Yoshie Imai, Akiko Abe, 村上 好恵, 武田 祐子, 川崎 優子, Takae Bando, Aki Takahashi, Yuta Inoue, 阪本 朋香 and Kanako Yoshida : Emotions of patients with hereditary breast and ovarian cancer syndrome after risk reducing salpingo-oophorectomy, Journal of Hereditary Tumors, Vol.22, No.3, 68-74, 2022.
(Keyword)
乳癌患者 / 遺伝性乳癌卵巣癌症候群患者 / リスク低減卵管卵巣摘出術 / breast cancer patients / hereditary breast and ovarian cancer syndrome(HBOC) / risk reducing salpingo-oophorectomy (RRSO)
Takako Kawakita, Toshiyuki Yasui, Kanako Yoshida, Sumika Matsui and Takeshi Iwasa : Correlations of Androstenediol with Reproductive Hormones and Cortisol According to Stages during the Menopausal Transition in Japanese Women. J, The Journal of Steroid Biochemistry and Molecular Biology, Vol.214, 106009, 2021.
(Summary)
Associations of androstenediol, which has both androgenic and estrogenic activities, with circulating reproductive hormones and stress hormone in women during the menopausal transition may be different depending on the menopausal stage. The aim of this study was to determine the changes in circulating androstenediol during the menopausal transition in Japanese women and the associations of androstenediol with estrogen, androgen and cortisol for each stage of the menopausal transition. We divided the 104 subjects into 6 stages by menstrual regularity and follicle-stimulating hormone level: mid reproductive stage, late reproductive stage, early menopausal transition, late menopausal transition, very early postmenopause and early postmenopause. Levels of dehydroepiandrosterone sulfate (DHEAS), estradiol, estrone, testosterone (T), free T, androstenedione and cortisol were measured. Serum androstenediol concentration was measured by using liquid chromatography mass spectrometry. There were no significant differences in androstenediol levels among the 6 stages. Levels of DHEA-S and testosterone showed significant and positive correlations with androstenediol in all stages. Estradiol levels showed negative correlations with androstenediol levels in the late menopausal transition and very early postmenopause (r=-0.452, p = 0.052 and r=-0.617, p = 0.006, respectively). Cortisol levels showed significant and positive correlations with androstenediol levels in the mid and late reproductive stages (r = 0.719, p = 0.003 and r = 0.808, p < 0.001, respectively).The associations of androstenediol with estradiol and cortisol were different depending on the stage of the menopausal transition. Androstenediol may play a compensatory role for estrogen deficiency from late menopausal transition to very early postmenopause.
Takako Kawakita, Takeshi Iwasa, Shuhei Kamada, Kanako Yoshida and Takeshi Katou : Effects of gonadal status and the estrogen milieu on hypothalamic oxytocin gene expression and serum oxytocin levels in female rats., Hormones and Behavior, Vol.133, No.8, 105005, 2021.
(Summary)
Oxytocin (OT) and its receptor (OTR) play various roles in the central and peripheral regulation of appetite and body weight. Previously, we have shown that the administration of OT markedly decreased appetite and body weight gain in ovariectomized (OVX) obese rats. In addition, recent studies have shown that the endogenous OT system is also affected by endogenous or exogenous estrogen. In this study, we showed that ovariectomy decreased rats' hypothalamic OT/OTR mRNA and serum OT levels, but did not affect their visceral fat OTR mRNA levels. The chronic administration of estradiol (E2) abrogated these ovariectomy-induced changes; i.e., it increased the rats' hypothalamic OT/OTR mRNA and serum OT levels, and may be associated with reductions in food intake and body weight gain. In addition, acute E2 administration increased the rats' hypothalamic OTR mRNA and serum OT levels, but did not affect their hypothalamic OT mRNA levels. Taken together, these results suggest that endogenous OT and/or OTR expression might be positively regulated by E2 and that the suppressive effects of E2 on appetite and body weight gain might be mediated, at least in part, by the OT system. Thus, we consider that OT might be a target hormone to pursue subsequent interventions of menopause for menopause-induced metabolic disorders.
Kana Kasai, Takeshi Katou, Yuri Kadota, Otgontsetseg Erdenebayar, Kaoru Keyama, Takako Kawakita, Kanako Yoshida, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Intraperitoneal administration of activin A promotes development of endometriotic lesions in a mouse model of endometriosis., The Journal of Medical Investigation : JMI, Vol.66, No.1.2, 123-127, 2019.
(Summary)
This study aimed to investigate the effect of intraperitoneal administration of activin on the occurrence of endometriosis using a mouse model of endometriosis. A mouse model of endometriosis was prepared by intraperitoneally administering endometrial tissue and blood collected from donor mice to C57BL/6J 7-8- week-old recipient mice. A total of 400 μg of activin A was intraperitoneally administered to model mice in the activin group for 5 days. Intraperitoneal endometriotic lesions were confirmed macroscopically and IL-6 and TNF-α levels in washed ascites were measured by ELISA. Endometriotic lesions were observed in all mice. In the activin group, the maximum diameter of endometriotic lesions was significantly larger than that in control group (4.7?1.3 vs 2.9?0.9 mm, p?0.01). The total area of the lesion was also significantly higher in the activin group than in the control group (21.1?9.9 vs 8.8?5.4 mm,p?0.01). Furthermore, IL-6 and TNF-α levels in ascites were significantly higher in the activin group than in the control group (IL-6 : 85.8?15.3 vs 75.1?19.3 pg/ml, p?0.05 ; TNF-α : 629.8?15.4 vs 605.9?11.4 pg/ml, p?0.05). Activin promotes occurrence of endometriosis. Inflammatory cytokines are also elevated by activin administration,suggesting that they may contribute to progression of endometriosis J. Med. Invest. 66 : 123-127, February, 2019.
Kaoru Keyama, Takeshi Katou, Yuri Kadota, Otgontsetseg Erdenebayar, Kana Kasai, Takako Kawakita, Anna Tani, Sumika Matsui, Takeshi Iwasa, Kanako Yoshida, Masahiko Maegawa, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Lipopolysaccharide promotes early endometrial-peritoneal interactions in a mouse model of endometriosis., The Journal of Medical Investigation : JMI, Vol.66, No.1.2, 70-74, 2019.
(Summary)
The aims of this study were to clarify the effects of lipopolysaccharide (LPS) on the early development of endometriosis and on the production of cytokines and chemokines in the murine peritoneal cavity. Endometriotic lesions were induced in C57BL/6J adult female mice by intraperitoneal injection of endometrial fragments plus blood or endometrial fragments plus blood with LPS. On day 7, endometriotic lesions were assessed by gross and microscopic evaluations. Time-dependent changes in the secretion of TNF-α,IL-6,and CXCL2/MIP-2 in peritoneal lavage fluid after the intraperitoneal injection of LPS (50 µg/body) were measured by their respective enzyme-linked immunosorbent assays. The areas of endometriotic lesions in the LPS group (10.8 8.6 mm) were significantly larger than those in the control group (3.1 3.7 mm).The levels of TNF-α and IL-6 peaked within 2 hours and the level of MIP-2 reached a maximum on day 1 after the injection of LPS. LPS promotes development of the early stages of murine endometriotic lesions. J. Med. Invest. 66 : 70-74, February, 2019.
Kanako Yoshida, Masato Nishimura, Akiko Abe, Takeshi Katou, Hiroyuki Furumoto and Minoru Irahara : Can systematic lymphadenectomy be omitted for low-risk endometrial cancer?, The Journal of Medical Investigation : JMI, Vol.65, No.3,4, 221-224, 2018.
(Summary)
The objective of this study was to identify pathological indicators that could be used to identify a subgroup of patients with apparent stage I endometrial cancer who do require retroperitoneal lymphadenectomy. 188 T1 endometrial cancer patients underwent primary surgery at Tokushima University Hospital. We retrospectively evaluated their clinical records and histopathological factors. Systematic lymphadenectomy was performed for 149 patients, and 39 patients (grade 1 with < 5 mm of myometrial invasion) were treated without lymphadenectomy. Lymph node metastases were found in 19 (12.8%) of the lymphadenectomy cases. Twenty-four patients with a T1a endometrium-limited lesion did not exhibit lymph node metastasis. Three (3.1%) of the 95 patients with a T1a lesion exhibited lymph node metastasis, and these 3 cases exhibited approximately 50% myometrial invasion. The 39 low-risk patients who did not undergo systematic lymphadenectomy remain alive without recurrence. Systematic lymphadenectomy could be omitted for patients with a grade 1 tumor and minor myometrial invasion of less than 5mm. J. Med. Invest. 65:221-224, August, 2018.
Sumika Matsui, Toshiyuki Yasui, Kana Kasai, Kanako Yoshida, Takeshi Katou, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Circulating dehydroepiandrosterone-sulphate decreases even with a slight change in oestradiol., Journal of Obstetrics and Gynaecology, Vol.38, No.2, 231-235, 2017.
(Summary)
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.
Sumika Matsui, Toshiyuki Yasui, Kana Kasai, Kaoru Keyama, Kanako Yoshida, Takeshi Katou, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Sex hormone-binding globulin and antithrombin III activity in women with oral ultra-low-dose estradiol., Journal of Obstetrics and Gynaecology, Vol.37, No.5, 627-632, 2017.
(Summary)
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 g) every day (oral ultra-low-dose group) and 20 women received a transdermal patch (50 g) as a transdermal group. In addition, the women received dydrogesterone continuously (5g) except for women who underwent hysterectomy. Circulating SHBG, antithrombin III (ATIII) activity, d-dimer, thrombin-antithrombin complex and plasmin- 2 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.
Takeshi Katou, Kaoru Keyama, Sumika Matsui, Mikio Yamasaki, Kanako Yoshida and Minoru Irahara : Step Up from Salpingo-Oophorectomy to Total Laparoscopic Hysterectomy Incorporating Incision Dissectiong Procedures., Journal of Minimally Invasive Gynecology, Vol.22, No.6S, S217, 2015.
Yasuyo Saijo, Hiroyuki Furumoto, Kanako Yoshida, Masato Nishimura and Minoru Irahara : Clinical Significance of Vascular Endothelial Growth Factor Expression and Microvessel Density in Invasive Cervical Cancer., The Journal of Medical Investigation : JMI, Vol.62, No.3-4, 154-160, 2015.
(Summary)
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.
河見 貴子, Hiroyuki Furumoto, Kanako Yoshida, Takeshi Katou, Masato Nishimura and Minoru Irahara : Effectiveness and tolerability of hysterectomy for the local recurrence of cervical cancer after radiation therapy, Modern Trends in Obstetrics & Gynecology, Vol.61, No.2, 321-324, 2013.
(Keyword)
recurrent uterine cervical cancer / concurrent chemoradiation (CCRT) / hysterectomy
Kanako Yoshida, Hiroyuki Furumoto, Akiko Abe, Takeshi Katou, Masato Nishimura and Minoru Irahara : The possibility of vertical transmission of human papillomavirus through maternal milk, Journal of Obstetrics and Gynaecology, Vol.31, No.6, 503-506, 2011.
(Summary)
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.
Akiko Abe, Hiroyuki Furumoto, Kanako Yoshida, Takeshi Katou, Yasuyo Saijo and Minoru Irahara : Gene gun-mediated skin transfection with FL gene suppresses the growth of murine fibrosarcoma., The Journal of Medical Investigation : JMI, Vol.58, No.1-2, 39-45, 2011.
(Summary)
Particle-mediated transfection is known as an efficient method of non-viral gene transfer. Flt3 ligand (FL) is a growth factor for hematopoietic progenitors; it promotes the growth of dendritic cells (DC). DCs are powerful antigen-presenting cells (APCs) and show a remarkable capacity to stimulate antigen-specific T-cell responses. In this study, we intended to investigate the suppressive effect on tumor growth by gene gun-mediated transfer of FL in a murine model. C57BL/6J mice were injected intradermally with MCA205 cells. DNA (pNGVL-hFLex)-coated gold particles were delivered to the mouse skin surrounding the target tumor. The expression of FL was determined by RT-PCR. Analyses by immunohistochemistry and fluorescence-activated cell sorter (FACS) revealed an increase in the number of DC after treatment with FL. Gene gun-mediated pNGVL-hFLex transfer significantly inhibited the growth of the MCA205 tumor. FL transfer markedly increased the number of CD11c(+) DCs in the tumor tissue. Further, the FL-transfected mice exhibited a significantly higher number of CD80(+) MHC-II cells. We successfully performed FL therapy using an in vivo gene gun in order to effectively mobilize DCs in situ and induce suppressive immunity.
Toshiyuki Yasui, Yukie Matsuura, Takako Kawakita and Kanako Yoshida : OC・LEPの有害事象, Japanese Journal of Medicine and Pharmaceutical Science, Vol.77, No.10, 1367-1374, 2020.
Kanako Yoshida, 門田 友里, Kana Kasai, Takako Kawakita, Takeshi Katou and Minoru Irahara : 妊娠中の腹腔鏡下卵巣腫瘍手術におけるアプローチ法の工夫, The Journal of Japan Society for Menopause and Women's Health, Vol.26, Oct. 2018.
12.
Kanako Yoshida, Kadota Yuri, Kasai Kana, Kawakita Takako, Takeshi Katou and Minoru Irahara : Healthcare for young gynecologic malignant tumor patients at our hospital, Acta Obstetrica et Gynaecologica Japonica, Vol.70, No.2, 637, Feb. 2018.
13.
Kanako Yoshida, 門田 友里, Kana Kasai, Takako Kawakita, Takeshi Katou and Minoru Irahara : 妊娠中の腹腔鏡下卵巣腫瘍手術におけるアプローチ法の工夫, Japanese Journal of Gynecologic and Obstetric Endoscopy, Vol.34, 2018.
14.
松井 寿美佳, Toshiyuki Yasui, Kana Kasai, Kanako Yoshida, Takeshi Katou, Hirokazu Uemura and Minoru Irahara : ホルモン補充療法中，デヒドロエピアンドロステロンサルフェートは，わずかなエストロゲンの増加でも低下する, 第32回日本女性医学学会学術集会, Nov. 2017.
15.
Kanako Yoshida : ワークショップ:深部子宮内膜症に対する治療戦略 子宮腺筋症患者における術前MRIによる深部子宮内膜症の評価, 第29回日本内視鏡外科学会総会, Dec. 2016.
Kanako Yoshida : 特別講演:婦人科がん治療後のヘルスケアにおける現状と課題, FUJI women's health regional webinar, Oct. 2021.
2.
Takako Kawakita, Takeshi Katou, Yuri Kadota, 笠井 可菜, Kanako Yoshida and Minoru Irahara : International Session Workshop : New mouse model of uterine adenomyosis., 第72回日本産科婦人科学会学術講演会, Apr. 2021.
3.
Kanako Yoshida : 教育講演: 子宮内膜症の治療における手術療法と薬物療法, 第64回徳島不妊・内分泌研究会, Feb. 2019.
4.
Kanako Yoshida : パネルディスカッション: 高齢出産時代の女性のからだとキャリア形成, 平成24年度徳島産科婦人科学会市民公開講座, Mar. 2013.
5.
Masato Nishimura, Hiroyuki Furumoto, 東元 あゆか, Kanako Yoshida and Minoru Irahara : シンポジウム: 幽門腺化生∼悪性腺腫の頸管粘液中の胃型ムチンと細胞像, 第26回日本臨床細胞学会中国四国連合会学術集会, Jul. 2011.