483 research outputs found

    Standardization of BCR-ABL1 p210 Monitoring: From Nested to Digital PCR

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    The introduction of tyrosine kinase inhibitors in 2001 as a targeted anticancer therapy has significantly improved the quality of life and survival of patients with chronic myeloid leukemia. At the same time, with the introduction of tyrosine kinase inhibitors, the need for precise monitoring of the molecular response to therapy has emerged. Starting with a qualitative polymerase chain reaction, followed by the introduction of a quantitative polymerase chain reaction to determine the exact quantity of the transcript of interest-p210 BCR-ABL1, molecular monitoring in patients with chronic myeloid leukemia was internationally standardized. This enabled precise monitoring of the therapeutic response, unification of therapeutic protocols, and comparison of results between different laboratories. This review aims to summarize the steps in the diagnosis and molecular monitoring of p210 BCR-ABL1, as well as to consider the possible future application of a more sophisticated method such as digital polymerase chain reaction

    CALR-positive myeloproliferative disorder in a patient with Ph-positive chronic myeloid leukemia in durable treatment-free remission: a case report

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    Current diagnostic criteria for Philadelphia-negative myeloproliferative neoplasia (MPN) have been redefined by the discovery of Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL) and calreticulin (CALR) genetic alterations. Only few cases of coexistence of CALR-mutated MPN and Philadelphia-positive chronic myeloid leukemia (CML) have been described so far. Here we report the case of a patient with CML diagnosed in 2001, treated with imatinib and pegylated interferon (IFN) frontline. She reached complete molecular remission (CMR) and discontinued imatinib, maintaining treatment free remission. Due to persistent thrombocytosis, we repeated bone marrow (BM) analysis and diagnosed CARL-mutated essential thrombocythemia (ET). A CALR-positive clone was found to be present since 2001, and was unaffected by imatinib treatment, possibly representing a molecular abnormality arising at stem cell level

    Characterization of a Novel Polymorphism in PPARG Regulatory Region Associated with Type 2 Diabetes and Diabetic Retinopathy in Italy

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    Peroxisome proliferator-activated receptor gamma polymorphisms have been widely associated with type 2 diabetes, although their role in the pathogenesis of vascular complications is not yet demonstrated. In this study, a cohort of 211 type 2 diabetes, 205 obese, and 254 control individuals was genotyped for Pro12Ala, C1431T, C-2821T polymorphisms, and for a newly identified polymorphism (A-2819G). The above-mentioned polymorphisms were analyzed by gene-specific PCR and direct sequencing of all samples. A significant difference was found for -2819G frequency when patients with type 2 diabetes—particularly diabetic women with the proliferative retinopathy—were compared with healthy control individuals. In conclusion, we identified a novel polymorphism, A-2819G, in PPARG gene, and we found it to be associated with type 2 diabetes and proliferative retinopathy in diabetic females. In the analyzed population, this variant represents a genetic risk factor for developing the diabetic retinopathy, whereas Pro12Ala and C1431T do not

    Baseline Tumor Size as Prognostic Index in Patients With Advanced Solid Tumors Receiving Experimental Targeted Agents

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    Abstract Background Baseline tumor size (BTS) has been associated with outcomes in patients with cancer treated with immunotherapy. However, the prognostic impact of BTS on patients receiving targeted therapies (TTs) remains undetermined. Methods We reviewed data of patients with advanced solid tumors consecutively treated within early-phase clinical trials at our institution from 01/2014 to 04/2021. Treatments were categorized as immunotherapy-based or TT-based (biomarker-matched or not). BTS was calculated as the sum of RECIST1.1 baseline target lesions. Results A total of 444 patients were eligible; the median BTS was 69 mm (IQR 40-100). OS was significantly longer for patients with BTS lower versus higher than the median (16.6 vs. 8.2 months, P < .001), including among those receiving immunotherapy (12 vs. 7.5 months, P = .005). Among patients receiving TT, lower BTS was associated with longer PFS (4.7 vs. 3.1 months, P = .002) and OS (20.5 vs. 9.9 months, P < .001) as compared to high BTS. However, such association was only significant among patients receiving biomarker-matched TT, with longer PFS (6.2 vs. 3.3 months, P < .001) and OS (21.2 vs. 6.7 months, P < .001) in the low-BTS subgroup, despite a similar ORR (28% vs. 22%, P = .57). BTS was not prognostic among patients receiving unmatched TT, with similar PFS (3.7 vs. 4.4 months, P = .30), OS (19.3 vs. 11.8 months, P = .20), and ORR (33% vs. 28%, P = .78) in the 2 BTS groups. Multivariate analysis confirmed that BTS was independently associated with PFS (P = .03) and OS (P < .001) but not with ORR (P = .11). Conclusions Higher BTS is associated with worse survival outcomes among patients receiving biomarker-matched, but not biomarker-unmatched TT

    Endometrial Carcinoma and Bisphenol A:A Pilot Case-Control Study

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    Female cancers represent one of the major causes of morbidity and mortality in the adult population

    Ghrelin, Sleep Reduction and Evening Preference: Relationships to CLOCK 3111 T/C SNP and Weight Loss

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    Circadian Locomotor Output Cycles Kaput (CLOCK), an essential element of the positive regulatory arm in the human biological clock, is involved in metabolic regulation. The aim was to investigate the behavioral (sleep duration, eating patterns and chronobiological characteristics) and hormonal (plasma ghrelin and leptin concentrations) factors which could explain the previously reported association between the CLOCK 3111T/C SNP and weight loss.We recruited 1495 overweight/obese subjects (BMI: 25-40 kg/m(2)) of 20-65 y. who attended outpatient obesity clinics in Murcia, in southeastern Spain. We detected an association between the CLOCK 3111T/C SNP and weight loss, which was particularly evident after 12-14 weeks of treatment (P = 0.038). Specifically, carriers of the minor C allele were more resistant to weight loss than TT individuals (Mean±SEM) (8.71±0.59 kg vs 10.4±0.57 kg) C and TT respectively. In addition, our data show that minor C allele carriers had: 1. shorter sleep duration Mean ± SEM (7.0±0.05 vs 7.3±0.05) C and TT respectively (P = 0.039), 2. higher plasma ghrelin concentrations Mean ± SEM (pg/ml) (1108±49 vs 976±47)(P = 0.034); 3. delayed breakfast time; 4. evening preference and 5. less compliance with a Mediterranean Diet pattern, as compared with TT homozygotes.Sleep reduction, changes in ghrelin values, alterations of eating behaviors and evening preference that characterized CLOCK 3111C carriers could be affecting weight loss. Our results support the hypothesis that the influence of the CLOCK gene may extend to a broad range of variables linked with human behaviors

    26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

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    This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

    Test of Lepton Flavour Universality using the B_s^0→D_s^- τ^+ ν_τ with 3 prongs τ^+ decays and validation of the new opto-electronics for the RICH Upgrade at the LHCb experiment

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    The Standard Model (SM) of particle physics assumes that the couplings between leptons and the electroweak gauge bosons are independent of the lepton flavour up to a correction due to the mass. This property is known as Lepton Flavour Universality (LFU). Ideal laboratories to test the LFU are the b-hadron semileptonic decays which can be studied through the ratios of branching fractions between decays with the τ lepton and the ones with the μ lepton in the final state: R(Hc) =B(Hb → Hcτν)/B(Hb → Hcμν), with Hb and Hc the b−hadron which originates the decay and the c−hadron produced in the decay respectively. Experimental results on LFU tests have been obtained by Belle, BaBar and LHCb collaborations and show tension with the SM prediction of about 3.4σ when considering the combination of the measurement of R(D) and R(D∗). Exploiting the abundance of the b-hadron produced in the LHCb environment and the features of the detector, that allow to reconstruct the b-hadron decay vertex with high precision and to perform particle identification, this thesis documents the preliminary studies for the measurement of R(Ds) using the τ decaying in 3 charged pions. The data sample used for the studies corresponds to an integrated luminosity of 2 fb^{−1} of proton-proton collision events at a centre-of-mass energy of 8 TeV collected by the LHCb experiment in 2012. Given the request of high precision measurements to further test the SM in many other sectors, the LHCb experiment is currently being upgraded to be able to operate at a luminosity of about 2×10^33cm^{−2}s^{−1} from the start of Run3 in 2022. To cope with the challenge of a five-fold increased instantaneous luminosity, and the need to read-out the full LHCb detector at a rate of 40 MHz, the photon detectors and the electronics chain of both the Ring Imaging CHerenkov (RICH) detectors have been replaced. This thesis also describes the quality assurance and test protocols on the new opto-electronics and reports of the commissioning activities.ITA: Il Modello Standard (MS) della fisica delle particelle elementari assume che l’accoppiamento elettrodebole tra i leptoni e i bosoni di gauge sia indipendente dalla famiglia leptonica a meno di correzioni dovute alla massa. Tale proprietà è conosciuta come Universalità Leptonica (Lepton Flavour Universality o LFU). I decadimenti semileptonici di adroni b sono laboratori ideali per testare la LFU attraverso il confronto tra i rapporti di diramazione dei decadimenti nel cui stato finale sono coinvolti un leptone τ o un leptone μ: R(Hc) = B(Hb → Hcτν)/ B(Hb → Hcμν), dove Hb e Hc sono rispettivamente l’adrone b da cui si origina il decadimento e l’adrone c prodotto nel decadimento. Risultati sperimentali su test di LFU sono stati ottenuti dalle collaborazioni Belle, Babar e LHCb e mostrano tensioni con le predizioni del MS di circa 3.4σ quando si considera la combinazione delle misure di R(D) and R(D∗). Questa tesi, sfruttando l’abbondanza di adroni b prodotti in LHCb e le caratteristiche del rivelatore, documenta gli studi preliminari per la misura di R(Ds) richiedendo nello stato finale un leptone τ che decade in 3 pioni carichi. I dati analizzati per questi studi sono stati raccolti da LHCb nel 2012, sono relativi a collisioni protone protone con energia nel centro di massa pari a 8TeV, e corrispondono ad una luminosità integrata di 2 fb^{−1}. Data la richiesta di misure sempre più precise per testare ulteriormente il MS, l’esperimento LHCb è stato sottoposto ad un upgrade per essere in grado di operare alla luminosità di circa 2×10^33cm^{−2}s^{−1} dall’inizio del Run3 nel 2022. Per fronteggiare la sfida di una luminosità istantanea aumentata di cinque volte rispetto al Run2 e alla necessità di acquisire i dati ad una frequenza di 40 MHz, i rivelatori di fotoni e l’intera catena di elettronica di entrambi i sottorivelatori Ring Imaging CHerenkov sono stati sostituiti. Questa tesi descrive, inoltre, i protocolli di controllo qualità, i test effettuati sulla nuova optoelettronica, e le attività di istallazione e messa in opera dei nuovi sottorivelatori