Details of a Researcher - Chiyoda, Tatsuyuki

Papers - Chiyoda, Tatsuyuki

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CLINICOPATHOLOGICAL BACKGROUND AND PROGNOSIS OF ADVANCED OVARIAN CANCER PATIENTS WITHOUT OPTIMAL CYTOREDUCTION AT PRIMARY SURGERY

Saotome K., Nomura H., Dozen A., Nanki Y., Yoshihama T., Iwasa N., Chiyoda T., Yamagami W., Kataoka F., Hirasawa A., Aoki D.

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 28 828 - 828 2018.09

ISSN 1048-891X

UNSUCCESSFUL HIGH-DOSE HORMONAL THERAPY FOR ENDOMETRIAL CANCER OR ATYPICAL ENDOMETRIAL HYPERPLASIA.

Tamagawa M, Yamagami W, Hirano T, Makabe T, Sakai K, Ninomiya T, Chiyoda T, Nomura H, Kataoka F, Hirasawa A, Banno K, Susumu N, Aoki D

INTERNATIONAL JOURNAL OF GYNECOLOGIC CANCER 28 ( S2 ) 1189 - 1189 2018.09

Research paper (conference, symposium, etc.), Joint Work, Accepted

THE RELATIONSHIP BETWEEN THE COPY NUMBER AMPLIFICATION OF FGF3/FGF4 AND THE EFFICACY OF SORAFENIB IN GYNECOLOGIC CANCER

Yamagami W., Kataoka F., Hirano T., Sakai K., Makabe T., Chiyoda T., Nomura H., Hirasawa A., Tsuda H., Nishio K., Aoki D.

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 28 218 - 218 2018.09

ISSN 1048-891X

THE EFFICACY OF REPEATED HORMONAL THERAPY FOR INTRAUTERINE RECURRENCE FOLLOWING FERTILITY PRESERVING HORMONAL THERAPY FOR ENDOMETRIAL CANCER OR ATYPICAL ENDOMETRIAL HYPERPLASIA.

Hirano T, Yamagami W, Susumu N, Makabe T, Sakai K, Ninomiya T, Chiyoda T, Nomura H, Kataoka F, Hirasawa A, Banno K, Aoki D

INTERNATIONAL JOURNAL OF GYNECOLOGIC CANCER 28 ( S2 ) 1092 - 1092 2018.09

Research paper (conference, symposium, etc.), Joint Work, Accepted, ISSN 1048-891X

PREGNANCY RATES BY AGE GROUPS IN FERTILITY-PRESERVING HORMONAL THERAPY IN YOUNG PATIENTS WITH EARLY STAGE ENDOMETRIAL CANCER.

Susumu N., Yamagami W., Hirano T., Makabe T., Sakai K., Chiyoda T., Nomura H., Kataoka F., Saitoh E., Hirasawa A., Aoki D.

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 28 55 - 55 2018.09

ISSN 1048-891X

HIGH-DOSE MEDROXYPROGESTERONE ACETATE FOR ATYPICAL POLYPOID ADENOMYOMA OF THE UTERUS; A VALID FERTILITY-PRESERVING METHOD

Chiyoda T., Yamagami W., Hirano T., Kiyokawa S., Makabe K., Sakai K., Nomura H., Kataoka F., Susumu N., Aoki D.

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 28 1060 - 1060 2018.09

ISSN 1048-891X

CORRELATION BETWEEN THE RELATIVE DOSE INTENSITY OF PACLITAXEL PLUS CARBOPLATIN THERAPY AND CLINICAL BACKGROUND FACTORS IN PATIENTS WITH OVARIAN CANCER

Dozen A., Nomura H., Saotome K., Nanki Y., Yoshihama T., Iwasa N., Chiyoda T., Yamagami W., Kataoka F., Hirasawa A., Aoki D.

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 28 666 - 666 2018.09

ISSN 1048-891X

PARP inhibitors and quality of life in ovarian cancer

Aoki, Daisuke, Chiyoda, Tatsuyuki

LANCET ONCOLOGY 19 ( 8 ) 1012 - 1014 2018.08

Research paper (scientific journal), ISSN 1470-2045

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Ascites-derived and tissue-derived ovarian cancer cell primary 3D cultures aimed for personalized medicine.

Nanki Yoshiko, Hirasawa Akira, Nomura Hiroyuki, Okubo Aki, Itoh Manabu, Akahane Tomoko, Chiyoda Tatsuyuki, Kataoka Fumio, Tominaga Eiichiro, Aoki Daisuke

CLINICAL CANCER RESEARCH 24 ( 15 ) 72 - 72 2018.08

ISSN 1078-0432

有害事象によりベバシズマブ投与を中止した婦人科がん症例の検討

AOKI DAISUKE

東京産科婦人科学会会誌 ((一社)東京産科婦人科学会) 67 ( 3 ) 396 - 400 2018.07

Joint Work, ISSN 2186-0599

ベバシズマブは婦人科がんにおいて日常的に用いられる分子標的薬となっているが、特有の有害事象により投与継続が困難となるケースを経験する。そこで本研究ではベバシズマブ投与中止の原因となった重篤な有害事象と臨床的背景を明らかにすることを目的とした。ベバシズマブ併用化学療法を2013年12月から開始した上皮性卵巣癌、卵管癌、腹膜癌(以下卵巣癌)48例および2017年1月から開始した子宮頸癌12例の計60例について後方視的に有害事象とその発現時期を検討した。卵巣癌は初発投与19例、再発投与29例の計48例、子宮頸癌は初発投与1例、再発投与11例の計12例を組み入れた。卵巣癌の年齢中央値は54歳(37〜76歳)、ベバシズマブ投与サイクル数中央値は15回(1〜68回)であった。子宮頸癌の年齢中央値は50歳(33〜68歳)、ベバシズマブ投与サイクル数中央値は5.5回(1〜10回)であった。卵巣癌48例中有害事象による投与中止例は4例あり、内訳は高度蛋白尿・ネフローゼ2例(4.2%)、腸炎1例(2.08%)、血栓塞栓症1例(2.08%)であった。子宮頸癌12例中有害事象による投与中止例は3例あり、全例血栓塞栓症(25%)であった。血液毒性、高血圧による投与中止例は認めず、出血および消化管穿孔、瘻孔は認めなかった。有害事象の発現時期について高度蛋白尿・ネフローゼは17、23サイクル終了時、血栓塞栓症はそれぞれ1、1、2、8サイクル終了時に認めた。高度蛋白尿・ネフローゼは投与数を重ねてから出現し、血栓塞栓症は投与開始後早期に認めた。検討した症例数は少ないものの、子宮頸癌では卵巣癌に比較して血栓塞栓症を多く認める可能性が示唆され、今後症例の蓄積が必要である。(著者抄録)

Development of pseudoaneurysm in cesarean section scar pregnancy: a case report and literature review

Kiyokawa, Shunki, Chiyoda, Tatsuyuki, Ueno, Kazunori, Saotome, Keiko, Kim, Seon-Hye, Nakada, Sakura

JOURNAL OF MEDICAL ULTRASONICS (Springer Tokyo) 45 ( 2 ) 357 - 362 2018.04

Research paper (scientific journal), Joint Work, ISSN 1346-4523

Cesarean scar pregnancy (CSP) is a rare type of ectopic pregnancy. It is becoming more common, but it can lead to uterine rupture and severe hemorrhage. Here, we report a case of a 37-year-old woman with CSP complicated with pseudoaneurysm. The pseudoaneurysm emerged following focal injection of methotrexate (MTX) and potassium chloride with systemic MTX treatment. Due to a risk of sudden bleeding, uterine artery embolization (UAE) was recommended, but the patient hoped to avoid this if possible. Because the serum human chorionic gonadotropin level and the gestational sac were still persistent, dilation and curettage were performed with interventional radiologists on standby. Severe hemorrhage occurred and continued during the procedure, which necessitated emergent UAE. We reviewed six CSP case reports with vascular abnormalities, and all of them necessitated UAE, surgical excision, or hysterectomy. In the case of CSP combined with pseudoaneurysm, treatment should be planned carefully considering the risk of massive hemorrhage.

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Hysteroscopic Transcervical Resection for Atypical Polypoid Adenomyoma of the Uterus: AValid, Fertility-Preserving Option

Chiyoda, Tatsuyuki, Lin, Bao-Liang, Saotome, Keiko, Kiyokawa, Shunki, Nakada, Sakura

JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY (Elsevier B.V.) 25 ( 1 ) 163 - + 2018.01

Research paper (scientific journal), Joint Work, ISSN 1553-4650

Study Objective To evaluate hysteroscopic transcervical resection (TCR) for atypical polypoid adenomyoma of the uterus (APA). Design Retrospective study (Canadian Task Force classification II-2). Setting Single tertiary hospital. Patients Women who underwent TCR for APA at Kawasaki Municipal Hospital between 2003 and 2015. Interventions Clinical records were obtained. Measurements and Main Results Thirty-five patients with APA were evaluated. The median patient age was 35 years (range, 23–43 years), and the median tumor diameter was 22 mm (range, 9–51 mm). The median duration of observation after the first TCR was 34.0 months (range, 4.2–133.7 months). In 19 patients, the tumor recurred after the first TCR. A second TCR was performed in 13 patients, 11 of whom experienced recurrence. A third TCR was performed in 7 patients, all 7 of whom experienced recurrence. A fourth TCR was performed in 4 patients, 3 of whom experienced recurrence. The recurrence rate after the second TCR was higher than that after the first TCR (71.4%–84.6% vs 54.3%
p &lt
.01, t test). The median disease-free interval was 12.4 months after the first TCR, 15.3 months after the second TCR, 10.5 months after the third TCR, and 10.9 months after the fourth TCR. Seven patients progressed to endometrial cancer
however, there was no mortality. Six of the 35 patients conceived, and 4 had a normal spontaneous delivery. Conclusion Owing to disease-free intervals that follow treatment, TCR is a promising treatment modality as a fertility-preserving option for patients with APA under careful observation. Twenty percent of patients with APA develop cancer
however, the present study showed no mortality.

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【婦人科がん最近の話題】遺伝性乳癌卵巣癌

Chiyoda Tatsuyuki

東京産婦人科医会誌 , 2018, (51), p.20 51 20 2018

【遺伝性がんはここまで解明された】遺伝性卵巣がん（解説/特集）

Chiyoda Tatsuyuki　#HHirasawa Akira</U　#H Aoki Daisuke</U

成人病と生活習慣病 (東京医学社) 47 ( 7 ) 861 - 866 2017.07

Research paper (scientific journal), Joint Work

Loss of BRCA1 in the cells of origin of ovarian cancer induces glycolysis

Chiyoda Tatsuyuki, Hart Peter C., Eckert Mark A., McGregor Stephanie M., Lastra Ricardo R., Hamamoto Ryuji, Nakamura Yusuke, Yamada S. Diane, Olopade Olufunmilayo I., Lengyel Ernst, Romero Iris L.

Cancer Prevention Research (AMER ASSOC CANCER RESEARCH) 10 ( 4 ) 255 - 266 2017.04

ISSN 1940-6207

Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of developing epithelial ovarian cancer. However, beyond the role of BRCA1 in DNA repair, little is known about other mechanisms by which BRCA1 impairment promotes carcinogenesis. Given that altered metabolism is now recognized as important in the initiation and progression of cancer, we asked whether the loss of BRCA1 changes metabolism in the cells of origin of ovarian cancer. The findings show that silencing BRCA1 in ovarian surface epithelial and fallopian tube cells increased glycolysis. Furthermore, when these cells were transfected with plasmids carrying deleterious BRCA1 mutations (5382insC or the P1749R), there was an increase in hexokinase-2 (HK2), a key glycolytic enzyme. This effect was mediated by MYC and the STAT3. To target the metabolic phenotype induced by loss of BRCA1, a drug-repurposing approach was used and aspirin was identified as an agent that counteracted the increase in HK2 and the increase in glycolysis induced by BRCA1 impairment. Evidence from this study indicates that the tumor suppressor functions of BRCA1 extend beyond DNA repair to include metabolic endpoints and identifies aspirin as an ovarian cancer chemopreventive agent capable of reversing the metabolic derangements caused by loss of BRCA1.

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Elevated preoperative neutrophil

Nanki Yoshiko, Chiyoda Tatsuyuki, Kataoka Fumio, Nomura Hiroyuki, Nakadaira Naoki, Iwasa Naomi, Hashimoto Shiho, Arima Hirokazu, Susumu Nobuyuki, Aoki Daisuke

Journal of Obstetrics and Gynaecology Research (WILEY) 43 ( 4 ) 744 - 748 2017.04

ISSN 1341-8076

Aim: To examine the usefulness of the neutrophil : lymphocyte (N/L) ratio as a cost-effective and simple diagnostic marker of mature cystic teratoma (MCT) with malignant transformation (MT). Methods: A retrospective chart review was performed between 1998 and 2013 of 12 MCT patients with MT and between 2009 and 2013 of 130 patients with benign MCT. Data were collected on age, tumor size, white blood cell count with differential counts, tumor marker levels, and presenting features. Results: Older age, greater tumor size, higher CA19-9 or CA125, higher neutrophil count, and higher N/L ratio were associated with MT on univariate analysis. White blood cell count; lymphocyte count; and the tumor marker squamous cell carcinoma antigen were not associated with MT. Older age (≥median), larger tumor size (≥10 cm), and high N/L ratio (≥5.0) were predictors of MT (hazard ratio, 11.51, 5.87, and 11.11, respectively). Six of 12 patients were diagnosed with MT on preoperative magnetic resonance imaging and five of 12 had an N/L ratio ≥5.0. Conclusions: Neutrophil : lymphocyte ratio is a potential preoperative diagnostic marker of MT. The optimal cut-off should be determined in future large-scale studies.

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Retrospective Analysis on the Feasibility and Efficacy of Docetaxel-Cisplatin Therapy for Recurrent Endometrial Cancer

Ninomiya Tomomi, Yamagami Wataru, Susumu Nobuyuki, Makabe Takeshi, Sakai Kensuke, Wada Michiko, Takigawa Aya, Chiyoda Tatsuyuki, Nomura Hiroyuki, Kataoka Fumio, Hirasawa Akira, Banno Kouji, Aoki Daisuke

Anticancer Research (INT INST ANTICANCER RESEARCH) 36 ( 4 ) 1751 - 1758 2016.04

ISSN 0250-7005

AIM: There is poor evidence regarding effective treatment for recurrent endometrial cancer. We treated patients with recurrent endometrial cancer with docetaxel-cisplatin (DP) therapy as second-line or third-line chemotherapy. We aimed to evaluate the feasibility and efficacy of DP therapy for patients with recurrent endometrial cancer.PATIENT AND METHODS: We included 26 patients diagnosed with recurrent endometrial cancer, who underwent DP chemotherapy at our Institution. Docetaxel at 70 mg/m(2)and cisplatin at 60 mg/m(2)were administered by intravenous injection every 3 weeks. We retrospectively analyzed the clinicopathological factors associated with the response rate (RR) and prognosis. We also analyzed the adverse effects of DP therapy.RESULTS: Median follow-up was 33.8 months and the median number of therapy cycles was six. Grade 3 or 4 adverse effects included leukopenia (66%), neutropenia (81%), anemia (9%), diarrhea (12%), general fatigue (12%), liver dysfunction (4%), peripheral neuropathy (4%), and hyponatremia (4%). RR was 58% and the median progression-free survival (PFS) was 7.5 months. The group with a treatment-free interval of 6 months or more tended to have better PFS than that with less than 6 months (p=0.01). The group with a platinum-free interval of 6 months or more had significantly better PFS than that with less than 6 months (p=0.09). Although the history of taxane usage was not relevant to prognosis, a taxane-free interval of 12 months or more was associated with a tendency for better PFS (p=0.06).CONCLUSION: DP therapy was fully feasible and demonstrated efficacy for patients with recurrent endometrial cancer.

LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C

Masuda Kenta, Chiyoda Tatsuyuki, Sugiyama Naoyuki, Segura-Cabrera Aldo, Kabe Yasuaki, Ueki Arisa, Banno Koji, Suematsu Makoto, Aoki Daisuke, Ishihama Yasushi, Saya Hideyuki, Kuninaka Shinji

PLoS One (PUBLIC LIBRARY SCIENCE) 10 ( 2 ) 2015.02

ISSN 1932-6203

In budding yeast, the Mitotic Exit Network (MEN) regulates anaphase promoting complex/cyclosome (APC/C) via the Dbf2-Cdc14 signaling cascade. Dbf2 kinase phosphorylates and activates Cdc14 phosphatase, which removes the inhibitory phosphorylation of the APC/C cofactor Cdh1. Although each component of the MEN was highly conserved during evolution, there is presently no evidence supporting direct phosphorylation of CDC14 by large tumor suppressor kinase 1 (LATS1), the human counterpart of Dbf2; hence, it is unclear how LATS1 regulates APC/C. Here, we demonstrate that LATS1 phosphorylates the Thr7 (T7) residue of the APC/C component CDC26 directly. Nocodazole-induced phosphorylation of T7 was reduced by knockdown of LATS1 and LATS2 in HeLa cells, indicating that both of these kinases contribute to the phosphorylation of CDC26 in vivo. The T7 residue of CDC26 is critical for its interaction with APC6, a tetratricopeptide repeat-containing subunit of APC/C, and mutation of this residue to Asp (T7D) reduced the interaction of CDC26 with APC6. Replacement of endogenous CDC26 in HeLa cells with exogenous phosphor-mimic T7D-mutated CDC26 increased the elution size of APC/C subunits in a gel filtration assay, implying a change in the APC/C assembly upon phosphorylation of CDC26. Furthermore, T7D-mutated CDC26 promoted the ubiquitination of polo-like kinase 1, a well-known substrate of APC/C. Overall, these results suggest that LATS1/2 are novel kinases involved in APC/C phosphorylation and indicate a direct regulatory link between LATS1/2 and APC/C.

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Effectiveness of third-line chemotherapy in recurrent ovarian cancer patients

Yoshihama T., Chiyoda T., Kataoka F., Nomura H., Iguchi Y., Hashimoto S., Yamagami W., Tominaga E., Susumu N., Tsuda H., Aoki D.

European Journal of Gynaecological Oncology (I R O G CANADA, INC) 36 ( 4 ) 424 - 427 2015

ISSN 0392-2936

Objective: Despite recent advances in the treatment of recurrent ovarian cancer, little evidence exists describing the benefit of third-line chemotherapy. The present authors previously reported that the treatment-free interval (TFI) after second-line chemotherapy may predict a survival benefit of third-line chemotherapy, however the length of TFI was uncertain due to limited cases. In this study, the authors evaluated the length of TFI, which is correlated with the effectiveness of third-line chemotherapy and a prognostic factor of third-line chemotherapy. Materials and Methods: The authors reviewed the medical records of 85 women with recurrent ovarian cancer who received third-line chemotherapy after a paclitaxel/carboplatin (PC) regimen as first-line chemotherapy. Results: The response rate [complete response (CR) + partial response (PR)] and clinical benefit rate [(CBR): CR + PR + stable disease (SD)] during the TFI after second-line chemotherapy for 0-3 months, 3-6 months, and 6-12 months and ≥ 12 months were 9.8%, 0%, 0%, 43.8% and 15.7%, 50%, 66.7%, and 93.8%, respectively. The median overall survival (OS) from the onset of third-line chemotherapy was longer for TFI ≥3 months than for TFI 0-3 months (795 days vs. 281 days, p < 0.001). Finally, according to univariate (HR = 0.256;p < 0.001) and multivariate (HR = 0.264; p < 0.001) analyses, TFI was the independent significant prognostic factor for OS. Conclusions: TFI less than three months after second-line chemotherapy may predict little survival benefit of third-line chemotherapy.

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IGF2 preserves osteosarcoma cell survival by creating an autophagic state of dormancy that protects cells against chemotherapeutic stress

Shimizu Takatsune, Sugihara Eiji, Yamaguchi-Iwai Sayaka, Tamaki Sakura, Koyama Yuko, Kamel Walied, Ueki Arisa, Ishikawa Tomoki, Chiyoda Tatsuyuki, Osuka Satoru, Onishi Nobuyuki, Ikeda Hiroko, Kamei Junzo, Matsuo Koichi, Fukuchi Yumi, Nagai Toshihiro, Toguchida Junya, Toyama Yoshiaki, Muto Akihiro, Saya Hideyuki

Cancer Research (AMER ASSOC CANCER RESEARCH) 74 ( 22 ) 6531 - 6541 2014.11

ISSN 0008-5472

Osteosarcoma is a malignant bone tumor in children and adolescents characterized by intrinsic therapeutic resistance. The IGF2 is expressed at elevated levels in osteosarcoma after treatment with chemotherapy, prompting an examination of its functional contributions to resistance. We found that continuous exposure to IGF2 or insulin in the absence of serum created a dormant growth state in osteosarcoma cells that conferred resistance to various chemotherapeutic drugs in vitro. Mechanistic investigations revealed that this dormant state correlated with downregulation of downstream signaling by the IGF1 receptor, heightened cell survival, enhanced autophagy, and the presence of extracellular glutamine. Notably, inhibiting autophagy or depleting glutamine was sufficient to increase chemotherapeutic sensitivity in osteosarcoma xenografts in mice. Clinically, we confirmed that IGF expression levels were elevated in human osteosarcoma specimens from patients who received chemotherapy. Together, our results suggest that activation of IGF or insulin signaling preserves the survival of osteosarcoma cells under chemotherapeutic stress, providing a drug-resistant population that may engender minimal residual disease. Attenuating this survival mechanism may help overcome therapeutic resistance in osteosarcoma.

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