Download or read book Development of an in Vitro Model of Brain Tumor Invasion written by Arun Amar and published by . This book was released on 1993 with total page 84 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Brain Tumor Invasion written by Tom Mikkelsen and published by Wiley-Liss. This book was released on 1998-05-05 with total page 494 pages. Available in PDF, EPUB and Kindle. Book excerpt: Brain Tumor Invasion Biological, Clinical, and Therapeutic Considerations Edited by Tom Mikkelsen Rolf Bjerkvig Ole Didrik Laerum Mark L. Rosenblum Recent advances in molecular biology have given us profound new insights into the behavior of primary brain tumors. Not only are such tumors more diffuse in their infiltration of brain tissue and therefore less amenable to surgery than brain tumors originating elsewhere in the body—it now appears that the central nervous system and the normal brain itself constitute a biological environment conducive to the uncontrolled spread of primary tumors. Brain Tumor Invasion is the first comprehensive reference devoted to the invasive behavior of primary brain tumors. It examines the biological mechanisms responsible for the increased ability of gliomas to metastasize in the central nervous system, and discusses the role of chemical carcinogens, growth factors, oncogenes, and tumor suppressors in the progression of such metastases. This book surveys the latest research in the field, reviews present and future prospects of anti-invasive brain tumor therapy, and even translates preclinical trials and other research results into potential new therapies. The material is divided into five main categories: Developmental biology and molecular neuro-oncology Pathological and clinical features of malignant brain tumors Models for the study of brain tumor invasion in vivo and in vitro Mechanisms of invasion New therapeutic strategies Brain Tumor Invasion offers dozens of maps and photographs that illustrate topics under discussion. This in-depth introduction to one of the most difficult problems in the management of brain tumors is indispensable to neuro-oncologists involved in brain tumor research and therapy. It is also useful to researchers in cancer biology, neuroscience, cell biology, and molecular genetics.
Download or read book Invasion and Evasion written by Gregory Joseph Baker and published by . This book was released on 2014 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt: As glioma cells infiltrate the brain they associate with various microanatomic structures such as blood vessels and myelinated white matter tracts. How distinct invasion patterns coordinate tumor growth and influence clinical outcomes remains poorly understood. We have investigated how perivascular invasion affects glioma growth patterning and response to anti-angiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to commonly invade and proliferate within brain perivascular space. This form of brain tumor growth and invasion also characterizes de-novo endogenous mouse brain tumors, biopsies of primary human glioblastoma and peripheral cancer metastasis to the human brain. Perivascularly invading brain tumors are vascularized by preexisting normal brain microvessels as individual gliomas cells use perivascular space as a conduit for tumor invasion. Agent-based computational modeling recapitulated biological perivascular glioma growth without the need for neoangiogenesis. We tested the requirement for neoangiogenesis in perivascular glioma empirically by treating animals with the angiogenesis inhibitors bevacizumab and DC101. These inhibitors induced the expected vessel-normalization, yet failed to reduce tumor growth or improve survival of mice bearing orthotopic or endogenous gliomas while exacerbating brain tumor invasion. The results of these studies provide compelling experimental evidence in support of the recently described failure of clinically used anti-angiogenics to extend the overall survival of human patients with newly diagnosed glioblastoma. To identify molecular factors driving perivascular invasion, we examined genome-wide microarray data from mouse GL26 gliomas harvested from the brains of syngeneic C57BL/6 mice. This analysis revealed that galectin-1 (mLgals1) was the most abundantly expressed mRNA transcript in mouse GL26 glioma. We tested the role of this gene in perivascular invasion based on its known role in mediating cell-extracellular matrix interactions and its correlation with increasing malignancy and poor patient prognosis in clinical glioma. Unexpectedly, shRNA-mediated galectin-1 knockdown did not inhibit perivascular glioma invasion, but led to the complete eradication of intracranial tumor implants in RAG1-/- mice, which grew normally in more severely immunocompromised NOD-scid IL2Rgnull mice. Natural killer cell depletion in both RAG1-/- and C57BL/6J mice permitted the growth of galectin-1-deficient glioma. Orthotopic galectin-1-deficient glioma implants in RAG1-/- mice contained more granzyme B+ cells. Interferon gamma ELISpot assays were used to assess the level of tumor-specific adaptive immunity raised against galectin-1-deficient glioma. These experiments showed that galectin-1-deficient glioma was eradicated prior to, and independent of, adaptive anti-tumor immunity. Further in vitro experiments demonstrated that galectin-1-deficient GL26-Cit glioma cells were approximately 3-fold more sensitive to natural killer cell-mediated tumor lysis compared to their galectin-1 expressing counterparts. These findings suggest that galectin-1 suppression in human glioma cells could improve patient survival by restoring natural killer cell immune surveillance, which we have demonstrated to be capable of eradicating these tumors. Further experiments were performed to elucidate the mechanism by which galectin-1-deficient glioma is rejected by natural killer cells at the cellular level. Our results indicate that a population of Gr-1+/CD11b+ myeloid cells from blood are crucial for stimulating natural killer cell-mediated eradication of galectin-1-deficient glioma. We show that immunodepletion of Gr-1+ cells in RAG1-/- mice permits galectin-1-deficient glioma growth and significantly reduces the amount of tumor-infiltrating granzyme B+ cells. In vitro experiments demonstrate that monocytic Gr-1+/CD11b+ myeloid cells isolated from peripheral blood upregulate NK1.1 and granyzme B expression in response to the presence of galectin-1-deficient glioma cells, and that these cells enhance natural killer cell-mediated tumor lysis. Since we demonstrate that monocytic Gr-1+/CD11b+ myeloid cells lack tumor lytic potential themselves, we postulate that these cells act by stimulating anti-tumor cytotoxic potential in natural killer cells. In vivo experiments reveal that 7-fold more Gr-1+/CD11b+ myeloid cells infiltrate galectin-1-deficient gliomas 48 hrs post-tumor implantation compared to gliomas expressing normal levels of galectin-1. On the contrary, the number of tumor-infiltrating natural killer cells is found to be the same between the two tumor types, suggesting that galectin-1 specifically inhibits the entry of Gr-1+/CD11b+ myeloid cells. Our most recent experiments indicate that glioma-derived galectin-1 acts as a molecular switch for monocytic Gr-1+/CD11b+ myeloid cells to become anti-inflammatory. We demonstrate that the application of recombinant mouse galectin-1 protein onto monocytic Gr-1+/CD11b+ myeloid cells co-cultured with glioma cells and natural killer cells inhibits the enhanced tumor lysis attributed to the addition of the monocytic myeloid cells. This view of galectin-1 as a protein with anti-inflammatory effects on monocytic myeloid cells helps explain why the few Gr-1+/CD11b+ myeloid cells that do infiltrate galectin-1-replete gliomas fail to active natural killer cell-mediated anti-tumor cytotoxicity. Together, our data suggest that glioma-derived galectin-1 acts to inhibit anti-tumor natural killer cell immune surveillance through a tripartite mechanism: (1.) by blocking the infiltration of Gr-1+/CD11b+ myeloid cells into the tumor microenvironment which stimulate cytotoxic activity in natural killer cells, (2.) by provoking immunosuppressive function in those Gr-1+/CD11b+ myeloid cells that do infiltrate the gal-1-replete tumor microenvironment, thus inhibiting the stimulation of natural killer cells by Gr-1+/CD11b+ myeloid cells, and (3.) by imparting an intrinsic resistance to natural killer cell-mediated tumor cell lysis as demonstrated by us previously. We now plan to perform enzyme-linked immunosorbent assays, quantitative reverse transcription polymerase chain reaction, and genome-wide gene expression profiling on monocytic Gr-1+/CD11b+ myeloid cells to identify genes/proteins responsible for the enhancement of natural killer cell-mediated lysis of galectin-1-deficient glioma. Ultimately, through a deeper understanding of the mechanisms of natural killer cell-mediated anti-tumor immune surveillance, we hope to design novel innate immunotherapeutic strategies to be tested in patients suffering from glioblastoma.
Download or read book Untangling Glioblastoma Invasion written by Danny Jomaa and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Glioblastoma is the most common and most lethal primary brain tumor to affect adults. While current treatment options provide temporary recourse, the majority of patients experience tumor recurrence and few survive five years past their initial diagnosis. Recently, tumor microtubes (TMs) were identified in an in vivo model of glioblastoma. These membrane-bound structures formed physical connections between tumor cells, over short and long distances, and facilitated intratumoral communication, invasion, treatment resistance, and post-treatment tumor recovery. To date, this is the first instance of TMs being reported in glioblastoma. The lack of an in vitro model for these structures has delayed further characterization of how TMs form between cells, facilitate intercellular exchange, and how they can be therapeutically targeted to increase treatment susceptibility. The study presented here is the first instance of TMs characterized in an in vitro model of primary glioblastoma (PriGO) cells. These TMs recapitulated many of the structural and functional properties of those observed in vivo, making it a suitable model for further experimentation. Using this model, Rac1, a known orchestrator of cytoskeletal remodeling and motility, was shown to be integral to establishing a TM network between PriGO cells, as demonstrated by siRNA-mediated protein knockdowns. PREX1, a GEF necessary for Rac1 signaling activity, also played a role in PriGO TM formation as evidenced by CRISPR/Cas9-based knockouts. Re-introducing a PREX1 domain with Rac-GEF activity into cells lacking the protein led to a functional rescue of TM growth, thus confirming PREX1's involvement. Characterizing a cell culture model of glioblastoma TMs is a necessary first step in the study of these structures, ultimately paving the way for future development of therapies that disrupt this network.
Download or read book Development of an in Vitro Model for the Study of Tumor Cell Invasion Into the Urinary Bladder written by Marc Craig Brande and published by . This book was released on 1987 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Transgenic Mouse Methods and Protocols written by Marten H. Hofker and published by Springer Science & Business Media. This book was released on 2008-02-04 with total page 382 pages. Available in PDF, EPUB and Kindle. Book excerpt: Marten Hofker and Jan van Deursen have assembled a multidisciplinary collection of readily reproducible methods for working with mice, and particularlyfor generating mouse models that will enable us to better understand gene function. Described in step-by-step detail by highly experienced investigators, these proven techniques include new methods for conditional, induced knockout, and transgenic mice, as well as for working with mice in such important research areas as immunology, cancer, and atherosclerosis. Such alternative strategies as random mutagenesis and viral gene transduction for studying gene function in the mouse are also presented.
Download or read book Scientific Modeling and Simulations written by Sidney Yip and published by Springer Science & Business Media. This book was released on 2010-04-07 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt: Although computational modeling and simulation of material deformation was initiated with the study of structurally simple materials and inert environments, there is an increasing demand for predictive simulation of more realistic material structure and physical conditions. In particular, it is recognized that applied mechanical force can plausibly alter chemical reactions inside materials or at material interfaces, though the fundamental reasons for this chemomechanical coupling are studied in a material-speci c manner. Atomistic-level s- ulations can provide insight into the unit processes that facilitate kinetic reactions within complex materials, but the typical nanosecond timescales of such simulations are in contrast to the second-scale to hour-scale timescales of experimentally accessible or technologically relevant timescales. Further, in complex materials these key unit processes are “rare events” due to the high energy barriers associated with those processes. Examples of such rare events include unbinding between two proteins that tether biological cells to extracellular materials [1], unfolding of complex polymers, stiffness and bond breaking in amorphous glass bers and gels [2], and diffusive hops of point defects within crystalline alloys [3].
Download or read book Metastatic Cancer Clinical and Biological Perspectives written by Rahul Jandial and published by CRC Press. This book was released on 2013-08-08 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: Most cancer deaths are a result of metastasis. The spread of a primary tumor to colonize neighboring and distant organs is the relentless endgame that defines the neoplastic process. Patients who have been diagnosed with cancer are treated to prevent both the recurrence of the tumor at the site of origin and metastasis that would re-stage them as advanced stage IV cancer. Historically and still with some types of cancer, stage IV is perceived by patients as “terminal.” Fortunately, recent molecular therapies have extended the lives of patients with advanced cancer and reassuringly people living with metastatic disease increasingly visit our clinics. What is the path forward? Given that the consilience of science and medicine is a dynamic art from which therapies arise, it would be misguided to consider any single work adequate at capturing the horizon for research. So with humility we constructed this text as primer for scientists. It begins with a broad introduction to the clinical management of common cancers. This is intended to serve as a foundation for investigators to consider when developing basic science hypotheses. Unquestionably, medical and surgical care of cancer patients reveals biology and dictates how novel therapeutics will ultimately be evaluated in clinical trials. The second section of this text offers provocative and evolving insights that underscore the breadth of science involved in the elucidation of cancer metastasis biology. The text concludes with information that integrates scientific and clinical foundations to highlight translational research. This book serves as a framework for scientists to conceptualize clinical and translational knowledge on the complexity of disease that is metastatic cancer.
Download or read book Spheroid Culture in Cancer Research 1991 written by Rolf Bjerkvig and published by CRC Press. This book was released on 2017-11-22 with total page 458 pages. Available in PDF, EPUB and Kindle. Book excerpt: Spheroid Culture in Cancer Research describes the various techniques now available for establishing spheroid tissue culture, including spheroid culture from normal tissues and from tumor cell lines. The book also describes how the spheroid system can be used to study interactions between normal and malignant cells. Microenvironmental conditions in spheroids and how this micromilieu may promote cellular heterogeneity and histiotypic structures not observed in corresponding monolayer cultures are discussed. The biological importance of oxygen tension, pH gradients, diffusions of nutrients, and cell-cell communication in spheroids are also examined. The book will be profoundly important to researchers in experimental chemotherapy, radiotherapy, immunotherapy, and hyperthermia.
Download or read book CNS Cancer written by Erwin G. Van Meir and published by Springer Science & Business Media. This book was released on 2009-08-15 with total page 1294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancers of the central nervous system are among the most lethal of human neoplasms. They are recalcitrant to even intensive multimodality therapies that include surgery, radiotherapy, and chemotherapy. Moreover, especially in children, the consequences of these therapies can itself be devastating and involve serious cognitive and developmental disorders. It is small wonder that such cancers have come under the intense scrutiny of each of the subspecialties of clinical care and investigation as well as attracting some of the best basic research scientists. Their joint efforts are gradually peeling away the mysteries surrounding the genesis and progression of these tumors and inroads are being steadily made into understanding why they resist therapies. This makes it an especially opportune time to assemble some of the best investigators in the field to review the ‘‘state of the art’’ in the various arenas that comprise the assault on CNS tumors. The breadth of this effort by the clinical and basic neuro-oncology community is quite simply amazing. To a large extent, it evolves from the knowledge of the human genome and its regulation that has been hard won over the past two decades.
Download or read book Endothelial Cell Culture written by Roy Bicknell and published by Cambridge University Press. This book was released on 1996-09-28 with total page 156 pages. Available in PDF, EPUB and Kindle. Book excerpt: The aim of the Handbooks in Practical Animal Cell Biology is to provide practical workbooks for those involved in primary cell culture. Each volume addresses a different cell lineage, and contains an introductory section followed by individual chapters on the culture of specific differentiated cell types. The authors of each chapter are leading researchers in their fields and use their first-hand experience to present reliable techniques in a clear and thorough manner. Endothelial Cell Culture contains chapters on endothelial cells derived from 1) lung, 2) bone marrow, 3) brain, 4) mammary glands, 5) skin, 6) adipose tissue, 7) female reproductive system, and 8) synovium.
Download or read book Childhood Acute Lymphoblastic Leukemia written by Ajay Vora and published by Springer. This book was released on 2017-04-21 with total page 345 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive and up-to-date review of all aspects of childhood Acute Lymphoblastic Leukemia, from basic biology to supportive care. It offers new insights into the genetic pre-disposition to the condition and discusses how response to early therapy and its basic biology are utilized to develop new prognostic stratification systems and target therapy. Readers will learn about current treatment and outcomes, such as immunotherapy and targeted therapy approaches. Supportive care and management of the condition in resource poor countries are also discussed in detail. This is an indispensable guide for research and laboratory scientists, pediatric hematologists as well as specialist nurses involved in the care of childhood leukemia.
Download or read book Tumor Microenvironment written by Alexander Birbrair and published by Springer Nature. This book was released on 2021-10-18 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume discusses novel concepts in cancer biology, focusing on different factors that affect the tumor microenvironment. Topics covered include sex-based differences in the tumor microenironment, dormancy in the tumor microenvironment, the influence of obesity on the tumor microenvironment, and much more. Taken alongside its companion volumes, Tumor Microenvironment: Novel Concepts covers the latest research on various aspects of the tumor microenvironment, as well as future directions. Useful for introducing the newer generation of researchers to the history of how scientists studied the tumor microenvironment as well as how this knowledge is currently applied for cancer treatments, it will be essential reading for advanced cell biology and cancer biology students, as well as researchers seeking an update on research on the tumor microenvironment.
Download or read book Experimental Metastasis Modeling and Analysis written by Anastasia Malek and published by Springer Science & Business Media. This book was released on 2013-12-02 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metastatic dissemination of cancer is a main cause of cancer related deaths, therefore biological mechanisms implicated in metastatic process presents an essential object of cancer research. This research requires creation and utilization of adequate laboratory models. The book describes main approaches to model processes of metastatic cancer dissemination and metastases development. The book is structured in according with various metastatic pathways reflecting molecular specificity of metastatic process as well as anatomical specificity of aria of dissemination. Each chapter is introduced by short discussion of clinical aspects of certain metastatic pathway. Especial attention is paid for methods of visualization, quantification and analysis of the modeled metastases. Additional chapter is devoted to methods of mathematic modeling of tumor spread. The data presented in the book may be helpful for cancer researchers and oncologists.
Download or read book Cancer Cell Lines Part 1 written by John Masters and published by Springer Science & Business Media. This book was released on 2006-04-11 with total page 295 pages. Available in PDF, EPUB and Kindle. Book excerpt: Continuous cell lines derived from human cancers are the most widely used resource in laboratory-based cancer research. The first 3 volumes of this series on Human Cell Culture are devoted to these cancer cell lines. The chapters in these first 3 volumes have a common aim. Their purpose is to address 3 questions of fundamental importance to the relevance of human cancer cell lines as model systems of each type of cancer: 1. Do the cell lines available accurately represent the clinical presentation? 2. Do the cell lines accurately represent the histopathology of the original tumors? 3. Do the cell lines accurately represent the molecular genetics of this type of cancer? The cancer cell lines available are derived, in most cases, from the more aggressive and advanced cancers. There are few cell lines derived from low grade organ-confined cancers. This gap can be filled with conditionally immortalized human cancer cell lines. We do not know why the success rate for establishing cell lines is so low for some types of cancer and so high for others. The histopathology of the tumor of origin and the extent to which the derived cell line retains the differentiated features of that tumor are critical. The concept that a single cell line derived from a tumor at a particular site is representative of tumors at that site is naïve and misleading.
Download or read book Comparative Oncology written by Alecsandru Ioan Baba and published by . This book was released on 2007 with total page 787 pages. Available in PDF, EPUB and Kindle. Book excerpt:
