Download or read book Organotypic Models in Drug Development written by Monika Schäfer-Korting and published by Springer Nature. This book was released on 2021-03-25 with total page 325 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides latest findings in organotypic models in drug development and provides the scientific resonance needed in an emerging field of research in disciplines, such as molecular medicine, physiology, and pathophysiology. Today the research on human-based test systems has gained major interest and funding in the EU and the US has increased over the last years. Moreover, so-called 3R (reduce, replace, refine animal experiments) centres have been established worldwide.
Download or read book Three Dimensional Human Organotypic Models for Biomedical Research written by Fabio Bagnoli and published by Springer Nature. This book was released on 2021-05-20 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt: This edited volume discusses the application of very diverse human organotypic models in major areas of biomedical research. The authors lay a main focus on infectious diseases, cancer, allergies, as well as drug/vaccine discovery and toxicology studies. Representing a valid alternative to laboratory animals, these models are relevant for most areas of translational research. As the contemporary research shows, many human tissues can today be cultivated in vitro and used for several research objectives. This book provides an unprecedented overview of recent developments in an exciting field of research methodology. It is a reference guide for scientists in both academia and industry. Readers can update their knowledge and get hands-on recommendations on how to set up an organotypic model in their lab. Chapters 'Progress on Reconstructed Human Skin Models for Allergy Research and Identifying Contact Sensitizers' and 'Human Organotypic Models for Anti-infective Research' of this book are available open access under a CC BY 4.0 license at link.springer.com.
Download or read book In vivo Models for Drug Discovery written by José Miguel Vela and published by John Wiley & Sons. This book was released on 2014-07-31 with total page 600 pages. Available in PDF, EPUB and Kindle. Book excerpt: This one-stop reference is the first to present the complete picture -- covering all relevant organisms, from single cells to mammals, as well as all major disease areas, including neurological disorders, cancer and infectious diseases. Addressing the needs of the pharmaceutical industry, this unique handbook adopts a broad perspective on the use of animals in the early part of the drug development process, including regulatory rules and limitations, as well as numerous examples from real-life drug development projects. After a general introduction to the topic, the expert contributors from research-driven pharmaceutical companies discuss the basic considerations of using animal models, including ethical issues. The main part of the book systematically surveys the most important disease areas for current drug development, from cardiovascular to endocrine disorders, and from infectious to neurological diseases. For each area, the availability of animal models for target validation, hit finding and lead profiling is reviewed, backed by numerous examples of both successes and failures among the use of animal models. The whole is rounded off with a discussion of perspectives and challenges. Key knowledge for drug researchers in industry as well as academia.
Download or read book Engineered Organotypic Breast Tumor Model for Mechanistic Studies of Tumor stromal Interactions and Drug Discovery written by Sunil Singh and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is the second leading cause of mortality in the United States. The National Cancer Institute estimated 1.7 million new cases of cancer and 0.6 million cancer deaths in the United States in 2019. Cancer is a heterogeneous disease that involves not only cancer cells, but also different cells and proteins in the tumor stroma. Various cells such as fibroblasts, infiltrating immune cells, and endothelial cells, the extracellular matrix (ECM) proteins, growth factors, chemokines, cytokines, and other bioactive agents constitute the tumor microenvironment (TME). Traditional cancer treatments only target cancer cells but growing evidence has established pivotal roles for the TME in driving tumor progression and chemoresistance. As such, targeting the TME and its interactions with cancer cells (known as tumor-stromal interactions) is now being pursued as a new approach to improve treatment outcomes for patients. However, preclinical models such as standard in vitro cell cultures and animal models routinely used in cancer drug discovery fail to recapitulate tumor-stromal interactions of human tumors. To overcome limitations of existing tumor models, we developed a three-dimensional (3D) organotypic tumor model that enables mechanistic studies of tumor-stromal interactions to enable drug discovery efforts against the TME. The organotypic model incorporates three key components of the TME: a mass of cancer cells, fibroblasts, and collagen as the ECM. The resulting model resembles the architecture of solid tumors and spatial distribution of cells within the TME. We used a novel cell and protein micropatterning approach based on an aqueous two-phase system (ATPS) to first generate a cancer cell spheroid and then overlay it with a collagen solution containing fibroblasts. We automated this technology and adapted it to a high throughput 384-well plate format to enable both mechanistic and phenotypic studies of tumor-stromal interactions and testing arrays of drugs. We focused on triple negative breast cancer (TNBC) as a disease model because TNBC is the most aggressive subtype of breast cancer with very limited targeted therapy options and poor patient outcomes from cytotoxic chemotherapies, underscoring an unmet need for new treatment strategies. We leveraged our organotypic tumor model to demonstrate the feasibility of mechanistic studies of tumor-stromal interactions in TNBC, focusing on cancer-associated fibroblasts (CAFs) as the most abundant stromal cells in breast tumors. To establish the validity of our model, we used a well-known chemokine-receptor interaction mechanism in TNBC. Specifically, we showed that fibroblasts-secreted CXCL12 chemokine promotes the ECM invasion of CXCR4+ TNBC cells by activating oncogenic mitogen-activated protein kinase (MAPK) pathway. Additionally, the fibroblast cells remodeled the ECM through the RhoA/ROCK/myosin light chain-2 pathway. Following the validation step, we incorporated patient-derived CAFs in our model and studied their dynamic interactions with TNBC cells to explore whether CAFs-TNBC interactions would present therapy targets. Our mechanistic studies showed that hepatocyte growth factor (HGF) secreted by CAFs predominantly activates MET receptor tyrosine kinase on TNBC cells to promote proliferation, invasiveness, and epithelial-to-mesenchymal transition (EMT) of TNBC cells. This interaction axis led to activation of oncogenic pathways such as MAPK, phosphatidylinositol 3-kinase-Akt (PI3K/Akt), and signal transducer and activator of transcription (STAT) in TNBC cells. Importantly, we found that TNBC cells become resistant to single-agent treatment with a potent MAPK pathway inhibitor (trametinib) and demonstrated a design-driven approach to select drug combinations that effectively inhibit pro-metastatic functions of TNBC cells. We also demonstrated that the HGF-MET axis is implicated in lung metastasis of TNBC and that blocking this signaling axis is a potential approach against both primary TNBC tumorigenesis and metastases formation in the lung. Future studies are needed to study long-term effectiveness of drug combinations in our organotypic tumor model. Overall, this work established the utility of our 3D organotypic tumor model to elucidate the role of tumor stroma in promoting pro-metastatic functions of TNBC cells, thereby facilitating the design and development of novel therapeutic approaches against tumor-stromal interactions. This technology will facilitate future studies to incorporate other components of tumor stroma and patient-derived cancer and stromal cells to expedite the translation of the findings.
Download or read book Tumor Organoids written by Shay Soker and published by Humana Press. This book was released on 2017-10-20 with total page 213 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.
Download or read book Use of 3D Models in Drug Development and Precision Medicine Advances and Outlook written by Luigi Bonacina and published by Frontiers Media SA. This book was released on 2021-04-12 with total page 153 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dr. Davide Staedler is CEO of TIBIO Sagl, a consulting company, and chief scientific officer of Scitec Research S.A., a private analytical laboratory. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
Download or read book Drug Absorption Studies written by Carsten Ehrhardt and published by Springer Science & Business Media. This book was released on 2007-12-22 with total page 711 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is a well thought-out, highly practical text covering contemporary ‘in vitro’ techniques for drug absorption studies. Starting at the molecular level of investigation, it continues with cell monolayer models (both primary and cell lines) and culminates with in situ techniques as a final testing format. In addition, chapters on high-throughput assays, in vitro-in vivo correlation, bioinformatics and regulatory issues are covered, giving a comprehensive overview of available models and techniques. Moreover, an appendix consisting of a number of practical protocols is available online, updated as needed, and should prove very helpful to apply the techniques directly to the benchside.
Download or read book Concepts and Models for Drug Permeability Studies written by Bruno Sarmento and published by Elsevier. This book was released on 2024-02-23 with total page 708 pages. Available in PDF, EPUB and Kindle. Book excerpt: Concepts and Models for Drug Permeability Studies: Cell and Tissue Based in Vitro Culture Models, Second Edition, summarizes the most important developments in in vitro models for predicting the permeability of drugs. This book is structured around three different approaches, summarizing the most recent achievements regarding models comprising (i) immortalized cells with an intrinsic ability to grow as monolayers when seeded in permeable supports, (ii) primary cells isolated from living organisms and directly cultured as barrier monolayers, and (iii) tissue-based models constructed with cell lines and extracellular matrix that resembles the tridimensional structure of mucosae and other biological membranes, or animal/patient-derived tissues. Each model is covered in detail, including the protocol of generation and application for specific drugs/drug delivery systems. The equivalence between in vitro cell and tissue models and in vivo conditions is discussed, highlighting how each model may provisionally resemble different drug absorption route. Chapters included in the first edition were updated with relevant data published in recent years, while four new chapters were included to reflect new emerging directions and trends in drug permeability models. Concepts and Models for Drug Permeability Studies: Cell and Tissue Based in Vitro Culture Models, Second Edition, is a critical reference for drug discovery and drug formulation scientists interested in delivery systems intended for the administration of drugs through mucosal routes and other important tissue barriers (e.g. the BBB). Researchers studying mucosal biology can use this book to familiarize themselves and exploit the synergic effect of mucosal delivery systems and biomolecules. Summarizes the current advances in the use of permeability models in drug transport Covers the most important buccal, gastric, intestinal, pulmonary, nasal, vaginal, ocular, renal, skin, and blood–brain barrier in vitro models. Includes case studies to facilitate understanding of various concepts in computer-aided applications Updates in the second edition include organ-on-chip devices, 3D advanced models (multiple layered tissues, organoids, etc.), and multicompartmentalized tissue models
Download or read book The Impact of Food Bioactives on Health written by Kitty Verhoeckx and published by Springer. This book was released on 2015-04-29 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: “Infogest” (Improving Health Properties of Food by Sharing our Knowledge on the Digestive Process) is an EU COST action/network in the domain of Food and Agriculture that will last for 4 years from April 4, 2011. Infogest aims at building an open international network of institutes undertaking multidisciplinary basic research on food digestion gathering scientists from different origins (food scientists, gut physiologists, nutritionists...). The network gathers 70 partners from academia, corresponding to a total of 29 countries. The three main scientific goals are: Identify the beneficial food components released in the gut during digestion; Support the effect of beneficial food components on human health; Promote harmonization of currently used digestion models Infogest meetings highlighted the need for a publication that would provide researchers with an insight into the advantages and disadvantages associated with the use of respective in vitro and ex vivo assays to evaluate the effects of foods and food bioactives on health. Such assays are particularly important in situations where a large number of foods/bioactives need to be screened rapidly and in a cost effective manner in order to ultimately identify lead foods/bioactives that can be the subject of in vivo assays. The book is an asset to researchers wishing to study the health benefits of their foods and food bioactives of interest and highlights which in vitro/ex vivo assays are of greatest relevance to their goals, what sort of outputs/data can be generated and, as noted above, highlight the strengths and weaknesses of the various assays. It is also an important resource for undergraduate students in the ‘food and health’ arena.
Download or read book Animal Experimentation Working Towards a Paradigm Change written by Kathrin Herrmann and published by BRILL. This book was released on 2019-04-30 with total page 749 pages. Available in PDF, EPUB and Kindle. Book excerpt: Animal experimentation has been one of the most controversial areas of animal use, mainly due to the intentional harms inflicted upon animals for the sake of hoped-for benefits in humans. Despite this rationale for continued animal experimentation, shortcomings of this practice have become increasingly more apparent and well-documented. However, these limitations are not yet widely known or appreciated, and there is a danger that they may simply be ignored. The 51 experts who have contributed to Animal Experimentation: Working Towards a Paradigm Change critically review current animal use in science, present new and innovative non-animal approaches to address urgent scientific questions, and offer a roadmap towards an animal-free world of science.
Download or read book Concepts and Models for Drug Permeability Studies written by Bruno Sarmento and published by Woodhead Publishing. This book was released on 2015-09-30 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book intends to be an updated compilation of the most important buccal, gastric, intestinal, pulmonary, nasal, vaginal, ocular, skin and blood-brain barrier in vitro models for predicting the permeability of drugs. Concepts and Models for Drug Permeability Studies focuses on different approaches and comprises of various models. Each model describes the protocol of seeding and conservation, the application for specific drugs, and takes into account the maintenance of physiologic characteristics and functionality of epithelium, from the simplest immortalized cell-based monoculture to the most complex engineered-tissue models. Chapters also discuss the equivalence between in vitro cell and tissue models and in vivo conditions, highlighting how each model may provisionally resemble a different drug absorption route. Updated information regarding the most recent in vitro models to study the permeability of drugs Short and concise chapters covering all the biological barriers with interest in drug permeability A combination of bibliographic information related with individual models and footnote instructions of technical procedures for construction of cell and tissue-based models Simple and clear scientific content, adaptable for young scientists and experimented researchers
Download or read book Animal Models in Cancer Drug Discovery written by Asfar Azmi and published by Academic Press. This book was released on 2019-04-16 with total page 470 pages. Available in PDF, EPUB and Kindle. Book excerpt: Animal Models in Cancer Drug Discovery brings forward the most cutting-edge developments in tumor model systems for translational cancer research. The reader can find under this one volume virtually all types of existing and emerging tumor models in use by the research community. This book provides a deeper insight on how these newer models could de-risk modern drug discovery. Areas covered include up to date information on latest organoid derived models and newer genetic models. Additionally, the book discusses humanized animal tumor models for cancer immunotherapy and how they leverage personalized therapies. The chapter on larger animal, canine models and their use in and their use in pre-investigational new drug (pre-IND) development makes the volume unique. Unlike before, the incorporation of several simplified protocols, breeding methodologies, handling and assessment procedures to study drug intervention makes this book a must read. Animal Models in Cancer Drug Discovery is a valuable resource for basic and translational cancer researchers, drug discovery researchers, contract research organizations, and knowledge seekers at all levels in the biomedical field. Encompasses discussions on innovative animal models, xenograft, genetic models, primary models, organoid systems, humanized and other models in modern biology paradigms that are enhancing research in the field of drug discover Covers the use of these models in personalized medicine, immunotherapy, toxicology, pre-IND assessments and related drug development arenas Presents protocols, procedures, and a comprehensive glossary to help new readers understand technical terms and specialized nomenclature
Download or read book Cancer Drug Resistance written by Beverly A. Teicher and published by Springer Science & Business Media. This book was released on 2007-11-09 with total page 611 pages. Available in PDF, EPUB and Kindle. Book excerpt: Leading experts summarize and synthesize the latest discoveries concerning the changes that occur in tumor cells as they develop resistance to anticancer drugs, and suggest new approaches to preventing and overcoming it. The authors review physiological resistance based upon tumor architecture, cellular resistance based on drug transport, epigenetic changes that neutralize or bypass drug cytotoxicity, and genetic changes that alter drug target molecules by decreasing or eliminating drug binding and efficacy. Highlights include new insights into resistance to antiangiogenic therapies, oncogenes and tumor suppressor genes in therapeutic resistance, cancer stem cells, and the development of more effective therapies. There are also new findings on tumor immune escape mechanisms, gene amplification in drug resistance, the molecular determinants of multidrug resistance, and resistance to taxanes and Herceptin.
Download or read book Blood Brain Barrier in Drug Discovery written by Li Di and published by John Wiley & Sons. This book was released on 2015-02-02 with total page 604 pages. Available in PDF, EPUB and Kindle. Book excerpt: Focused on central nervous system (CNS) drug discovery efforts, this book educates drug researchers about the blood-brain barrier (BBB) so they can affect important improvements in one of the most significant – and most challenging – areas of drug discovery. • Written by world experts to provide practical solutions to increase brain penetration or minimize CNS side-effects • Reviews state-of-the-art in silico, in vitro, and in vivo tools to assess brain penetration and advanced CNS drug delivery strategies • Covers BBB physiology, medicinal chemistry design principles, free drug hypothesis for the BBB, and transport mechanisms including passive diffusion, uptake/efflux transporters, and receptor-mediated processes • Highlights the advances in modelling BBB pharmacokinetics and dynamics relationships (PK/PD) and physiologically-based pharmacokinetics (PBPK) • Discusses case studies of successful CNS and non-CNS drugs, lessons learned and paths to the market
Download or read book Ovarian Cancer written by M. Sharon Stack and published by Springer Science & Business Media. This book was released on 2009-09-18 with total page 411 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ovarian carcinoma continues to be responsible for more deaths than all other gynecologic malignancies combined, due to a continued inability to achieve detection of early (rather than advanced) stage disease and the lack of effective tumor-specific therapeutics. Ovarian carcinogenesis, invasion, and metastatic dissemination require a complex cascade of interrelated genetic, molecular, and biochemical events that regulate the neoplastic transition of normal ovarian surface epithelium. This updated second edition includes exciting new advances in ovarian cancer detection and treatment and provides an analysis of current research into aspects of malignant transformation, growth control, and metastasis. A more detailed understanding of these processes may ultimately translate into the development of novel approaches for the detection and control of ovarian cancer.
Download or read book Drug Discovery in Cancer Epigenetics written by Gerda Egger and published by Academic Press. This book was released on 2015-11-19 with total page 499 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug Discovery in Cancer Epigenetics is a practical resource for scientists involved in the discovery, testing, and development of epigenetic cancer drugs. Epigenetic modifications can have significant implications for translational science as biomarkers for diagnosis, prognosis or therapy prediction. Most importantly, epigenetic modifications are reversible and epigenetic players are found mutated in different cancers; therefore, they provide attractive therapeutic targets. There has been great interest in developing and testing epigenetic drugs, which inhibit DNA methyltransferases, histone modifying enzymes or chromatin reader proteins. The first few drugs are already FDA approved and have made their way into clinical settings. This book provides a comprehensive summary of the epigenetic drugs currently available and aims to increase awareness in this area to foster more rapid translation of epigenetic drugs into the clinic. Highlights the potential of epigenetic alterations in cancer for drug development Covers the tools and methods for epigenetic drug discovery, preclinical and clinical testing, and clinical implications of epigenetic therapy Provides important information regarding putative epigenetic targets, epigenetic technologies, networks and consortia for epigenetic drug discovery and routes for translation
Download or read book Microfluidic Cell Culture Systems written by Christopher Bettinger and published by William Andrew. This book was released on 2012-12-14 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The fields of microfluidics and BioMEMS are significantly impacting cell biology research and applications through the application of engineering solutions to human disease and health problems. The dimensions of microfluidic channels are well suited to the physical scale of biological cells, and the many advantages of microfluidics make it an attractive platform for new techniques in biology. This new professional reference applies the techniques of microsystems to cell culture applications. The authors provide a thoroughly practical guide to the principles of microfluidic device design and operation and their application to cell culture techniques. The resulting book is crammed with strategies and techniques that can be immediately deployed in the lab. Equally, the insights into cell culture applications will provide those involved in traditional microfluidics and BioMEMS with an understanding of the specific demands and opportunities presented by biological applications. The goal is to guide new and interested researchers and technology developers to the important areas and state-of-the-practice strategies that will enhance the efficiency and value of their technologies, devices and biomedical products.
