Molecular Characterization of High-Risk MDS Patients Treated with Azacitidine and Lenalidomide: Role of Inositide-Dependent Signalling, Mutations and Microrna

2017 ◽  
Vol 55 ◽  
pp. S54-S55
Author(s):  
M.Y. Follo ◽  
A. Pellagatti ◽  
R.N. Armstrong ◽  
S. Mongiorgi ◽  
A. Astolfi ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1575
Author(s):  
Lucia Zanoni ◽  
Riccardo Mei ◽  
Lorenzo Bianchi ◽  
Francesca Giunchi ◽  
Lorenzo Maltoni ◽  
...  

The primary aim of the study was to evaluate the role of [18F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [11C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax; target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology; subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected (n = 95). For both tracers, the location of the “blinded” prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [18F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [18F]Fluciclovine or [11C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [18F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively; whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.


Shock ◽  
1997 ◽  
Vol 7 (3) ◽  
pp. 157-163 ◽  
Author(s):  
Edward Kelly ◽  
Nishit S. Shah ◽  
Nathan N. Morgan ◽  
Simon C. Watkins ◽  
Andrew B. Peitzman ◽  
...  

Blood ◽  
2015 ◽  
Vol 125 (22) ◽  
pp. 3388-3392 ◽  
Author(s):  
Olli Silvennoinen ◽  
Stevan R. Hubbard

Abstract The critical role of Janus kinase-2 (JAK2) in regulation of myelopoiesis was established 2 decades ago, but identification of mutations in the pseudokinase domain of JAK2 in myeloproliferative neoplasms (MPNs) and in other hematologic malignancies highlighted the role of JAK2 in human disease. These findings have revolutionized the diagnostics of MPNs and led to development of novel JAK2 therapeutics. However, the molecular mechanisms by which mutations in the pseudokinase domain lead to hyperactivation of JAK2 and clinical disease have been unclear. Here, we describe recent advances in the molecular characterization of the JAK2 pseudokinase domain and how pathogenic mutations lead to constitutive activation of JAK2.


2015 ◽  
Vol 70 (9) ◽  
pp. 2488-2498 ◽  
Author(s):  
Sushmita D. Lahiri ◽  
Robert E. McLaughlin ◽  
James D. Whiteaker ◽  
Jane E. Ambler ◽  
Richard A. Alm

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
K Dinesh ◽  
S Hirenallur ◽  
Avinash G Telang ◽  
Santhosh K Mishra

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