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 225 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 Mammography and Beyond written by National Research Council and published by National Academies Press. This book was released on 2001-06-04 with total page 34 pages. Available in PDF, EPUB and Kindle. Book excerpt: X-ray mammography screening is the current mainstay for early breast cancer detection. It has been proven to detect breast cancer at an earlier stage and to reduce the number of women dying from the disease. However, it has a number of limitations. These current limitations in early breast cancer detection technology are driving a surge of new technological developments, from modifications of x-ray mammography such as computer programs that can indicate suspicious areas, to newer methods of detection such as magnetic resonance imaging (MRI) or biochemical tests on breast fluids. To explore the merits and drawbacks of these new breast cancer detection techniques, the Institute of Medicine of the National Academy of Sciences convened a committee of experts. During its year of operation, the committee examined the peer-reviewed literature, consulted with other experts in the field, and held two public workshops. In addition to identifying promising new technologies for early detection, the committee explored potential barriers that might prevent the development of new detection methods and their common usage. Such barriers could include lack of funding from agencies that support research and lack of investment in the commercial sector; complicated, inconsistent, or unpredictable federal regulations; inadequate insurance reimbursement; and limited access to or unacceptability of breast cancer detection technology for women and their doctors. Based on the findings of their study, the committee prepared a report entitled Mammography and Beyond: Developing Technology for Early Detection of Breast Cancer, which was published in the spring of 2001. This is a non-technical summary of that report.
Download or read book Patient Derived Tumor Xenograft Models written by Rajesh Uthamanthil and published by Academic Press. This book was released on 2016-10-13 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt: Patient Derived Tumor Xenograft Models: Promise, Potential and Practice offers guidance on how to conduct PDX modeling and trials, including how to know when these models are appropriate for use, and how the data should be interpreted through the selection of immunodeficient strains. In addition, proper methodologies suitable for growing different type of tumors, acquisition of pathology, genomic and other data about the tumor, potential pitfalls, and confounding background pathologies that occur in these models are also included, as is a discussion of the facilities and infrastructure required to operate a PDX laboratory. Offers guidance on data interpretation and regulatory aspects Provides useful techniques and strategies for working with PDX models Includes practical tools and potential pitfalls for best practices Compiles all knowledge of PDX models research in one resource Presents the results of first ever global survey on standards of PDX development and usage in academia and industry
Download or read book Soft Matter for Biomedical Applications written by Dr Helena S Azevedo and published by Royal Society of Chemistry. This book was released on 2021-06-11 with total page 788 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dynamic soft materials that have the ability to expand and contract, change stiffness, self-heal or dissolve in response to environmental changes, are of great interest in applications ranging from biosensing and drug delivery to soft robotics and tissue engineering. This book covers the state-of-the-art and current trends in the very active and exciting field of bioinspired soft matter, its fundamentals and comprehension from the structural-property point of view, as well as materials and cutting-edge technologies that enable their design, fabrication, advanced characterization and underpin their biomedical applications. The book contents are supported by illustrated examples, schemes, and figures, offering a comprehensive and thorough overview of key aspects of soft matter. The book will provide a trusted resource for undergraduate and graduate students and will extensively benefit researchers and professionals working across the fields of chemistry, biochemistry, polymer chemistry, materials science and engineering, nanosciences, nanotechnologies, nanomedicine, biomedical engineering and medical sciences.
Download or read book Developing Technologies for Early Detection of Breast Cancer written by National Research Council and published by National Academies Press. This book was released on 2000-07-06 with total page 24 pages. Available in PDF, EPUB and Kindle. Book excerpt: In November 1999, the Institute of Medicine, in consultation with the Commission on Life Sciences, the Commission on Physical Sciences, Mathematics, and Applications, and the Board on Science, Technology and Economic Policy launched a one year study on technologies for early detection of breast cancer. The committee was asked to examine technologies under development for early breast cancer detection, and to scrutinize the process of medical technology development, adoption, and dissemination. The committee is gathering information on these topics for its report in a number of ways, including two public workshops that bring in outside expertise. The first workshop on "Developing Technologies for Early Breast Cancer Detection" was held in Washington DC in February 2000. The content of the presentations at the workshop is summarized here. A second workshop, which will focus on the process of technology development and adoption, will be held in Washington, DC on June 19-20. A formal report on these topics, including conclusions and recommendations, will be prepared by the committee upon completion of the one-year study.
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 Biomechanics in Oncology written by Cheng Dong and published by Springer. This book was released on 2018-10-27 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers multi-scale biomechanics for oncology, ranging from cells and tissues to whole organ. Topics covered include, but not limited to, biomaterials in mechano-oncology, non-invasive imaging techniques, mechanical models of cell migration, cancer cell mechanics, and platelet-based drug delivery for cancer applications. This is an ideal book for graduate students, biomedical engineers, and researchers in the field of mechanobiology and oncology. This book also: Describes how mechanical properties of cancer cells, the extracellular matrix, tumor microenvironment and immuno-editing, and fluid flow dynamics contribute to tumor progression and the metastatic process Provides the latest research on non-invasive imaging, including traction force microscopy and brillouin confocal microscopy Includes insight into NCIs’ role in supporting biomechanics in oncology research Details how biomaterials in mechano-oncology can be used as a means to tune materials to study cancer
Download or read book Mesenchymal Stromal Cells Preclinical and Clinical Challenges written by Joan Oliva and published by Frontiers Media SA. This book was released on 2022-08-12 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Second Harmonic Generation Imaging written by Francesco S. Pavone and published by Taylor & Francis. This book was released on 2016-04-19 with total page 465 pages. Available in PDF, EPUB and Kindle. Book excerpt: Second-harmonic generation (SHG) microscopy has shown great promise for imaging live cells and tissues, with applications in basic science, medical research, and tissue engineering. Second Harmonic Generation Imaging offers a complete guide to this optical modality, from basic principles, instrumentation, methods, and image analysis to biomedical a
Download or read book Patient Derived Xenograft Models of Human Cancer written by Yuzhuo Wang and published by Springer. This book was released on 2017-06-27 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive, state-of-the-art review of PDX cancer models. In separately produced chapters, the history and evolution of PDX models is reviewed, methods of PDX model development are compared in detail, characteristics of available established models are presented, current applications are summarized and new perspectives about use of PDX models are proposed. Each chapter is written by a world-renowned expert who is conducting cutting-edge research in the field. Each of the subsections provide a comprehensive review of existing literature addressing the particular topic followed by a conclusive paragraph detailing future directions. Extensive illustrations make this an interactive text. Patient-Derived Xenograft Models of Human Cancer will serve as a highly useful resource for researchers and clinicians dealing with, or interested in, this important topic. It will provide a concise yet comprehensive summary of the current status of the field that will help guide preclinical and clinical applications as well as stimulate investigative efforts. This book will propagate innovative concepts and prompt the development of ground-breaking technological solutions in this field.
Download or read book Immunodeficient Animals written by Wolfgang Arnold and published by S. Karger AG (Switzerland). This book was released on 1996 with total page 252 pages. Available in PDF, EPUB and Kindle. Book excerpt: The classic immunodeficient mutants nude, scid and rnu have an important function in experimental cancer research: they allow unique methods of investigation and provide data of clinical relevance. This volume presents the state of the art of research work based on the use of these immunodeficient animal models. One section is dedicated to the biological aspects and immunological properties of immunodeficient mutants. Another part includes articles on xenogenous transplantation of human tumors, focusing on the establishment of transplantable lines, growth characteristics and tumor markers. Special attention is given to new approaches in the fields of chemotherapy, radiation therapy and immunotherapy. Various contributors consider in vitro methods as alternative models. In addition to current data, this publication contains useful technical and methodological information and is therefore valuable not only for specialists but also for scientists entering the field of experimental cancer research.
Download or read book Cancer Immunology and Immunotherapy written by Glenn Dranoff and published by Springer Science & Business Media. This book was released on 2011-04-11 with total page 313 pages. Available in PDF, EPUB and Kindle. Book excerpt: The interplay between tumors and their immunologic microenvironment is complex, difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. The present review discusses tumor-immune interactions in several human cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact of local immune reactions on clinical outcome. Current active immunotherapy trials have shown durable tumor regressions in a fraction of patients. However, clinical efficacy of current vaccines is limited, possibly because tumors skew the immune system by means of myeloid-derived suppressor cells, inflammatory type 2 T cells and regulatory T cells (Tregs), all of which prevent the generation of effector cells. To improve the clinical efficacy of cancer vaccines in patients with metastatic disease, we need to design novel and improved strategies that can boost adaptive immunity to cancer, help overcome Tregs and allow the breakdown of the immunosuppressive tumor microenvironment.
Download or read book Unraveling the Safety Profile of Nanoscale Particles and Materials written by Andreia Ferreira de Castro Gomes and published by BoD – Books on Demand. This book was released on 2018-03-21 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt: As nanomaterials become increasingly present in our daily lives, pertinent questions regarding their safety arise. Nanomaterial risk assessment, as in other areas, directs much of the effort worldwide in defining guidelines that may be translated into national or international directives. Nanomaterials encompass different entities, from nanoparticles to nanostructured materials, with specific effects over cells, tissues, organisms and ecosystems depending on their biophysical characteristics. Such interactions will directly affect the impact of novel nanotechnologies. This book aims to provide the reader with a comprehensive overview of the current state of the art in nanotoxicology, featuring the most important developments and critical issues regarding the use of and exposure to nanoparticles.
Download or read book Cancer Nanotechnology written by and published by Academic Press. This book was released on 2018-06-23 with total page 222 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Cancer Research, Volume 139, provides invaluable information on the exciting and fast-moving field of cancer research. Original reviews are presented on a variety of topics relating to the rapidly developing intersection between nanotechnology and cancer research, with unique sections in the new release focusing on Exosomes as a theranostic for lung cancer, Nanotechnology and cancer immunotherapy, Ultrasound imaging agents and delivery systems, Dendronized systems for the delivery of chemotherapeutics, Thermosensitive liposomes for image-guided drug delivery, Supramolecular Chemistry in Tumor Analysis and Drug Delivery, Gold nanoparticles for delivery of cancer therapeutics, and Single cell barcode microchip for cancer research and therapy. Provides the latest information on cancer research Offers outstanding and original reviews on a range of cancer research topics Serves as an indispensable reference for researchers and students alike
Download or read book Concepts and Principles of Pharmacology written by James E. Barrett and published by Springer Nature. This book was released on 2019-12-24 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: Celebrating 100 years of HEP, this volume will discuss key pharmacological discoveries and concepts of the past 100 years. These discoveries have dramatically changed the medical treatment paradigms of many diseases and these concepts have and will continue to shape discovery of new medicinies. Newly evolving technologies will similarly be discussed as they will shape the future of the pharmacology and, accordingly, medical therapy.
Download or read book Principles of Bone Biology written by John P. Bilezikian and published by Academic Press. This book was released on 2008-09-29 with total page 2074 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
