Bellharrell0443
Abnormalities in the intrinsic apoptosis pathway, associated with single nucleotide variants (SNVs) in caspase (CASP) genes, alter head and neck squamous cell carcinoma (HNSCC) proliferation and progression. This prospective study aimed to evaluate whether CASP9 c.-1339A>G and CASP3 c.-1191A>G SNVs influence the outcome of patients with HNSCC. Two hundred sixty-two HNSCC patients were enrolled in the study.
DNA and RNA of peripheral blood samples were analyzed using real-time polymerase chain reaction (PCR) for genotyping and quantitative PCR method for gene expression, respectively. Differences in CASP3 expressions were analyzed using the Mann-Whitney test. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier curves, log-rank test, and Cox analyses.
CASP3 c.-1191AG or GG genotype was associated with higher CASP3 expression when compared with AA genotype (0.50 arbitrary units (AUs)±0.29 standard deviation (SD) vs 0.28 AUs±0.12 SD; P=.02). Patients with CASP9 c.-1339GG genotype had 1.54 more chance of presenting disease progression or relapse than patients with CASP9 c.-1339AA or AG genotype. Patients with CASP9 c.-1339GG and CASP3 c.-1191GG combined genotype had 2.64 more chance of presenting progression or relapse of the disease and 2.84 more chance of evolving to death than those with the remaining combined genotypes.
Our findings provide, for the first time, preliminary evidence that inherited abnormalities in the intrinsic apoptosis pathway, related to CASP9 c.-1339A>G and CASP3 c.-1191A>G SNVs, act as predictors of HNSCC patients' survival.
G SNVs, act as predictors of HNSCC patients' survival.Minimal residual disease (MRD) assessment is of high clinical relevance in patients with mantle cell lymphoma (MCL). In mature B-cell malignancies, the presence of somatic hypermutations (SHM) in Variable-Diversity-Joining Heavy chain (VDJH) rearrangements leads to frequent mismatches between primers, probes, and the target, thus impairing tumor cells quantification. Alternative targets, such as immunoglobulin kappa-deleting-element (IGK-Kde) rearrangements, might be suitable for MRD detection. We aimed at evaluating the applicability of IGK-Kde rearrangements for MRD quantification in MCL patients by real-time quantitative polymerase chain reaction (RQ-PCR)/digital-droplet-PCR (ddPCR). IGK screening was performed on bone marrow samples from two cohorts the first from Turin (22 patients enrolled in the FIL-MCL0208 trial, NCT02354313) and the second from Rome (15 patients). IGK-Kde rearrangements were found in 76% (28/37) of cases, representing the sole molecular marker in 73% (8/11) of IGH-BCL1/IGH negative cases. MRD RQ-PCR monitoring was possible in 57% (16/28) of cases, showing a 100% concordance with the conventional targets. However, the frequent background amplification affected the sensitivity of the assay, that was lower in MCL compared to acute lymphoblastic leukemia and in line with multiple myeloma published results. ddPCR had a good concordance with RQ-PCR and it might help to identify false positive/negative results. From a clinical perspective, we suggest that IGK-Kde can be a candidate target for MRD monitoring and deserves a validation of its predictive value in prospective MCL series.BRAFV600E mutation is highly prevalent in patients with papillary thyroid carcinoma (PTC), and TERT promoter (TERTp) mutation is strongly associated with cancer-related mortality. However, predictive power of the two mutations remains inconclusive. We aimed to verify the prognostic effects of both mutations to assess the value of mutation detection for risk stratification in terms of PTC prognosis and tumour invasion, to guide PTC diagnosis and treatment. We conducted a literature search in the MEDLINE (PubMed), EMBASE, Web of Science and CENTRAL (Cochrane library) databases, from inception to February 2020. Basic characteristics, prognoses and clinicopathological features were collected from the included studies for further analysis. Twelve studies involving 4184 PTC patients were enrolled in our analysis. In total, 2412 (57.6%) of the patients carried either BRAFV600E or TERTp mutation, and 290 (6.9%) patients had both mutations. TERTp mutation was more common in patients with BRAFV600E mutation (RR = 1.75 [95% CI 1.44-2.13]). Patients with both mutations had a worse prognosis compared with those with a single mutation (vs BRAFV600E only RR = 5.34 [4.20-6.78] vs TERTp only RR = 2.12 [1.41-3.19]). TERTp mutation alone independently increased the risk of a poor prognosis (RR = 2.90 [1.93-4.35]) in terms of mortality (RR = 15.09 [7.75-29.37]), disease persistence (RR = 4.00 [2.03-7.90]), recurrence (RR = 4.34 [4.20-6.78]), lymph node metastasis (RR = 1.57 [1.24-1.99]) and distant metastasis (RR = 2.94 [1.13-7.65]). We found that PTC patients with BRAFV600E mutation were more likely to have TERTp mutation. TERTp mutation was an independent predictive factor for poor prognosis of PTC patients, but the predictive value of BRAFV600E mutation remains inconclusive. Patients with both mutations have remarkably higher risks of adverse outcomes compared with those with a single mutation. PTC patients could benefit from mutation detection for aiding risk stratification (BRAF + TERT+ > BRAF - TERT+ > BRAF + TERT-).High tibial osteotomy (HTO) is a well-established treatment for medial compartment knee osteoarthritis (OA), which shifts the weight-bearing axis from the medial to the lateral side of the knee. FM19G11 in vitro As the adjacent ankle joint may be directly affected by the change in biomechanics, this study aimed to evaluate the change in the intersegmental foot and ankle motion after HTO in patients with genu varum. The study included 24 patients who underwent HTO, and 48 older healthy participants as a control group. Segmental foot kinematics were evaluated using a 3D multisegment foot model, and gait data of temporal and spatial parameters were obtained. After HTO, normalized stride length significantly increased with a tendency for increases in gait speed. In hallux kinematics relative to the forefoot, the sagittal motions of both the patients and the control group were similar throughout the majority of the gait cycle. In forefoot kinematics relative to the hindfoot, the pre-HTO state revealed significant pronation throughout the gait cycle, while the post-HTO state showed a similar position and motion to the control group.