p53 Status Correlates with the Risk of Recurrence in Non-Muscle Invasive Bladder Cancers Treated with Bacillus Calmette–Guérin: A Meta-Analysis

<div><p>Objective</p><p>Published studies have yielded inconsistent results on the relationship between p53 status and the prognosis of non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette–Guérin (BCG) intravesical therapy. Therefore, we performed a meta-analysis to evaluate the prognostic value of p53 in NMIBC treated with BCG.</p><p>Methods</p><p>We systematically searched for relevant literature in PubMed, EMBASE, CNKI, and Chinese Wanfang databases. Hazard ratios (HRs) with 95% confidence intervals (CIs) were combined as the effect size (ES) across studies for recurrence-free survival (RFS) and progression-free survival (PFS).</p><p>Results</p><p>A total of 11 studies, consisting of 1,049 participants, met the criteria. Overall, there was no clear relationship between p53 status and RFS or PFS for NMIBC patients treated with BCG (HR: 1.40, 95% CI: 0.91-2.16; HR: 1.37, 95% CI: 0.90-2.09, respectively). Obvious heterogeneity was observed across the studies (I² = 69.5%, <i>P</i> = 0.001; I² = 44.7%, <i>P</i> = 0.081, respectively). In stratified analysis by region, p53 overexpression was a predictor of poor RFS in Asian populations (HR: 1.57, 95% CI: 1.08-2.27). In addition, after excluding the studies that possibly contributed to the heterogeneity by the Galbraith plot, the overall association for RFS became statistically significant (HR: 1.38 95% CI: 1.08-1.77) without evidence of heterogeneity (I² = 0.0%, <i>P</i> = 0.499).</p><p>Conclusion</p><p>This meta-analysis suggests that p53 overexpression in NMIBC patients treated with BCG may be associated with RFS, especially in Asian populations. Because of the heterogeneity and other limitations, further studies with rigid criteria and large populations are still warranted to confirm our findings.</p></div

Flowchart of study selection.

<p>Flowchart of study selection.</p

Subgroup results of RFS and heterogeneity test.

<p>Subgroup results of RFS and heterogeneity test.</p

Subgroup results of PFS and heterogeneity test.

<p>Subgroup results of PFS and heterogeneity test.</p

Forest plots of HRs estimated for the relationship between p53 expression and RFS (A) or PFS (B) among NMIBC patients treated with BCG.

<p>Forest plots of HRs estimated for the relationship between p53 expression and RFS (A) or PFS (B) among NMIBC patients treated with BCG.</p

Main characteristics of all studies included in this meta-analysis.

<p>No., number; NMIBC, non-muscle-invasive bladder cancer; RFS, recurrence-free survival; PFS, progression-free survival.</p><p>Main characteristics of all studies included in this meta-analysis.</p

Galbraith plot analysis was used to evaluate heterogeneity.

<p>It suggested that two studies were the potential source of heterogeneity for RFS (A), while one for PFS (B).</p

Subgroup results of RFS and heterogeneity test.

<p>Subgroup results of RFS and heterogeneity test.</p

Polymeric Micelles with Uniform Surface Properties and Tunable Size and Charge: Positive Charges Improve Tumor Accumulation

The influence of surface charge on biodistribution and tumor accumulation remains debatable because most research has been carried out by changing the surface functional groups of nanocarriers. In this work, to avoid the interference of different surface properties such as chemical composition and hydrophilicity, polymeric micelles with uniform PEG coatings and continuously tunable sizes or zeta potentials were developed via a facile route. Therefore, the influence of surface charge on the biological functions of micelles with the same size and surface properties could be well-explored. In this case, positive charge was found to enhance both tumor cellular uptake and tumor accumulation. Immunofluorescence staining indicated that the improved tumor accumulation was mainly due to the tumor vasculature targeting of positively charged micelles. It is predicted that efficient drug delivery systems for both tumor vasculature and cancer cell targeting can be realized based on positively charged micelles

Structure of decision analytic model.

<p>ART, antiretroviral therapy.</p