ObjectiveGlycogen synthase kinase 3β (GSK3β) is a pluripotent protein kinase involved in the development of cancers through regulation of numerous oncogenic molecules. Cyclin D1, an important regulator of G1 to S phase transition in various cells, is one of target proteins that GSK3β regulate. Our objective was to assess the expression of GSK3β and cyclin D1 in cervical neoplasm of different histologic grades and to identify their correlation in cervical carcinogenesis.MethodsImmunohistochemical analysis of GSK3β and cyclin D1 was performed in a total of 137 patients with 12 normal, 62 cervical intraepithelial neoplasia (CIN) (31 CIN1 and 31 CIN3) and 63 invasive cancers including 56 squamous cell carcinomas and 7 adenocarcinomas.ResultsThe expression of GSK3β increased in parallel with the lesion grade, while that of cyclin D1 decreased with severity of the lesion (P<0.001). There was a significant inverse correlation between GSK3β and cyclin D1 expression in overall cervical neoplasia (Φ=-0.413, P<0.001). GSK3β expression was higher in squamous cell carcinoma than in adenocarcinoma (P=0.049).ConclusionThese results suggest that the expressional increase in GSK3β plays a role in cervical carcinogenesis and has inverse correlation with cyclin D1 expression in this process. In addition, GSK3β expression appears to be associated with the histologic type of cervical cancer, especially squamous cell carcinoma.

In this study, HER2 RNA aptamers were conjugated to mertansine (DM1) and the anti-cancer effectiveness of the conjugate was evaluated in HER2-overexpressing breast cancer models. The conjugate of HER2 aptamer and anticancer drug DM1 (aptamer-drug conjugate, ApDC) was prepared and analyzed using HPLC and mass spectrometry. The cell-binding affinity and cytotoxicity of the conjugate were determined using confocal microscopy and WST-1 assay. The in vivo anti-tumoral efficacy of ApDC was also evaluated in mice carrying BT-474 breast tumors overexpressing HER2. The synthesized HER2-specific RNA aptamers were able to specifically and efficiently bind to HER-positive BT-474 breast cancer cells, but not to HER2-negative MDA-MB-231 breast cancer cells. Also, the HER2-specific ApDC showed strong toxicity to the target cells, BT-474, but not to MDA-MB-231 cells. According to the in vivo analyses drawn from the mouse xenografts of BT-747 tumor, the ApDC was able to more effectively inhibit the tumor growth. Compared to the control group, the mice treated with the ApDC showed a significant reduction of tumor growth. Besides, any significant body weight losses or hepatic toxicities were monitored in the ApDC-treated mice. This research suggests the HER2 aptamer-DM1 conjugate as a target-specific anti-cancer modality and provides experimental evidence supporting its enhanced effectiveness for HER2-overexpressing target tumors. This type of aptamer-conjugated anticancer drug would be utilized as a platform structure for the development of versatile targeted high-performance anticancer drugs by adopting the easy deformability and high affinity of aptamers.

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This study aimed to evaluate the association between menopause and blood mercury concentrations in South Korean women. Women aged ≥20 years who participated in the Korean National Health and Nutrition Examination Survey 2008-2011 were included in this study. Primary and secondary analyses included women aged ≥20 years (n = 1,642) and 45-55 years (i.e., perimenopausal; n = 325), respectively. For all analyses, the mercury levels were log-transformed. The linear regression model for mercury levels was adjusted for age, body mass index, household income, menopausal status, hormone replacement therapy, use of oral contraceptives, smoking history, alcohol intake, physical activity, number of pregnancies, serum ferritin levels, and fish consumption. After adjusting for covariates, log-transformed blood mercury levels were significantly lower in women who were menopausal [β-coefficient -0.1488; 95 % confidence interval -0.2586, -0.0389; P = 0.01) than in those who were premenopausal. A similar relationship was identified in perimenopausal women (β-coefficient -0.1753; 95 % confidence interval -0.3357, -0.015; P = 0.03). The blood mercury concentration was lower in postmenopausal women than in premenopausal women. There was a significant positive correlation between blood mercury concentrations and both the frequency of alcohol intake and serum ferritin levels.