ABSTRACT
[Objective]To study the resistance reversion of rapamycin on ovarian cancer cell line SKOV3/DDP,and ex-plore its underlying molecular mechanisms.[Methods]MTT method was used to detect the cell toxicity,drug-resistant multi-ple and reversing multiple of cisplatin-resistant ovarian cancer cell line SKOV3/DDP;Western blot was used to detect the changes of Akt/mTOR Pathway induced by rapamycin.[Results]① MTT detected that when rapamycin concentration was 25,50,100,500 and 1 000 μg/L,its inhibition rates on cisplatin-resistant ovarian cancer cell line SKOV3/DDP were 4.48%,25.30%,35.86%,67.82%,81.43%.The concentration of 25 μg/L was selected to be the reversal concentration,be-cause its maximum rate was less than 5%.②The resistant index(RI)of cisplatin-resistant ovarian cancer cell line SKOV3/DDP was 2.21. ③ The reversal fold of 25 μg/L rapamycin on cisplatin-resistant ovarian cancer cell line SKOV3/DDP was 1.63.④Western blot results:After the addition of rapamycin,expression of p-mTOR and its downstream protein p-p70s6k in SKOV3 and SKOV3/DDP was significantly reduced. Meanwhile,there was a feedback increase in p-Akt.[Conclusions]Rapamycin has a reversal effect on cisplatin-resistant ovarian cancer cell line SKOV3/DDP. Its reversal mechanism may be inhibiting the cell proliferation and promoting cell apoptosis by depressing the expression of p-mTOR and its downstream pro-tein p-p70s6k in Akt/mTOR Pathway.
ABSTRACT
<p><b>BACKGROUND</b>Occult invasive cervical cancer discovered after simple hysterectomy is not common, radical parametrectomy (RP) is a preferred option for young women. However, the morbidity of RP was high. The aim of our study is to assess the incidence of parametrial involvement in patients who underwent radical parametrectomy for occult cervical cancer or radical hysterectomy for early-stage cervical cancer and to suggest an algorithm for the triage of patients with occult cervical cancer to avoid RP.</p><p><b>METHODS</b>A total of 13 patients with occult cervical cancer who had undergone RP with an upper vaginectomy and pelvic lymphadenectomy were included in this retrospective study. Data on the clinicopathologic characteristics of the cases were collected. The published literature was also reviewed, and low risk factors for parametrial involvement in early-stage cervical cancer were analyzed.</p><p><b>RESULTS</b>Of the 13 patients, 9 had a stage IB1 lesion, and 4 had a stage IA2 lesion. There were four patients with grade 1 disease, seven with grade 2 disease, and two with grade 3 disease. The median age of the entire patients was 41 years. The most common indication for extrafascial hysterectomy was cervical intraepithelial neoplasia 3. Three patients had visible lesions measuring 10-30 mm, in diameter and ten patients had cervical stromal invasions with depths ranging from 4 to 9 mm; only one patient had more than 50% stromal invasion, and four patients had lymph-vascular space invasion (LVSI). Perioperative complications included intraoperative bowel injury, blood transfusion, vesico-vaginal fistula, and ileus (1 case for each). Postoperative pathologic examination results did not show residual disease or parametrial involvement. One patient with positive lymph nodes received concurrent radiation therapy. Only one patient experienced recurrence.</p><p><b>CONCLUSIONS</b>Perioperative complications following RP were common, whereas the incidence of parametrial involvement was very low among selected early-stage cervical cancer patients. Based on these results, we thought that patients with very low-risk parametrial involvement(tumor size ≤ 2 cm, no LVSI, less than 50% stromal invasion, negative lymph nodes) may benefit from omitting RP. Further prospective data are warranted.</p>