PMC8329360_01
Observation via colposcopy before and after REBACIN  treatment. After one (A, C) or two (B) courses of REBACIN  treatment, the examination of TCT and cervical histopathology showed normal TCT (A), CIN1 (B) and CIN2 (C), respectively in lower panels. Upper panels in (A-C) showed the examination before REBACIN  treatment; representative pictures were shown.
fmed-08-627355-g0001.jpg
PMC8329360_01_fmed-08-627355-g0001.jpg
F1
There was no recurrence for the 4th patient during her follow-up for up to 12 months after the regression; the 6th patient displayed normal cervical cytology (Figure 1A), but showed chronic inflammation of the cervix via cervical biopsy. After additional second course treatment, there was no improvement according to colposcopy and cervical biopsy (Figures 1B, 2). So far, there was no recurrence during six-month follow-up; the 13th patient was still diagnosed as LSIL, and also CIN2 according to cervical biopsy (Figure 1C).
Histopathological examination before and after REBACIN  treatment. (A) Before REBACIN  treatment, the patient was diagnosed as CIN2 via the histopathology of cervical biopsy, showing a moderate atypical hyperplasia. The cells including obvious atypia cells were arranged disorderedly; the abnormally proliferating cells occupied 2/3 of the subepithelial layer. (B) After two courses of REBACIN  treatment, the patient was diagnosed as CIN1, showing a mild atypical hyperplasia. The cells including some atypia cells were arranged irregularly, but still maintained polarity. The abnormally proliferating cells are limited to the lower 1/3 of the subepithelial layer.
fmed-08-627355-g0002.jpg
PMC8329360_01_fmed-08-627355-g0002.jpg
F2
After additional second course treatment, there was no improvement according to colposcopy and cervical biopsy (Figures 1B, 2).
PMC8329360_02
PMC8329360_03
REBACIN  inhibits the expression of hrHPV E6/E7. (A) REBACIN  inhibits hrHPV E6/E7 mRNA. After one course (3 months) of REBACIN  treatment, the expression level of E6/E7 mRNAs in cervical specimens was evaluated using Aptima HPV E6/E7 mRNA assay. Specimens with S/CO values of >=0.5 were considered as positive. (B) REBACIN  inhibits HPV16 E7 oncoprotein expression. Ca Ski cells with expression of HPV16 E7 were treated by different concentration of REBACIN  for 48 h, expression of the E7 oncoprotein was then evaluated by Western blot. REBACIN  clearly inhibited HPV16 E7 expression in a dose-dependent manner. (C) The results in (B) were quantified and shown in (C). Histograms show mean +- SEM of three independent experiments performed in duplicate. **, p < 0.01; ***, p < 0.001 vs. control (0 mug/ml REBACIN ) analyzed by one-way analysis of variance followed by Bonferroni test (GraphPad Prism 6).
fmed-08-627355-g0003.jpg
PMC8329360_03_fmed-08-627355-g0003.jpg
F3
Assay results are interpreted on the basis of the signal-to-cutoff ratio (S/CO), and specimens with S/CO values of >=0.5 were considered positive. As shown in Figure 3A, after one course (3 months) of REBACIN  treatment, the E6/E7 mRNA in hrHPV-infected patients was reduced remarkably, which most of them were became negative. REBACIN  significantly inhibited the expression of HPV16 E7 oncoprotein in a human epidermoid cervical cancer cell line of Ca Ski, and showed a dose-effect relationship (Figures 3B,C).