Suppressing tumor growth of nasopharyngeal carcinoma by hTERTC27 polypeptide delivered through adeno-associated virus plus adenovirus vector cocktail

Nasopharyngeal carcinoma(NPC) is a metastatic carcinoma that is highly prevalent in Southeast Asia. Our laboratory has previously demonstrated that the C-terminal 27-kDa polypeptide of human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human glioblastoma and melanoma cells. In this study, we investigated the antitumor effect of hTERTC27 in human C666-1 NPC cells xenografted in a nude mouse model. A cocktail of vectors comprising recombinant adeno-associated virus (rAAV) and recombinant adenovirus (rAdv) that each carry hTERTC27 (rAAV-hTERTC27 and rAdv- hTERTC27; the cocktail was abbreviated to rAAV/rAdv-hTERTC27) was more effective than either rAAV- hTERTC27 or rAdv-hTERTC27 alone in inhibiting the growth of C666-1 NPC xenografts. Furthermore, we established three tumors on each mouse and injected rAAV/rAdv-hTERTC27 into one tumor per mouse. Although hTERTC27 expression could only be detected in the injected tumors, reduced tumor growth was observed in the injected tumor as well as the uninjected tumors, demonstrating that the vector cocktail could provoke an antitumor effect on distant, metastasized tumors. Further studies showed the observed antitumor effects included inducing necrosis and apoptosis and reducing microvessel density. Together, our data suggest that the rAAV/rAdv-hTERTC27 cocktail can potently inhibit NPC tumor growth in both local and metastasized tumors and should be further developed as a novel gene therapy strategy for NPC.

Application of the Mathieu combined tunnel technique for repairing glans dehiscence after failed hypospadias repair

Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons.Here,we introduced and evaluated a newly modified Mathieu technique,Mathieu combined tunnel(MCT),which involves multiple custom-designed flaps for the shortage of flap source material after repeated operations;we also constructed a tunnel to avoid the glans incision that may carry new risks of dehiscence.This retrospective study included 26 patients who were consecutively admitted to the First Affiliated Hospital of Sun Yat-Sen University(Guangzhou,China)for glans dehiscence repair after failed hypospadias repair from October 2014 to October 2020;sixteen patients underwent surgery using the MCT(MCT group)and ten patients underwent surgery using the tubularized incised plate(TIP)technique(TIP group).The operative time,blood loss,postoperative complications,normal urethral meatus rate,success rate,and Hypospadias Objective Penile Evaluation(HOPE)score were compared between the two groups.The MCT group achieved an overall satisfactory penile appearance and voiding function,with a higher rate of normal urethral meatus(15/16,93.8%)and a lower rate of glans dehiscence(1/16,6.2%),compared with the TIP group(70.0%and 30.0%,respectively).However,these differences were not statistically significant,possibly because of the limited number of patients(all P>0.05).Mean postoperative HOPE scores were similar in the MCT group(mean±standard deviation:8.83±0.89)and TIP group(8.94±0.57)(P>0.05).No significant differences were found between the two groups in terms of blood loss and success rate,nor in the rates of various complications(e.g.,fistula,urethral stricture,and glans dehiscence).In conclusion,the MCT technique appears to be feasible and reliable for repairing glans dehiscence after failed hypospadias repair.