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Immunotherapy for Tumor in the Brain: Insights From - and For - Other Tumor Sites

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455355 Year: Pages: 95 DOI: 10.3389/978-2-88945-535-5 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2019-01-23 14:53:42
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Tumor immunotherapy has now shown its promise for many, its disappointments and failings for others. Going forward, brain tumor patients can both benefit and contribute.Tumor immunotherapy is steadily progressing. As experience accumulates, it is important to consider its generality. The reviews herein emphasize the brain’s place among other tumor sites. Two major topics are addressed.THE SITE: WHAT CAN WE EXPECT FROM IMMUNOTHERAPY WHEN THE TARGET IS IN THE BRAIN?Experience with immunotherapy for different targets in the brain, including tumor and also pathogens, is reviewed. Long-standing assumptions are confronted. The potential for beneficial responses is stressed.BRAIN TUMOR IMMUNOTHERAPY: WHAT HAVE WE LEARNED SO FAR?Clinical experience with brain tumor immunotherapy, from a variety of centers, is reviewed. Primary tumors, emphasizing glioblastoma, and brain metastases are each considered.

Targeting Tumor Perfusion and Oxygenation Modulates Hypoxia and Cancer Sensitivity to Radiotherapy and Systemic Therapies (Book chapter)

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ISBN: 9789533077031 Year: DOI: 10.5772/23332 Language: English
Publisher: IntechOpen Grant: FP7 Ideas: European Research Council - 243188
Subject: Science (General)
Added to DOAB on : 2019-01-17 11:47:59
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Hypoxia, a partial pressure of oxygen (pO2) below physiological needs, is a limiting factor affecting the efficiency of radiotherapy. Indeed, the reaction of reactive oxygen species&#xD;&#xD;(ROS, produced by water radiolysis) with DNA is readily reversible unless oxygen stabilizes&#xD;&#xD;the DNA lesion. While normal tissue oxygenation is around 40 mm Hg, both rodent and&#xD;&#xD;human tumors possess regions of tissue oxygenation below 10 mm Hg, at which tumor cells&#xD;&#xD;become increasingly resistant to radiation damage (radiobiological hypoxia) (Gray, 1953).&#xD;&#xD;Because of this so-called “oxygen enhancement effect”, the radiation dose required to&#xD;&#xD;achieve the same biologic effect is about three times higher in the absence of oxygen than in&#xD;&#xD;the presence of normal levels of oxygen (Gray et al., 1953; Horsman & van der Kogel, 2009).&#xD;&#xD;Hypoxic tumor cells, which are therefore more resistant to radiotherapy than well&#xD;&#xD;oxygenated ones, remain clonogenic and contribute to the therapeutic outcome of&#xD;&#xD;fractionated radiotherapy (Rojas et al., 1992).

Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision

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ISBN: 9783038976349 / 9783038976356 Year: Pages: 202 DOI: 10.3390/books978-3-03897-635-6 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Therapeutics --- Pathology --- Urology
Added to DOAB on : 2019-02-21 09:26:53
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This Special Issue has been introduced with the aim of offering the possibility to publish new research results from old and new pioneers in the field of bladder cancer basic research. While editing this Special Issue we learned that an enormous enthusiasm is necessary to go on in bladder cancer research. In our eyes, bladder cancer is on one hand a very heterogenous malignancy, which is what makes it so difficult to focus on only one bladder cancer marker in bladder cancer diagnostics and follow-up. On the other hand, it is very important to find prognostic and predictive factors for bladder cancer due to its high incidence and its enormous costs, as one of the most expensive malignancies in the world. Finding and developing new bladder cancer markers is still a very dynamic field. Because there are many of these markers, it is impossible to report all of them. This Special Issue attempts to highlight the role of bladder cancer markers in diagnosis, and the most important biomarkers that have been recently studied and reported. This Special Issue highlights some of the most important markers. Further determination of recurrence and progression markers will contribute to establishing better treatments for individual patients. Molecular staging of urological tumors will allow the selection of cases that will require systemic treatment. It is necessary and important to integrate basic and clinical research under the same objectives.

Tumor Cell/Dendritic Cell Interactions and the Influence of Tumors on Dendritic Cell-mediated Anti-Tumor Immune Responses and Dendritic Cell-Based Tumor Immunotherapies

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192458 Year: Pages: 160 DOI: 10.3389/978-2-88919-245-8 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology --- Oncology
Added to DOAB on : 2015-11-16 15:44:59
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Significant efforts over the last two decades have been made to better understand the factors that control DC maturation and activation and the impact of these processes on overall host immunity. In addition to the well-characterized role of DC in the induction of immunity to pathogens, a role for these cells as critical regulators of anti-tumor immune responses has more recently become apparent. These findings have generated interest in understanding how tumor/DC interactions impact the quality of anti-tumor immune responses, and they have contributed to increased enthusiasm for a variety of DC-based cancer immunotherapies. Such strategies have included DNA- or peptide-based vaccines that involve uptake and processing of tumor antigens by endogenous DC in cancer patients or the administration of tumor antigen-loaded exogenous DC-based vaccines. Additionally, many adjuvant, cytokine, and monoclonal antibody therapies aim either to enhance the immunostimulatory capacity of endogenous DC or to supplement the activity of these cells by targeting costimulatory receptors on T cells. Despite the promise of such therapeutic approaches for cancer treatment, their success is often limited, and much remains to be understood about how tumors influence DC function and the quality of DC-mediated immune responses. Tumor/DC interactions have therefore become an increasingly active area of investigation, and many studies have described effects of tumors on DC phenotype and function that include an accumulation of immature DC within tumors, tumor-altered differentiation of DC precursors into myeloid-derived suppressor cells, and the generation of tumor-associated DC with immunoregulatory properties. As this field moves forward, it will be important to gain mechanistic insights into the basis for both tumor-mediated DC dysfunction as well as the induction of either suboptimal or immunosuppressive adaptive anti-tumor immune responses by tumor-associated DC. Progress in these areas of tumor immunology will greatly improve our understanding of the factors that contribute to effective DC-mediated anti-tumor immune control versus DC-associated anti-tumor immune dysfunction and subsequent tumor immune escape. Such information is vital for improving current and developing novel immunotherapeutic strategies for interfering with tumor-associated DC dysfunction and enhancing the functional quality of endogenous DC in cancer patients as well as the efficacy of exogenous DC-based anti-tumor vaccines. The articles contained within this special issue highlight these important topics and bring focus not only to our current understanding of tumor/DC interactions but also to major areas of investigation that remain ongoing in this field.

Harnessing oncolytic virus-mediated immunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194506 Year: Pages: 110 DOI: 10.3389/978-2-88919-450-6 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-02-05 17:24:33
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Oncolytic viruses (OVs) have emerged as a promising anticancer treatment. OVs selectively infect, replicate in, and kill tumor cells. Oncolytic viral therapy occurs in two phases: an initial phase where the virus mediates direct oncolysis of tumor cells, and a second phase where an induced post-oncolytic immune response continues to mediate tumor destruction and retards progression of the disease. For a long time, the therapeutic efficacy was thought to depend mainly on the direct viral oncolysis based on their tumor selective replication and killing activities. But the post-oncolytic anti-tumor activity induced by the OV therapy is also a key factor for an efficient therapeutic activity. The topic adresses various strategies how to optimize OVs anti-tumor activity.

Self-Eating on Demand: Autophagy in Cancer and Cancer Therapy

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454228 Year: Pages: 111 DOI: 10.3389/978-2-88945-422-8 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2018-11-16 17:17:57
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Macroautophagy, the major lysosomal pathway for recycling intracellular components including whole organelles, has emerged as a key process modulating tumorigenesis, tumor–stroma interactions, and cancer therapy. An impressive number of studies over the past decade have unraveled the plastic role of autophagy during tumor development and dissemination. The discoveries that autophagy may either support or repress neoplastic growth and contextually favor or weaken resistance and impact antitumor immunity have spurred efforts from many laboratories trying to conceptualize the complex role of autophagy in cancer using cellular and preclinical models. This complexity is further accentuated by recent findings highlighting that various autophagy-related genes have roles beyond this catabolic mechanism and interface with oncogenic pathways, other trafficking and degradation mechanisms and the cell death machinery. From a therapeutic perspective, knowledge of how autophagy modulates the tumor microenvironment is crucial to devise autophagy-targeting strategies using smart combination of drugs or anticancer modalities. This eBook contains a collection of reviews by autophagy researchers and provides a background to the state-of-the-art in the field of autophagy in cancer, focusing on various aspects of autophagy regulation ranging from its molecular components to its cell autonomous role, e.g. in cell division and oncogenesis, miRNAs regulation, cross-talk with cell death pathways as well as cell non-autonomous role, e.g. in secretion, interface with tumor stroma and clinical prospects of autophagy-based biomarkers and autophagy modulators in anticancer therapy. This eBook is part of the TransAutophagy initiative to better understand the clinical implications of autophagy in cancer.

Soft Tissue and Bone Sarcoma

ISBN: 9783906980461 9783906980584 Year: Pages: 156 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2015-01-12 11:17:42
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Soft tissue and bone sarcomas disproportionately affect children, adolescents, and young adults. Although considered a rare disease, sarcomas continue to have a devastating effect on these patients and their loved ones, and their impact on our society far exceed their relatively low prevalence. Because of its rarity and heterogeneity, clinical decision making on management of sarcomas are often individualized and without a consensus treatment strategy. Furthermore, research to improve clinical outcomes are particularly challenging as sizeable studies are hard to produce. By improving our knowledge about the molecular biology of sarcomas, we hope to identify new treatment strategies and targets for further drug development. [...]

The regulation of angiogenesis by tissue cell-macrophage interactions

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193172 Year: Pages: 113 DOI: 10.3389/978-2-88919-317-2 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Angiogenesis is the physiological process where new blood vessels grow from existing ones, in order to replenish tissues suffering from inadequate blood supply. Perhaps the most studied angiogenic process occurs in solid tumors whose growing mass and expanding cells create a constant demand for additional supply of oxygen and nutrients for survival. However, other physiological and clinical conditions, such as wound healing, ischemic events, autoimmune and age-related diseases also involve angiogenesis. Angiogenesis is a well-structured process that begins when oxygen and nutrients are depleted, leading to the release of chemokines and growth factors that attract immune cells, particularly macrophages and endothelial cells to the site. Macrophages that are recruited to the site, as well as tissue cells and endothelial cells, secrete pro-angiogenic mediators that affect endothelial cells and promote angiogenesis. These mediators include growth factors such as vascular endothelial cell growth factor (VEGF), matrix metalloproteinases (MMPs), as well as low levels of mediators that are usually seen as pro-inflammatory but are pro-angiogenic when secreted in low levels (e.g. nitric oxide (NO) and TNFa). Thus, macrophages play a major role in angiogenesis. Macrophages exhibit high plasticity and are capable of shifting between different activation modes and functions according to their changing microenvironment. Small differences in the composition of activating factors (e.g. TLR ligands such as LPS, anti-inflammatory cytokines, ECM molecules) in the microenvironment may differently activate macrophages to yield classically activated macrophages (or M1 macrophages) that can kill pathogen and tumor cells, alternatively activated macrophages (or M2 macrophages) that secrete antiinflammatory cytokines, resolution macrophages (rM?) that are involved in the resolution of inflammation, or regulatory macrophages (e.g. Myeloid-Derived Suppressor Cells - MDSCs) that control the function of other immune cells. In fact, macrophages may be activated in a spectrum of subsets that may differently contribute to angiogenesis, and in particular non-classically activated macrophages such as tumor-associated macrophages (TAMs) and Tie2-expressing monocytes (TEMs) can secrete high amounts of pro-angiogenic factors (e.g. VEGF, MMPs) or low levels of pro-inflammatory mediators (e.g. NO or TNFa) resulting in pro-angiogenic effects. Although the importance of macrophages as major contributors and regulators of the angiogenic process is well documented, less is known about the interactions between macrophages and other cell types (e.g. tumor cells, normal epithelial cells, endothelial cells) that regulate angiogenesis. We still have only limited understanding which proteins or complexes mediate these interactions and whether they require cell-cell contact (e.g. through integrins) or soluble factors (e.g. the EGF-CSF-1 loop), which signaling pathways are triggered in each of the two corresponding cell types, and how this leads to secretion of pro- or antiangiogenic factors in the microenvironment. The regulation of such interactions and through them of angiogenesis, whether through post-translational modifications of proteins or via the involvement of microRNA, is still unclear. The goal of this Research Topic is to highlight these interactions and their regulation in the context of both physiological and pathological conditions.

Mesothelioma Heterogeneity: Potential Mechanisms

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ISBN: 9783038974734 / 9783038974741 Year: Pages: 204 DOI: 10.3390/books978-3-03897-474-1 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology --- Oncology
Added to DOAB on : 2019-01-11 11:18:51
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Mesothelioma is a rare aggressive cancer that develops from the mesothelium. Recent molecular analyses have defined four different types of mesothelioma based on gene expression and two major molecularly-defined groups based on prognosis. In this volume, potential mechanisms causing this heterogeneity are explored. The different chapters include heterogeneity learned from experimental animal models in NF2/Hippo pathway signaling, stem cell signaling pathways, the tumor microenvironment, and micro RNA secretome. Novel aspects deserving attention such as the implication of long, non-coding RNA in disease heterogeneity are described. The volume also includes the description of tools useful to address some specific questions such as an assessment of the copy number variations of two tumor suppressors frequently mutated in mesothelioma or an investigation of Macrophage Inhibition Factor signaling in mesothelioma.

Cancer Immunotherapy & Immuno-monitoring: Mechanism, Treatment, Diagnosis, and Emerging Tools

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193806 Year: Pages: 97 DOI: 10.3389/978-2-88919-380-6 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2015-12-03 13:02:24
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In the past decade, significant progresses have taken place in the field of cancer immunotherapy. Tumor-targeting immunotherapies are being developed for most human cancers, including melanoma, prostate cancer, glioblastoma, sarcoma, lung carcinoma and hepatocellular carcinoma. The FDA has approved multiple molecular immunotherapeutics, such as Ipilimumab; cellular immunotherapies (e.g. adoptive cell transfer) are being tested in phase II/III clinical trials. Immunotherapetics has evolved into a sophisticated field: Multimodal therapeutic regimens are administrated to induce focused responses, curtail side- effects and improve therapeutic efficacy. The lack of effective clinical assessment tools remains a major challenge. Because of the intricacy of antitumor response, it is essential to scrutinize individual tumor-targeting immune cells and their functions at the finest details - molecules. In this regard, flow cytometry analysis modernized hematology and allows characterization of surface molecular signature on individual cells. More recently, microchip technologies and new variations of cytometry have enormously expanded the spectrum, throughout and multiplexity of single cell analysis. Nowadays, tens of millions of readouts can be generated through the course of a cancer immunotherapy to monitor the abundance, phenotype and a myriad of effector functions of single immune cells. At the same time, big data analytics and data mining methodologies have been adapted to achieve sensible diagnostic interpretations. Such a marriage of technology and analytics opens the door for informative point-of-care assessment of therapeutic efficacy and ensures timely therapeutic decisions. The new generation of personalized clinical diagnostics will revolutionize healthcare in the years to come.

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