Angiogenesis Regulates Prostate Cancer Metastasis PDF Download
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Author:
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Category :
Languages : en
Pages : 0
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Book Description
Cancer progression depends upon the establishment of an adequate blood supply. The purpose of our studies has been to evaluate the relevance of angiogenesis in the progression of prostate cancer by evaluating the roles of three different angiogenic molecules (vascular endothelial growth factor VEGF), interleukin 8 IL-8, and basic fibroblast growth factor BFGF).
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Category :
Languages : en
Pages : 0
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Book Description
Cancer progression depends upon the establishment of an adequate blood supply. The purpose of our studies has been to evaluate the relevance of angiogenesis in the progression of prostate cancer by evaluating the roles of three different angiogenic molecules (vascular endothelial growth factor VEGF), interleukin 8 IL-8, and basic fibroblast growth factor BFGF).
Author: Wen G. Jiang
Publisher: Springer Science & Business Media
ISBN: 0306483998
Category : Medical
Languages : en
Pages : 310
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Book Description
about the involvement of signaling Transforming growth factor in tumor development and metastasis. plays a central role in the signaling network that controls morphogenesis, 2. THE BASICS OF growth and cell differentiation in SIGNALING multicellular organisms. The different members of this pleiotropic family of 2. 1. receptor signaling growth and differentiation factors seem to The family of growth factors regulate many processes in human disease consists of more than thirty members in and, in particular, tumor development. humans alone (15, 16). They cluster in Our understanding of how two major groups, the group composed of initiated signals are mediated has both the bone morphogenetic proteins increased dramatically in the last fifteen (BMP) and growth and differentiation years. Firstly, the prototype of factors (GDFs), and the group formed by this still constantly growing family, was the Activins, and Nodals. The two identified and cloned (1). Secondly, the groups differ in their use of receptors for family receptors were transmembrane receptors and the identified by expression cloning from subsequent activation of the mammalian tissue culture (2-7). Thirdly, transcriptional mediators (for recent genetic screens in Drosophila reviews see (13, 14, 17)).
Author: Christina Lee Grant
Publisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages :
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The Prostate Specific Membrane Antigen (PSMA) transmembrane peptidase is highly expressed on endothelial cells of tumor vasculature and on epithelial cells in advanced and metastatic prostate carcinoma where its expression correlates with tumor progression. While the expression pattern of PSMA makes it a potentially attractive target for therapeutic development, the precise function of PSMA in either tumor associated endothelium or prostate epithelial cells is not clear. PSMA has been shown to be significantly and universally up-regulated on the vasculature of solid tumors, while it is absent in normal, quiescent vessels suggesting it may play a role in pathologic angiogenesis. Inhibiting the enzymatic activity of PSMA leads to a decrease in endothelial cell adhesion, invasion and migration in vitro, processes which are necessary for angiogenesis. Taken together, these findings suggest that PSMA may play a role in angiogenesis in vivo. We examined tumor initiation, growth and metastasis in a transgenic model of tumor progression in wild-type and PSMA-null animals. We also investigated the relative contribution of tumor vs. endothelial PSMA expression using PSMA positive tumor allografts into wild type or PSMA null mice, and show that PSMA expression on endothelial cells is necessary for tumor angiogenesis. We also showed that PSMA contribution to pathologic angiogenesis was not restricted to tumor angiogenesis, using a mouse model of retinopathy of prematurity to show that PSMA function changes outcome in this model. Understanding the contribution of PSMA to angiogenesis progression will further understanding of diseases involving pathologic blood vessel growth. While angiogenesis occurs during normal development and in healing wounds, it is also involved in processes which involve the growth of new blood vessels, such as tumor growth and metastasis and the pathologic overgrowth of vessels into the eye which often results in blindness. Better understanding of the molecules regulating this process may lead to new therapies for tumor metastasis and for diseases involving detrimental angiogenesis.
Author: Sarah Nock
Publisher:
ISBN:
Category : Anoxemia
Languages : en
Pages : 43
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Book Description
Hypoxia is known to be a characteristic of the inner tumor environment. In order to restore oxygen to the tumor, cancer cells will increase production of vascular endothelial growth factor (VEGF) which is necessary for angiogenesis and, therefore, tumor growth. VEGF is present in different splice forms, with the predominant in cancer cells being VEGF121 and VEGF165. These splice forms have distinct characteristics which allow for different patterns of blood vessel formation within the tumor. VEGF121 lacks the heparin binding domain that is present in VEGF165, and thus is capable of diffusing away from the site of origin through the extracellular matrix and recruiting larger, pre-existing blood vessels. VEGF165, however, can bind to the heparin in the extracellular matrix and is sequestered locally, allowing it to create more internal microvessels than VEGF121. VEGF121 has also been implicated in more aggressive, metastatic cancer types. We hypothesized that VEGF expression in prostate cancer cells would increase in response to hypoxic conditions, favoring the VEGF121 isoform. We examined VEGF splice form mRNA production in both LNCaP and PC3 cells, which are prostate cancer cell lines with different metastatic potentials. Our findings suggest that hypoxia does cause an increase in both splice forms relative to expression under normoxic conditions, with a greater increase in fold change observed for VEGF121. These results of elevated VEGF121 indicate an increase in the potential for angiogenic and metastatic prostate cancer growth. Overall this work highlights the role of the hypoxic tumor microenvironment in regulating the functionally distinct VEGF isoforms in cancer cells.
Author: Yoshiro Maru
Publisher: Springer Nature
ISBN: 9811617570
Category : Medical
Languages : en
Pages : 531
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Book Description
This book, now in a thoroughly revised and updated second edition, provides the latest information on cancer metastasis from the perspective of inflammation and presents new ideas on the complicated mechanisms of metastasis and potential therapeutic targets. Key features include discussion of mechanisms recently identified to be involved in the resolution phase of inflammation, presentation of the latest evidence regarding the roles of endogenous TLR4 ligands in metastasis, and thorough explanation of the concept of homeostatic inflammation and current understanding of the significance of its dysregulation for metastasis. Structure-based thinking is another important element of the book, and it is proposed that inflammation forms a functional triangle with angiogenesis and coagulation, at the center of which cancer is located. Examples of the many additional specific topics covered in this edition include the functional involvement of new types of RNA in cancer, the insights offered by recent advances in bioinformatics, and the potential of a casein kinase 1α inhibitor in the treatment of acute myeloid leukemia. The book will be a valuable update and resource for both experienced and younger researchers. Homeostasis, originated from an idea of internal milieu by Claude Bernard, is eventually maintained by endogenous elements. The essential features of inflammation are leukocyte mobilization and increased vascular permeability, which could take place in many homeostatic or physiological conditions at low levels. Homeostatic inflammation is a concept to explain pathological settings such as metastasis in which irrespective of its level those inflammatory features are misused with endogenous molecules (see Chap. 14,15). As inflammation comprises many biological fields, targeting a single molecule for a disease could potentially make a therapeutic contribution to other diseases. For example, one focus is applied here to the roles of calprotectin in lung metastasis, which is implicated in psychiatric disorders and COVID-19 as shown by recent evidence.
Author: Jeremy Bryant Burton
Publisher:
ISBN:
Category :
Languages : en
Pages : 316
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Book Description
Author: Megan N. Thobe
Publisher:
ISBN:
Category :
Languages : en
Pages : 147
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Book Description
Prostate cancer is a leading cause of cancer related death among men in the United States, and despite current therapies, once the cancer progresses and metastasizes, the mortality rate is dramatically increased. Therefore, advances in our understanding of prostate cancer signaling pathways involved in prostate tumor progression are critical for the development of new therapeutic options. Prostate tumor angiogenesis has been shown to be critical for prostate tumor growth and metastasis, and the production of angiogenic chemokines is important for tumor vascularization. Angiogenic chemokines are a group of cytokines that act as chemoattractants for endothelial cells, and have been implicated in the pathogenesis of prostate cancer. A receptor tyrosine kinase termed Ron has also been implicated in several human cancers, including prostate cancer. In our studies, we sought to determine the impact of Ron receptor signaling in prostate cancer cells on the production of angiogenic chemokines. Our data show that Ron is highly expressed in human prostate cancer specimens compared to normal prostate tissue, and is also highly expressed in PC-3 and DU145 prostate cancer cell lines. Interestingly, Ron expression correlated with angiogenic chemokine production in prostate cancer cells. Inhibition of Ron in PC-3 or DU145 cells resulted in decreased angiogenic chemokine production, with no effect on VEGF or on the angiostatic chemokine CXCL10. The impact of Ron on the production of angiogenic chemokines is at least partially dependent on the activation of the NF-kappaB transcription factor, which has previously been shown to regulate angiogenic chemokine production in prostate cancer cells. Additionally, overexpression of Ron in LNCaP prostate cancer cells is sufficient to induce production of the angiogenic chemokine CXCL8, and these levels can be abrogated using an inhibitor of NF-kappaB. Furthermore, compared with control PC-3 cells, Ron-knockdown PC-3 cells orthotopically transplanted into the prostates of nude mice resulted not only in decreased prostate tumor growth, but also in decreased prostate microvessel density, further validating our hypothesis that Ron is indeed a regulator of prostate tumor angiogenesis. These data are further discussed in Chapter 3. We also sought to determine the role of the Ron receptor tyrosine kinase in vivo, by utilizing the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse model. We found that prostate tumors taken from TRAMP mice have overexpression of Ron compared to wild-type mouse prostate. Furthermore, TRAMP mice crossed with mice lacking functional Ron exhibited decreased prostate tumor size correlating with reduced prostate vasculature. Utilizing cell lines derived from TRAMP mouse prostates lacking functional Ron or cells derived from TRAMP mouse prostates expressing Ron, we found Ron-deficient TRAMP cells to be less viable than Ron-expressing TRAMP cells. Interestingly, there is no difference in apoptosis between cell lines, however our data suggests Ron-expressing TRAMP cells have a survival advantage. These results are discussed in further detail in Chapter 4. Taken together, our studies demonstrate for the first time that Ron receptor signaling is critical for angiogenic chemokine production in prostate cancer cells. Additionally, Ron is necessary for prostate tumor growth and angiogenesis in vivo, and is a regulator of cellular viability in cells derived from TRAMP mouse prostates. These studies provide novel insight into how the Ron receptor impacts prostate cancer, and enhances our understanding of Ron receptor signaling in tumor angiogenesis.
Author: Gilles Lugassy
Publisher: CRC Press
ISBN: 1135411891
Category : Medical
Languages : en
Pages : 241
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Book Description
This text provides comprehensive and timely coverage of the current knowledge of cancer-associated thrombosis, its pathogenesis, clinical features, prevention, and therapy. It specifically addresses the relationship between hemostatic systems and cancer, thus providing a unique and much needed focus. All of the contributors are acknowledged specialists in their fields and have experience conducting large clinical trials in oncology and thrombosis. Their discussions cover all aspects of the topic, from long-term complications to cancer surgery. It will be of interest to general practitioners, internists, oncologists, hematologists, and all physicians involved in the management of cancer patients.
Author: Rahul Jandial
Publisher: CRC Press
ISBN: 9781587066597
Category : Medical
Languages : en
Pages : 312
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Book Description
Most cancer deaths are a result of metastasis. The spread of a primary tumor to colonize neighboring and distant organs is the relentless endgame that defines the neoplastic process. Patients who have been diagnosed with cancer are treated to prevent both the recurrence of the tumor at the site of origin and metastasis that would re-stage them as advanced stage IV cancer. Historically and still with some types of cancer, stage IV is perceived by patients as “terminal.” Fortunately, recent molecular therapies have extended the lives of patients with advanced cancer and reassuringly people living with metastatic disease increasingly visit our clinics. What is the path forward? Given that the consilience of science and medicine is a dynamic art from which therapies arise, it would be misguided to consider any single work adequate at capturing the horizon for research. So with humility we constructed this text as primer for scientists. It begins with a broad introduction to the clinical management of common cancers. This is intended to serve as a foundation for investigators to consider when developing basic science hypotheses. Unquestionably, medical and surgical care of cancer patients reveals biology and dictates how novel therapeutics will ultimately be evaluated in clinical trials. The second section of this text offers provocative and evolving insights that underscore the breadth of science involved in the elucidation of cancer metastasis biology. The text concludes with information that integrates scientific and clinical foundations to highlight translational research. This book serves as a framework for scientists to conceptualize clinical and translational knowledge on the complexity of disease that is metastatic cancer.
Author: Rebecca Elisabeth Conway
Publisher:
ISBN: 9781109909265
Category :
Languages : en
Pages : 147
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Prostate Specific Membrane Antigen (PSMA), a transmembrane peptidase classically expressed in prostate cancer, is also up-regulated in the vasculature of solid tumors. However, its functional contribution to angiogenesis has not been previously studied. Therefore, we investigated whether PSMA is required for angiogenesis in vivo. We demonstrate that growth factor-induced neovascularization is drastically reduced in PSMA-null animals compared to wild type littermates in the Matrigel implant model, suggesting that PSMA is necessary during angiogenesis. To elucidate the mechanisms governing this process, we assessed endothelial cell function in response to loss of PSMA activity or expression; we find that PSMA specifically regulates endothelial cell invasion by modulating laminin-specific integrin activity. Signaling pathways downstream of integrins are also modulated by PSMA, including activation of focal adhesion kinase (FAK) and p21-activated kinase (PAK-1). Interestingly, we find that mechanism during endothelial cell invasion. We hypothesize that the actin binding protein filamin A mechanistically links PAK to PSMA regulation; our data support this idea, as PSMA interacts with filamin A in endothelial cells to regulate invasion. Because filamin A is a known substrate of PAK, and phosphorylation of filamin modulates its interaction with cell-surface proteins, we propose that PSMA-activated PAK phosphorylates filamin A. PAK-mediated filamin A phosphorylation could result in reduced interaction with PSMA, thus decreasing PSMA activity and supporting productive motility by carefully modulating activation of the migratory machinery of the cell. The results of the current study implicate PSMA as an important contributor to angiogenesis and describe a novel mechanism for PSMA in this process.
