Comparative effectiveness of first-line systemic treatments for metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.

OBJECTIVES: No head-to-head trials had been performed to estimate the relative effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSi) in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). We aimed to perform a systematic review and network meta-analysis to evaluate the comparative effectiveness of various systemic treatment agents for patients with mCRPC. METHODS: A comprehensive literature search was conducted for abstracts and full-text articles from the database's inception through April 27, 2023. The study concentrated on assessing radiographic progression-free survival (rPFS) for both overall and homologous recombination repair mutation (HRRm) population, with overall survival (OS) as the secondary measure. Under the Bayesian framework, the overall effect was pooled using the fixed-effects model in base case analysis. Scenario analysis using restricted mean survival time (RMST) methods was performed to test the robustness of the results. RESULTS: Nine studies with 6,830 patients and 8 unique treatment options were included. Network meta-analysis demonstrated that talazoparib in combination with enzalutamide (TALA + ENZA; overall population, hazard ratio [HR], 0.20; 95% credible interval [CrI]: 0.16-0.26; RMST, 3.51; 95% confidence interval [CI] 2.46-4.60; HRRm population, HR, 0.15; 95% CrI: 0.09-0.23; RMST, 4.14; 95% CI 2.84-5.39) was superior to other treatments in the first-line setting in terms of rPFS. The results of Bayesian framework and RMST models showed consistent efficacy ranks. When extrapolated to overall survival benefit, within the Bayesian framework, olaparib plus abiraterone acetate and prednisone (OLAP + AAP) achieved the highest OS benefit for the overall population, which was not statistically significant when compared to TALA + ENZA. However, TALA + ENZA achieved the highest OS benefit at 3 years by applying RMST. CONCLUSIONS: We suggest that talazoparib in combination with enzalutamide is probably a preferred treatment agent for the overall population and HRRm patients with mCRPC. Given the limitations of network framework and the modeling assumptions undertaken to finalize the analyses, results should be cautiously interpreted.

Slow freezing versus vitrification for the cryopreservation of zebrafish (Danio rerio) ovarian tissue.

The aim of the present study was to compare the efficiency of vitrification and slow freezing techniques for the cryopreservation of zebrafish ovarian tissue containing immature follicles. In Experiment 1, assessment of cell membrane integrity by trypan blue exclusion staining was used to select the best cryoprotectant solution for each cryopreservation method. Primary growth (PG) oocytes showed the best percentage of membrane integrity (63.5 ± 2.99%) when SF4 solution (2 M methanol + 0.1 M trehalose + 10% egg yolk solution) was employed. The vitrification solution, which presented the highest membrane integrity (V2; 1.5 M methanol + 5.5 M Me2SO + 0.5 M sucrose + 10% egg yolk solution) was selected for Experiment 2. Experiment 2 aimed to compare the vitrification and slow freezing techniques in the following parameters: morphology, oxidative stress, mitochondrial activity, and DNA damage. Frozen ovarian tissue showed higher ROS levels and lower mitochondrial activity than vitrified ovarian tissue. Ultrastructural observations of frozen PG oocytes showed rupture of the plasma membrane, loss of intracellular contents and a large number of damaged mitochondria, while vitrified PG oocytes had intact mitochondria and cell plasma membranes. We conclude that vitrification may be more effective than slow freezing for the cryopreservation of zebrafish ovarian tissue.

Production of live larvae following in vitro maturation of zebrafish oocytes.

This study aimed to assess the effects of carp pituitary extract (CPE), follicle stimulating hormone (FSH) and luteinizing hormone (LH) on zebrafish oocyte maturation and the ability of these mature oocytes to be fertilized and developed until hatching. Stage III follicles were matured in eight treatments: five concentrations of CPE (16, 32, 48, 64 and 80 µg/mL), one of FSH (0.5 µg/mL), one of LH (0.5 µg/mL), or one combination of FSH (0.5 µg/mL) and LH (0.5 µg/mL). Maturation rates in CPE treatments were 12.8% (16 µg/mL), 24.8% (32 µg/mL), 27.0% (48 µg/mL), 22.7% (64 µg/mL) and 9.6% (80 µg/mL); in FSH was 15.7% (0.5 µg/mL), in LH was 31.8% (0.5 µg/mL) and in FSH (0.5 µg/mL) combined with LH (0.5 µg/mL) it was 50.4%. In vitro fertilization was performed in all treatments; however, only the treatment combining FSH and LH resulted in fertilized oocytes. After maturation using FSH combined with LH, the cleavage rate was 33.3% and hatching rate of live larvae was 20.0%. These results showed that FSH combined with LH was effective in IVM of zebrafish oocyte.