Details of a Researcher - SAITOU Tsuyoshi

Papers - SAITOU Tsuyoshi

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田中綾一, 寺本瑞絵, 西澤庸子, 竹浪奈穂子, 玉手雅人, 幅田周太朗, 鈴木美和, 高橋円, 郷久晴朗, 岩崎雅宏, 齋藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 67 ( 2 ) 864 - 864 2015.02

Associations of serum isoflavone, adiponectin and insulin levels with risk for epithelial ovarian cancer: Results of a case-control study

Seiko Otokozawa, Ryoichi Tanaka, Hiroshi Akasaka, Eiki Ito, Sumiyo Asakura, Hirofumi Ohnishi, Shigeyuki Saito, Tetsuji Miura, Tsuyoshi Saito, Mitsuru Mori

Asian Pacific Journal of Cancer Prevention ( Asian Pacific Organization for Cancer Prevention ) 16 ( 12 ) 4987 - 4991 2015 [Refereed]

Background: The aim of this study was to examine the association of serum isoflavones, adiponectin, and insulin levels with ovarian cancer risk. Materials and Methods: We gathered cases with histologically confirmed epithelial ovarian cancer at Sapporo Medical University Hospital from October 2010 to September 2012. Potential controls were recruited from female inpatients without any history of cancer or diabetes mellitus in different wards of the same hospital over the same period of time. Serum isoflavones, adiponectin, and insulin levels were measured in order to estimate associations with ovarian cancer risk in a case-control study. Data from 71 cases and 80 controls were analyzed with a logistic regression model adjusting for known risk factors. Results: A significant reduction in ovarian cancer risk was observed for the high tertile of serum daidzein level versus the low (P< inf> trend< /inf> < 0.001). A significant reduction in ovarian cancer risk was also observed for the high tertile of serum glycitein level versus the low (P< inf> trend< /inf> =0.005). Furthermore, a significant reduction in ovarian cancer risk was observed for the high tertile of serum adiponectin level versus the low (P< inf> trend< /inf> =0.004). Conversely, serum insulin level showed significantly elevated risk for ovarian cancer with the high tertile versus the low P< inf> trend< /inf> < 0.001). Conclusions: Decreased serum isoflavones levels, such as those for daidzein and glycitein, decreased serum adiponectin levels, and increased serum insulin levels could be shown to be associated with elevated risk of ovarian cancer.

DOI PubMed

Fibroblasts induce expression of FGF4 in ovarian cancer stem-like cells/cancer-initiating cells and upregulate their tumor initiation capacity

Kazuyo Yasuda, Toshihiko Torigoe, Tasuku Mariya, Takuya Asano, Takafumi Kuroda, Junichi Matsuzaki, Kanae Ikeda, Makoto Yamauchi, Makoto Emori, Hiroko Asanuma, Tadashi Hasegawa, Tsuyoshi Saito, Yoshihiko Hirohashi, Noriyuki Sato

LABORATORY INVESTIGATION ( NATURE PUBLISHING GROUP ) 94 ( 12 ) 1355 - 1369 2014.12 [Refereed]

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cells within cancer that contribute to cancer initiation and progression. Cancer-associated fibroblasts (CAFs) are stromal fibroblasts surrounding tumor cells, and they have important roles in tumor growth and tumor progression. It has been suggested that stromal fibroblasts and CSCs/CICs might mutually cooperate to enhance their growth and tunnorigenic capacity. In this study, we investigated the effects of fibroblasts on tumor-initiating capacity and stem-like properties of ovarian CSCs/CICs. CSCs/CICs were isolated from the ovarian carcinoma cell line HTBoA as aldehyde dehydrogenase 1 high (ALDH1(high)) population by the ALDEFLUOR assay. Histological examination of tumor tissues derived from ALDH1(high) cells revealed few fibrous stroma, whereas those derived from fibroblast-mixed ALDH1(high) cells showed abundant fibrous stroma formation. In vivo tumor-initiating capacity and in vitro sphere-forming capacity of ALDH1(high) cells were enhanced in the presence of fibroblasts. Gene expression analysis revealed that fibroblast-mixed ALDH1(high) cells had enhanced expression of fibroblast growth factor 4 (FGF4) as well as sternness-associated genes such as SOX2 and POU5F1. Sphere-forming capacity of ALDH1(high) cells was suppressed by small-interfering RNA (siRNA)-mediated knockdown of FGFR2, the receptor for FGF4 which was expressed preferentially in ALDH1(high) cells. Taken together, the results indicate that interaction of fibroblasts with ovarian CSCs/CICs enhanced tumor-initiating capacity and stem-like properties through autocrine and paracrine FGF4-FGFR2 signaling.

DOI PubMed

Prognostic Impact of Human Leukocyte Antigen Class I Expression and Association of Platinum Resistance with Immunologic Profiles in Epithelial Ovarian Cancer

Tasuku Mariya, Yoshihiko Hirohashi, Toshihiko Torigoe, Takuya Asano, Takafumi Kuroda, Kazuyo Yasuda, Masahito Mizuuchi, Tomoko Sonoda, Tsuyoshi Saito, Noriyuki Sato

CANCER IMMUNOLOGY RESEARCH ( AMER ASSOC CANCER RESEARCH ) 2 ( 12 ) 1220 - 1229 2014.12 [Refereed]

Epithelial ovarian cancer (EOC) is one of the most deadly carcinomas in females. Immune systems can recognize EOCs; however, a defect of human leukocyte antigen (HLA) class I expression is known to be a major mechanism for escape from immune systems, resulting in poor prognosis. The purpose of this study is to identify novel correlations between immunologic responses and other clinical factors. We investigated the expression of immunologic components in 122 cases of EOCs for which surgical operations were performed between 2001 and 2011. We immunohistochemically stained EOC specimens using an anti-pan HLA class I monoclonal antibody (EMR8-5) and anti-CD3, -CD4, and -CD8 antibodies, and we analyzed correlations between immunologic parameters and clinical factors. In multivariate analysis that used the Cox proportional hazards model, independent prognostic factors for overall survival in advanced EOCs included low expression level of HLA class I [risk ratio (RR), 1.97; 95% confidence interval (CI), 1.01-3.83; P = 0.046] and loss of intraepithelial cytotoxic T lymphocyte (CTL) infiltration (RR, 2.11; 95% CI, 1.06-4.20; P = 0.033). Interestingly, almost all platinum-resistant cases showed a significantly low rate of intraepithelial CTL infiltration in the x 2 test (positive vs. negative: 9.0% vs. 97.7%; P < 0.001). Results from a logistic regression model revealed that low CTL infiltration rate was an independent factor of platinum resistance in multivariate analysis (OR, 3.77; 95% CI, 1.08-13.12; P = 0.037). Platinum-resistant EOCs show poor immunologic responses. The immune escape system of EOCs may be one of the mechanisms of platinum resistance. (C) 2014 AACR.

DOI

Importance of uterine cervical cerclage to maintain a successful pregnancy for patients who undergo vaginal radical trachelectomy

Miseon Kim, Shin-ichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Yushi Akashi, Miyuki Morishita, Hidefumi Adachi, Tsuyoshi Saito

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY ( SPRINGER JAPAN KK ) 19 ( 5 ) 906 - 911 2014.10 [Refereed]

We have performed 36 vaginal radical trachelectomies (RTs) for patients with early invasive uterine cervical cancer and experienced 10 deliveries. Pregnancy after RT has far higher risks of prematurity and complications such as preterm premature rupture of the membrane (pPROM) and chorioamnionitis. We report the significance of transabdominal cerclage in the follow-up of pregnancy after vaginal RT. Our operative procedure is based on that of Dargent et al. We amputated the cervix approximately 10 mm below the isthmus. For the removal of the parametrium, we cut at the level of type II hysterectomy. A nylon suture is also placed around the residual cervix. Pregnancy courses after vaginal RT were studied in 9 patients (10 pregnancies) with respect to cervical length and several infectious signs. Obstetric prognosis after RT was improved with our follow-up modality. Four patients who were followed up with this modality were able to continue their pregnancies until late in the third trimester. However, it was not effective for four patients who showed cervical incompetence due to slack cerclage. They suffered from pPROM without any infectious signs and uterine contraction. Though we performed transabdominal uterine cervical cerclage for one patient in her 19th week of pregnancy, it was unsuccessful. Cervical cerclage placed at the time of RT played an important role in preventing dilatation of the uterine cervix and the subsequent occurrence of pPROM. Transabdominal cervical cerclage should be performed earlier in pregnancy or before pregnancy in patients who have experienced problems with cervical cerclage.

DOI PubMed

BAG3 upregulates Mcl-1 through downregulation of miR-29b to induce anticancer drug resistance in ovarian cancer

Asuka Sugio, Masahiro Iwasaki, Shutaro Habata, Tasuku Mariya, Miwa Suzuki, Hiroyuki Osogami, Masato Tamate, Ryoichi Tanaka, Tsuyoshi Saito

GYNECOLOGIC ONCOLOGY ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 134 ( 3 ) 615 - 623 2014.09 [Refereed]

Objective. Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its often late diagnosis and its chemoresistance. We identified a set of microRNAs whose expression is altered upon BAG3 knockdown. Our primary objective was to examine the relationships between BAG3, miR-29b and Mcl-1, an antiapoptotic Bcl-2 family protein, in ovarian cancer cells. Methods. Ovarian cancer cells were cultured and their responsiveness to paclitaxel was tested. Microarray analysis was performed to identify microRNAs differentially expressed in E52 BAG3 knockdown ovarian cancer cells and their control cells. Primary ovarian cancer tissues were obtained from 56 patients operated on for ovarian cancer. The patients' clinical and pathological data were obtained from their medical records. Results. BAG3 knockdown increased the chemosensitivity to paclitaxel of ES2 ovarian clear cell carcinoma cells to a greater degree than AMOC2 serous adenocarcinoma cells. gRT-PCR analysis showed that miR-29b expression was significantly upregulated in primary cancer tissue expressing low levels of BAG3, as compared to tissue expressing high levels. Moreover, levels of miR-29b correlated significantly with progression-free survival. Upregulation of miR-29b also reduced levels of Mcl-1 and sensitized ES2 cells to low-dose paclitaxel. Conclusions. BAG3 knockdown appears to downregulate expression of Mcl-1 through upregulation of miR-29b, thereby increasing the chemosensitivity of ovarian clear cell carcinoma cells. This suggests that BAG3 is a key determinant of the responsiveness of ovarian cancer cells, especially clear cell carcinoma, to paclitaxel and that BAG3 may be a useful therapeutic target for the treatment of ovarian cancer. (C) 2014 Elsevier Inc. All rights reserved.

DOI PubMed

婦人科癌における癌精巣抗原BORISの発現ならびに癌幹細胞性の検討(Expression and characterization of the cancer/testis/stem antigen BORIS in gynecologic cancer stem cells)

浅野拓也, 廣橋良彦, 真里谷奨, 黒田敬史, 浅沼広子, 鳥越俊彦, 齋藤豪, 佐藤昇志

日本癌学会総会記事 ( (一社)日本癌学会 ) 73回 P - 1164 2014.09

卵巣癌幹細胞におけるMMP10による幹細胞性の制御について(MMP10 regulates stemness of ovarian cancer stem cells)

真里谷奨, 廣橋良彦, 浅野拓也, 黒田敬史, 水内将人, 鳥越俊彦, 齋藤豪, 佐藤昇志

日本癌学会総会記事 ( (一社)日本癌学会 ) 73回 P - 1162 2014.09

Rap1GAPの発現と子宮体部類内膜腺癌の分化度(Expression of Rap1GAP and differentiation of endometrioid adenocarcinoma in endometrial cancer)

玉手雅人, 田中綾一, 幅田周太朗, 杉尾明香, 松浦基樹, 郷久晴朗, 岩崎雅宏, 齋藤豪

日本癌学会総会記事 ( (一社)日本癌学会 ) 73回 P - 2080 2014.09

Prediction of the therapeutic effect of dienogest in ovarian endometrial cysts using the apparent diffusion coefficient

Motoki Matsuura, Masato Tamate, Yuta Tabuchi, Sakura Takada, Ryoichi Tanaka, Masahiro Iwasaki, Tsuyoshi Saito

GYNECOLOGICAL ENDOCRINOLOGY ( INFORMA HEALTHCARE ) 30 ( 8 ) 597 - 599 2014.08 [Refereed]

The purpose of this study was to investigate whether apparent diffusion coefficient (ADC) mean values can be used for predicting the treatment response in ovarian endometrial cyst patients with dienogest (DNG) administration. Eighteen patients received DNG (2 mg/day, orally) for 60 days, among whom 26 ovarian endometrial cysts were retrospectively identified. Mean ADC values of individual ovarian endometrial cysts were obtained by ADC maps inside the tumor. There was a significant correlation between ADC values and reduction ratio. When calculating the mean ADC values for three groups; more than 50%, 50-25% and less than 25%, ADC values significantly increased with increasing reduction ratio; 2.05 x 10(-3) mm(2)/s, 1.28 x 10(-3) mm(2)/s and 0.94 x 10(-3) mm(2)/s, respectively (p = 0.0180). Multiple regression analysis by reduction ratio (%), ADC mean values (x 10(-3) mm(2)/s), tumor longest diameter (cm) and CA125 (Wml) revealed that tumor reduction ratio by DNG administration could be predicted by the following equation; R=19.3 + 24.0x - 0.4y + 0.1z (R: Reduction ratio, x: ADC mean, y: Longest diameter, z: CA125). In conclusion, the ADC mean value is useful for the prediction of the treatment response in ovarian endometrial cyst patients with DNG administration.

DOI PubMed

Common hypothetical etiology of excess androgen exposure in female-to-male transsexualism and polycystic ovary syndrome

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Tsuyoshi Saito

Gender Identity: Disorders, Developmental Perspectives and Social Implications ( Nova Science Publishers, Inc. ) 253 - 270 2014.07

Gender identity disorder is recognized as a rare disease. The prevalence of this disorder is different among regions and races. In Japan, the prevalence of female-to-male transsexual (FTM-TS) patients is estimated to be 1 in 12,500 women, which is approximately twice as many as male-to-female transsexual patients. There are two interesting facts in association with FTM-TS: 1) the complication rate of polycystic ovary syndrome (PCOS) is high among FTM-TS patients and 2) natal female patients with congenital adrenal hyperplasia (CAH) tend to have gender identity problems more often than the normal population. PCOS is a common disease and it affects 5-10% of women of reproductive age. PCOS is characterized by ovulation disorder, hyperandrogenism, and polycystic ovarian morphology. Additionally, PCOS is correlated with insulin resistance, and predisposes to type 2 diabetes mellitus, atherosclerosis, and metabolic syndrome. The etiology of PCOS is still obscure, but excess androgen exposure during the fetal period is considered to be a dominant hypothesis. CAH is an autosomal recessive disorder impairing adrenal steroid metabolism, which causes excess androgenemia from the fetal period. A review on 250 natal female cases with CAH showed that 13 (5.2%) of the patients had serious gender identity problems. Surprisingly, the occurrence of FTM-TS in CAH is extremely high. The pathogenesis of FTM-TS is still uncertain. However, excess androgen exposure may be related to FTM-TS according to the above-mentioned findings. In humans, experimental androgen administration to women is impossible. However, cross-sex hormone administration to FTM-TS patients is not associated with any problems because it is a standard tactic for treatment. If excess androgen exposure is a cause of PCOS, androgen-treated FTM-TS patients may be a disease model of PCOS. Assessment of the effects of androgen administration on metabolic parameters is informative because FTM-TS patients with PCOS may have potent insulin resistance. In this chapter, we discuss endocrinological aspects of FTM-TS, the effect of crosssex hormones, and the hypothetical etiology in FTM and PCOS.

Long-term treatment with dehydroepiandrosterone may lead to follicular atresia through interaction with anti-Mullerian hormone

Keiko Ikeda, Tsuyoshi Baba, Miyuki Morishita, Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito

JOURNAL OF OVARIAN RESEARCH ( BIOMED CENTRAL LTD ) 7 46 2014.04 [Refereed]

Background: Hyperandrogenism is the primary manifestation of polycystic ovary syndrome (PCOS), which appears to be caused by excess exposure to androgen. As such, androgenized animal models have been developed and investigated to study the etiology of PCOS. Anti-Mullerian hormone (AMH) is known to be associated with follicle growth, and its levels are two to three times higher in women with PCOS than in those with normal ovaries. We studied how duration of androgen administration affects folliculogenesis and AMH expression. Methods: We divided 30 immature (3-week-old) Sprague Dawley rats into six groups. Three groups were injected each evening with dehydroepiandrosterone (DHEA) (6 mg/100 g body weight/0.2 ml sesame oil) for 7, 15 or 30 days, respectively. The three control groups were injected with 0.2 ml of sesame oil for the corresponding lengths of time. Resected ovaries were sectioned and examined to determine follicle numbers at each developmental stage, and immunostained to assess AMH expression. Results: On day 7, follicle numbers and AMH expression levels at each developmental stage of follicle growth were similar in the respective control and DHEA groups. On day 15, the total follicle number (P = 0.041), the percentage of primordial follicles (P = 0.039) and AMH expression were significantly greater in the DHEA than the control group. On day 30, the percentages of primordial (P = 0.005), primary (P = 0.0002) and atretic (P = 0.03) follicles were significantly greater in the DHEA group, whereas the percentage of intermediary follicles (early pre-antral, late preantral, and early antral follicles) was significantly lower in the DHEA group (P = < 0.0001). AMH expression in DHEA-treated rats on day 30 was seen exclusively in the primordial (P = 0.0413) and late antral follicles (p = 0.028). Conclusions: Androgen administration increases AMH production in a process that regulates the growth of primordial follicles. That is, androgen-induced AMH expression provides local negative feedback to folliculogenesis augmented by androgen.

DOI PubMed

エストロゲン産生を示す低分化型セルトリ・間質細胞腫瘍の一例

恐神博行, 田中綾一, 玉手雅人, 杉尾明香, 鈴木美和, 郷久晴朗, 寺本瑞絵, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 32 ( 2 ) 253 - 256 2014.04

低分化型のセルトリ・間質細胞腫瘍は性索間質細胞腫瘍に分類され、卵巣悪性腫瘍の0.2%を占める非常に稀な腫瘍である。我々は、エストラジオール値の上昇を認めた卵巣低分化型セルトリ・間質細胞腫瘍を経験したので報告する。症例は65歳、1経妊1経産。主訴は不正性器出血で、画像所見から右卵巣原発の性索間質性腫瘍が疑われた。エストラジオール値が57.6pg/mlと上昇していた。腹式単純子宮全摘出術および両側付属器切除術を施行し、低分化型セルトリ・間質細胞腫瘍と診断された。免疫組織染色では、Inhibin-α、calretinin、CD56およびMIN2/CD99が陽性、EMAは陰性であった。現在まで再発徴候は認められていない。(著者抄録)

Low-dose SN-38 with paclitaxel induces lethality in human uterine cervical adenocarcinoma cells by increasing caspase activity

Mizue Teramoto, Takahiro Suzuki, Seiro Satohisa, Yushi Akashi, Motoki Matsuura, Miwa Suzuki, Ryoichi Tanaka, Tsuyoshi Saito

MEDICAL MOLECULAR MORPHOLOGY ( SPRINGER JAPAN KK ) 47 ( 1 ) 31 - 37 2014.03 [Refereed]

Combination of anticancer drugs may provide a rational molecular basis for novel chemotherapeutic strategies. Paclitaxel and SN-38 (an active metabolite of CPT-11) are effective for many kinds of cancer. Therefore, we investigated the possibility that combination of these drugs could be effective against cervical adenocarcinoma cells. In this study, we examined cell growth inhibition after 96 h using the MTT assay and examined the release of fragmented DNA into the cytoplasm during apoptotic cell death by PI staining. Single and combined use of paclitaxel and SN-38 produced significant cytolethality against the cervical adenocarcinoma cell line CAC-1. Addition of a low concentration of SN-38 reduced the IC50 value of paclitaxel compared to that without SN-38, although the low concentration of paclitaxel did not enhance the cytotoxicity of SN-38. FACS scan analysis suggested that these drugs induced apoptosis and cell cycle arrest, and that caspase-3 and -7 were activated in the process. MTT assay and the IC50 demonstrated that paclitaxel had strong cytotoxicity against CAC-1 as well as other cancer cells. In this study, though only a single cell line was used for the experiment and the data are limited, our results suggest that paclitaxel together with low-dose CPT-11 is a promising basis for a new combination cancer chemotherapy.

DOI PubMed

婦人科癌における癌精巣抗原BORISの発現ならびに癌幹細胞性の検討

浅野拓也, 廣橋良彦, 真里谷奨, 黒田敬史, 鳥越俊彦, 齋藤豪, 佐藤昇志

日本病理学会会誌 ( (一社)日本病理学会 ) 103 ( 1 ) 266 - 266 2014.03

上皮性卵巣癌122例のHLA Class I発現およびCTL腫瘍内浸潤の臨床的因子との関連

真里谷奨, 廣橋良彦, 浅野拓也, 黒田敬史, 安田和世, 鳥越俊彦, 齋藤豪, 佐藤昇志

日本病理学会会誌 ( (一社)日本病理学会 ) 103 ( 1 ) 371 - 371 2014.03

子宮体癌・発癌と進展子宮体がんの転移、浸潤におけるBAG3の役割 micro RNAとの関連を検討する

幅田周太朗, 岩崎雅宏, 杉尾明香, 玉手雅人, 恐神博行, 鈴木美和, 田中綾一, 斎藤豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 ) 66 ( 2 ) 459 - 459 2014.02

Excessive androgen exposure as an etiological factor of polycystic ovary syndrome

Tsuyoshi Baba, Toshiaki Endo, Sayaka Adachi, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Yoshika Kuno, Hiroyuki Honnma, Tamotsu Kiya, Tsuyoshi Saito

Journal of Mammalian Ova Research ( Japanese Society of Mammalian Ova Research ) 31 ( 1 ) 23 - 30 2014

Polycystic ovary syndrome (PCOS) is a heterogeneous group of disorders characterized by ovulation disorder, hyperandrogenism, and polycystic ovarian morphology (PCOM). Several diagnostic criteria suggest that hyperandrogenism is a core symptom of PCOS. Androgens are believed to cause preantral follicle growth and arrest the growth of antral follicles. This results in accumulation of small antral follicles in the ovaries, thus forming PCOM. Observational studies of patients with female-to-male transsexualism or congenital adrenal hyperplasia indicate that androgen administration to these patients does not produce typical PCOS-like features. However, endogenous androgen exposure in early life may lead to some traits of PCOS in adulthood. To reveal the association between the timing of excess androgen exposure and reproductive function, various animal models have been investigated using androgen administration. Rhesus monkeys exposed to excess androgen during the early fetal period show a PCOS-like phenotype, including metabolic and hypothalamic- pituitary characteristics. This finding implies that exposure to excess androgen during this critical period programs the hypothalamic-pituitary-ovary axis and metabolic organs. Although findings obtained in animal studies will not necessarily be replicated in humans, prenatal androgen excess is the dominant PCOS hypothesis. ©2014 Japan Society for Ova Research.

DOI

Difficulty in the management of pregnancy after vaginal radical trachelectomy

Sakura Takada, Shin-Ichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Miyuki Morishita, Yushi Akashi, Masahito Mizuuchi, Hidefumi Adachi, Miseon Kim, Tsuyoshi Saito

International Journal of Clinical Oncology 18 ( 6 ) 1085 - 1090 2013.12 [Refereed]

Background: We have performed 26 vaginal radical trachelectomies (RTs) for patients with early invasive uterine cervical cancer since 2003 and, to date, have experienced 8 deliveries. The procedure has a high risk for preterm labor and the subsequent occurrence of preterm premature rupture of membranes (pPROM). We report the present situation and the limits of follow-up of pregnancy after vaginal RT. Methods: Our operative procedure is based on that of Dargent et al. We usually amputate the cervix approximately 10 mm below the isthmus. To remove the parametrium, we cut at the level of type II hysterectomy. Pregnancy courses after vaginal RT were studied in 8 patients with respect to symptoms, cervical length, and several infectious signs. Results: We recommended that patients enter hospital early in their second trimester, and prophylactic daily vaginal disinfection with povidone-iodine and an ulinastatin vaginal suppository were administered. Careful checking for vaginal infectious signs, as well as cervical length and abdominal tension of patients was also performed. Four patients followed up with this modality were able to continue their pregnancies until late in the third trimester. However, this follow-up modality was not effective for patients who showed cervical incompetence due to slack cervical cerclage. They suffered from pPROM at 26 and 19 weeks of gestation. Conclusion: We need a new approach for the management of pregnant patients after vaginal RT with cervical incompetence due to slack cervical cerclage to prevent cervical infection. © 2012 Japan Society of Clinical Oncology.

DOI PubMed

Regulation of tight junctions by sex hormones in normal human endometrial epithelial cells and uterus cancer cell line Sawano

Masayuki Someya, Takashi Kojima, Marie Ogawa, Takafumi Ninomiya, Kazuaki Nomura, Akira Takasawa, Masaki Murata, Satoshi Tanaka, Tsuyoshi Saito, Norimasa Sawada

CELL AND TISSUE RESEARCH ( SPRINGER ) 354 ( 2 ) 481 - 494 2013.11 [Refereed]

The number of patients with uterine endometrial carcinoma, the cause of which involves sex hormones, has recently been growing rapidly because of increases in life expectancy and obesity. Tight junction proteins claudin-3 and -4 are receptors of Clostridium perfringens enterotoxin (CPE) and increase during endometrial carcinogenesis. In the present study of normal human endometrial epithelial (HEE) cells and the uterus cancer cell line Sawano, we investigate changes in the expression of tight junction proteins including claudin-3 and -4, the fence and barrier functions of the tight junction and the cytotoxic effects of CPE by sex hormones. In primary cultured HEE cells, treatment with progesterone (P4) but not estradiol (E2), induced claudin-1, -3, -4 and -7 and occludin, together with the downregulation of the barrier function but not the fence function. In Sawano cells, claudin-3 and -4 were upregulated by E2 but not by P4, together with a disruption of both the barrier and fence function. In primary cultured HEE cells, claudin-3 and -4 were localized at the apicalmost regions (tight junction areas) and no cytotoxicity of CPE was observed. In Sawano cells, claudin-3 and -4 were found not only in the apicalmost regions but also at the basolateral membrane and the cytotoxicity of CPE was enhanced by E2. Thus, tight junctions are physiological regulated by sex hormones in normal HEE cells during the menstrual cycle suggesting that safer and more effective therapeutic methods targeting claudins in uterine cancer can be developed.

DOI PubMed

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Papers - SAITOU Tsuyoshi