Download or read book Identification of CDH11 as a Candidate Tumor Suppressor in Retinoblastoma and Characterization of Its Role in Retina and Retinoblastoma written by Mellone Noelene Marchong and published by . This book was released on 2007 with total page 244 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since Kundson's two hit hypothesis of the retinoblastoma tumor susceptibility gene in 1971 and the subsequent cloning of RB1 in 1986 and 1987, pRB has been the highlight of cancer research. It represents the prototypical model for inherited cancers and has since lead to better understanding of cancer genetics. The disease is unique in that its initiating mutational events are known, loss of both alleles of RB1, mutational events 1 and 2 (M1 and M2). Investigation of mutational events, M3-Mn, that lead to its progression will be useful for better understanding of retinoblastoma tumorigenesis, which can ultimately translate to the development of new and better therapeutics that can be used to halt retinoblastoma progression at a very early stage. Loss of chromosomal region 16q22 is a significant genomic change recognized not only in retinoblastoma but in numerous other cancers. Using loss of heterozygosity (LOB) and quantitative multiplex PCR (QM-PCR) techniques on a total of 76 retinoblastoma tumors we were able to narrow down the genomic region of loss on chromosome 16q22. We identified a gene, CDH11, to be a candidate tumor suppressor in retinoblastoma, as it was found to display copy number loss in 58% of 71 tumors and protein expression loss in tumors of both human and murine retinoblastoma. To study the role of cadherin-11 in retinogenesis, I compared developing retinae of Cdh11+/+, Cdh11+/- and Cdh11-/- mouse littermates, and report that Cdh11 plays a subtle role during murine retinogenesis, whereby it supports the development of the retinoblastoma susceptibility cells in the transgenic SV40 large T-antigen mouse model of retinoblastoma (TAg-RB). I also report that retinoblastoma tumors in mice with mutant alleles of Cdh11 grow faster than tumors in mice with normal Cdh11 alleles. These results herein, concur with characteristics identifying tumor suppressor genes. Thus, I provide compelling evidence to support a tumor suppressor role for Cdh11 in retinoblastoma progression.
Download or read book Cdh11 Acts as a Tumor Suppressor in a Murine Retinoblastoma Model by Facilitating Tumor Cell Death written by Christine Yurkowski and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Dissertation Abstracts International written by and published by . This book was released on 2008 with total page 800 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Identification of DEK and E2F3 as Candidate 6p22 Oncogenes in Retinoblastoma written by Marija Orlic-Milacic and published by . This book was released on 2007 with total page 308 pages. Available in PDF, EPUB and Kindle. Book excerpt: The study of retinoblastoma, the malignant tumor of the retina, has set the fundamentals of cancer genetics and the genetics of familial cancer syndromes through discovery of the first tumor suppressor gene RB1. Retinoblastoma is an excellent disease model of the multistep nature of cancer. The initiation events, leading to the loss of function of both alleles of the RBI gene, hence named mutations 1 and 2 (Ml and M2) are well characterized, as well as the number of recurrent chromosomal aberrations that are positively selected for during tumor progression. Recurrent regions of chromosomal gain and loss are hypothesized to carry oncogenes and tumor suppressor genes, respectively, which are targeted by mutational events M3-Mn. One of the most frequently gained chromosomal regions is the short arm of chromosome 6, 6p, with the minimal region of gain mapping to the chromosomal band 6p22. In this thesis, through comparative expression analysis of retinoblastoma and healthy retina, the number of candidate 6p22 oncogenes is narrowed to two genes, DEK and E2F3. The functional analysis of the oncogenic potential of DEK and E2F3 in retinoblastoma cell lines through RNA interference shows that both genes display oncogenic properties, since the knockdown of any of the two adversely affects the growth of retinoblastoma when 6p22 genomic gain is present. In addition, it is shown that, besides increase in the genomic copy number of 6p22, some retinoblastoma cell lines exhibit translocations between chromosomal arms 6p and 6q, with a recurrent translocation breakpoint at 6p22, in the vicinity of DEK and E2F3 loci, emphasizing the involvement of chromosomal band 6p22 in the etiology of retinoblastoma. Based on the work presented. DEK and E2F3 are the promising new targets for treatment and prevention of retinoblastoma.
Download or read book Cdh11 Acts as a Tumor Suppressor in a Murine Retinoblastoma Model by Facilitating Tumor Cell Death written by Christine Laura Yurkowski and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Hereditary Tumors written by Heike Allgayer and published by John Wiley & Sons. This book was released on 2009-05-13 with total page 559 pages. Available in PDF, EPUB and Kindle. Book excerpt: Summarizing molecular aspects, diagnostic as well as therapeutic issues, this book is the very first and most comprehensive on hereditary aspects of tumor diseases. All the contributors have been made fellows of the Ingrid zu Solms Foundation due to their outstanding achievements in scientific research, and they discuss here the latest aspects in the diagnosis, disease management, and treatment of hereditary tumor diseases and syndromes. A must-have ready reference for medical and biology students, MDs, PhDs, physicians, and researchers.
Download or read book Retinoblastoma written by Carlos Rodriguez Galindo and published by Springer Science & Business Media. This book was released on 2010-03-10 with total page 162 pages. Available in PDF, EPUB and Kindle. Book excerpt: Although rare, retinoblastoma has been at the fore- fortunate; while in the developed world eye preser- front of cancer research and treatment for the last tion has become a priority, developing countries c- three decades. The two-hit hypothesis of oncogenesis tinue to face delays in diagnosis, poor access to care, proposed by Alfred Knudson provided the conceptual and suboptimal treatment – the problem in the less framework for tumor suppressor gene research and developed world is cure. led to the discovery of the retinoblastoma pathway as In this book, we have invited a team of experts to a key element in cancer development. More recently, address all those important aspects of retinoblastoma the treatment of children with retinoblastoma has also research and therapy - from biology to epidemiology provided a model for modern approach to the can- to treatment. We hope that in subsequent editions we cer patient; state of the art retinoblastoma treatment will be able to continue to provide updates on such can only be conceived in the context of the multidis- exciting subjects.
Download or read book The Molecular Progression from Retina Through Retinoma to Retinoblastoma and the Role of the P75 subscript N subscript T subscript R Neurotrophin Receptor written by Helen Dimaras and published by . This book was released on 2007 with total page 316 pages. Available in PDF, EPUB and Kindle. Book excerpt: Retinoblastoma, a childhood cancer of the retina, is initiated by the loss of RB1; genomic gains of oncogenes (KIF14, DEK, E2F3, MYCN) and loss of tumor suppressor genes (CDH11) are essential for malignant progression. These genes are not involved in apoptosis, the disruption of which is thought to be a hallmark of tumorigenesis. A gene that may play such a role is p75NTR, which functions in retinal apoptosis. Retinoma, a benign retinal tumor, is also associated with mutation of RB1, however it is unknown if its development requires additional somatic inactivation of the second RB1 allele or additional disruption of the downstream retinoblastoma-associated candidate genes. In this thesis, I looked at a potential role for p75NTR in retinoblastoma and retinoma development, and analyzed the status of RB1 in retinoma. Retinoma results after complete RB1 loss, but prior to p75NTR loss, evident only in retinoblastoma. Unlike retina or retinoblastoma, retinoma expresses senescence marker p16 INK4a. Expression of candidate retinoblastoma oncogenes and tumor suppressor genes is not similarly altered in retinoma. Early, but not advanced, tumors from the TAg-RB murine retinoblastoma model expressed p75NTR, which was also correlated with expression of apoptosis marker activated caspase-3. A retinoblastoma model that lacked p75NTR at the onset of TAg-RB development displayed lager tumor area at equivalent stages as the TAg-RB mouse, presumably due to a decrease in apoptosis during the early stages of tumor development. In conclusion, retinoma is a senescent RB1-/- precursor to retinoblastoma, only progressing to full retinoblastoma after the disruption p75NTR and senescence, leading to the subsequent specific changes highlighted in this study.
Download or read book Comprehensive Molecular and Clinical Characterization of Retinoblastoma written by Meriem Sefta and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Retinoblastoma is a rare pediatric cancer of the developing retina. In high-income countries, survival rates near 100%; however, enucleation of the affected eye has to be performed in over 70% of patients. Knudson's 1971 two-hit hypothesis led to the discovery that this cancer usually initiates after a bi-allelic loss of the RB1 gene. Despite this early finding, little is known about the other molecular underpinnings of retinoblastoma. For instance, few genome-wide studies have described the genetic and epigenetic characteristics of these tumors. Furthermore, there is still no clear consensus regarding this cancer's cell of origin, or whether or not it is homogenous disease. In this study, we built a comprehensive molecular and clinical portrait of retinoblastoma. Several lines of evidence led us to conclude that retinoblastoma is in fact a heterogeneous disease, with two distinct subtypes. We first uncovered the subtypes through a strategy that coupled an independent component analysis (ICA) of tumor transcriptomes to tumor immunohistochemical stainings. Retinoblastomas of the first subtype, called “cone-like”, homogeneously display cone-like differentiation, while those of the second subtype, called “bivalent-type”, exhibit strong intratumoral heterogeneity, with areas of cone-like differentiation intertwined with areas of ganglion-like differentiation. Further analysis of the transcriptomic data, as well as of copy number alteration data revealed that both subtypes may rely on different pathways and oncogenes. We notably observed a quasi-systematic presence of MDM4 gains or MYCN amplifications in bivalent-type tumors. We next turned to retinoblastomas' methylomes; these considerably varied between the subtypes. ICA allowed us to decompose this inter-subtype methylomic heterogeneity, which was found to go beyond methylation due to cone-like or ganglion-like differentiation. We next studied the tumors' clinical data, and found that cone-like tumors are most often diagnosed in very young patients with exophytic tumor growth, while bivalent-type tumors are found in older patients with endophytic tumor growth. Furthermore, patients with germline inactivations of RB1 mostly developed cone-like retinoblastomas, indicating that these tumors may initiate earlier during retinal development. In the final part of our study, we performed whole exome sequencing of 74 tumor-normal pairs. Like many pediatric cancers, the tumors had very low background mutation rates (0.1 mutations per megabase). Recurrent somatic mutations were found in RB1, BCOR and ARID1A, and these genes were also found to be in minimal regions of chromosomal losses. Importantly, both inactivations often had very high allelic frequencies, indicating that these events occur very early on in retinoblastoma tumorigenesis.Taken together, our study outlines a first comprehensive genomic portrait of retinoblastomas, points to the existence of two distinct subtypes, and provides insights into the cells-or-origin and the molecular mechanisms underlying these subtypes.
Download or read book The Role of the Retinoblastoma Protein in Retinal Development written by Irina D. Burcescu and published by . This book was released on 2001 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Although 'RB1' was the first tumor suppressor gene identified, its role during retinal development is poorly understood. We first attempted to determine this by performing 'in vivo' misexpression studies in the post-natal rat retina. Retroviral lineage analysis revealed that clone size in pRB-infected eyes was significantly reduced when compared to control eyes. This suggested that pRB has a role in regulating progenitor cell cycle in the developing retina. The results from 'in vivo' misexpression studies also suggested a possible pRB involvement in cell fate determination and/or re-specification, but more experiments must be performed before concluding this. 'In vitro' rescue experiments with the RB-/- retina is the second experimental approach that may help us clarify the role of pRB in retinal development. To this end, we established a retinal culturing protocol wherein development 'in vitro' mimics that ' in vivo', thus laying the groundwork for future rescue experiments in the RB-/- retina. This study presents significant findings that may help us elucidate the role pRB plays during retinal development.
Download or read book Tumors of the Central Nervous System Volume 8 written by M.A. Hayat and published by Springer Science & Business Media. This book was released on 2012-06-14 with total page 363 pages. Available in PDF, EPUB and Kindle. Book excerpt: With tens of thousands of new CNS tumor cases each year in the US alone, this series of publications is a valuable aid to the diagnosis and treatment of these problematic neoplasms. Now, the eighth in the set returns to the topic of brain tumors, dealing with seven distinct types: astrocytoma, medulloblastoma, retinoblastoma, chordoma, craniopharyngioma, oligodendroglioma, and ependymoma. After updating the classification of medulloblastoma the volume provides an overview of ependymoma as well as describing the delineation of prognosis based on the genetic aberrations of the latter patients. The material offers key insights into the molecular pathways involved in tumor biology, such as the role of E-cadherin gene instability, carbonic anhydrase II, urokinase plasminogen activator, and Wnt signaling in meningioma. Contributors explain the genetic and clinical features associated with recurring meningioma, including the role played by erythropoietin receptor, and examine the way in which OTX2 transcription factor functions as an oncogene in medulloblastoma. With much more besides, including discussion of the molecular mechanisms that result in resistance to chemotherapy in medulloblastoma, this volume and its companions have a positive role to play in inspiring a new generation of researchers to design new drugs that are better targeted—and thus more effective.
Download or read book Cancer Research written by and published by . This book was released on 2007 with total page 900 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Advances in Vision Research Volume II written by Gyan Prakash and published by Springer. This book was released on 2018-11-03 with total page 464 pages. Available in PDF, EPUB and Kindle. Book excerpt: This second volume continues with a focus on the state of the art in genetic eye research in Asia and the Pacific. Though there has been an explosion of information on genetic eye research in western countries, more than sixty percent of the human genes involved in eye diseases in the Asian and Pacific population remain unknown. However, new efforts and a new awareness have sparked important discussions on the subject, and new plans are being implemented to discover the genes responsible for many eye diseases in the population. The book reviews the latest findings; its content ranges from genetic aspects of human migration to DNA sequence analysis, genome-wide association analysis, and disease phenotypes. The efforts of the Asian Eye Genetic Consortium (AEGC) are also discussed. The book’s editors have been instrumental in developing strategies for discovering the new Asian genes involved in many eye diseases. All chapters were written by leading researchers working on Asian eye genetics from the fields of Human Genetics, Ophthalmology, Molecular Biology, Biochemistry, Sensory Sciences, and Clinical Research. Advances in Vision Research, Volume II will prove to be a major resource for all researchers, clinicians, clinical researchers, and allied eye health professionals with an interest in eye diseases among the Asian population.
Download or read book Tumor Suppressor Genes in Human Cancer written by David E. Fisher and published by Springer Science & Business Media. This book was released on 2000-10-26 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt: David Fisher, MD, PhD, and an authoritative panel of academic, cutting-edge researchers review and summarize the current state of the field. Describing the broad roles of tumor suppressors from a perspective based in molecular biology and genetics, the authors detail the major suppressors and the pathways they regulate, including cell cycle progression, stress responses, apoptosis, and responses to DNA damage. Leading-edge and forward-looking, Tumor Suppressor Genes in Human Cancer illuminates what is currently known of tumor suppressor genes and their regulation, work that is already beginning to revolutionize cancer target elucidation, drug discovery, and treatment design.
Download or read book Textbook of Radiation Oncology written by Steven A. Leibel and published by . This book was released on 2004 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Thoroughly revised and updated, the 2nd Edition presents all of the latest advances in the field, including the most recent technologies and techniques. For each tumor site discussed, readers will find unparalleled coverage of multiple treatment plans, histology and biology of the tumor, its anatomic location and routes of spread, and utilization of specialized techniques. This convenient source also reviews all of the basic principles that underlie the selection and application of radiation as a treatment modality, including radiobiology, radiation physics, immobilization and simulation, high dose rate, intraoperative irradation, and more. Comprehensively reviews each topic, with a distinct clinical orientation throughout. Serves as a foundation for the basic principles that underlie the selection and application of radiation as a treatment modality, including radiobiology, radiation physics, immobilization and simulation, high dose rate, intraoperative irradation, and more. Guides readers through all stages of treatment application with step-by-step techniques for the assessment and implementation of radiotherapeutic options. Presents latest information on brachytherapy * 3-dimensional conformal treatment planning * sterotactic radiosurgery * and radiolabeled antibodies. Discusses the recent use of radiotherapy in the treatment of primary lymphoma, leukemia, multiple myeloma, and cancers of the prostate and central nervous system. Includes the latest AJCC staging system guidelines. Offers the latest advances in techniques, allowing you to deliver doses precisely to areas affected by malignancy and spare healthy tissue. Presents new chapters on the hottest topics including Three Dimensional Conformal Radiotherapy * Intensity Modulated Radiotherapy * Breathing Synchronized Radiotherapy * Plasma Cell Tumors: Multiple Myeloma and Solitary Plasmacytoma * Extracranial Stereotactic Radioablation * and [Imaging of the] Head and Neck * Thorax * Abdomen * and Pelvis.
Download or read book Clinical Ophthalmic Oncology written by Jesse L. Berry and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by internationally renowned experts, the 3rd edition of this six volume textbook provides detailed practical guidance and advice on the diagnosis and management of the complete range of ocular cancers. Supplying the reader with state-of-the-art knowledge required in order to identify these cancers early and to treat them as effectively as possible, this book is divided into six volumes: Basic Principles, Eyelid and Conjunctival Tumors, Orbital Tumors, Uveal Tumors, Retinal Tumors, and Retinoblastoma. The information presented enables readers to provide effective patient care using the latest knowledge on ophthalmic oncology and to verify diagnostic conclusions based on comparison with numerous full-color clinical photographs from the authors' private collections, histopathologic microphotographs, imaging studies, and crisp illustrations.
Download or read book Ryan s Retina E Book written by Charles P. Wilkinson and published by Elsevier Health Sciences. This book was released on 2017-04-17 with total page 2893 pages. Available in PDF, EPUB and Kindle. Book excerpt: The undisputed gold standard text in the field, Ryan's Retina is your award-winning choice for the most current, authoritative information on new technologies, surgical approaches, scientific advances and diagnostic and therapeutic options for retinal diseases and disorders. Packed with timely updates throughout, new illustrations, and a dedicated team of editors who extend Dr. Ryan’s legacy in retina, this outstanding 6th Edition is a must-have reference for retinal specialists, ophthalmologists, and fellows in training. Offers the most comprehensive content available on retina, balancing the latest scientific research and clinical correlations, covering everything you need to know on retinal diagnosis, treatment, development, structure, function, and pathophysiology. Provides a truly global perspective from five highly esteemed section editors and more than 350 other world authorities from across Europe, Asia, Australasia, and the Americas. Bullets Includes new chapters on widefield imaging, intraoperative OCT imaging, medical management of diabetes mellitus and age-related macular degeneration, and senile retinoschisis. Includes more than 1,150 brand-new illustrations, scans, and photographs throughout. Covers the explosion of new imaging options across optical coherence tomography (OCT), fundus imaging, and autofluorescence imaging, including a greatly expanded OCT imaging chapter that features crucial information on OCT-Angiography (OCT-A). Presents new pharmacotherapy data and the latest approaches in anti-VEGF therapy for age-related macular degeneration, diabetic retinopathy, and venous occlusive disease. Features an expanded online video library highlighting the latest surgical techniques and new coverage of complications of vitreoretinal surgery. Contains thorough content updates in every area of retina, including advanced imaging technologies, gene therapy, inflammation and immune responses, white dot syndromes, epigenetic mechanisms, transplantation frontiers to improve retinal function, macular hole, myopic eye disease, ocular trauma, drug delivery to the posterior segment, advances in macular surgery, vitrectomy and complex retinal detachment, tumors, and retinal genetics and biology. Expert ConsultTM eBook version included with purchase. This enhanced eBook experience allows you to search all of the text, figures, Q&As, and references from the book on a variety of devices.
