Factors associated with human papillomavirus persistence after loop electrosurgical excision procedure in patients with cervical squamous intraepithelial lesion.

AIM: To seek the high-risk factors of human papillomavirus (HPV) persistence and residual lesion or recurrence after loop electrosurgical excision procedure (LEEP) focus on the predictive value of intraoperative human papilloma virus (IOP-HPV) testing. METHODS: Intraoperative endocervical sample was obtained with a cytobrush from the remained cervix of 292 patients immediately after LEEP. HPV Genotyping was performed using a polymerase chain reaction technique. All patients followed by HPV genotyping and cytology every 3-6 months. The IOP-HPV testing results and possible risk factors such as age, cytology grade, menopause status, margin involvement, preoperative HPV status, and cervical lesion grade were assessed in predicting persistence of HPV and residual lesion or recurrence after surgery. RESULTS: There were 61 (20.9%) patients presented persistent HPV infection. Multivariate analyses showed that IOP-HPV positive, post-menopause and preoperative HPV multiplex infection was strongly associated with HPV persistence after LEEP, IOP-HPV positive and post-menopause was also associated with residua or recurrent disease after LEEP. CONCLUSIONS: IOP-HPV positive, post-menopause, and preoperative HPV multiplex infection are independent predictors of HPV persistence in patients with cervical squamous intraepithelial lesion treated by LEEP. IOP-HPV test is a new approach that may potentially allow for early identification of patients at high risk of HPV persistence and residua or recurrent disease after LEEP, thereby possibly facilitate an attenuated follow-up schedule for negative patients those at low risk of persistent HPV infection.

HNRNPU-AS1 Regulates Cell Proliferation and Apoptosis via the MicroRNA 205-5p/AXIN2 Axis and Wnt/ß-Catenin Signaling Pathway in Cervical Cancer.

Long noncoding RNAs (lncRNAs) have key functions in modulating cervical cancer (CC) genesis and progression. This work focused on exploring lncRNA HNRNPU-AS1's function in CC and the underlying mechanism. HNRNPU-AS1, AXIN2, and microRNA 205-5p (miR-205-5p) levels in CC cases were measured through reverse transcription-quantitative PCR. The relationship between miR-205-5p and AXIN2 or HNRNPU-AS1 was validated through a dual-luciferase assay. Cell proliferation was examined by CCK-8 and cell apoptosis by colony formation and flow cytometry analysis. HNRNPU-AS1 expression loss could be observed in CC patients and cell lines, which predicted the dismal prognosis of CC cases. Moreover, it was identified that the miR-205-5p level was upregulated, which acted as an inhibitory target of HNRNPU-AS1 and AXIN2. HNRNPU-AS1 inhibited cell proliferation and promoted apoptosis. As revealed by Kaplan-Meier curve, CC cases showing low HNRNPU-AS1, high miR-205-5p, and low AXIN2 levels had the poorest prognosis. AXIN2 reversed the CC cell proliferation-promoting, apoptosis-inhibiting, and Wnt/ß-catenin signaling-activating behavior mediated by miR-205-5p or HNRNPU-AS1 knockout. In conclusion, the overexpression of lncRNA HNRNPU-AS1 suppressed CC progression by inhibiting the Wnt/ß-catenin pathway through the miR-205-5p/AXIN2 axis.

Apigenin induces apoptosis and counteracts cisplatin-induced chemoresistance via Mcl-1 in ovarian cancer cells.

Ovarian cancer (OC) is one of the prominent causes of mortality in female patients diagnosed with gynecologic malignancies. While it has previously been demonstrated that apigenin inhibits cell growth in colon and breast cancer cells, the effect of apigenin in OC cells is not fully understood. Therefore, the aim of the present study was to investigate the impact of apigenin on cell death and resistance to cisplatin in OC cells. It was found that apigenin inhibited proliferation, hindered cell cycle progression and promoted SKOV3 cell apoptosis. Moreover, these effects were also observed in cisplatin-resistant SKOV3/DDP cells. Furthermore, apigenin reduced the mitochondrial transmembrane potential, and elevated the ratios of cleaved caspase-3/caspase-3 and Bax/Bcl-2 in the two cell types. Reverse transcription-quantitative PCR and western blotting results demonstrated that apigenin significantly downregulated Mcl-1 at the transcriptional and translational levels in SKOV3 and SKOV3/DDP cells, which was responsible for its cytotoxic functions and chemosensitizing effects. Collectively, the present results identified the impact of apigenin on OC cell death and resistance to cisplatin, and the potential molecular mechanisms. However, additional studies are required to further elucidate the underlying mechanisms.

Smad4 induces cell death in HO-8910 and SKOV3 ovarian carcinoma cell lines via PI3K-mTOR involvement.

IMPACT STATEMENT: This study investigated the effect and mechanism of Smad4 in ovarian carcinoma (OC) cell viability and demonstrated that Smad4 acted as a tumor suppressor in OC, which may contribute to the understanding of molecular mechanisms underlying OC occurrence and progression. Smad4 expression was decreased in the OC specimens, but Smad4 recovery in the OC cell lines impaired the survival and viability of OC cells by increasing autophagy and apoptosis. Further investigation showed that Smad4 interacted with the P85 subunit of PI3K and caused deactivation of the PI3K/mTOR pathway. Therefore, Smad4 could be considered as a target in cancer therapy due to its regulatory effect in OC carcinogenesis.

Hypomethylation of DNA promoter upregulates ADAMTS7 and contributes to HTR-8/SVneo and JEG-3 cells abnormalities in pre-eclampsia.

INTRODUCTION: Accumulating evidences have suggested a crucial role of epigenetics in the initiation and progression of pre-eclampsia (PE). Here, we studied the expression of the metalloproteinase ADAMTS7 and the methylation level of its promoter in PE placentas and investigated ADAMTS7 role in the pathogenesis of PE. METHODS: We first explored ADAMTS7 expression in PE and normal placentas by reverse transcription quantitative PCR (RT-qPCR), western blot, and immunohistochemistry. Methylation specific PCR (MSP) and bisulfite sequencing PCR (BSP) were performed to evaluate the methylation status of ADAMTS7 promoter. Treatment with 5'-Aza was used to induce demethylation and thereby to explore the direct relationship between promoter methylation and ADAMTS7 expression. CCK8 assay, colony formation assay, and trans-well assay were conducted to assess the viability, migration, and invasion of HTR-8/SVneo and JEG-3 cells. RESULTS: Our results showed that ADAMTS7 expression was upregulated in PE placentas. Methylation analysis revealed a hypomethylated status of ADAMTS7 promoter regions in PE placenta tissues. Besides, demethylation induced by 5'-Aza directly restored ADAMTS7 expression in trophoblast cells. Finally, overexpression of ADAMTS7 inhibited viability, migration, and invasion of HTR-8/SVneo and JEG-3 cells, while silence of ADAMTS7 by RNA interference reciprocally facilitated cell viability, migration and invasion in vitro. DISCUSSION: Upregulation of ADAMTS7 by promoter hypomethylation in placenta might contribute to the etiology of PE via suppressing cell functions of trophoblasts.

Novel triazole analogs of apigenin-7-methyl ether exhibit potent antitumor activity against ovarian carcinoma cells via the induction of mitochondrial-mediated apoptosis.

Ovarian cancer is one of the main causes of cancer-associated mortality across the world. Currently, ovarian cancer is mainly treated with chemotherapy. However, ovarian cancer is detected at advanced stages and chemotherapy has numerous side effects. In addition, the results of current chemotherapy on the treatment of ovarian cancer are less than satisfactory. Therefore, there is an urgent need to develop novel and more viable chemotherapeutic agents that can be used to treat ovarian cancer. The present study was designed to synthesize a series of novel triazole analogs of the bioactive apigenin-7-methyl ether to evaluate its anticancer activity against three human ovarian cancer cell lines. A total of eight novel triazole derivatives were synthesized and screened for their anticancer activity. Of all the derivatives, a derivative named 3d exhibited significant and dose-dependent anticancer activity against the SKOV3 ovarian cancer cell line. The IC50 of 3d was found to be 10 µM against the SKOV3 cancer cell line. It was also observed that 3d induced apoptosis in SKOV3 cancer cells through the accretion of reactive oxygen species and reduction in mitochondrial membrane potential. The molecule also modulated the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein. Taken together, these results showed that the apigenein-7-methyl ether novel derivative 3d may prove an important lead molecule for the treatment of ovarian cancer.

Hormone therapy as a management strategy for lung metastasis after 5 years of endometrial cancer: A case report and literature review.

RATIONALE: Endometrial cancer patients with lung metastases are rare, and more rarely with long-term management of progesterone after recurrence. PATIENT CONCERNS: Informed consent of the patients and their families. DIAGNOSES: Endometrial cancer (IVB) (Refer to 2009 FIGO stag of endometrial cancer). INTERVENTIONS: the patient was treated with Megestrol Acetate Dispersible Tablets (trade name Yilizhi), 160 mg, orally, once daily, without interruption. OUTCOMES: The patient has been treated with progesterone therapy for stable conditions and her survival time is already roughly a decade (December 2006-October 2016). LESSONS: Hormone therapy may as a long-term management for hormone receptor-positive patients with recurrent endometrial cancer.