Author: Cory Abate-Shen Publisher: ISBN: 9781621820031 Category : SCIENCE Languages : en Pages : 0
Book Description
"99% of mouse protein-coding genes have an equivalent homolog in the human genome, despite the striking differences in appearance between mouse and man. This remarkable genetic similarity, together with our ability to finely engineer the murine genome, has made the mouse the ideal animal in which to model and analyze human biology and disease. This
Author: Marten H. Hofker Publisher: Springer Science & Business Media ISBN: 1592593402 Category : Science Languages : en Pages : 382
Book Description
Marten Hofker and Jan van Deursen have assembled a multidisciplinary collection of readily reproducible methods for working with mice, and particularlyfor generating mouse models that will enable us to better understand gene function. Described in step-by-step detail by highly experienced investigators, these proven techniques include new methods for conditional, induced knockout, and transgenic mice, as well as for working with mice in such important research areas as immunology, cancer, and atherosclerosis. Such alternative strategies as random mutagenesis and viral gene transduction for studying gene function in the mouse are also presented.
Author: Jeffrey E. Green Publisher: Springer Science & Business Media ISBN: 0387698051 Category : Medical Languages : en Pages : 639
Book Description
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.
Author: Eric C. Holland Publisher: John Wiley & Sons ISBN: 047144460X Category : Science Languages : en Pages : 504
Book Description
Mice have become the species of choice for modeling the complex interactions between tumor cells and the host environment. Mouse genetics are easily manipulated, and a growing array of technology exists for this purpose. Mouse models allow investigators to better understand causal relationships between specific genetic alterations and tumors, utilize new imaging techniques, and test novel therapies. Recent developments along these lines show great promise for the development of new anti-cancer treatments. Mouse Models of Human Cancer provides researchers and students with a complete resource on the subject, systematically presenting the principles, methodologies, applications, and challenges associated with this exciting field. Offering a survey of the latest research and a description of future areas of interest, this text: Presents real experimental data Describes organ site-specific mouse models Clearly identifies suitable models for further drug testing Critically analyzes current methodologies and their limitations Features numerous recognizable expert contributors Lists key Web sites, reagents, and companies From mouse handling and genetic engineering to preclinical trials, Mouse Models of Human Cancer is a comprehensive guide to using these models and relating them to human disease. Its uniform presentation describes organ-specific models in clinical, imaging, and molecular terms, and lays out the relevant genetics, experimental approaches, histological comparisons with human disease, and conclusions. Combining stellar chapter authors, rich illustrations, and clear, up-to-date coverage, Mouse Models of Human Cancer is an invaluable resource for advanced students and cutting-edge researchers.
Author: Publisher: Academic Press ISBN: 0128225351 Category : Science Languages : en Pages : 258
Book Description
Carcinogen-Driven Mouse Models of Oncogenesis, Volume 163 contains a series of protocols written by world-leading experts in the field. Each manuscript provides a detailed methodological description to drive carcinogen-mediated oncogenesis in mice. Chapters in this new release include Chemical carcinogenesis in mice as a model of human cancer: Pros and cons, MPA/DMBA-driven mammary carcinomas, Dimethylbenz(a)anthracene-Induced Mammary Tumorigenesis in mice, Urethane-induced lung carcinogenesis, Methylcholanthrene-induced fibrosarcomas, BBN-driven bladder carcinomas, Oral squamous cell carcinomas driven by 4NQO, Analyzing skin tumor development in mice by the DMBA/TPA model, and much more. Other sections cover DSS/AOM-driven colorectal carcinomas, Diethylnitrosamine-induced liver tumorigenesis in mice, Two-stage 3-methylcholanthrene and butylated hydroxytoluene-induced lung carcinogenesis in mice, Lung carcinomas induced by NNK and LPS, Pristane-induced mammary carcinomas, The 4-NQO mouse model: an update on a well-established in vivo model of oral carcinogenesis, and more. Provides protocols provided by renowned experts in the field Presents detailed descriptions of protocols, hence allowing appropriate reproduction of the models Includes author notes for each protocol, covering useful tips and troubleshooting
Author: Muhan Chen Publisher: Open Dissertation Press ISBN: 9781361430156 Category : Languages : en Pages :
Book Description
This dissertation, "Application of Transgenic Mice Models in Functional Study of Two Putative Oncogenes: ALC-1 and EIF5A2" by Muhan, Chen, 陳牧唅, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: ABSTRACT Chen Muhan Abstract of thesis entitled APPLICATION OF TRANSGENIC MICE MODELS IN FUNCTIONAL STUDY OF TWO PUTATIVE ONCOGENES: ALC-1 AND EIF5A2 Submitted by Chen Muhan For the degree of Doctor of Philosophy at the University of Hong Kong In February, 2007 DNA sequence amplification and subsequent overexpression of oncogene within the amplicon has been shown to play an important role in the pathogenesis and progression of various solid tumors, probably because overexpression of the amplified target gene confers a selective advantage. Therefore, isolation and characterization of oncogenes from frequently amplified region is imperative to understand the molecular mechanism of tumorigenesis. Amplification of the long arm of chromosome 1 with a minimal amplified region at 1q21 is the most frequently detected alteration in 58-78% hepatocellular carcinoma (HCC). Similarly, amplification of 3q26 has been frequently detected in several cancers including ovarian cancer. These suggest that these regions may harbor candidate oncogenes associated with tumorigenesis. Recently, two novel candidate oncogenes, ALC-1 (amplification in liver cancer-1) and eIF5A2 (eukaryotic translation initiation factor 5A2), have been isolated from 1q21 and 3q26 in our laboratory, respectively. Previous in vitro studies have demonstrated the oncogenic roles of ALC-1 and eIF5A2 played in cancer development. However, the in vivo functions of these genes in development and tumor pathogenesis are still unclear. In ii ABSTRACT Chen Muhan this study, transgenic mice models of ALC-1 and eIF5A2 are generated and their in vivo functions are characterized. Four independent ALC-1 transgenic founders were obtained and two of them were used for in vivo functional studies. The results strongly supported that ALC-1 plays an important role in tumor pathogenesis including: 1) to cause spontaneous tumor formation in transgenic mice; and 2) to dramatically shorten the latency of tumor formation by alcohol intoxication. The possible molecular mechanism is that overexpression of ALC-1 can up-regulate cyclin D1, D3/CDK6 expression and down-regulate p27 expression, which promotes G1/S transition. This was further supported by the results of FACS analysis, which showed that overexpression of ALC-1 tend to keep MEFs in cell cycling. In addition, DNA synthesis was accelerated in hepatocytes of transgenic mice comparing to their wild-type siblings during liver regeneration after partial hepatectomy. However, ALC-1 overexpression had minor effects on mouse development. In the second part of the thesis, three independent eIF5A2 transgenic founders were obtained and two of them were further studied. EIF5A2 overexpression led to pre- mature aging phenotypes in transgenic mice, with the typical syndromes of shortened longevity, kyphosis, reduced body weight and size and delay of wound healing etc. Two interesting findings revealed the mechanism of eIF5A2 implicated in aging-inducing process. The first one is the increase of chromosomal instability in transgenic mice characterized with numerical chromosome changes, which might be caused by errors in chromosome segregation during the mitosis. Because higher frequencies of micronuclei, misaligned and lagging chromosome were detected in iii ABSTRACT Chen Muhan eIF5A2 transgenic mice compared to
Author: Daniel Bassi Publisher: Biota Publishing ISBN: 1615045090 Category : Medical Languages : en Pages : 60
Book Description
Many proprotein convertases (PC), especially furin and PACE4, are involved in pathological processes such as viral infection, inflammation, hypercholesterolemia, and cancer, and have been postulated as therapeutic targets for some of these diseases. In this chapter, we review mostly our work using animal models of squamous cancers that have been induced by chemical or UV carcinogenesis protocols to highlight the role of PCs in the development and progression of experimental tumors. After demonstrating in wild type mice the role of PACE4 in tumor progression as well as detecting the expression of PACE4 and furin in human non-melanoma skin cancers, we developed transgenic mice that over-express either PACE4 or furin in squamous epithelia, including the epidermis. This was accomplished by targeting the expression of the corresponding PC by using the promoter of the bovine keratin 5. Both K5-PACE4 and K5-Furin transgenic mice showed increased susceptibility to a two-stage carcinogenesis protocol of chemical carcinogenesis. Similar studies conducted in K5-PACE4 mice also showed an increased sensitivity to ultraviolet B radiation carcinogenesis. In most of these experiments, we were able to demonstrate that compared to the control wild type mice, the over-expression of the transgene in the epidermis increased the number of benign and malignant skin tumors and also had an effect on tumor progression as evidenced by the presence of less differentiated tumors and more frequent local and distant metastases in many of the transgenic lines. Interestingly, double transgenic mice in which PACE4 and furin are targeted to the epidermis did not show any additive effect, pointing to a probable in vivo overlap of functions at least in cutaneous tissues. The tumor-enhancing effects of PACE4 and furin further support their possible role as therapeutic targets. Furthermore, a proof of principle for PC inhibition as a therapeutic tool has been substantiated by an in vivo experiment in which the PC-inhibitor, decanoyl-RVKRchloromethylketone, was topically administrated to the skin of wild type and transgenic mice treated with chemical carcinogenesis protocols, resulting in a significant decrease of tumor development and progression.
Author: Beverly A. Teicher Publisher: Springer Science & Business Media ISBN: 1592591000 Category : Medical Languages : en Pages : 745
Book Description
Beverly A. Teicher and a panel of leading experts comprehensively describe for the first time in many years the state-of-the-art in animal tumor model research. The wide array of models detailed form the basis for the selection of compounds and treatments that go into clinical testing of patients, and include syngeneic models, human tumor xenograft models, orthotopic models, metastatic models, transgenic models, and gene knockout models. Synthesizing many years experience with all the major in vivo models currently available for the study of malignant disease, Tumor Models in Cancer Research provides preclinical and clinical cancer researchers alike with a comprehensive guide to the selection of these models, their effective use, and the optimal interpretation of their results.