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https://www.readbyqxmd.com/read/28527004/comparative-volumetric-analysis-of-the-extent-of-resection-of-molecularly-and-histologically-distinct-low-grade-gliomas-and-its-role-on-survival
#1
Chikezie I Eseonu, Francisco Eguia, Karim ReFaey, Oscar Garcia, Fausto J Rodriguez, Kaisorn Chaichana, Alfredo Quinones-Hinojosa
The authors investigate the role of extent of resection (EOR) and genetic markers on patient outcome and survival for LGGs. We conducted a retrospective cohort between 2005 and 2015, of 109 adult patients who underwent surgery for a LGG by a single surgeon. Volumetric computations of MRI studies were conducted to evaluate the EOR, and genetic markers (IDH1, 1p/19q co-deletion, and p53) were assessed and their effects on survival and neurological outcome were evaluated. The median EOR was 88.1%. Permanent postoperative neurological deficits were seen in 4...
May 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28521409/evaluation-of-a-novel-approach-to-circulating-tumor-cell-isolation-for-cancer-gene-panel-analysis-in-patients-with-breast-cancer
#2
Soo Jeong Lee, Cham Han Lee, Sung Ho Choi, Sei Hyun Ahn, Byung Ho Son, Jong Won Lee, Jong Han Yu, Nak-Jung Kwon, Woo Chung Lee, Kap-Seok Yang, Dong Hyoung Lee, Du Yeol Han, Mi So Choi, Pyeong-Soo Park, Hyun Kyung Lee, Myoung Shin Kim, Jinseon Lee, Byung Hee Jeon
Liquid biopsy isolation of circulating tumor cells (CTCs) allows the genomic analysis of CTCs, which is useful in the determination of personalized cancer therapy. In the present study, CTCs from patients with breast cancer were enriched and successfully analyzed using cancer gene panel analysis. Blood samples from 11 patients with breast cancer were collected and CTCs enriched for using size-based filtration. The enriched CTCs were analyzed using immunofluorescence staining with antibodies directed against epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 45...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28508327/assessment-of-molecular-markers-demonstrates-concordance-between-samples-acquired-via-stereotactic-biopsy-and-open-craniotomy-in-both-anaplastic-astrocytomas-and-glioblastomas
#3
Florian Gessler, Peter Baumgarten, Joshua D Bernstock, Patrick Harter, Stephanie Lescher, Christian Senft, Volker Seifert, Gerhard Marquardt, Lutz Weise
The classification, treatment and prognosis of high-grade gliomas has been shown to correlate with the expression of molecular markers (e.g. MGMT promotor methylation and IDH1 mutations). Acquisition of tumor samples may be obtained via stereotactic biopsy or open craniotomy. Between the years 2009 and 2013, 22 patients initially diagnosed with HGGs via stereotactic biopsy, that ultimately underwent open craniotomy for resection of their tumor were prospectively included in an institutional glioma database...
May 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28507382/prognostic-significance-of-idh-1-mutation-in-patients-with-glioblastoma-multiforme
#4
Inamullah Khan, Muhammad Waqas, Muhammad Shahzad Shamim
Focus of brain tumour research is shifting towards tumour genesis and genetics, and possible development of individualized treatment plans. Genetic analysis shows recurrent mutation in isocitrate dehydrogenase (IDH1) gene in most Glioblastoma multiforme (GBM) cells. In this review we evaluated the prognostic significance of IDH 1 mutation on the basis of published evidence. Multiple retrospective clinical analyses correlate the presence of IDH1 mutation in GBM with good prognostic outcomes compared to wild-type IDH1...
May 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/28498812/structure-based-discovery-of-clomifene-as-a-potent-inhibitor-of-cancer-associated-mutant-idh1
#5
Mengzhu Zheng, Weiguang Sun, Suyu Gao, Shanshan Luan, Dan Li, Renqi Chen, Qian Zhang, Lixia Chen, Jiangeng Huang, Hua Li
Isocitrate dehydrogenase (IDH) plays an indispensable role in the tricarboxylic acid cycle, and IDH mutations are present in nearly 75% of glioma and 20% of acute myeloid leukemia. One IDH1R132H inhibitor (clomifene citrate) was found by virtual screening method, which can selectively suppress mutant enzyme activities in vitro and in vivo with a dose-dependent manner. The molecular docking indicated that clomifene occupied the allosteric site of the mutant IDH1. Enzymatic kinetics also demonstrated that clomifene inhibited mutant enzyme in a non-competitive manner...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28497806/management-of-diffuse-low-grade-gliomas-in-adults-use-of-molecular-diagnostics
#6
REVIEW
Jan Buckner, Caterina Giannini, Jeanette Eckel-Passow, Daniel Lachance, Ian Parney, Nadia Laack, Robert Jenkins
Diffuse WHO grade II gliomas are histologically and genetically heterogeneous. The 2016 WHO classification redefines grade II gliomas with respect to morphological and molecular tumour alterations: grade II oligodendrogliomas are defined by the presence of whole-arm codeletion in chromosomal arms 1p/19q, whereas isocitrate dehydrogenase (IDH) mutations define subclasses of astrocytoma. Although histological grade remains useful, the prognoses of patients with glioma are more tightly associated with molecular alterations than with grade, and chromosomal and gene array technologies are becoming increasingly beneficial in understanding tumour genetic heterogeneity...
May 12, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28497669/mapping-seizure-foci-and-tumor-genetic-factors-in-glioma-associated-seizure-patients
#7
Mao Yunhe, Yang Yuan, Wang Xiang, Liu Yanhui, Mao Qing
BACKGROUND: Epilepsy, which is the most common symptom accompanying gliomas, was reported as an independent favorable prognosis factor for glioma patients. However, the correlation between glioma location and epilepsy prognosis, genesis and genetic phenotypes of the glioma associated seizure (GAS) patients is far from clear, the purpose of the current study was to provide probabilistic radiographic atlases reflecting seizure susceptible regions, relationship between tumor associated biomarkers and seizure initiation and poor epilepsy prognosis areas...
May 11, 2017: Journal of Neurosurgical Sciences
https://www.readbyqxmd.com/read/28493366/frequent-idh2-r172-mutations-in-undifferentiated-and-poorly-differentiated-sinonasal-carcinomas
#8
Snjezana Dogan, Deborah J Chute, Bin Xu, Ryan N Ptashkin, Raghu Chandramohan, Jacklyn Casanova-Murphy, Khedoudja Nafa, Justin A Bishop, Simion I Chiosea, Edward B Stelow, Ian Ganly, David G Pfister, Nora Katabi, Ronald A Ghossein, Michael F Berger
Sinonasal undifferentiated carcinoma (SNUC) is a high-grade malignancy with limited treatment options and poor outcome. A morphologic spectrum of 47 sinonasal tumors including 17 (36.2%) SNUCs were analyzed at genomic level. Thirty carcinomas (Cohort 1) were subjected to a hybridization exon-capture next-generation sequencing assay (MSK-IMPACT(TM) ) to interrogate somatic variants in 279 or 410 cancer-related genes. Seventeen sinonasal tumors (Cohort 2) were examined only for presence of IDH1/2 exon 4 mutations by Sanger sequencing...
May 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28492066/progression-inference-for-somatic-mutations-in-cancer
#9
Leif E Peterson, Tatiana Kovyrshina
Computational methods were employed to determine progression inference of genomic alterations in commonly occurring cancers. Using cross-sectional TCGA data, we computed evolutionary trajectories involving selectivity relationships among pairs of gene-specific genomic alterations such as somatic mutations, deletions, amplifications, downregulation, and upregulation among the top 20 driver genes associated with each cancer. Results indicate that the majority of hierarchies involved TP53, PIK3CA, ERBB2, APC, KRAS, EGFR, IDH1, VHL, etc...
April 2017: Heliyon
https://www.readbyqxmd.com/read/28484589/idh1-or-2-mutations-do-not-predict-outcome-and-do-not-cause-loss-of-5-hydroxymethylcytosine-or-altered-histone-modifications-in-central-chondrosarcomas
#10
Arjen H G Cleven, Johnny Suijker, Georgios Agrogiannis, Inge H Briaire-de Bruijn, Norma Frizzell, Attje S Hoekstra, Pauline M Wijers-Koster, Anne-Marie Cleton-Jansen, Judith V M G Bovée
BACKGROUND: Mutations in isocitrate dehydrogenase (IDH)1 or -2 are found in ~50% of conventional central chondrosarcomas and in up to 87% of their assumed benign precursors enchondromas. The mutant enzyme acquires the activity to convert α-ketoglutarate into the oncometabolite d-2-hydroxyglutarate (d-2-HG), which competitively inhibits α-ketoglutarate dependent enzymes such as histone- and DNA demethylases. METHODS: We therefore evaluated the effect of IDH1 or -2 mutations on histone modifications (H3K4me3, H3K9me3 and H3K27me3), chromatin remodeler ATRX expression, DNA modifications (5-hmC and 5-mC), and TET1 subcellular localization in a genotyped cohort (IDH, succinate dehydrogenase (SDH) and fumarate hydratase (FH)) of enchondromas and central chondrosarcomas (n = 101) using immunohistochemistry...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28484171/current-diagnosis-and-treatment-for-pediatric-acute-myeloid-leukemia
#11
Norio Shiba
Acute myeloid leukemia (AML) is a complex disease caused by chromosomal aberrations, mutations, epigenetic modifications, and the deregulated expression of genes, leading to increased myeloid cell proliferation and decreased hematopoietic progenitor cell differentiation. Although most of these aberrations are correlated with prognosis, accurate risk stratification remains a challenge even after incorporating these molecular markers. Currently, some genetic mutations that allow risk stratification have been identified in adult AML, including DNMT3A and IDH1/2...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28481241/biomarker-and-histopathology-evaluation-of-patients-with-recurrent-glioblastoma-treated-with-galunisertib-lomustine-or-the-combination-of-galunisertib-and-lomustine
#12
David Capper, Andreas von Deimling, Alba A Brandes, Antoine F Carpentier, Santosh Kesari, Juan M Sepulveda-Sanchez, Helen R Wheeler, Olivier Chinot, Lawrence Cher, Joachim P Steinbach, Pol Specenier, Jordi Rodon, Ann Cleverly, Claire Smith, Ivelina Gueorguieva, Colin Miles, Susan C Guba, Durisala Desaiah, Shawn T Estrem, Michael M Lahn, Wolfgang Wick
Galunisertib, a Transforming growth factor-βRI (TGF-βRI) kinase inhibitor, blocks TGF-β-mediated tumor growth in glioblastoma. In a three-arm study of galunisertib (300 mg/day) monotherapy (intermittent dosing; each cycle =14 days on/14 days off), lomustine monotherapy, and galunisertib plus lomustine therapy, baseline tumor tissue was evaluated to identify markers associated with tumor stage (e.g., histopathology, Ki67, glial fibrillary acidic protein) and TGF-β-related signaling (e.g., pSMAD2). Other pharmacodynamic assessments included chemokine, cytokine, and T cell subsets alterations...
May 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28473643/g6pd-deficiency-does-not-affect-the-cytosolic-glutathione-or-thioredoxin-antioxidant-defense-in-mouse-cochlea
#13
White Karessa, Mi-Jung Kim, Dalian Ding, Chul Han, Hyo-Jin Park, Zaimary Meneses, Masaru Tanokura, Paul Linser, Richard Salvi, Shinichi Someya
Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway; it catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate and NADP(+) to NADPH, and is thought to be the principal source of NADPH for the cytosolic glutathione and thioredoxin antioxidant defense systems. We investigated the roles of G6PD in the cytosolic antioxidant defense in the cochlea of G6pd hypomorphic mice that were backcrossed onto normal-hearing CBA/CaJ mice. Young G6pd-deficient mice displayed a significant decrease in cytosolic G6PD protein levels and activities in the inner ears...
May 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28471392/taking-a-bad-turn-compromised-dna-damage-response-in-leukemia
#14
REVIEW
Nadine Nilles, Birthe Fahrenkrog
Genomic integrity is of outmost importance for the survival at the cellular and the organismal level and key to human health. To ensure the integrity of their DNA, cells have evolved maintenance programs collectively known as the DNA damage response. Particularly challenging for genome integrity are DNA double-strand breaks (DSB) and defects in their repair are often associated with human disease, including leukemia. Defective DSB repair may not only be disease-causing, but further contribute to poor treatment outcome and poor prognosis in leukemia...
May 4, 2017: Cells
https://www.readbyqxmd.com/read/28467784/in-silico-gene-expression-analysis-reveals-glycolysis-and-acetate-anaplerosis-in-idh1-wild-type-glioma-and-lactate-and-glutamate-anaplerosis-in-idh1-mutated-glioma
#15
Mohammed Khurshed, Remco J Molenaar, Krissie Lenting, William P Leenders, Cornelis J F van Noorden
Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) initiate low-grade glioma and secondary glioblastoma and induce a neomorphic activity that converts α-ketoglutarate (α-KG) to the oncometabolite D-2-hydroxyglutarate (D-2-HG). It causes metabolic rewiring that is not fully understood. We investigated the effects of IDH1 mutations (IDH1MUT) on expression of genes that encode for metabolic enzymes by data mining The Cancer Genome Atlas. We analyzed 112 IDH1 wild-type (IDH1WT) versus 399 IDH1MUT low-grade glioma and 157 IDH1WT versus 9 IDH1MUT glioblastoma samples...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465358/mutant-idh1-regulates-the-tumor-associated-immune-system-in-gliomas
#16
Nduka M Amankulor, Youngmi Kim, Sonali Arora, Julia Kargl, Frank Szulzewsky, Mark Hanke, Daciana H Margineantu, Aparna Rao, Hamid Bolouri, Jeff Delrow, David Hockenbery, A McGarry Houghton, Eric C Holland
Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying the differences in survival between these two tumor types, immune-related differences in cell content are potentially important contributors. In order to investigate the role of IDH mutations in immune response, we created a syngeneic pair mouse model for mutant IDH1 (muIDH1) and wtIDH1 gliomas and demonstrated that muIDH1 mice showed many molecular and clinical similarities to muIDH1 human gliomas, including a 100-fold higher concentration of 2-hydroxygluratate (2-HG), longer survival time, and higher CpG methylation compared with wtIDH1...
May 2, 2017: Genes & Development
https://www.readbyqxmd.com/read/28456748/reprogramming-acute-myeloid-leukemia-into-sensitivity-for-retinoic-acid-driven-differentiation
#17
REVIEW
Noortje van Gils, Han J M P Verhagen, Linda Smit
The success of all-trans retinoic acid (ATRA) therapy for acute promyelocytic leukemia (APL) provides a rationale to use retinoic acid-based therapy also for other subtypes of acute myeloid leukemia (AML). Recently, several studies showed that ATRA may efficiently drive leukemic cells into differentiation and/or apoptosis in a subset of AML patients with a NPM1 mutation, a FLT3-ITD, an IDH1 mutation, and patients overexpressing EVI-1. Since not all patients within these molecular subgroups respond to ATRA and clinical trials that tested ATRA response in non-APL AML patients have been very disappointing, the identification of additional biomarkers may help to identify patients that strongly respond to ATRA-based therapy...
April 26, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28451993/key-rates-for-the-grades-and-transformation-ability-of-glioma-model-simulations-and-clinical-cases
#18
Elizabeth Scribner, James R Hackney, Hannah C Machemehl, Reina Afiouni, Krishna R Patel, Hassan M Fathallah-Shaykh
Tumor progression to higher grade is a fundamental property of cancer. The malignant advancement of the pathological features may either develop during the later stages of cancer growth (natural evolution) or it may necessitate new mutations or molecular events that alter the rates of growth, dispersion, or neovascularization (transformation). Here, we model the pathological and radiological features of grades 2-4 gliomas at the times of diagnosis and death and study grade development and the progression to higher grades...
April 27, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28451406/anaplastic-astrocytoma-cells-not-detectable-on-autopsy-following-long-term-temozolomide-treatment-a-case-report
#19
Hirofumi Hirano, Takashi Kawahara, Masaki Niiro, Hajime Yonezawa, Tomoko Takajyou, Yasuyo Ohi, Ikumi Kitazono, Kiyohiro Sakae, Kazunori Arita
We herein present an autopsy case of a glioma patient who received long-term treatment with temozolomide (TMZ). The patient, a 35-year-old man with a hypointense tumor of the left frontal lobe, without contrast enhancement following gadolinium (Gd) administration on T1-weighted images, underwent tumor removal surgery, after which the tumor was diagnosed as anaplastic astrocytoma. By the third round of surgery, the tumor had progressed to anaplastic astrocytoma with contrast enhancement following Gd administration, and the patient received 60 Gy of external beam radiotherapy and nimustine hydrochloride (ACNU)-based chemotherapy...
March 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28445981/mir-148a-increases-glioma-cell-migration-and-invasion-by-downregulating-gadd45a-in-human-gliomas-with-idh1-r132h-mutations
#20
Daming Cui, Pandey Sajan, Jinlong Shi, Yiwen Shen, Ke Wang, Xianyu Deng, Lin Zhou, Pingping Hu, Liang Gao
High-grade gliomas are severe tumors with poor prognosis. An R132H mutation in the isocitrate dehydrogenase (IDH1) gene prolongs the life of glioma patients. In this study, we investigated which genes are differentially regulated in IDH1 wild type (IDH1WT) or IDH1 R132H mutation (IDH1R132H) glioblastoma cells. Growth arrest and DNA-damage-inducible protein (GADD45A) was downregulated and microRNA 148a (miR-148a) was upregulated in in IDH1R132H human glioblastomas tissues. The relationship between GADD45A and miR-148a is unknown...
April 11, 2017: Oncotarget
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