In vitro studies suggested that glucose metabolism through the oxidative pentose phosphate pathway (oxPPP) can paradoxically feed superoxide-generating enzymes in failing hearts. We therefore tested the hypothesis that acute inhibition of the oxPPP reduces oxidative stress and enhances function and metabolism of the failing heart, in vivo. In 10 chronically instrumented dogs, congestive heart failure (HF) was induced by high-frequency cardiac pacing. Myocardial glucose consumption was enhanced by raising arterial glycemia to levels mimicking postprandial peaks, before and after intravenous administration of the oxPPP inhibitor 6-aminonicotinamide (80 mg/kg). Myocardial energy substrate metabolism was measured with radiolabeled glucose and oleic acid, and cardiac 8-isoprostane output was used as an index of oxidative stress. A group of five chronically instrumented, normal dogs served as control. In HF, raising glycemic levels from ∼ 80 to ∼ 170 mg/dL increased cardiac isoprostane output by approximately twofold, whereas oxPPP inhibition normalized oxidative stress and enhanced cardiac oxygen consumption, glucose oxidation, and stroke work. In normal hearts glucose infusion did not induce significant changes in cardiac oxidative stress. Myocardial tissue concentration of 6P-gluconate, an intermediate metabolite of the oxPPP, was significantly reduced by ∼ 50% in treated versus nontreated failing hearts, supporting the inhibitory effect of 6-aminonicotinamide. Our study indicates an important contribution of the oxPPP activity to cardiac oxidative stress in HF, which is particularly pronounced during common physiological changes such as postprandial glycemic peaks.

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Accepted tools for early cancer detection run the gamut from Pap staining to detect cervical cancer detection to colonoscopy and biopsy for colorectal cancer detection to imaging (mammogram and, in high risk women, magnetic resonance imaging) and biopsy for breast cancer detection. These modalities use standard cytopathologic assessment to determine if disease is present. There are few biologic (DNA, RNA, protein or carbohydrate) markers (biomarkers) that are in general use for the detection of any cancer, or to identify individuals at increased cancer risk. Biomarkers have been identified that provide information to physicians on disease prognosis. Panels of biomarkers are being developed to predict response to treatment in individuals with known cancer, and some are currently in use. Nonethless, there is a great need to identify accurate biomarkers for the early detection of a new cancer, to identify individuals at increased cancer risk, and among those with cancer, to determine their likelihood of responding to a given treatment, risk of disease relapse and death. Micro (mi)RNAs hold promise as biomarkers for determining at risk individuals, for early cancer detection, and among those with cancer, to assess how likely a person is to respond a given treatment, their risk of disease recurrence and death

Received : 2016.11.20; Accepted: 2016.12.23; Published: 2017.01.01 Abstract Introduction: Chemotherapy-induced thrombocytopenia (CIT) is the principal dose-limiting toxicity in patients with glioma undergoing chemotherapy, affecting up to 25% of such patients. Methods: This is a retrospective, unblinded case series. Patients undergoing chemotherapy for glioma (astrocytoma, oligodendroglioma or glioblastoma) who developed CIT were prescribed a thrombopoetin receptor agonist (TRA, i.e. eltrombopag or romiplostim). Doses were increased on a weekly basis, as required, until platelets were > 100×10 9 /L or this goal was not achieved with maximum dosing. Chemotherapy was resumed if possible and patients were followed as long as they remained on treatment. Results: A TRA was effective for CIT in 26/27 (96%). Once treated, all patients were able to resume chemotherapy as planned. Chemotherapy was continued for a median (range) of 11 months (2-28) and patients received an additional 5625 (0-16000) mg/m 2 of temozolomide, 0 (0-720) mg/m 2 of lomustine and 75 (0-390) mg/kg of bevacizumab. No patients in this series stopped chemotherapy due to completion of a planned regimen. Conclusions: By using TRAs for CIT, we were able to continue chemotherapy for a longer time and at higher doses than would have been possible without this treatment. A larger series is necessary in order to determine whether this translates into improved clinical outcomes. CIT is a common problem throughout oncology, and therefore we believe that use of TRA's for this purpose should be further investigated.