Characterizing the Roles of IL-11 and CD68 in Breast Cancer Bone Metastasis

Characterizing the Roles of IL-11 and CD68 in Breast Cancer Bone Metastasis PDF Author: McCoy Erin Mills
Publisher:
ISBN:
Category :
Languages : en
Pages : 106

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Book Description
The molecular mechanisms regulating the preferential metastasis of breast cancer to bone have not been fully elucidated, but it is hypothesized that local conditions in the bone create an environment conducive to colonization by breast cancer cells and that the breast cancer cells interact directly with cells in the bone. In this dissertation, two goals were pursued: (1) to explore breast cancer secreted interleukin (IL)-11's role on osteoclast function and (2) investigate the expression and potential role of CD68 in breast cancer adhesion to bone. Higher rates of bone metastasis occur in human breast cancer tumors expressing IL-11, a cytokine shown to promote osteoclast formation, but the specific mechanisms are controversial. I determined that breast cancer secreted IL-11 was unable to directly support osteoclast survival or formation in sub-optimal RANKL conditions but instead supports a population of osteoclast progenitors. These findings clarify IL-11's specific role in breast cancer bone metastasis, and future studies are warranted to address the therapeutic potential of IL-11 for treating and preventing breast cancer induced osteolysis. For the second aim, I examined breast cancer cell lines and found that CD68, a lysosomal associated membrane protein associated with breast cancer recurrence, is upregulated in breast cancer lines that have a high capacity to metastasize to bone. A fragment of CD68 was independently identified in a phage display assay to pan for bone adhesion molecules, suggesting CD68 may be involved in breast cancer bone metastasis by acting as a bone adhesion molecule. Expression of CD68 correlated with ability of breast cancer cell lines to adhere to bone, but more specific assays failed to reveal a direct role of CD68 in adhesion to bone. Future studies are needed to characterize CD68's exact role in breast cancer, but the discovery of breast cancer expression may have implications for the common use of CD68 as a macrophage marker, and may provide insight into CD68's correlation as a risk factor for breast cancer recurrence. These studies contribute to the foundation of work necessary for developing specific therapeutics by contributing to a better understanding of the mechanisms regulating breast cancer bone metastasis.

Characterizing the Roles of IL-11 and CD68 in Breast Cancer Bone Metastasis

Characterizing the Roles of IL-11 and CD68 in Breast Cancer Bone Metastasis PDF Author: McCoy Erin Mills
Publisher:
ISBN:
Category :
Languages : en
Pages : 106

Get Book Here

Book Description
The molecular mechanisms regulating the preferential metastasis of breast cancer to bone have not been fully elucidated, but it is hypothesized that local conditions in the bone create an environment conducive to colonization by breast cancer cells and that the breast cancer cells interact directly with cells in the bone. In this dissertation, two goals were pursued: (1) to explore breast cancer secreted interleukin (IL)-11's role on osteoclast function and (2) investigate the expression and potential role of CD68 in breast cancer adhesion to bone. Higher rates of bone metastasis occur in human breast cancer tumors expressing IL-11, a cytokine shown to promote osteoclast formation, but the specific mechanisms are controversial. I determined that breast cancer secreted IL-11 was unable to directly support osteoclast survival or formation in sub-optimal RANKL conditions but instead supports a population of osteoclast progenitors. These findings clarify IL-11's specific role in breast cancer bone metastasis, and future studies are warranted to address the therapeutic potential of IL-11 for treating and preventing breast cancer induced osteolysis. For the second aim, I examined breast cancer cell lines and found that CD68, a lysosomal associated membrane protein associated with breast cancer recurrence, is upregulated in breast cancer lines that have a high capacity to metastasize to bone. A fragment of CD68 was independently identified in a phage display assay to pan for bone adhesion molecules, suggesting CD68 may be involved in breast cancer bone metastasis by acting as a bone adhesion molecule. Expression of CD68 correlated with ability of breast cancer cell lines to adhere to bone, but more specific assays failed to reveal a direct role of CD68 in adhesion to bone. Future studies are needed to characterize CD68's exact role in breast cancer, but the discovery of breast cancer expression may have implications for the common use of CD68 as a macrophage marker, and may provide insight into CD68's correlation as a risk factor for breast cancer recurrence. These studies contribute to the foundation of work necessary for developing specific therapeutics by contributing to a better understanding of the mechanisms regulating breast cancer bone metastasis.

Breast Cancer Metastasis and Drug Resistance

Breast Cancer Metastasis and Drug Resistance PDF Author: Aamir Ahmad
Publisher: Springer Nature
ISBN: 3030203018
Category : Medical
Languages : en
Pages : 427

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Book Description
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.

Tertiary Lymphoid Structures

Tertiary Lymphoid Structures PDF Author: Marie-Caroline Dieu-Nosjean
Publisher: Humana Press
ISBN: 9781493987085
Category : Medical
Languages : en
Pages : 289

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Book Description
This volume explores the various methods used to study tertiary lymphoid structures (TLS) in pathological situations. Pre-clinical models are also discussed in detail to show how TLS structure, development, and maintenance can be targeted and studied in vivo. The chapters in this book cover topics such as humans and mice; strategies to quantify TLS in order to use it in stained tissue sections; classifying a gene signature form fixed and paraffin-embedded tissues; and development of murine inflammatory models to help look at TLS in the context of infection or malignancy. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Tertiary Lymphoid Structures: Methods and Protocols is a valuable resource that increases the reader’s knowledge on immune functions and how they will pave the way to future therapeutic applications.

Tumor Vascularization

Tumor Vascularization PDF Author: Domenico Ribatti
Publisher: Academic Press
ISBN: 0128194944
Category : Science
Languages : en
Pages : 198

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Book Description
Tumor Vascularization discusses the different types of growth of tumor blood vessels and their implications on research and healthcare. The book is divided into three parts: the first one, General Mechanisms, discusses different vessel growth mechanisms, such as sprouting angiogenesis, non-angiogenesis dependent growth, intussusceptive microvascular growth, vascular co-option and vasculogenic mimicry. The second and third parts, entitled Clinical Implications and Therapeutic Implications are dedicated to translating recent findings in this field to patient treatment and healthcare. This book is a valuable source for cancer researchers, oncologists, graduate students and members of the biomedical field who are interested in tumor progression and blood vessels. Explains new, non-orthodox concepts recently developed and related to the modality of growth of tumor blood vessels Provides information on the types of angiogenesis, non-angiogenesis dependent growth and vascular co-option, discussing both their similarities and differences Encompasses a discussion on clinical implications of tumor vascularization to translate research findings into treatment

Bone and Soft Tissue Pathology

Bone and Soft Tissue Pathology PDF Author: Andrew L. Folpe, MD
Publisher: Elsevier Health Sciences
ISBN: 0443066884
Category : Medical
Languages : en
Pages : 477

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Book Description
Bone and Soft Tissue Pathology: A Volume in the Diagnostic Pathology Series, by Andrew L. Folpe, MD and Carrie Y. Inwards, MD, packs today's most essential bone and soft tissue pathology know-how into a compact, high-yield format! The book's pragmatic, well-organized approach-complemented by abundant full-color, high-quality illustrations and at-a-glance tables-makes it easy to access the information you need to quickly and accurately identify pathology specimens. Best of all, Expert Consult functionality provides online access to the full text of the book, downloadable illustrations for your personal use, and more. The result is a practical, affordable reference for study and review as well as for everyday clinical practice. Includes access to the complete contents online, fully searchable, downloadable illustrations for your personal use, and more, allowing you to consult the text a quick, convenient manner. Reviews normal histology before examining abnormal findings, enabling you to conveniently compare their characteristics in one place at one time. Covers both neoplastic and non-neoplastic conditions of bone and soft tissue to equip you to meet a wide range of diagnostic challenges. Uses a consistent, user-friendly format to explore each entity's clinical features, pathologic features (gross and microscopic), ancillary studies, differential diagnoses, and prognostic and therapeutic considerations...making it easy to locate specific information on a particular entity. Features abundant boxes and tables throughout that enhance the presentation and accessibility of the material. Offers nearly 1,000 full-color, high-quality illustrations that demonstrate the key features of a wide variety of pathologic lesions to facilitate greater accuracy in identification of specimens. The Foundations in Diagnostic Pathology Series answers the call for fresh, affordable, and easy-to-use guidance. Each region-specific volume provides all of the most essential information on the pathologic entities encountered in practice. Series Editor: John R. Goldblum, MD, FACP, FASCP, FACG Your purchase entitles you to access the web site until the next edition is published, or until the current edition is no longer offered for sale by Elsevier, whichever occurs first. Elsevier reserves the right to offer a suitable replacement product (such as a downloadable or CD-ROM-based electronic version) should access to the web site be discontinued.

Hematopathology

Hematopathology PDF Author: Faramarz Naeim
Publisher: Academic Press
ISBN: 0080919480
Category : Science
Languages : en
Pages : 612

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Book Description
This comprehensive, full color hematopathology reference book emphasizes immunophenotpic features, cytogenetic studies, and diagnostic molecular aspects. Hematopathology begins with introductions to morphologic evaluation of the hematopoietic tissues and principles of immunophenotyping, cytogenetics and molecular studies followed by chapters dedicated to different types of hematologic disorders. Each chapter starts with a basic overview of hematopathlogy followed by a comprehensive review of immunophenotypic, cytogenetic and molecular findings. The text is balanced with large numbers of full color images, graphs, charts, and tables to assist the reader in understanding these highly technical issues. - Emphasizes the immunophenotypic features, cytogenetic studies, and diagnostic molecular aspects of hematology - Features hundreds of images, charts and tables for the identification of hematologic disorders not only based on histopathologic features, but also with the use of advanced accessory techniques

Cancer and IgE

Cancer and IgE PDF Author: Manuel L. Penichet
Publisher: Springer Science & Business Media
ISBN: 1607614510
Category : Medical
Languages : en
Pages : 290

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Book Description
Erika Jensen-Jarolim and Manuel L. Penichet 1. 1 Background Infectious diseases, being the major burden in the history of mankind worldwide th until the beginning of the 20 century, were important triggers in the understanding of immunological mechanisms. In contrast to infectious diseases, reports of all- gies and cancers were less common, but increased tremendously within the last century. Based on the US mortality data of the National Center for Health Statistics, Centers for Disease Control and Prevention 2009, a recent report from the American Cancer Society indicated that the number of cancer deaths increased approximately from 100,000 to 550,000 per year between 1930 and 2006, paralleling the increase of the total population during this period. Leading causes of death from cancer are lung and bronchus cancer, in men prostate cancer, and in women breast c- cer [1, 2]. Normalization to population size shows that the cancer death rate for most malignancies has been generally stable, although the mortality rate of certain malignancies, such as lung and bronchus cancer, has increased over the last 50 years [1-3]. In allergy, the situation is less clear, because for the time period around the turn of th the 19 century, only imprecise information is available. However, within the last 30 years the incidences of allergies has doubled not only in industrial countries, but in developing countries as well [4].

In Situ Molecular Pathology and Co-Expression Analyses

In Situ Molecular Pathology and Co-Expression Analyses PDF Author: Gerard J. Nuovo
Publisher: Academic Press
ISBN: 0124160018
Category : Science
Languages : en
Pages : 298

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Book Description
In Situ Molecular Pathology and Co-Expression Analyses explains, in easy-to-understand language, simplified ways of understanding and performing in situ hybridization and immunohistochemistry tests. The book also focuses on straightforward protocols used to simultaneously detect two or more proteins/nucleic acids within intact tissue by doing co-expression analyses. The fields of in situ hybridization and immunohistochemistry have expanded rapidly due to the use of computer-based analysis. To get the most out of these automated platforms, researchers and diagnostic biomedical investigators must have a solid understanding of the basics of in situ-based tests, protocols, and regimens for troubleshooting. Practicing molecular pathologists, clinical chemists, and toxicologists, as well as clinicians and researchers in training, will benefit from this book's clear presentation of protocols and theoretical framework. - Includes over 200 easy-to-follow experimental protocols - Features chapter-ending summaries of "Key Points to Remember" to bring beginners up to speed with any seasoned veteran in the field - Offers two chapters written by industry leaders in the fields of in situ hybridization, immunohistochemistry, and computer software for co-expression analyses

Leong's Manual of Diagnostic Antibodies for Immunohistology

Leong's Manual of Diagnostic Antibodies for Immunohistology PDF Author: Runjan Chetty
Publisher: Cambridge University Press
ISBN: 1316592065
Category : Medical
Languages : en
Pages : 525

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Book Description
Providing a unique A-Z guide to antibodies for immunohistology, this is an indispensable source for pathologists to ensure the correct application of immunohistochemistry in daily practice. Each entry includes commercial sources, clones, descriptions of stained proteins/epitopes, the full staining spectrum of normal and tumor tissues, staining pattern and cellular localization, the range of conditions of immunoreactivity, and pitfalls of the antibody's immunoprofile, giving pathologists a truly thorough quick-reference guide to sources, preparation and applications of specific antibodies. Appendices provide useful quick-reference tables of antibody panels for differential diagnoses, as well as summaries of diagnostic applications. Expanded from previous editions with over forty new entries, this handbook for diagnostic, therapeutic, prognostic and research applications of antibodies is an essential desktop book for practicing pathologists as well as researchers, residents and trainees.

Immune Surveillance

Immune Surveillance PDF Author: Richard T. Smith
Publisher: Elsevier
ISBN: 0323146260
Category : Nature
Languages : en
Pages : 553

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Book Description
Immune Surveillance deals with the issues regarding tumor immunology and surveillance, in which the central theme is all about the life span of the mammalian host that is depleted by the environment with mutagenic agents and solutions. The book is divided into six chapters. It includes discussions on the organization and modulation of cell membrane receptors, as well as the origin and expression of membrane antigens. It also covers the topics on the triggering mechanisms for and effector mechanisms activated by the cellular recognition. These topics analyze and evaluate alternatives for the recognition and destruction mechanisms in the knowledge of cell cooperation and requirements for immune recognition. A chapter provides discourse on a solution for the paradox of thriving tumors based on the demonstrable in vitro host immunity. Another discusses the generation of antibody diversity and the theory of self-tolerance. The last chapter explains the evaluation of the evidence for immune surveillance. This reference will be invaluable to those who specialize in immunology.