Details of a Researcher - SAITOU Tsuyoshi

Papers - SAITOU Tsuyoshi

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The Tight-Junction Protein Claudin-6 Induces Epithelial Differentiation from Mouse F9 and Embryonic Stem Cells

Kotaro Sugimoto, Naoki Ichikawa-Tomikawa, Seiro Satohisa, Yushi Akashi, Risa Kanai, Tsuyoshi Saito, Norimasa Sawada, Hideki Chiba

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 8 ( 10 ) e75106 2013.10 [Refereed]

During epithelialization, cell adhesions and polarity must be established to maintain tissue assemblies and separate the biological compartments in the body. However, the molecular basis of epithelial morphogenesis, in particular, a role of cell adhesion molecules in epithelial differentiation from stem cells, remains unclear. Here, we show that the stable and conditional expression of a tight-junction protein, claudin-6 (Cldn6), triggers epithelial morphogenesis in mouse F9 stem cells. We also demonstrate that Cldn6 induces the expression of other tight-junction and microvillus molecules including Cldn7, occludin, ZO-1 alpha+, and ezrin/radixin/moesin-binding phosphoprotein50. These events were inhibited by attenuation of Cldn6 using RNA interference or the C-terminal half of Clostridium Perfringens enterotoxin. Furthermore, similar results were obtained in mouse embryonic stem cells. Thus, we have uncovered that the Cldn6 functions as a novel cue to induce epithelial differentiation.

DOI PubMed

ALDH1-High Ovarian Cancer Stem-Like Cells Can Be Isolated from Serous and Clear Cell Adenocarcinoma Cells, and ALDH1 High Expression Is Associated with Poor Prognosis

Takafumi Kuroda, Yoshihiko Hirohashi, Toshihiko Torigoe, Kazuyo Yasuda, Akari Takahashi, Hiroko Asanuma, Rena Morita, Tasuku Mariya, Takuya Asano, Masahito Mizuuchi, Tsuyoshi Saito, Noriyuki Sato

PLoS ONE ( 6 ) 8 ( 6 ) e65158 2013.06 [Refereed]

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1high) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1high cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1high cells. ALDH1high cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis. © 2013 Kuroda et al.

DOI PubMed

Assisted reproductive technique increases the risk of placental polyp

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Tamotsu Kiya, Shin-Ichi Ishioka, Tsuyoshi Saito

Gynecological Endocrinology ( 6 ) 29 ( 6 ) 611 - 614 2013.06 [Refereed]

The purpose of this study was to clarify the risk factors and outcomes of placental polyp. This retrospective study was conducted on 1645 patients delivered or aborted in Sapporo Medical University from 2007 through 2011. Transvaginal color Doppler ultrasonography, hysteroscopy, contrast-enhanced MRI or 3D-CT angiography were performed. There were 1532 deliveries and 113 abortions. Seventy-one (4.3%) were ART-conceived and the remaining 1574 (95.7%) were non-ART pregnancies. Fifteen (0.91%) cases were confirmed as having placental polyp. Nine cases of placental polyp were identified among the 1574 (0.57%) as non-ART-related pregnancies, and 6 were identified among the 71 (8.5%) as ART-related pregnancies. Thus, pregnancies achieved through ART showed 20x greater incidence of complicating placental polyp than pregnancies achieved through without ART (p=9.02×10-6 odds ratio, 19.59 95% confidence interval, 5.27-72.84, logistic regression analysis). Evaluation of blood flow within the polyp showed that in five of seven patients with low blood flow, the polyps spontaneously dropped off 79-115 days postpartum. Thus, ART-related pregnancies may be a risk factor of placental polyp, and spontaneous drop-off of the polyp is often observed in cases with low blood flow within the mass. © 2013 Informa UK Ltd.

DOI PubMed

子宮筋腫合併妊娠の妊娠経過及び分娩への影響に関する検討

竹浪奈穂子, 玉手雅人, 谷垣衣理, 郷久晴朗, 早川修, 齋藤豪

日本周産期・新生児医学会雑誌 ( (一社)日本周産期・新生児医学会 ) 49 ( 2 ) 774 - 774 2013.06

最近経験した鼠径部腫瘍5症例の検討

寺本瑞絵, 岩崎雅宏, 嶋田浩志, 鈴木利理, 竹浪奈穂子, 染谷真行, 田渕雄大, 池田桂子, 鈴木美和, 高橋円, 長澤邦彦, 田中綾一, 伊東英樹, 斉藤豪

産婦人科手術 ( (株)メジカルビュー社 ) ( 24 ) 159 - 159 2013.05

ヒト上皮性卵巣癌におけるアルデヒド脱水素酵素遺伝子ALDH1の発現とstemnessの検討

黒田敬史, 廣橋良彦, 鳥越俊彦, 安田和世, 浅沼広子, 高橋あかり, 浅野拓也, 真里谷奨, 水内将人, 斉藤豪, 佐藤昇志

日本病理学会会誌 ( (一社)日本病理学会 ) 102 ( 1 ) 348 - 348 2013.04

Excessive androgen exposure in female-to-male transsexual persons of reproductive age induces hyperplasia of the ovarian cortex and stroma but not polycystic ovary morphology

Keiko Ikeda, Tsuyoshi Baba, Hiroko Noguchi, Kunihiko Nagasawa, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito

HUMAN REPRODUCTION ( OXFORD UNIV PRESS ) 28 ( 2 ) 453 - 461 2013.02 [Refereed]

Does administration of androgen to female-to-male transsexual persons (FTMs) of reproductive age induce polycystic ovary (PCO) morphology? Administration of high-dose androgen to women causes pathognomonic changes to the ovarian cortex and stroma that resemble SteinLeventhal syndrome but it does not induce PCO morphology. Androgen is thought to play a key role in follicular development and to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). In several experimental models, animals given high-dose androgen show ovarian changes similar to those in women with PCOS. In previous human studies, the ovaries of FTMs who received androgen for long periods also exhibited PCO morphology. We conducted a retrospective casecontrol study of women, all without PCOS, undergoing salpingo-oophorectomy. The case group consisted of 11 FTMs taking testosterone (duration range: 17 months to 14 years), while the control group consisted of 10 patients with gynaecologic malignancies who did not receive testosterone. Resected ovaries from both groups were compared histologically with respect to changes in the cortex and stroma, and the number of follicles at each maturation stage. Compared with controls, the FTM group had a thicker ovarian cortex (P 0.0001), and more hyperplastic collagen (P 0.001), ovarian stromal hyperplasia (P 0.003) and stromal luteinization, i.e. luteinized stromal cells with a small dark central nucleus surrounded by clear cytoplasm (P 0.004). Isolated clusters of such stromal luteinized cells were found only in the testosterone-treated ovaries of FTMs. The number of primordial follicles was similar in the two groups (P 0.22). The numbers of early stage (primary, pre-antral and early antral) follicles, which are dependent on androgen, were also similar (P 0.81), as were the numbers of antral follicles (P 0.97). In contrast, significantly greater numbers of atretic follicles were seen in the FTM than that in the control group (P 0.01). In addition to the low numbers in the study groups, the histological changes in FTMs were investigated after testosterone administration, therefore it is possible that some of the observed changes were already present, before androgen administration. Our results are at variance with those of earlier studies and suggest that excessive androgen exposure in women of reproductive age may not be a factor in the pathogenesis of PCOS. None.

DOI PubMed

Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population.

Yasuda K, Torigoe T, Morita R, Kuroda T, Takahashi A, Matsuzaki J, Kochin V, Asanuma H, Hasegawa T, Saito T, Hirohashi Y, Sato N

PloS one ( 8 ) 8 e68187 2013 [Refereed]

DOI PubMed

A myotonic dystrophy 1 patient complicated with placental adherence after miscarriage of one dichorionic diamniotic twin following her tenth in vitro fertilization and embryo transfer.

Endo T, Baba T, Sugio A, Morishita M, Takahashi M, Akashi Y, Ishioka S, Tachi N, Imai T, Tamakawa M, Saito T

Archives of gynecology and obstetrics ( 6 ) 286 1605 - 1608 2012.12 [Refereed]

DOI PubMed

Weight reduction and pioglitazone ameliorate polycystic ovary syndrome after removal of a Sertoli-stromal cell tumor

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Tamotsu Kiya, Shin-Ichi Ishioka, Tsuyoshi Saito

International Journal of Women's Health 4 ( 1 ) 607 - 611 2012.11 [Refereed]

This report presents an unusual case of Sertoli-stromal cell tumor and polycystic ovary syndrome successfully treated with weight reduction and an insulin-sensitizing agent. A 22-year-old woman, gravida 0, para 0, visited our hospital for the first time with a 12-year history of secondary amenorrhea and hypertrichosis. Transvaginal ultrasonography revealed a solid tumor in the right ovary. Right salpingo-oophorectomy was performed and pathological examination confirmed a Sertoli-stromal cell tumor. The patient's serum androgen levels declined postoperatively, but remained above normal. Pioglitazone treatment for 6 months also significantly reduced serum androgen levels, but they still remained above normal. However, after losing 12 kg of body weight, the patient's serum androgen levels declined to normal, and spontaneous menstruation became regular. Weight reduction with pioglitazone is an effective means of treating hyperandrogenism. © 2012 Baba et al, publisher and licensee Dove Medical Press Ltd.

DOI PubMed

母児ともに救命し得た大動脈解離合併妊娠の3例

嶋田浩志, 岡村直樹, 染谷真行, 齋藤雅恵, 竹田倫子, 浅野拓也, 明石祐史, 馬場剛, 石岡伸一, 遠藤俊明, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 60回 90 - 90 2012.09

160kg高度肥満妊婦に対する帝王切開の経験

中嶋千紗, 馬場剛, 森下美幸, 金美善, 足立英文, 明石祐史, 浅野拓也, 嶋田浩志, 杉尾明香, 石岡伸一, 遠藤俊明, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 60回 87 - 87 2012.09

Epidermal growth factor modulates claudins and tight junctional functions in ovarian cancer cell lines.

Ogawa M, Kojima T, Someya M, Nomura K, Takasawa A, Murata M, Tanaka S, Saito T, Sawada N

Histochemistry and cell biology ( 2 ) 138 323 - 338 2012.08 [Refereed]

DOI PubMed

Trophectoderm morphology significantly affects the rates of ongoing pregnancy and miscarriage in frozen-thawed single-blastocyst transfer cycle in vitro fertilization.

Hiroyuki Honnma, Tsuyoshi Baba, Masahiro Sasaki, Yoshiki Hashiba, Hiroshi Ohno, Takanori Fukunaga, Toshiaki Endo, Tsuyoshi Saito, Yoshimasa Asada

Fertility and sterility 98 ( 2 ) 361 - 7 2012.08 [International journal]

OBJECTIVE: To determine which parameter of blastocyst morphology is the most important predictor of ongoing pregnancy or miscarriage. DESIGN: Retrospective analysis. SETTING: One in vitro fertilization (IVF) center. PATIENT(S): Women who underwent a total of 1,087 frozen-thawed single-blastocyst transfer cycles. INTERVENTION(S): First IVF treatment with blastocysts after frozen-thawed cycle. MAIN OUTCOME MEASURE(S): Ongoing pregnancy and miscarriage rates as related to blastocyst morphology (blastocyst expansion, inner cell mass, and trophectoderm), and interaction tests in unadjusted logistic regression models to assess clinical factors affecting outcomes. RESULT(S): After adjustment for trophectoderm, inner cell mass, and age as confounders, trophectoderm was determined to be statistically significantly related to the rate of ongoing pregnancy. Trophectoderm was also statistically significantly related to the miscarriage rate. By contrast, neither inner cell mass nor blastocyst expansion was statistically significantly related. CONCLUSION(S): In frozen-thawed embryo transfer cycles, trophectoderm morphology is statistically significantly related to the rates of ongoing pregnancy and miscarriage after adjusting for confounders. Trophectoderm morphology may be the most important parameter when selecting a single blastocyst for transfer.

DOI PubMed

Simultaneous presentation of tubal and primary abdominal pregnancies following clomiphene citrate treatment

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Naoko Takenami, Ayumi Shimizu, Miyuki Morishita, Hiroyuki Honnma, Hideyuki Ikeda, Tsuyoshi Saito

ARCHIVES OF GYNECOLOGY AND OBSTETRICS ( SPRINGER HEIDELBERG ) 286 ( 2 ) 395 - 398 2012.08 [Refereed]

Abdominal pregnancy is a rare condition that is potentially life-threatening for the mother. We present a case of simultaneous ectopic pregnancies (EPs) in the right fallopian tube and in the vesicouterine pouch. A 26-year-old woman had undergone prior ovulation induction with clomiphene citrate and human chorionic gonadotropin (hCG) at an outside hospital for unexplained infertility. The patient was referred to our hospital for a suspected ectopic pregnancy at 6 weeks gestation. Transvaginal ultrasonography detected a viable fetus at the anterior left side of the uterus; therefore, we suspected a left tubal pregnancy. However, laparoscopic surgery revealed that EPs were located in both the left vesicouterine pouch and in the right fallopian tube. Resection of the right salpinx and abdominal implant were performed. Histopathological examination confirmed the simultaneous presentation of a primary abdominal pregnancy and a right tubal pregnancy. After surgery, the patient's serum hCG level returned to normal. Concurrent EPs and abdominal pregnancy are very rare. However, it should be noted that reproductive technologies sometimes cause unusual clinical situations. A thorough abdominal inspection is needed.

DOI

[Mechanism of metastasis in endometrial cancer].

Saito T, Tanaka R, Iwasaki M

Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 4 317 - 320 2012.06 [Refereed]

PubMed

Novel oligomannose liposome-DNA complex DNA vaccination efficiently evokes anti-HPV E6 and E7 CTL responses.

Mizuuchi M, Hirohashi Y, Torigoe T, Kuroda T, Yasuda K, Shimizu Y, Saito T, Sato N

Experimental and molecular pathology ( 1 ) 92 185 - 190 2012.02 [Refereed]

DOI PubMed

Evaluation of cervical conization as a definitive treatment for microinvasive cervical carcinoma and cervical intraepithelial neoplasia grade 3.

Takeda N, Suzuki T, Suzuki M, Matsuura M, Tanaka R, Fujii M, Ito E, Saito T

Archives of gynecology and obstetrics 285 ( 2 ) 453 - 457 2012.02 [Refereed]

DOI PubMed

Continuous follicle-stimulating hormone exposure from pituitary adenoma causes periodic follicle recruitment and atresia, which mimics ovarian hyperstimulation syndrome.

Mika Kanaya, Tsuyoshi Baba, Yoshimitsu Kitajima, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Hiroyuki Honnma, Toshiaki Endo, Tsuyoshi Saito

International journal of women's health 4 427 - 31 2012 [International journal]

CONTEXT: Follicle-stimulating hormone (FSH)-secreting pituitary adenoma is usually a nonfunctioning tumor, but in rare cases it may develop into ovarian hyperstimulation. Several reports have revealed that serum FSH levels are normal to slightly high in patients with combined FSH-secreting pituitary adenoma with ovarian hyperstimulation. This finding is different from iatrogenic ovarian hyperstimulation syndrome (OHSS), which is associated with extremely high levels of FSH. OBJECTIVE: To describe the clinical course of two patients who developed OHSS from FSH-secreting pituitary adenoma. RESULTS: Endocrine studies of the two cases revealed that FSH levels were normal or slightly increased, but luteinizing hormone levels were low to undetectable. Their estradiol (E2) levels were intriguing: levels fluctuated drastically over 6 weeks in Case 1, but stayed flat in Case 2. Ultrasonographic examinations showed bilaterally enlarged multicystic ovaries, and magnetic resonance imaging indicated pituitary tumors. Transsephenoidal resection of the tumors ameliorated the symptoms and pathological diagnosis revealed FSH-secreting pituitary adenomas. CONCLUSION: As is not the case in iatrogenic OHSS, even a small to moderate amount of FSH stimulation, which is continuously secreted by a pituitary adenoma, can cause ovarian hyperstimulation. Although FSH-secreting pituitary adenoma can cause ovarian hyperstimulation, an extremely high amount of E2 biosynthesis from granulosa cells seldom occurs.

DOI PubMed

First case of vaginal radical trachelectomy in a pregnant Japanese woman

Nanako Iwami, Shin-ichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Kunihiko Nagasawa, Madoka Takahashi, Asuka Sugio, Sakura Takada, Tasuku Mariya, Masahiro Mizunuma, Tsuyoshi Saito

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY ( SPRINGER TOKYO ) 16 ( 6 ) 737 - 740 2011.12 [Refereed]

A diagnosis of cervical cancer during pregnancy poses difficult management and ethical problems. Survival of the patient is the foremost concern, but fetal viability and well-being must also be addressed. Radical trachelectomy (RT) has recently begun to be performed as a possible treatment modality for early stage invasive uterine cervical cancer in pregnant patients who would like to continue their pregnancy. A 32-year-old Japanese woman visited a local hospital for prenatal care, and was diagnosed with a FIGO I B1 adenocarcinoma of the uterine cervix. She had a strong desire to avoid pregnancy termination, so she was admitted to our hospital for fertility-preserving surgery. After extensive counseling, vaginal radical trachelectomy with abdominal pelvic lymphadenectomy was performed in the 16th gestational week. The excised uterine cervix and lymph nodes were pathologically negative for cancer. To maintain her pregnancy, daily vaginal disinfection with povidone iodine, bed rest, and administration of ritodrine and an ulinastatin vaginal suppository were continued until the delivery. At 34 weeks' gestation, an emergency cesarean section was performed because of sudden premature rupture of the membranes. A baby girl was born weighing 2112 g, with Apgar score of 8/9. The mother remains without evidence of recurrence at the time of this report. This is the first case of successful pregnancy and delivery in Japan after vaginal RT.

DOI

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Papers - SAITOU Tsuyoshi