Maspin
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Maspin
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Author : Mary J.C. Hendrix
language : en
Publisher: CRC Press
Release Date : 2002-08-01
Maspin written by Mary J.C. Hendrix and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002-08-01 with Science categories.
This book represents the first compilation of the major research findings regarding Maspin a mammary serpin (or serine) protease inhibitor. Maspin was originally discovered through subtractive hybridization and differential display analyses, comparing the differences in gene expression in normal mammary epithelium and invasive carcinoma cells. T
Functional Study Of Maspin In Breast Cancer
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Author :
language : en
Publisher:
Release Date : 1999
Functional Study Of Maspin In Breast Cancer written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999 with categories.
The object of this proposal is to understand the tumor suppressor function of maspin, a novel serine protease inhibitor, and to test directly maspin as a therapeutic agent for breast cancer. Transgenic and knockout mouse models will be employed to study the effects of gain and loss of maspin function on mouse mammary tumorigenesis and development. We hypothesize that overexpression of maspin should be protective against mammary tumorigenesis and metastasis, while loss of maspin will render mice more susceptible to tumor formation and metastasis. The proposal is based upon our previous experiments, primarily performed in conventional cell culture models, demonstrating that maspin has tumor suppressor activity. Recently, we have established transgenic mice overexpressing maspin in the mammary gland, and generated maspin knockout mice. We have crossed maspin transgenic mice with a breast tumor WAP-Tag strain. Our data suggest that maspin functions directly as a metastasis inhibitor. We have also shown in this report the mechanism by which maspin inhibits normal mammary development during pregnancy in WAP-maspin transgenic mice, and we are testing maspin against tumor progression in mice. Continuation of these tasks in the next few years will help us understand the role of maspin in tumor metastasis and angiogenesis, and hopefully leading to the development of new therapies for the treatment of breast cancer.
Maspin Expression And Its Metastasis Suppressing Function In Prostate Cancer
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Author : Eswar Shankar
language : en
Publisher:
Release Date : 2016
Maspin Expression And Its Metastasis Suppressing Function In Prostate Cancer written by Eswar Shankar and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with Medicine categories.
Mammary Serine Protease Inhibitor (Maspin) is a unique member of the serpin family with tumor suppressive properties. Maspin is a secreted protein encoded by a class II tumor suppressor gene, expressed in normal prostate luminal and basal cells but reduced or absent in prostate cancer. Currently, there is a consensus that maspin expression in prostate cancer is an indicator of a better prognosis and is a predictive marker for therapeutic response in prostate cancer. Experimental evidence consistently indicates that maspin suppresses tumor growth, invasion, and metastasis and promotes apoptosis in cancer cells. In this chapter, we discuss regulation of maspin expression, binding partners of maspin, and pathways through which maspin exerts its tumor suppressive properties. In addition, we summarize the progress that investigators have made in clarifying the role of maspin in prostate cancer biology and in assessing its role as a diagnostic marker and therapeutic agent.
Maspin A Tumor Suppressor Gene Is Expressed In Human Basal Breast Epithelial Cells But Not In Breast Carcinoma Cells
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Author : Maki Saitoh
language : en
Publisher:
Release Date : 2004
Maspin A Tumor Suppressor Gene Is Expressed In Human Basal Breast Epithelial Cells But Not In Breast Carcinoma Cells written by Maki Saitoh and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2004 with Antioncogenes categories.
Dna Methylation Epigenetics And Metastasis
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Author : Manel Esteller
language : en
Publisher: Springer Science & Business Media
Release Date : 2005-06-09
Dna Methylation Epigenetics And Metastasis written by Manel Esteller and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2005-06-09 with Medical categories.
This book provides a broad and rich outline of the epigenetic mechanisms involved in cancer progression and the generation of metastasis. It describes the tumor suppressor genes undergoing transcriptional silencing by CpG island promoter hypermethylation in the different tumor types of the human anatomy and their association with tumoral behaviour. It also provides a comprehensive insightful look at the molecular players involved in DNA methylation, histone modification and chromatin remodelling complexes causing epigenetic lesions linked to the metastasic phenotypes. Finally, it explains how epigenetic lesions associated with cancer spreading can be targeted using new and potent chemotherapy drugs. The book is a state-of-the-art reference to all scientific researchers and clinicians interested in the understanding of the biological processes leading to tumor dissemination and to those that are keen to translate this knowledge to a better management of cancer patients. Each contributor is a specialist in their epigenetic area and their joint effort has created a unique view of the DNA methylation, histone and chromatin changes that define cancer metastasis.
New Developments In Metastasis Suppressor Research
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Author : Paul Jackson
language : en
Publisher: Nova Publishers
Release Date : 2007
New Developments In Metastasis Suppressor Research written by Paul Jackson and has been published by Nova Publishers this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007 with Antioncogenes categories.
The spread of cancer cells from their organ of origin to distant tissues is called metastasis. Cancer metastasis is the main cause of death from cancer, and in many cases is difficult to detect or treat. The process by which tumour cells become metastatic is complex and involves many stages, including detachment of cells from the main tumour mass, degradation of the surrounding extra-cellular matrix, invasion into nearby blood vessels, travel and survival through the circulatory system, attachment to a vessel wall, extra-vasation, degradation of the extra-cellular matrix into a distant tissue/organ, and the development of a novel blood supply. In order to accomplish this process, the cells acquire characteristics which are important for each stage. Recently, a class of genes known as metastasis suppressors' has been the subject of intense investigation. For some metastasis suppressor genes, there is strong evidence from both in vitro and in vivo studies to demonstrate key roles in the metastatic process, for others data is much more limited, and their importance uncertain. In this book, chapters are devoted to providing up-to-date summaries of our understanding of individual metastasis suppressor genes. Each is written by a leading authority in the study of that gene. Topics covered include discussions on how each metastasis suppressor was discovered, the mechanisms underlying their loss of expression in tumours and tumour cell lines, their proposed molecular functions, and the consequences to a tumour cell of the loss of this function. This compilation aims to provide, in a single volume, comprehensive information that will be valuable to all scientists working in cancer research, to students needing to understand molecular events that regulate tumour progression and the acquisition of metastasis, and to clinicians who might wish to know more of the roles of potentially new markers for cancer diagnosis and prognosis.
Characterisation Of The Cellular Roles Of The Non Inhibitory Serpin Maspin
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Author : Lorna Elizabeth Ravenhill
language : en
Publisher:
Release Date : 2010
Characterisation Of The Cellular Roles Of The Non Inhibitory Serpin Maspin written by Lorna Elizabeth Ravenhill and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
Maspin is a non-inhibitory member of the serine protease inhibitor (serpin) family. Maspin functions as a class II tumour suppressor, resulting from its ability to negatively influence cell migration, invasion, proliferation and angiogenesis, whilst positively regulating cell adhesion and apoptosis. The expression of maspin has been shown to correlate with an increased survival rate for patients diagnosed with several cancers, including those of the breast and the prostate. The overall aim of this work was to characterise the cellular roles of maspin focusing on its effects on cellular morphology, migration and adhesion and the underlying influence of the extracellular matrix. In addition, we aimed to provide an insight into the currently unclear molecular mechanism that maspin uses to exert its tumour suppressor effects. Insect Drosophila S2 cells were used to express and produce wild type maspin protein. The biological activity of recombinant maspin was confirmed through cell migration and cell adhesion assays. We also manipulated wild type maspin gene using siRNA in mammalian cell lines and used site directed mutagenesis to generate constructs point mutated at sites potentially involved in protein-protein interaction. These mutant constructs were transfected alongside wild type maspin into maspin-null breast and prostate cancer cell lines in an attempt to identify structural motifs critical to maspin's biological function. The addition of recombinant maspin protein or the transfection of wild type maspin gene promoted a mesenchymal-epithelial transition (MET), decreased cell motility and enhanced cell adhesion. Mutation to maspin's [alpha]-helix G attenuated its epithelialmesenchymal transition (EMT) and disabled its ability to reduce migration and increase adhesion. The influence of maspin on these cell behaviours was mimicked by wild type and mutant maspin peptides that spanned its [alpha]-helical G region; supporting the evidence that this helical structure is important. We also showed that maspin changed the affinity state of [beta]1 integrins; an ability also dependent on its [alpha]-helix G. The importance of maspin to mediate its non-metastatic effects, via its [alpha]-helix G, were consistent on collagen I, fibronectin and fibrillar matrices. However, an intact [alpha]-helical G region was not essential for maspin's ability to decrease cell migration, nor its ability to increase MET and adhesion, when plated onto laminin. Thus, in the presence of laminin, maspin must use a different mechanism of action.
Localisation And Function Of Mammary Serine Protease Inhibitor Maspin
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Author : Soo Yee Sonia Teoh
language : en
Publisher:
Release Date : 2012
Localisation And Function Of Mammary Serine Protease Inhibitor Maspin written by Soo Yee Sonia Teoh and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.
Maspin (SERPINB5), a member of the clade B subgroup of the serpin superfamily, isreported to function as a tumour suppressor, but its mechanism remains to be elucidated, asboth extracellular and intracellular functions have been proposed. Members of the clade Bserpin lack a classical secretory peptide and thus, are predominantly intracellular andnucleocytoplasmic. Despite this, numerous studies still suggest an extracellular mechanism offunction for maspin without providing evidence of its release from cells. In addition, proposedmechanisms of function for maspin are based on single cell clones of cancer cells engineeredto overexpress maspin, which leaves open the possibility that these observations may be dueto clonal artefacts. Taken together with the contrasting results from epidemiological reports invarious cancers regarding the prognostic utility of maspin, these observations suggest thatmaspin may not function as a tumour suppressor.This thesis shows, using immortalised, non-transformed human mammary epithelialcells naturally expressing maspin, that maspin is an obligate intracellular serpin and cannot besecreted even when provided with a conventional signal sequence. Maspin has anucleocytoplasmic localisation, but redistributes to the cytosol following differentiation of theepithelial cells. Furthermore, based on studies using whole populations of transduced, butuncloned, breast cancer cells, this study also shows that maspin re-expression does not inhibitcancer cell invasion, migration and clonogenicity in vitro, or primary tumour growth andmetastasis in vivo. Hence, maspin is unlikely to be a tumour suppressor.
Maspin
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Author : Mary Hendrix
language : en
Publisher: Eurekah.Com Incorporated
Release Date : 2002
Maspin written by Mary Hendrix and has been published by Eurekah.Com Incorporated this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002 with Medical categories.
Rational Derivatives Of Maspin As Candidate Tumor Suppressive Agents Of Breast Cancer
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Author :
language : en
Publisher:
Release Date : 2000
Rational Derivatives Of Maspin As Candidate Tumor Suppressive Agents Of Breast Cancer written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000 with categories.
We proposed to generate and characterize six rational derivatives of maspin as candidate tumor suppressive agents of breast cancer. We plan to produce these novel maspin variants as purified proteins (Specific Objective 1), and as re-expressed proteins in breast tumor cells that are transfected with the corresponding coding cDNAs (Specific Objective 2). The biological functions of these six maspin derivatives as well as the wild type maspin will be examined using comprehensive cellular and biochemical as says that have been established in my laboratory. In particular, I will focus on the effect of these molecules on tumor growth, cell adhesion, cell motility and invasion. In addition the biochemical and biophysical properties of these new molecules will be evaluated. Our unexpected results prompted a new investigation of the role of maspin in breast tumor progression. To further explore the clinical application of maspin in human cancer, it is critical to understand the in vivo biological function of maspin in tumor progression. To this end, one of the most powerful models used to examine multistage carcinogenesis has been MMTV/TGF-alpha; transgenic mouse. Elevated levels of TGF-alpha; have been detected in transformed keratinocytes and in a variety of naturally occurring human tumor types (Gottlieb, 1988; Reddy, 1994). In addition, the role of TGF-alpha; in neoplasia has been confirmed in a variety of experimental systems, including transgenic mice in which initially hyperplasia and later neoplasia of liver and mammary glands were observed (Thappan, 1990; Matsui, 1990; Sandgren, 1990). In collaboration with Dr. Kaladhar Reddy at WSU, we evaluated the role of maspin as a tumor suppressor using MMTV/TGF-alpha; transgenic mouse model.