Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 62
Get Book Here
Book Description
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.
Author: Dimitrios Kardamakis
Publisher: Springer Science & Business Media
ISBN: 1402098197
Category : Medical
Languages : en
Pages : 404
Get Book Here
Book Description
Bone Metastases: A Translational and Clinical Approach serves as both an introductory and reference book focusing on the field of metastatic bone disease. Featuring contributions from experts in the field, this volume: describes the molecular and cellular mechanisms involved in the formation of bone metastases, comments on the role of angiogenesis, presents the newer advances made in the understanding of the clinical picture and symptoms of patients, analyses the role of bone markers in research and clinical practice deals with all aspects of imaging modalities applied for the detection and evaluation of bone metastases. This volume also covers the use of radiotherapy, surgery and systemic treatments for the management of metastatic bone disease and new therapeutic approaches. Moreover it may also serve as a guide for the clinical and therapeutic management of patients with metastatic bone disease. Overall this volume presents a thorough overview of all aspects of metastatic bone disease and provides a comprehensive and concise information resource for medical researchers, oncologists, orthopaedic surgeons and clinicians.
Author: Qifeng Yang
Publisher: Frontiers Media SA
ISBN: 2889747298
Category : Medical
Languages : en
Pages : 274
Get Book Here
Book Description
Author: Gurmit Singh
Publisher: Springer Science & Business Media
ISBN: 1592598927
Category : Medical
Languages : en
Pages : 343
Get Book Here
Book Description
A state-of-the-art review of the molecular underpinnings of bone-seeking cancers, current treatment approaches for them, and future therapeutic strategies. The authors illuminate the role of various autocrine, paracrine, and immunological factors involved in the progression and establishment of bone metastases, highlighting the physiological processes that lead to bone degradation, pain, angiogenesis, and dysregulation of bone turnover. They also discuss the various strategies that appear to have promise and are currently deployed in treatment or are at the experimental stage.
Author: Aamir Ahmad
Publisher: Springer Science & Business Media
ISBN: 1461456479
Category : Medical
Languages : en
Pages : 415
Get Book Here
Book Description
This volume comprehensively covers recent prrogress in breast cancer research. In an effort to successfully treat breast cancer, it is imperative to a) fully understand the disease with all its heterogeneity, b) understand the factors that influence the metastasis of breast cancer to distant organs making it lethal and c) understand the underlying processes that lead to the phenomenon of drug-resistance making the disease particularly incurable. The book explores all of these issues, including the phenomenon of epithelial-mesenchymal-transition, cancer stem cells as well as microRNAs in an attempt to better understand the disease in connection to its heterogeneity/metastasis/drug-resistance as well as to propose novel signaling pathways for therapeutic intervention. The profiling of tumors to molecularly classify breast cancers is also investigated so that customized targeted therapies can be developed.
Author: Dianwen Song
Publisher: Frontiers Media SA
ISBN: 2889741834
Category : Medical
Languages : en
Pages : 164
Get Book Here
Book Description
Author: John P. Bilezikian
Publisher: Academic Press
ISBN: 0080568750
Category : Medical
Languages : en
Pages : 2074
Get Book Here
Book Description
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
Author: Bhavna Murali
Publisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages : 146
Get Book Here
Book Description
The tumor microenvironment plays a pivotal role in tumor progression, and there is mounting evidence for synergistic action between tumor cells and microenvironmental cells that help the former thrive and even metastasize to other organs. This dissertation is focused on investigating the potential of therapeutically targeting the microenvironment to reduce breast cancer metastases and chemotherapy-induced bone loss. In Chapter 2 we investigate the efficacy of p38MAPK/MK2 inhibitors in limiting breast cancer metastasis by targeting the stromal compartment. Chapter 3 is centered around identification of mechanisms that drive chemotherapy-induced bone loss and the potential role for chemotherapy-induced senescence in this bone loss.Tumor-associated stromal cells are notorious for secreting factors that have pro-tumorigenic capabilities. The stress kinase, p38MAPK, is known to regulate the expression of several of these tumor-promoting stromal factors that in fact, have been found in the stroma of breast cancer patients. Moreover, p38MAPK[alpha] is frequently upregulated in a variety of cancers including breast cancer, and its expression correlates with poor prognosis. In earlier work, we demonstrated that inhibition of p38MAPK resulted in attenuated primary tumor growth and this effect is through blocking secretion of stromal factors. This effect at the primary site, led us to investigate whether inhibition of p38MAPK[alpha] could reduce breast cancer metastases in a clinically relevant model. In this dissertation, we show that orally administered, small-molecule inhibitors of p38MAPK[alpha] and its downstream kinase, MK2, each limited outgrowth of metastatic breast cancer cells in the bone and visceral organs. We demonstrate that this effect is due to the inhibition of the p38MAPK[alpha] pathway within the stromal compartment. In addition, these inhibitors effectively inhibited tumor-associated and chemotherapy-induced bone loss, which represent significant comorbidities for cancer patients. We show that targeting the stromal p38MAPK-MK2 pathway limits metastatic breast cancer growth while preserving bone quality and extending survival.The second part of this dissertation focuses on investigating estrogen-independent mechanisms that drive bone loss following chemotherapy treatment. Patients who receive chemotherapy treatment experience significant loss in bone density. Chemotherapy is thought to lead to bone loss by inducing premature menopause, which subsequently results in estrogen loss. Given that estrogen plays an important role in bone homeostasis, the loss of ovarian function is thought to drive bone loss in women undergoing chemotherapy. While it is clear estrogen is important in bone homeostasis and its loss following chemotherapy contributes to bone loss, these observations do not fully explain why post-menopausal women, who have already undergone physiological ovarian failure, lose significant bone density following therapy. Further, therapy-induced bone loss is more rapid and severe than bone loss seen with aging or post-menopause. Together, these observations suggest that factors or mechanisms in addition to estrogen loss contribute to chemotherapy-induced bone loss. Given that chemotherapeutic agents robustly induce senescence in vitro and in vivo, we postulated that chemotherapy-induced senescence and SASP activation contributes to bone loss. We used a Doxorubicin-induced bone loss model in mice and observed that chemotherapy reduced bone volume significantly more than the classic OVX model of estrogen deficiency both in young (6-week old) and skeletally mature (16-week old) mice in C57BL/6 and FVB/NJ strains. To evaluate the role of senescence in chemotherapy-induced bone loss, we profiled the expression of several senescence-associated factors in bones devoid of marrow. We observed induction of senescence marker p16, and factors including IL-6 and Dkk1, in 6-week old mice at the early (48 hour post Doxorubicin) timepoint and 16-week old chemotherapy mice at the final (10 days post Doxorubicin) timepoint. However, the upregulation did not repeat in 16-week old mice, leaving some questions of inconsistencies that will be addressed in prospective studies. In line with our hypothesis, we treated mice with p38MAPK and MK2 inhibitors to block production of senescence-associated proresorptive factors and observed preservation of bone integrity in chemotherapy-treated mice. In conclusion, we established that there are estrogen-independent mechanisms involved in chemotherapy-induced bone loss. However, the contribution of senescence and the mechanism of bone preservation by p38i and MK2Pi requires further evaluation.Overall, targeting the microenvironment with the intent of disrupting the stromal-tumoral collaboration may be a viable therapeutic strategy to combat tumor progression and related pathologies that result from cancer treatments.
Author: Aamir Ahmad
Publisher: Springer Nature
ISBN: 3030203018
Category : Medical
Languages : en
Pages : 427
Get Book Here
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.
Author: Claude Jasmin
Publisher: John Wiley & Sons
ISBN: 0470011602
Category : Medical
Languages : en
Pages : 582
Get Book Here
Book Description
The epidemiological and clinical importance of bone metastases has long been recognised. For example, the incidence of bone metastases in breast and prostate cancers is 70%, whereas it is only 30 to 40% in metastatic lung cancer. In clinical terms, bone metastases have substantial negative effects on the patient's quality of life. Bone metastases have generally received insufficient attention because of the difficulty in quantifying them, which has left them outside the scope of therapeutic trials This textbook is the result of the remarkable progress made in the understanding of the molecular and cellular mechanisms involved in osteogenesis and osteolysis, and their development for therapeutic purposes. The treatment of malignant hypercalcaemia has also been revolutionised by the use of bisphosphonates. The Textbook of Bone Metastases presents a broad approach to recent progress in all fields related to bone metastases, ranging from epidemiology to the physiopathology of bone metastases and therapeutics. It provides a better understanding of recent advances and, more importantly, will give clinicians all the information needed to help them in the clinical and therapeutic management of patients with bone metastases.
