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      Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment

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          Abstract

          Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system tumors. Despite advances in treatment modalities it remains largely incurable. The objective of our review is to provide a holistic picture of GBM epidemiology, etiology, pathogenesis, clinical findings and treatment. A literature search was conducted for GBM at PubMed and Google Scholar, with relevant key words like glioblastoma multiforme, pathogenesis, signs and symptoms, treatment etc., and papers published until 2015 were reviewed. It was found that radiation and certain genetic syndromes are the only risk factors identified to date for GBM. Depending on the tumor site patients may present to the clinic with varying symptoms. To confirm the presence and the extent of tumor, various invasive and non-invasive imaging techniques require employment. The literature survey revealed the pathogenesis to involve aberrations of multiple signaling pathways through multiple genetic mutations and altered gene expression. Although several treatment options are available, including surgery, along with adjuvant chemo- and radio-therapy, the disease has a poor prognosis and patients generally succumb within 14 months of diagnosis.

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          Most cited references36

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          Genetic pathways to primary and secondary glioblastoma.

          Glioblastoma is the most frequent and most malignant human brain tumor. The prognosis remains very poor, with most patients dying within 1 year after diagnosis. Primary and secondary glioblastoma constitute distinct disease subtypes, affecting patients of different age and developing through different genetic pathways. The majority of cases (>90%) are primary glioblastomas that develop rapidly de novo, without clinical or histological evidence of a less malignant precursor lesion. They affect mainly the elderly and are genetically characterized by loss of heterozygosity 10q (70% of cases), EGFR amplification (36%), p16(INK4a) deletion (31%), and PTEN mutations (25%). Secondary glioblastomas develop through progression from low-grade diffuse astrocytoma or anaplastic astrocytoma and manifest in younger patients. In the pathway to secondary glioblastoma, TP53 mutations are the most frequent and earliest detectable genetic alteration, already present in 60% of precursor low-grade astrocytomas. The mutation pattern is characterized by frequent G:C-->A:T mutations at CpG sites. During progression to glioblastoma, additional mutations accumulate, including loss of heterozygosity 10q25-qter ( approximately 70%), which is the most frequent genetic alteration in both primary and secondary glioblastomas. Primary and secondary glioblastomas also differ significantly in their pattern of promoter methylation and in expression profiles at RNA and protein levels. This has significant implications, particularly for the development of novel, targeted therapies, as discussed in this review.
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            Epidemiology of primary brain tumors: current concepts and review of the literature.

            The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines.
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              Glioblastoma multiforme: a review of where we have been and where we are going.

              Malignant gliomas such as glioblastoma multiforme (GBM) present some of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements in oncology. Even with aggressive surgical resections using state-of-the-art preoperative and intraoperative neuroimaging, along with recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal: median survival after diagnosis is about 14 months. Established good prognostic factors are limited, but include young age, high Karnofsky Performance Status (KPS), high mini-mental status examination score, O6-methylguanine methyltransferase promoter methylation, and resection of > 98% of the tumor. Standard treatment includes resection, followed by concurrent chemotherapy and radiotherapy. GBM research is being conducted worldwide at a remarkable pace, with some of the more recent promising studies focused on identification of aberrant genetic events and signaling pathways, tumor stem cell identification and characterization, modulation of tumor immunological responses, combination therapies, and understanding of the rare long-term survivors. Past treatment strategies have failed for various reasons; however, newer strategies in trials today and on the horizon encourage optimism. To help illustrate 'where we have been' with this fatal disease and 'where we are going' with contemporary studies, we include in this review a detailed history of Phase III clinical trials for GBM, with a final emphasis on exciting new treatment strategies that offer hope for future GBM therapy.
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                Author and article information

                Journal
                Asian Pac J Cancer Prev
                Asian Pac. J. Cancer Prev
                Asian Pacific Journal of Cancer Prevention : APJCP
                West Asia Organization for Cancer Prevention (Iran )
                1513-7368
                2476-762X
                2017
                : 18
                : 1
                : 3-9
                Affiliations
                [1 ] Department of Biomedical Sciences, Institute of Basic Medical Sciences, Dow University of Health Sciences
                [2 ] Panjwani Center for Molecular Medicine and Drug Research
                [4 ] Pharmacology Unit, HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, University Road Karachi
                [3 ] Department of Biological and Biomedical Sciences, The Aga Khan Khan University Medical College, P.O Box 3500, Stadium Road Karachi
                [5 ] Department of Biochemistry, Baqai Medical University, Super Highway, Karachi, Pakistan
                Author notes
                [* ] For Correspondence: shabana.simjee@ 123456iccs.edu
                Article
                APJCP-18-3
                10.22034/APJCP.2017.18.1.3
                5563115
                28239999
                89208347-8f65-453f-8435-17e7984bdc19
                Copyright: © Asian Pacific Journal of Cancer Prevention

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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                Review

                glioblastoma multiforme,epidemiology,mri scan,mutations,temozolomide

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