Upregulated pigment epithelium-derived factor (PEDF) promotes trophoblast apoptosis and inhibits invasion in preeclampsia.

Preeclampsia (PE) is a severe pregnancy-specific disorder. Previous findings indicated that pigment epithelium-derived factor (PEDF) was upregulated in placentas of women with PE. Here, we investigated the role of PEDF in trophoblast function, especially under hypoxia. The effects of hypoxia on the morphology of extravillous trophoblast (EVT)-derived HTR-8Svneo cells were observed under inverted microscope. Transfections with Lipofectamine LTX were performed according to the manufacturer's protocol. The expression of PEDF protein and mRNA were confirmed by immunofluorescence (IF) and quantitative real-time PCR (qPCR). Apoptosis was detected by transferase-mediated dUTP nick end labeling (TUNEL) assay, and proliferation of trophoblast was detected by CCK-8 method. The invasion capacity of trophoblast was assessed by Transwell assay. PEDF was expressed in HTR-8/SVneo under both normoxia and hypoxic stress. However, cells of hypoxia groups had higher expression level of PEDF, increased apoptosis and decreased invasion capability, as compared with normoxia group. Moreover, after transfection with plasmid expressing PEDF gene, overexpression of PEDF modulated trophoblast activities. In addition, PEDF expression was negatively associated with invasion while positively correlated with apoptosis.Our data suggest that PEDF is an important factor to maintain the biological function of trophoblast cells, thus representing a rational therapeutic target in PE.

Synthesis, biological activity, molecular docking studies of a novel series of 3-Aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives as the acetylcholinesterase inhibitors.

The acetylcholinesterase inhibitors play a critical role in the drug therapy for Alzheimer's disease. In this study, twenty-nine novel 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and assayed for their human acetylcholinesterase (hAChE) inhibitory activities. Inhibitory ratio values of seventeen compounds were above 55% with 4c having the highest value as 77.19%. The compounds with the halogen atoms in the aromatic ring, and N,N-diethylamino or N,N-dimethylamino groups in the side chains at C-3 positions exhibited good inhibitory activity. SAR study was carried out by means of molecular docking technique. According to molecular docking results, the common interacting site for all compounds were found to be peripheral anionic site whereas highly active compounds were interacting with the catalytic active site too. HIGHLIGHTSA novel series of 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and assayed for their human acetylcholinesterase (hAChE) inhibitory activities.The SAR study of the target 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives was summarized.The active sites in the acetylcholinesterase were analyzed by molecular docking technique.Communicated by Ramaswamy H. Sarma.

Prevalence and genotypes of human papilloma virus infection in CIN3 in Beijing, China.

BACKGROUND: To investigate the incidence of single and multiple human papillomavirus (HR-HPV) infection in CIN3 patients before operation. METHODS: The complete clinical data of patients with CIN3 by biopsy were collected. HPV23 typing in the first 3 months of the treatment was detected. The infection rate of HPV was analyzed. RESULTS: One thousand and fifty-one HPV subtypes were detected in 679 patients with HPV (+) CIN3 with primary conization, of which the top ten were HPV16, 33, 31, 58, 6, 52, 18, 43, 51, 11, 68, respectively. Among them, single subtype HPV infection accounted for 64.36%, while multiple HPV infection accounted for 35.64%. For multiplex HPV infection, there were 2, 3, 4 species, and 148 (21.80%), 69 (10.16%), 16 (2.36%), 9 (1.33%) cases of multiple HPV infection of 5 and above HPV subtypes respectively. The incidence of multiple HPV infection in CIN3 patients in 2015 was higher than that in 2012 (39.01% vs. 30.08%, P=0.019), and the proportion of multiple infections in HPV was higher than that in the 2014 group. CONCLUSIONS: The top 10 HPV subtypes of the CIN3 patients were included in HPV nine valence vaccines except HPV43 and 51.

A retrospective analysis of cisplatin/carboplatin plus paclitaxel in advanced or recurrent cervical cancer.

To compare the efficacy and safety of paclitaxel plus carboplatin (TC) and paclitaxel plus cisplatin (TP) in the treatment of advanced or recurrent cervical cancer, this retrospective study included 116 advanced or recurrent cervical cancer cases treated at Beijing Obstetrics and Gynecology Hospital between June 2002 and June 2014. Of these cases, 52 were treated with TC (TC group) and 64 were treated with TP (TP group). We found that the overall survival and response and disease-control rates were not significantly different between the two groups. The TC group had a markedly lower incidence of Grade III-IV gastrointestinal toxicity reactions and a shorter hospitalisation stay than the TP group. The incidences of Grade III-IV bone marrow suppression and renal toxicity were not significantly different between the TP and TC groups. These findings suggest that TC may be a safe and effective alternative to TP for the treatment of advanced or recurrent cervical cancer. Impact Statement What is already known on this subject: Paclitaxel plus cisplatin (TP) is regarded as the standard regimen for cervical cancer, nevertheless, cisplatin is always associated with nephrotoxicity and requires hydration therapy. Carboplatin is a platinum analogue with milder nephrotoxicity than cisplatin. It is reported that carboplatin may be a viable and less toxic alternative to cisplatin in the management of advanced or recurrent cervical cancer, but another study shows that the therapeutic efficacy of paclitaxel plus carboplatin (TC) is non-inferior to that of TP. What the results of this study add: This study compared the efficacy and safety of TC and TP, and found that the TC and TP groups had similar overall response and disease-control rates and survival, but the TC group was better tolerated with a markedly lower incidence of Grades III-IV gastrointestinal toxicity reactions and had a shorter hospitalisation stay than the TP group. What the implications are of these findings for clinical practice and/or further research: TC may be a safe and effective alternative to TP for the treatment of advanced or recurrent cervical cancer in clinical practice.

Incidence of radiation enteritis in cervical cancer patients treated with definitive radiotherapy versus adjuvant radiotherapy.

OBJECTIVE: The study aimed to evaluate the incidence of early and late radiation enteritis in cervical cancer patients receiving definitive or adjuvant radiotherapy (RT). MATERIALS AND METHODS: Three hundred and twenty-four cervical cancer patients receiving definite or adjuvant RT in our hospital from January 2010 to December 2012 were divided into definitive (132 patients) or adjuvant RT (192 patients) and performed detailed analysis. RESULTS: Early radiation enteritis was found in 54.3%, and late radiation enteritis was found in 17.9% of cervical patients. Early (P < 0.007) and late (P < 0.003) radiation enteritis appeared more frequently in patients treated with definitive RT than that with adjuvant RT. In the definitive RT group, incidence of both early and late radiation enteritis in the RT group was higher than in the radiochemotherapy (RCHT) group, and the difference was statistically significant (P < 0.004). Severe cases of late radiation enteritis (Grade 3 and 4) can be seen higher in the definitive radiation group (both the RT and RCHT group) than in the adjuvant radiation group, and the difference was statistically significant (P < 0.005). CONCLUSION: The incidence of both early and late radiation enteritis in the definitive RT group is higher than in the adjuvant RT group. The occurrence of side effects was associated with the prolongation of total irradiation time due to necessary interruptions of RT. Methods to decrease the interruptions in the RT and the irradiated volume of the small bowel will further lessen enteric morbidity.

Does hysteroscopy worsen prognosis in women with type II endometrial carcinoma?

BACKGROUND: Prior studies evaluating the impact of hysteroscopy on outcomes in endometrial cancer have predominantly evaluated type I tumors. We sought to evaluate whether hysteroscopy worsens prognosis in type II endometrial cancer. METHODS: A retrospective cohort analysis of 140 patients from two institutions with type II endometrial cancer was performed. Women who underwent either diagnostic hysteroscopy (HSC) or dilation and curettage (D&C) for cancer diagnosis from June 2001 until June 2010 were included. The clinical and pathologic characteristics, including peritoneal cytology results were reviewed. The primary endpoint was disease-specific survival (DSS). The exposure of interest was hysteroscopy. Survival curves were projected using the Kaplan-Meier method and compared using the log-rank test. RESULTS: There was no difference in age, histology, stage, depth of myometrial invasion, adnexal involvement, or nodal metastasis between HSC and D&C patients. Positive cytology was found in 16/54 (30%) patients following HSC and in 10/86 (12%) following D&C (p = 0.008). Fourteen patients with stage I and II disease had positive peritoneal cytology, with 11/40 (27.5%) patients in the HSC group and 3/59 (5%) patients in the D&C group(p = 0.002). Median DSS was clinically different for the HSC and D&C groups, but statistical significance was not reached (53 versus 63.5 months, p = 0.34). For stage I and II patients, 18/99 (18%) were dead of EC, with a median DSS of 60 months for HSC and 71 months for D&C (p = 0.82). Overall 46 (33%) patients developed a recurrence, with 18/54 (33%) in the HSC group compared to 28/86 (32%) in the D&C group (p = 0.92). There was no difference in recurrence location between groups. CONCLUSIONS: Diagnostic hysteroscopy significantly increased the rate of positive peritoneal cytology at the time of surgical staging in this cohort of patients with type II EC. However, we were unable to detect a difference in prognosis as measured by DSS.

The negative conversion of high-risk human papillomavirus and its performance in surveillance of cervical cancer after treatment: a retrospective study.

PURPOSE: To determine the negative conversion regularity of high-risk human papillomavirus (HR-HPV) and to evaluate the prognostic implications of HR-HPV testing in patients with cervical cancer after treatment. METHODS: A retrospective post-treatment analysis of 173 patients with cervical cancer was performed from January 2011 to December 2012. Patients who had HR-HPV infection before treatment were included. Clinical and pathological characteristics, as well as follow-up information, were reviewed. RESULTS: The negative conversion rate of HR-HPV reached 68.9 % within half a year and increased most rapidly within the first 2 years after treatment. Univariate and multivariate analyses suggested that the negative conversion rate of HR-HPV was significantly correlated with clinical stage, treatment regimens, and HR-HPV type (P < 0.05). In our analysis of 173 patients, we found that HR-HPV status was predictive of 3-year survival rate and disease recurrence (P < 0.05). Pelvic recurrence, but not distant metastasis, was influenced by HR-HPV status (P < 0.05). Through 2 × 2 table analysis, we found that HR-HPV was more sensitive (71.43 %) and specific (94.20 %) than cervical cytology (sensitivity 62.86 % and specificity 78.26 %). CONCLUSIONS: The negative conversion rate of HR-HPV increased most rapidly within the first 2 years of cervical cancer surveillance. Persistent HPV infection was associated with a poor prognosis and had an impact on recurrence sites. Further large and multi-center prospective studies should be performed, but these results of this study suggested that HR-HPV monitoring is necessary to be used as a means of cervical cancer surveillance.

Effect of preoperative radiotherapy on stage IB2 and IIA2 cervical cancer: A retrospective cohort study.

INTRODUCTION: The aim of the retrospective study was to investigate the therapeutic efficiency of the preoperative intracavitary radiotherapy combined with radical surgery on postoperative complications and long-term survival in patients with stage IB2 and IIA2 cervical cancer (CC). METHODS: From January 1995 to December 2012, a total of 171 patients with stage IB2 or IIA2 CC were recruited into the study. They were divided into two groups according to the treatment modality provided: preoperative radiotherapy followed by radical surgery (n = 80), and radical surgery alone (n = 91). The clinical curative effect, postoperative complications and the postoperative prognosis of patients were evaluated and compared in two groups. The tumor response and survival of patients in two groups were observed in follow-up study. RESULTS: There were no significant differences in the incidence of postoperative complications, intraoperative blood loss and surgery duration (P > 0.05) between the two groups. Preoperative radiotherapy did not improve the postoperative prognosis yet. Though patients undergoing preoperative radiotherapy showed the similar 1- (92.50% vs. 84.62%), 3- (85.00% vs. 81.32%) and 5-year (80.00% vs. 74.72%) survival rates, the 3- and 5-year locoregional control rates of them were much higher than those undergoing surgery alone (P < 0.05). CONCLUSION: Preoperative radiotherapy combined with radical surgery could improve locoregional control rate and would not increase the risk of postoperative complications. It may be a feasible treatment mode for early stage CC carcinoma.

Knockdown of hTERT and Treatment with BIBR1532 Inhibit Cell Proliferation and Invasion in Endometrial Cancer Cells.

Telomerase activity and expression of the catalytic protein hTERT are associated with cell proliferation and advanced stage in endometrial cancer. Our objective was to evaluate the effect of inhibition of hTERT by siRNA and BIBR1532 on cell growth, apoptosis and invasion in endometrial cancer cells. Knockdown of hTERT or treatment of the cells with BIBR1532 decreased telomerase activity, inhibited cell proliferation, induced apoptosis, and reduced cell invasion in Ishikawa and ECC-1 cells. Either hTERT siRNA or BIBR1532 in combination with paclitaxel promoted a synergistic inhibitory effect on cell growth through induction of Annexin V expression and a remarkable reduction in cell invasion through reduction of protein expression of MMP9, MMP2, and MMP3. Increased telomerase activity and hTERT protein expression by transfections enhanced the protein expression of MMPs and increased the cell invasion ability. BIBR1532 significantly antagonized cell invasion induced by increased hTERT expression. These findings suggest that telomerase and hTERT facilitate cell invasion via MMP family in human endometrial cancer cells.