Analysis of pregnancy outcomes in patients undergoing ultrasound-indicated cerclage and identification the influence factors for predicting preterm birth: A retrospective study of 87 cases.

OBJECTIVE: To investigate the factors influencing preterm birth in patients after ultrasound-indicated cerclage with different cervical lengths (CL), and explore the optimal cut-off value of CL. MATERIALS AND METHODS: The retrospective study included 87 pregnant women with a history of preterm birth and second-trimester loss that received ultrasound-indicated cerclage in our hospital between January 2004 and April 2021. Groups were divided by CL at the demarcation point of 1.0, 1.5 and 2.0 cm respectively. The pregnancy outcomes were compared. Logistic regression analysis was performed to assess the independent influence factors. Receiver-operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was used to compare the prediction capability of the associated factors. RESULTS: Significant difference was found in terms of patients delivered at ≥32 weeks of gestation (19 [55.9%]vs. 41 [77.4%], p < 0.05) and neonatal birth weight (2495 [1138,3185]vs. 2995 [2155,3235] g, p < 0.05), when the CL was categorized at the demarcation point of 1.5 cm. Body mass index (BMI) (odds ratio [OR] = 1.224, p < 0.05), a history of preterm birth and second-trimester loss (OR = 3.153, p < 0.05), and C-reactive protein (CRP) > 5 mg/L (OR = 8.097, p < 0.05) were independent risk factors for gestational age more than 28 weeks. The AUC of joint predictor A included those factors was 0.849 (95% CI: 0.701-0.998, p < 0.05). CRP>5 mg/L was found to be a significant independent risk factor for different gestational age at delivery. CONCLUSIONS: A CL of 1.5 cm was the optimal cut-off value that could help women who underwent serial CL surveillance choose ultrasound-indicated cerclage at an appropriate time. High BMI, more history of preterm birth and second-trimester loss and abnormal CRP could be used as combined predictors to recognize the risk of preterm birth (<28 weeks) post-surgery.

Analysis of maternal and neonatal outcomes using cervical cerclage or conservative treatment in singleton gestations with a sonographic short cervix.

ABSTRACT: To investigate the effect of cervical cerclage or conservative treatment on maternal and neonatal outcomes in singleton gestations with a sonographic short cervix, and further compare the relative treatment value.A retrospective study was conducted among women with singleton gestations who had a short cervical length (<25 mm) determined by ultrasound during the period of 14 to 24 weeks' gestation in our institution. We collected clinical data and grouped the patients according to a previous spontaneous preterm birth (PTB) at <34 weeks of gestation or second trimester loss (STL) and sub-grouped according to treatment option, further comparing the maternal and neonatal outcomes between different groups.In the PTB or STL history cohort, the cerclage group had a later gestational age at delivery (35.3 ±â€Š3.9 weeks vs 31.6 ±â€Š6.7 weeks) and a lower rate of perinatal deaths (2% vs 29.3%) compared with the conservative treatment group. In the non-PTB-STL history cohort, the maternal and neonatal outcomes were not significantly different between the cerclage group and conservative treatment group. More importantly, for patients with a sonographic short cervix who received cervical cerclage, there was no significant difference in the maternal and neonatal outcomes between the non-PTB-STL group and PTB or STL group.For singleton pregnant with a history of spontaneous PTB or STL and a short cervical length (<25 mm), cervical cerclage can significantly improve maternal and neonatal outcomes; however, conservative treatment (less invasive and expensive than cervical cerclage) was more suitable for those pregnant women without a previous PTB and STL history.

WNT1, a target of miR-34a, promotes cervical squamous cell carcinoma proliferation and invasion by induction of an E-P cadherin switch via the WNT/ß-catenin pathway.

PURPOSE: Persistent infection with high-risk human papillomavirus (HR-HPV) is thought to play a prominent role in the initiation and progression of almost all cases of cervical cancer. Previously, we and others found that microRNA 34a (miR-34a) may be regulated by HR-HPV E6 to contribute to the development of cervical cancer. Here, we aimed to identify the oncogenic potential and clinical significance of a known miR-34a target, WNT1, in cervical squamous cell carcinoma (SCC) development and to investigate the associated mechanisms underlying cervical SCC cell proliferation and invasion. METHODS: WNT1 and miR-34a expression levels were assessed in primary cervical lesions using immunohistochemistry and qRT-PCR, respectively. The cellular effects and the expression of its associated genes were examined in cervical SCC-derived Siha and Caski cells after siRNA-WNT1 (downregulation) or miR-34a mimic (upregulation) treatment. A cervical SCC xenograft mouse model was used to investigate the in vivo effects of miR-34a overexpression. HPV-16 E6/E7 expression was inhibited by gene promoter siRNA targeting, after which the levels of miR-34a and WNT1 were examined. RESULTS: WNT1 protein upregulation was found to be associated with a poor prognosis in cervical SCC patients. In vitro assays in Siha and Caski cells revealed that WNT1 downregulation decreased cell proliferation and invasion, inhibited WNT/ß-catenin activation and affected the expression of E-cadherin and P-cadherin. MiR-34a upregulation resulted in decreased WNT1 expression. An inverse correlation between miR-34a and WNT1 expression was also observed in primary cervical SCC tissues. In addition, we found that MiR-34a could regulate an E-cadherin to P-cadherin switch (E-P cadherin switch) to inhibit cell proliferation and tumorigenesis in vitro and in vivo via inactivation of the WNT1/ß-catenin pathway. Finally, we found that decreased HPV-16 E6/E7 expression resulted in miR-34a upregulation and WNT1 downregulation in Siha and Caski cells. CONCLUSIONS: From our results we conclude that WNT1, as a target of miR-34a, can promote cervical SCC cell proliferation and invasion by induction of an E-P cadherin switch via the WNT1/ß-catenin pathway. Our results may provide new options for the treatment of patients with cervical SCC.

Pregnancy outcomes and factors affecting the clinical effects of cervical cerclage when used for different indications: A retrospective study of 326 cases.

OBJECTIVE: To compare pregnancy outcomes resulting from the use of cervical cerclage for different indications and investigate factors that might influence the clinical effects of cervical cerclage. MATERIALS AND METHODS: This was a retrospective study of pregnant women who received cervical cerclage in The Women's Hospital, Zhejiang University School of Medicine, China. Patients were divided into three groups: a history-indicated group; an ultrasound-indicated group and a physical examination-indicated group. The pregnancy outcomes of the three groups were then compared. Univariate and multivariate logistic regression analysis were performed to assess the independent risk factors. RESULTS: Statistical differences were evident when the history-indicated group and the ultrasound-indicated group were compared with the physical examination-indicated group for gestational age at delivery [37.3(33.3-38.9), 35.4(28.9-38.4) vs. 26.1 (24.3-28.4) weeks, respectively, P < 0.05], percentage of cases delivered at < 28 weeks of gestation (13.4%, 20.3% vs. 74.3%, respectively, P < 0.05), percentage of cases delivered at < 37 weeks of gestation (42.7%, 54.2% vs. 91.4%, respectively, P < 0.05) and fetal survival rate (88.4%, 81.4% vs. 40.0%, respectively, P < 0.05). The history-indicated group and the ultrasound-indicated group were similar with regards to these outcomes. The independent risk factors affecting the clinical effects of cervical cerclage include age, body mass index (BMI), history of prior preterm birth and second-trimester loss, C-reactive protein (CRP) >5 mg/L and cervical dilation ≥3 cm (P < 0.05). CONCLUSION: Pregnancy outcomes were similar when compared between history-indicated and ultrasound-indicated cerclage. Serial cervical surveillance is beneficial for pregnant with a history of cervical insufficiency, and the placement of cervical cerclages in response to ultrasonographically detected shortening of the cervical length is a medically acceptable alternative to the use of history-indicated cerclage.

YM155 enhances docetaxel efficacy in ovarian cancer.

YM155 (Sepantronium bromide) is a potent small molecule inhibitor of survivin by suppression of survivin expression and shows the promising anticancer activity in many types of cancers. Docetaxel (Taxotere®) is a member of the taxane drugs used in the treatment of a number of cancers in clinic. Despite the therapeutic efficacy of docetaxel is encouraging, the emergent resistance is an urgent issue. In this study, we investigate the effect of YM155 on docetaxel efficacy in ovarian cancer cells. Our data showed that YM155 actively induced cell growth inhibition, cell cycle arrest and apoptosis with downregualtion of survivin in ovarian cancer cells. Moreover, YM155 increased the intracellular ROS levels, and pretreatment with either NAC or GSH partially reversed the YM155-induced ROS accumulation and apoptosis only in the parental A2780 cells, but not in the resistant A2780/Taxol cells. Furthermore, YM155 enhanced docetaxel efficacy to inhibit the growth and induce apoptosis in ovarian cancer cells. Take together, our results suggested that combination of YM155 and docetaxel may be a feasible strategy for the treatment of ovarian cancer.

Crizotinib synergizes with cisplatin in preclinical models of ovarian cancer.

Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene. However, the anticancer effect of crizotinib on ovarian cancer is still unclear. In this study, our data show that crizotinib can actively induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreasing phosphorylation of the downstream signaling effectors AKT and ERK in human ovarian cancer cells. Crizotinib also increases the intracellular reactive oxidative species (ROS) levels, and pretreating with ROS scavenger N-acety-L-cysteine partially reverses crizotinib-induced apoptosis. Moreover, crizotinib can synergistically inhibit ovarian cancer cells growth in vitro and in vivo when combines with cisplatin. Altogether, crizotinib potently potentiates the activity of cisplatin in ovarian cancer, suggesting the synergistic effect of crizotinib and cisplatin may be valuable for ovarian cancer patients' treatment.

Preoperative platelet count improves the prognostic prediction of the FIGO staging system for operable cervical cancer patients.

BACKGROUND: Increased platelet has been identified as an independent and unfavorable prognostic indicator in various cancers including cervical cancer. In our study, the prognostic value of preoperative platelet count combining with FIGO (International Federation of Gynecology and Obstetrics) stage in patients with operable cervical cancer was investigated. METHODS: A large cohort study including 800 operable cervical cancer patients was conducted from May 2005 to December 2012. Cancer-related biomarkers such as platelet count, hematocrit, hemoglobin, RDW was evaluated together with FIGO staging system in stage IA1-IIA2 cervical cancer patients. The prediction validity of platelet together with FIGO stage was then evaluated by receiver operating characteristic (ROC) curve, and the areas under the curve (AUCs) were compared by Z test. RESULTS: Univariate cox proportional hazard analysis demonstrated that hematocrit, platelet count, hemoglobin, FIGO stage, tumor differentiation, PLN (pelvic lymph node metastasis), LVSI (vascular lymph node invasion) were associated with overall survival (OS) and disease free survival (DFS), instead of RDW (red cell distribution width), age and histological subtype. Multivariate analysis demonstrated that preoperative platelet and FIGO stage were independent predictors for OS and DFS in cervical cancer. Furthermore, significant improvements were found after the combination of platelet count and FIGO stage in predicting OS and DFS for cervical cancer patients (P=0.0128 and P=0.0385, respectively). CONCLUSIONS: Combination of platelet count and FIGO stage improved the prediction performance of FIGO staging and provide additional risk stratification for operable cervical cancer patients.

Sequential combination therapy of ovarian cancer with cisplatin and γ-secretase inhibitor MK-0752.

OBJECTIVE: Ovarian cancer is one of the most lethal of women cancers and lack potent therapeutic options. There have many evidences demonstrate the Notch signaling has deregulation in variety of human malignancies.MK-0752 is a novel potent γ-secretase inhibitor and now assessed in clinical trial for treatment of several types of cancer, our objective was to investigate the anticancer effects and mechanisms of MK-0752 alone or combined with cisplatin in ovarian cancer. METHODS: Cell lines used: A2780, OVCAR3, SKOV3, HO8910PM, the effects of MK-0752 and cisplatin on cell proliferation were measured by MTT assay. The effect of combination treatment was examined by isobologram analysis. The distribution of cell cycle and cell apoptosis were analyzed using PI and Annexin V-FITC/PI staining by flow cytometric analysis. The mechanism in biochemistry was analyzed by using Western blot. Mouse xenograft model of A2780 was established to observe the anti-ovarian cancer effects in vivo setting, nude mice were randomized into four groups (n=6 per group) and treated every 4 days with control (solvent) group, MK-0752(25mg/kg) group, cisplatin (2mg/kg)group, combination group (both of MK-0752 and cisplatin). RESULTS: MK-0752 alone actively induced cell growth inhibition, G2/M phase cell cycle arrest and apoptosis with down-regulation of Notch1 and its downstream effectors including Hes1, XIAP, c-Myc and MDM2 in a dose- and time-dependent manner. Moreover, sequential combination of cisplatin prior to MK-0752 significantly promoted cell apoptosis and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. CONCLUSION: Our data supports the sequential combination of cisplatin prior to MK-0752 is a highly promising novel experimental therapeutic strategy against ovarian cancer.

Volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer.

Volasertib (BI 6727), a highly selective and potent inhibitor of PLK1, has shown broad antitumor activities in the preclinical and clinical studies for the treatment of several types of cancers. However, the anticancer effect of volasertib on cervical cancer cells is still unknown. In the present study, we show that volasertib can markedly induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreased protein expressions of PLK1 substrates survivin and wee1 in human cervical cancer cells. Furthermore, volasertib also enhances the intracellular reactive oxidative species (ROS) levels, and pretreated with ROS scavenger N-acety-L-cysteine totally blocks ROS generation but partly reverses volasertib-induced apoptosis. In addition, volasertib significantly potentiates the activity of cisplatin to inhibit the growth of cervical cancer in vitro and in vivo. In brief, volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer, suggesting the combination of volasertib and cisplatin may be a promising strategy for the treatment of patients with cervical cancer.