Search results for "Isocitrate Dehydrogenase"
showing 10 items of 16 documents
Quantitative Imaging of D-2-Hydroxyglutarate in Selected Histological Tissue Areas by a Novel Bioluminescence Technique
2016
Abstract Patients with malignant gliomas have a poor prognosis with average survival of less than one year. Whereas in other tumor entities the characteristics of tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in brain tumors, notably in gliomas. One metabolic feature characteristic of gliomas, in particular diffuse astrocytomas and oligodendroglial tumors, is the variable content of D-2-hydroxyglutarate (D2HG), a metabolite, which was discovered first in this tumor entity. D2HG is generated in large amounts due to various “gain-of–function” mutations in the isocitrate dehydrogenases IDH-1 and IDH-2. Meanwhile, D2HG has been detected in se…
Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.
2019
Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…
Concept of Spectrobiopsy Facing Gliomas: Rational and Future Perspectives Related to Target Therapy
2020
Gliomas represent the most common primary intracranial tumors with an estimated incidence of 31% of all central nervous system neoplasms. Lesions originated from glial cells are extremely heterogeneous, ranging from low grade to high grade with different clinical and biological malignancy. Glioblastoma multiforme (GBM) is the most aggressive and frequent primary malignant tumor of the central nervous system in adults. Even though in the past decades considerable efforts have been made in the therapeutic management of this type of tumor,2 the prognosis after diagnosis of GBM remains extremely poor, reaching a median overall survival of 12–18 months. In 2016 the World Health Organization clas…
Magnetic Resonance Spectrobiopsy for Prediction of Isocitrate Dehydrogenase Mutation in Glioma
2020
Despite the existence of multimodal therapy paradigm, high-grade gliomas (HGGs) remain devastating tumors associated with one of the worst prognoses. Glioblastoma (GBM) is the most frequent reported histologic type with a median survival, after surgery and combined treatment with chemotherapy and radiotherapy, ranging from 12 to 16 months. The poor prognosis is due to the lack of therapeutic efficacy of chemical agents and irradiation in hypoxic tumor areas. Experimental studies have investigated several molecules with the aim to counteract several downstream signaling important in tumor progression, unfortunately without conclusive results. Several studies have shown that the extent of res…
WHO-defined ‘myelodysplastic syndrome with isolated del(5q)’ in 88 consecutive patients: survival data, leukemic transformation rates and prevalence …
2010
The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with 'myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age >or=70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or >or=2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, r…
Assessing the genetic diversity ofCentaurea parlatorisgroup (sect.Dissectae, Compositae) in Sicily using isozymes
2011
Abstract The Centaurea parlatoris group belongs to sect. Dissectae and is one of the most taxonomically critical groups in Sicily. The taxa included in it inhabit dry slopes, pastures and rocky places. Some of them are narrow endemics to Sicily, and others to Italy. The great morphological variability at the intrapopulation level has not permitted the creation of an adequate taxonomic scheme. The recent proposal of two new species from Sicily confirms the insufficient knowledge of the taxonomic diversity. This study involves eight Sicilian populations of the C. parlatoris group. Seven loci from nine enzyme systems [isocitrate dehydrogenase (IDH), malate dehydrogenase (MDH), 6-phosphoglucona…
D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice.
2014
Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in several cancer types and cause the neurometabolic syndrome D2-hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in production of D2-hydroxyglutaric acid (D-2HG). To study the pathophysiological consequences of the accumulation of D-2HG, we generated transgenic mice with conditionally activated IDH2R140Q and IDH2R172K alleles. Global induction of mutant IDH2 expression in adults resulted in dilated cardiomyopathy, white matter abnormalities throughout the central nervous system (CNS), and muscular dystrophy. Embryonic activation of mutant IDH2 resulted in more pronounced ph…
PICCA study: panitumumab in combination with cisplatin/gemcitabine chemotherapy in KRAS wild-type patients with biliary cancer—a randomised biomarker…
2017
Abstract Background Combination chemotherapy has shown benefit in the treatment of biliary cancer and further improvements might be achieved by the addition of a biological agent. We report here the effect of chemotherapy with the monoclonal EGFR antibody panitumumab as therapy for KRAS wild-type biliary cancer. Patients and methods Patients with advanced biliary tract cancer were randomised (2:1) to receive cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and day 8/q3w with (arm A) or without panitumumab (arm B; 9 mg/kg BW, i.v q3w). The primary end-point was the evaluation of progression-free survival (PFS) at 6 months. Secondary end-points included objective response rate (ORR), ov…
Effects of training on regional substrate oxidation in the hearts of ageing rats.
1989
23-month-old male rats were trained by running for 20 weeks. The oxidation rates of succinate, glutamate+malate, palmitoylcarnitine, and pyruvate and the activities of lactate dehydrogenase, citrate synthase, isocitrate dehydrogenase and cytochrome oxidase were measured in the subendocardium and subepicardium and in the right ventricle. Regional differences of substrate oxidation rates in the myocardium of old sedentary or trained rats were less than in young rats, suggesting that regional differences in the cardiac work load disappear during ageing. Training did not improve oxidation rates, in contradiction to some previous results.
Multivariable non-invasive association of isocitrate dehydrogenase mutational status in World Health Organization grade II and III gliomas with advan…
2020
Aim To investigate multivariable analyses for noninvasive association of the isocitrate dehydrogenase (IDH) mutational status in grade II and III gliomas including evaluation of T2 mapping-sequences. Methods Magnetic resonance imaging (MRI) examinations with histopathologically proven World Health Organization grade II and III gliomas were retrospectively enrolled. Multivariate receiver operating characteristics (ROC) analyses to associate IDH mutational status were performed containing quantitative T2 mapping analyses and qualitative characteristics (sex, age, localization, heterogeneity, oedema, necrosis and diameter). Relaxation times were calculated pixelwise by means of standardized RO…