Details of a Researcher - SAITOU Tsuyoshi

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Nuclear localization of beta-catenin in normal and carcinogenic endometrium

H Nei, T Saito, H Yamasaki, H Mizumoto, E Ito, R Kudo

MOLECULAR CARCINOGENESIS ( WILEY-LISS ) 25 ( 3 ) 207 - 218 1999.07

We have previously shown that the connexin (Cx) 26 and 32 genes are expressed during the secretory phase of the human endometrium and that their expression is downregulated during the proliferative phase, suggesting a role for intercellular transduction in cell growth control in human endometrium. To further study the possible role of cell-to-cell interaction in growth regulation, we immunohistochemically analyzed 80 endometrial samples (30 of normal endometrium, 20 of endometrial hyperplasia, and 30 of endometrial cancer) for the expression of E-cadherin; alpha-, beta-, and gamma-catenin; adenomatous polyposis coli (APC) protein, and sex-steroid hormone receptors at three points in the cells: the cell-to-cell border, the cytoplasm, and the nucleus. In this study, moderate or strong staining of beta-catenin in the nuclei was observed in 60.0% of endometrial hyperplasia samples and 30.0% of endometrial cancer samples, although the beta-catenin gene was mutated in only two of the nine samples that showed the intensive nuclear staining. Western blotting analysis showed that the samples that had intense nuclear staining of beta-catenin had much higher expression of beta-catenin than the samples that did not have nuclear staining. Furthermore, normal endometrium showed nuclear localization, especially in the mid- and late-proliferative and early-secreting phases of the menstrual cycle. The results suggest that the nuclear localization of beta-catenin observed in endometrial hyperplasia and endometrial cancer, as in other tumors, implies that beta-catenin/wnt-1 signal transduction is highly activated in carcinogenesis of the endometrium as well as in normal physiological conditions. (C) 1999 Wiley-Liss, Inc.

DOI PubMed CiNii

当科における過去10年間の胚細胞腫瘍の後方視的検討

本間寛之, 杉村政樹, 芥川典之, 岩崎雅宏, 水元久修, 斎藤豪, 寒河江悟, 工藤隆一

日本産科婦人科学会東北連合地方部会報 ( 日本産科婦人科学会-東北連合地方部会 ) ( 46 ) 68 - 68 1999.03

当科における過去10年間の上皮性卵巣癌(I・II期)の検討

杉村政樹, 本間寛之, 芥川典之, 岩崎雅宏, 水元久修, 斎藤豪, 寒河江悟, 工藤隆一

日本産科婦人科学会東北連合地方部会報 ( 日本産科婦人科学会-東北連合地方部会 ) ( 46 ) 68 - 68 1999.03

Primary malignant melanoma of the uterine cervix: A case report

Masaki Takehara, Eiki Ito, Tsuyoshi Saito, Yoshihiro Nishioka, Ryuichi Kudo

Journal of Obstetrics and Gynaecology Research ( University of Tokyo Press ) 25 ( 2 ) 129 - 132 1999

DOI PubMed

Combination Chemotherapy with Cisplatin, Aclacinomycin A, and Mitomycin C for Primary, Advanced, or Recurrent Cervical Adenocarcinoma

J Gynecol Tech 5 151 - 155 1999

[Small cell lung cancer associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome]

Nihon Kokyuki Gakkai Zasshi 37 992 - 6 1999

Induction of cell transformation by mutated 16K vacuolar H+-ATPase (ductin) is accompanied by down-regulation of gap junctional intercellular communication and translocation of connexin 43 in NIH3T3 cells

T Saito, R Schlegel, T Andresson, L Yuge, M Yamamoto, H Yamasaki

ONCOGENE ( STOCKTON PRESS ) 17 ( 13 ) 1673 - 1680 1998.10

The 16 K subunit of the vacuolar H+-ATPase (ductin) has been suggested to also play a role in gap junction channels. Since mutated 16 K subunits have transforming ability when transfected into NIH3T3 cells and since aberrant gap junctional intercellular communication (GJIC) is a hallmark of cancer cells, we hypothesized that mutated 16 K subunits might transform these cells via alteration of GJIC, When GJIC was measured by the dye-transfer assay, NIH3T3 cells transfected with the mutant 16 K protein genes (deletion of the fourth transmembrane domain or a point mutation at codon 143 from glutamic acid to arginine) showed significantly lower levels of GJIC than those transfected with the vector alone or with the wild-type 16 K subunit gene. GJIC levels of NIH3T3 cells transformed by v-ras and v-src were not significantly decreased, suggesting that low GJIC levels are not necessarily the result of cell transformation pel se. NIH3T3 cells express Cx 43 as a major connexin gene. Although cells transfected with mutated 16 K subunits showed a level of Cx 43 protein expression similar to non-transfectants, their Cx43 protein was localized aberrantly, i.e. intracytoplasmically, These results indicate that mutant 16 K subunits with transforming ability translocate Cx43 proteins, thus inhibiting GJIC of NIH3T3 cells.

DOI PubMed CiNii

Electron microscopic examination of cytologic samples

E Ito, H Nei, M Noda, T Saito, M Koizumi, R Kudo

ACTA CYTOLOGICA ( SCI PRINTERS & PUBL INC ) 42 ( 5 ) 1095 - 1103 1998.09

OBJECTIVE: To review the results of observations of cytologic samples performed in our laboratory by light microscopy (LM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) performed in succession (LM-SEA I-TEM examination) using the same cytologic sample and to assess the diagnostic value of this method of successive examination. STUDY DESIGN: Using a previously reported method of LM-SEM-TEM sample preparation and observation, we analyzed 201 cytologic specimens over a seven-year period (1986-1993) and investigated whether the histologic origin and malignancy can be estimated from SEM and TEM findings on the cells. RESULTS: Observations of many cytologic samples over a seven-year period (by LM, SEM and TEM) showed that several basic interpretations of cellular ultrastructure are possible. In cases where cell identification was difficult by LM, electron microscopic findings were sometimes useful for determining the biologic characteristics of cells and for estimating their tissue origin. Electron microscopic findings also provided important information for cytodiagnosis. CONCLUSION: SEM and/or TEM findings are useful for determining the morphologic (including biologic) characteristics of cells in cases where they cannot be determined by LM. With the accumulation of data on electron microscopic examination of cytologic samples, it is expected that in the future, electron microscopy will continue to provide new information that can be used to improve the accuracy of cytodiagnosis by LM.

A case of protein-losing gastroenteropathy in association with mixed connective tissue disease which was successfully treated with cyclophosphamide pulse therapy

K. Nosho, H. Takahashi, Y. Ikeda, Y. Hanai, T. Mizukoshi, R. Murakami, T. Tokunou, Y. Kawahito, Y. Makiguchi, K. Imai, S. Inomata, T. Saito, T. Ikeda

Ryumachi 38 ( 6 ) 818 - 824 1998

A 47-year-old man had been given a diagnosis of mixed connective tissue disease (MCTD) on 1987 when he had presented with Raynaud's phenomenon, polyarthralgia, sclerodactyly, and a high titre of anti-RNP antibody. Once his symptoms had improved following the administration of prednisolone orally and the treatment was discontinued since 1995. He noticed dyspnea and chest pain in February 1997. The bilateral pleural effusion was pointed out in the local hospital and he was admitted to our hospital in March 1997 for further examination. In addition to pleural effusion and ascites, laboratory studies revealed hypoalbuminemia and low serum levels of complements. Renal and liver function tests were normal and the urine gave a trace test for protein. The presence of protein loss in the gut was confirmed by an elevated 1/4 - antitrypsin clearance and 99mTc-albumin scintigraphy showing abnormal radioactivity in the gastrointestinal tract. Although endoscopic examination showed no abnormal findings macroscopically and gastrointestinal biopsies revealed nonspecific inflammation only, immunofluorescent studies demonstrated deposits of C3, C4 and IgG in the stomach, colon, and pleura. These findings supported the pathogenesis that immune deposits in tissues caused protein-losing gastroenteropathy (PLGE) in MCTD. Intravenous administration of cyclophosphamide started since July 1997, while the high- dose corticosteroid therapy including methylprednisolone pulse therapy were not effective. Hypoalbuminemia and low serum levels of complements improved remarkably and the pleural effusion and ascites disappeared after cyclophosphamide pulse therapy four times monthly. Cyclophosphamide pulse therapy should be considered as a possibly effective treatment for PLGE in association with collagen disease resistant to corticosteroid therapy.

PubMed

Co-ordinated expression of connexins 26 and 32 in human endometrial glandular epithelium during the reproductive cycle and the influence of hormone replacement therapy

T Saito, M Oyamada, H Yamasaki, M Mori, R Kudo

INTERNATIONAL JOURNAL OF CANCER ( WILEY-LISS ) 73 ( 4 ) 479 - 485 1997.11

Hormones are involved in the regulation of intercellular communication, and gap junction intercellular communication may play an important role in the prevention of endometrial cancer. We have investigated changes in the expression of the gap junction proteins connexin 26 (Cx26) and Cx32 in human endometrial glandular epithelium during the reproductive cycle as well as the influence of hormone replacement therapy. Frozen sections from 71 endometrial tissue samples (53 taken from women who had undergone hysterectomy during the menstrual cycle, 3 early pregnancy deciduae and 15 from menopausal women, some of whom were receiving estrogen alone or estrogen plus progesterone) were analyzed by immunofluorescence and confocal laser scanning microscopy. Cx26 and Cx32 were expressed weakly in the proliferative phase, markedly during ovulation and most strongly in the mid-secretory phase; by the late secretory phase, they decreased drastically. Cx26 and Cx32 also were expressed in early pregnancy. Women who had received estrogen and progesterone expressed the Cxs, but those who had received estrogen only or no therapy did not. These results were confirmed by Western blot analysis. They indicate that expression of Cx26 and Cx32 is correlated with cell differentiation and with the glandular function of the endometrial epithelium and suggest that expression of Cxs is controlled by serum progesterone. (C) 1997 Wiley-Liss, Inc.

DOI PubMed CiNii

Proliferation-associated regulation of telomerase activity in human endometrium and its potential implication in early cancer diagnosis

T Saito, A Schneider, N Martel, H Mizumoto, M BulgayMoerschel, R Kudo, H Nakazawa

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ( ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS ) 231 ( 3 ) 610 - 614 1997.02

Telomerase activity was detected in normal endometrium in association with proliferation and regulated during the menstrual cycle in a hormone-dependent manner. The activity was maximal at the late-proliferative phase to mid-secreting phase, and was absent or extremely low at early-proliferative phase and late-secreting phase. Activity was also detected in all endometrial simple hyperplasias tested (16 of 16) and in most cancers (25 of 30), but none was detected in endometrial of either pregnant or postmenopausal women ill the absence of hyperplasia. Our data provide evidence that the telomerase activity in postmenopausal endometrium reflects a hyperproliferative condition. Therefore, we conclude that telomerase can provide a novel marker for early endometrial cancer diagnosis. Hormone-dependent regulation of telomerase suggests the possibility of therapeutic and preventive strategies for endometrial cancers through the management of ovarian steroid hormones or other agents that regulate telomerase activity. (C) 1997 Academic Press.

DOI PubMed CiNii

Connexin 37 mutations in rat hepatic angiosarcomas induced by vinyl chloride

T Saito, A Barbin, Y Omori, H Yamasaki

CANCER RESEARCH ( AMER ASSOC CANCER RESEARCH ) 57 ( 3 ) 375 - 377 1997.02

Connexin genes have been shown to restore normal cell growth when transfected into certain tumorigenic cells and thus are considered to form a family of tumor suppressor genes, In this study, we have analysed mutations of the connexin 37 (Cx37) gene in rat hepatic angiosarcomas induced by vinyl chloride. A total of 25 rat liver tumors (22 hepatic angiosarcomas and 3 hepatocellular carcinomas) were analysed by PCR-single-strand conformation polymorphism analysis and DNA sequencing, Four mutations were detected in three tumors: (a) one GGG(Gly) to GAG(Glu) mutation at codon 168; and (b) three silent mutations, CGA(Arg) to CGC(Arg), at codon 166, In addition, we found that codon 88 is polymorphic (GAG(Glu) to GAA(Glu)). Cx37 proteins are detectable in endothelial cells of normal liver by immunohistochemical analysis, but none of the angiosarcomas showed Cx37-positive spots, These results suggest that Cx37-mediated gap junctional intercellular communication may be disturbed in most of these angiosarcomas, but mutation of the Cx37 gene is rare.

A new operative procedure for vaginal extended hysterectomy

J Gynecol Tech 3 41 - 51 1997

Expression of component desmosomal proteins in uterine endometrial carcinoma and their relation to cellular differentiation

H Nei, T Saito, H Tobioka, E Itoh, M Mori, R Kudo

CANCER ( WILEY-LISS ) 78 ( 3 ) 461 - 470 1996.08

BACKGROUND. While the assessment of the malignancy of neoplasms is based on morphologic studies of cells and tissues, use of objective molecular markers is leading to a better understanding and more biologically meaningful classification of neoplasms. In recent years, changes in the expression of cell adhesion molecules, especially E-cadherin, catenin, and adenomatous polyposis coli (APC), in carcinomas have attracted the attention of researchers. However, little is known about desmosomes in the uterine endometrium or in endometrial carcinomas. In this study, we semiquantified the desmosomal components desmoplakin I and II and desmoglein, in tissue sections using confocal laser scanning microscopy (LSM), and examined their relationship to the pathological type, the occurrence of lymph node metastases, and the extent of myometrial invasion. METHOD, Frozen sections of 31 specimens of normal endometrium, 5 specimens of atypical hyperplasia, and 41 specimens of endometrial carcinoma were stained by the immunofluorescence method using antidesmoplakin I and II and antidesmoglein, and these markers were then semiquantified in tissue sections by LSM. RESULTS, The expression and location of desmoplakin I and II and desmoglein were similar, and their expression decreased with loss of differentiation. The expression was lower in cases of lymph node metastasis than in negative cases and was lower in the cases with > one-half myometrial invasion than in cases with < one-half myometrial invasion. CONCLUSIONS. Reduction of desmoplakin I and II and desmoglein expression may play an important role in the invasiveness and metastatic activity of human endometrial carcinoma. They can therefore be used as differentiation markers for endometrial carcinoma. (C) 1996 American Cancer Society.

DOI PubMed CiNii

内視鏡と膣拡大鏡診, 生検診の方法

図説産婦人科VIEW 17 184 - 187 1995

生検診の方法

図説産婦人科VIEW，14内視鏡と膣拡大鏡診，メジカルビュー社 1995

MONOCLONAL-ANTIBODY 7H6 REACTS WITH A NOVEL TIGHT JUNCTION-ASSOCIATED PROTEIN DISTINCT FROM ZO-1, CINGULIN AND ZO-2

Y ZHONG, T SAITOH, T MINASE, N SAWADA, K ENOMOTO, M MORI

JOURNAL OF CELL BIOLOGY ( ROCKEFELLER UNIV PRESS ) 120 ( 2 ) 477 - 483 1993.01

The tight junction is an essential element of the intercellular junctional complex; yet its protein composition is not fully understood. At present, only three proteins, ZO-1 (Stevenson, B. R., J. D. Siliciano, M. S. Mooseker, and D. A. Goodenough. 1986. J. Cell Biol. 103:755-766), cingulin (Citi, S., H. Sabanay, R. Jakes, B. Geiger, and J. Kendrick-Jones. 1988. Nature (Lond.). 333:272-275) and ZO-2 (Gumbiner, B., T. Lowenkopf, and D. Apatira. 1991. Proc. Natl. Acad. Sci. USA. 88:3460-3464) are known to be associated with the tight junction. We have generated a monoclonal antibody (7H6) against a bile canaliculus-rich membrane fraction prepared from rat liver. This 7H6 antigen was preferentially localized by immunofluorescence at the junctional complex regions of hepatocytes and other epithelia, and 7H6-affiliated gold particles were shown electron microscopically to localize at the periphery of tight junctions. Immunoblot analysis of a bile canaliculus-rich fraction of rat liver using 7H6, anti-ZO-1 antibody (R26.4C), and anticingulin antibody revealed that 7H6 reacted selectively with a 155-kD protein, whereas R26.4C reacted only with a 225-kD protein. Anti-cingulin antibody reacted solely with 140 and 108-kD proteins, indicating that the protein recognized by 7H6 is immunologically different from ZO-1 and cingulin. Immunoprecipitation of detergent extracts obtained from metabolically labeled MDCK cells with R26.4C coprecipitated a 160-kD protein, which corresponds to ZO-2, with ZO-1. However, 7H6 did not react with the 160-kD protein. These results strongly suggest that the 7H6 antibody recognizes a novel tight junction-associated protein different from ZO-1, cingulin and ZO-2.

DOI PubMed CiNii

ULTRASTRUCTURAL DEMONSTRATION OF PRE-S2 ANTIGEN ON THE INFECTED LIVER-CELL SURFACE

T SAITO, H SHINZAWA, T TAKAHASHI, M ISHIKAWA

HEPATOLOGY ( W B SAUNDERS CO ) 12 ( 4 ) 884 - 884 1990.10

Research paper, summary (international conference)

A MALIGNANT MIXED MESODERMAL TUMOR OF THE UTERINE CORPUS WITH HYPERCATECHOLAMINEMIA

T UEDE, T SAITO, T MINASE, T MIURA, K KIKUCHI, O IIMURA, S KON, H IWAKI, M MORI, K KIKUCHI

ACTA PATHOLOGICA JAPONICA ( BLACKWELL SCIENCE ) 40 ( 4 ) 293 - 300 1990.04

STRUCTURE AND FUNCTION OF THE CYTOSKELETAL SYSTEM IN HEPATOCYTES

M MORI, M OYAMADA, MI SATOH, T SAITOH, T MINASE

JOURNAL OF ELECTRON MICROSCOPY 39 ( 2 ) 130 - 130 1990.04

Research paper, summary (international conference)

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