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Author: Ronald H. Goldfarb
Publisher: Springer Science & Business Media
ISBN: 1461526221
Category : Medical
Languages : en
Pages : 186
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Book Description
It is widely appreciated that the pathophysiology of advanced brain cancer is intimately related to the extent of tumor invasiveness. A prerequisite for comprehensively understanding neuro-oncology is therefore the elucidation of the biochemical and molecular properties of tumor cells that contribute to their invasiveness. An understanding of tumor invasion for central nervous system tumors is crucial since malignant brain tumors are very highly invasive and extensively destroy adjacent neural brain tissue. Moreover, they are angiogenesis-dependent and lead to the death of patients by expanding within the limited space of the cranium. As more specific insights are gained towards a full understanding of the complex process of tumor invasiveness of brain tumor cells, it should be possible to design strategies for the early diagnosis and treatment of invasive, advanced brain tumors. There is therefore an urgent need to better understand the cellular properties of brain tumor cells responsible for invasiveness. This special issue of the JOURNAL OF NEURO-ONCOLOGY provides a state-of-the-art review of the general understanding of the process of tumor invasion. In addition, the articles emphasize specific aspects of aggressive brain cancers which are particularly important for deriving new insights for therapeutic approaches for advanced brain cancer that will target tumor invasiveness. The ideas discussed will stimulate further studies directed towards the translation of these important invasion-related studies to clinical approaches for the effective treatment of brain cancer.
Author: Ronald H. Goldfarb
Publisher: Springer Science & Business Media
ISBN: 1461526221
Category : Medical
Languages : en
Pages : 186
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Book Description
It is widely appreciated that the pathophysiology of advanced brain cancer is intimately related to the extent of tumor invasiveness. A prerequisite for comprehensively understanding neuro-oncology is therefore the elucidation of the biochemical and molecular properties of tumor cells that contribute to their invasiveness. An understanding of tumor invasion for central nervous system tumors is crucial since malignant brain tumors are very highly invasive and extensively destroy adjacent neural brain tissue. Moreover, they are angiogenesis-dependent and lead to the death of patients by expanding within the limited space of the cranium. As more specific insights are gained towards a full understanding of the complex process of tumor invasiveness of brain tumor cells, it should be possible to design strategies for the early diagnosis and treatment of invasive, advanced brain tumors. There is therefore an urgent need to better understand the cellular properties of brain tumor cells responsible for invasiveness. This special issue of the JOURNAL OF NEURO-ONCOLOGY provides a state-of-the-art review of the general understanding of the process of tumor invasion. In addition, the articles emphasize specific aspects of aggressive brain cancers which are particularly important for deriving new insights for therapeutic approaches for advanced brain cancer that will target tumor invasiveness. The ideas discussed will stimulate further studies directed towards the translation of these important invasion-related studies to clinical approaches for the effective treatment of brain cancer.
Author: Tom Mikkelsen
Publisher: Wiley-Liss
ISBN:
Category : Medical
Languages : en
Pages : 494
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Book Description
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.
Author: Alexander Birbrair
Publisher: Springer Nature
ISBN: 3030731197
Category : Medical
Languages : en
Pages : 548
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Book Description
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.
Author: Ronald H Goldfarb
Publisher:
ISBN: 9781461526230
Category :
Languages : en
Pages : 94
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Book Description
Author: Gregory Joseph Baker
Publisher:
ISBN:
Category :
Languages : en
Pages : 265
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Book Description
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.
Author: Arun Amar
Publisher:
ISBN:
Category : Brain
Languages : en
Pages : 84
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Book Description
Author: Sherri Treasurywala
Publisher:
ISBN:
Category : Gliomas
Languages : en
Pages : 214
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Book Description
Author: G. J. Pilkington
Publisher:
ISBN:
Category :
Languages : en
Pages : 70
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Book Description
Author: Ana Lucia Abujamra
Publisher: BoD – Books on Demand
ISBN: 9533075880
Category : Medical
Languages : en
Pages : 436
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Book Description
Brain Tumors: Current and Emerging Therapeutic Strategies focuses on tumor models, the molecular mechanisms involved in the pathogenesis of this disease, and on the new diagnostic and treatment strategies utilized to stage and treat this malignancy. A special section on immunotherapy and gene therapy provides the most up-to-date information on the pre-clinical and clinical advances of this therapeutic venue. Each chapter in Brain Tumors: Current and Emerging Therapeutic Strategies is authored by international experts with extensive experience in the areas covered.
Author: Ghazaleh Tabatabai
Publisher: MDPI
ISBN: 3039282603
Category : Science
Languages : en
Pages : 784
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Book Description
Glioblastoma is an aggressive incurable primary tumor of the central nervous system. Median overall survival is in the range of 1.5 years even in selected clinical trials populations. Many features contribute to this therapeutic challenge including high intratumoral and intertumoral heterogeneity, resistance to therapy, migration and invasion, immunosuppression. With the access of novel highthroughput technologies, significant progress has been made to understand molecular and immunological signatures underlying the pathology of glioblastoma. Clinical trial designs have shifted from investigating broad “one-for-all” treatment approaches to precision oncology designs. The collection of contributions in this book aim at providing researchers and clinicians an update on different aspects of glioblastoma, i.e. progress in basic, preclinical and clinical research.
