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XELOX(capecitabine plus oxaliplatin)plus bevacizumab(anti-VEGF-A antibody)with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer:a multicenter,open-label,randomized,controlled,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2104-2113页

作者： Qiu-Zhong Pan Jing-Jing Zhao Liang Liu Dong-Sheng Zhang Li-Ping Wang Wen-Wei Hu De-Sheng Weng Xiang Xu Yi-Zhuo Li Yan Tang Wei-Hong Zhang Jie-Yao Li Xiao Zheng Qi-Jing Wang Yong-Qiang Li Tong Xiang Li Zhou Shuang-Ning Yang Chen Wu Rong-Xing Huang Jia He Wei-Jiao Du Lu-Jun Chen Yue-Na Wu Bin Xu Qiong Shen Yi Zhang Jing-Ting Jiang Xiu-Bao Ren Jian-Chuan Xia State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Department of Biotherapy Sun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin 300060PR China Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060PR China Department of Biotherapy/Immunology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060PR China Department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052PR China Department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu 213003PR China Jiangsu Engineering Research Center for Tumor Immunotherapy ChangzhouJiangsu 213003PR China Institute for cell Therapy of Soochow University ChangzhouJiangsu 213003PR China Department of stem cell&Regenerative Medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042PR China Imaging Diagnosis and Interventional Center Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060PR China

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer(mCRC),but the prognosis remains *** phase 3 trial(***:NCT03950154)assessed the efficacy and adverse events(AEs)of the combination of PD-1 blockade-activated DC-CIK(PD1-T)cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab(the control group,n=102)or the same regimen plus autologous PD1-T cell immunotherapy(the immunotherapy group,n=100)every 21 days for up to 6 cycles,followed by maintenance treatment with capecitabine and *** main endpoint of the trial was progression-free survival(PFS).The median follow-up was 19.5 *** PFS was 14.8 months(95%CI,11.6-18.0)for the immunotherapy group compared with 9.9 months(8.0-11.8)for the control group(hazard ratio[HR],0.60[95%CI,0.40-0.88];p=0.009).Median overall survival(OS)was not reached for the immunotherapy group and 25.6 months(95%CI,18.3-32.8)for the control group(HR,0.57[95%CI,0.33-0.98];p=0.043).Grade 3 or higher AEs occurred in 20.0%of patients in the immunotherapy group and 23.5%in the control groups,with no toxicity-associated deaths *** addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

关键词： PD1 immunotherapy bevacizumab

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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher E.Mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of stem cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Regulatory networks between Polycomb complexes and non-coding RNAs in the central nervous system

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Journal of Molecular cell Biology 2020年第5期12卷 327-336页

作者： Ya-Jie Xu Pei-Pei Liu Shyh-Chang Ng Zhao-Qian Teng Chang-Mei Liu State Key Laboratory of stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China Institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China

High-throughput sequencing has facilitated the identification of many types of non-coding RNAs(ncRNAs)involved in diverse cellular *** as epigenetic mediators play key roles in neuronal development,maintenance,and dysfunction by controlling gene expression at multiple *** may not only target specific DNA or RNA for gene silence but may also directly interact with chromatin-modifying proteins like Polycomb group(PcG)proteins to drive orchestrated transcriptional *** significant progress has been made in characterizing ncRNAs and PcG proteins involved in transcriptional,post-transcriptional,and epigenetic *** importantly,dysregulation of ncRNAs,PcG proteins,and interplay among them is closely associated with the pathogenesis of central nervous system(CNS)*** this review,we focus on the interplay between ncRNAs and PcG proteins in the CNS and highlight the functional roles of the partnership during neural development and diseases.

关键词： epigenetics Polycomb complexes non-coding RNAs central nervous system neurological diseases

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Heparan Sulfate Mediates the Proliferation and Differentiation of Rat Mesenchymal stem cells

Heparan Sulfate Mediates the Proliferation and Differentiati...

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第三届国际骨质疏松及骨矿盐疾病学术会议

作者： C.Dombrowski X.Lim E.Susanto A.A.Sawyer D.W Hutmacher V.Nurcombe S.M Cool stem cells and Tissue Repair group Institute of Molecular and Cell Biology stem cells and Tissue Repair group Institute of Molecular and Cell Biology stem cells and Tissue Repair group Institute of Molecular and Cell Biology stem cells and Tissue Repair group Institute of Molecular and Cell Biology stem cells and Tissue Repair group Institute of Molecular and Cell Biology stem cells and Tissue Repair group Institute of Molecular and Cell Biology stem cells and Tissue Repair group Institute of Molecular and Cell Biology

＜正＞Objectives:Heparan sultate（HS）covalently attached to their core protein existing extracellular matrix are thought to act as low affinity co-receptors and promoting the binding of these growth factors to their high affinity *** binds to hepadn-binding growth factors（HBGFs） that have been shown to play an important role in

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Metabolism of pluripotent stem cells

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Frontiers in Biology 2016年第5期11卷 355-365页

作者： Liang Hu Edward Trope Qi-Long Ying Eli and Edythe Broad Center for Regenerative Medicine and stem cell Research at USC Department of Stem Cell Biology and Regenerative Medicine Keck School of Medicine University of Southern California Los Angeles CA 90033 USA

BACKGROUND： Recently, growing attention has been directed toward stem cell metabolism, with the key observation that metabolism not only fuels the proper functioning of stem cells but also regulates the fate of these cells. There seems to be a clear link between the self-renewal ofpluripotent stem cells （PSCs）, in which cells proliferate indefinitely without differentiation, and the activity of specific metabolic pathways. The unique metabolism in PSCs plays an important role in maintaining pluripotency by regulating signaling pathways and resetting the epigenome. OBJECTIVE： To review the most recent publications concerning the metabolism of pluripotent stem cells and the role of metabolism in PSC self-renewal and differentiation. METHODS： A systematic literature search related to the metabolism of PSCs was conducted in databases including Medline, Embase, and Web of Science. The search was performed without language restrictions on all papers published before May 2016. The following keywords were used：＂metabolism＂ combined with either ＂embryonic stem cell＂ or ＂epiblast stem cell.＂ RESULTS： Hundreds of papers focusing specifically on the metabolism of pluripotent stem cells were uncovered and summarized. CONCLUSION： Identifying the specific metabolic pathways involved in pluripotency maintenance is crucial for progress in the field of developmental biology and regenerative medicine. Additionally, better understanding of the metabolism in PSCs will facilitate the derivation and maintenance of authentic PSCs from species other than mouse, rat, and human.

关键词： metabolism pluripotent stem cells pluripotency epigenetics

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The N-terminal domain is a transcriptional activation domain required for Nanog to maintain ES cell self-renewal

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Chinese Science Bulletin 2009年第18期54卷 3271-3277页

作者： GUO YunQian ZHANG Juan YE Li CHEN Mo YAO Dong PAN GuangJin ZHANG JieQiong PEI DuanQing Laboratory of stem cell Biology Department of Biological Sciences & Biotechnology State Key Laboratory of Biomembrane andMembrane Biotechnology institutes of Biomedicine School of Medicine Tsinghua University Beijing 100084 China stem cell and Cancer Biology group Key Laboratory of Regenerative Biology South China Institute for Stem Cell Biology and Re-generative Medicine Guangzhou Istitute of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510663 China National Engineering Laboratory for Tree Breeding Key Laboratory of Genetics and Breeding in Forest Trees and OrnamentalPlants Ministry of Education Beijing Forestry University Beijing 100083 China

Nanog is a transcription factor identified by its ability to maintain the self-renewal of ES cells in the absence of leukemia inhibitory factor (LIF). Nanog protein contains an N-terminal domain (ND), a DNA-binding homeobox domain (HD) and a C-terminal domain (CD). We previously reported that the CD in Nanog is a transcriptional activation domain essential for the in vivo function of Nanog. Here we demonstrated that the ND in Nanog is also functionally important. Deletion of the ND reduces the transcriptional activity of Nanog on either artificial reporters or native Nanog promoters. This truncated Nanog is also less effective in regulating the endogenous Nanog target genes. Furthermore, the ND truncation disrupted the ability of Nanog to maintain ES cell self-renewal as well. We found that the ND is not required for the nuclear localization of Nanog. These results suggest that the regulation of endogenous pluripotent genes such as oct3/4 and rex-1 is required for the in vivo function of Nanog.

关键词： Nanog 胚胎干细胞转录激活结构域白血病抑制因子转录因子细胞重建转录活性

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Angelica sinensis polysaccharides ameliorate 5-flourouracil-induced bone marrow stromal cell proliferation inhibition via regulating Wnt/β-catenin signaling

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BIOcell 2021年第4期45卷 1045-1058页

作者： HANXIANZHI XIAO RONGJIA QI ZILING WANG MINGHE XIAO YUE XIANG YAPING WANG LU WANG Laboratory of stem cell and Tissue Engineering Department of Histology and EmbryologyChongqing Medical UniversityChongqing40012China

Chemotherapy may cause cellular oxidative stress to bone *** damage of bone marrow hematopoietic microenvironment is closely related to chronic myelosuppression after chemotherapeutic *** sinensis polysaccharides(ASP)are major effective ingredients of traditional Chinese medicine Angelica with multi-target anti-oxidative stress *** the current study,we investigated the protective roles and mechanisms of ASP on chemotherapy-induced bone marrow stromal cell(BMSC)*** human bone marrow stromal cell line HS-5 cells were divided into control group,5-FU group,5-FU+ASP group,and 5-FU+LiCl group to investigate the mechanism of ASP to alleviate 5-FU-induced BMSC proliferation *** results showed that 5-FU inhibits the growth of HS-5 cells in a time and dose-dependent manner;however,ASP partially counteracted the 5-FU-induced decrease in cell viability,whereas Wnt signaling inhibitor Dkk1 antagonized the effect of ASP on HS-5 *** reversed the decrease in total cytoplasmicβ-catenin,p-GSK-3β,and CyclinD1 following 5-FU treatment and modulated nuclear expression ofβ-catenin,Lef-1,and C-myc ***,ASP also enhanced the antioxidant capacity of cells and reduced 5-FU-induced oxidative stress,attenuated FoxO1 expression,thus weakened its downstream apoptosis-related proteins and G0/G1 checkpoint-associated p27^(Kip1) expression to alleviate 5-FU-induced apoptosis and to promote cell cycle *** the results above suggest that the protective role of ASP in 5-FU-treated BMSCs proliferation for the chemotherapy may be related to its activating Wnt/β-catenin signaling and keeping homeostasis betweenβ-catenin and FoxO1 under oxidative *** study provides a potential therapeutic strategy for alleviating chemotherapeutic damage on BMSCs.

关键词： Angelica sinensis polysaccharides 5-Fluorouracil Wnt/β-catenin signaling pathway Oxidative stress cell proliferation FoxO1

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Differentiation of embryonic stem cells in adult bone marrow

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Journal of Genetics and Genomics 2010年第7期37卷 431-439页

作者： Yueying Li Jing He Fengchao Wang Zhenyu Ju Sheng Liu Yu Zhang Zhaohui Kou Yanfeng Liu Tao Cheng Shaorong Gao State Key Laboratory of Experimental Hematology Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin 300020 China National Institute of Biological Sciences Beijing 102206 China Max-Planck-Partner group on stem cell Aging Institute of Laboratory Animal Science Chinese Academy of Medical Sciences Beijing 100021 China Center for stem cell Medicine Chinese Academy of Medical Sciences Beijing 100730 China.

Embryonic stem cells （ESCs） are a potential source of generating transplantable hematopoietic stem and progenitor cells,which in turn can serve as ＂seed＂ cells for hematopoietic *** this study,we aimed to gauge the ability of mouse ESCs directly differentiating into hematopoietic cells in adult bone marrow （BM）.To this end,we first derived a new mouse ESC line that constitutively expressed the green fluorescent protein （GFP） and then injected the ESCs into syngeneic BM via *** progeny of the transplanted ESCs were then analyzed at different time points after ***,however,most injected ESCs differentiated into non-hematopoietic cells in the BM whereas only a minority of the cells acquired hematopoietic cell surface *** study provides a strategy for evaluating the differentiation potential of ESCs in the BM micro-environment,thereby having important implications for the physiological maintenance and potential therapeutic applications of ESCs.

关键词： embryonic stem cells differentiation bone marrow transplantation

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Insights into female germ cell biology： from in vivo development to in vitro derivations

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Asian Journal of Andrology 2015年第3期17卷 415-420页

作者： Dajung Jung Kehkooi Kee Department of Basic Medical Sciences Center for Stem Cell Biology and Regenerative Medicine School of Medicine Tsinghua University Beijing 100084 China

Understanding the mechanisms of human germ cell biology is important for developing infertility treatments. However, little is known about the mechanisms that regulate human gametogenesis due to the difficulties in collecting samples, especially germ cells during fetal development. In contrast to the mitotic arrest of spermatogonia stem cells in the fetal testis, female germ cells proceed into meiosis and began folliculogenesis in fetal ovaries. Regulations of these developmental events, including the initiation of meiosis and the endowment of primordial follicles, remain an enigma. Studying the molecular mechanisms of female germ cell biology in the human ovary has been mostly limited to spatiotemporal characterizations of genes or proteins. Recent efforts in utilizing in vitro differentiation system of stem cells to derive germ cells have allowed researchers to begin studying molecular mechanisms during human germ cell development. Meanwhile, the possibility of isolating female germline stem cells in adult ovaries also excites researchers and generates many debates. This review will mainly focus on presenting and discussing recent in vivo and in vitro studies on female germ cell biology in human. The topics will highlight the progress made in understanding the three main stages of germ cell developments： namely, primordial germ cell formation, meiotic initiation, and folliculogenesis.

关键词： embryonic stem cell female germline stem cell folliculogenesis in vitro derivations meiotic initiation primordial germ cell

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Small regulators making big impacts:regulation of neural stem cells by small non-coding RNAs

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Neural Regeneration Research 2017年第3期12卷 397-398页

作者： Zhong Liu Rui Zhao Department of Biochemistry and Molecular Genetics Stem Cell InstituteUniversity of Alabama at BirminghamBirminghamALUSA

Neurodegeneration and traumatic brain injuries are leading causes of disability and present an enormous disease burden both in terms of patient suffering and healthcare *** of brain lesions remains as a major challeng... 详细信息

关键词： NSCs cell Small regulators making big impacts:regulation of neural stem cells by small non-coding RNAs stem

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