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Eligibility of C-BIOPRED severe asthma cohort for type-2 biologic therapies

Chinese Medical Journal 2023年第2期136卷 230-232页

作者： Zhenan Deng Meiling Jin Changxing Ou Wei Jiang Jianping Zhao Xiaoxia Liu Shenghua Sun Huaping Tang Bei He Shaoxi Cai Ping Chen Penghui Wu Yujing Liu Jian Kang Yunhui Zhang Mao Huang Jinfu Xu Kewu Huang Qiang Li Xiangyan Zhang Xiuhua Fu Changzheng Wang Huahao Shen Lei Zhu Guochao Shi Zhongmin Qiu Zhongguang Wen Xiaoyang Wei Wei Gu Chunhua Wei Guangfa Wang Ping Chen Lixin Xie Jiangtao Lin Yuling Tang Zhihai Han Kian Fan Chung Qingling Zhang Nanshan Zhong C-BIOPRED Consortium Pulmonary and Critical Care Medicine Guangzhou Institute of Respiratory HealthNational Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineState Key Laboratory of Respiratory DiseasesThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510120China Department of Respiratory Medicine Zhongshan HospitalShanghai 200433China Guangzhou Medical University GuangzhouGuangdong 510180China AstraZeneca Shanghai 200085China Department of Respiratory Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Respiratory Medicine Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Respiratory Medicine The Third Xiangya Hospital of Central South UniversityChangshaHunan 410013China Department of Respiratory Medicine Qingdao Municipal HospitalQingdaoShandong 266001China Department of Respiratory Medicine Peking University Third HospitalBeijing 100191China Department of Respiratory Medicine Nanfang Hospital of Southern Medical UniversityGuangzhouGuangdong 510515China Department of Respiratory Medicine General Hospital of Northern Theater CommandShenyangLiaoning 110016China Department of Respiratory Medicine The First Hospital of China Medical UniversityShenyangLiaoning 110001China Department of Respiratory Medicine The First people’s Hospital of Yunnan ProvinceKunmingYunnan 363880China Department of Respiratory Medicine The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Respiratory Medicine Shanghai Pulmonary HospitalShanghai 200433China Department of Respiratory Medicine Beijing Chao-Yang HospitalBeijing 100020China Department of Respiratory Medicine Shanghai General HospitalShanghai 200080China Department of Respiratory Medicine Guizhou Province People’s HospitalGuiyangGuizhou 550002China Department of Respiratory Medicine The Affiliated Hospital of Inner Mongolia Me

To the Editor:Patients with severe persistent asthma experience greater morbidity with more impairment in quality of life despite higher use of health care resources and being treated with existing asthma treatments such as inhaled corticosteroids and b-agonists,and sometimes oral corticosteroid(OCS)therapy.Type-2(T2)high asthma has been identified as a phenotype that responds to targeted T2 biologic therapies such as anti-IgE,anti-interleukin(IL)5,or anti-IL5Ra and anti-IL4Ra monoclonal antibodies,which are currently available in Europe and North America,and are currently introduced in the rest of the world.[1]

关键词： asthma therapies impairment

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The new wave of p75 neurotrophin receptor targeted therapies

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Neural Regeneration Research 2022年第1期17卷 95-96页

作者： Amanda M.Crooks Rick B.Meeker UNC School of Medicine University of North CarolinaChapel HillNCUSA(Crooks AM)Department of NeurologyUniversity of North CarolinaChapel HillNCUSA

Neurotrophins have been recognized for decades for their beneficial effects on growth,survival,and maintenance in the central nervous system,all of which suggest potential therapeutic utility.Although understanding and harnessing the activity of neurotrophins has proven difficult,the past several years have seen significant strides in the development of deliverable therapies that modulate neurotrophin activity(Shen et al.,2019;Yang et al.,2020;Xie et al.,2021).These recent studies have primarily focused on the multifunctional p75 neurotrophin receptor(p75NTR)which is upregulated in central nervous system disease and injury,thus offering a unique target for intervention.

关键词： al. therapies p75

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Injectable versus oral first-line multiple sclerosis therapies:knows and unknowns from observational studies

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Neural Regeneration Research 2022年第3期17卷 567-568页

作者： Emanuele D’Amico Aurora Zanghì Carlo Avolio Department“G.F.Ingrassia” MS CenterUniversity of CataniaCataniaItaly Department of Medical and Surgical Sciences University of Foggia Multiple Sclerosis Center Department of NeurosciencesPoliclinico Riuniti HospitalFoggiaItaly

The approval of oral disease modifying therapies(DMTs) for relapsing-remitting multiple sclerosis(RRMS) has changed considerably the therapeutic scenario and they often represent the first therapeutic choice for patie... 详细信息

关键词： al. therapies sclerosis

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IGF1-PI3K-induced physiological cardiac hypertrophy:Implications for new heart failure therapies,biomarkers,and predicting cardiotoxicity

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Journal of Sport and Health Science 2021年第6期10卷 637-647,I0001页

作者： Sebastian Bass-Stringer Celeste M.K.Tai Julie R.McMullen Baker Heart and Diabetes Institute MelbourneVIC 3004Australia Department of Physiology Anatomy and MicrobiologyLa Trobe UniversityBundooraVIC 3086Australia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourneVIC 3004Australia Department of Physiology and Department of Medicine Alfred Hospital Monash UniversityMelbourneVIC 3004Australia

Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.

关键词： Cardiac protection Cardiotoxicity Exercise Heart failure IGF1 PI3K therapies

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Combination therapies with mitogen-activated protein kinase kinase inhibitors and immune checkpoint inhibitors in non-small cell lung cancer

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Chinese Medical Journal 2020年第20期133卷 2495-2497页

作者： Jia-Li Xu Xin-Zhu Wang Hu-Ning Jiang Yi Chen Rong Wang Yong-Qian Shu Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China First Clinical Medical College Nanjing Medical UniversityNanjingJiangsu 210029China

In the past few decades,tremendous advances have been made in terms of advaneed non-small cell lung cancer(NSCLC).The identification of oncogenic drivers and the development of targeted therapies led to the development of"pre&sion"medicine.On the other hand,more attention has been paid to cancer immune escape and a new class of immunomodulatory agents has been developed.It is very attractive to explore the combination strategies of the two approaches,which may also be meaningful from the perspective of immunology.

关键词： lung cancer therapies

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Targeted therapies in gynecological cancers:a comprehensive review of clinical evidence

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1261-1294页

作者： Qiao Wang Hongling Peng Xiaorong Qi Min Wu Xia Zhao Department of Gynecology and Obstetrics Development and Related Diseases of Women and Children Key Laboratory of Sichuan ProvinceKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenMinistry of EducationWest China Second HospitalSichuan UniversityChengduSichuan 610041P.R.China Department of Biomedical Sciences School of Medicine and Health SciencesUniversity of North DakotaGrand ForksND 58203USA

Advanced and recurrent gynecological cancers are associated with poor prognosis and lack of effective treatment.The developments of the molecular mechanisms on cancer progression provide insight into novel targeted therapies,which are emerging as groundbreaking and promising cancer treatment strategies.In gynecologic malignancies,potential therapeutic targeted agents include antiangiogenic agents,poly(ADP-ribose)polymerase(PARP)inhibitors,tumor-intrinsic signaling pathway inhibitors,selective estrogen receptor downregulators,and immune checkpoint inhibitors.In this article,we provide a comprehensive review of the clinical evidence of targeted agents in gynecological cancers and discuss the future implication.

关键词： clinical therapies prognosis

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Targeting nuclear acid-mediated immunity in cancer immune checkpoint inhibitor therapies

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Signal Transduction and Targeted Therapy 2020年第1期5卷 235-248页

作者： Miaoqin Chen Shiman Hu Yiling Li Ting Ting Jiang Hongchuan Jin Lifeng Feng Laboratory of Cancer Biology Key lab of Biotherapy in Zhejiang ProvinceCancer Institute of Zhejiang UniversitySir Run Run Shaw hospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310016China Department of Radiation Oncology Sir Run Run Shaw HospitalMedical School of Zhejiang UniversityHangzhou 310016China

Cancer immunotherapy especially immune checkpoint inhibition has achieved unprecedented successes in cancer treatment.However,there are many patients who failed to benefit from these therapies,highlighting the need for new combinations to increase the clinical efficacy of immune checkpoint inhibitors.In this review,we summarized the latest discoveries on the combination of nucleic acid-sensing immunity and immune checkpoint inhibitors in cancer immunotherapy.Given the critical role of nuclear acid-mediated immunity in maintaining the activation of T cell function,it seems that harnessing the nuclear acidmediated immunity opens up new strategies to enhance the effect of immune checkpoint inhibitors for tumor control.

关键词： immunity cancer therapies

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Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1584-1606页

作者： Rodolfo Daniel Cervantes-Villagrana Damaris Albores-García Alberto Rafael Cervantes-Villagrana Sara Judit García-Acevez Department of Pharmacology Center for Research and Advanced Studies of the National Polytechnic Institute(CINVESTAV-IPN)07360 Mexico CityMexico Department of Environmental Health Sciences Florida International University(FIU)MiamiFlorida 33199USA Laboratorio de investigación en Terapéutica Experimental Unidad Académica de Ciencias QuímicasÁrea de Ciencias de la SaludUniversidad Autónoma de Zacatecas(UAZ)ZacatecasMéxico Dirección de Proyectos e Investigación Grupo Diagnóstico Médico Proa06400 CDMX CuauhtémocMéxico

Normal cells are hijacked by cancer cells forming together heterogeneous tumor masses immersed in aberrant communication circuits that facilitate tumor growth and dissemination.Besides the well characterized angiogenic effect of some tumor-derived factors;others,such as BDNF,recruit peripheral nerves and leukocytes.The neurogenic switch,activated by tumor-derived neurotrophins and extracellular vesicles,attracts adjacent peripheral fibers(autonomic/sensorial)and neural progenitor cells.Strikingly,tumor-associated nerve fibers can guide cancer cell dissemination.Moreover,IL-1β,CCL2,PGE2,among other chemotactic factors,attract natural immunosuppressive cells,including T regulatory(Tregs),myeloid-derived suppressor cells(MDSCs),and M2 macrophages,to the tumor microenvironment.These leukocytes further exacerbate the aberrant communication circuit releasing factors with neurogenic effect.Furthermore,cancer cells directly evade immune surveillance and the antitumoral actions of natural killer cells by activating immunosuppressive mechanisms elicited by heterophilic complexes,joining cancer and immune cells,formed by PD-L1/PD1 and CD80/CTLA-4 plasma membrane proteins.Altogether,nervous and immune cells,together with fibroblasts,endothelial,and bone-marrow-derived cells,promote tumor growth and enhance the metastatic properties of cancer cells.Inspired by the demonstrated,but restricted,power of anti-angiogenic and immune cell-based therapies,preclinical studies are focusing on strategies aimed to inhibit tumor-induced neurogenesis.Here we discuss the potential of anti-neurogenesis and,considering the interplay between nervous and immune systems,we also focus on anti-immunosuppression-based therapies.Small molecules,antibodies and immune cells are being considered as therapeutic agents,aimed to prevent cancer cell communication with neurons and leukocytes,targeting chemotactic and neurotransmitter signaling pathways linked to perineural invasion and metastasis.

关键词： PD1 therapies invasion

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Pharmacologic adjunctive to insulin therapies in type 1 diabetes:The journey has just begun

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World Journal of Diabetes 2019年第4期10卷 234-240页

作者： Spyridon N Karras Theocharis Koufakis Pantelis Zebekakis Kalliopi Kotsa Division of Endocrinology and Metabolism and Diabetes Center First Department of Internal MedicineMedical School Aristotle University of Thessaloniki AHEPA University Hospital

Treatment of type 1 diabetes(T1 D) is currently based exclusively on insulin replacement therapy. However, there is a need for better glycemic control, lower hypoglycemia rates, more effective weight management, and further reduction of cardiovascular risk in people with T1 D. In this context, agents from the pharmaceutical quiver of type 2 diabetes are being tested in clinical trials, as adjunctive to insulin therapies for T1 D patients. Despite the limited amount of relevant evidence and the inter-class variability, it can be said that these agents have a role in optimizing metabolic control, assisting weight management and reducing glycemic variability in people with T1 D. Specific safety issues, including the increased risk of hypoglycemia and diabetic ketoacidosis, as well as the effects of these treatments on major cardiovascular outcomes should be further assessed by future studies, before these therapeutic choices become widely available for T1 D management.

关键词： Type 1 diabetes Insulin Adjunctive therapies Cardiovascular risk

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Single-cell sorting based on secreted products for functionally defined cell therapies

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Microsystems & Nanoengineering 2022年第4期8卷 17-34页

作者： Hiromi Miwa Robert Dimatteo Joseph de Rutte Rajesh Ghosh Dino Di Carlo Department of Bioengineering University of California-Los AngelesLos AngelesCA 90095USA Department of Chemical and Biomolecular Engineering University of California-Los AngelesLos AngelesCA 90095USA Partillion Bioscience Los AngelesCA 90095USA Department of Mechanical and Aerospace Engineering University of California-Los AngelesLos AngelesCA 90095USA California NanoSystems Institute(CNSI) University of California-Los AngelesLos AngelesCA 90095USA

Cell therapies have emerged as a promising new class of“living”therapeutics over the last decade and have been particularly successful for treating hematological malignancies.Increasingly,cellular therapeutics are being developed with the aim of treating almost any disease,from solid tumors and autoimmune disorders to fibrosis,neurodegenerative disorders and even aging itself.However,their therapeutic potential has remained limited due to the fundamental differences in how molecular and cellular therapies function.While the structure of a molecular therapeutic is directly linked to biological function,cells with the same genetic blueprint can have vastly different functional properties(e.g.,secretion,proliferation,cell killing,migration).Although there exists a vast array of analytical and preparative separation approaches for molecules,the functional differences among cells are exacerbated by a lack of functional potency-based sorting approaches.In this context,we describe the need for next-generation single-cell profiling microtechnologies that allow the direct evaluation and sorting of single cells based on functional properties,with a focus on secreted molecules,which are critical for the in vivo efficacy of current cell therapies.We first define three critical processes for single-cell secretion-based profiling technology:(1)partitioning individual cells into uniform compartments;(2)accumulating secretions and labeling via reporter molecules;and(3)measuring the signal associated with the reporter and,if sorting,triggering a sorting event based on these reporter signals.We summarize recent academic and commercial technologies for functional single-cell analysis in addition to sorting and industrial applications of these technologies.These approaches fall into three categories:microchamber,microfluidic droplet,and lab-on-a-particle technologies.Finally,we outline a number of unmet needs in terms of the discovery,design and manufacturing of cellular therapeutics and how the next generation of single-cell functi

关键词： therapies sorting realization

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