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https://www.readbyqxmd.com/read/28327577/metabolic-profiling-of-idh-mutation-and-malignant-progression-in-infiltrating-glioma
#1
Llewellyn E Jalbert, Adam Elkhaled, Joanna J Phillips, Evan Neill, Aurelia Williams, Jason C Crane, Marram P Olson, Annette M Molinaro, Mitchel S Berger, John Kurhanewicz, Sabrina M Ronen, Susan M Chang, Sarah J Nelson
Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM)...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28319049/resisting-fatal-attraction-a-glioma-oncometabolite-prevents-cd8-t-cell-recruitment
#2
Liliana E Lucca, David A Hafler
Immunotherapy has emerged as a potent approach for treating aggressive cancers, such as non-small-cell lung tumors and metastatic melanoma. Clinical trials are now in progress for patients with malignant gliomas; however, a better understanding of how these tumors escape immune surveillance is required to enhance antitumor immune responses. With gliomas, the recruitment of CD8+ T cells to the tumor is impaired, in part preventing containment or elimination of the tumor. In this issue of the JCI, Kohanbash and colleagues present an elegant dissection of how gliomas exploit an enzymatic activity acquired through a common mutation to abrogate the migration of CD8+ T cells to the tumor...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28319047/isocitrate-dehydrogenase-mutations-suppress-stat1-and-cd8-t-cell-accumulation-in-gliomas
#3
Gary Kohanbash, Diego A Carrera, Shruti Shrivastav, Brian J Ahn, Naznin Jahan, Tali Mazor, Zinal S Chheda, Kira M Downey, Payal B Watchmaker, Casey Beppler, Rolf Warta, Nduka A Amankulor, Christel Herold-Mende, Joseph F Costello, Hideho Okada
Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28315358/isocitrate-dehydrogenase-idh-inhibition-as-treatment-of-myeloid-malignancies-progress-and-future-directions
#4
REVIEW
Vivek A Upadhyay, Andrew M Brunner, Amir T Fathi
Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme. Over the last two decades, there has been a growing focus on the metabolic derangements that occur with IDH1 and IDH2 mutations. The altered IDH protein leads to accumulation of 2-hydroxyglutarate (2-HG), a metabolite with oncogenic activity via epigenetic mechanisms. The advent of IDH inhibitors has engendered hope in novel and targeted therapies in IDH1/2 mutant myeloid malignancies. We here summarize the basic physiology of IDH, the metabolic and oncogenic consequences of mutant IDH1/2, and the clinical significance of IDH inhibition in hematologic malignancies...
March 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28302331/novel-recursive-partitioning-analysis-classification-for-newly-diagnosed-glioblastoma-a-multi-institutional-study-highlighting-the-mgmt-promoter-methylation-and-idh1-gene-mutation-status
#5
Chan Woo Wee, Eunji Kim, Nalee Kim, In Ah Kim, Tae Min Kim, Yu Jung Kim, Chul-Kee Park, Jin Wook Kim, Chae-Yong Kim, Seung Hong Choi, Jae Hyoung Kim, Sung-Hye Park, Gheeyoung Choe, Soon-Tae Lee, Jong Hee Chang, Se Hoon Kim, Chang-Ok Suh, Il Han Kim
BACKGROUND AND PURPOSE: To refine the recursive partitioning analysis (RPA) classification for glioblastoma incorporating the MGMT methylation and IDH1 mutation status. METHODS AND MATERIALS: Three-hundred forty patients were treated with radiotherapy plus concurrent and adjuvant temozolomide in three tertiary-referral hospitals. MGMT methylation and IDH1 mutation status were available in all patients. Methylation of the MGMT (MGMTmeth) and mutation of IDH1 (IDH1mut) were observed in 42...
March 13, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28297624/genomics-of-acute-myeloid-leukemia-diagnosis-and-pathways
#6
Lars Bullinger, Konstanze Döhner, Hartmut Döhner
In recent years, our understanding of the molecular pathogenesis of myeloid neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery studies that use novel high-throughput sequencing techniques. AML, similar to most other cancers, is characterized by multiple somatically acquired mutations that affect genes of different functional categories, a complex clonal architecture, and disease evolution over time. Patterns of mutations seem to follow specific and temporally ordered trajectories...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28286924/treatment-of-relapsed-refractory-acute-myeloid-leukemia
#7
REVIEW
Prithviraj Bose, Pankit Vachhani, Jorge E Cortes
Approximately 40-45% of younger and 10-20% of older adults with acute myeloid leukemia (AML) will be cured with current standard chemotherapy. The outlook is particularly gloomy for patients with relapsed and/or refractory disease (cure rates no higher than 10%). Allogeneic hematopoietic stem cell transplantation (HSCT), the only realistic hope of cure for these patients, is an option for only a minority. In recent years, much has been learned about the genomic and epigenomic landscapes of AML, and the clonal architecture of both de novo and secondary AML has begun to be unraveled...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28285812/-a-case-report-of-chordoid-glioma-with-unusual-features-immunohistochemical-and-molecular-findings-and-differential-diagnoses
#8
Arnault Tauziède-Espariat, Gilles Robert, Patricia de Cremoux, Marc Polivka
We report the case of a 63-year-old healthy patient who was admitted for surgery of a suprasellar tumor with extension to the optic chiasm responsible of visual disturbance. Histopathological examination revealed a tumoral proliferation composed of epithelioid cells without atypia arranged in cords in a mucinous matrix surrounded by some lymphocytic inflammatory infiltrates. On immunohistochemistry, the neoplastic cells strongly expressed GFAP and CD34, a weak expression of EMA, an expression of TTF1 without immunoreactivity for brachyury...
March 9, 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28281182/evaluation-of-magnetonanoparticles-conjugated-with-new-angiogenesis-peptides-in-intracranial-glioma-tumors-by-mri
#9
Erica Aparecida de Oliveira, Jelena Lazovic, Lea Guo, Horacio Soto, Bluma Linkowski Faintuch, Massoud Akhtari, Whitney Pope
Angiogenesis plays a critical role in progression of malignant gliomas. The development of glioma-specific labeling molecules that can aid detection and visualization of angiogenesis can help surgical planning and improve treatment outcome. The aim of this study was to evaluate if two peptides (GX1 and RGD-GX1) linked to angiogenesis can be used as an MR-imaging markers of angiogenesis. MR imaging was performed in U87 glioblastoma-bearing NOD-SCID mice at different time points between 15 and 120 min post-injection to visualize particle distribution...
March 9, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28273187/-the-role-of-driver-and-subclonal-mutations-in-pathogenesis-of-primary-myelofibrosis
#10
Réka Mózes, Ambrus Gángó, Zsófia Boha, Judit Csomor, Csaba Bödör
Primary myelofibrosis (PMF) is a Philadelphia chromosome negative, clonal myeloproliferative neoplasm characterised by a progressive nature. Morphologically, the bone marrow biopsy shows features of abnormal proliferation of terminally differentiated megakaryocytes and subsequent bone marrow fibrosis. The molecular landscape of PMF includes phenotypic driver mutations (JAK2 V617F, CALR and MPL) which represent major diagnostic criteria, and subclonal mutations that also occur in several other myeloid diseases, but have a prognostic value in disease progression of MF...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28271343/new-molecular-considerations-for-glioma-idh-atrx-braf-tert-h3-k27m
#11
REVIEW
Michael Karsy, Jian Guan, Adam L Cohen, Randy L Jensen, Howard Colman
PURPOSE OF REVIEW: This review will discuss the role of several key players in glioma classification and biology, namely isocitrate dehydrogenase 1 and 2 (IDH1/2), alpha thalassemia/mental retardation syndrome X-linked (ATRX), B-Raf (BRAF), telomerase reverse transcriptase (TERT), and H3K27M. RECENT FINDINGS: IDH1/2 mutation delineates oligoden-droglioma, astrocytoma, and secondary glioblastoma (GBM) from primary GBM and lower-grade gliomas with biology similar to GBM...
February 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28270234/genetic-and-epigenetic-stability-of-oligodendrogliomas-at-recurrence
#12
Koki Aihara, Akitake Mukasa, Genta Nagae, Masashi Nomura, Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Junji Shibahara, Miwako Takahashi, Toshimitsu Momose, Shota Tanaka, Shunsaku Takayanagi, Shunsuke Yanagisawa, Takahide Nejo, Satoshi Takahashi, Mayu Omata, Ryohei Otani, Kuniaki Saito, Yoshitaka Narita, Motoo Nagane, Ryo Nishikawa, Keisuke Ueki, Hiroyuki Aburatani, Nobuhito Saito
Among diffuse gliomas, oligodendrogliomas show relatively better prognosis, respond well to radiotherapy and chemotherapy, and seldom progress to very aggressive tumors. To elucidate the genetic and epigenetic background for such behavior and tumor evolution during tumor relapse, we comparatively analyzed 12 pairs of primary and recurrent oligodendrogliomas with 1p/19q-codeletion. Initial treatment for these patients was mostly chemotherapy alone. Temozolomide was used for 3, and procarbazine, nimustine and vincristine (PAV chemotherapy) were used for 7 patients...
March 7, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28263929/secondary-glioblastoma-molecular-and-clinical-factors-that-affect-outcome-after-malignant-progression-of-a-lower-grade-tumor
#13
Florian Gessler, Johannes Zappi, Juergen Konczalla, Joshua D Bernstock, Marie-Therese Forster, Marlies Wagner, Michel Mittelbronn, Volker Seifert, Christian Senft
BACKGROUND: There is limited information on prognostic factors and associated outcomes in patients with secondary glioblastoma (sGBM). OBJECTIVE: Herein we report on the outcomes of patients with sGBM and identify clinically relevant prognostic factors. METHODS: We retrospectively analyzed our institutional database for patients with histological evidence of WHO grade II-III gliomas that went on to develop WHO grade IV sGBM. The assessment of the isocitrate dehydrogenase-1 (IDH1) R132H mutation was performed via immunohistochemical (IHC) staining...
March 2, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28260349/somatic-structural-variations-in-pediatric-brain-tumors-an-update
#14
Zhengwei Li, Qingzeng Sun, Yingchun Shi
Pediatrics brain tumours are the second most frequent malignancy in children, and the most common cause of cancer-related deaths in both the 0-14-year and the 15-24-year age group. Although, pediatrics high-grade glioma (pHGG) is a histologically similar tumour to that arising in adults, these are distinct biological diseases, differing in copy number profiles and driver genetic alterations. Recent sequencing initiatives have conclusively shown the existence of subgroups of HGG marked by distinct driver mutations, which are significantly enriched in young children (H3F3A K27M), teenagers and young adults (H3F3A G34R/V), and middle- aged adults (IDH1/2)...
March 3, 2017: Minerva Pediatrica
https://www.readbyqxmd.com/read/28251430/atrx-status-correlates-with-11%C3%A2-c-methionine-uptake-in-who-grade-ii-and-iii-gliomas-with-idh1-mutations
#15
Takahiro Ogishima, Kaoru Tamura, Daisuke Kobayashi, Motoki Inaji, Shihori Hayashi, Reina Tamura, Tadashi Nariai, Kenji Ishii, Taketoshi Maehara
Recent studies on gliomas have shown frequent alterations in the alpha-thalassemia/mental retardation syndrome X-linked gene (ATRX). This study was designed to determine whether ATRX status correlates with uptake of (11)C-methionine in WHO grades II and III gliomas. Sixty-two patients underwent (11)C-methionine positron emission tomography scans prior to histological diagnosis. The tumor-to-normal ratio (T/N) of (11)C-methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain...
January 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28248117/-update-on-the-2016-who-classification-of-tumors-of-the-central-nervous-system-part-1-diffusely-infiltrating-gliomas
#16
Marian Švajdler, Boris Rychlý, Josef Zámečník, Peter Švajdler
Revised WHO 2016 classification of tumors of the central nervous system (CNS) incorporates for the first time genetic information in addition to morphology for classification of many tumor entities. One of the most important changes is restructuring the chapter of diffuse gliomas. Based on shared genetic driver mutations, diffusely infiltrating astrocytomas and oligodendrogliomas are now classified together, separately from "other" glial tumors with a more circumscribed growth pattern, different pathogenesis and clinical outcome...
2017: Ceskoslovenská Patologie
https://www.readbyqxmd.com/read/28246275/correlation-between-isocitrate-dehydrogenase-gene-aberrations-and-prognosis-of-patients-with-acute-myeloid-leukemia-a-systematic-review-and-meta-analysis
#17
Qingyu Xu, Yan Li, Na Lv, Yu Jing, Yihan Xu, Yuyan Li, Wenjun Li, Zilong Yao, Xiaosu Chen, Sai Huang, Li Li Wang, Yonghui Li, Li Yu
PURPOSE: Whether isocitrate dehydrogenase (IDH) gene aberrations affected prognosis of patients with acute myeloid leukemia (AML) was controversial. Here, we conducted a meta-analysis to evaluate their prognostic value. EXPERIMENTAL DESIGN: PubMed, Embase, Cochrane and Chinese databases were searched to identify studies exploring how IDH gene aberrations affected AML outcome. Pooled hazard ratios (HR) and relative risks (RR) were calculated, along with 95% confidence intervals (CI)...
February 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28239886/fibrocartilaginous-mesenchymoma-of-bone-a-single-institution-experience-with-molecular-investigations-and-a-review-of-the-literature
#18
M Gambarotti, A Righi, D Vanel, S Cocchi, S Benini, F M Elli, G Mantovani, P Ruggieri, S Boriani, D Donati, M Sbaraglia, A P Dei Tos, P Picci
AIMS: Fibrocartilaginous mesenchymoma is a rare intraosseous lesion with a total of 25 cases described in the literature. This study describes the clinical, radiological, and histological features of eight new cases of fibrocartilaginous mesenchymoma collected at a single institution between 1982 and 2016. The presence of GNAS and IDH1/2 mutations and MDM2 amplification was explored to evaluate possible links between fibrocartilaginous mesenchymoma, fibrous dysplasia, dedifferentiated chondrosarcoma, and low-grade osteosarcoma...
February 26, 2017: Histopathology
https://www.readbyqxmd.com/read/28236063/finding-of-idh1-r132h-mutation-in-histologically-non-neoplastic-glial-tissue-changes-surgical-strategies-a-case-report
#19
Christian Baastrup Søndergaard, David Scheie, Astrid Marie Sehested, Jane Skjøth-Rasmussen
INTRODUCTION: In 2016, the WHO classification of diffuse astrocytoma began to include isocitrate dehydrogenase (IDH) mutation in addition to histology. RESULTS: We here demonstrate a case where a 14-year-old boy presented with a parietal tumor with no histological evidence of neoplasia but with an IDH1 mutation. Due to the IDH1 R132H mutation, the patient was diagnosed with diffuse astrocytoma WHO grade II and underwent successful gross total resection of this near-eloquently located tumor...
February 24, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28235541/targeted-knockdown-of-polo-like-kinase-1-alters-metabolic-regulation-in-melanoma
#20
Rosie Elizabeth Ann Gutteridge, Chandra K Singh, Mary Ann Ndiaye, Nihal Ahmad
A limited number of studies have indicated an association of the mitotic kinase polo-like kinase 1 (PLK1) and cellular metabolism. Here, employing an inducible RNA interference approach in A375 melanoma cells coupled with a PCR array and multiple validation approaches, we demonstrated that PLK1 alters a number of genes associated with cellular metabolism. PLK1 knockdown resulted in a significant downregulation of IDH1, PDP2 and PCK1 and upregulation of FBP1. Ingenuity Pathway Analysis (IPA) identified that 1) glycolysis and the pentose phosphate pathway are major canonical pathways associated with PLK1, and 2) PLK1 inhibition-modulated genes were largely associated with cellular proliferation, with FBP1 being the key modulator...
February 22, 2017: Cancer Letters
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