Kanako Yoshida

The possibility of vertical transmission of human papillomavirus through maternal milk

Human papillomavirus (HPV) DNA has been detected in the oral cavity of infants and breast cancer tissue, suggesting its vertical transmission through maternal milk. We determined whether HPV is detected in maternal milk and is vertically transmitted by breast-feeding. Informed consent was obtained, and maternal milk samples (n=80) were analysed for high-risk HPV DNA. In 43 women, this DNA was measured in the uterine cervix. In women with positive samples, this DNA was measured in the oral cavities of their children. The domain including HPV E6 and E7 was amplified by polymerase chain reaction using consensus primers, and HPV serotype determined by electrophoresis after restriction enzyme digestion. High-risk HPV-16 was detected in two of 80 samples (2.5%), and in these two cases, high-risk HPV was not detected in the uterine cervix or oral cavity of the child. It was concluded that the infection of HPV in maternal milk is rare (2/80); vertical transmission through maternal milk was not detected in this study (0/80). HPV infection through maternal milk may occur, but its likelihood is low.

Clinical Significance of Vascular Endothelial Growth Factor Expression and Microvessel Density in Invasive Cervical Cancer

To determine whether vascular endothelial growth factor (VEGF) expression and microvessel density are predictive of prognosis in cases of invasive cervical cancer, correlations among VEGF expression, microvessel density, and clinicopathological parameters were identified. VEGF expression was evaluated in 50 cervical cancer samples by immunohistochemical staining. Microvessel density was assessed by immunostaining for CD31-positive endothelial cells in the most vascularized areas of tumors. VEGF expression and microvessel density were significantly higher in adenocarcinomas than in squamous cell carcinomas. However, in cases of adenocarcinoma, no significant correlations were found among VEGF expression, microvessel density, and clinicopathological parameters. In contrast, for squamous cell carcinomas, microvessel density was significantly higher in cases at an advanced stage and in those with several other poor prognostic factors. The finding that cervical adenocarcinomas exhibited greater VEGF expression and microvessel density than squamous cell carcinomas may explain the poorer prognosis of adenocarcinoma compared with squamous cell carcinoma. Moreover, microvessel density in squamous cell carcinomas was significantly correlated with poor prognostic factors. Therefore, there is possibility that bevacizumab, a humanized monoclonal antibody against VEGF-A, may be useful in the initial treatment targeting angiogenesis for early-stage cervical cancer.

Circulating dehydroepiandrosterone-sulphate decreases even with a slight change in oestradiol

Abstract The aim of this study was to determine the effect of hormone replacement therapy (HRT) on changes in circulating dehydroepiandrosterone-sulphate (DHEA-S) with focus on the relationship between oestrogen level and change in DHEA-S. Forty-two women were enrolled in this longitudinal study. Nineteen women received oral oestradiol and twenty-three women received transdermal oestradiol continuously. Twenty women received progesterone continuously except for women who had undergone hysterectomy. Circulating oestradiol, follicle-stimulating hormone, luteinising hormone and DHEA-S levels before and at 3 months after commencement of HRT were measured. Circulating DHEA-S level was significantly decreased at 3 months (p < .001). Oestradiol level at 3 months ranged from 6.5 pg/ml to 159 pg/ml. There was no significant correlation of ΔDHEA-S (DHEAS level at 3 months—DHEA-S level at baseline) with Δoestradiol (r = 0.114, p = .471). Circulating DHEA-S level was significantly decreased at 3 months in all the four quartiles and divided according to Δoestradiol, and ΔDHEA-S did not show significant differences. In conclusion, circulating DHEA-S decreases even with a slight increase in oestradiol level. Impact statement What is already known on this subject: A transient increase in DHEA-S in women during the menopausal transition may be involved in the occurrence of menopausal symptoms and/or unfavourable metabolic changes. Hormone replacement therapy decreases circulating DHEA-S level. However, dose dependency of the change in DHEA-S on oestrogen has not been reported. What the results of this study add: Circulating DHEA-S decreases even with a slight increase in oestradiol level. What the implications are of these findings for clinical practice and/or further research: Adrenal function may respond to a small change in oestrogen.

Sex hormone-binding globulin and antithrombin III activity in women with oral ultra-low-dose estradiol

Abstract Oral oestrogen increases the risk of venous thromboembolism (VTE) and increases production of sex hormone-binding globulin (SHBG) in a dose-dependent manner. SHBG has been suggested to be involved in venous thromboembolism. We examined the effects of oral ultra-low-dose oestradiol on circulating levels of SHBG and coagulation parameters, and we compared the effects to those of transdermal oestradiol. Twenty women received oral oestradiol (500 μg) every day (oral ultra-low-dose group) and 20 women received a transdermal patch (50 μg) as a transdermal group. In addition, the women received dydrogesterone continuously (5 mg) except for women who underwent hysterectomy. Circulating SHBG, antithrombin III (ATIII) activity, d-dimer, thrombin–antithrombin complex and plasmin–α2 plasmin inhibitor complex were measured before and 3 months after the start of treatment. SHBG was significantly increased at 3 months in the oral ultra-low-dose group, but not in the transdermal group. However, percent changes in SHBG were not significantly different between the two groups. In both groups, ATIII was significantly decreased at 3 months. In conclusion, even ultra-low-dose oestradiol orally increases circulating SHBG level. However, the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. Impact statement Oral oestrogen replacement therapy increases production of SHBG which may be related to increase in VTE risk. However, the effect of oral ultra-low-dose oestradiol on SHBG has not been clarified. Even ultra-low-dose oestradiol orally increases circulating SHBG levels, but the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. VTE risk in women receiving oral ultra-low-dose oestradiol may be comparable to that in women receiving transdermal oestradiol.

High Androgenicity and Unfavorable Cardiovascular risk profiles in Non-Obese Women around Menopausal Transition

High Androgenicity and Unfavorable Cardiovascular risk profiles in Non-Obese Women around Menopausal Transition Objective Metabolic changes related to atherogenic diseases have already occurred during menopausal transition rather than after menopause. Also, a change in androgenicity as well as estrogen deficiency occurs around the time of menopausal transition. Focusing on around menopausal transition, we examined the relationships of androgens and sex hormone-binding globulin (SHBG) with blood pressure, lipid profiles and insulin resistance in healthy non-obese women. Methods We conducted a cross-sectional study in healthy non-obese women around menopausal transition (107 women in menopausal transition and 106 women in early postmenopause). Serum levels of estradiol, total testosterone, dehydroepiandrosterone-sulfate, SHBG, lipid profiles, glucose and insulin as well as blood pressure were measured. Results There were significant positive correlations of total testosterone, free testosterone and bioavailable testosterone with systolic and diastolic blood pressure. Total testosterone, free testosterone and bioavailable testosterone showed significant positive correlations with triglyceride and negative correlations with high-density lipoprotein cholesterol (HDL-C). SHBG showed a significant positive correlation with HDL-C and negative correlations with triglyceride and glucose. Conclusions High androgenicity indicated by high levels of free testosterone and bioavailable testosterone or low level of SHBG has unfavorable effects on blood pressure, lipid profiles and glycometabolism in non-obese women around menopausal transition.. .

Abstract 433: mTOR overexpression is associated with radio-resistance and worse prognosis of cervical cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC mTOR is an important factor for cell proliferation. It is reported that overexpression of mTOR is associated with poor prognosis in many cancers. We examined mTOR expression in cervical cancer and association with clinico-pathological findings. 34 patients were examined about mTOR expression by immuno-histochemistry. The result was classified into 3 categories, i.e negative, weak positive and strong positive. 25 patients were treated with concurrent chemoradiotherapy, 8 ptients were treated with hysterectomy and one patient was treated with chemotherapy as main treatment. Overexpression of mTOR was recognized in 24(71%) patients. The frequency of parametrial invasion and lymphnode metastasis in mTOR positive and negative were 17/24 (71%) versus 3/10 (30%) (p=0.027) and 14/24 (58%) versus 2/10 (20%) (p=0.041). In 25 cases treated with radiotherapy, mTOR overexpression was seen in 19 cases (76%). Averages of tumor diameter in mTOR positive and negative cases were 4.8 cm and 5.0cm respectively (n.s). In 5 local recurrent cases treated with chemo-radiotherpy, tumor diameters of pre-treatment were 0, 3.5, 5.5, 7 and 7cm. Small tumor was included in local recurrence in mTOR positive cases. It is suggested that mTOR overexpression promotes lymphnode and parametrial metastasis and is associated with radio-resistance. In case of mTOR overexpression, we need to consider treatment by hysterectomy if the tumor is resectable or usage of mTOR inhibitor at chemo-radiation, and control of mTOR expression is important in treatment of cervical cancer. Citation Format: Masato Nishimura, Kanako Yoshida, Hiroyuki Furumoto, Minoru Irahara. mTOR overexpression is associated with radio-resistance and worse prognosis of cervical cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 433. doi:10.1158/1538-7445.AM2013-433