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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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Genomic medicine in clinical practice:national genomic medicine program in Japan

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Cancer Biology & Medicine 2024年第1期21卷 4-9页

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~*** statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in *** surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has *** 38,000 people died of cancer in *** national Cancer center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： Cancer cancer death

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Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2748-2760页

作者： Hua-yang Fan Ming-da Zhao Hong-jie Jiang Zhen-wei Yu Yu-jiang Fan Xin-hua Liang Ya-ling Tang Yong Sun State Key Laboratory of Oral Diseases&national center for Stomatology&national Clinical Research center for Oral Diseases&Department of Oral and Maxillofacial Surgery West China Hospital of StomatologySichuan UniversityChengdu 610041China national Engineering Research center for Biomaterials Sichuan UniversityChengdu 610065China State Key Laboratory of Oral Diseases&national center for Stomatology&national Clinical Research center for Oral Diseases&Department of Oral pathology West China Hospital of StomatologySichuan UniversityChengdu 610041China

Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC *** analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC ***-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p ***-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC *** results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC ***,we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC *** findings provide a new perspective for the development of OSCC treatments.

关键词： Oral squamous cell carcinoma CircRNA MiRNA sponge Antagomir MiRNA delivery Cisplatin-based nanoparticles Drug delivery systems Tumor elimination

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Mesenchymal-epithelial transition factor amplification correlates with adverse pathological features and poor clinical outcome in colorectal cancer

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1395-1406页

作者： Qiu-Xiao Yu Ping-Ying Fu Chi Zhang Li Li Wen-Ting Huang Department of pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116Guangdong ProvinceChina

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and the second most common cause of cancer-related mortality ***-epithelial transition factor(MET)gene participates in multiple tumor biology and shows clinical potential for pharmacological manipulation in tumor *** amplification has been reported in CRC,but data are very *** pathological values of MET in CRC may provide new therapeutic and genetic screening options in future clinical *** To determine the pathological significance of MET amplification in CRC and to propose a feasible screening *** A number of 205 newly diagnosed CRC patients undergoing surgical resection without any preoperative therapy at Shenzhen Cancer Hospital of Chinese Academy of Medical Sciences were *** patients were without RAS/RAF mutation or microsatellite *** amplification and c-MET protein expression were analyzed using fluorescence in situ hybridization(FISH)and immunohistochemistry(IHC),*** between MET aberration and pathological features were detected using the chi-squared *** free survival(PFS)during the two-year follow-up was detected using the Kaplan-Meier method and log rank *** results of MET FISH and IHC were com pared using one-way *** Polysomy-induced MET amplification was observed in 14.4%of cases,and focal MET amplification was not ***-induced MET amplification was associated with a higher frequency of lymph node metastasis(LNM)(P<0.001)and higher tumor budding grade(P=0.02).In the survival analysis,significant difference was detected between patients with amplified-and non-amplified MET in a two-year follow-up after the first diagnosis(P=0.001).C-MET scores of 0,1+,2+,and 3+were observed in 1.4%,24.9%,54.7%,and 19.0%of tumors,respectively.C-MET overexpression correlated with higher frequency of LNM(P=0.002),but no significant difference of PFS was dete

关键词： Colorectal cancer MET Amplification Pathological features Prognosis Fluorescence in situ hybridization

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Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

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International Journal of Oral Science 2024年第2期16卷 349-358页

作者： Xinjia Cai Heyu Zhang Yanjin Wang Jianyun Zhang Tiejun Li Department of Oral pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina Department of Oral pathology Shanghai Stomatological Hospital&School of StomatologyFudan UniversityShanghaiChina Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence *** combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin ***,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw *** of the different prognosis,differential diagnosis of several cysts can contribute to clinical *** collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of *** Inception_v3 neural network was utilized to train and test models developed from patch-level ***,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning *** AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of *** advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide ***,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the ***,we have developed the robust diagnostic and prognostic models for *** AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

关键词： diagnosis pathology prognosis

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Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

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World Journal of Pediatrics 2024年第4期20卷 413-421页

作者： Zhe-Wen Qin Qian-Nan Ren Hong-Xi Zhang Ya-Ru Liu Ke Huang Wei Wu Guan-Ping Dong Yan Ni Jun-Fen Fu Division of Endocrinology National Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalDepartment of EndocrinologyNational Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalZhejiang University School of MedicineHangzhou310052China

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver *** anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with *** A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation *** external validation cohort comprised 77 *** assessment of liver fat content was performed using proton magnetic resonance *** and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation *** Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive *** The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner *** adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in ***,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

关键词： Biochemical markers Children Magnetic resonance spectroscopy Nonalcoholic fatty liver disease Pediatric obesity

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A stepwise-responsive editor integrated with three copper ions for the treatment of oral squamous cell carcinoma

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Nano Research 2024年第6期17卷 5424-5434页

作者： Jinna Ren Jingying Hu Fan Dong Yan Xu Yang Peng Yuping Qian Guanmeng Zhang Min Wang Yuguang Wang Department of Prosthodontics Hospital of StomatologyJilin UniversityChangchun 130021China Department of General Dentistry II Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China center of Digital Dentistry Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Department of Nursing Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China The VIP Department School and Hospital of StomatologyChina Medical UniversityLiaoning Provincial Key Laboratory of Oral DiseasesShenyang 110002China

Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic ***,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune *** this basis,the editor can be combined with optical therapy to improve patient *** this study,the metal ratio was regulated in response to the nanocarrier of acid response ***,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell *** on these results,the nanoparticles were cracked in an acidic environment and then released copper ***,the nanoparticles contributed to cuprotosis and immunogenic *** addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without *** rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for ***,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell *** all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.

关键词： cuprotosis immunogenic death photothermal therapy tumor microenvironment immunotherapy

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Ferromagnetism and insulating behavior with a logarithmic temperature dependence of resistivity in Pb_(10-x)Cux(PO_(4))_(6)O

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Science China(Physics,Mechanics & Astronomy) 2024年第1期67卷 106-111页

作者： Yuhang Zhang Cong Liu Xiyu Zhu Hai-Hu Wen center for Superconducting Physics and Materials National Laboratory of Solid State Microstructures and Department of PhysicsNational Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China

Recent claim of discovering above-room-temperature superconductivity(Tc≈400 K)at ambient pressure in copper doped apatite Pb10(PO_(4))_(6)O has stimulated world-wide enthusiasm and impulse of motion.A lot of follow-up works have been carried out with controversial *** check whether superconductivity is really present or absent in the material,we need samples which should have a rather pure phase of Pb_(10-x)Cux(PO_(4))_(6)*** we report the characterization results from the Pb_(10-x)Cux(PO_(4))_(6)O with a fraction of about 97 wt.%inferred from the fitting to the X-ray diffraction pattern,if assuming Cu2S as the only *** resistivity measurements show that it is a semiconductor characterized roughly by a ln(1/T)temperature dependence in wide temperature region without trace of *** measurements show that it has a general ferromagnetic signal with a weak superparamagnetic *** grains of the sample show clear interactions with a Nb Fe B *** detected Cu concentration is much lower than the expected nominal *** results show the absence of metallicity and superconductivity in Pb_(10-x)Cux(PO_(4))_(6)O at ambient pressure,and suggest the presence of strong correlation effect.

关键词： superconductivity Pb10(PO4)6O ferromagnetic correlation effect

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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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Transmembrane serine protease 4 expression in the prognosis of radical resection for biliary tract cancer

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2555-2564页

作者： Yoshiyuki Shibata Takeshi Sudo Sho Tazuma Naoki Tanimine Takashi Onoe Yosuke Shimizu Atsushi Yamaguchi Kazuya Kuraoka Shinya Takahashi Hirotaka Tashiro Department of Surgery National Hospital Organization Kure Medical Center and Chugoku Cancer CenterHiroshima 737-0023Japan Department of Gastroenterology National Hospital Organization Kure Medical Center and Chugoku Cancer CenterHiroshima 737-0023Japan Department of Diagnostic pathology National Hospital Organization Kure Medical Centerand Chugoku Cancer CenterHiroshima 737-0023Japan Department of Surgery Graduate School of Biochemical and Health ScienceHiroshima UniversityHiroshima 734-8551Japan

BACKGROUND Recent advancements in biliary tract cancer(BTC)treatment have expanded beyond surgery to include adjuvant therapy,yet the prognosis remains *** prognostic biomarkers could enhance the assessment of patients who have undergone radical resection for *** To determine transmembrane serine protease 4(TMPRSS4)utility as a prognostic biomarker of radical resection for *** Medical records of patients who underwent radical resection for BTC,excluding intrahepatic cholangiocarcinoma,were retrospectively *** associations between TMPRSS4 expression and clinicopathological factors,overall survival,and recurrence-free survival were *** Among the 85 patients undergoing radical resection for BTC,46(54%)were *** TMPRSS4-positive group exhibited significantly higher preoperative carbohydrate antigen 19-9(CA19-9)values and greater lymphatic invasion than the TMPRSS4-negative group(P=0.019 and 0.039,respectively).Postoperative overall survival and recurrence-free survival were significantly worse in the TMPRSS4-positive group(median survival time:25.3 months vs not reached,P<0.001;median survival time:28.7 months vs not reached,P=0.043,respectively).Multivariate overall survival analysis indicated TMPRSS4 positivity,pT3/T4,and resection status R1 were independently associated with poor prognosis(P=0.032,0.035 and 0.030,respectively).TMPRSS4 positivity correlated with preoperative CA19-9 values≥37 U/mL and pathological tumor size≥30 mm(P=0.016 and 0.038,respectively).CONCLUSION TMPRSS4 is a potential prognostic biomarker of radical resection for BTC.

关键词： Biliary tract cancer Biomarker Prognosis Radical resection Transmembrane serine protease 4

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