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Author: Fabrizio Marcucci Publisher: Frontiers E-books ISBN: 2889193500 Category : Cancer Languages : en Pages : 130
Book Description
The main scope of this topic is to give an update on pharmacologic and non-pharmacologic approaches to enhance uptake and penetration of cancer drugs into tumors. Inadequate accumulation of drugs in tumors has emerged over the last decade as one of the main problems underlying therapeutic failure and drug resistance in the treatment of cancer. Insufficient drug uptake and penetration is causally related to the abnormal tumor architecture. Thus, poor vascularization, increased resistance to blood flow and impaired blood supply represent a first obstacle to the delivery of antitumor drugs to tumor tissue. Decreased or even inverted transvascular pressure gradients compromise convective delivery of drugs. Eventually, an abnormal extracellular matrix offers increased frictional resistance to tumor drug penetration. Abnormal tumor architecture also changes the biology of tumor cells, which contributes to drug resistance through several different mechanisms. The variability in vessel location and structure can make many areas of the tumor hypoxic, which causes the tumor cells to become quiescent and thereby resistant to many antitumor drugs. In addition, the abnormally long distance of part of the tumor cell population from blood vessels provides a challenge to delivering cancer drugs to these cells. We have recently proposed additional mechanisms of tumor drug resistance, which are also related to abnormal tumor architecture. First, increased interstitial fluid pressure can by itself induce drug resistance through the induction of resistance-promoting paracrine factors. Second, the interaction of drug molecules with vessel- proximal tumor cell layers may also induce the release of these factors, which can spread throughout the cancer, and induce drug resistance in tumor cells distant from blood vessels. As can be seen, abnormal tumor architecture, inadequate drug accumulation and tumor drug resistance are tightly linked phenomena, suggesting the need to normalize the tumor architecture, including blood vessels, and/or increase the accumulation of cancer drugs in tumors in order to increase therapeutic effects. Indeed, several classes of drugs (that we refer to as promoter drugs) have been described, that promote tumor uptake and penetration of antitumor drugs, including those that are vasoactive, modify the barrier function of tumor vessels, debulk tumor cells, and overcome intercellular and stromal barriers. In addition, also non-pharmacologic approaches have been described that enhance tumor accumulation of effector drugs (e.g. convection-enhanced delivery, hyperthermia, etc.). Some drugs that have already received regulatory approval (e.g. the anti-VEGF antibody bevacizumab) exert antitumor effects at least in part through normalization of the tumor vasculature and enhancement of the accumulation of effector drugs. Other drugs, acting through different mechanisms of action, are now in clinical development (e.g. NGR-TNF in phase II/III studies) and others are about to enter clinical investigation (e.g. JO-1).
Author: Fabrizio Marcucci Publisher: Frontiers E-books ISBN: 2889193500 Category : Cancer Languages : en Pages : 130
Book Description
The main scope of this topic is to give an update on pharmacologic and non-pharmacologic approaches to enhance uptake and penetration of cancer drugs into tumors. Inadequate accumulation of drugs in tumors has emerged over the last decade as one of the main problems underlying therapeutic failure and drug resistance in the treatment of cancer. Insufficient drug uptake and penetration is causally related to the abnormal tumor architecture. Thus, poor vascularization, increased resistance to blood flow and impaired blood supply represent a first obstacle to the delivery of antitumor drugs to tumor tissue. Decreased or even inverted transvascular pressure gradients compromise convective delivery of drugs. Eventually, an abnormal extracellular matrix offers increased frictional resistance to tumor drug penetration. Abnormal tumor architecture also changes the biology of tumor cells, which contributes to drug resistance through several different mechanisms. The variability in vessel location and structure can make many areas of the tumor hypoxic, which causes the tumor cells to become quiescent and thereby resistant to many antitumor drugs. In addition, the abnormally long distance of part of the tumor cell population from blood vessels provides a challenge to delivering cancer drugs to these cells. We have recently proposed additional mechanisms of tumor drug resistance, which are also related to abnormal tumor architecture. First, increased interstitial fluid pressure can by itself induce drug resistance through the induction of resistance-promoting paracrine factors. Second, the interaction of drug molecules with vessel- proximal tumor cell layers may also induce the release of these factors, which can spread throughout the cancer, and induce drug resistance in tumor cells distant from blood vessels. As can be seen, abnormal tumor architecture, inadequate drug accumulation and tumor drug resistance are tightly linked phenomena, suggesting the need to normalize the tumor architecture, including blood vessels, and/or increase the accumulation of cancer drugs in tumors in order to increase therapeutic effects. Indeed, several classes of drugs (that we refer to as promoter drugs) have been described, that promote tumor uptake and penetration of antitumor drugs, including those that are vasoactive, modify the barrier function of tumor vessels, debulk tumor cells, and overcome intercellular and stromal barriers. In addition, also non-pharmacologic approaches have been described that enhance tumor accumulation of effector drugs (e.g. convection-enhanced delivery, hyperthermia, etc.). Some drugs that have already received regulatory approval (e.g. the anti-VEGF antibody bevacizumab) exert antitumor effects at least in part through normalization of the tumor vasculature and enhancement of the accumulation of effector drugs. Other drugs, acting through different mechanisms of action, are now in clinical development (e.g. NGR-TNF in phase II/III studies) and others are about to enter clinical investigation (e.g. JO-1).
Author: Yasuhiro Matsumura Publisher: Springer Nature ISBN: 4431568808 Category : Medical Languages : en Pages : 325
Book Description
This book proposes the importance of new systems of drug design and delivery based on cancer pathophysiology in addition to cancer molecular and cellular biology. The current studies based on molecular and cellular biology while ignoring pathophysiology and pharmacology may be leading the development of antitumor drugs in the wrong direction and wasting a lot of money. Although there have been numerous reports of genetic and phenotypic changes in tumors, a large body of pathological and clinical evidence supports the conclusion that there are no pivotal changes in tumor cells that distinguish them consistently and reliably from normal dividing cells. Unlike using antibiotics against bacterial infection, therefore, anticancer agents (ACAs) need to be delivered selectively to tumor tissues and should be kept there long enough to reproduce the concentrations they reach in the Petri dish, which is a closed space where the cytocidal effects of any anticancer agents (ACAs) including molecular targeting agents are very strong. In the body, however, administered ACAs are cleared with the passage of time. Furthermore, most human cancers possess abundant stroma that hinders the penetration of drugs into the tumor microenvironment. Therefore, to overcome these difficulties, novel drug delivery systems have been designed, such as nanoparticles and ACA conjugated antibodies to stromal components and to cancer cell surface antigens. These advances are described in this book after the first section, which describes core features of the pathophysiology of the cancer microenvironment, on which these new developments are based.
Author: Pierre Savagner Publisher: Springer Science & Business Media ISBN: 0387286713 Category : Science Languages : en Pages : 341
Book Description
Epithelial phenotype is a dynamic stage of differentiation that can be modulated during several physiological or pathological events. The rapid conversion to a mesenchymal-like phenotype is called an epithelial-mesenchymal transition (EMT). The Rise and Fall of Epithelial Phenotype is the first book to comprehensively introduce the concept of EMT. The first part of this volume describes main examples and models and explains their physiological relevance. These examples include hydra morphogenesis, gastrulation in mouse, drosophila and sea urchin, as well as neural crest cell migration and heart morphogenesis in vertebrates. Part two reviews in detail, specific EMT molecular pathways covering extracellular induction, transduction and transcription response and modulation of cell-cell adhesion structures. It emphasizes new specific pathways with potential medical applications. EMTs can also be linked to pathological events such as wound healing and cancer progression, as detailed in this section of the book.
Author: You Han Bae Publisher: Springer Science & Business Media ISBN: 1461478766 Category : Medical Languages : en Pages : 717
Book Description
This book was conceived from a simple question as to why cancer is so difficult to treat. Ultimately we want to find ways to cure cancers, but that may be an elusive dream at least with the technologies we have now and expect to have in the near future. This leads the question of whether it is possible to improve current cancer treatment methods, especially from the perspective of enhancing targeted drug delivery to tumors. This volume is designed to provide information related to the difficulties in treating cancers through targeted drug delivery, our current understanding of cancer biology, and potential technologies that might be used to achieve enhanced drug delivery to tumors. An ideal drug delivery system for treating cancers would maximize the therapeutic efficacy with minimal side effects in clinical applications. The seemingly improved anticancer efficacy of the current nanoparticle-based formulations needs to be viewed from the context of very poor success rates for translation to human applications. The results of in vitro cell culture models and small animal in vivo experiments have not been extrapolated to clinical applications. Finding the reasons for the lack of successful translation is required if we are to discover approaches to substantially extend the survival time of cancer patients, and hopefully identify cures. Cancer Targeted Drug Delivery: Elusive Dream describes some answers of achieving the so far elusive dream of treating cancers like other chronic diseases with therapies that focus using improved drug delivery systems designed to better align with the unique biological and physiological properties of cancer.
Author: Vinod Kumar Yata Publisher: Springer Nature ISBN: 3030471209 Category : Technology & Engineering Languages : en Pages : 340
Book Description
This book is the third volume on this subject and focuses on the recent advances of nanopharmaceuticals in cancer, dental, dermal and drug delivery applications and presents their safety, toxicity and therapeutic efficacy. The book also includes the transport phenomenon of nanomaterials and important pathways for drug delivery applications. It goes on to explain the toxicity of nanoparticles to different physiological systems and methods used to assess this for different organ systems using examples of in vivo systems.
Author: Rama H. Grantab Publisher: ISBN: 9780494398616 Category : Languages : en Pages : 348
Book Description
The penetration of anticancer drugs has been shown to be limited to the tumor periphery or the few cell layers proximal to the nearest blood vessel, excluding many of the viable cells distant from blood vessels in the tumor core, thereby reducing chemotherapeutic efficacy. Modifiers of cell-cell adhesion and ECM have been shown to enhance the distribution and the chemotherapeutic efficacy of a number of anticancer drugs. The development of multilayered cultures (MCC), in which tumor cells are grown on a semi-permeable Teflon support membrane, has facilitated the quantification of drug penetration through solid tissue. We compared the properties of MCC grown from two epithelioid (E) and round (R) sub-clones of HCT-8 colon carcinoma cell lines that generated MCC with different packing density. The penetration of methotrexate, doxorubicin, paclitaxel, and 5-fluorouracil were shown to be greater through MCC derived from the loosely packed HCT-81R1 and Ra sublines compared with the tightly packed parental HCT-8E11 and Ea sublines. In MCC treated with doxorubicin, we observed greater survival in the tightly-packed than the loosely-packed cell lines. The results reported in this thesis support the initial hypothesis that cellular adhesion and packing density limit the penetration of chemotherapeutic agents in solid tumors, and that the administration of agents that modify cell adhesion and/or packing density can enhance drug penetration and chemotherapeutic efficacy. Tumor xenografts established from HCT-8 sublines exhibited significant differences in cellular packing density: greater packing density was observed in the HCT-8E11 and Ea than the HCT-81R1 and Ra tumors respectively. Doxorubicin distribution was observed to be significantly greater in the loosely packed HCT-81R1 and Ra tumor xenografts compared to the tightly packed HCT-8E11 and Ea tumors. The proteasome inhibitor bortezomib was used to modify the tumor microenvironment. Bortezomib pre-treatment was shown to reduce cellular packing density, improve drug penetration, and enhance the cytotoxicity of doxorubicin and gemcitabine in MCC derived from HCT-8Ea and E11 cell lines. In vivo administration of bortezomib was shown to reduce interstitial fluid pressure (IFP) and to enhance doxorubicin distribution in HCT-8E11 and Ea tumor xenografts.
Author: Emilio I. Alarcon Publisher: Springer Nature ISBN: 3030312615 Category : Technology & Engineering Languages : en Pages : 208
Book Description
This book fills the gap between fundamental and applied research in the use of nanomaterials in biomedical applications, covering the most relevant areas, such as the fundamental concepts of the preparation of nanostructures and regulatory requirements for their safe use in biomedical devices. It also critically discusses what has been achieved in the field, and what needs to be urgently addressed and reviews the state-of-the-art medical uses of nanomaterials for treating damaged organs and tissues. Combining the expertise of clinical researchers working in the field of tissue engineering and novel materials, the book explores the main topics regarding the characterization of materials, specific organ-oriented biomaterials and their applications, as well as regulations and safety. Further, it also examines recent advances, difficulties, and clinical requirements in terms of human bone, cornea, heart, skin and the nervous system, allowing readers to gain a clear and comprehensive understanding of current nanomaterial use in biomedical applications and devices, together with the challenges and future trends. This book is a valuable tool for multidisciplinary scientists and experts interested in fundamental concepts and synthetic routes for preparing nanomaterials. It is also of interest to students and researchers involved in cross-disciplinary research in nanomaterials for clinical applications and offers practical insights for clinicians as well as engineers and materials scientists working in nanoengineering.
Author: Challa S. S. R. Kumar Publisher: Wiley-VCH ISBN: Category : Medical Languages : en Pages : 448
Book Description
This first comprehensive overview on nanotechnological approaches to cancer therapy brings together therapeutic oncology and nanotechnology, showing the various strategic approaches to selectively eliminating cancerous cells without damaging the surrounding healthy tissue. The strategies covered include magnetic, optical, microwave and neutron absorption techniques, nanocapsules for active agents, nanoparticles as active agents, and active and passive targeting, while also dealing with fundamental aspects of how nanoparticles cross biological barriers. A valuable single source gathering the many articles published in specialized journals often difficult to locate for members of the other disciplines involved.
Author: Huile Gao Publisher: Academic Press ISBN: 012814002X Category : Medical Languages : en Pages : 502
Book Description
Brain Targeted Drug Delivery Systems: A Focus on Nanotechnology and Nanoparticulates provides a guide on nanoparticulates to both academic and industry researchers. The book discusses key points in the development of brain targeted drug delivery, summarizes available strategies, and considers the main problems and pitfalls evidenced in current studies on brain targeted drug delivery systems. As the brain is the most important organ in the human body, and disorders of the central nervous system (CNS) are the most serious threat to human life, this book highlights advances and new research in drug delivery methods to the brain. Provides an overview of brain targeting drug delivery that is useful to both academic and industry-based researchers Discusses key points in developing brain targeting drug delivery systems Summarizes and presents currently available strategies for brain targeting drug delivery Covers not only current studies and their strengths, but also gives insight into the pitfalls of current research
Author: Fabrizio Marcucci
Author: Fabrizio Marcucci
Author: Yasuhiro Matsumura
Author: Pierre Savagner
Author: You Han Bae
Author: Vinod Kumar Yata
Author: Rama H. Grantab
Author: Thomas Tyrel Goodman
Author: Emilio I. Alarcon
Author: Challa S. S. R. Kumar
Author: Huile Gao