Anti-Human PAX2 monoclonal Antibody

Congenital anomalies of the kidney and urinary tract (CAKUT) are common genetic malformations. Since the PAX2 gene has a role in kidney organogenesis, this study investigated the association of PAX2 gene polymorphisms with CAKUT in general and with specific phenotypes of CAKUT in a Brazilian pediatric population. This study included 241 individuals with antenatal hydronephrosis and 259 healthy controls. For genotyping and allelic discrimination we used the probes to rs2077642, rs4244341, rs6421335, rs11190698, and rs11190693. No statistical differences in allele and genotype frequencies were observed for the single nucleotide polymorphism (SNP) rs11190693. At the SNPs rs4244341 and rs11190698, the frequencies of the ancestral alleles were significantly higher among CAKUT patients (rs4244341 allele G: 0.86 vs. 0.78; rs11190698 allele A: 0.85 vs. 0.79). At the SNP rs4244341, the genotype GG was increased in CAKUT group (0.72 vs. 0.61, P = 0.013), while the TT was higher in controls (0.01 vs. 0.05, P = 0.001). At the SNP rs11190698, the genotype CC was increased in controls (0.02 vs. 0.06, P = 0.01). The most frequent CAKUT phenotypes were vesicoureteral reflux (VUR), multicystic dysplastic kidney (MCDK), and ureteropelvic junction obstruction (UPJO). In patients with VUR, the frequencies of the monozygotic ancestral alleles decreased at the SNP rs11190693 (AA 0.13 vs. 0.26, P = 0.04) and increased at the SNP rs4244341 (GG 0.77 vs. 0.61, P = 0.03). No statistical differences were detected between controls and patients with UPJO and with MCDK for all SNPs. The PAX2 gene seems to be involved with the pathogenesis of VUR in our sample.

CP-31398, a styrylquinazoline, emerges from a screen for therapeutic agents that restore the wild-type DNA-binding conformation of mutant p53 to suppress tumors in vivo, but its effects on cervical cancer (CC) remain unknown. Hence, this study aimed to explore the effects CP-31398 has on the CC cells and to investigate whether it is associated with paired box 2 (PAX2) expression. CC cells were treated with different concentrations of CP-31398 (1, 2, 4, 6, 8, and 10 mu g/ml) to determine the optimum concentration using fluorometric microculture cytotoxicity assay. After constructing the sh-PAX2 vector, CC cells were transfected with sh-PAX2 or treated with CP-31398. The effects of CP-31398 or PAX2 silencing on CC cell proliferation, apoptosis, invasion, and migration were evaluated. Epithelial mesenchymal transition (EMT)-related genes such as E-cadherin, vimentin, N-cadherin, snail, and twist in CC cells were detected. Tumor formation experiment in nude mice was performed to observe tumor growth. The optimum concentration of CP-31398 was 2 mu g/ml. PAX2 was overexpressed in CC cells. CC cells treated with CP-31398 or treated with sh-PAX2 inhibited proliferation, invasion, and migration but promoted apoptosis with decreased PAX2 expression. The EMT process in CC cells was also reversed after treatment with CP-31398 or sh-PAX2. Moreover, the tumor formation experiment in nude mice revealed the inhibitory activity of CP-31398 in CC tumor in nude mice by suppressing PAX2. Our results provide evidence that CP-31398 could inhibit EMT and promote apoptosis of CC cells to curb CC tumor growth by downregulating PAX2.