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Author: Eleonora Patsenker
Publisher: Humana
ISBN: 9781493992478
Category : Medical
Languages : en
Pages : 226
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Book Description
This volume collects a variety of techniques and methodologies developed to facilitate research on integrin biology and to identify ideal targets and approaches for the treatment of multiple organ diseases, with a focus on cancer in particular. The chapters consecutively describe the tools for structural analysis, identification and detection of integrins as biomarkers, and include thorough laboratory and clinically-related methods on different strategies for generation, synthesis and evaluation of probes, carriers, peptides or small particles for integrin targeting, imaging, and drug delivery. As part of the Methods in Pharmacology and Toxicology series, this book contains the practical details that are invaluable in the laboratory. Authoritative and advantageous, Integrin Targeting Systems for Tumor Diagnosis and Therapy serves readers from a wide spectrum, including researchers and students seeking an overview of existing developments, as well as leading professionals aiming to become more familiar with integrin-related innovative technologies in cancer research.
Author: Eleonora Patsenker
Publisher: Humana
ISBN: 9781493992478
Category : Medical
Languages : en
Pages : 226
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Book Description
This volume collects a variety of techniques and methodologies developed to facilitate research on integrin biology and to identify ideal targets and approaches for the treatment of multiple organ diseases, with a focus on cancer in particular. The chapters consecutively describe the tools for structural analysis, identification and detection of integrins as biomarkers, and include thorough laboratory and clinically-related methods on different strategies for generation, synthesis and evaluation of probes, carriers, peptides or small particles for integrin targeting, imaging, and drug delivery. As part of the Methods in Pharmacology and Toxicology series, this book contains the practical details that are invaluable in the laboratory. Authoritative and advantageous, Integrin Targeting Systems for Tumor Diagnosis and Therapy serves readers from a wide spectrum, including researchers and students seeking an overview of existing developments, as well as leading professionals aiming to become more familiar with integrin-related innovative technologies in cancer research.
Author: Byron Hua Kwan
Publisher:
ISBN:
Category :
Languages : en
Pages : 160
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Book Description
Integrins are a family of heterodimeric cell surface receptors that are functionally important for cell adhesion, migration and proliferation. Certain integrins, especially those that are known to recognize the arginine-glycine-aspartate (RGD) motif, are heavily overexpressed in many cancers relative to healthy tissue, making them attractive targets for therapeutic intervention. However, prior attempts to antagonize these integrins as a cancer therapy have all failed in the clinic. In this thesis, we instead exploit integrins as a target tumor antigen in the context of immunotherapy. The engineered cysteine knot peptide, 2.5F, is highly crossreactive and capable of recognizing multiple RGD-binding integrins. Our initial attempts to utilize this binder as a targeting moiety for delivering IL-2 as an immunocytokine failed. Mathematical modeling results indicated that immunocytokines, unless adhering to specific design criteria, are unlikely to benefit from targeting and may actually exhibit limited efficacy. Therefore, we "deconstructed" this immunocytokine into its functional parts: extended half-life IL-2 and 2.5F-Fc, the antibody-like construct directed against RGD-binding integrins. This combination immunotherapeutic approach was able to synergistically control tumor growth in three syngeneic murine models of cancer, including durable cures and development of immunological memory. Contrary to prior attempts at integrin-targeting, the mechanism of action was independent of functional integrin antagonism, including effects on angiogenesis and tumor proliferation. In fact, efficacy of this therapy depended solely upon the adaptive and innate arms of immunity, specifically CD8+ T cells, macrophages, and dendritic cells. Furthermore, checkpoint blockade, the gold standard for immunotherapy to date, can further enhance the efficacy of this therapeutic approach. This signifies that the combination of IL-2 and 2.5F-Fc exerts a distinct, yet complementary immune response that opens the door for clinical translation.
![Development of Doxorubicin-E-[c(RGDfK)2] Delivery Systems for Integrin-targeted Cancer Therapy PDF](https://books.google.com/books/content/images/frontcover/ydWqnQAACAAJ?fife=w80-h100)
Author: Dina Polyak
Publisher:
ISBN:
Category :
Languages : en
Pages : 52
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Book Description
![Bone-induced Expression of Tumoral Integrin [beta]3 Enables Targeted Nanotherapy of Breast Cancer Metastases PDF](https://books.google.com/books/content/images/frontcover/vDm2uQEACAAJ?fife=w80-h100)
Author: Michael H. Ross (Molecular cell biologist)
Publisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages : 151
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Book Description
Breast cancer is the most common cancer for women worldwide, representing approximately 25% of all new cancer cases in this population. While early detection and removal of breast cancer still confined to the primary site results in a good prognosis, approximately one- third of patients will develop distant metastases. In these patients, overall survival is markedly reduced. Of the common sites for breast cancer metastasis, the skeletal system is the most frequent. Treating breast cancer bone metastases has proven particularly difficult for several reasons, such as dissemination of metastases throughout the skeleton, poor drug localization to sites of interest, a lack of tumor-specific targets expressed across breast cancer subtypes, and the chemo-protective nature of the bone microenvironment. This dissertation is focused on investigating a potential tumor-target expressed on breast cancer bone metastases, and to improve drug treatment efficacy against tumor cells in the bone microenvironment. Integrins are heterodimeric cell surface receptors, composed of an [alpha] and [beta] subunit from a large family of selectively-compatible integrin subunits. As a heterodimeric complex, integrins can bind to components of the extracellular matrix or to other cells. One particular integrin complex, integrin [alpha]v[beta]3, is composed of the tightly regulated integrin subunit [beta]3 and the more widely expressed [alpha]v subunit. I examined the expression of integrin [beta]3 on primary breast cancer as compared to metastases in murine cancer models, and observed that integrin expression is significantly elevated on bone metastases as compared to the primary tumors or visceral metastases. In addition, I evaluated tumor-associated integrin [beta]3 expression on a tissue microarray (TMA) composed of primary breast cancer and patient-matched bone metastatic tissue from 42 patients. Across nearly all patients, tumor-associated integrin [beta]3 expression was significantly elevated on bone metastases as compared to the primary tumor. For the first time, I demonstrate that tumor-associated integrin [beta]3 is elevated on bone metastases across all breast cancer subtypes, supporting the translational potential of targeting integrin [beta]3 in breast cancer patients with bone metastases. Integrin [beta]3 was weakly expressed on tumor cells in vitro and on tumor cells in the primary mammary fat pad (MFP). Additional analysis demonstrated that integrin [beta]3 on circulating tumor cells is dispensable for strong expression of integrin [beta]3 on subsequent bone metastases, suggested that integrin [beta]3 may be induced within the bone microenvironment. I identified transforming growth factor beta (TGF-[beta]) to be a potent inducer of integrin [beta]3 in vitro, and further demonstrate canonical TGF-[beta] signaling through the SMAD2 and SMAD3 (SMAD2/3) pathway is responsible for breast cancer upregulation of integrin [beta]3 induction on bone metastases, both in vitro and in vivo. Utilizing this information, I sought to evaluate the targeting potential of nanotherapy coated with a targeting ligand specific for integrin [alpha]v[beta]3. Nanotherapy has the potential to increase therapeutic efficacy and reduce toxicity versus traditional chemotherapies by enhancing drug delivery to specific targets of interest. I explored the localization potential of two nanoparticles with significantly different sizes: polysorbate (tween) 80 micelle nanoparticles (MPs, ~12.5 nm) or perfluorocarbon (PFC) nanoparticles (~250 nm). The smaller integrin [alpha]v[beta]3- targeted micelle nanoparticle ([alpha]v[beta]3-MP) could more effectively penetrate breast cancer bone metastases than larger integrin [alpha]v[beta]3-targeted PFC nanoparticles ([alpha]v[beta]3-PFCs). With these observations, I evaluated whether [alpha]v[beta]3-MP-mediated drug delivery could more effectively attenuate bone metastatic tumor burden and bone destruction than free drug delivery. Using the chemotherapeutic agent docetaxel (DTX), a potent microtubule inhibitor that is a first-line therapy for metastatic breast cancer, I observe that DTX is only weakly tumor- suppressive in our mouse model of breast cancer metastases. However, treating mice bearing breast cancer metastases with [alpha]v[beta]3-MP-delivery of a docetaxel-prodrug (DTX-PD) significantly reduced bone tumor burden and bone destruction, and with less hepatotoxicity. I observed a significant decrease in bone-residing tumor cell proliferation in mice treated with [alpha]v[beta]3-MP- delivery of DTX-PD, without overt osteoclast killing or inhibition of osteoclast formation. Together, these results provide support that nanotherapy-mediated attenuation of bone metastases and bone destruction occurs through enhanced drug efficacy against breast cancer cells within the bone. In this Dissertation, Chapter 1 will provide an overview of breast cancer, bone metastases, integrins, and the therapeutic potential of nanotherapy. In Chapter 2, my work on the expression and physiologic regulation of integrin [beta]3 on breast cancer during metastases will be explored. In Chapter 3, the role of the cytokine TGF-[beta] in regulating tumoral expression of integrin [beta]3 will be discussed. And in Chapter 4, I discuss the use of integrin [alpha]v[beta]3-targeted nanotherapy directed against breast cancer metastases. Collectively, I provide evidence that chemotherapeutic efficacy against breast cancer cells within bone can be enhanced by exploiting the expression of tumoral integrin [beta]3 at that metastatic site.
Author: Michel Pagé
Publisher: PennWell Corporation
ISBN: 9780896039193
Category : Medical
Languages : en
Pages : 478
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Book Description
In Tumor Targeting in Cancer Therapy, Dr. Michel Pagé and a panel of authoritative experts from the drug industry, clinics, and academia introduce the principles and techniques of tumor targeting and critically survey their applications from laboratory to bedside. By concisely synthesizing the many technical details, the authors illuminate this innovative technique, ranging from the fundamentals of drug targeting and in vivo and in vitro experimentation, to such emerging therapeutic uses as radioimmunotherapy, radioimmunodetection, therapy with cytotoxic antibodies, immunotoxins, enzyme prodrug immunotherapy, and immunotherapeutics with fusion proteins. There are also reviews of targeting tumors with radioimmunoconjugates, photodynamic therapy, and magnetic drugs, as well as discussions of the internalization of antibodies, bioconjugation and biodistribution, the use of cytotoxic drugs, and the pros and cons of targeting by antibody or ligand.
Author: Erkki Ruoslahti
Publisher: Academic Press
ISBN:
Category : Medical
Languages : en
Pages : 680
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Book Description
This publication presents a collection of essays that reflect current research and technical advances in extracellular matrix field, which has undergone remarkable expansion since publication of Volume 82 of 'Methods in Enzymology' in 1982.
Author: National Academy of Engineering
Publisher: National Academies Press
ISBN: 030945039X
Category : Technology & Engineering
Languages : en
Pages : 145
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Book Description
This volume presents papers on the topics covered at the National Academy of Engineering's 2016 US Frontiers of Engineering Symposium. Every year the symposium brings together 100 outstanding young leaders in engineering to share their cutting-edge research and innovations in selected areas. The 2016 symposium was held September 19-21 at the Arnold and Mabel Beckman Center in Irvine, California. The intent of this book is to convey the excitement of this unique meeting and to highlight innovative developments in engineering research and technical work.
Author: Ali Demir Sezer
Publisher: BoD – Books on Demand
ISBN: 9535122479
Category : Medical
Languages : en
Pages : 400
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Book Description
This contribution book collects reviews and original articles from eminent experts working in the interdisciplinary arena of novel drug delivery systems and their uses. From their direct and recent experience, the readers can achieve a wide vision on the new and ongoing potentialities of different smart drug delivery systems. Since the advent of analytical techniques and capabilities to measure particle sizes in nanometer ranges, there has been tremendous interest in the use of nanoparticles for more efficient methods of drug delivery. On the other hand, this reference discusses advances in the design, optimization, and adaptation of gene delivery systems for the treatment of cancer, cardiovascular, diabetic, genetic, and infectious diseases, and considers assessment and review procedures involved in the development of gene-based pharmaceuticals.
Author: Ali Demir Sezer
Publisher: BoD – Books on Demand
ISBN: 9535108107
Category : Medical
Languages : en
Pages : 516
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Book Description
This contribution book collects reviews and original articles from eminent experts working in the interdisciplinary arena of novel drug delivery systems and their uses. From their direct and recent experience, the readers can achieve a wide vision on the new and ongoing potentialities of different drug delivery systems. Since the advent of analytical techniques and capabilities to measure particle sizes in nanometer ranges, there has been tremendous interest in the use of nanoparticles for more efficient methods of drug delivery. On the other hand, this reference discusses advances in the design, optimization, and adaptation of gene delivery systems for the treatment of cancer, cardiovascular, pulmonary, genetic, and infectious diseases, and considers assessment and review procedures involved in the development of gene-based pharmaceuticals.
Author: Letícia Rangel
Publisher:
ISBN: 9789535171409
Category :
Languages : en
Pages : 630
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Book Description
Cancer Treatment: Conventional and Innovative Approaches is an attempt to integrate into a book volume the various aspects of cancer treatment, compiling comprehensive reviews written by an international team of experts in the field. The volume is presented in six sections: i) Section 1: Cancer treatment: Conventional and innovative pharmacological approaches; ii) Section 2: Combinatorial strategies to fight cancer: Surgery, radiotherapy, backytherapy, chemotherapy, and hyperthermia; iii) Section 3: The immunotherapy of cancer; iv) Section 4: Multidisciplinarity in cancer therapy: nutrition and beyond; v) Section 5: Supportive care for cancer patients; vi) Section 6: Perspectives in cancer biology and modeling. Ultimately, we hope this book can enlighten important issues involved in the management of cancer, summarizing the state-of-the-art knowledge regarding the disease control and treatment; thus, providing means to improve the overall care of patients that daily battle against this potentially lethal condition.
