Comparing a biosimilar follitropin alfa (Cinnal-fⓇ) with Gonal-fⓇ in women undergoing ovarian stimulation: An RCT.

BACKGROUND: Advances in recombinant DNA technology led to the development of recombinant follitropin alfa. Recombinant human follicle-stimulating hormone products are used to stimulate follicular maturation. OBJECTIVE: To compare the efficacy and safety of a biosimilar-candidate recombinant human follicle-stimulating hormone (Cinnal-fⓇ; CinnaGen, Iran) with the reference product (Gonal-fⓇ; Merck Serono, Germany) in women undergoing ovarian stimulation for intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: In this randomized controlled trial, a total sample size of 200 women (age < 35 yr, candidate for ICSI) was calculated. Participants began a pituitary downregulation protocol with buserelin. They received 150 IU daily of either Cinnal-fⓇ or Gonal-fⓇ from the second day of their cycle. The primary outcome of the study was the percentage of metaphase II (MII) oocytes. The secondary outcomes included the number and quality of oocytes retrieved, duration of stimulation, fertilization rate, embryo quality, the number of clinical and ongoing pregnancies, and the incidence of ovarian hyperstimulation syndrome (as an important safety marker). RESULTS: A total of 208 women were enrolled, of whom, 200 completed the study period. Ovarian stimulation with Cinnal-fⓇ resulted in a comparable percentage of MII oocytes as with Gonal-fⓇ (78.64% vs 80.02%, respectively; p = 0.81). No statistically significant difference was seen in the secondary outcomes between the groups. CONCLUSION: Cinnal-fⓇ proved non-inferior to Gonal-fⓇ, based on the percentage of MII oocytes in women aged < 35 yr undergoing ICSI. Our findings confirm that the efficacy and safety profiles of Cinnal-fⓇ and Gonal-fⓇ are similar.

Celecoxib Treatment Alters p53 and MDM2 Expression via COX-2 Crosstalk in A549 Cells.

Cyclooxygenase-2 (COX-2) has a pivotal role in the pathogenesis of the lung cancer. It is known that COX-2 negatively regulates the activity of a number of tumor suppressors, including p53. Consequently, inhibition of COX-2 signaling is anticipated to be a promising approach to stabilize p53 functionality. In this regard, we investigated the effect of COX-2 signaling blockade on p53 and COX-2expression in A549 cells. Cell viability was assessed using MTT and protein expression was measured using Western Blot assay. Results revealed that Celecoxib dose-dependently induced growth inhibition within 24 h. However, prolonged exposure to the drug up to 48 h led to increase cell viability compared to the corresponding control. Western blot analysis demonstrated that Celecoxib could augment p53 expression within 24 h, independently of COX-2 inhibition. In contrast, Celecoxib treatment not only returned p53 to the control level, but also strikingly induced COX-2 expression within 48 h. Of further relevance, Celecoxib exposure could significantly result in MDM2 elevation at 48 h. These findings represent p53 as a molecular target being interconnected with COX-2 signaling axis upon Celecoxib treatment. Moreover, our data point toward the possibility that Celecoxib treatment may not be a proper therapeutic strategy in lung cancer cells owing to its potential role in the activation of oncogenes, including COX-2 and MDM2 which seemingly confers a chemoresistance circumstance to the cell. Consequently, these results underscore intensive preclinical assessment prior to applying COX-2 inhibitors in the treatment of lung tumors.