Selenium and vitamin E for prevention of non–muscle-invasive bladder cancer recurrence and progression

Importance Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non–muscle-invasive bladder cancer. Objective To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC. Design, Setting, and Participants This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required. Interventions Oral selenium (200 μg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo. Main Outcome and Measures Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022). Results The study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment. Conclusions and Relevance In this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required

Dynamic Light Scattering (DLS) for nanoparticle size-distribution acquisiton III

Particle size distributions (PSDs) of Ti3C2 MXene nanoparticles in aqueous suspension using DLS are obtained. See uploaded pdf for details.</p

Quantitative phase analysis of powder X-ray diffraction patterns of Ti3C2Tz MXene synthesis products

Rietveld refinement was performed on powder diffraction patterns of a triphasic system, where one phase constitutes an internal standard, to be able to quantify the proportion of product (Ti3C2 MXene) and reactant (Ti3AlC2 MAX phase) present after a synthesis trial. Synthesis trial parameters are determined in a Design of Experiments (DoE) screening design. See file 2022-12-06 - Quantitative-Phase-Analysis-QPA-of-MXene-synthesis-product-PXRD-patterns.pdf for full dataset details.</p

EDXRF of MXene synthesis products I

Perform EDXRF on Ti3C2 MXene synthesis products to verify both composition and purity</p

Zeta-potential measurement of MXene suspensions II

Zetasizer used to measure zeta potential of Ti3C2 MXene nanoparticles in aqueous suspension. See pdf for more details.</p

SEM - FEI Quanta 200 II

Obtain micrographs to reassess vacuum oven-dried Ti3C2 film homogeneity with a combination of backscatter and secondary electron detectio

SEM - Tescan Mira3 II

Obtain micrographs to investigate vacuum oven-dried Ti3C2 film morpholog

SEM - Tescan Mira3 III

Obtain micrographs to investigate vacuum oven-dried Ti3C2 film morphology and homogeneit

XRD analysis of vacuum-oven dried MXene film - PANalytical X'Pert Pro

Characterise vacuum-oven dried MXene film using X-ray diffractio

SEM - Zeiss EVO 50 III

Investigate morphology of MAX phase particles and vacuum oven-dried MXene film with imaging and ED