13 research outputs found
Chromothripsis in acute myeloid leukemia: Biological features and impact on survival
Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study defines incidence of chromothripsis in 395 newly diagnosed adult acute myeloid leukemia (AML) patients from three institutions, its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array (Affymetrix\uae) were performed on all samples. We detected chromothripsis with a custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher age (p = 0.002), ELN high risk (HR) (p < 0.001), lower white blood cell (WBC) count (p = 0.040), TP53 loss, and/or mutations (p < 0.001) while FLT3 (p = 0.025), and NPM1 (p = 0.032) mutations were mutually exclusive with chromothripsis. Chromothripsis-positive patients showed a worse overall survival (OS) (p < 0.001) compared with HR patients (p = 0.011) and a poor prognosis in a COX-HR optimal regression model. Chromothripsis presented the hallmarks of chromosome instability [i.e., TP53 alteration, 5q deletion, higher mean of copy number alteration (CNA), complex karyotype, alterations in DNA repair, and cell cycle] and focal deletions on chromosomes 4, 7, 12, 16, and 17. CBA. FISH showed that chromothripsis is associated with marker, derivative, and ring chromosomes. In conclusion, chromothripsis frequently occurs in AML (6.6%) and influences patient prognosis and disease biology
Four weeks one-leg training and high fat diet does not alter PPAR alpha protein or mRNA expression in human skeletal muscle
Overexpression of Cdc20 in clinically localized prostate cancer: Relation to high Gleason score and biochemical recurrence after laparoscopic radical prostatectomy
Targeting DNA Damage Response in Prostate Cancer by Inhibiting Androgen Receptor-CDC6-ATR-Chk1 Signaling
Influence of chronic inflammation on Bcl-2 and PCNA expression in prostate needle biopsy specimens
Four weeks one-leg training and high fat diet does not alter PPARalpha protein or mRNA expression in human skeletal muscle
Fatty acid metabolism is influenced by training and diet with exercise training mediating this through activation of nuclear hormone receptor peroxisome proliferator-activated receptor α (PPARα) in skeletal muscle. This study investigated the effect of training and high fat or normal diet on PPARα expression in human skeletal muscle. Thirteen men trained one leg (T) four weeks (31.5 h in total), while the other leg (UT) served as control. During the 4 weeks six subjects consumed high fat (FAT) diet and seven subjects maintained a normal (CHO) diet. Biopsies were obtained from vastus lateralis muscle in both legs before and after training. After the biopsy, one-leg extension exercise was performed in random order with both legs 30 min at 95% of workload max. A training effect was evident as citrate synthase activity increased (P < 0.05) by 15% in the trained, but not the control leg in both groups. During exercise respiratory exchange ratio was lower in FAT (0.86 ± 0.01, 0.83 ± 0.01, mean ± SEM) than CHO (0.96 ± 0.02, 0.94 ± 0.03) and in UT than T legs, respectively. The PPARα protein (144 ± 44, 104 ± 28, 79 ± 15, 79 ± 14, % of pre level) and PPARα mRNA (69 ± [2, 2], 78 ± [7, 6], 92 ± [22, 18], 106 ± [21, 18], % of pre level, geometric mean ± SEM) expression remained unchanged by diet and training in FAT (UT, T) and CHO (UT, T), respectively. After the training and diet CS, HAD, PPARα, UCP2, UCP3 and mFABP mRNA content remained unchanged, whereas GLUT4 mRNA was lower in both groups and LDHA mRNA was lower (P < 0.05) only in FAT. In conclusion: 4 weeks one leg knee extensor training did not affect PPARα protein or mRNA expression. Furthermore, higher fat oxidation during exercise after fat rich diet was not accompanied by an increased PPARα protein or mRNA expression after 4 weeks.J. W. Helge, D. Bentley, P. Schjerling, M. Willer, M. J. Gibala, J. Franch, M. A. Tapia-Laliena, J. R. Daugaard, J. L. Anderse