👤 Amin H Nassar

Osteoporosis (OP) is the most prevalent metabolic bone disease. Numerous genetic loci are strongly related to OP. AXIN1 is a significant gene that serves an important role in the WNT signaling pathway. The aim of this study was to explore the association between the AXIN1 genetic polymorphism (rs9921222) and OP susceptibility. A total of 101 subjects were enrolled in the study (50 patients with OP and 51 healthy individuals). Genomic DNA was extracted from whole blood using the QIAamp DNA Blood Mini Kit, and the AXIN1 gene polymorphism (rs9921222) was genotyped by TaqMan allelic discrimination assays. A logistic regression analysis was used to assess the association between genotypes and OP risk. We found that AXIN1 rs9921222 had a significant association with the susceptibility of OP under the homozygote model (TT vs. CC: OR = 16.6, CI = 2.03-136.4, p = 0.009), (CT vs. CC: OR = 6.3, CI = 1.23-31.8, p = 0.027), recessive genetic model (TT vs.TC-CC: OR = 13.6, CI = 1.7-110.4, p = 0.015), and the dominant model (TT-TC vs. CC: OR = 9.7, CI = 2.6-36.3, p < 0.001). Allele T was significantly associated with OP risk (T vs. C: OR = 10.5, CI = 3.5-31.15, p = 0.001). There was a statistically significant difference between genotypes in mean platelet volume (p = 0.004), and platelet distribution width (p = 0.025). In addition, lumbar spine bone density, and femur neck bone density were significantly different between genotypes (p < 0.001). AXIN1 rs9921222 was associated with OP susceptibility in the Egyptian population and should be considered a potential determinant risk for OP. Show less

Everolimus monotherapy use for metastatic renal cell carcinoma (mRCC) has diminished due to recent approvals of immune checkpoint and VEGF inhibitors. We hypothesized that gene expression associated with everolimus benefit may provide rationale to select appropriate patients. To address this hypothesis, tumors from a phase I/II trial that compared everolimus alone or with BNC105P, a vascular disrupting agent, were profiled using Nanostring as a discovery cohort. A phase III trial (CheckMate 025) was used for validation. Clinical benefit (CB) was defined as response or stable disease for ≥6 months. A propensity score covariate adjustment was used, and model discrimination performance was assessed using the area under the ROC curve (AUC). In a discovery cohort of 82 patients, 35 (43%) were treated with everolimus alone and 47 (57%) received everolimus + BNC105P. Median PFS (mPFS) was 4.9 (95% CI, 2.8-6.2) months. A four-gene signature (ASXL1, DUSP6, ERCC2, and HSPA6) correlated with CB with everolimus ± BNC105P [AUC, 86.9% (95% CI, 79.2-94.7)]. This was validated in 130 patients from CheckMate 025 treated with everolimus [AUC, 60.2% (95% CI, 49.7-70.7)]. Among 43 patients (52.4%) with low expression of an 18-gene signature, everolimus + BNC105P was associated with significantly longer mPFS compared with everolimus alone (10.4 vs. 6.9 months; HR, 0.49; 95% CI, 0.24-1.002; Show less