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Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer

Asian Journal of Andrology 2016年第4期18卷 580-585页

作者： Jun Luo Department of Urology James Buchanan Brady Urological Institute Johns Hopkins University Baltimore MD USA.

Prostate cancer cells demonstrate a remarkable ＂addiction＂ to androgen receptor （AR） signaling in all stages of disease progression. As such, suppression of AR signaling remains the therapeutic goal in systemic treatment of prostate cancer. A number of molecular alterations arise in patients treated with AR-directed therapies. These molecular alterations may indicate the emergence of treatment resistance and may be targeted for the development of novel agents for prostate cancer. The presence of functional androgen receptor splice variants may represent a potential explanation for resistance to abiraterone and enzalutamide, newer AR-directed agents developed to treat metastatic castration-resistant prostate cancer （mCRPC）. In the last 8 years, many androgen receptor splice variants have been identified and characterized. Among these, androgen receptor splice variant-7 （AR-V7） has been investigated extensively. In AR-V7, the entire COOH-terminal ligand-binding domain of the canonical AR is truncated and replaced with a variant-specific peptide of 16 amino acids. Functionally, AR-V7 is capable of mediating constitutive nuclear localization and androgen receptor signaling in the absence of androgens, or in the presence of enzalutamide. In this review, we will focus on clinical translational studies involving detection/measurement of AR-V7. Methods have been developed to detect AR-V7 in clinical mCRPC specimens. AR-V7 can be reliably measured in both tissue and circulating tumor cells derived from mCRPC patients, making it possible to conduct both cross-sectional and longitudinal clinical correlative studies. Current evidence derived from studies focusing on detection of AR-V7 in mCRPC support its potential clinical utility as a treatment selection marker.

关键词： androgen receptor androgen receptor splice variant-7 (AR-V7) castration-resistance prostate cancer circulating tumorcells treatment selection

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Electro-chemotactic stimuli for cell replacement therapy in neurosensory retina

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Neural Regeneration Research 2020年第3期15卷 450-452页

作者： Maribel Vazquez Department of Biomedical Engineering Rutgers University:The State University of New Jersey

Focus of perspective:Numbers of visually-impaired adults are rising rapidly around the *** transplantation therapies show great promise to restore vision,but have been severely impeded by poor synaptic positioning within retinal *** perspectives article highlights our group’s abilities to remarkably direct the migration of transplantable cells by applying electro-chemical fields within retina-customized *** of our in vitro results with current ex vivo and in vivo studies has the potential to transformatively impact outcomes of cell replacement therapy.

关键词： Focus impaired vivo

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Tcf1 at the crossroads of CD4^＋ and CD8^＋ T cell identity

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Frontiers in Biology 2017年第2期12卷 83-93页

作者： Jodi A. Gullicksrud Qiang Shan Hai-Hui Xue Department of Microbiology Carver College of Medicine University of Iowa Iowa City IA 52242 USA Interdisciplinary Immunology Graduate Program Carver College of Medicine University of Iowa Iowa City IA 52242 USA

Transcription factors and DNA/histone modification enzymes work in concert to establish and maintain cell identity. CD4^＋ and CD8^＋ T cells are key players in cellular immunity with distinct functions. Recent studies offer novel insights into how their identities are established in the thymus and maintained in the periphery during immune responses. During thymic maturation, Thpok, HDAC1 and HDAC2 guard CD4^＋ T cells from activation of CD8^＋ cytotoxic genes, and Tcfl and Left utilize their intrinsic HDAC activity to shut down CD4^＋ lineage-associated genes in CD8^＋ T cells. In activated CD4＋ T cells, Tcfl and Left act upstream of the Bc16-Blimpl axis to direct differentiation of follicular helper T （Tfh） cells, and prevent diversion of Tfh to IL-17-producing cells. In parallel, T-bet, together with Eomes or Blimpl, ensures proper induction of the cytotoxic program in CD8^＋ effectors elicited by acute infection, and prevents generation of pathogenic, IL-17-producing CD8^＋ effector T cells. Antigen persistence due to chronic viral infection leads to CD8^＋ T cell exhaustion. A portion of exhausted CD8^＋ T cells has the capacity to activate the Tfh program in a Tcfl-dependent manner. Those Tfh-like CD8^＋ T cells exhibit enhanced proliferative capacity in response to PD-1 blockage therapy and are more effective in curtailing viral replication. Thus, dissecting the molecular aspects of T cell identity, during development and immune responses, may lead to new therapies for treating autoimmunity, tumors, and persistent infections.

关键词： Tcf1 Lef1 HDAC CD4^+ T cells CD8^+ T cells cell identity

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Bioconjugated Silica Nanoparticles: Development and Applications

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Nano Research 2008年第2期1卷 99-115页

作者： Lin Wang Wenjun Zhao Weihong Tan Lilly Research Laboratories Eli Lilly and CompanyIndianapolisIN 46285USA Chinese Academy of Inspection and Quarantine Huixinli 241Chaoyang DistrictBeijing 100029China Center for Research at the Bio/Nano Interface Department of Chemistry and Department of Physiology and Functional GenomicsShands Cancer CenterUF Genetics Institute and McKnight Brain InstituteUniversity of FloridaGainesvilleFL 32611-7200USA

Advanced bioanalysis,including accurate quantitation,has driven the need to understand biology and medicine at the molecular *** silica nanoparticles have the potential to address this emerging *** intriguing diagnostic and therapeutic applications in cancer and infectious disease as well as uses in gene and drug delivery,have also been found for silica *** this review,we describe the synthesis,bioconjugation,and applications of silica nanoparticles in different bioanalysis formats,such as selective tagging,barcoding,and separation of a wide range of biomedically important ***,we envisage that further development of these nanoparticles will provide a variety of advanced tools for molecular biology,genomics,proteomics and medicine.

关键词： Nanoscience nanotechnology silica nanoparticles bioanalysis biomedicine

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Emerging roles of deubiquitinating enzymes in human cancer

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Acta Pharmacologica Sinica 2007年第9期28卷 1325-1330页

作者： Jin-ming YANG Department of Pharmacology,The Cancer Institute of New Jersey,University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School,New Brunswick,New Jersey 08903,usA Department of Pharmacology The Cancer Institute of New Jersey University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School New Brunswick USA

Protein modifications by the covalent linkage of ubiquitin have significant in-volvement in many cellular processes,including stress response,oncogenesis,viral infection,transcription,protein turnover,organelle biogenesis,DNA repair,cellular differentiation,and cell cycle *** ubiquitination and subse-quent degradation by the proteasome require the participation of bothubiquitinating enzymes and deubiquitinating *** deubiquitinatingenzymes constitute a large family in the ubiquitin system,the study of this class ofproteins is still in its infant *** studies have revealed a variety ofmolecular and biological functions of deubiquitinating enzymes and their associa-tion with human *** this review we will discuss the possible roles thatdeubiquitinating enzymes may play in cancers.

关键词： ubiquitin cancer deubiquitinating enzymes

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Latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases

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Genes & Diseases 2022年第5期9卷 1194-1207页

作者： XiaoYi He Stephanie Tan Zhong Shao Xiao Wang Department of Neurology Affiliated Zhongshan Hospital of Dalian UniversityDalianLiaoning 116001PR China The Third Hospital of Fushun FushunLiaoning 113004PR China Stanley Manne Children’s Research Institute Ann&Robert H.Lurie Children’s Hospital of ChicagoChicagoIL 60611USA Department of Pediatrics Feinberg School of MedicineNorthwestern UniversityChicagoIL 60611USA

Macrophages are dominant innate immune *** demonstrate remarkable het-erogeneity and plasticity that are essential for homeostasis and host *** heterogeneity of tissue macrophages is shaped by the ontogeny,tissue factors,and environmental signals,a pattern in a tissue-associated latitudinal *** the same time,macrophages have long been considered as mainly plastic *** cells respond to stimulation quickly and in a stimulus-specific way by utilizing a longitudinal cascaded activation,including coordination of signal trans-ducer,epigenetic elements,and transcription factors,conclusively determine the macrophage phenotypes and *** the development of cutting-edge technologies,such as fate-mapping,single-cell transcriptomics,ipsc platform,nanotherapeutic materials,etc.,our under-standing of macrophage biology and the roles in the pathogenesis of diseases is much *** review summarizes recent progress on the latitudinal and longitudinal regulation of tissue macrophages in inflammatory *** latitudinal regulation covers the tissue macrophage or-igins,tissue factors,and environmental signals,reflecting the macrophage *** lon-gitudinal regulation focuses on how multiple factors shape the phenotypes and functions of macrophage subsets to gain plasticity in inflammatory diseases(i.e.,inflammatory bowel disease).In addition,how to target macrophages as a potential therapeutic approach and cutting edge-technologies for tissue macrophage study are also discussed in this review.

关键词： Epigenetic regulation Inflammatory disease microRNA Macrophage origin Macrophage polarization Single-cell RNA-sequencing Tissue macrophage

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A Robin-Robin Domain Decomposition Method for a Stokes-Darcy Structure Interaction with a Locally Modified Mesh

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Numerical Mathematics(Theory,Methods and Applications) 2014年第4期7卷 435-446页

作者： Zhaohui Wang Zhilin Li Sharon Lubkin Department of Mathematics and Center for Research in Scientific Computation(CRSC) North Carolina State UniversityRaleighNC 27695USA

A new numerical method based on locally modified Cartesian meshes is proposed for solving a coupled system of a fluid flow and a porous media *** fluid flow is modeled by the Stokes equations while the porous media flow is modeled by Darcy’s *** method is based on a Robin-Robin domain decomposition method with a Cartesian mesh with local modifications near the *** computational examples are presented and discussed.

关键词： Stokes-Darcy fluid structure interactions Robin-Robin domain decomposition method body fitted mesh locally modified mesh BJS interface condition

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An Adaptive Mesh Refinement Strategy for Immersed Boundary/Interface Methods

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Communications in Computational Physics 2012年第7期12卷 515-527页

作者： Zhilin Li Peng Song Center for Research in Scientific Computation&Department of Mathematics North Carolina State UniversityRaleighNC 27695USA Nanjing Normal University China Operations Research Program North Carolina StateUniversityRaleighNC 27695USA

An adaptive mesh refinement strategy is proposed in this paper for the Immersed Boundary and Immersed Interface methods for two-dimensional elliptic interface problems involving singular *** interface is represented by the zero level set of a Lipschitz functionϕ(x,y).Our adaptive mesh refinement is done within a small tube of|ϕ(x,y)|δwith finer Cartesian *** discrete linear system of equations is solved by a multigrid *** AMR methods could obtain solutions with accuracy that is similar to those on a uniform fine grid by distributing the mesh more economically,therefore,reduce the size of the linear system of the *** examples presented show the efficiency of the grid refinement strategy.

关键词： Adaptive mesh refinement immersed boundary method immersed interface method elliptic interface problem Cartesian grid method level set representation singular sources

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The Sensitivity Analysis for the Flow Past Obstacles Problem with Respect to the Reynolds Number

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Advances in Applied Mathematics and Mechanics 2012年第1期4卷 21-35页

作者： Kazufumi Ito Zhilin Li Zhonghua Qiao Center for Research in Scientific Computation&Department of Mathematics North Carolina State UniversityRaleighNC 27695-8205USA School of Mathematical Sciences Nanjing Normal UniversityNo.1 Wenyuan RoadYadong New DistrictNanjing 210046China Department of Mathematics Hong Kong Baptist UniversityKowloon TongHong Kong

In this paper,numerical sensitivity analysis with respect to the Reynolds number for the flow past obstacle problem is *** carry out such analysis,at each time step,we need to solve the incompressible Navier-Stokes equations on irregular domains twice,one for the primary variables;the other is for the sensitivity variables with homogeneous boundary *** Navier-Stokes solver is the augmented immersed interface method for Navier-Stokes equations on irregular *** of the most important contribution of this paper is that our analysis can predict the critical Reynolds number at which the vortex shading begins to develop in the wake of the *** interesting experiments are shown to illustrate how the critical Reynolds number varies with different geometric settings.

关键词： Navier-Stokes equations sensitivity analysis flow past cylinder embedding technique immersed interface method irregular domain augmented system projection method fluid-solid interaction

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Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity

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Bone Research 2020年第4期8卷 393-405页

作者： Xin Yi Laura E.Wright Gabriel M.Pagnotti Gunes Uzer Katherine M.Powell Joseph M.Wallace Uma Sankar Clinton T.Rubin Khalid Mohammad Theresa A.Guise William R.Thompson Department of Physical Therapy School of Health and Rehabilitation SciencesIndiana UniversityIndianapolisIN 46202USA Department of Medicine Division of EndocrinologySchool of MedicineIndiana UniversityIndianapolisIN 46202USA Department of Mechanical and Biomedical Engineering Boise State UniversityBoiseID 83725USA Department of Biomedical Engineering Purdue School of Engineering and TechnologyPurdue UniversityIndianapolisIN 46202USA Department of Anatomy&Cell Biology Indiana UniversityIndianapolisIN 46202USA Department of Biomedical Engineering Stony Brook UniversityStony BrookNY 11794USA

Exercise benefits the musculoskeletal system and reduces the effects of *** effects of exercise are multifactorial,where metabolic changes and tissue adaptation influence *** signals,a principal component of exercise,are anabolic to the musculoskeletal system and restrict cancer *** examined the mechanisms through which cancer cells sense and respond to low-magnitude mechanical signals introduced in the form of ***-magnitude,high-frequency vibration was applied to human breast cancer cells in the form of low-intensity vibration(LIV).LIV decreased matrix invasion and impaired secretion of osteolytic factors PTHLH,IL-11,and ***,paracrine signals from mechanically stimulated cancer cells,reduced osteoclast differentiation and resorptive *** the nucleus by knockdown of SUN1 and SUN2 impaired LIV-mediated suppression of invasion and osteolytic factor *** increased cell stiffness;an effect dependent on the LINC *** data show that mechanical vibration reduces the metastatic potential of human breast cancer cells,where the nucleus serves as a mechanosensory apparatus to alter cell structure and intercellular signaling.

关键词： invasion impaired skeletal

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