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https://www.readbyqxmd.com/read/27904446/somatic-mutations-of-isocitrate-dehydrogenases-1-and-2-are-prognostic-and-follow-up-markers-in-patients-with-acute-myeloid-leukaemia-with-normal-karyotype
#1
Marijana Virijevic, Teodora Karan-Djurasevic, Irena Marjanovic, Natasa Tosic, Mirjana Mitrovic, Irena Djunic, Natasa Colovic, Ana Vidovic, Nada Suvajdzic-Vukovic, Dragica Tomin, Sonja Pavlovic
BACKGROUND: Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. PATIENTS AND METHODS: In our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome...
December 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27895504/deferred-radiotherapy-and-upfront-procarbazine-acnu-vincristine-administration-for-1p19q-codeleted-oligodendroglial-tumors-are-associated-with-favorable-outcome-without-compromising-patient-performance-regardless-of-who-grade
#2
Nobuhiro Hata, Koji Yoshimoto, Ryusuke Hatae, Daisuke Kuga, Yojiro Akagi, Satoshi O Suzuki, Toru Iwaki, Tadahisa Shono, Masahiro Mizoguchi, Koji Iihara
Recently updated phase III trials revealed the favorable effect of add-on procarbazine-lomustine-vincristine chemotherapy (CT) to radiotherapy (RT) in treating anaplastic oligodendrogliomas with 1p19q codeletion (codel). However, the underlying rationality of deferring RT and upfront CT administration for these tumors is yet to be elucidated. Here, we retrospectively analyzed the long-term outcome of our case series with oligodendroglial tumors treated with deferred RT and upfront procarbazine+nimustine+vincristine (PAV) in the introduction administration...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27893285/recent-advances-in-subtyping-tumors-of-the-central-nervous-system-using-molecular-data
#3
Jens Schittenhelm
Primary brain tumors account for substantial morbidity and mortality. They often infiltrate the brain diffusely, continue growing, and cause adverse events, such as headaches, seizures, and neurological deficits. The classification of primary brain tumors, based for decades on histology, has been fundamentally changed by the World Health Organization in 2016 by incorporation of molecular data. Areas covered: Literature from glioblastomas, high- and low-grade astrocytic, oligodendroglial, glioneuronal and ependymal tumors from the last five years were reviewed...
November 28, 2016: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/27890252/aml-in-2016-where-we-are-now
#4
REVIEW
Jacob M Rowe
A high relapse rate for patients with acute myeloid leukemia (AML) is still a major barrier to the long-term survival of these patients. Nevertheless, considerable progress has been made both in the biology and therapy of the disease. Specifically, progress has been made in the areas of integrated genomic analysis for prognosis, the widening application of minimal residual disease (MRD) monitoring in clinical practice, the development of new agents, and the increasing use of drugs, such as IDH and FLT3 inhibitors, as a bridge to transplant...
December 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27888628/impact-of-epidemiological-characteristics-of-supratentorial-gliomas-in-adults-brought-about-by-the-2016-world-health-organization-classification-of-tumors-of-the-central-nervous-system
#5
Haihui Jiang, Yong Cui, Junmei Wang, Song Lin
The latest World Health Organization (WHO) classification of tumors of the central nervous system (CNS) integrates both histological and molecular features in the definition of diagnostic entities. This new approach enrolls novel entities of gliomas. In this study, we aimed to reveal the epidemiological characteristics, including age at diagnosis, gender ratio, tumor distribution and survival, of these new entities. We retrospectively reclassified 1210 glioma samples according to the 2016 CNS WHO diagnostic criteria...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27880937/prognostic-relevance-of-mirna-155-methylation-in-anaplastic-glioma
#6
Maximilian Georg Schliesser, Rainer Claus, Thomas Hielscher, Christiane Grimm, Dieter Weichenhan, Jonas Blaes, Benedikt Wiestler, Peter Hau, Johannes Schramm, Felix Sahm, Elisa K Weiß, Markus Weiler, Constance Baer, Friederike Schmidt-Graf, Gabriele Schackert, Manfred Westphal, Anne Hertenstein, Patrick Roth, Norbert Galldiks, Christian Hartmann, Torsten Pietsch, Joerg Felsberg, Guido Reifenberger, Michael Christoph Sabel, Frank Winkler, Andreas von Deimling, Christoph Meisner, Peter Vajkoczy, Michael Platten, Michael Weller, Christoph Plass, Wolfgang Wick
The outcome of patients with anaplastic gliomas varies considerably depending on single molecular markers, such as mutations of the isocitrate dehydrogenase (IDH) genes, as well as molecular classifications based on epigenetic or genetic profiles. Remarkably, 98% of the RNA within a cell is not translated into proteins. Of those, especially microRNAs (miRNAs) have been shown not only to have a major influence on physiologic processes but also to be deregulated and prognostic in malignancies.To find novel survival markers and treatment options we performed unbiased DNA methylation screens that revealed 12 putative miRNA promoter regions with differential DNA methylation in anaplastic gliomas...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27864835/intrahepatic-cholangiocarcinoma-frequently-shows-loss-of-bap1-and-pbrm1-expression-and-demonstrates-specific-clinicopathologic-and-genetic-characteristics-with-bap1-loss
#7
Kento Misumi, Akimasa Hayashi, Junji Shibahara, Junichi Arita, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Masashi Fukayama
AIMS: BAP1 and PBRM1 expression loss has been observed in multiple cancers, including intrahepatic cholangiocarcinoma (ICC). We investigated BAP1 and PBRM1 expression in ICC using immunohistochemistry, and analyzed its association with clinicopathological and genetic features, including two histologic subtypes. METHODS AND RESULTS: Whole-section slides of 108 consecutive primary ICC cases were immunostained against BAP1 and PBRM1. Complete loss of BAP1 and PBRM1 was observed in 21 (19...
November 19, 2016: Histopathology
https://www.readbyqxmd.com/read/27852392/-clinical-outcome-of-intramyocardial-dissecting-hematoma-after-acute-myocardial-infarction
#8
Y Zhao, L Sun, J C Han, W X Liu, T T Man, Z Chen, Y H He
Objective: To observe the clinical outcome of intramyocardial dissecting hematoma (IDH) after acute myocardial infarction (MI). Methods: The clinical characteristics and outcomes of nine patients with IDH after acute MI in Beijing Anzhen Hospital from 2010 to 2014 were retrospectively assessed, and all the patients were followed up. Results: The mean age of nine IDH patients (7 males, 2 females) was (61±5) years. One patient was diagnosed as right ventricular IDH and died before surgery because of deteriorated cardiac and renal failure...
November 1, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27852048/igfbp2-expression-predicts-idh-mutant-glioma-patient-survival
#9
L Eric Huang, Adam L Cohen, Howard Colman, Randy L Jensen, Daniel W Fults, William T Couldwell
Mutations of the isocitrate dehydrogenase (IDH) 1 and 2 genes occur in ~80% of lower-grade (WHO grade II and grade III) gliomas. Mutant IDH produces (R)-2-hydroxyglutarate, which induces DNA hypermethylation and presumably drives tumorigenesis. Interestingly, IDH mutations are associated with improved survival in glioma patients, but the underlying mechanism for the difference in survival remains unclear. Through comparative analyses of 286 cases of IDH-wildtype and IDH-mutant lower-grade glioma from a TCGA data set, we report that IDH-mutant gliomas have increased expression of tumor-suppressor genes (NF1, PTEN, and PIK3R1) and decreased expression of oncogenes(AKT2, ARAF, ERBB2, FGFR3, and PDGFRB) and glioma progression genes (FOXM1, IGFBP2, and WWTR1) compared with IDH-wildtype gliomas...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27849434/less-invasive-phenotype-found-in-isocitrate-dehydrogenase-mutated-glioblastomas-than-in-isocitrate-dehydrogenase-wild-type-glioblastomas-a-diffusion-tensor-imaging-study
#10
Stephen J Price, Kieren Allinson, Hongxiang Liu, Natalie R Boonzaier, Jiun-Lin Yan, Victoria C Lupson, Timothy J Larkin
Purpose To explore the diffusion-tensor (DT) imaging-defined invasive phenotypes of both isocitrate dehydrogenase (IDH-1)-mutated and IDH-1 wild-type glioblastomas. Materials and Methods Seventy patients with glioblastoma were prospectively recruited and imaged preoperatively. All patients provided signed consent, and the local research ethics committee approved the study. Patients underwent surgical resection, and tumor samples underwent immunohistochemistry for IDH-1 R132H mutations. DT imaging data were coregistered to the anatomic magnetic resonance study and reconstructed to provide the anisotropic and isotropic components of the DT...
November 16, 2016: Radiology
https://www.readbyqxmd.com/read/27837434/prediction-of-genetic-subgroups-in-adult-supra-tentorial-gliomas-by-pre-and-intraoperative-parameters
#11
Shunsuke Nakae, Kazuhiro Murayama, Hikaru Sasaki, Masanobu Kumon, Yuya Nishiyama, Shigeo Ohba, Kazuhide Adachi, Shinya Nagahisa, Takuro Hayashi, Joji Inamasu, Masato Abe, Mitsuhiro Hasegawa, Yuichi Hirose
Recent progress in neuro-oncology has validated the significance of genetic diagnosis in gliomas. We previously investigated IDH1/2 and TP53 mutations via Sanger sequencing for adult supratentorial gliomas and reported that PCR-based sequence analysis classified gliomas into three genetic subgroups that have a strong association with patient prognosis: IDH mutant gliomas without TP53 mutations, IDH and TP53 mutant gliomas, and IDH wild-type gliomas. Furthermore, this analysis had a strong association with patient prognosis...
November 11, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27824159/oncometabolite-d-2-hydroxyglurate-directly-induces-epithelial-mesenchymal-transition-and-is-associated-with-distant-metastasis-in-colorectal-cancer
#12
Hugh Colvin, Naohiro Nishida, Masamitsu Konno, Naotsugu Haraguchi, Hidekazu Takahashi, Junichi Nishimura, Taishi Hata, Koichi Kawamoto, Ayumu Asai, Kenta Tsunekuni, Jun Koseki, Tsunekazu Mizushima, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Deranged metabolism is a hallmark of cancer, playing a significant role in driving the disease process. One such example is the induction of carcinogenesis by the oncometabolite D-2 hydroxyglutarate (D-2HG), which is produced by the mutated enzyme isocitrate dehydrogenase (IDH) occurring in subsets of leukaemias and brain tumours. The oncogenic property of D-2HG appears to stem from its ability to interfere with the activities of α-ketoglutarate-dependent dioxygenases, including the Jumonji family histone demethylases...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27823638/molecular-characteristics-of-biliary-tract-cancer
#13
REVIEW
Davendra P S Sohal, Shiva Shrotriya, Mohamed Abazeed, Michael Cruise, Alok Khorana
Biliary tract cancers (intrahepatic, perihilar and extrahepatic cholangiocarcinoma, and gallbladder and cystic duct cancers) are uncommon but highly lethal malignancies. Clinical presentation is often late, precluding curative surgical resection in most cases. For advanced disease, therapeutic options are limited to systemic chemotherapy, with suboptimal outcomes. An understanding of the molecular characteristics of biliary tract cancers may allow the clinical development of therapies targeting actionable alterations with the ultimate goal of improving clinical outcomes...
November 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27810736/oxalomalate-reduces-expression-and-secretion-of-vascular-endothelial-growth-factor-in-the-retinal-pigment-epithelium-and-inhibits-angiogenesis-implications-for-age-related-macular-degeneration
#14
Sung Hwan Kim, Hyunjin Kim, Hyeong Jun Ku, Jung Hyun Park, Hanvit Cha, Seoyoon Lee, Jin Hyup Lee, Jeen-Woo Park
Clinical and experimental observations indicate a critical role for vascular endothelial growth factor (VEGF), secreted by the retinal pigment epithelium (RPE), in pathological angiogenesis and the development of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). RPE-mediated VEGF expression, leading to angiogenesis, is a major signaling mechanism underlying ocular neovascular disease. Inhibiting this signaling pathway with a therapeutic molecule is a promising anti-angiogenic strategy to treat this disease with potentially fewer side effects...
October 24, 2016: Redox Biology
https://www.readbyqxmd.com/read/27809598/emerging-targeted-therapy-for-glioma
#15
Julie J Miller, Patrick Y Wen
Gliomas are the most common malignant primary brain tumors in adults. Despite aggressive treatment with surgery, radiation and chemotherapy, these tumors are incurable and invariably recur. Molecular characterization of these tumors in recent years has advanced our understanding of gliomagenesis and offered an array of pathways that can be specifically targeted. Areas Covered: The most commonly dysregulated signaling pathways found in gliomas will be discussed, as well as the biologic importance of these disrupted pathways and how each may contribute to tumor development...
November 4, 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27800031/long-term-survival-in-a-patient-with-glioblastoma-on-antipsychotic-therapy-for-schizophrenia-a-case-report-and-literature-review
#16
REVIEW
Shahdabul Faraz, Susan Pannullo, Marc Rosenblum, Andrew Smith, A Gabriella Wernicke
Glioblastoma is not only the most common primary brain tumor, but also the most aggressive. Currently, the most effective treatment of surgery, chemotherapy and radiation therapy allows for a modest median survival of 15 months. Here, we report a case of a 57-year-old male with histologically confirmed glioblastoma with unfavorable prognostic characteristics (poor performance status and persistent neurological symptoms after surgery), whose expected 5-year survival is 0%. Further genetic analysis offered a mixed prognostic picture with positive methylation of 0-6-methylguinine-DNA (deoxyribonucleic acid) methyltransferase (MGMT; favorable prognosis) and wild-type isocitrate dehydrogenase 1 (IDH-1; unfavorable prognosis)...
November 2016: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/27791984/droplet-digital-pcr-is-a-powerful-technique-to-demonstrate-frequent-fgfr1-duplication-in-dysembryoplastic-neuroepithelial-tumors
#17
Frédéric Fina, Doriane Barets, Carole Colin, Corinne Bouvier, Laëtitia Padovani, Isabelle Nanni-Metellus, L'Houcine Ouafik, Didier Scavarda, Andrey Korshunov, David T W Jones, Dominique Figarella-Branger
Dysembryoplastic neuroepithelial tumors (DNT) share V600E mutation in the BRAF gene with other low grade neuroepithelial tumors (LGNTs). FGFR1 internal tandem duplication of the tyrosine-kinase domain (FGFR1-ITD), another genetic alteration that also leads to MAP kinase pathway alteration, has been previously reported in LGNTs by whole-genome sequencing. In the present study we searched for FGFR1-ITD by droplet digital PCR (DDPCR™) and for FGFR1 point mutations by HRM-sequencing in a series of formalin-fixed paraffin-embedded (FFPE) LGNTs including 12 DNT, 2 oligodendrogliomas lacking IDH mutation and 1p/19q co- deletion (pediatric-type oligodendrogliomas; PTOs), 3 pediatric diffuse astrocytomas (PDAs), 14 gangliogliomas (GGs) and 5 pilocytic astrocytomas (PAs)...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27788029/establishment-of-anti-human-atrx-monoclonal-antibody-amab-6
#18
Satoshi Ogasawara, Yuki Fujii, Mika K Kaneko, Hiroharu Oki, Hemragul Sabit, Mitsutoshi Nakada, Hiroyoshi Suzuki, Koichi Ichimura, Takashi Komori, Yukinari Kato
Gliomas are the most frequently occurring brain tumors with a heterogeneous molecular background. The molecular subgrouping of gliomas more prognostically stratifies patients into distinct groups compared with conventional histological classification. The most important molecules for the subtype diagnosis of diffuse gliomas are mutations of isocitrate dehydrogenase (IDH), TERT promoter, and α-thalassemia/mental-retardation-syndrome-X-linked (ATRX) and the codeletion of 1p/19q. Among them, IDH and ATRX mutations can be diagnosed using specific monoclonal antibodies (mAbs)...
October 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/27780605/idh1-2-gene-hotspot-mutations-in-central-nervous-system-tumours-analysis-of-922-chinese-patients
#19
Ni Chen, Tianpin Yu, Jing Gong, Ling Nie, Xueqin Chen, Mengni Zhang, Miao Xu, Junya Tan, Zhengzheng Su, Jinjing Zhong, Qiao Zhou
Mutations of isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) genes have been identified as early molecular events in the development of astrocytomas and oligodendrogliomas. Data regarding the status and prevalence of IDH1/2 mutations in Chinese patients are limited. Herein we report our data from West China Hospital, a major Chinese medical centre. IDH1(R132H) mutation was analysed by immunohistochemistry with the mutation-specific IDH1(R132H) antibody in 1011 patients, including 922 central nervous system (CNS) tumours and 89 non-neoplastic CNS lesions, and PCR-based direct sequencing of IDH1/2 gene mutation in 570 of these samples...
October 22, 2016: Pathology
https://www.readbyqxmd.com/read/27772642/intensive-hemodialysis-and-treatment-complications-and%C3%A2-tolerability
#20
Jose A Morfin, Richard J Fluck, Eric D Weinhandl, Sheru Kansal, Peter A McCullough, Paul Komenda
Hemodialysis (HD) treatment can be difficult to tolerate. Common complications are intradialytic hypotension (IDH) and long time to recovery after an HD session. IDH, as defined by nadir systolic blood pressure < 90mmHg and intradialytic decline > 30mmHg, occurs in almost 8% of HD sessions. IDH may be caused by aggressive ultrafiltration in response to interdialytic weight gain, can lead to myocardial stunning and cardiac arrhythmias, and is associated with increased risk for death. Long recovery time after a treatment session is also common...
November 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
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