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)
Akiko Abe, Masao Yuasa, Yoshie Imai, Tomohiro Kagawa, Ayuka Mineda, Masato Nishimura, Chisato Tonoiso, Akiko Kubo, Takashi Kawanaka, Hitoshi Ikushima and Takeshi Iwasa : Extreme leanness, lower skeletal muscle quality, and loss of muscle mass during treatment are predictors of poor prognosis in cervical cancer treated with concurrent chemoradiation therapy, International Journal of Clinical Oncology, Vol.27, No.5, 983-991, 2022.
(要約)
Human papillomavirus vaccination is not widespread in Japan, and the low screening rates result in many cases of locally advanced cervical cancer. We investigated the prognostic significance of sarcopenia in patients with cervical cancer to guide healthcare policies to improve treatment outcomes. This retrospective study included 83 patients with cervical cancer without distant metastasis who underwent primary concurrent chemoradiotherapy between 2013 and 2018. We analyzed the indicators of physical condition and muscle quantity using the SYNAPSE VINCENT software. Muscle mass and the relationship between treatment toxicity and prognosis were evaluated. The patients' median age was 60 (range 33-80) years. Cancer stage distribution was as follows: cT2b or higher, 84.3%; N1, 65.1%; and MA, 27.7%. The overall sarcopenia (skeletal muscle index [SMI] < 38.5) rate was 30.1%, and the rate was 33.9 and 22.2% in patients aged < 64 and ≥ 65 years, respectively. No correlation was observed between clinical stage and musculoskeletal indices. Treatment resulted in decreased body weight and SMI; after treatment, the sarcopenia rate increased to 37.3%. A higher intramuscular adipose tissue content (IMAC) reduced the number of chemotherapy cycles needed. Treatment-associated SMI decreases of ≥ 7% indicated poor prognosis, with significant differences in progression-free survival and overall survival (p = 0.013 and p = 0.012, respectively). Patients who were very lean (body mass index < 18.5 kg/m) before treatment had a poor prognosis (p = 0.016 and p < 0.001). Our findings emphasize the importance of assessing original nutritional status and maintaining muscle mass and quality during the treatment of patients with cervical cancer.
The purpose of this study is to explore the psychological adjustments female cancer survivors undergo with respect to their femininity. Semi-structured interviews were performed with 29 female cancer(breast or gynecologic cancer)survivors in their20s to50s. Qualitative descriptive study data was interpreted according to Krippendorff's content analysis method.As a result, six categories were generated as psychological adjustments utilized by female cancer survivors from the viewpoint of femininity : "I like the way I am" ; "I am charming as a woman" ; "I live independently as a woman" ; "I am expanding my life as a woman" ; "I can feel connected with someone" ; and "I have graduated from pessimism." These could be interpreted as psychological adaptations that reflect feminine emotions and reflect the strength and resilience of female cancer survivors. In order for female cancer survivors to adjust to living with cancer in a psychologically healthy way, it was suggested that nursing support was important to restore the feelings of the survivors from the perspective of these feminine characteristics.
(キーワード)
Female cancer / Cancer survivors / Psychological adjustment / Femininity
Ayuka Mineda, Masato Nishimura, Tomohiro Kagawa, Eri Takiguchi, Takako Kawakita, Akiko Abe and Minoru Irahara : Resveratrol suppresses proliferation and induces apoptosis of uterine sarcoma cells by inhibiting the Wnt signaling pathway., Experimental and Therapeutic Medicine, Vol.17, No.3, 2242-2246, 2019.
(要約)
Resveratrol, a natural product and peroxisome proliferator-activated receptor (PPAR) agonist, has been reported to exert anti-cancer effects in several tumor models. A previous study by our group reported that prostaglandin J2, a PPARγ ligand, inhibited cell proliferation in a uterine sarcoma cell line. The aim of the present study was to investigate the role of the Wnt signaling pathway in resveratrol-induced apoptosis and inhibition of cell proliferation in the MES-SA human uterine sarcoma cell line. A WST-1 assay demonstrated that resveratrol inhibited cell proliferation in the MES-SA cell line, and flow cytometry revealed that the number of apoptotic cells increased in a resveratrol dose-dependent manner. The mechanisms underlying these effects of resveratrol were speculated to involve the expression of β-catenin and its target gene, c-myc, which were examined using western blot analysis. The results revealed a dose-dependent downregulation of this β-catenin and c-myc. This effect was blunted by a pharmacological inhibitor of glycogen synthase kinase 3β. Therefore, it is likely that resveratrol inhibited the cell proliferation and increased the number of apoptotic cells, at least partially, via the Wnt signaling pathway. The present results suggest that resveratrol is a potential candidate for the treatment of uterine sarcoma.
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.
(要約)
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.
Akiko Abe, Masato Nishimura and Minoru Irahara : See and treat LEEP biopsy for cervical intraepithelial neoplasia grade 2/3, European JOURNAL of Gynaecological Oncology, Vol.39, No.6, 958-962, 2018.
Eri Takiguchi, Masato Nishimura, Ayuka Mineda, Takako Kawakita, Akiko Abe and Minoru Irahara : Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells., Experimental and Therapeutic Medicine, Vol.14, No.5, 4293-4299, 2017.
(要約)
Uterine cervical adenocarcinoma has a poor clinical prognosis when compared with squamous cell carcinoma. Therefore, the development of new treatment strategies for uterine cervical adenocarcinoma is necessary. Src is a proto-oncogene that is important in cancer progression. Dasatinib is a Src inhibitor that has been reported to be effective when used in combination with anticancer drugs. The present study aimed to confirm Src expression in human cervical adenocarcinoma cell lines and to determine the mechanism underlying the inhibitory effect of dasatinib on Src signaling . Western blot analysis was performed to investigate Src expression in cervical adenocarcinoma cell lines (HeLa and TCO-2 cells). The cells were cultured for 48 h with the addition of different concentrations of anticancer drugs (paclitaxel or oxaliplatin). Viable cell count was measured using a colorimetric (WST-1) assay. The concentrations of anticancer agents were fixed according to the results obtained, and the same experiments were performed using the drugs in combination with dasatinib at various concentrations to determine the concentrations that significantly affected the number of viable cells. The presence or absence of apoptosis was investigated using a caspase-3/7 assay. Signal transduction in each cell line was examined using western blotting. Src was activated in the two cell lines, and cell proliferation was significantly suppressed by each anticancer drug in combination with 10 µM dasatinib. Caspase-3/7 activity was also increased and Src signaling was suppressed by each anticancer drug in combination with dasatinib. In conclusion, Src is overexpressed in cervical adenocarcinoma cell lines, and dasatinib inhibits intracellular Src signaling and causes apoptosis. The results of the present study suggest that Src may be targeted in novel therapeutic strategies for cervical adenocarcinoma.
Takako Kawakita, Masato Nishimura, Eri Takiguchi, Akiko Abe and Minoru Irahara : Cytotoxic effects of 15-deoxy-Δ12,14-prostaglandin J2 alone and in combination with dasatinib against uterine sarcoma ., Experimental and Therapeutic Medicine, Vol.13, No.6, 2939-2945, 2017.
(要約)
Effective chemotherapeutic strategies for uterine sarcoma are lacking; existing therapies achieve poor response rates. Previous studies have identified the prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) as a potential anticancer treatment; however, its effectiveness in uterine sarcoma has not been examined. Furthermore, the molecular mechanisms underlying the cytotoxic mechanism of 15d-PGJ2 remain unclear. Here, we evaluated the effects of 15d-PGJ2 alone and in combination with the tyrosine kinas inhibitor (TKI) dasatinib in uterine sarcoma cell lines (MES-SA, MES-SA/DX5 and SKN). 15d-PGJ2 inhibited cell growth and increased apoptosis. Western blotting demonstrated that 15d-PGJ2 treatment increased MEK and ERK phosphorylation, and decreased levels of phosphorylated AKT. Dasatinib in combination with 15d-PGJ2 significantly reduced cell proliferation compared with 15d-PGJ2 alone, and repressed both the AKT and MAPK pathways. The cell growth inhibition rate in the PGJ2 was 21.5±12.0, 35.3±5.4 and 28.3±4.2%, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the cell growth inhibition rate in the combination therapy was significantly higher compared with 15d-PGJ2 alone (MES-SA; 64.2±0.8, MES-SA/DX5;23.9±8.2 and SKN; 41.4±17.6%). The PGJ2 IC determined by MTT assay was 27.41,10.46 and 17.38 µmol/l, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the dasatinib IC was 6.68,17.30 and 6.25 µmol/l, respectively. Our findings demonstrate that 15d-PGJ2 suppresses proliferation by inactivating the AKT pathway in uterine sarcoma. Furthermore, combining 15d-PGJ2 with dasatinib produced a synergistic effect on cancer cell inhibition by repressing 15d-PGJ2-mediated activation of MAPK signaling, and further repressing AKT signaling. These results suggest that 15d-PGJ2 could be used in combination with dasatinib as a potential therapeutic approach for uterine sarcoma.
Akiko Abe, Maki Matoda, Sanshiro Okamoto, Eiji Kondo, Kazuyoshi Kato, Kohei Omatsu, Kenji Umayahara, Kuniko Utsugi and Nobuhiro Takeshima : Resection of the vaginal vault for vaginal recurrence of cervical cancer after hysterectomy and brachytherapy, World Journal of Surgical Oncology, Vol.13, 137, 2015.
(要約)
We describe our experiences with vaginal vault resection for vaginal recurrence of cervical cancer after hysterectomy and radiotherapy. After operative treatment, the rate of vaginal vault recurrence of uterine cervical cancer is reported to be about 5%. There is no consensus regarding the treatment for these cases. Between 2004 and 2012, eight patients with vaginal vault recurrence underwent removal of the vaginal wall via laparotomy after hysterectomy and radiotherapy. The median patient age was 45 years (range 35 to 70 years). The median operation time was 244.5 min (range 172 to 590 min), the median estimated blood loss was 362.5 mL (range 49 to 1,890 mL), and the median duration of hospitalization was 24.5 days (range 11 to 50 days). Two patients had intraoperative complications: a grade 1 bowel injury and a grade 1 bladder injury. The following postoperative complications were observed: one patient had vaginal vault bleeding, three patients developed vesicovaginal fistulae, and one patient had repeated ileus. Two patients needed clean intermittent catheterization. Local control was achieved in five of the eight cases. Vaginal vault resection is an effective treatment for vaginal recurrence of cervical cancer after hysterectomy and radiotherapy. However, complications of this procedure can be expected to reduce quality of life. Therefore, this operation should be selected with great care.
Akiko Abe, Y Sugiyama, R. Furuta, N. Furuta, M. Matoda and N. Takeshima : Usefulness of intraoperative imprint cytology in ovarian germ cell tumors, Acta Cytologica, Vol.57, No.2, 171-176, 2013.
(要約)
This study retrospectively investigated the usefulness of intraoperative diagnosis based on imprint cytology and frozen sections for ovarian germ cell tumor. Intraoperative studies were reviewed for 23 cases with ovarian germ cell tumor treatment for which both frozen sections and imprint cytology were available. Final histopathologic diagnoses were compared with those based on intraoperative examinations. Underlying pathologies included dysgerminoma (n = 6), yolk sac tumor (n = 1), non-gestational choriocarcinoma (n = 1), mature cystic teratoma with malignant transformation (n = 1), immature teratoma (n = 11), and mixed germ cell tumor (n = 3). Discrepancies between intraoperative imprint cytology and definitive histologic diagnosis were seen in 6 of the 23 cases. Accuracy was 54.5% (6/11) for immature teratoma and 91.7% (11/12) for other tumors. Cytologic examination facilitated accurate diagnosis in both of our cases, and intraoperative diagnosis by frozen section proved inaccurate. These results demonstrate that intraoperative assessment based on imprint cytology for immature teratoma has a relatively lower sensitivity, but an acceptable sensitivity for other germ cell tumors. Diagnostic approaches combining frozen sections and imprint cytology are advisable to improve the yield for intraoperative diagnosis.
(キーワード)
Adolescent / Adult / Child / Choriocarcinoma, Non-gestational / Cytodiagnosis / Dysgerminoma / Endodermal Sinus Tumor / Female / Frozen Sections / Humans / Intraoperative Care / Middle Aged / Neoplasms, Germ Cell and Embryonal / Ovarian Neoplasms / Predictive Value of Tests / Retrospective Studies / Sensitivity and Specificity / Teratoma / Young Adult
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.
(要約)
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.
(要約)
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.
Akiko Abe, Hiroyuki Furumoto, Minoru Irahara, Hiroyasu Ino, Masaharu Kamada, Osamu Naka, Masaru Sasaki, Toshiaki Kagawa, Osamu Okitsu and Norio Kushiki : The impact of systematic para-aortic and pelvic lymphadenectomy on survival in patients with optimally debulked ovarian cancer., The Journal of Obstetrics and Gynaecology Research, Vol.36, No.5, 1023-1030, 2010.
(要約)
The objective of this study was to verify the impact of systematic retroperitoneal lymphadenectomy on survival in patients with ovarian cancer.
Akiko Abe, Hiroshi Ikawa and Saki Ikawa : Desensitization treatment with cisplatin after carboplatin hypersensitivity reaction in gynecologic cancer, The Journal of Medical Investigation : JMI, Vol.57, No.1,2, 163-167, 2010.
(要約)
Platinum-based chemotherapy is the standard regimen for the treatment of gynecologic cancers; however, hypersensitivity reactions (HR) to platinum often lead to discontinuation of this effective treatment. Here we performed a desensitization protocol for platinum infusion in 3 patients who required platinum re-administration after developing HR. Two patients (Case 1 and 2) were treated with the desensitization protocol successfully without developing HR during the subsequent 3 courses. Case 3 tolerated desensitization well for 2 courses, but in the 3(rd) course, she developed severe HR immediately after the initiation of cisplatin infusion because the desensitization protocol was unintentionally omitted. These cases show the usefulness and effectiveness of the desensitization protocol for the continuation of platinum treatment in patients who have undergone an extended number of treatments.
Akiko Abe, H Furumoto, K Yoshida, M Nishimura, M Irahara, E Kudo and T Sano : A case of ovarian endometrioid adenocarcinoma with a yolk sac tumor component., International Journal of Gynecological Cancer, Vol.18, No.1, 168-172, 2007.
(要約)
Endometrioid adenocarcinoma of the ovary coexists very rarely with yolk sac tumor (YST). This unusual mixed tumor is thought to be a rare variant of endometrioid ovarian carcinoma because of its aggressive behavior, lack of response to chemotherapy, and unfavorable prognosis. We report a case of ovarian endometrioid adenocarcinoma with a YST component in a postmenopausal woman. The patient was treated by surgery and a combination of bleomycin, etoposide, and cisplatin and taxol and carboplatin. She has been clinically free of tumor for 20 months. Immunohistochemically, the YST component reacted for alpha-fetoprotein. YST areas were negative for both CA125 and sex-hormone receptors. Cytokeratin7 and epithelial membrane antigen were negative in YST, but positive in endometrioid adenocarcinoma. The occurrence of this unusual case suggests that even somatic carcinomas may acquire an extraembryonal germ cell differentiation.
Akiko Abe, Akira Kuwahara, Tomohiro Kagawa, Ayuka Mineda and Masato Nishimura : A survey of germline mutations with epithelial ovarian cancer in Japanese patients., ESGO Annual Meeting 2019, Greece, Nov. 2019.
2.
Akiko Abe : A survey of germline mutations with epithelial ovarian cancer in Japanese patients., The American Society of Human Genetics, Oct. 2018.
3.
Chisato Tonoiso, Hitoshi Ikushima, Akihiro Haga, Shunsuke Furutani, Takashi Kawanaka, Akiko Kubo, Masato Nishimura, Akiko Abe, Minoru Irahara and Masafumi Harada : Investigation of prognostic factors of cervical cancer using pre-treatment MRI images, The 2018 International Gynecologic Cancer Society Meeting, Sep. 2018.
4.
Akiko Abe, Masato Nishimura, Eri Takiguchi, Takako Kawakita, TANIGUCHI Yuka, Yuri Yamamoto, YAMASAKI Mikio, Takeshi Iwasa, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Survey on oncologist and gynecologist concerned with fertility for cancer survivors in reproductive age., IFFS/JSRM International Meeting,2015, Yokohama, Apr. 2015.
5.
Masato Nishimura, Eri Takiguchi, Takako Kawakita, Akiko Abe, TANIGUCHI Yuka, Yuri Yamamoto, YAMASAKI Mikio, Takeshi Iwasa, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Efficacy and pregnant outcomes of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical endometrial hyperplasia in young women., IFFS/JSRM International Meeting,2015, Yokohama, Apr. 2015.