 20 to 49 years in China from 2000 to 2017:a population-based registry study

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Science China(Life Sciences) 2024年第4期67卷 711-719页

作者： Yi Teng Changfa Xia He Li Maomao Cao Fan Yang Xinxin Yan Siyi He Mengdi Cao Shaoli Zhang Qianru Li Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

An increasing cancer incidence among adults younger than 50 years has been reported for several types of cancer in multiple *** aimed to report cancer profiles and trends among young adults in *** from the China cancer Registry Annual Report were used to estimate incidence and mortality among young adults(ages 20–49 years)in China in 2017,and an age-period-cohort model was employed to estimate the average annual percent change(AAPC)in incidence and mortality from 2000 to *** 25 cancer types were grouped into obesity-or overweight-associated cancers(12 cancer types)and additional cancers(13 cancer types).In 2017,there were 681,178new cases and 214,591 cancer deaths among young adults in *** young adults,the most common cancers were thyroid,breast,cervical,liver,lung,and colorectal cancer,and the leading causes of cancer deaths were liver,lung,cervical,stomach,breast,and colorectal *** 2000 to 2017,the cancer incidence increased for all cancers combined among young adults,with the highest AAPC(1.46%)for adults aged 20–24 years,while cancer mortality decreased,with the highest AAPC(-1.63%)for those aged 35–39 *** conclusion,the cancer incidence in China has increased among young adults,while cancer mortality has decreased for nearly all *** control measures,such as obesity control and appropriate screening,may contribute to reducing the increasing cancer burden among young adults.

关键词： young adults incidence mortality trends China

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cancer profiles in China and comparisons with the USA:a comprehensive analysis in the incidence,mortality,survival,staging,and attribution to risk factors

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Science China(Life Sciences) 2024年第1期67卷 122-131页

作者： Siyi He Changfa Xia He Li Maomao Cao Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

China faces a disproportionate cancer burden to the population size and is undergoing a transition in the cancer *** extracted data in five aspects of cancer incidence,mortality,survival,staging distributions,and attribution to risk factors in China,the USA and worldwide from open-source *** conducted a comprehensive secondary analysis of cancer profiles in China in the above aspects,and compared cancer statistics between China and the USA.A total of 4,546,400 new cancer cases and 2,992,600 deaths occurred in China in 2020,accounting for 25.1%and 30.2%of global cases,***-related cancers including lung cancer,colorectal cancer,and breast cancer showed an upward trend and have been the leading cancer types in China.41.6%of new cancer cases and 49.3%of cancer deaths occurred in digestive-system cancers in China,and the cancers of esophagus,nasopharynx,liver,and stomach in China accounted for over 40%of global ***-related cancers showed the highest population-attributable fractions among Chinese adults,and most cancers could be attributed to behavioral and metabolic *** proportions of stage I for most cancer types were much higher in the USA than in China,except for esophageal cancer(78.2%vs.41.1%).The 5-year relative survival rates in China have improved substantially during 2000–2014,whereas survival for most cancer types in the USA was significantly higher than in China,except for upper gastrointestinal *** findings suggest that although substantial progress has been made in cancer control,especially in digestive system cancers in China,there was still a considerable disparity in cancer burden between China and the *** robust policies on risk factors and standardized screening practices are urgently warranted to curb the cancer growth and improve the prognosis for cancer patients.

关键词： cancer burden survival rate neoplasm staging risk factors China

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Incidence and Mortality of cancers in Female Genital Organs—China,2022

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China CDC weekly 2024年第10期6卷 195-202,I0003,I0004页

作者： Kexin Sun Bingfeng Han Hongmei Zeng Shaoming Wang Li Li Ru Chen Rongshou Zheng Wenqiang Wei National Central cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Introduction:This study presented the incidence and mortality rates of cancers affecting the female genital organs in China,along with their trends spanning from 2010 to ***:700 population-based cancer registries provided relevant cancer incidence and mortality data for the year *** these,106 registries had continuous monitoring data suitable for trend analysis from 2010 to *** focused specifically on cancers affecting female genital organs(ICD10=C51-C54,C56)and projected their incidences and mortalities in China for 2022 based on data from 2018 and the trends observed from 2010 to ***-standardized incidence rate(ASIR)and mortality rate(ASMR)were calculated using Segi’s world standard ***:In 2022,there were an estimated 296,300 new cases and 104,900 deaths from female cancers in *** for vulva(C51),vagina(C52),cervix uteri(C53),corpus uteri(C54),and ovary(C56)were 0.32,0.23,13.83,6.84,and 5.68 per 100,000 *** for corpus uteri and ovary cancers were higher in urban *** for vulva,vagina,cervix,corpus uteri,and ovary cancers were 0.14,0.08,4.54,1.05,and 2.64 per 100,000 population,*** for ovarian cancer was higher in urban *** and ASMRs for most female genital organ cancers increased from 2010 to 2018,although the rate of increase for vulvar and cervical cancers in rural areas has slowed ***:Tailored cancer prevention and control programs specific to each region are necessary to address the growing disease burden.

关键词： ICD10 mortality organs

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Weight change and all-cause and cause-specific mortality:A 25-year follow-up study

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Chinese Medical Journal 2024年第10期137卷 1169-1178页

作者： Huan Yang Jianbing Wang Xiaokun Wang Wanyi Sun Chenyunhao Tong Jinhu Fan Youlin Qiao Christian *** Department of cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Public Health Zhejiang University School of MedicineNational Clinical Research Center for Children’s HealthHangzhouZhejiang 310058China Metabolic Epidemiology Branch Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleMD 20850USA

Background:Whether the dynamic weight change is an independent risk factor for mortality remains *** study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial(NIT)***:Body weight of 21,028 healthy residents of Linxian,Henan province,aged 40-69 years was measured two times from 1986 to *** events were prospectively collected up to *** maintenance group(weight changecancer(HR_(cancer)=1.12,95%CI:1.03-1.21,P=0.009),and heart disease(HR_(Heart diseases)=1.21,95%CI:1.11-1.31,Pcancer)=0.89,95%CI:0.79-0.99,P=0.033)lower risk of cancer mortality and 23%higher risk of stroke mortality(HR_(Stroke)=1.23,95%CI:1.12-1.34,Pcancer death(HR_(Overweight to normal)=1.20,95%CI:1.04-1.39;HR_(Becoming underweight)=1.44,95%CI:1.24-1.67),while stable overweight could increase the risk of total death(HR_(Stable overweight)=1.11,95%CI:1.05-1.17)and death from stroke(HR_(Stable overweight)=1.44,95%CI:1.33-1.56).Interaction effects were observed between age and weight change on cancer mortality,as well as between baseline BMI and weight change on all-cause,heart disease,and stroke mortality(all P_(

关键词： Weight change All-cause mortality cancer Stroke Heart diseases Body mass index

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