Download or read book A GNAQ 11 driven Zebrafish Cancer Model Identifies MITF and YAP as Key Determinants for Uveal Melanoma written by Hannah R. Hagen and published by . This book was released on 2019 with total page 183 pages. Available in PDF, EPUB and Kindle. Book excerpt: Uveal melanoma (UM) is a cancer of eye melanocytes that has a particularly poor prognosis and a dearth of treatment options. In contrast to cutaneous melanoma (CM), which is driven by oncogenic mutation of BRAF or NRAS, UM is driven by oncogenic mutations in GNAQ or GNA11 (>80% of patients). We developed a zebrafish model of UM by expressing GNAQ[superscript Q209L] in the melanocytes of p53-/- zebrafish. In this model, oncogenic GNAQ activates biological programs involved in pigmentation and tumorigenesis. The melanocyte lineage transcription factor MITF plays a well-defined role in CM tumorigenesis, wherein MITF expression is absolutely necessary for tumorigenesis and regulates proliferative versus invasive tumor phenotypes. In contrast, here we elucidated a novel tumor suppressor function for MITF in UM. In the context of oncogenic GNAQ, loss of mitfa accelerates tumorigenesis and reduces tumor reliance on p53 mutation. Expression of oncogenic GNAQ can also overcome mitfa-/- tumor inhibition in BRAF-driven CM. Moreover, mitfa's tumor suppressive role is generalizable to UM and mitfa-/- accelerates tumorigenesis driven by oncogenic GNA11 or CYSLTR2, a GNAQ/11 upstream receptor. Interestingly, we show that GNAQ directly regulates pigment programs, as evidenced by hyperpigmentation patches that develop even in the absence of mitfa. Furthermore, the pigmentation and tumorigenesis phenotypes are decoupled, suggesting differential regulation of these programs downstream of oncogenic GNAQ. The observation that mitfa has different roles in CM vs UM led us to investigate the different signaling mechanisms of BRAF- vs GNAQ-driven melanoma. Oncogenic GNAQ activates the downstream pathways YAP and PLC[beta], and there is conflicting evidence implicating the relative importance of these two signaling axes in driving UM tumorigenesis. Here, we outline a central role for YAP for in in vivo UM tumorigenesis. Constitutively active YAP[superscript S127A;S381A] drives rapid UM tumorigenesis, furthermore, YAP staining was ubiquitous across UM tumors. Finally, we show here for the first time that PLCB4D630Y was sufficient to drive tumors at long latency. Together, these findings clarify the genetic pathways that drive UM formation.

Download or read book Establishment of MITF and TAZ as Major Determinants of Uveal Melanoma written by Grace B. Phelps and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Uveal melanoma (UM) is a cancer that arises from transformed melanocytes that exist in the uvea of the eye. Although UM is relatively rare, it is extremely deadly, due to the lack of treatment options for the metastatic disease. In contrast, cutaneous melanoma (CM), which is derived from transformed skin melanocytes, has multiple approved therapies, which have not worked in UM patients. Thus, there is great need to gain a deeper understanding of UM, and how it differs from CM, to inform effective therapeutic strategies. The vast majority of UM patients present with activating mutations in the GNAQ/11 pathway, which signals through PLC[beta]4-MAPK and YAP, whereas CM is primarily driven by activation of the MAPK pathway. It has been well established that CM tumors are dependent on MITF, the master melanocyte transcription factor. Here, in stark contrast, we establish that MITF serves as a tumor suppressor in an oncogenic GNAQ/11 UM zebrafish model. Moreover, we show that resulting MITF-deficient tumors are more de-differentiated and down-regulate PLC[beta]4-MAPK signaling, but retain active YAP. Furthermore, we establish that YAP, and not PLC[beta]4, is sufficient to drive MITF-wildtype tumorigenesis. Thus, our data de-emphasize the role of the PLC[beta]4-MAPK pathway in UM. We further show that YAP is surprisingly wholly dispensable for oncogenic GNAQ tumorigenesis in an autochthonous zebrafish model, but resulting tumors display active TAZ, a YAP paralog. Moreover, we establish that TAZ is an extremely potent oncogene in UM using autochthonous zebrafish models, even moreso than YAP. Furthermore, we show that higher TAZ expression, but not YAP expression, significantly correlates with decreased UM patient survival. Thus, this suggests that the role of TAZ does not entirely mirror that of YAP in UM. Lastly, we provide molecular characterization of the MITF-deficient s tate, and develop a system in which to screen UM therapies in vivo. Overall, our work establishes a tumor suppressor role for MITF, de-emphasizes the role of the MAPK pathway, and further underscores the importance of YAP/TAZ signaling in UM.

Download or read book Oncogenic Mutation of GNAQ 11 Disrupts Melanocyte Biology in a Zebrafish Model of Uveal Melanoma written by Dahlia E. Pérez and published by . This book was released on 2016 with total page 158 pages. Available in PDF, EPUB and Kindle. Book excerpt: Uveal melanoma (UM) is the most common primary intraocular cancer in humans. These tumors arise from nonclassical melanocytes found in the choroid, iris, and ciliary body (collectively called the uvea). Over 80% of UM tumors contain activating mutations in one of two genes encoding the homologous G[alpha] proteins GNAQ or GNA 11, which are the [alpha subunit of a heterotrimeric G protein receptor. Here we report that we have successfully used Tol-mediated transgenesis to develop a zebrafish model of UM driven by melanocyte specific expression of human oncogenic GNAQ/11Q 209L alleles. In cooperation with tp53M214K/M214K mutation, these GNAQ/11Q 209L transgenic zebrafish develop both uveal and cutaneous melanomas with nearly complete penetrance, causing early lethality. Furthermore, immunohistochemical analysis (IHC) reveals that these melanomas do indeed recapitulate the human disease in that they drive expression of oncogenic GNAQ and show increased expression of YAP. Interestingly, the transgenic zebrafish display an array of internal and external pigmentation defects compared to nontransgenic clutchmate controls. These pigment defects are independent of tp53 mutation. Zebrafish stripe patterning has been previously exploited to elucidate mechanisms in melanocyte signaling; therefore, to learn about the consequences of oncogenic GNAQ/1 1 signaling in melanocytes we pursued in vivo and in vitro study of transgenic melanocytes. The in vivo pigment phenotypes in these mutants include hyperpigmentation, mislocalized melanocyte and aberrant melanocyte morphology, and are detectable through all developmental phases beginning as early as 3 days post fertilization. In vitro, upon transgene expression the mutant melanocytes exhibit increased dendricity, motility, and survival. To understand the mechanisms underlying these phenotypes, we performed RNAseq on transgenic and nontransgenic melanocyte populations. Transcriptome analysis revealed a list of 353 differentially expressed genes. Functional analysis of this gene set implied changes in categories related to axon guiding, cell adhesion and cell cycle regulation. Taken together, our results reveal that persistent alterations in melanocyte biology occur as a result of oncogenic GNAQ/11 expression in a novel zebrafish model of UM. These observations provide the ground work for elucidating the mechanisms by which the oncogenic GNAQ/11 mutations are tumorigenic and for potentially generating therapies for this poorly understood disease.

Download or read book Experimental Metastasis Modeling and Analysis written by Anastasia Malek and published by Springer Science & Business Media. This book was released on 2013-12-02 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metastatic dissemination of cancer is a main cause of cancer related deaths, therefore biological mechanisms implicated in metastatic process presents an essential object of cancer research. This research requires creation and utilization of adequate laboratory models. The book describes main approaches to model processes of metastatic cancer dissemination and metastases development. The book is structured in according with various metastatic pathways reflecting molecular specificity of metastatic process as well as anatomical specificity of aria of dissemination. Each chapter is introduced by short discussion of clinical aspects of certain metastatic pathway. Especial attention is paid for methods of visualization, quantification and analysis of the modeled metastases. Additional chapter is devoted to methods of mathematic modeling of tumor spread. The data presented in the book may be helpful for cancer researchers and oncologists.

Download or read book Transpupillary Thermotherapy written by J. G. Journée-de Korver and published by Kugler Publications. This book was released on 1998 with total page 122 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Lee s Ophthalmic Histopathology written by Fiona Roberts and published by Springer Science & Business Media. This book was released on 2013-11-12 with total page 486 pages. Available in PDF, EPUB and Kindle. Book excerpt: Completely revised and updated third edition of Lee’s Ophthalmic Histopathology, this well-illustrated and practically-oriented text has retained its general layout and style and division into specimen-based chapters. The visual image remains key to explaining the pathological processes - facilitated by full colour photography throughout the text. The text and illustrations are also provided as a searchable CD-ROM. The book emphasizes pertinent recent advances, particularly in the molecular basis of disease and in the diagnosis and classification of tumours. including improvements in immunohistochemistry and cytogenetic and molecular biological studies. This book is an invaluable source of reference for ophthalmic pathologists, general pathologists and ophthalmologists.

Download or read book Ophthalmic Oncology written by Bita Esmaeli and published by Springer Science & Business Media. This book was released on 2011-01-06 with total page 483 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book highlights the unique aspects of oncologic ophthalmology as a medical and surgical discipline practiced at a comprehensive cancer center. Multi-disciplinary management of ocular, orbital and adnexal cancers are highlighted using simple and tried-and-true algorithms. In addition, ocular problems caused as a direct result of cancer treatment are reviewed using illustrative photographs and case presentations. The content is provided by full-time ophthalmology faculty and fellows at M. D. Anderson Cancer Center. Experts in complementary disciplines such as ophthalmic pathology, dermatopathology, radiation oncology, radiology, and other surgical subspecialties have brought their unique perspective to each chapter. The book is abundant with clinical photographs as well as interesting case presentations that will help the clinician correctly diagnose cancers of the orbit, eye, and adnexal structures, initiate appropriate management, as well as recognize and treat common ocular complications of cancer therapy.

Download or read book Catalog of Cell Lines written by and published by . This book was released on 1982 with total page 956 pages. Available in PDF, EPUB and Kindle. Book excerpt: Classified listing of cells currently available. Each entry gives repository number, necessary identifying information, and brief remarks. Catalog also includes detailed ordering information and prices. Miscellaneous appendixes. Repository, diagnosis indexes.

Download or read book Clinical Ophthalmic Oncology written by Arun D. Singh and published by Springer Science & Business Media. This book was released on 2013-11-26 with total page 239 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by internationally renowned experts, Clinical Ophthalmic Oncology provides practical guidance and advice on the diagnosis and management of the complete range of ocular cancers. The book supplies all of the state-of-the-art knowledge required in order to identify these cancers early and to treat them as effectively as possible. Using the information provided, readers will be able to provide effective patient care using the latest knowledge on all aspects of ophthalmic oncology, to verify diagnostic conclusions based on comparison with numerous full-color clinical photographs, and to locate required information quickly owing to the clinically focused and user-friendly format. This volume provides essential information on cancer epidemiology, etiology, pathology, angiogenesis, immunology, genetics, and staging systems and explains the principles underlying different therapeutic approaches.​

Download or read book Ocular Tumours written by Bertil Damato and published by Butterworth-Heinemann. This book was released on 2000 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: Beautifully illustrated in colour with the information presented in a clear and succinct format * The systematic approach covers all aspects of the disease * Provides the trainee and practitioner with a clear and concise account of the management of the most common intraocular tumours

Download or read book Genetics of Melanoma written by Carlos A. Torres-Cabala and published by Springer. This book was released on 2016-05-11 with total page 291 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses the molecular, biological, pathological, and clinical aspects of melanoma, with special emphasis in the new concepts of melanoma genetics. A multidisciplinary group of experts in Genetics, Dermatology, Pathology, and Melanoma Medical Oncology contribute state-of-the-art knowledge in melanoma research and clinical management, not only exposing the current status of knowledge of the topics but also providing their personal experiences and ideas about the future and potential practical application of the genetic aspects of melanoma. During the last few years we have witnessed an impressive amount of discoveries in the field of melanoma genetics which have changed our approach in understanding the pathogenesis and treatment of this lethal disease. Genetics of Melanoma is a practical approach to melanoma genetic mechanisms and their application in the diagnosis and treatment of this malignancy. It is an essential source of updated information and a powerful tool for clinicians, pathologists, and basic scientists who wish to understand, apply, and investigate the multiple new aspects of melanoma genetics.

Download or read book Imaging for Oncology written by Royal College of Radiologists (Great Britain). Faculty of Clinical Oncology. Board and published by . This book was released on 2004 with total page 28 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Sunscreens and Tanning written by U.S. Food and Drug Administration and published by GPO FCIC. This book was released on 2009 with total page 2 pages. Available in PDF, EPUB and Kindle. Book excerpt: Spending time in the sun is fun but can also cause skin cancer, sunburn, wrinkling, and skin aging. Find out how to protect yourself as you enjoy the sun.

Download or read book Hyaluronan in Cancer Biology written by Robert Stern and published by Academic Press. This book was released on 2009-03-07 with total page 467 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hyaluronan biology is being recognized as an important regulator of cancer progression. Paradoxically, both hyaluronan (HA) and hyaluronidases, the enzymes that eliminate HA, have also been correlated with cancer progression. Hyaluronan, a long-chain polymer of the extracellular matrix, opens up tissue spaces through which cancer cells move and metastasize. It also confers motility upon cells through interactions of cell-surface HA with the cytoskeleton. Embryonic cells in the process of movement and proliferation use the same strategy. It is an example of how cancer cells have commandeered normal cellular processes for their own survival and spread. There are also parallels between cancer and wound healing, cancer occasionally being defined as a wound that does not heal. The growing body of literature regarding this topic has recently progressed from describing the association of hyaluronan and hyaluronidase expression associated with different cancers, to understanding the mechanisms that drive tumor cell activation, proliferation, drug resistance, etc. No one source, however, discusses hyaluronan synthesis and catabolism, as well as the factors that regulate the balance. This book will offer a comprehensive summary and cutting-edge insight into Hyaluronan biology, the role of the HA receptors, the hyaluronidase enzymes that degrade HA, as well as HA synthesis enzymes and their relationship to cancer. - Offers a comprehensive summary and cutting-edge insight into Hyaluronan biology, the role of the HA receptors, the hyaluronidase enzymes that degrade HA, as well as HA synthesis enzymes and their relationship to cancer - Chapters are written by the leading international authorities on this subject, from laboratories that focus on the investigation of hyaluronan in cancer initiation, progression, and dissemination - Focuses on understanding the mechanisms that drive tumor cell activation, proliferation, and drug resistance

Download or read book Ocular Anatomy Embryology and Teratology written by Frederick A. Jakobiec and published by HarperCollins Publishers. This book was released on 1982 with total page 1172 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Monoclonal Antibodies and Their Functional Fragments in Research Diagnosis and Therapy written by Menotti Ruvo and published by . This book was released on 2022-02-11 with total page 278 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Cell Death Inflammation and Oxidative Stress in Neurodegenerative Diseases written by Anne Vejux and published by Mdpi AG. This book was released on 2022-01-17 with total page 232 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurogenerative diseases encompass very different pathologies, which can be demyelinating or nondemyelinating, but which have common mechanisms such as cell death, oxidative stress and inflammation. A better understanding of these mechanisms allows the search for biomarkers and targets for new therapies. This special issue brings together different data on Alzheimer's disease, Parkinson's disease, and multiple sclerosis, detailing the mechanisms of cell death (necroptosis, ferroptosis), oxidative stress and inflammation but also the possibilities of neuroprotection via 5 research articles and 6 review articles. The different reviews allow us to take stock of cell death, oxidative stress and neuroinflammation in the context of neurodegenerative diseases but also in relation to other pathologies where these processes are involved.