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

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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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Quantitative assessment of the impact of a triage physician on the Accreditation Council for Graduate Medical Education resident milestones in the emergency department

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World Journal of Emergency medicine 2024年第3期15卷 220-222页

作者： Julie Cueva Duncan Grossman Vishnu Muppala Arlene Chung Mahlaqa Butt Jefferson Drapkin Antonios Likourezos Errel Khordipour Department of Emergency medicine Maimonides Medical CenterNew York 11219USA

The “door-to-doctor” time for patients to be seen by a physician is an increasingly studied *** may shorten this time by implementing a triage physician (TP).The exact role of a TP may vary across *** put in preliminary orders for lab work,imaging,and treatment,and decide treatment location for further *** the prevalence of TPs grows,its effect on resident education in academic emergency departments (EDs) remains *** implemented a TP in the spring of 2016 and assessed resident physicians before and after implementation.

关键词： physician doctor treatment

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Understanding the eff ect of recreational drug use on bone health and musculoskeletal disease in the establishment of pain regimens

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World Journal of Emergency medicine 2024年第5期15卷 356-364页

作者： Ariella Gartenberg Alexander Petrie Winston Yen Woojn Cho Emergency medicine Department Montefi ore Medical Center and Jacobi Medical CenterNew York 10461USA Emergency medicine Department Jacobi Medical Center and North Central BronxNew York 10461USA Touro College of Osteopathic medicine Touro UniversityNew York 10027USA

BACKGROUND:The widespread use of recreational drugs has raised concerns regarding their eff ects on various organ *** use of cannabis and opioids in chronic pain management increases their prevalence among patients with musculoskeletal conditions whose bone health may already be *** article aims to review the pathophysiology and toxic eff ects of recreational drug use on musculoskeletal health to establish appropriate pain regimens for patients with substance ***:Medical literature published from 1970 until 2022 was identifi ed utilizing MEDLINE/PubMed and the Cochrane *** addition to the databases,references were obtained through the use of reference lists of published articles identifi ed by the aforementioned *** initial search terms included opioids,inhalants,hallucinogens,cannabis,stimulants,and bone *** were no methodological limitations in relation to the initial acquisition and analysis of ***:A total of 55 research articles were included in this ***,stimulants,opioids,and inhalants impact bone maintenance,specifically osteoblast and osteoclast activity,as well as impede hormone *** substances inhibit bone remodeling and development,manifesting as lower bone mineral density and increased fracture risk in chronic ***:Although the current literature suggests a deleterious effect of recreational drugs on bone health and musculoskeletal disease,further research is warranted to evaluate the clinical effects of long-term substance *** evaluation of such effects will aid in establishing appropriate pain regimens,as well as appropriate screening and treatment plans for recreational drug users.

关键词： Musculoskeletal disorders Bone health Cannabis Opioids Stimulants

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Zinc-based metal-organic frameworks as efficient carriers for anticancer drug to reduce toxicity and increase efficacy

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Rare Metals 2024年第10期43卷 5152-5163页

作者： Dong-Wei Ma Jing-Sheng Lu Xiang-Xin Cao Yan-Wei Cheng Gang Wang Zi-Qian Zhang Bo-Cheng Chen Ning Lin Qing Chen College of Pharmacy Guangxi Scientific Research Center of Traditional Chinese MedicineGuangxi University of Chinese Medicine Guangxi Zhuang Yao medicine center of Engineering and Technology

The rational design of a specific co-drug delivery platform that can address the unavoidable resistance, toxic side effects and low targeting efficiency of traditional cancer treatments is of great ***, Zn-based MOF-zeolitic imidazole framework-90(ZIF-90) was selected as the drug delivery carrier, with the cancer therapeutic drug mercaptopurine(6-MP) and glucose oxidase(GOD) as the drug models, hyaluronic acid(HA) was used for protection and targeted delivery, which designed and fabricated an intelligent drug delivery platform(6-MP@ZIF-90@GOD@HA). This platform aims to reduce the toxic side effects of 6-MP and enhance its efficacy while improving the targeting ability of GOD,thereby further enhancing the treatment outcome. Notably,results from both in vitro and in vivo experiments demonstrate that the targeted synergistic chemo/reactive oxygen species(ROS)-mediated/starvation therapy inhibited the cancer cell growth while reducing the chemotherapy toxicity, which provides new possibilities for the development of more precise and effective treatment strategies.

关键词： Cancer treatment Combination therapy Drug delivery Metal-organic framework Reduced toxicity

Application of nanoscale metal–organic frameworks in tumor immunotherapy

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Rare Metals 2024年第10期43卷 4867-4883页

作者： Xiao-Xuan Zeng Jing-Sheng Lu Dong-Wei Ma Yu-Ting Huang Ling Chen Gang Wang Qing Chen Ning Lin College of Pharmacy Guangxi Scientific Research Center of Traditional Chinese MedicineGuangxi University of Chinese Medicine Guangxi Zhuang Yao medicine center of Engineering and Technology

Immunotherapy has attracted wide attention because it can not only kill tumor cells but also effectively prevent tumor recurrence. However, due to the poor efficacy of the monotherapy in tumor immunotherapy, combination therapies are needed to enhance their efficacy,such as chemodynamic therapy/immunotherapy, photodynamic therapy/immunotherapy, sonodynamic therapy/immunotherapy and so on. Nanoscale metal–organic frameworks(nMOFs) are widely used for drug delivery because of their rich and variable composition, high drug loading capacity and good biodegradability. Compared with other conventional drug delivery systems(DDSs),nMOFs play more advantageous role in inducing immune cell death of tumor cells and combination therapies. This article focuses on the application of n MOFs in tumor immunotherapy in terms of their use as gatekeepers, supplementary agents and drug carriers, respectively, with the aim of providing some ideas and references for the design of smart nanoscale DDS for tumor immunotherapy.

关键词： Drug delivery system Immunotherapy Metal–organic frameworks Tumor

Nociceptors and Macrophages in Bacterial Meningitis:Partners in Crime?

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Neuroscience Bulletin 2024年第3期40卷 418-420页

作者： Fang Gao Hongzhen Hu The Kimberly and Eric J.Waldman Department of Dermatology Icahn School of Medicine at Mount SinaiNew York NY10029USA The Nash Family Department of Neuroscience Icahn School of Medicine at Mount SinaiNew York NY10029USA The Mark Lebwohl center for Neuroinfammation and Sensation Icahn School of Medicine at Mount SinaiNew York NY10029USA Friedman Brain Institute Icahn School of Medicine at Mount SinaiNew York NY10029USA

Bacterial meningitis is a serious and potentially life-threatening infection that affects the protective layers surrounding the brain and spinal cord,known as the *** types of bacteria,including Streptococcus pneumoniae,Neisseria meningitidis,and Haemophilus influenzae,can cause this *** populations,such as infants,children,immunocompromised adults,and the elderly,are particularly vulnerable to these *** of bacterial meningitis can manifest suddenly and may include high fever,severe and persistent headache,stiff neck,vomiting,sensitivity to light,and confusion or changes in mental state[1,2].Identifying these symptoms in infants can be more challenging and may lead to long-term disability or death[3].Despite the effectiveness of vaccines,it is crucial to understand how bacteria invade the brain and how our innate immune system responds to infection(Fig.1).

关键词： protective infection suddenly

CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3519-3532页

作者： Alvaro Quintanal-Villalonga Kenta Kawasaki Esther Redin Fathema Uddin Swanand Rakhade Vidushi Durani Amin Sabet Moniquetta Shafer Wouter R.Karthaus Samir Zaidi Yingqian A.Zhan Parvathy Manoj Harsha Sridhar Dennis Kinyua Hong Zhong Barbara P.Mello Metamia Ciampricotti Umesh K.Bhanot Irina Linkov Juan Qiu Radhika A.Patel Colm Morrsey Sanjoy Mehta Jesse Barnes Michael C.Haffner Nichlas D.Socci Richard P.Koche Elisa de Stanchina Sonia Molina-Pinelo Sohrab Salehi Helena A.Yu Joseph M.Chan Charles M.Rudin Department of medicine Thoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Cancer Biology and Genetics Program Sloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Vagelos College of Physicians and Surgeons Columbia UniversityNew YorkNYUSA Weill Cornell Graduate School of Medical Sciences Weill Cornell MedicineNew YorkNYUA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNYUSA center for Epigenetics Research Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Pathology Core Facilty Department of Pathology and Laboratory MedicineMSKCCNew YorkNYUSA Antitumor Assessment Core Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Divisionsof Human Biology and Clinical Research Fred Hutchinon Cancer CenterSeattleWAUSA Deparmentof Urology University of WashingtonSeattleWAUSA Gene Editing&Screening Core Facility Memorial Sloan Kettering Cancer center New YorkNYUSA Department of Laboratory medicine and Pathology University of WashingtonSeattleWAUSA Bioinfomatics CoreFacility Memorial Soan Kettering Cancer CenterNew YorkNYUSA Institute of Biomedicine of Seille(Bis) HURCSCUniversidad de SevillaSevilleSpain Computational Oncology Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Well Cornell Medical College new York NYUSA Present address:Swiss Institute for Experimental Cancer Research(ISREC) School of Life SciencesEPFLLausanneSwitzerland

Neuroendocrine(NE)transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor *** to date,even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53(TP53)and Retinoblastoma Transcriptional Corepressor 1(RB1)mutations in their tumors,no therapeutic strategies are available to prevent or delay histological *** of the cell cycle kinase Cell Division Cycle 7(CDC7)occurred in tumors during the initial steps of NE transformation,already after TP53/RB1 co-inactivation,leading to induced sensitivity to the CDC7 inhibitor ***7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen(MYC),implicated in stemness and histological *** overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy,even in the presence of ***7 inhibition also markedly extended response to standard cytotoxics(cisplatin,irinotecan)in lung and prostate small cell carcinoma *** results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity,as well as to effectively treat NE tumors de novo or after *** simurosertib clinical efficacy trials are ongoing,this concept could be readily translated for patients at risk oftransformation.

关键词： tumors markedly transformation

The Largest Chinese Cohort Study Indicates Homologous Recombination Pathway Gene Mutations as Another Major Genetic Risk Factor for Colorectal Cancer with Heterogeneous Clinical Phenotypes

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Research 2024年第3期6卷 191-203页

作者： Yun Xu Kai Liu Cong Li Minghan Li Fangqi Liu Xiaoyan Zhou Menghong Sun Megha Ranganathan Liying Zhang Sheng Wang Xin Hu Ye Xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Pathology Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Pathology Tissue BankFudan University Shanghai Cancer CenterShanghaiP.R.China Department of medicine Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Department of Pathology and Laboratory medicine David Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA Precision Cancer Medical center Fudan University Shanghai Cancer CenterShanghaiP.R.China

While genetic factors were associated with over 30% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2015 to December 2018, we retrospectively enrolled 2,181 patients from 8,270 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 462 pathogenic variants were detected in 19.3% of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of 2.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

关键词： susceptibility category Major

Summarizing the evidence for robotic-assisted bladder neck reconstruction: Systematic review of patency and incontinence outcomes

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Asian Journal of Urology 2024年第3期11卷 341-347页

作者： Tenny R.Zhang Ashley Alford Lee C.Zhao Department of Urology NewYork-Presbyterian Hospital/Weill Cornell MedicineNew YorkNYUSA Department of Urology NYU Langone Medical CenterNew YorkNYUSA

Objective:Bladder neck contracture and vesicourethral anastomotic stenosis are difficult to manage endoscopically,and open repair is associated with high rates of *** recent years,there have been increasing reports of robotic-assisted bladder neck reconstruction in the ***,existing studies are small,heterogeneous case *** objective of this study was to perform a systematic review of robotic-assisted bladder neck reconstruction to better evaluate patency and incontinence ***:We performed a systematic review of PubMed from first available date to May 2023 for all studies evaluating robotic-assisted reconstructive surgery of the bladder neck in adult *** in non-English,author replies,editorials,pediatric-based studies,and reviews were *** of interest were patency and incontinence rates,which were pooled when ***:After identifying 158 articles on initial search,we included only ten studies that fit all aforementioned criteria for robotic-assisted bladder neck *** were case series published from March 2018 to March 2022 ranging from six to 32 men,with the median follow-up of 5e23 months.A total of 119 patients were included in our analysis.A variety of etiologies and surgical techniques were *** rates ranged from 50%to 100%,and pooled patency was 80%(95/119).De novo incontinence rates ranged from 0%to 33%,and pooled incontinence was 17%(8/47).Our findings were limited by small sample sizes,relatively short follow-ups,and heterogeneity between studies.

关键词： Bladder neck Continence Incontinence Patency Posterior urethra Reconstructive surgery Robotic surgery Stenosis Stricture Surgical outcome