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      Radioresistance in Glioblastoma and the Development of Radiosensitizers

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          Abstract

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          Numerous mechanisms of glioblastoma (GBM) radioresistance have been identified but have not yet resulted in development of effective radiosensitizer that can increase the efficacy of radiotherapy. In this review, the authors review the mechanisms of GBM radioresistance along with current status of radiation treatment and imaging techniques used in GBM diagnosis and radiotherapy. In addition, they summarize the current GBM radiosensitizers that are being investigated or enrolled in clinical trials. This review emphasizes on the importance of developing an effective radiosensitizers to increase the outcome of GBM radiotherapy. The authors highlight the importance of discovering of novel mechanism(s) of GBM radioresistance that will lead in developing an effective radiosensitizer.

          Abstract

          Ionizing radiation is a common and effective therapeutic option for the treatment of glioblastoma (GBM). Unfortunately, some GBMs are relatively radioresistant and patients have worse outcomes after radiation treatment. The mechanisms underlying intrinsic radioresistance in GBM has been rigorously investigated over the past several years, but the complex interaction of the cellular molecules and signaling pathways involved in radioresistance remains incompletely defined. A clinically effective radiosensitizer that overcomes radioresistance has yet to be identified. In this review, we discuss the current status of radiation treatment in GBM, including advances in imaging techniques that have facilitated more accurate diagnosis, and the identified mechanisms of GBM radioresistance. In addition, we provide a summary of the candidate GBM radiosensitizers being investigated, including an update of subjects enrolled in clinical trials. Overall, this review highlights the importance of understanding the mechanisms of GBM radioresistance to facilitate the development of effective radiosensitizers.

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            • Article: not found

            Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma

            Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety. Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients. The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity. Copyright 2005 Massachusetts Medical Society.
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              MicroRNAs: target recognition and regulatory functions.

              MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                03 September 2020
                September 2020
                : 12
                : 9
                : 2511
                Affiliations
                [1 ]Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA 52242, USA; ali-mdyousuf@ 123456uiowa.edu
                [2 ]Free Radical & Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA; claudia-oliva@ 123456uiowa.edu (C.R.O.); bryan-allen@ 123456uiowa.edu (B.G.A.); prabhat-goswami@ 123456uiowa.edu (P.C.G.); douglas-spitz@ 123456uiowa.edu (D.R.S.)
                [3 ]Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA; john-buatti@ 123456uiowa.edu
                [4 ]Department of Biochemistry and Molecular Biology, The University of Chittagong, Chittagong 4331, Bangladesh; asmnoman.bmb@ 123456cu.ac.bd
                [5 ]Department of Pathology, McGill University, Montreal, QC H3A 2B4, Canada
                [6 ]Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA; yousef-zakharia@ 123456uiowa.edu (Y.Z.); varun-monga@ 123456uiowa.edu (V.M.)
                Author notes
                Author information
                https://orcid.org/0000-0002-1185-5448
                https://orcid.org/0000-0001-8499-3721
                Article
                cancers-12-02511
                10.3390/cancers12092511
                7564557
                32899427
                d7034ab5-5144-4e85-967d-8dd5a683b80a
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 July 2020
                : 28 August 2020
                Categories
                Review

                glioblastoma,radioresistance,radiosensitizer
                glioblastoma, radioresistance, radiosensitizer

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