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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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JW-1-283 inhibits melanoma tumor growth via stabilization of the p53 pathway

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Genes & Diseases 2024年第3期11卷 18-21页

作者： Yang Xie Ruida Hou Kelli LHartman Jianxiong Jiang Zhongzhi Wu Wei Li Drug discovery center College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN38163USA

Melanoma is a lethal skin malignancy and the fifth most diagnosed cancer in the United States.1 Currently,for unresectable melanoma,the recommended treatment options include checkpoint inhibitor immunotherapy targeting programmed cell death 1(PD-1),and inhibitors targeting the mitogen-activated protein kinase(MAPK)***,the response rate may vary among the patients,and therefore demanding the development of novel treatment *** suppressor TP53has been suggested as one of the critical regulators mediating the aggressiveness and progression of melanoma.

关键词： melanoma suppressor death

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Transcriptional regulation in the development and dysfunction of neocortical projection neurons

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Neural Regeneration Research 2024年第2期19卷 246-254页

作者： Ningxin Wang Rong Wan Ke Tang Precise genome Engineering center School of Life SciencesGuangzhou UniversityGuangzhouGuangdong ProvinceChina

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal *** development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and *** processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural *** generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

关键词： autism spectrum disorders cognition differentiation excitatory circuits intellectual disability neocortex neurodevelopmental disorders projection neuron specification transcriptional regulation

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A novel high-Cr CoNi-based superalloy with superior high-temperature microstructural stability, oxidation resistance and mechanical properties

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International Journal of Minerals,Metallurgy and Materials 2024年第6期31卷 1373-1381页

作者： Xiaorui Zhang Min Zou Song Lu Longfei Li Xiaoli Zhuang Qiang Feng Beijing Advanced Innovation center for Materials genome Engineering State Key Laboratory for Advanced MetalsUniversity of Science and Technology BeijingBeijing 100083China

A novel multicomponent high-Cr CoNi-based superalloy with superior comprehensive performance was prepared,and the evaluation of its high-temperature microstructural stability,oxidation resistance,and mechanical properties was conducted mainly using its cast polycrystalline *** results disclosed that the morphology of theγ′phase remained stable,and the coarsening rate was slow during the long-term aging at 900–1000℃.The activation energy forγ′precipitate coarsening of alloy 9CoNi-Cr was(402±51)kJ/mol,which is higher compared with those of CMSX-4 and some other Ni-based and Co-based ***,there was no indica-tion of the formation of topologically close-packed phases during this *** these factors demonstrated the superior microstructural stability of the *** mass gain of alloy 9CoNi-Cr was 0.6 mg/cm^(2) after oxidation at 1000℃ for 100 h,and the oxidation resistance was comparable to advanced Ni-based superalloys CMSX-4,which can be attributed to the formation of a continuous Al_(2)O_(3) protective ***,the compressive yield strength of this cast polycrystalline alloy at high temperatures is clearly higher than that of the conventional Ni-based cast superalloy and the compressive minimum creep rate at 950℃ is comparable to that of the conventional Ni-based cast superalloy,demonstrating the alloy’s good mechanical properties at high *** is partially because high Cr is bene-ficial in improving theγandγ′phase strengths of alloy 9CoNi-Cr.

关键词： CoNi-based superalloys microstructure coarsening oxidation mechanical properties

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Multi-performance evaluation of high-throughput accelerated corrosion test for high-strength low-alloy 921A steel

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Journal of Iron and Steel Research(International) 2024年第5期31卷 1260-1278页

作者： Cong-cong Du Ming-hua Qin Zhan-fang Wu Dong-ling Li Lei Zhao Xiang-yang Li Hai-zhou Wang Beijing Advanced Innovation center for Materials genome Engineering National Center for Materials Service SafetyUniversity of Science and Technology BeijingBeijing100083China China Iron and Steel Research Institute Group Co. Ltd.Beijing100081China Beijing Advanced Innovation center for Materials genome Engineering Central Iron and Steel Research InstituteBeijing100081China

The corrosion behavior of high-strength low-alloy 921A steel in a simulated marine atmospheric environment was studied using a high-throughput experimental *** corrosion behavior,corrosion morphology,and corrosion products of 921A steels were analyzed using various techniques,including corrosion mass loss method,polarization curve,white-light interferometry,scanning electron microscopy,energy-dispersive spectrometry,microbeam X-ray fluorescence spectrometry,X-ray diffraction technique,and X-ray photoelectron *** test results indicated that 921A steel exhibits better corrosion resistance than Q450NQR1 steel in simulated harsh atmospheric environments,as evidenced by a lower corrosion mass loss rate throughout the corrosion *** corrosion products of both steels consisted ofα-FeOOH,Fe_(3)O_(4),andγ-FeOOH,withα-FeOOH being more prevalent in the rust layer of 921A steel than in Q450NQR1 *** inner rust layer of 921A steel also exhibited an appositional enrichment region of Cr,Ni,Mo,and V,leading to its superior corrosion resistance compared to that of Q450NQR1 *** efficacy of high-throughput accelerated corrosion experimental methods was highlighted for evaluating the corrosion resistance of steel materials in harsh environmental *** findings suggest that 921A steel exhibits better corrosion resistance compared to Q450NQR1 steel and has the potential to be more suitable in harsh marine atmospheric *** characterization of the rust layer structures and composition reveals the parallel enrichment of certain elements in the inner rust layer of 921A steel,which enhances its corrosion resistance.

关键词： Atmospheric corrosion High-throughput experimental method High-strength low-alloy steel Corrosion characteristics Rust layer Element enrichment

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Improving flangeability of multiphase steel by increasing microstructural homogeneity

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Journal of Iron and Steel Research(International) 2024年第7期31卷 1736-1745页

作者： Xiao-yu Yang Yong-gang Yang Xing Fang Han-long Zhang Zhen-li Mi Beijing Advanced Innovation center for Materials genome Engineering Institute of Engineering TechnologyUniversity of Science and Technology BeijingBeijing 100083China Shanghai Baosteel Group Corp.Technology center Shanghai 201900China

Multiphase microstructure significantly increases the strength,usually at the expense of flangeability because of lacking microstructure *** further improve the strength-flangeability of multiphase steel,the microstructural homogeneity was advanced by adjusting the hard martensite/austenite(M/A)*** strength-flangeability was measured via uniaxial tensile tests and hole expansion *** microstructures were characterized using a scanning electron microscope equipped with an electron backscatter diffraction detector and a transmission electron *** tests were supplementally used to quantitatively reveal the microstructural homogeneity of the *** show that the adjusted multiphase steel achieves an excellent ultimate tensile strength(~800 MPa)and flangeability(~135%hole expansion ratio).A promising homogeneous multiphase microstructure was obtained by controlling undercooled austenite transformed at about 600℃.This microstructure consists of soft polygonal ferrite,blocky bainitic ferrite,and hard M/A *** volume fraction of M/A islands is around 5%,and the average size is less than l *** nanoindentation analysis indicated that the participation of M/A islands impressively influenced the microstructural *** strain partition and better mechanical compatibility were present in the adjusted multiphase steel since the plasticity initiation started late,which resulted in a positive ***,avoiding M/A islands distributed in the chain along the rolling direction on the matrix hindered the possibility of voids coalescing into cracks and stabilized the flanging performance.

关键词： Multiphase steel Flangeability Martensite/austenite island-Microstructural homogeneity-Microstructure Compact strip production process

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genome-wide CRISPR screening reveals key genes and pathways associated with 20-hydroxyecdysone signal transduction in the silkworm(Bombyx mori)

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Insect Science 2024年第1期31卷 47-58页

作者： Hao Sun Jingya Chen Ruolin Wang Dan Liu Na Zhang Tong Zhang Ling Jia Sanyuan Ma Qingyou Xia State Key Laboratory of Silkworm genome Biology Southwest UniversityChongqingChina Biological Science Research center Southwest UniversityChongqingChina

Metamorphosis is a complex developmental process involving multiple pathways and a large number of genes that are regulated by juvenile hormone(JH)and 20-hydroxyecdysone(20E).Despite important progress in understanding various aspects of silkworm biology,the hormone signaling pathway in the silkworm remains poorly ***-wide screening using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)-based libraries has recently emerged as a novel method for analyzing genome function,enabling further research into essential genes,drug targets,and virus-host ***,we constructed a genome-wide CRISPR/Cas9-based library of the silkworm(Bombyx mori)and successfully revealed the genes involved in biotic or abiotic stress factor *** this study,we used our silkworm CRISPR library and large-scale genome-wide screening to analyze the key genes in the silkworm 20E signaling pathway and their mechanisms of *** annotation showed that 20E regulates key proteins in processes that mainly occur in the cytoplasm and *** enrichment analysis showed that 20E can activate phosphorylation and may affect innate immunity,interfere with intracellular nutrition and energy metabolism,and eventually cause cell *** screening results were experimentally validated by generating cells with knockout alleles of the relevant genes,which had increased tolerance to *** findings provide a panoramic overview of signaling in response to 20E in the silkworm,underscoring the utility of genome-wide CRISPR mutant libraries in deciphering hormone signaling pathways and the mechanisms that regulate metamorphosis in insects.

关键词： CRISPR/Cas9 CRISPR library screening ecdysone 20E signal transduction silkworm whole genome editing

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Inhibition mechanisms of CRISPR-Cas9 by Acr ⅡA25.1 and AcrⅡA32

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Science China Life Sciences 2024年第9期67卷 1781-1791页

作者： Jianlin Zheng Yuwei Zhu Tengjin Huang Wenbo Gao Jiale He Zhiwei Huang HIT center for Life Sciences School of Life Science and Technology Harbin Institute of Technology Westlake center for genome Editing Westlake Laboratory of Life Sciences and Biomedicine School of Life Sciences Westlake University

In the ongoing arms race between bacteria and bacteriophages, bacteriophages have evolved anti-CRISPR proteins to counteract bacterial CRISPR-Cas systems. Recently, Acr ⅡA25.1 and Acr ⅡA32 have been found to effectively inhibit the activity of Spy Cas9 both in bacterial and human cells. However, their molecular mechanisms remain elusive. Here, we report the cryo-electron microscopy structures of ternary complexes formed by Acr ⅡA25.1 and Acr ⅡA32 bound to Spy Cas9-sg RNA. Using structural analysis and biochemical experiments, we revealed that Acr ⅡA25.1 and Acr ⅡA32 recognize a novel, previously-unidentified anti-CRISPR binding site on Spy Cas9. We found that both Acr ⅡA25.1 and Acr ⅡA32 directly interact with the WED domain, where they spatially obstruct conformational changes of the WED and PI domains, thereby inhibiting Spy Cas9 from recognizing protospacer adjacent motif(PAM) and unwinding double-stranded DNA. In addition,they may inhibit nuclease activity by blocking the dynamic conformational changes of the Spy Cas9 surveillance complex. In summary, our data elucidate the inhibition mechanisms of two new anti-CRISPR proteins, provide new strategies for the modulation of Spy Cas9 activity,and expand our understanding of the diversity of anti-CRISPR protein inhibition mechanisms.

关键词： anti-CRISPR cryo-EM SpyCas9 AcrIIA25.1 AcrIIA32 inhibiton

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Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

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cancer Communications 2024年第2期44卷 287-293页

作者： Kouya Shiraishi Atsushi Takahashi Yukihide Momozawa Yataro Daigo Syuzo Kaneko Takahisa Kawaguchi Hideo Kunitoh Shingo Matsumoto Hidehito Horinouchi Akiteru Goto Takayuki Honda Kimihiro Shimizu Masahiro Torasawa Daisuke Takayanagi Motonobu Saito Akira Saito Yuichiro Ohe Shun-ichi Watanabe Koichi Goto Masahiro Tsuboi Katsuya Tsuchihara Sadaaki Takata Tomomi Aoi Atsushi Takano Masashi Kobayashi Yohei Miyagi Kazumi Tanaka Hiroyuki Suzuki Daichi Maeda Takumi Yamaura Maiko Matsuda Yoko Shimada Takaaki Mizuno Hiromi Sakamoto Teruhiko Yoshida Yasushi Goto Tatsuya Yoshida Taiki Yamaji Makoto Sonobe Shinichi Toyooka Kazue Yoneda Katsuhiro Masago Fumihiro Tanaka Megumi Hara Nobuo Fuse Satoshi S.Nishizuka Noriko Motoi Norie Sawada Yuichiro Nishida Kazuki Kumada Kenji Takeuchi Kozo Tanno Yasushi Yatabe Kuniko Sunami Tomoyuki Hishida Yasunari Miyazaki Hidemi Ito Mitsuhiro Amemiya Hirohiko Totsuka Haruhiko Nakayama Tomoyuki Yokose Kazuyoshi Ishigaki Toshiteru Nagashima Yoichi Ohtaki Kazuhiro Imai Ken Takasawa Yoshihiro Minamiya Kazuma Kobayashi Kenichi Okubo Kenji Wakai Atsushi Shimizu Masayuki Yamamoto Motoki Iwasaki Koichi Matsuda Johji Inazawa Yuichi Shiraishi Hiroyoshi Nishikawa Yoshinori Murakami Michiaki Kubo Fumihiko Matsuda Yoichiro Kamatani Ryuji Hamamoto Keitaro Matsuo Takashi Kohno Division of genome Biology National Cancer Center Research InstituteTokyoJapan Department of Clinical Genomics National Cancer Center Research InstituteTokyoJapan Laboratory for Statistical Analysis Center for Integrative Medical SciencesRIKENYokohamaJapan Department of Genomic Medicine Research InstituteNational Cerebral and Cardiovascular CenterOsakaJapan Laboratory for Genotyping Development Center for Integrative Medical SciencesRIKENYokohamaJapan center for Antibody and Vaccine Therapy Research HospitalInstitute of Medical ScienceThe University of TokyoTokyoJapan Department of Medical Oncology and cancer center and Center for Advanced Medicine against CancerShiga University of Medical ScienceOtsuJapan Division of Medical AI Research and Development National Cancer Center Research InstituteTokyoJapan center for Genomic Medicine Graduate School of MedicineKyoto UniversityKyotoJapan Department of Medical Oncology Japanese Red Cross Medical CenterTokyoJapan Department of Thoracic Oncology National Cancer Center Hospital EastJapan Department of Thoracic Oncology National Cancer Center HospitalTokyoJapan Department of Cellular and Organ Pathology Graduate School of MedicineAkita UniversityAkitaJapan Department of Respiratory Medicine Tokyo Medical and Dental UniversityBunkyo-kuTokyoJapan Division of General Thoracic Surgery Department of SurgeryShinshu University School of MedicineMatsumotoNaganoJapan Department of General Surgical Science Division of General Thoracic SurgeryGunma University Graduate School of MedicineIntegrative Center of General SurgeryGunma University HospitalGunmaJapan Department of Gastrointestinal Tract Surgery Fukushima Medical University School of MedicineFukushimaJapan StaGen Co. LtdTokyoJapan Division of Thoracic Surgery National Cancer Center HospitalTokyoJapan Department of Thoracic Surgery National Cancer Center Hospital EastChibaJapan Division of Translational Informatics Exploratory Oncology Research and Clinical Trial Center(EPOC

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

关键词： adenocarcinoma lung Lung

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