Search results for: insertional-mutagenesis-strategies-in-cancer-genetics

Insertional Mutagenesis Strategies in Cancer Genetics

Author : Adam J. Dupuy
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The goal of this work is summarize the contribution that insertional mutagenesis has made to our understanding of cancer. A variety of insertional mutagens are presented that have been used to study a variety of tumor types in several model organisms. In addition, the impact of insertional mutagenesis in several gene therapy trials is discussed along with strategies to avoid such complications in future clinical trials.

Insertional Mutagenesis Strategies in Cancer Genetics

Author : Adam J. Dupuy
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The goal of this work is summarize the contribution that insertional mutagenesis has made to our understanding of cancer. A variety of insertional mutagens are presented that have been used to study a variety of tumor types in several model organisms. In addition, the impact of insertional mutagenesis in several gene therapy trials is discussed along with strategies to avoid such complications in future clinical trials.

Identification of Tumor Suppressor Genes in Breast Cancer by Insertional Mutagenesis and Functional Inactivation

Author : YAN. SU
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The development and progression of cancer result from multiple genetic changes accumulated in the cells. The identification of tumor suppressor genes inactivated and proto-oncogenes activated in mammary epithelial cells is essential to understand the genetic basis of breast cancer and is a prerequisite for development of strategies for prevention, diagnosis, and treatment. In breast cancer, loss of heterozygosity (LOH) was detected frequently on chromosome 17 and other chromosomes, suggesting unrecognized tumor suppressor genes. We are applying the novel retroviral-tagging strategy to identify the genes using chromosome 17-suppressed (independent of p53 and BRCAl) breast cancer cell lines. In contrast to the parental tumorigenic cell line CAL51, the suppressed sublines CAL/17-3 and CAL/17-5 display retard growth in flasks, no growth in soft-agar culture and athymic nude mice. In this annual report, we present preparation of biological materials including cell culture, isolation of DNA and RNA, construction of cDNA library and packaging retrovirus particles. In order to provide antisense and mutant proteins to inhibit activities of tumor suppressor genes, poly-(A)+RNA was isolated from the suppressed subline CAL17-3 and used to construct the library. We are now in the process to package cDNA library into retrovirus particles for transduction.

Colon Polyps and Colorectal Cancer

Author : Omer Engin
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This thoroughly revised and extended second edition of the book clearly explains the nature of colon polyps and their relationship to colorectal cancer in light of new developments. It discusses in detail new topics, including polyp development, risk factors and prevention measures, and also describes surgical, medical oncology and radiotherapy treatments of colon cancer. In cases of advanced colon cancer, it clearly demonstrates how to perform surgical interventions in the presence of urinary tract metastases and gynecologic organ metastases. The book also includes chapters on medical treatment and radiotherapy in distant metastases of colorectal cancer. Further, it presents resection of liver metastases and transplantation options. Carefully examining the risk factors, and the treatment of colon cancer from the early to the advanced stages, the book is invaluable not only for medical specialists and students, but also for general readers and patients.

Colon Polyps and the Prevention of Colorectal Cancer

Author : Omer Engin
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​This book explains clearly the nature of colon polyps and their relationship with colorectal cancer, which is among the three most common cancers in both men and women. Up-to-date information is provided on anatomy, pathology, types of polyp and their treatment, and the performance of colonoscopy. Particular attention is devoted to the risk factors for development of colorectal cancer, with detailed guidance on its prevention and early diagnosis and treatment. While the book is primarily intended for medical specialists and students, a deliberate and consistent effort has been made to use plain language that will enable other interested persons, including patients, to understand all aspects of the subject.

Pattern Recognition in Bioinformatics

Author : Alioune Ngom
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This book constitutes the refereed proceedings of the 8th IAPR International Conference on Pattern Recognition in Bioinformatics, PRIB 2013, held in Nice, France, in June 2013. The 25 revised full papers presented were carefully reviewed and selected from 43 submissions. The papers are organized in topical sections on bio-molecular networks and pathway analysis; learning, classification, and clustering; data mining and knowledge discovery; protein: structure, function, and interaction; motifs, sites, and sequence analysis.

The Mouse in Biomedical Research

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Diseases, the second volume in the four volume set, The Mouse in Biomedical Research, departs from the first edition, by discussing specific disease causing microorganisms, rather than the format used in the first edition which discussed infectious diseases affecting specific organs and tissues. As such, the volume consists of 26 chapters subdivided into RNA viruses and DNA viruses, as well as bacterial, mycotic, and parasitic infections. These chapters not only provide updates on pathogenesis, epidemiology and prevention of previously recognized murine pathogens, but also include information on newly recognized disease-causing organisms: mouse parvovirus, cilia associated respiratory bacilli and Helicobacter spp. A separate category, consisting of 3 chapters, discusses zoonoses, tumor pathology of genetically engineered mice, and spontaneous diseases in commonly used mouse strains.

Genetically Engineered Mice for Cancer Research

Author : Jeffrey E. Green
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Genetically-engineered mouse models for cancer research have become invaluable tools for studying cancer biology and evaluating novel therapeutic approaches. This volume focuses on state-of-the-art methods for generating, analyzing and validating such models for studying aspects of human cancer biology. Additionally, these models are emerging as important pre-clinical systems in which to test cancer prevention and therapeutic strategies in order to select compounds for testing in clinical trials.

Safety and Efficacy of Gene Based Therapeutics for Inherited Disorders

Author : Nicola Brunetti-Pierri
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In this book, leading international experts analyze state-of-the-art advances in gene transfer vectors for applications in inherited disorders and also examine the toxicity profiles of these methods. The authors discuss the strengths and weaknesses of available vectors in the clinical setting, and specifically focus on the challenges and possible solutions that researchers are testing in order to improve the safety of gene therapy for genetic diseases. This comprehensive and authoritative overview of vector development is a necessary text for researchers, toxicologists, pharmacologists, molecular biologists, physicians, and students in these fields.

Validation based Insertional Mutagenesis VBIM Technology Identifies Adenomatous Polypossis Coli APC Like Protein ALP as a Novel Negative Regulator of NF kB

Author : Rasika S. Mundade
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Colorectal cancer (CRC) is the third leading cause of cancer related deaths in the United States. The nuclear factor kB (NF-kB) is an important family of transcription factors whose aberrant activation has been found in many types of cancer, including CRC. Therefore, understanding the regulation of NF-kB is of ultimate importance for cancer therapy. Using a novel validation-based insertional mutagenesis (VBIM) strategy, our lab has identified the novel adenomatous polyposis coli (APC) like protein (ALP) gene as a negative regulator of NF-kB. Preliminary studies from our lab demonstrated that overexpression of ALP led to decreased NF-kB activity by kB reporter assay and electrophoresis mobility gel shift assay (EMSA). The current project aims to further evaluate the role of ALP in the regulation of NF-kB signaling in CRC cells. We found that overexpression of ALP in human CRC HT29 cells greatly reduced both the number and the size of colonies that were formed in a soft agar assay. ALP overexpression also decreased the cell growth rate and cell migration ability, while shRNA mediated knockdown of ALP showed opposite effects, confirming that ALP is a tumor suppressor in CRC HT29 cells. Overexpression of ALP led to decreased NF-kB activity by kB reporter assay and condition media assay in CRC HT29 cells. Furthermore, immunohistochemical analysis with human colon vii tissues revealed that there is a gradual loss of ALP protein with tumor progression. We also found that ALP predominantly localizes in the cytoplasm, and binds to the p65 subunit of NF-kB, and might be functioning downstream of IkB kinase (IKK). In summary, in this study, we provide evidence regarding the tumor suppressor role of ALP in CRC by functioning as novel negative regulator of NF-kB. This discovery could lead to the establishment of ALP as a potential biomarker and therapeutic target in CRC.