A multicenter, randomized, open, controlled trial to evaluate the efficacy of Honglilai Vaginal Cream and Premarin Vaginal Cream for Genitourinary Syndrome of Menopause in different subgroups of Chinese postmenopausal women.

AIM: In a randomized, multicenter, open, controlled trial, we compared the effects of Honglilai Vaginal Cream and Premarin Vaginal Cream in different age subgroups and menopausal year subgroups (trial registration numbers: 02003L00493). METHODS: Postmenopausal women with Genitourinary Syndrome of Menopause (GSM) were divided into Honglilai group (n = 319) and Premarin group (n = 116), while subgroups were divided according to their different characteristics of age and menopausal years. Honglilai Vaginal Cream (0.625 mg/g) or Premarin Vaginal Cream (0.625 mg/g) once daily for 3 weeks. RESULTS: In the subgroup of participates >60 years, there were no significant differences of Vaginal Cell Maturation Index (VMI) between the two groups after treatment (p = .171). In the subgroup of 50-59 years, the VMI of Honglilai group was significantly lower than Premarin group (Honglilai group: 74.37 ± 22.76; Premarin group: 80.06 ± 16.15; p = .02). There were no significant differences of Vaginal symptom scores between Honglilai group and Premarin group in every sub-group (p > .05). CONCLUSIONS: Honglilai Vaginal Cream had comparable efficacy with Premarin Vaginal Cream in Chinese women older than 60 years.

Twist-1 Stimulates the Malignant Behaviors of Hydatidiform Mole via the PI3K/AKT Pathway.

BACKGROUND: Hydatidiform mole (HM) is a common pregnancy disease among women of gestational age. Twist-related protein 1 (Twist-1) is involved in the development of various tumors, but its role in HM is poorly defined. This study aimed to explore Twist-1 expression and its biological function in HM cells. METHODS: Twist-1 expression in HM was detected by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). The effects of silencing Twist-1 on choriocarcinoma (CCA) cell proliferation were detected by cell counting kit-8 (CCK-8) and clone formation assays. CCA cell migration and invasion were detected through transwell assay. Western blot was used to detect epithelial-mesenchymal transition (EMT) and the expression of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins. RESULTS: Twist-1 expression was upregulated in HM tissues (p < 0.001) and CCA cells (p < 0.01). Twist-1 silencing inhibited proliferation of BeWo and JAR cells (p < 0.01, p < 0.05) as shown by CCK-8 assay (p < 0.01) and clone formation assays (p < 0.01, p < 0.05). Twist-1 silencing inhibited the migration (p < 0.01) and invasion activity (p < 0.01, p < 0.05) of BeWo and JAR cells. Western blot results showed that Twist-1 silencing promoted E-cadherin (p < 0.01) expression, and inhibited N-cadherin (p < 0.01, p < 0.05) and vimentin (p < 0.01, p < 0.05) expression in BeWo and JAR cells. Twist-1 downregulation decreased protein levels of p-PI3K (p < 0.01) and p-AKT (p < 0.01, p < 0.05) in BeWo and JAR cells. CONCLUSIONS: Silencing Twist-1 inhibits the malignant behavior of CCA cells, which may play a part by inhibiting the EMT process and the PI3K/AKT pathway.

OLFM4 Inhibits Epithelial-Mesenchymal Transition and Metastatic Potential of Cervical Cancer Cells.

OLFM4 has been shown to play an important role in tumor initiation and progression. This study aims to investigate the role of OLFM4 in metastatic cervical cancer and its underlying mechanism. Here we discover that OLFM4 expression is significantly reduced in metastatic cervical cancer. Accordingly, overexpression of OLFM4 inhibits epithelial-mesenchymal transition (EMT), migration, and invasion in human cervical cancer cells. To further explore its molecular mechanisms, we reveal that OLFM4 augmentation interferes with mTOR signaling pathway, and the suppressive effects of OLFM4 on cell migration and invasion are largely weakened by phosphatidic acid (PA)-induced mTOR signal activation, which implicates the potential role of the mTOR pathway in OLFM4-related cervical metastasis. In conclusion, our results confirm OLFM4 as a tumor suppressor that inhibits cervical cancer metastasis by regulating mTOR signal pathway.

The expression of Tim-3 in peripheral blood of ovarian cancer.

Ovarian cancer remains a challenging disease for which improved treatments are urgently needed. Tim-3 acts as a negative regulatory molecule and plays a critical role in immune tolerance. In the current study, we investigated the expression of Tim-3 on peripheral CD4+ T and CD8+ T cells in ovarian cancer. A total of 52 ovarian cancer patients and 56 healthy controls were recruited and leukocytes from peripheral blood mononuclear cells were analyzed for Tim-3 surface expression by flow cytometry. Data showed that expression of Tim-3 was significantly increased in both CD4+ and CD8+ T cells in ovarian cancer cases than in controls (p<0.0001 and p<0.0001, respectively). Patients who had recurrent ovarian cancer had a higher proportion of Tim-3+CD4+ T cells than when they were newly diagnosed (p=0.013). When analyzing Tim-3 expression with cancer progression, results revealed elevated Tim-3 expression in both CD4+ and CD8+ T cells in cases with advanced International Federation of Gynecology and Obstetrics (FIGO) staging (III/IV) than those with stage I and II (p=0.009 and p=0.037, respectively). We also tested Tim-3 with tumor grade, and observed that patients with a higher tumor grade (G3) demonstrated further augmented Tim-3 expression in CD4+ and CD8+ T cells compared to those with lower tumor grades (p=0.010 and p=0.042, respectively). Our study suggested that Tim-3 may participate in the development and progression of ovarian cancer by its negative regulation on various T-cell subsets, and Tim-3 expression in CD4+ T cells could serve as a predictive marker for anticancer therapies.

Lysyl oxidase G473A polymorphism is associated with increased risk of ovarian cancer.

Despite the knowledge of many genetic alterations present in ovarian cancer, the complexity of this disease precludes placing its biology into a simple conceptual framework. Lysyl oxidase (LOX) is an extracellular matrix enzyme that catalyzes the cross-linking of collagens or elastin in the extracellular compartment. A novel polymorphism in the LOX gene, G473A (rs1800449), has been reported as being a risk factor for different diseases. The objective of this study was to investigate the association between the LOX G473A polymorphism and the susceptibility to ovarian cancer in the Chinese population. The LOX variant G473A was detected by a polymerase chain reaction-restriction fragment length polymorphism in 233 ovarian cancer cases and 246 age-matched controls. Data were analyzed using the chi-square test. Data showed that frequencies of the LOX 473AA genotype and the A allele were significantly higher in ovarian cancer patients than in controls (odds ratio [OR]=2.52, 95% confidence interval [CI] 1.28-4.96, p=0.006; and OR=1.62, 95% CI 1.18-2.20, p=0.002). In addition, the prevalence of the GA genotype, AA genotype, and A allele were significantly increased in recurrent ovarian cancer cases compared with primary ovarian cancer cases. Our data suggest that the G473A polymorphism of the LOX gene is associated with increased susceptibility to ovarian cancer.