Engineered Autologous Stromal Cells for the Delivery of Kringle 5, a Potent Endothelial Cell Specific Inhibitor for Anti-Angiogenic Breast Cancer Therapy PDF Download
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Languages : en
Pages : 27
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Book Description
The plasminogen kringle 5 (K5) domain - which is distinct from angiostatin - possesses potent anti-angiogenic properties on its own which can be exploited in cancer therapy. We have previously shown that K5 suppresses cancer growth in tumor xenograft models, its modulation of inflammation in experimental mice with intact immune systems is unknown. To determine whether K5 possesses immune proinflammatory properties, we investigated the effects of K5 in an immune competent model of breast cancer and observed that tumor rejection is substantially reduced in NOD-SCID and BALB/c nude when compared to wild-type BALB/c mice, suggesting an important role for T-lymphoid cells in the anti-tumor effect of K5. Tumor explant analysis demonstrates that K5 enhances tumor recruitment of CD3+ lymphoid cells, in particular the NKT phenotype. We also observed a significant decrease in tumor-associated microvessel length and density consistent with anti-angiogenic activity. Histological analysis of K5 tumors also revealed a robust neutrophilic infiltrate, which may be explained by the neutrophil chemotactic activity of K5 as well as its ability to promote CD64 upregulation within the CD11b+ adhesive neutrophil population. In sum, our findings confirm that the K5 protein acts as a potent angiostatic agent and possesses a novel proinflammatory role via its ability to recruit tumor-associated neutrophils and NKT-lymphocytes, leading to a potent anti-tumor response.
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Publisher:
ISBN:
Category :
Languages : en
Pages : 27
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Book Description
The plasminogen kringle 5 (K5) domain - which is distinct from angiostatin - possesses potent anti-angiogenic properties on its own which can be exploited in cancer therapy. We have previously shown that K5 suppresses cancer growth in tumor xenograft models, its modulation of inflammation in experimental mice with intact immune systems is unknown. To determine whether K5 possesses immune proinflammatory properties, we investigated the effects of K5 in an immune competent model of breast cancer and observed that tumor rejection is substantially reduced in NOD-SCID and BALB/c nude when compared to wild-type BALB/c mice, suggesting an important role for T-lymphoid cells in the anti-tumor effect of K5. Tumor explant analysis demonstrates that K5 enhances tumor recruitment of CD3+ lymphoid cells, in particular the NKT phenotype. We also observed a significant decrease in tumor-associated microvessel length and density consistent with anti-angiogenic activity. Histological analysis of K5 tumors also revealed a robust neutrophilic infiltrate, which may be explained by the neutrophil chemotactic activity of K5 as well as its ability to promote CD64 upregulation within the CD11b+ adhesive neutrophil population. In sum, our findings confirm that the K5 protein acts as a potent angiostatic agent and possesses a novel proinflammatory role via its ability to recruit tumor-associated neutrophils and NKT-lymphocytes, leading to a potent anti-tumor response.
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Category :
Languages : en
Pages : 52
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Book Description
Cancer growth and spread depends on the orchestrated proliferation of tumor-associated blood supply. Cancer cells release signals that instruct the body to build new blood vessels, angiogenesis, required to feed the tumor as it increases in size. Pharmacological agents, i.e. proteins and derivatives, that interfere with angiogenesis, in cancer bearing mice, stop cancer growth and lead to its regression. Animal modeling has revealed that repeated administration of large amounts of such antiangiogenic proteins is required for anti- cancer effect. This may be logistically difficult to achieve in larger beings such as humans. A remedy to this problem would involve a combined cell and gene therapy approach. We propose that normal tissue such as marrow stromal cells (MSCs) can be harvested from patients, genetically engineered, and subsequently returned to the patient as an implant releasing on a continuous basis therapeutic proteins that interfere with cancer growth and spread. We have already developed and published most of the key components required to develop this novel therapeutic modality, such as vectors, MSCs, and matrices. Also thus far, we have shown significant decrease in tumor progression over time with Interleukin-l2-secreting MSCs in the 4T1 mouse model of breast cancer and ascertained reproducibility of these results.
Author: Ravi Salgia
Publisher: Springer
ISBN: 3030178323
Category : Medical
Languages : en
Pages : 238
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Book Description
This book contextualizes translational research and provides an up to date progress report on therapies that are currently being targeted in lung cancer. It is now well established that there is tremendous heterogeneity among cancer cells both at the inter- and intra-tumoral level. Further, a growing body of work highlights the importance of targeted therapies and personalized medicine in treating cancer patients. In contrast to conventional therapies that are typically administered to the average patient regardless of the patient’s genotype, targeted therapies are tailored to patients with specific traits. Nonetheless, such genetic changes can be disease-specific and/or target specific; thus, the book addresses these issues manifested in the somatically acquired genetic changes of the targeted gene. Each chapter is written by a leading medical oncologist who specializes in thoracic oncology and is devoted to a particular target in a specific indication. Contributors provide an in-depth review of the literature covering the mechanisms underlying signaling, potential cross talk between the target and downstream signaling, and potential emergence of drug resistance.
Author: Padma V. Devarajan
Publisher: Springer Nature
ISBN: 3030291685
Category : Medical
Languages : en
Pages : 560
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Book Description
This book elaborates on drug delivery targeting via intracellular delivery, specifically through the Receptor Mediated Endocytosis (RME) approach, due to the involvement of cellular receptors in various grave diseases. Targeted delivery relies on two basic approaches, passive and active targeting. While passive targeting approaches have shown great promise, the improved selectivity achieved with active targeting approaches has resulted in significantly higher efficacy. Interestingly there are numerous strategies for active targeting, many of which are already highlighted in , Targeted Drug Delivery: Concepts and Applications. Nevertheless an exciting and practical strategy for active targeting, which could enable high intracellular delivery, is through exploitation of RME. Cells in the body express receptors to enable various physiological and biochemical processes. As a result, many of these receptors are overexpressed in pathological conditions, or newer receptors expressed due to defective cellular functioning. RME is based on exploitation of such receptors to achieve intracellular delivery. While targeted delivery can have manifold applications, in this book we focus on two major and challenging therapeutic areas; i) Cancer and ii) Infectious Diseases. Targeted Intracellular Drug Delivery by Receptor Medicated Endocytosis discusses the major receptors that are useful for targeted delivery for these afflictions. A major section of this book is dedicated to details regarding their occurrence and location, the recognition domain of the receptor, structure activity relationship of substrate /ligand for selective binding, ligands explored, antagonists for ligand binding and relevance of these aspects for therapy of cancer and infectious diseases. These facets are elucidated with the help of specific examples from academic research and also emphasize commercial products, wherever relevant. In vitro cellular models relied on for assessing receptor mediated cellular targeting and in vivo models depicting clinical efficacy are focused on in a separate section. Finally, we briefly discuss the regulatory and toxicity issues that may be associated specifically with the RME approach of intracellular drug delivery.
Author: Antonio Llombart-Bosch
Publisher: Springer Science & Business Media
ISBN: 1461500818
Category : Medical
Languages : en
Pages : 290
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Book Description
Given the latest advances in cancer research, which includes basic research and its derived diagnostic, clinical, and therapeutic applications, the book New Trends in Cancer for the 21st Century is written by individuals such as molecular biologists, whose tasks are to decipher, after sequencing the human genome, those new genes and pathways involved in the carcinogenesis process; clinical and molecular pathologists, who apply these discoveries for the molecular diagnosis and characterization of the tumor; and clinical oncologists, who treat patients. Pharmacogenetics introduces new perspectives in the translational fields with the design of drugs against specific targets, which at this moment are in clinical trials phases. This book achieves a state of the art in every field of cancer research and discusses the new perspectives that will open the future for cancer treatment (basic research, new technologies, new drugs, therapies...). For this reason, the book is intended for pathologists, clinicians, and biologists, as well as fellows and students of physiology and medicine.
Author: Harvey I. Pass
Publisher: Springer Science & Business Media
ISBN: 0387282742
Category : Medical
Languages : en
Pages : 862
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Book Description
Malignant Mesothelioma brings together the most current diagnostic criteria and treatment plans from the world’s leading experts on this rare but devastating cancer. The first edition was a critical and commercial success and this revision builds on that reputation. The editors have brought together the world’s leading experts to fully explore the latest scientific breakthroughs in carcinogenesis, immunotherapy, potential vaccination strategies, and gene therapy. The clinical aspects of the book are equally strong, with thorough discussion of epidemiology, etiology, different clinical presentations, imaging (including interventional pulmonology), treatment of benign disease, strategies for multimodality treatment of malignant disease. Editors: Harvey I. Pass, M.D, Chief, Thoracic Surgery, New York University, New York, NY; Nicholas Vogelzang, M.D, Director, Nevada Cancer Institute, Las Vegas, NV; University of Chicago, Michele Carbone, M.D., Ph.D, Researcher and Director, Thoracic Oncology Program, Cancer Research Center of Hawaii, Honolulu, HI; and Anne S. Tsao, M.D, Department of Thoracic/Head & Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX.
Author: Giuseppe Orlando
Publisher: Academic Press
ISBN: 012398520X
Category : Science
Languages : en
Pages : 1050
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Book Description
Regenerative Medicine Applications in Organ Transplantation illustrates exactly how these two fields are coming together and can benefit one another. It discusses technologies being developed, methods being implemented, and which of these are the most promising. The text encompasses tissue engineering, biomaterial sciences, stem cell biology, and developmental biology, all from a transplant perspective. Organ systems considered include liver, renal, intestinal, pancreatic, and more. Leaders from both fields have contributed chapters, clearly illustrating that regenerative medicine and solid organ transplantation speak the same language and that both aim for similar medical outcomes. The overall theme of the book is to provide insight into the synergy between organ transplantation and regenerative medicine. Recent groundbreaking achievements in regenerative medicine have received unprecedented coverage by the media, fueling interest and enthusiasm in transplant clinicians and researchers. Regenerative medicine is changing the premise of solid organ transplantation, requiring transplantation investigators to become familiar with regenerative medicine investigations that can be extremely relevant to their work. Similarly, regenerative medicine investigators need to be aware of the needs of the transplant field to bring these two fields together for greater results. - Bridges the gap between regenerative medicine and solid organ transplantation and highlights reasons for collaboration - Explains the importance and future potential of regenerative medicine to the transplant community - Illustrates to regenerative medicine investigators the needs of the transplant discipline to drive and guide investigations in the most promising directions
Author: Derek J. Chadwick
Publisher: John Wiley & Sons
ISBN: 0470319429
Category : Science
Languages : en
Pages : 260
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Book Description
The formation of blood vessels is an essential aspect of embryogenesis in vertebrates. It is a central feature of numerous post-embryonic processes, including tissue and organ growth and regeneration. It is also part of the pathology of tumour formation and certain inflammatory conditions. In recent years, comprehension of the molecular genetics of blood vessel formation has progressed enormously and studies in vertebrate model systems, especially the mouse and the zebrafish, have identified a common set of molecules and processes that are conserved throughout vertebrate embryogenesis while, in addition, highlighting aspects that may differ between different animal groups. The discovery in the past decade of the crucial role of new blood vessel formation for the development of cancers has generated great interest in angiogenesis (the formation of new blood vessels from pre-existing ones), with its major implications for potential cancer-control strategies. In addition, there are numerous situations where therapeutic treatments either require or would be assisted by vasculogenesis (the de novo formation of blood vessels). In particular, post-stroke therapies could include treatments that stimulate neovascularization of the affected tissues. The development of such treatments, however, requires thoroughly understanding the developmental properties of endothelial cells and the basic biology of blood vessel formation. While there are many books on angiogenesis, this unique book focuses on exactly this basic biology and explores blood vessel formation in connection with tissue development in a range of animal models. It includes detailed discussions of relevant cell biology, genetics and embryogenesis of blood vessel formation and presents insights into the cross-talk between developing blood vessels and other tissues. With contributions from vascular biologists, cell biologists and developmental biologists, a comprehensive and highly interdisciplinary volume is the outcome.
Author: Daan J. A. Crommelin
Publisher: CRC Press
ISBN: 9780415285018
Category : Medical
Languages : en
Pages : 456
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Book Description
The field of pharmaceutical biotechnology is evolving rapidly. A whole new arsenal of protein pharmaceuticals is being produced by recombinant techniques for cancer, viral infections, cardiovascular and hereditary disorders, and other diseases. In addition, scientists are confronted with new technologies such as polymerase chain reactions, combinatorial chemistry and gene therapy. This introductory textbook provides extensive coverage of both the basic science and the applications of biotechnology-produced pharmaceuticals, with special emphasis on their clinical use. Pharmaceutical Biotechnology serves as a complete one-stop source for undergraduate pharmacists, and it is valuable for researchers and professionals in the pharmaceutical industry as well.
Author: Yiyun Cheng
Publisher: Springer
ISBN: 3319778668
Category : Technology & Engineering
Languages : en
Pages : 361
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Book Description
The series Topics in Current Chemistry Collections presents critical reviews from the journal Topics in Current Chemistry organized in topical volumes. The scope of coverage is all areas of chemical science including the interfaces with related disciplines such as biology, medicine and materials science. The goal of each thematic volume is to give the non-specialist reader, whether in academia or industry, a comprehensive insight into an area where new research is emerging which is of interest to a larger scientific audience. Each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the field. The chapter "Polymeric Nanoparticle-Mediated Gene Delivery for Lung Cancer Treatment" is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
