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cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

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Genes & Diseases 2024年第1期11卷 189-204页

作者： Ebrahim H.Maleki Ahmad Reza Bahrami Maryam M.Matin Department of biology Faculty of ScienceFerdowsi University of Mashhad*** MashhadIran Jagiellonian Centre for Experimental therapeutics(JCET) Jagiellonian University31-007 KrakowPoland Doctoral School of Exact and Natural Sciences Jagiellonian University30-348 KrakowPoland Industrial Biotechnology Research group Institute of BiotechnologyFerdowsi University of Mashhad*** MashhadIran Novel Diagnostics and therapeutics Research group Institute of BiotechnologyFerdowsi University of Mashhad***MashhadIran Stem Cell and Regenerative Medicine Research group Iranian Academic Center for EducationCulture and Research(ACECR)Khorasan Razavi Branch917751376 MashhadIran

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer *** tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the *** on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against *** discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"***,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer *** understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to ***-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in ***,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.

关键词： cancer stem cells(CSCs) Carcinoma Cell cycle heterogeneity Quiescence Therapy resistance Therapy tolerance Tumor dormancy

Mission of the National cancer Center Hospital in Japan to promote clinical trials for precision medicine

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cancer biology & Medicine 2024年第1期21卷 1-3页

作者： Kazuaki Shimada Kenichi Nakamura Noboru Yamamoto Department of Hepatobiliary and Pancreatic Surgery National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental therapeutics National Cancer Center HospitalTokyo 104-0045Japan

Precision medicine is a growing field *** its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical *** main obstacles are associated... 详细信息

关键词： clinical cancer overcome

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

From the unknown to spotlight:newly identified hormone adjusts hepatic cholesterol synthesis to dietary uptake

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2845-2847页

作者： Yakum Bertrand Nkeh Resul Gökberk Elgin Gesine Saher Project group biology of Lipids Department of NeurogeneticsMax Planck Institute for Multidisciplinary SciencesGöttingenGermany

In a study published in Cell,Hu and colleagues discovered that the signaling activity of the intestinal hormone Cholesin leads to the attenuation of hepatic cholesterol synthesis in response to intestinal absorption thereby maintaining homeostatic levels of circulating cholesterol.1 These findings have major translational implications as they provide a potential new target for the management of hypercholesterolemia and associated disorders.

关键词： cholesterol hepatic synthesis

High-resolution spatiotemporal mapping:a comprehensive view of eukaryotic cell cycle proteome dynamics

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2354-2356页

作者： Jing Zou Ziran Qin Long Zhang Life Sciences Institute Second Affiliated Hospital of the Zhejiang University School of MedicineThe MOE Key Laboratory of Biosystems Homeostasis&Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell BiologyZhejiang UniversityHangzhouZhejiangChina The MOE Basic Research and Innovation Center for the Targeted therapeutics of Solid Tumors The First Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchangChina cancer Center Zhejiang UniversityHangzhouZhejiangChina

In a recent study published in Cell,Litsios et *** a highresolution spatiotemporal map of the eukaryotic cell cycle proteome.1 They identified proteome-level changes in both abundance and spatial distribution throughout the cell cycle and provided a valuable resource for future exploration into the global proteome dynamics that drive cell cycle progression(https://***/cellcycle).

关键词： al. cycle dynamics

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

All types of base conversions allowed by base editors

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Science China(Life Sciences) 2024年第2期67卷 431-433页

作者： Shun-Qing Liang Wen Xue RNA therapeutics Institute UMass Chan Medical SchoolWorcester 01655USA Department of Molecular Cell and Cancer BiologyUMass Chan Medical SchoolWorcester 01655USA Department of Molecular Medicine UMass Chan Medical SchoolWorcester 01655USA Li Weibo Institute for Rare Diseases Research UMass Chan Medical SchoolWorcester 01655USA

Base editors(BEs) hold great promise as tools for introducing single-base-pair changes in both basic research and therapeutic applications(Rees and Liu,2018).Base editors are composed of a Cas9 nickase fused to a DNA-modifying enzyme,which chemically modifies nucleobases within a specific targeting window near the Cas9-binding site.

关键词： base bases allowed

Foraging valor linked with aggression:selection against completely abandoning aggression in the high-elevation ant Tetramorium alpestre?

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Insect Science 2024年第3期31卷 953-970页

作者： Marie-Luise Contala Patrick Krapf Florian M.Steiner Birgit C.Schlick-Steiner Molecular Ecology group Department of EcologyUniversitat InnsbruckInnsbruckAustria rganismal&Evolutionary biology Research Programme University of HelsinkiHelsinkiFinland

Aggression has multiple benefits and is often coupled with other behaviors("behavioral syndromes").The level of aggressiveness is influenced by an adaptive benefit-cost ratio suggesting that benefits should outweigh the costs of ***,we assess if several behaviors are coupled in two behaviorally different populations(aggressive,peaceful)of the high-elevation ant Tetramorium *** three weeks,we collected colony fragments and analyzed boldness,exploring,foraging,and risk-taking *** hypothesized that the aggressive population is bolder,more explorative and risk-prone,and forages more food than the peaceful *** test whether(a)the combination of experiments and parameters used yields a good setup,(b)populations differ behaviorally,and(c)populations display behavioral syndromes,we assessed(a)the frequency of repeatable behaviors of each experiment,(b)the behavioral means among populations,and(c)the behavioral repeatability,*** found that(a)boldness and exploring were most repeatable and represent a good experimental setup,(b)the aggressive population was bolder and more explorative and risk-prone than the peaceful population,(c)boldness and exploring behaviors were highly repeatable in both populations,thus corroborating our *** results suggest that boldness,exploring,and risk-taking but not foraging are presumably coupled with aggression and indicate the presence of behavioral syndromes in this *** specific ecological conditions,aggression may be coupled with other behaviors and important for finding *** is probably adaptive in ***,possibly indicating that selection favors aggression at least partially,which may counteract the complete loss of intraspecific aggression.

关键词： adaptive value behavioral syndromes boldness exploration repeatability trade-off

Characterization of the infectivity of an Indonesian Zika virus strain in mammalian cell lines

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Asian Pacific Journal of Tropical Biomedicine 2024年第5期14卷 215-224页

作者： Justus Thomas Obiajulu Sievers Anom Bowolaksono R.Tedjo Sasmono Graduate School of biology Department of BiologyFaculty of Mathematics and Natural SciencesUniversitas IndonesiaDepok 16424Indonesia Eijkman Research Center for Molecular biology National Research and Innovation AgencyCibinong 16911Indonesia Cellular and Molecular Mechanisms in Biological System Research group Department of BiologyFaculty of Mathematics and Natural SciencesUniversitas IndonesiaDepok 16424Indonesia

Objective:To characterize the infection patterns and growth characteristics of the Zika virus(ZIKV)strain JMB-185 from Indonesia in various mammalian cell ***:ZIKV was grown in human(A549,HEK293,HepG2,Huh7,Jurkat,and THP-1)and non-human mammalian(RAW264.7,Vero,and Vero76)cell *** replication kinetics were measured using plaque assay,while intra-and extracellular viral RNA concentrations were assessed using *** cytometry was used to quantify the infected cells and cell viability was measured using an MTT *** ability of ZIKV to infect cell lines was visualized using a fluorescence immunostaining ***:This ZIKV strain preferentially infected the lung,kidney,and liver cell lines A549,HEK293,Huh7,Vero,and Vero76,but not the immune cells Jurkat,RAW264.7,and *** contrast,the ZIKV showed no sign of infection in HepG2 cells,while maintaining viral titer over 3 days post-infection,with no infection recorded in immunostaining,no increase in viral RNA,and no indication of cell ***:The Indonesian ZIKV strain has a similar infection profile as other strains,except for its poor infectivity on HepG2 *** on the growth characteristics of Indonesia ZIKV will help expand our understanding of the biology of ZIKV which will be useful for various applications including antiviral discovery.

关键词： Zika virus Infectivity Replication Cell lines In vitro