Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

Prognostic value of E-cadherin expression and CDH1 promoter methylation in patients with endometrial carcinoma.

The primary aim of this study is to evaluate the clinical significance of E-cadherin protein expression and the methylation status in CDH1 promoter in endometrial cancer. The expression of E-cadherin and methylation in its promoter region was analyzed, retrospectively, in 152 clinical tissue samples from patients with endometrial lesions. We found that the hypermethylation of CDH1 promoter, which caused low expression of E-cadherin in endometrial cancer, was associated with not only clinicopathological progress of endometrial cancer but also with the overall 5-year clinical survival rate. The findings provide the potential therapeutic and prognostic target molecule for patients with endomethrial cancer.

Case Report: Noninvasive Clinical Intervention of REBACIN® on Histologic Regression of High Grade Cervical Intraepithelial Neoplasia.

High-risk human papillomavirus (hrHPV) persistent infection is the major cause of cervical cancer. Clinical intervention of hrHPV-associated high-grade squamous intraepithelial lesion (HSIL) is critical to prevent cervical cancer, and current treatment is surgery (an invasive therapy). However, some patients refuse to do so for an afraid of potential adverse effects on future fertility or other concerns which creates a critical need for development of non-invasive therapeutic strategies. Here, we report for the first time the cases of non-invasive intervention with REBACIN®, a proprietary antiviral biologics, in clinical treatment of HSIL. From 12,958 visiting patients assessed for eligibility, 18 HSIL-patients with cervical intraepithelial neoplasia-grade 2, positive of both diffused overexpression of p16 and high-risk HPV were enrolled in this non-invasive clinical intervention mainly due to concerns of future fertility. REBACIN® was administered intravaginally every other day for 3 months (one-course) except during menstrual period, and were followed up for 6-36 months for the examination of high-risk HPV DNA, cervical cytology, and histopathology. After one to three course treatments, most cases (16/18) displayed both the regression from HSIL (CIN2) to normal cervical cytology and clearance of high-risk HPV infection. Further studies demonstrated REBACIN® significantly suppressed HPV16 E7 oncoprotein expression in a human cervical cancer cell line, which is consistent with previous finding that REBACIN® inhibits the growth of tumors induced by expression of E6/E7 oncogenes of either HPV16 or HPV18. This report indicates REBACIN® as a novel effective non-invasive clinical intervention for HSIL-patients as well for high-risk HPV persistent infection, providing a new clinical option for the non-invasive treatment of hrHPV-associated high-grade squamous intraepithelial lesion, which is worthy of further research on clinical validation and application.

[Relationship between nucleotide excision repair gene ERCC1 and resistance to cisplatin in ovarian cancer].

OBJECTIVE: To study the relationship between nucleotide excision repair gene ERCC1 and resistance to cisplatin in ovarian cancer. METHODS: The expression of gene ERCC1 in 58 ovarian cancer tissues and 4 cell lines were examined and its relationship with resistance to cisplatin were analyzed, the changes of sensitivity to cisplatin were observed after interference of ERCC1 gene with small interfering RNA (siRNA) in ovarian cancer cell lines. RESULTS: In 58 ovarian cancer tissues, the positive rate of ERCC1 protein in chemoresistant cases (57.89%) was higher than that in chemo-sensitive cases (28.21%, P = 0.029). The mRNA levels of ERCC1 gene in ovarian cancer cell lines ES-2, SKOV3, COC1, COC1/DDP were related to cisplatin IC50 values (r = 0.932, P <0.05). The sensitivity of cell lines ES-2, SKOV3, COC1/DDP cells to cisplatin was increased by 53.88, 5.07, and 3.75 times, respectively, after RNA interfering ERCC1 gene. CONCLUSION: ERCC1 gene is associated with the resistance to cisplatin and the sensitivity to cisplatin can be enhanced by RNA interfering ERCC1 in ovarian cancer.

[Influence of mifepristone on DNA repair genes and cisplatin sensitivity in human ovarian cancer drug-resistance cells].

OBJECTIVE: To study the changes of DNA repair genes and enhanced anti-tumor effect of cisplatin induced by mifepristone in human ovarian cancer drug resistance cells. METHODS: The alterations of cisplatin concentration producing 50% inhibition (IC50 ) in the COC1/DDP cell lines were examined by methyl thiazolyl tetrazolium (MTT) assay. RT-PCR and flow cytometry were used to analyze the changes of the mRNA of ERCC1, BRCA1, hMLH1 genes and cell cycle and apoptosis. Subcutaneous implantation of COC1/DDP was established in nude mice and the enhanced anti-tumor effect of cisplatin by mifepristone was observed in vivo. RESULTS: Cisplatin IC50 values of COC1/DDP cell were decreased from (3.71 +/- 0.38) microg/ml to (3.18 +/- 0.46), (1.95 +/- 0.14), (0.64 +/- 0.18) microg/ml respectively when treated with 2.5, 5.0, 10.0 micromol/L mifepristone. Mifepristone could down-regulate the mRNA levels of ERCC1, BRCA1, hMLH1 genes and enhance G0/G1 phase block effect of cisplatin, and 2.5, 5.0, 10.0 micromol/L mifepristone combined with cisplatin increased rate of cell apoptosis from 0.08% to 5.11%, 9.13% and 12.24% respectively. The percentage of inhibition of xenograft tumor volume in combined treatment group was 70.1%, which was significantly different (P < 0.05). CONCLUSION: By down-regulating ERCC1, BRCA1, hMLH1 genes, blocking G0/G1 phase, and increasing apoptosis rate, mifepristone could enhance anti-tumor effect of cisplatin.

[Enhanced cisplatin cytotoxicity by RNA interfering the excision repair cross-complementing 1 gene in ovarian cancer cell lines].

OBJECTIVE: To study changes of cisplatin sensitivity by RNA interfering the excision repair cross-complementing (ERCC) 1 gene in ovarian cancer cell lines. METHODS: The small interference RNA (siRNA) targeting ERCC1 gene was designed and synthesized by transcription in vitro, and transfected to ovarian cancer cell line ES-2. The mRNA and protein of ERCC1 were evaluated by means of RT-PCR, western blot and immunocytochemistry. The changes of cisplatin sensitivity after interference were examined by methyl thiazolyl tetrazolium (MTT) assay. RESULTS: In ES-2 cell, the mRNA and protein levels of ERCC1 were dramatically decreased 24, 48 and 72 hours after transfection. The sensitivity to cisplatin of ES-2 cell line was increased by 53.88 times after disturbing the ERCC1 gene. CONCLUSION: The sensitivity to cisplatin of ovarian cancer cell lines ES-2 could be enhanced by RNA interfering ERCC1 gene.