Download or read book Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer written by and published by . This book was released on 2000 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our preliminary data indicated the presence of a breast carcinoma metastasis suppressor genes on human chromosome 11. The goal was to identify and begin characterizing the gene(s) responsible. Two approaches were proposed - (1) introduction of smaller pieces of chromosome 11 into cells with assessment of metastatic potential; and (2) identification of differentially expressed mRNA in metastasis suppressed cells. Progress using Approach #1 was not successful. Approach #2 was successful. We identified three novel cDNAs using differential display which were more highly expressed in the metastasis-suppressed neo11/435 hybrids. Moreover, one of those candidates, BRMS1, significantly suppressed metastasis in two human breast carcinoma cell lines when transfected and constitutively expressed. BRMS1 1 maps to 11q13, a site commonly involved in late-stage breast carcinoma. The mechanism of action appears to be novel, but was not determined during the funding period. In summary, we accomplished the stated ultimate objective for DAMD-17-96-1-6152. Results generated from DAMD-17- 96-1-6152 were used to successfully compete for funding from the National Cancer Institute to follow-up on these exciting findings.

Download or read book Chemoresistance and Metastasis in Breast Cancer Molecular Mechanisms and Novel Clinical Strategies written by Qifeng Yang and published by Frontiers Media SA. This book was released on 2022-03-18 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Bone Metastasis and Molecular Mechanisms written by Gurmit Singh and published by Springer Science & Business Media. This book was released on 2013-11-11 with total page 319 pages. Available in PDF, EPUB and Kindle. Book excerpt: Patients with advanced breast or prostate cancers usually develop bone metastases. The principal complications resulting from metastatic bone disease are pain, spinal cord compression, pathologic fractures and bone marrow suppression. Improving the management of bone metastases is crucial to quality of life for patients with breast and prostate cancer. Advances in understanding of the molecular mechanisms underlying the pathophysiology of bone metastasis are driving the development of new therapeutic strategies.

Download or read book Molecular Mechanisms of Drug Resistance And Strategies of Sensitization in Breast Cancer 2nd edition written by Yan Cheng and published by Frontiers Media SA. This book was released on 2024-01-11 with total page 198 pages. Available in PDF, EPUB and Kindle. Book excerpt: Basic scientific background Breast cancer is one of the most common cancer and the most frequent cause of cancer death among women worldwide. Currently, subtyping breast cancers into hormone receptor (HR) positive, human epidermal growth factor receptor-2 overexpressing (HER2+), and triple negative breast cancer (TNBC) is the basis of diagnosing and treating this disease. The main treatment strategies for breast cancer include surgery, endocrine therapy, molecular targeted therapy, chemotherapy, radiotherapy, immunotherapy and gene therapy. However, resistance of breast cancer cells to chemotherapeutic agents, molecular targeted therapies and immunotherapy may occur either intrinsically or de nova, and is often ultimately responsible for treatment failure. Therefore, drug resistance poses a major challenge to breast cancer treatment. Current developments: Drug resistance in breast cancer is a complex clinical condition originating from a wide range of molecular alterations. The development of endocrine therapy resistance is believed to be associated with many cellular changes, such as ESR1 gene mutations, bypassing estrogen signaling pathway and altered tamoxifen metabolism. Meanwhile, changes in immune response, alternation of drug-binding property and downstream pathways are involved in the mechanisms of drug resistance in HER2+ breast cancer. In addition, resistance to chemotherapeutic agents predominantly arises from increased drug efflux and cross resistance. Current studies suggest that treatment strategies and therapeutics have to be designed specifically to each patient in different clinical situations. The use of modern genomic, proteomic and functional analytical techniques has contributed to identify novel genes and signaling networks involved in breast cancer drug resistance. Moreover, the use of high-throughput techniques in combination with bioinformatics and systems biology approaches has aided the interrogation of clinical samples and allowed the identification of molecular signatures and genotypes that predict responses to certain drugs. Despite much progress has been made in the field of breast cancer drug resistance, such as combination therapy and drug-loaded nanoparticles, the complexity and variability of drug resistance mechanism still inevitably lead to the continuous occurrence of drug resistance. Therefore, with the increasing amounts of anti-breast cancer agents, there are now unprecedented opportunities to understand and overcome drug resistance through further research into mechanisms and corresponding strategies, which will help achieve lasting disease control and bring survival benefits to patients with advanced cancer. Papers of interest: The current Research Topic of Frontiers in Pharmacology focuses on publishing Original Research, Review articles and Case Reports focusing on (a) elucidating mechanisms of drug resistance in breast cancer, target mutations, tumor microenvironment, undiscovered genes and signaling pathways; (b) promising drug delivery systems that can enhance the sensitivity of anti- breast cancer agents to various tumors; (c) strategies that can improve patient care during bio-chemotherapeutic treatments; (d) small molecule compounds that are effective against drug-resistant breast tumors (e) biomarkers of chemotherapy resistance in breast cancer patients and (f) in vitro and in vivo models. Guidelines for article of submission: - Authors must stick to the set guidelines for ethical practices by the Frontiers journals. - The main content of the article must have certain innovation and research significance. - The authors should describe the construction method of drug-resistant cell lines when using them for experiments in the article.

Download or read book Defining the Molecular Mechanisms that Regulate Breast Cancer Cell Migration written by Alexander Kiepas and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Many physiological processes, including angiogenesis, neurodevelopment and wound healing, rely on the directed movement of cells through the extracellular matrix (ECM). Cell migration is also a fundamental process involved in cancer metastasis. Indeed, proteins that enhance focal adhesion and actin cytoskeletal dynamics are often upregulated in invasive and metastatic cancer cells. In this thesis, we show that the adapter proteins ShcA (p46/52 isoforms) and lipoma-preferred partner (LPP) are required for the migration and invasion of ErbB2-overexpressing breast cancer cells in response to transforming growth factor [beta] (TGF[beta]). Live-cell microscopy techniques reveal that ShcA and LPP are both required for TGF[beta]-enhanced assembly and disassembly of adhesions. Moreover, p46/52ShcA must be phosphorylated on three key tyrosine residues (Y239/Y240/Y313) and LPP must interact with the actin cytoskeleton through its [alpha]-actinin binding domain (ABD) to mediate these effects. Using a BioID proximity labeling approach, we show that p46/52ShcA exists in a complex with various adhesion and actin cytoskeletal proteins, including paxillin and LPP. Total internal reflection fluorescence (TIRF) and 3D super-resolution iPALM microscopy confirm that p46/52ShcA is a novel component of adhesions and its localization to these structures precedes LPP.In addition to acting as a scaffold, the ECM provides biophysical cues that direct cell migration. We demonstrate that LPP is required for ErbB2+ breast cancer cells to sense substrate stiffness. Cells expressing wildtype LPP exhibit enhanced migration rates on intermediate stiffnesses (30-50 kPa), and slower migration rates on soft (10 kPa) and stiff (90kPa) substrates; in contrast, cells lacking LPP expression migrate at a constant speed. ErbB2+ cells also modulate invasive activity based on substrate stiffness. In particular, cells invade maximally on soft (5 kPa) and hard (100 kPa) substrates where migration is significantly reduced. This is the first study to demonstrate that LPP mediates mechanosensitivity in breast cancer cells.Breast cancer is a highly heterogenous disease with considerable cellular, molecular and pathological differences between patients. We find that LPP also plays an important role during TGF[beta]-enhanced migration and invasion of triple-negative breast cancer (TNBC) cells. Human MDA-MB-231 cells with lower levels of LPP expression fail to exhibit TGF[beta]-enhanced migration and invasion. Mouse 4T1 cells, and 4T1 derivatives that preferentially metastasize to the lungs (4T1-526) and live (4T1-2776), also fail to exhibit TGF[beta]-enhanced migration and invasion when LPP expression is reduced. Consequently, 4T1-2776 cells lacking LPP develop fewer liver metastases following splenic injection.Many of experimental results described in this thesis were obtained with live-cell fluorescence microscopy. Fluorescence microscopy provides a convenient, selective and sensitive way to observe live-cell dynamics; however, phototoxicity is a significant limitation of this technique. In this thesis, we show that much of the phototoxicity and photobleaching experienced with live-cell fluorescence imaging occurs as a result of “illumination overhead” (IO). This occurs when a sample is illuminated but fluorescence emission is not being captured by the microscope camera. As a result, we developed a workflow to optimize imaging conditions on any standard microscope. The workflow includes a guide on how to (1) determine the maximum image exposure time for a dynamic process, (2) optimize excitation light intensity, and (3) assess cell health with mitochondrial markers"--

Download or read book Drug and Hormonal Resistance in Breast Cancer written by Robert Brent Dickson and published by Prentice Hall PTR. This book was released on 1995 with total page 474 pages. Available in PDF, EPUB and Kindle. Book excerpt: Featuring contributions from expert authors of international standing, this book explores emerging studies on the success and/or failure of chemotherapy in breast cancer. Covers the clinical resistance of breast cancer to treatment; chemo-hormonal reactions; anti-hormonal resistance; multidrug resistance; and fu/antimetabolites. For cancer and hormonal researchers and development scientists in pharmaceuticals and biomedicine. Previously announced in 7/93 PTR Catalog.

Download or read book Cellular and Molecular Mechanisms of Breast Cancer Metastasis to the Brain written by Christoph B. Wyss and published by . This book was released on 2016 with total page 165 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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 Metastasis written by Lalage Wakefield and published by IOS Press. This book was released on 2007 with total page 172 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metastasis is the most dreaded aspect of the carcinogenic process. More than ninety percent of all cancer deaths are attributable to the consequences of the primary tumor successfully colonizing distant organs. Unlike the situation with colon cancer, a patient with breast cancer can never be considered 'cured', since as many as a third of breast cancer patients who have apparently curative surgery for their primary tumors ultimately relapse with metastatic disease, sometimes decades later. Much effort is now devoted to understanding this process of metastasis, and finding ways to predict and prevent its occurrence.This publication covers recent advances in the field, specifically as they relate to breast cancer. The availability of new tools and technological approaches has prompted a reconsideration of the very definition of a metastasis. Furthermore, a number of commonly held myths are being explored and a new definition of a metastasis, with important implications for clinical staging, is being proposed. Also, a novel conceptual framework for cancer progression based on the system-level dynamics of regulatory networks is presented and the role of chemokines in mediating some of

Download or read book Molecular and Cellular Basis of Metastasis Road to Therapy written by and published by Academic Press. This book was released on 2016-09-03 with total page 392 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular and Cellular Basis of Metastasis: Road to Therapy, the latest in the Advances in Cancer Research series, provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics, with this volume covering the molecular and cellular basis of metastasis. Presents groundbreaking information on the molecular and cellular basis of metastasis Provides information on cancer research Outstanding and original reviews Suitable for both researchers and students

Download or read book Molecular Mechanisms of Breast Cancer Metastasis written by and published by . This book was released on 2003 with total page 18 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metastasis accounts for the majority of deaths associated with breast cancer. There is a need to identify prognostic/predictive indicators to accurately determine whether breast cancer cells are likely to metastasize. Hp1(Hs alpha) (Heterochromatin Protein 1) has been identified as a candidate breast cancer metastasis suppressor that is down-regulated in highly invasive/metastatic breast cancer cells compared to poorly invasive/non-metastatic cells. HP1(Hs alpha) is a non-histone chromosome protein that plays a role in chromosome segregation, chromatin packaging, and gene silencing.

Download or read book New Developments in Metastasis Suppressor Research written by Paul Jackson and published by Nova Publishers. This book was released on 2007 with total page 340 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Epithelial Mesenchymal Plasticity in Cancer Metastasis written by Mohit Kumar Jolly and published by MDPI. This book was released on 2020-12-29 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.

Download or read book Molecular Mechanisms of Metastatic Progression in Breast Cancer written by and published by . This book was released on 2003 with total page 19 pages. Available in PDF, EPUB and Kindle. Book excerpt: Clusterin is a multifunctional glycoproptein involved in tissue remodeling and apoptosis. However, recent studies have demonstrated that clusterin expression correlates with tumor grade in prostate cancer and in one retrospective study has been associated with tumor progression in breast cancer. Furthermore clusterin expression has been correlated with resistance to cytotoxic compounds such as TNF-alpha in prostate cancer, suggesting that clusterin may play a role in surviving cells. In our studies, we have focused on determining whether clusterin plays a causative role in the progression of human breast cancer by promoting cell survival, increasing cell motility and resistance to cytotoxic drugs. Our studies have utilized an ER-alpha positive non-invasive MCF-7 cell line, an MCF-7 cell line genetically engineered to overexpress clusterin(MCF-7CLU) and an ER-alpha negative breast negative invasive SUM-159PT cell line. Our major finding to date are that MCF-7CLU cells express 5-10 fold higher levels of intra- and extra-cellular clusterin as compared to parental MCF-7 cells. The MCF-7CLU cell line exhibits increased growth rates, altered cellular morphology, a dramatic increase (10-fold) in invasive potential and a delayed apoptotic response to cytotoxic compounds such as TNF-alpha and Tamoxifen in comparison to the parental MCF-7 cells.

Download or read book Rediscovering Cancer From Mechanism to Therapy written by Sayali Mukherjee and published by CRC Press. This book was released on 2018-09-04 with total page 599 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume presents a snapshot of some of the most important ongoing research in cancer. With cancer as the second leading cause of death worldwide, extensive research is going on globally to decipher the molecular mechanism underlying cancer that will help in finding better targets for drug therapy. The book brings together new research on molecular mechanism and cancer therapeutics in one place. With chapters from experts in their respective fields, chapters cover molecular mechanisms, etiology, prognosis, detection, and treatment of cancer. Emphasis has been given to the intricate mechanism behind the deregulation of cell division, disruption of cell cycle check points, mutation in oncogenes and tumor suppressor genes, apoptosis, and erratic cell signaling. The book discusses in detail topics such as angiogenesis and tumor microenvironment, which are increasingly receiving attention, especially in the field of neoplastic vascularization and metastasis. The book also includes chapters detailing the current understanding and the future perspective of cancer stem cells.

Download or read book A Study of Breast Cancer Heterogeneity and Molecular Mechanisms of Metastasis written by Daniel Patrick Hollern and published by . This book was released on 2015 with total page 311 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Chemical and Molecular Approach to Tumor Metastases written by Gianni Sava and published by MDPI. This book was released on 2018-07-05 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "Chemical and Molecular Approach to Tumor Metastases" that was published in IJMS