Download or read book Investigation of the Transcription Factor GATA2 as a Potential Therapeutic Target for Castration resistance Prostate Cancer written by Qianhui Yi and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "The androgen receptor (AR) serves as a key driver of the proliferation and survival of prostate cancer (PCa) cells. Current mainstay treatment is to block the AR signaling by androgen deprivation therapy and antiandrogens. Despite the short-term efficacy of suppressing AR signaling, the tumor eventually adapts resistance via constitutive activation of the AR axis and manifests in the form of castration-resistant prostate cancer (CRPC). So far, multiple molecular mechanisms behind castration-resistance have been reported, including persisted androgen synthesis, AR amplification, AR point mutation, AR splice variants and AR transcriptional co-regulators. Unfortunately, current AR-targeting agents are unable to prevent AR reactivation, and as a result, there is urgent need for alternative approaches to block AR signaling. Our study has provided several lines of evidence that the transcription factor GATA-binding protein 2 (GATA2) is a critical regulator of the development of resistance in androgen ablation and antiandrogen therapy, suggesting that GATA2 could be a valuable therapeutic target against CRPC. We initially observed rapid induction of GATA2 expression after androgen deprivation or antiandrogen treatment in PCa cell line. Moreover, this overexpression exclusively occurs in AR positive PCa cells and is especially greater in CRPC cells compared to androgen-dependent cells. Stable overexpression of GATA2 in androgen-dependent LNCaP cells (referred to as LNCaP-GATA2) consequently caused the cells to adopt multiple CRPC features. AR signaling in LNCaP-GATA2 cells is constitutively active in the absence of androgen, exhibited hypersensitivity to low level of androgen stimulation, and resistance to antiandrogen inhibition. Finally, castration resistant survival and proliferation was observed in LNCaP-GATA2 cells thus demonstrated GATA2's critical role in CRPC development.Our preliminary data demonstrated that androgen-deprivation and antiandrogen treatments substantially and rapidly induce GATA2 expression, which sustain AR signaling and in turn, result in resistance to those treatments. Collectively, our results suggest a critical feedback loop between AR and GATA2 that can be targeted to inhibit progression towards CRPC. Our effort to develop chemical inhibitors of GATA2 is in progress and initial results will be briefly discussed." --

Download or read book Response and Resistance in Castration Resistant Prostate Cancer written by Hung-Ming Lam and published by Frontiers Media SA. This book was released on 2020-12-24 with total page 99 pages. Available in PDF, EPUB and Kindle. Book excerpt: This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

Download or read book Targeting CXCR2 Neuroendocrine like Cells for the Treatment of Castration resistant Prostate Cancer written by Yanjing Li and published by . This book was released on 2017 with total page 34 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous malignancy in men and the second leading cause of cancer-related deaths in the US. Men with PCa that has recurred after surgery or radiation therapy usually respond to androgen deprivation therapy (ADT); however despite initial responses rate of 80 to 90 percent, nearly all men eventually develop progressive disease following ADT; this is referred to as castration-resistant prostate cancer (CRPC), which remains an incurable disease. It has been reported that neuroendocrine (NE) cell type in prostate cancer is highly associated with castration-resistant disease. However, the exact role of NE cells in promoting the transition from castration-sensitive cancer to castration-resistant disease is not fully understood. The goal of this study was to investigate the gene expression profile, cellular function and therapeutic resistant properties of NE cells purified through CXCR2 surface marker from prostate adenocarcinoma. We further investigated the role of CXCR2 in mediating CRPC carcinogenesis and explore the use of CXCR2 inhibitor combine with Enzalutamide as a potential therapy for advanced prostate cancer. In this research, we have identified a novel cross-talk between neuroendocrine cells in hormone nai ve prostate cancer with both prostate cancer progression and hormonal therapy resistance. We have demonstrated that C-X-C motif chemokine receptor 2 (CXCR2) is a unique surface marker of neuroendocrine cells in prostate cancer and it is over-expressed in metastatic castration resistant, high grade, and NEPC patient cases. Importantly, we discovered that CXCR2 plays a critical role in facilitating this intercellular communication and NEPC transformation from typical prostate adenocarcinoma. CXCR2 overexpression led to enzalutamide resistance, loss of AR expression, and lineage plasticity with acquisition of stem cell-like properties. We further demonstrated that CXCR2 inhibition can prevent/delay enzalutamide resistance and restore AR function, leading to reductions in tumor burden. This research provides the mechanism for the first time of therapeutic resistance mediated by NE cells and raises the possibility to the final cure of lethal prostate cancer through CXCR2 blocker.

Download or read book Molecular Mechanisms of Prostate Cancer Progression and Treatment Resistance written by Yezi Zhu and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate cancer is the most common type of cancer in American men and ranks second to lung cancer in cancer-related deaths. The growth and survival of primary prostate tumors requires physiological level of androgen. Thus hormone therapy has been used for treatment of primary prostate cancer. However, prostate cancer eventually progresses to a castration-resistant state. Understanding the molecular mechanisms leading to castration resistance is very critical for combat this lethal disease. The first part of this thesis will discuss the loss of Rho-GDP dissociation inhibitor [alpha] (RhoGDI[alpha]) as one of the molecular mechanisms leading to prostate cancer castration-resistant progression. My study demonstrated that RhoGDI[alpha] suppresses growth and survival of prostate cancer cells. In this part, I utilized the previously generated LNCaP-IL6+ cells which were able to grow in androgen-deprived condition. The protein expression profiles of LNCaP and LNCaP-IL6+ cells were compared using two-dimensional gel electrophoresis. Expression of RhoGDI[alpha] was reduced in LNCaP-IL6+ cells and was down-regulated in more aggressive prostate cancer cells compared to LNCaP cells. The effects of RhoGDI[alpha] in prostate cancer cells growth and survival were examined both in vitro and in vivo. Overexpression of RhoGDI[alpha] inhibited the growth and induced apoptosis of prostate cancer cells. RhoGDI[alpha] caused LNCaP-IL6+ cells reversal to androgen-sensitive state, and downregulation of RhoGDI[alpha] enhanced growth of androgen-sensitive LNCaP cells in androgen-deprived condition. In addition, RhoGDI[alpha] suppressed the tumorigenic ability and prostate-specific antigen (PSA) production of prostate tumor xenografts in vivo. The aberrant activation of androgen receptor (AR) is responsible for castration-resistant prostate cancer (CRPC) progression and regulation of AR-target genes such as PSA. My in vivo study showed RhoGDI[alpha] inhibited PSA production in the mice sera bearing tumors, indicating RhoGDI[alpha] inhibits AR signaling in prostate cancer cells. The effects of RhoGDI[alpha] on AR signaling will be further discussed. RhoGDI[alpha] was transiently or stably transfected into several prostate cancer cell lines including LNCaP, C4-2, CWR22Rv1 and DU145. The regulation of AR expression by RhoGDI[alpha] was analyzed by qRT-PCR and Western blot. Overexpression of RhoGDI[alpha] downregulated AR expression at both mRNA and protein levels. AR activity was measured by luciferase reporter assays and electrophoretic mobility shift analysis (EMSA). RhoGDI[alpha] was able to inhibit transactivation of AR target genes and prevent AR binding to androgen response element. Immunofluorescence assay was performed and overexpression of RhoGDI[alpha] prevented AR nuclear translocation induced by androgens. The interaction between RhoGDI[alpha] and AR was examined by co-immunoprecipitation assays. RhoGDI[alpha] was found to physically interact with the N-terminal domain of AR. Neuroendocrine differentiation (NED) is associated with castration-resistance of prostate cancer. It has been suggested as a marker of poor prognosis for prostate cancer. Paracrine interleukin-6 (IL-6) can mediate NED features in prostate cancer. The second part of this thesis will discuss the mechanism underlying IL-6-induced NED. RE1-silencing transcription factor (REST) is a main negative regulator of neurogenesis and represses expression of NED genes. I confirmed the IL-6-induced NED by cell morphological changes as well as the induction of NE markers such as neuron-specific enolase (NSE), chromogranin A (ChgA) and synaptophysin. The expression of REST was suppressed in IL-6-induced NED in LNCaP cells. To further study the impact of REST-mediated repression on NED in LNCaP cells, either wild-type REST or a dominant-positive form of REST, REST-VP16, in which both repressor domains of REST were replaced with the activation domain of the herpes simplex virus protein VP16, was introduced into LNCaP cells. Overexpression of exogenous wild type REST abrogated IL-6-induced NED in prostate cancer cells. Expression of the recombinant REST-VP16 fusion protein activated REST target genes and other neuronal differentiation genes and produced neuronal physiological properties. In addition, REST protein turnover was accelerated in IL-6 induced NE differentiated LNCaP cells via the ubiquitin-proteasome pathway, accompanied by a decrease in the expression of the deubiquitylase HAUSP, indicating that pathway(s) priming REST degradation may be involved in IL-6 induced NE differentiation. Docetaxel is the first-line standard treatment for CRPC. However, once tumors develop resistance to docetaxel, the treatment options are again limited. In the last part of this thesis, I will discuss the docetaxel resistance mechanisms and potential therapeutic strategies for docetaxel-resistant CRPC. I established a docetaxel resistant cell line, TaxR, by culturing C4-2B cells in docetaxel in a dose-escalation manner until cells were able to divide freely in 5 nM docetaxel. Global gene expression analysis by cDNA microarrays (approximately 28000 genes) was performed using mRNA from parental C4-2B and TaxR cells. ABCB1, which belongs to the ATP-binding cassette (ABC) transporter family, was identified among the top upregulated genes in TaxR cells. Overexpression of ABCB1 in TaxR cells has been validated by both real-time PCR and Western blot analysis. Downregulation of ABCB1 by specific shRNA or inhibiting ABCB1 activity by ABCB1 inhibitor elacridar restored docetaxel sensitivity in TaxR cells. Apigenin (4', 5, 7-trihydroxyflavone), a natural product belonging to the flavone family, downregulated ABCB1 protein expression in ubiquitin-proteasome pathway and overcame docetaxel resistance in TaxR cells. The effects of different anti-androgens like enzalutamide, abiraterone and bicalutamide on ABCB1 efflux activity were tested using rhodamine123 efflux assay. These antiandrogens inhibited ABCB1 efflux activity and reversed docetaxel resistance in TaxR cells in vitro. The reversal effect of bicalutamide was further confirmed in TaxR xenograft tumors, suggesting targeting ABCB1 could be a potential approach to resensitize docetaxel-resistant prostate cancer cells to docetaxel treatment.

Download or read book AR Signaling in Human Malignancies Prostate Cancer and Beyond written by Emmanuel S. Antonarakis and published by MDPI. This book was released on 2018-03-23 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "AR Signaling in Human Malignancies: Prostate Cancer and Beyond" that was published in Cancers

Download or read book Leong s Manual of Diagnostic Antibodies for Immunohistology written by Runjan Chetty and published by Cambridge University Press. This book was released on 2016-11-28 with total page 525 pages. Available in PDF, EPUB and Kindle. Book excerpt: Providing a unique A-Z guide to antibodies for immunohistology, this is an indispensable source for pathologists to ensure the correct application of immunohistochemistry in daily practice. Each entry includes commercial sources, clones, descriptions of stained proteins/epitopes, the full staining spectrum of normal and tumor tissues, staining pattern and cellular localization, the range of conditions of immunoreactivity, and pitfalls of the antibody's immunoprofile, giving pathologists a truly thorough quick-reference guide to sources, preparation and applications of specific antibodies. Appendices provide useful quick-reference tables of antibody panels for differential diagnoses, as well as summaries of diagnostic applications. Expanded from previous editions with over forty new entries, this handbook for diagnostic, therapeutic, prognostic and research applications of antibodies is an essential desktop book for practicing pathologists as well as researchers, residents and trainees.

Download or read book Prostate Cancer written by Scott M. Dehm and published by Springer Nature. This book was released on 2020-01-03 with total page 483 pages. Available in PDF, EPUB and Kindle. Book excerpt: The purpose of this book is to provide a contemporary overview of the causes and consequences of prostate cancer from a cellular and genetic perspective. Written by experts in the fields of epidemiology, toxicology, cell biology, genetics, genomics, cell-cell interactions, cell signaling, hormone signaling, and transcriptional regulation, the text covers aspects of prostate cancer from disease initiation to metastasis. Chapters explore in depth the cells of origin for prostate cancer, its genomic subtypes, neural transcription factors in disease progression, epigenetic regulation of chromatin, and many other topics. This book distinguishes itself from other texts on prostate cancer by its focus on cellular and genetic mechanisms, as opposed to clinical diagnosis and management. As a result, this book will be of broad interest to basic and translational scientists with familiarity of these topics, as well as to trainees at earlier stages of their research careers.

Download or read book Precision Molecular Pathology of Prostate Cancer written by Brian D. Robinson and published by Springer. This book was released on 2018-02-13 with total page 564 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume focuses on our current understanding of the molecular underpinnings of prostate cancer and their potential application for precision medicine approaches. The emergence and applications of new technologies has allowed for a rapid expansion of our understanding of the molecular basis of prostate cancer and has revealed a remarkable genetic heterogeneity that may underlie the clinically variable behavior of the disease. The book consists of five sections which provide insight about the following: (1) General principles; (2) Molecular signatures of primary prostate cancer; (3) Molecular signatures of advanced prostate cancer; (4) Key molecular pathways in prostate cancer development and progression; (5) and Precision medicine approach: Diagnosis, treatment, prognosis. Precision Molecular Pathology of Prostate Cancer is an important resource for the practicing oncologist, urologist, and pathologist, and will also be useful for researchers in the prostate cancer community.

Download or read book Patient Derived Xenograft Models of Human Cancer written by Yuzhuo Wang and published by Springer. This book was released on 2017-06-27 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive, state-of-the-art review of PDX cancer models. In separately produced chapters, the history and evolution of PDX models is reviewed, methods of PDX model development are compared in detail, characteristics of available established models are presented, current applications are summarized and new perspectives about use of PDX models are proposed. Each chapter is written by a world-renowned expert who is conducting cutting-edge research in the field. Each of the subsections provide a comprehensive review of existing literature addressing the particular topic followed by a conclusive paragraph detailing future directions. Extensive illustrations make this an interactive text. Patient-Derived Xenograft Models of Human Cancer will serve as a highly useful resource for researchers and clinicians dealing with, or interested in, this important topic. It will provide a concise yet comprehensive summary of the current status of the field that will help guide preclinical and clinical applications as well as stimulate investigative efforts. This book will propagate innovative concepts and prompt the development of ground-breaking technological solutions in this field.

Download or read book Tumor Microenvironments in Organs written by Alexander Birbrair and published by Springer Nature. This book was released on 2020-02-06 with total page 155 pages. Available in PDF, EPUB and Kindle. Book excerpt: Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research on the tumor microenvironment in over thirty human organs, including the parathyroid gland, heart, intestine, testicles, and more. Taken alongside its companion volumes, these books update us on what we know about the different aspects of the tumor microenvironments in distinct organs as well as future directions. Tumor Microenvironments in Organs: From the Brain to the Skin – Part A is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.

Download or read book Genomics Proteomics and Metabolomics written by Babak Arjmand and published by Springer Nature. This book was released on 2019-11-14 with total page 199 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides thorough coverage of high-throughput OMICs technologies for the monitoring of stem cells and regenerative medicine. Specific topics covered include the genomics, proteomics, and metabolomics aspects of regenerative medicine, metabolic profiling of mesenchymal stem cells, genome profiling of mesenchymal stem cells, OMICs monitoring of stem cell-derived exosomes, stem cell proteomics, lipidomics, OMICs profiling of cancer (stem) cells, and finally ethical considerations of OMICs-based investigations. Chapters are authored by world-renowned scientists who have valuable expertise in the field of OMICs and regenerative medicine. Genomics, Proteomics, and Metabolomics: Stem Cells Monitoring in Regenerative Medicine, part of Springer’s Stem Cell Biology and Regenerative Medicine series, is essential reading for researchers, clinicians, biologists, biochemists, and pharmaceutical experts conducting research in the fields of stem cell biology, molecular aspects of stem cell research, tissue engineering, regenerative medicine, cellular therapy, OMICs, bioinformatics, and ethics.

Download or read book Statistical Modelling and Machine Learning Principles for Bioinformatics Techniques Tools and Applications written by K. G. Srinivasa and published by Springer Nature. This book was released on 2020-01-30 with total page 318 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses topics related to bioinformatics, statistics, and machine learning, presenting the latest research in various areas of bioinformatics. It also highlights the role of computing and machine learning in knowledge extraction from biological data, and how this knowledge can be applied in fields such as drug design, health supplements, gene therapy, proteomics and agriculture.

Download or read book Exploration of Natural Product Leads for Multitarget Based Treatment of Cancer Computational to Experimental Journey written by Rajeev K. Singla and published by Frontiers Media SA. This book was released on 2022-03-14 with total page 249 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Immunophenotyping written by J Philip McCoy Jr and published by Humana. This book was released on 2019-09-29 with total page 375 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume presents the latest collection of immunophenotypic techniques and applications used in research and clinical settings. Chapters in this book cover topics such as constructions of high dimensions fluorescence and mass cytometry panels; fluorescence barcoding; using dried or lyophilized reagents; and immunophenotypic examples of specific cell types. The book concludes with a discussion on the critical roles of quality control and immunophenotyping in the clinical environment. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, Immunophenotyping: Methods and Protocols is a valuable resource for any researchers, clinician, or scientist interested in learning more about this evolving field.

Download or read book Receptor Tyrosine Kinases Family and Subfamilies written by Deric L. Wheeler and published by Springer. This book was released on 2015-07-31 with total page 888 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book devotes a chapter to each RTK family and the multiple receptors within each family, thoroughly covering all of the RTKs. The chapters all follow the same structure, presenting this essential information in an accessible and user-friendly format. Each chapter covers one specific family of receptors and begins with a general introduction to that family and a comprehensive discussion of that receptor’s family in development and human disease. Following are in-depth analyses of each family’s receptors with discussions on the gene, protein, ligands, activation, and signaling pathways along with discussion of receptor processing and signal attenuation. Further, cross talk with other receptors systems, post-translational modification and specific unique characteristics to each RTK are discussed. Because it isolates and explains each family, this book is an essential companion volume to Receptor Tyrosine Kinases: Structure, Functions and Role in Human Disease, by the same authors, which talks about RTKs more generally and without the family-by-family detail.

Download or read book Protein Tyrosine Phosphatases in Cancer written by Benjamin G. Neel and published by Springer. This book was released on 2016-08-05 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book aims to bridge the gap in understanding how protein-tyrosine phosphatases (PTPs), which carry out the reverse reaction of tyrosine phosphorylation, feature in cancer cell biology. The expertly authored chapters will first review the general features of the PTP superfamily, including their overall structure and enzymological properties; use selected examples of individual PTP superfamily members, to illustrate emerging data on the role of PTPs in cancer; and will review the current status of PTP-based drug development efforts. Protein Tyrosine Phosphatases in Cancer,from renowned researchers Benjamin Neel and Nicholas Tonks, is invaluable reading for researchers in oncology, stem cell signaling,and biochemistry.

Download or read book Principles of Cancer Genetics written by Fred Bunz and published by Springer. This book was released on 2016-03-01 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the second edition of a widely used textbook that consolidates the basic concepts of the cancer gene theory and provides a framework for understanding the genetic basis of cancer. Particular attention is devoted to the origins of the mutations that cause cancer, and the application of evolutionary theory to explain how the cell clones that harbor cancer genes tend to expand. Focused on the altered genes and pathways that cause the growth of the most common tumors, Principles of Cancer Genetics is aimed at advanced undergraduates who have completed introductory coursework in genetics, biology and biochemistry, medical students and medical house staff. For students with a general interest in cancer, this book provides a highly accessible and readable overview. For more advanced students contemplating future study in the field of oncology and cancer research, this concise book will be useful as a primer.