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Tislelizumab in previously treated,locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

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Chinese Journal of Cancer Research 2024年第3期36卷 257-269页

作者： Jian Li Ye Xu Aimin Zang Yunong Gao Quanli Gao Yanqiao Zhang Dong Wang Jianming Xu Ying Yuan Haiping Jiang Jieer Ying Chunmei Shi Yanhong Deng Jing Wang Tianshu Liu Yi Huang Xiaoping Qian Yueyin Pan Ying Cheng Sheng Hu Jin Wang Mengyue Shi Ke Wang Han Hu Lin Shen State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Department of Onco.ogy Fudan University Shanghai Cancer CenterShanghai 200032China Department of medical Onco.ogy Affiliated Hospital of Hebei UniversityBaoding 071000China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of GynecologyPeking University Cancer Hospital&InstituteBeijing 100142China Department of Immunotherapy Henan Cancer HospitalZhengzhou 450001China Department of Gastrointestinal Onco.ogy Affiliated Cancer Hospital of Harbin Medical UniversityHarbin 150086China Department of Gastrointestinal Onco.ogy Chongqing University Cancer HospitalChongqing 400030China Department of Gastrointestinal Onco.ogy the Fifth Medical CenterChinese PLA General HospitalBeijing 100048China Department of medical Onco.ogy the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of medical Onco.ogy the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of medical Onco.ogy Cancer Hospital of the University of Chinese Academy of SciencesHangzhou 310022China Department of medical Onco.ogy Fujian Medical University Union HospitalFuzhou 350001China Department of Onco.ogy the Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China Department of medical Onco.ogy Hunan Cancer HospitalChangsha 410013China Department of medical Onco.ogy Zhongshan HospitalFudan UniversityShanghai 200032China Department of Immunotherapy Hubei Cancer HospitalWuhan 430079China Department of medical Onco.ogy the Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China Department of medical Onco.ogy Anhui Provincial HospitalHefei 230001China Department of medical Onco.ogy Jilin Cancer Hospital

Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)***:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were *** received tislelizumab 200 mg intravenously every 3 *** response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review co.mittee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at *** had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%co.fidence interval(95%CI),35.1−58.6;one-sided Pco.orectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical co.trol ORR of 10%;five(6.7%)patients had co.plete *** DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety ***-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients disco.tinued treatment due to ***:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

关键词： Biomarkers DNA mismatch repair immune checkpoint inhibitors microsatellite instability phase II clinical trials programmed cell death 1 receptor

Recent advances in functional utilisation of environmentally friendly and recyclable high-performance green bioco.posites: A review

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Chinese Chemical Letters 2024年第4期35卷 73-85页

作者： Guiyang Zheng Xuelian Kang Haoran Ye Wei Fan Christian Sonne Su Shiung Lam Rock Keey Liew Changlei Xia Yang Shi Shengbo Ge co.Innovation Center of Efficient Processing and Utilization of Forest Resources College of Materials Science and EngineeringNanjing Forestry UniversityNanjing 210037China School of Textile Science and Engineering&Key Laboratory of Functional Textile Material and Product of Ministry of Education Xi'an Polytechnic UniversityXi'an 710048China Department of Bioscience Arctic Research Centre(ARC)Aarhus UniversityFrederiksborgvej 399PO Box 358DK-4000 RoskildeDenmark Sustainability Cluster School of EngineeringUniversity of Petroleum&Energy StudiesDehradunUttarakhand 248007India Higher Institution Centre of Excellence(HIco.) Institute of Tropical Aquaculture and Fisheries(AKUATROP)Universiti Malaysia Terengganu21030 Kuala NerusTerengganuMalaysia Center for Transdisciplinary Research Saveetha Institute of Medical and Technical SciencesSaveetha UniversityChennai 600072India NV Western PLT Georgetown 10400PenangMalaysia Aerospace Kaitian Environmental Technology co. Ltd.Changsha 410000China Hunan Hongsen Novel Material Technology co. Ltd.Yiyang 413407China

Humans have relied on biomass for survival and development since the Stone Age. All aspects of human needs for materials are co.ered by tools, fuel, and buildings. Nowadays, metals and petroleum-based materials are widely used in highly developed industries. Unfortunately, environmental co.tamination and the loss of natural resources have led to the reemergence of biomass resources as efficient and sustainable energy sources. Notably, simple and direct applications can no longer meet the demand for functionalization, high performance of materials and co.struction materials. Therefore, it is imperative to modify biomass and co.bine its utilisation to produce functionalization and high performance materials. For example, co.struction materials with superior mechanical properties and water resistance can be produced by reinforcing fibres to facilitate crosslinking. Water-oil separation or adsorption effects of hydrogels and aerogels are determined by the porosity and lightness of biomass, bioco.posite co.ductor is prepared by chimaeric co.ductive material. Here, we review the approaches that have been taken to devise an environmentally friendly yet fully recyclable and sustainable functionalised bioco.posites from biomass and its potential directions for future research.

关键词： Bioco.posite Renewable Sustainability Advanced functional material Pollution mitigation

创制人工熊胆——在医药需求和动物福利之间实现平衡的创新路径（英文）

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Engineering 2024年第7期 100-112页

作者：李勇黄宇虹冯楠张和平屈晶马双刚刘云宝李江徐少锋王玲张咪蔡杰王伟平冯茹于航于博梁待亮秦和平罗素芗李艳芬李美凤王瑞华马辰王琰岑小波徐孝先张伯礼王晓良庾石山 State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College The Seco.d Affiliated Hospital of Tianjin University of Traditional Chinese Medicine Zhongshan Belling Biotechnology co. Ltd. Zhongshan Anshi Biopharmaceutical co. Ltd. WestChina-Frontier Pharma Tech co. Ltd. Tianjin University of Traditional Chinese Medicine

Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine (TCM) for over 13 ***,the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear ***,we present a new approach for creating artificial bear bile (ABB)as a high-quality and sustainable alternative to natural bear *** study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary co.laborations across various fields,including resources,chemistry,biology,medicine,pharmaco.ogy,and TCM.A co.prehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established,allowing for the systematic screening of therapeutic *** the utilization of chemical synthesis and enzyme engineering technologies,our research has achieved the environmentally friendly,large-scale production of bear bile therapeutic co.pounds,as well as the optimization and reco.position of ABB *** resulting ABB not only closely resembles natural bear bile in its co.position but also offers advantages such as co.sistent product quality,availability of raw materials,and independence from threatened or wild *** preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from co.mercially available drained bear bile (DBB).Furthermore,preclinical toxico.ogical assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used *** innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs,thereby strengthening the integrity and sustainability of TCM.

关键词：

PRC2 primes bivalent genes for transcription induction independent of histone methyltransferase activity

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Science China Life Sciences 2024年第9期67卷 2033-2035页

作者： Meihan Gong Ye Yuan Zhongye Dai Xuejiao Lv Jiacheng Su Dawei Huo Lin Niu Xu Chen Xudong Wu State Key Laboratory of Experimental Hematology The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) Department of Cell Biology School of Basic Medical Sciences Tianjin Medical University Bone Marrow Transplantation Center the First Affiliated Hospital Zhejiang University School of Medicine Liangzhu Laboratory Institute of Hematology Zhejiang University

Dear Editor,Polyco.b group proteins, co.served epigenetic transcriptional repressors, are crucial for orchestrating diverse developmental gene expression programs(Schuettengruber et al., 2017). The polyco.b repressive co.plex 2(PRC2) catalyzes H3 lysine-27 trimethylation(H3K27me3) to establish a delicate balance with H3K4me3, forming a bivalent chromatin state at target gene promoters and thereby poising them for subsequent transcription activation(Bernstein et al.,2006).

关键词： REPRESSIVE co.PLEX 2 POLYco.B PROMOTERS

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Large-Scale CRISPR Screen of LDLR Pathogenic Variants

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Research 2024年第2期2023卷 213-225页

作者： Mengjing Li Lerong Ma Yiwu Chen Jianing Li Yanbing Wang Wenni You Hongming Yuan Xiaochun Tang Hongsheng Ouyang Daxin Pang Key Lab for Zoonoses Research Ministry of EducationAnimal Genome Editing Technology Innovation CenterCollege of Animal SciencesJilin UniversityChangchunJilin Province 130062China The institute of Translational Medicine Tianjin Union Medical Center of Nankai UniversityTianjin 300071China Chongqing Researchinstitute Jilin UniversityChongqing 401123China Chongqing Jitang Biotechnology Research institute co.Ltd. ChongqingChina

Familial hypercholesterolemia(FH)is a frequently occurring genetic disorder that is linked to early-onset cardiovascular *** left untreated,patients with this co.dition can develop severe cardiovascular ***,many patients remain undiagnosed,and even when diagnosed,the treatment is often not *** mutations in the LDLR gene are the primary cause of FH,predicting whether novel variants are pathogenic is not a straightforward *** the functionality of LDLR variants is crucial in unco.ering the genetic basis of *** study utilized CRISPR/Cas9 cytosine base editors in pooled screens to establish a novel approach for functionally assessing tens of thousands of LDLR variants on a large scale.A total of more than 100 single guide RNAs(sgRNAs)targeting LDLR pathogenic mutations were successfully screened with relatively high *** of these,5 sgRNAs were further subjected to functional verification studies,including 1 in the promoter,1 in the antisense RNA,1 in the exon,and 2 in the *** for the variant caused by the sgRNA located at intron 16,the functionalities of the other LDLR variants were all *** high similarity of LDLR intron sequences may lead to some false ***,these results co.firm the reliability of the large-scale screening strategy for functional analysis of LDLR variants,and the screened candidate pathogenic mutations co.ld be used as an auxiliary means of clinical gene detection to prevent FH-induced heart disease.

关键词： LDLR Screen straight

Harnessing innate immune pathways for therapeutic advancement in cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1506-1564页

作者： Ankang Hu Li Sun Hao Lin Yuheng Liao Hui Yang Ying Mao Department of Neurosurgery Huashan HospitalFudan UniversityShanghaiP.R.China institute for Translational Brain Research Shanghai Medical CollegeFudan University ShanghaiPR.China National Center for Neurological Disorders Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration Shanghai Clinical Medical Center of NeurosurgeryNeurosurgical Institute of Fudan UniversityHuashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China State Key Laboratory of medical Neurobiology and MOE Frontiers Center for Brain Science and MOE Frontiers Center for Brain Science Institutes of Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)and Key Laboratory of Metabolism and Molecular Medicine(Ministry of Education)and Molecular and Cell Biology LabInstitutes of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghaiP.R.China

The innate immune pathway is receiving increasing attention in cancer *** pathway is ubiquitous across various cell types,not only in innate immune cells but also in adaptive immune cells,tumor cells,and stromal *** targeting the innate immune pathway have shown profound changes in the tumor microenvironment(TME)and improved tumor prognosis in preclinical ***,to date,the clinical success of drugs targeting the innate immune pathway remains ***,recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor *** uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate *** this review,we observe that the role of the innate immune pathway demonstrates heterogeneity,linked to the tumor development stage,pathway status,and specific cell *** propose that within the TME,the innate immune pathway exhibits multidimensional *** diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling *** pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative *** our understanding of the tumor's innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinicalapplication.

关键词： drugs therapeutic innate

Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging

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Science China(Life Sciences) 2024年第4期67卷 745-764页

作者： Shujie Chen Liujing Huang Bingdong Liu Huimin Duan Ze Li Yifan Liu Hu Li Xiang Fu Jingchao Lin Yinlan Xu Li Liu Dan Wan Yulong Yin Liwei Xie Department of Endocrinology and Metabolism Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China State Key Laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and ApplicationGuangdong Open Laboratory of Applied MicrobiologyInstitute of MicrobiologyGuangdong Academy of SciencesGuangzhou 510070China School of Public Health Xinxiang Medical UniversityXinxiang 453003China Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Metabo-Profile Biotechnology(Shanghai)co.Ltd. Shanghai 201315China institute of Aging Research Guangdong Provincial Key Laboratory of Medical Molecular DiagnosticsSchool of Medical TechnologyGuangdong Medical UniversityDongguan 524023China Department of Rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China Laboratory of Animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical RegionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China Bioland Laboratory Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510005China

The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle ***,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains *** propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging *** investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total ***,employing multi-omics(e.g.,RNA-seq,16S r RNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,co.ld be the primary factor co.tributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle ***,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/*** butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and *** a result,butyrate co.ld serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle *** findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

关键词： gut microbiota aging satellite cells butyrate Slc16a1(Mct1)

Nonco.served epitopes dominate reverse preexisting T cell immunity in co.ID-19 co.valescents

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2984-2998页

作者： Xin Wang Jie Zhang Maoshun Liu Yuanyuan Guo Peipei Guo Xiaonan Yang Bingli Shang Min Li Jinmin Tian Ting Zhang Xi Wang Ronghua Jin Jikun Zhou George F.Gao Jun Liu Department of Epidemiology School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China NHC Key Laboratory of Biosafety Research Unit of Adaptive Evolution and Control of Emerging VirusesChinese Academy of Medical SciencesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)Beijing 102206China Beijing Key Laboratory of Emerging Infectious Diseases Institute of Infectious DiseasesBeijing Ditan HospitalCapital Medical UniversityBeijing 100015China Beijing institute of Infectious Diseases Beijing 100015China National Center for Infectious Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015P.R.China School of Laboratory Medicine and Life Sciences Wenzhou Medical UniversityWenzhou 325035China School of Ophthalmology&Optometry Wenzhou Medical UniversityWenzhou 325027China co.laborative Innovation Centre of Regenerative Medicine and medical BioResource Development and Application co.co.structed by the Province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China Shijiazhuang Fifth Hospital Shijiazhuang 050011China CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)Beijing 100101China Savaid medical School University of Chinese Academy of SciencesBeijing 100049China

The herd immunity against SARS-co.-2 is co.tinuously co.solidated across the world during the ongoing ***,the potential function of the nonco.served epitopes in the reverse preexisting cross-reactivity induced by SARS-co.-2 to other human co.onaviruses is not well *** our research,we assessed T cell responses to both co.served and nonco.served peptides shared by SARS-co.-2 and SARS-co.,identifying cross-reactive CD8^(+)T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining ***,in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide ***,single-cell T cell receptor reservoir was analyzed based on tetramer ***,we disco.ered that cross-reactive T cells targeting SARS-co. were present in individuals who had reco.ered from co.ID-19,and identified SARS-co.-2 CD8^(+)T cell epitopes spanning the major structural antigens.T cell responses induced by the nonco.served peptides between SARS-co.-2 and SARS-co. were higher and played a dominant role in the cross-reactivity in co.ID-19 ***-T cell reactivity was also observed within the identified series of CD8^(+)T cell *** representative immunodominant peptide pairs,although the HLA binding capacities for peptides from SARS-co.-2 and SARS-co. were similar,the TCR repertoires reco.nizing these peptides were *** results co.ld provide beneficial information for the development of peptide-based universal vaccines against co.onaviruses.

关键词： immunity co.served assessed

The effect of celastrol in co.bination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines

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Onco.ogy Research 2024年第7期32卷 1231-1237页

作者： MOHAMMAD-TAGHI MORADI DHIYA ALTEMEMY MAJID ASADI-SAMANI PEGAH KHOSRAVIAN MARZIYEH SOLTANI LEILA HASHEMI AZADEH SAMIEI-SEFAT medical Plants Research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran Department of Pharmaceutics College of PharmacyAl-Zahraa University for WomenKarbalaIraq Cellular and Molecular Research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran

Background:Despite the availability of chemotherapy drugs such as 5-ﬂuorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side *** study aimed to investigate the effect of celastrol in co.bination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines(AGS and EPG85-257).Materials and Methods:In this in vitro study,AGS and EPG85-257 cells were treated with different co.centrations of celastrol,5-FU,and their *** proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)*** synergistic effect of 5-FU and celastrol was studied using co.pusyn *** DNA co.tent at different phases of the cell cycle and apoptosis rate was measured usingﬂow ***:co.treatment with low co.centrations(10%inhibitory co.centration(IC10))of celastrol and 5-FU signiﬁcantly reduced IC50(pco.bination for AGS and EPG85-257 cells,*** mean percentage of apoptosis for AGS cells treated with celastrol,5-FU,and their co.bination was obtained 23.9,41.2,and 61.9,and for EPG85-257 cells 5.65,46.9,and 55.7,*** addition,the 5-FU and celastrol-5-FU co.bination induced cell cycle arrest in the synthesis ***:Although celastrol co.ld decrease the co.centration of 5-ﬂuorouracil that sufﬁced to suppress gastric cancer cells,additional studies are required to arrive at co.clusive evidence on the anticancer effects of celastrol.

关键词： Gastric cancer Celastrol Terpenoid Cell cycle regulation Apoptosis Synergism