Download or read book Metastasis Genes in Breast Cancer Metastasis to Bone written by and published by . This book was released on 2003 with total page 57 pages. Available in PDF, EPUB and Kindle. Book excerpt: The most prevalent site of breast cancer metastasis is bone. We will begin to elucidate the molecular mechanisms involved in bone metastasis. We propose to develop and utilize green (GFP) and/or red (dsRed) fluorescent protein-tagged breast carcinoma xenografts to measure bone metastasis following intracardiac injection. Cell lines developed will be used to test whether a metastasis suppressor (BRMSl) and a gene it down-regulates (osteopontin) alter the efficiency of bone colonization. Concomitantly, we will test the impact of changed gene expression on the ability of tumor cells to adhere to human osteoblast cell cultures or human bone marrow endothelium.

Download or read book Metastasis of Breast Cancer written by R.E. Mansel and published by Springer Science & Business Media. This book was released on 2007-06-14 with total page 439 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by experts in the subject area, the book covers a broad range of topics in the metastasis of breast cancer, from genetics, biology to clinical management. Main topics include genetic control, biology, growth factors, cell adhesion, cell motility and invasion, natures of bone metastasis, sentinel node therapies, hormonal links, new biomarkers and detection of micrometastasis and diagnosis. This timely book also covers the current treatment options.

Download or read book Identifying Breast Cancer Bone Metastasis Genes written by and published by . This book was released on 2007 with total page 9 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bone metastasis is one of the major causes of morbidity and mortality in breast cancer (BC) patients. However, only a few human BC cell lines can efficiently metastasize to bone whereas most BC cell lines cannot. Recently, it was shown that systemic administration of the conditioned medium by a melanoma cell line redirected the metastatic dissemination of a weakly metastatic lung carcinoma cell line to the organ sites that were metastasized by the melanoma cell due to the formation of metastasis-permissive niches by bone marrow-derived cells (BMDCs) in these organ sites. The current project was proposed to test the hypothesis that factors secreted by metastasis-competent BC cells may condition bone marrow for the successful homing and skeletal remodeling of circulating BC cells. Athymic nude mice were treated with media conditioned by metastasis-competent BC cells and then inoculated with nonmetastatic BC cells in arterial circulation. The treatment induced limited bone metastasis. Bone histology analysis is currently being performed.

Download or read book miRNAs and Target Genes in Breast Cancer Metastasis written by Seema Sethi and published by Springer. This book was released on 2014-10-13 with total page 83 pages. Available in PDF, EPUB and Kindle. Book excerpt: This SpringerBrief gives the latest research on the role of miRNAs in breast cancer metastasis. MicroRNAs (miRNAs) are recently described small endogenous noncoding RNAs implicated in the posttranscriptional control of gene expression. These tiny molecules are involved in developmental, physiologic phenomenon as well as pathologic processes including cancers. In fact, miRNAs have emerged as critical regulators of cancer progression, invasion and metastasis. This is mainly because a single miRNA can affect several downstream genes and signaling pathways with oncogenic or tumor suppressor actions depending on the target genes affected. Due to this multimodal downstream signaling effects, these small endogenous molecules hold great promise in metastasis prevention and treatment. Modulating the activity of miRNAs can provide opportunities for novel cancer interventions. Targeting miRNAs could become a novel prognostic and therapeutic strategy to prevent the future development of metastasis. Thus, miRNAs could also serve as a potential targets for anti-metastatic therapy. The book explores how the expression of miRNAs in the primary tumor could be silenced using antagomirs (chemically modified anti-miRNA oligonucleotides), which could prevent the development of metastasis; whereas once metastasis develops then it could be treated with miRNA mimics for inducing its expression for the treatment. Therefore, development of miRNA-based prophylactic therapies could serve as precision and personalized medicine against future development of metastasis of breast and other cancers.

Download or read book Mechanisms of Bone Metastasis from Breast Cancer Using a Clinically Relevant Model written by and published by . This book was released on 1999 with total page 62 pages. Available in PDF, EPUB and Kindle. Book excerpt: We have developed and characterised a model of breast cancer metastasis to bone that overcomes the deficiencies of earlier models. It utilises clones of a spontaneous mammary carcinoma that, after orthotopic injection of the tumor cells into the mammary gland, metastasise to bone and cause hypercalcemia. In addition, metastases are detected in some other organs, mainly lungs and liver. Other clones derived from the same primary tumor either do not metastasise, or metastasise only to lungs. In the past year, we have made substantial progress in two areas. One is in a study of the role of a gene, parathyroid hormone related protein (PTHrP), believed to be important in metastasis to bone. We have found that expression of PTHrP is not required for metastasis to bone, but once in the bone environment, high levels of PTHrP enhance tumor growth. This is consistent with a recent clinical study of the link between PTHrP and bone metastasis. Our genome wide screening for genes required for metastasis to bone has revealed several candidates, all but one of which have not been implicated previously in metastasis. They are caveolin- 1, bone morphometric protein-4, osteopontin, protease nexin-l and (33 integrin. Functional studies are underway with these genes.

Download or read book Molecular Mediators of Breast Cancer Bone Metastasis written by Anna Mourskaia and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Breast cancer is the most frequently diagnosed and the second leading cause of cancer deaths in Canadian women. The most devastating and deadly feature of the disease is the emergence of metastases. Breast cancer most commonly metastasizes to bone, often leading to a significantly decreased quality of life in affected patients. Despite progress in understanding the underlying molecular biology of breast tumors that relapse to bone, to date there are no therapies capable of curing the disease. Hence, it is essential to gain a more in-depth knowledge of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. Consequently, it was attempted to: 1) examine the efficacy of targeting a known pathway important for breast cancer metastasis to bone, 2) identify novel mediators of this process and 3) develop a stratification tool capable of identifying patients with breast cancer that possesses a high likelihood of spreading to bone. Transforming growth factor-beta (TGF-[beta]) signaling is a potent modulator of the invasive and metastatic behavior of breast cancer cells. The work in this thesis demonstrates that expression of a TGF-[beta] ligand trap, which neutralizes TGF-[beta]1 and TGF-[beta]3 in breast cancer cells, diminished their outgrowth in bone and reduced the severity of osteolytic lesion formation. It is further shown that a reduction or loss of host-derived TGF-[beta]1 reduced the incidence of breast tumor outgrowth in the skeleton. Moreover, tumor cells capable of growing within the bone of a TGF-[beta]1 deficient host up-regulated expression of all three TGF-[beta] isoforms within the tumor cells themselves, effectively bypassing the host-deficiency. Next, a gene discovery approach was undertaken to identify novel candidate mediators of breast cancer skeletal metastasis. Invasive breast epithelium was selectively isolated by laser capture microdissection (LCM) performed on bone metastases and primary tumors from patients displaying breast cancer with subsequent recurrence to the skeleton. In this search, ABCC5 was found to be overexpressed in osseous metastases compared to primary mammary tumors metastatic to bone. Furthermore, this protein was detected at substantially higher levels in human and mouse breast cancer cells, which metastasize to bone in animal models. Importantly, removal of this protein from these cells resulted in their decreased ability to induce osteolytic bone lesions, which was correlated with a decreased recruitment of osteoclasts, cells responsible for the bone resorption process. Finally, the molecular changes occurring within the primary breast tumor were investigated in an attempt to identify a prognostic bone metastatic signature. Gene expression profiling was performed on estrogen receptor (ER)-positive primary breast tumors metastastatic to bone and breast cancers, which spread to soft tissue. A 25-gene signature was derived from the top 100 differentially expressed probes and was found to be capable of discriminating breast tumors metastatic to bone from cancers recurring to visceral sites in an independent gene expression dataset." --

Download or read book Cancer and Bone Metastasis written by Chandi C. Mandal and published by Frontiers Media SA. This book was released on 2020-01-30 with total page 116 pages. Available in PDF, EPUB and Kindle. Book excerpt: This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

Download or read book MMP 8 A Breast Cancer Bone Metastasis Suppressor Gene written by and published by . This book was released on 2005 with total page 21 pages. Available in PDF, EPUB and Kindle. Book excerpt: In order to study the role of MMP-8 on inhibition of cancer growth and progression, we initiated our work to clone the human MMP-8 cDNA and express it in vitro. The pcDNA3.1 contains the following elements: human cytomegalovirus (CMV) immediate-early promoter/enhancer that permits efficient, high-level expression of recombinant protein and V5 epitope that allows detection of recombinant protein with anti-V5 antibody. The MMP-8 cDNA with a V5-epitope tag was cloned downstream into the CMV promoter sequence. The construct pCMV-MMP-1-V5 was sequenced to verify cloning of the MMP-8 cDNA insert in frame. The molecular mechanisms of how TGF-beta1 mediates stimulation of invasion and formation of bone metastases have yet to be completely determined. In my laboratory, we have found that ATF-3 (activating transcription factor- 3) is strongly stimulated and its level is sustained by TGF-beta1 in highly invasive and bone metastatic human breast cancer cells. A defect in repression of ATF-3 expression in breast cancer cells could lead to activation of genes that participate in multi-step breast cancer progression.

Download or read book Stromal Gene Expression and Function in Primary Breast Tumors that Metastasize to Bone Cancer written by and published by . This book was released on 2004 with total page 26 pages. Available in PDF, EPUB and Kindle. Book excerpt: A clinically relevant syngeneic model of breast cancer metastasis has been used to determine gene expression alterations that occur both between primary breast cancers with varying metastatic potential and between matched primary and bone metastases. We have immunopurified epithelial and endothelial cell populations and profiled them separately to identify differentially expressed genes, some of which have not previously been associated with breast cancer metastasis. Expression profiles of vascular endothelium derived from primary tumors of varying metastatic potential identified aberrant expression of genes involved in angiogenesis, cell cycle progression, cytoskeletal structure and tumor suppression. Those altered in the primary tumor epithelium included developmental genes, metastasis suppressors and genes involved in cytoskeletal organization, cell cycle progression, apoptosis and transformation. The microarray data was confirmed by quantitative RT-QPCR. Further analysis of epithelium from matched spine metastases revealed some genes that were upregulated further at the metastatic site. These included stefin Al (inhibitor of cathepsin S) that was upregulated in highly metastatic primary epithelium and increased a further 9-fold in matched bone metastases. The expression in spine metastases was verified by in situ hybridization whilst the expression of stefin Al in subsets of tumor cells in invasive human breast cancer was confirmed by immunohistochemistry.

Download or read book Cancer Metastasis Related Genes written by D.R. Welch and published by Springer Science & Business Media. This book was released on 2006-04-11 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt: Being diagnosed with cancer is devastating. But when the cancer cells have to spread to form secondary colonies, the prognosis for the patient is worse. If meaningful improvements in survival are to occur, then control of metastasis will be a foundation. Relatively little is known about the control of the metastatic process at the molecular level. This volume begins to explore our current knowledge regarding the underlying molecular and biochemical mechanisms controlling the metastatic phenotype. While all of the authors attempted to put their findings into a context for translation to the clinical situation, the state-of-the-art does not fully allow this. Nonetheless, we write these summaries of our work as an early effort toward that end. I am grateful to all of the authors who have contributed generously of their time and energies to make this volume a reality. To metastasize, neoplastic cells dissociate from the primary tumor, enter a circulatory compartment (typically lymphatics or blood vasculature), survive transport, arrest, exit the circulation and finally proliferate at a discontinuous site in response to local growth factors. Unless cells accomplish every step of the metastatic cascade, metastases cannot develop. The process is highly inefficient, i. e. ,

Download or read book Identification of Genetic Determinants of Breast Cancer Metastasis to the Bone written by Milica Pavlovic and published by . This book was released on 2016 with total page 195 pages. Available in PDF, EPUB and Kindle. Book excerpt: El objetivo de esta tesis era identificar determinantes genéticos de cáncer de mama con metástasis óseas. Para ello se utilizó un enfoque integral que se sustenta en células humanas de cáncer de mama, modelos experimentales de ratón y datos clínicos. En primer lugar, nos centramos en los genes específicamente adquiridos para la metástasis ósea, altamente expresados en las lesiones de metástasis óseas, pero no enriquecidos en los tumores primarios de mama que recaen en el hueso. Entre estos genes, el factor secretado NOG destaca como altamente expresado en células de cáncer de mama, principalmente ER-negativas, con alta capacidad de desarrollar metástasis ósea en modelos de ratón. La expresión de NOG aumenta la diferenciación de los osteoclastos y la capacidad de auto-renovación de las células tumorales de mama, estimulando el crecimiento de metástasis óseas. Por otra parte, también nos centramos en las alteraciones genómicas que se asocian significativamente con la recurrencia ósea en tumores primarios de mama. Hemos podido identificar que determinadas alteraciones genéticas fueron adquiridas en derivados altamente metastáticos a hueso comparado con las células parentales. Curiosamente, se seleccionó una ganancia del número de copias en muestras de tumor primario de cáncer de mama con elevado riesgo de recahída en el hueso. En consecuencia, la expresión del gen metastático, que se encuentra dentro de la región genómica, se incrementó en tumores primarios y se asoció con la recurencia al hueso. Dicho gen se perfila como posible mediador de la metástasis ósea del cáncer de mama.

Download or read book Metastatic Cancer Clinical and Biological Perspectives written by Rahul Jandial and published by CRC Press. This book was released on 2013-08-08 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Involvement of MicroRNA 30 Family in Metastatic Dissemination of Breast Cancer Cells to Bone written by Agnieszka Frackowiak and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bone metastasis is a common complication of advanced breast cancers and is clinically responsible of bone fractures, hypercalcemia and pain for which only palliative therapies are proposed. Breast tumor cells that preferentially invade bone express a set of deregulated genes that enhance bone tropism and facilitate bone marrow engraftment which may lead to the formation of overt osteolytic lesions. Molecular pathways underlining these steps are regulated through the tight control of genes expressed by cancer cells interacting with cells from the bone microenvironment. In this context, microRNAs act as regulators of gene expression and control multiple aspects of bone metastasis, including tumor cell escape from the primary site, dissemination, invasion of the bone marrow and secondary outgrowth. MicroRNA transcriptomic profiling of osteotropic breast cancer cell lines identified drastic down-regulation of the miR-30 family (miRs-30). In the clinic, low expression of miRs-30 in breast primary tumors is associated with poor distant metastasis-free survival and hormoneinsensitive status. In a model of human bone metastasis in vivo, the forced expression of miRs-30 in a breast cancer cell line that is highly and specifically metastatic to bone inhibited bone metastasis. We demonstrated that miRs-30 inhibit tumor cell invasiveness and stimulate osteoblastogenesis, in vitro, and reduces tumor burden and osteoclast activity, in vivo. Consistent with that, the expression of several genes that promote bone metastasis were inhibited by miRs- 30. Among these, expression of connective tissue growth factor (CTGF) was up-regulated in human bone metastasis. The early steps of bone metastasis were studied in a mouse model using spontaneously metastatic mouse breast cancer cell lines inoculated in the mammary gland. In this model, miRs-30 did not alter tumor growth or metastatic dissemination to bone. However, miRs-30 inhibited cell invasiveness and cancer stem cell-like phenotype of these metastatic cells. We conclude that miRs-30, by interfering negatively with bone metastasis, represent a potential therapy to repress gene targets that promote bone metastasis.

Download or read book Gap Junctional Intercellular Communication and Breast Cancer Metastasis to Bone written by and published by . This book was released on 2001 with total page 35 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the final report of a one year Concept Award. All three specific aims of the original proposal were successfully completed. We were also able to begin several additional experiments not proposed in the original application. We found that: 1) expressing the metastasis suppressing gene BRMS1 in diverse cancer cell lines, including breast and melanoma, restores homotypic gap junctional intercellular communication (GJIC); 2) that metastatic breast cancer cells express a different connexin profile ((Cx43(-)/Cx32(+)) than normal breast epithelial cells or metastases suppressed breast cancer cell lines ((Cx43(+)/Cx32(-)); 3) that metastatic breast cancer cells do not establish significant GJIC with normal breast epithelial cells but those expressing the metastasis suppressing gene BRMS1 do; 4) that while metastatic breast cancer cells do not establish GJIC with themselves they do establish heterotypic GJIC with bone cells; 5) that metastatic breast cancer cells express abundant OPN while those expressing the metastasis suppressing gene BRMS1 do not; and 6) expressing Cx43 in metastatic breast cancer cells dramatically reduces OPN expression and reestablishes homotypic GJIC. These results suggest that connexin expression and GJIC contribute to breast cancer metastasis to bone.

Download or read book Breast Cancer Metastasis and Drug Resistance written by Aamir Ahmad and published by Springer Nature. This book was released on 2019-08-27 with total page 427 pages. Available in PDF, EPUB and Kindle. Book excerpt: Resistance to therapies, both targeted and systemic, and metastases to distant organs are the underlying causes of breast cancer-associated mortality. The second edition of Breast Cancer Metastasis and Drug Resistance brings together some of the leading experts to comprehensively understand breast cancer: the factors that make it lethal, and current research and clinical progress. This volume covers the following core topics: basic understanding of breast cancer (statistics, epidemiology, racial disparity and heterogeneity), metastasis and drug resistance (bone metastasis, trastuzumab resistance, tamoxifen resistance and novel therapeutic targets, including non-coding RNAs, inflammatory cytokines, cancer stem cells, ubiquitin ligases, tumor microenvironment and signaling pathways such as TRAIL, JAK-STAT and mTOR) and recent developments in the field (epigenetic regulation, microRNAs-mediated regulation, novel therapies and the clinically relevant 3D models). Experts also discuss the advances in laboratory research along with their translational and clinical implications with an overarching goal to improve the diagnosis and prognosis, particularly that of breast cancer patients with advanced disease.

Download or read book Identification of Key Factors and Genes Involved in Breast Cancer Metastasis to the Bone and Development of Scaffolds Incorporating Germanium Nanowires for Biological Applications written by Anushree Dwivedi and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Principles of Bone Biology written by John P. Bilezikian and published by Academic Press. This book was released on 2008-09-29 with total page 2074 pages. Available in PDF, EPUB and Kindle. Book excerpt: Principles of Bone Biology provides the most comprehensive, authoritative reference on the study of bone biology and related diseases. It is the essential resource for anyone involved in the study of bone biology. Bone research in recent years has generated enormous attention, mainly because of the broad public health implications of osteoporosis and related bone disorders. Provides a "one-stop" shop. There is no need to search through many research journals or books to glean the information one wants...it is all in one source written by the experts in the field The essential resource for anyone involved in the study of bones and bone diseases Takes the reader from the basic elements of fundamental research to the most sophisticated concepts in therapeutics Readers can easily search and locate information quickly as it will be online with this new edition