Actinomycin D-Mediated Sensitization of Malignant Oral Cell Lines to Fas-Mediated Cytotoxicity : Implication of p53 and FAP-1

Itakura, Masayuki,Mori, Shunsuke,Park, No-Hee,Bonavida, Benjamin Korean Academy of Oral Biology and the UCLA Dental 1999 International Journal of Oral Biology Vol.24 No.3

Dysregulation of the normal apoptotic mechanism in normal cells can directly contribute to the pathogenesis of cancer and the development of resistance of tumor cells to cytotoxic drugs and lymphocytes. We have investigated the development of resistance to immune Fas-mediated apoptotic signals in oral cell lines as a function of progression from normal towards malignancy and the sensitizing effect of actinomycin D(ActD). Several lines of oral tissues that represent different stages of progression from the normal phenotype to the malignant phenotype were examined. Normal human oral keratinocytes (NHOK)were immortalized by transfection with the recombinant human papilloma virus ((HPV)-16 DNA (HoK-16B)). These cells were subsequently exposed to benzo(a)pyrene for 7days (HOK-16B-BaP) and remained non-tumorigenic in nude mice. HOK-16B-BaP exposed for longer periods (6 months) to benzo(a)pyrene (HOK-16B-BaP-T) developed tumors in nude mice when injected subcutaneously and a cell line was developed from the tumor (HOK-16B-BaP-T1). NHOK and HOK-16B were relatively more sensitive to anti-Fas antibody (CH-11) and Fas-ligand-mediated cytotoxicity than the more advanced lines. Western blot analysis and flow cytometry showed (a) decreaded surface espression of Fas, (b) decreased expression Of P53, (c) increased expression of Bcl-2 and decreased expression of Bax, as a function of tumor cell development from the normal to the malignant phenotype. Treatment with ActD augmented both anti-Fas antibody mediated and Fas ligand mediated cytotoxicity, and significantly up-regulated the p53 protein levels without changing the Bcl-2 and Bax protein levels. Fas-associated phosphatase-1 (FAP-1) is an anti-apoptotic molecule reported to interact with Fas and can block transduction of the apoptotic signal. Western blot analysis revealed that FAP-1 protein levels were increased with progression towards malignancy and was down-regulated by treatmint with ActD. These findings demonstrate the implication of several potential mechanisms by which oral cell lines become resistant to Fas-mediated apoptosis with the development of malignancy in vitro. These include decreased expression of pro-apoptotic proteins such as surface Fas, p53, and Bax, and increased expression of anti-apoptotic proteins such as Bcl-2 and FAP-1. Sensitization to Fas-apoptosis by ActD resulted in the upregulation of p53 and down-regulation of FAP-1 protein levels.

Sub 0.1mm Pattern Fabrication Using a 193-nm TSI Process

Shigeyasu Mori,Koichi Kuhara,Taku Morisawa,Nobuyuki Matsuzawa,Yuko Kaimoto,Masayuki Endo,Takahiro Matsuo,Masaru Sasago 대한전자공학회 1998 International Conference on Electronics, Informati Vol.- No.-

Nutritional Status Indicators Affecting the Tolerability of Postoperative Chemotherapy After Total Gastrectomy in Patients With Gastric Cancer

Toyota Kazuhiro,Mori Masayuki,Hirahara Satoshi,Yoshioka Shoko,Kubota Haruna,Yano Raita,Kobayashi Hironori,Hashimoto Yasushi,Sakashita Yoshihiro,Yokoyama Yujiro,Murakami Yoshiaki,Miyamoto Katsunari 대한위암학회 2022 Journal of gastric cancer Vol.22 No.1

Purpose: Nutritional problems after gastrectomy affect continuation of postoperative chemotherapy. There have been no studies limited to total gastrectomy, which is particularly prone to nutritional problems. In this study, we aimed to investigate the factors that predict the continuation of postoperative chemotherapy. Materials and Methods: We included 101 patients who underwent curative total gastrectomy and postoperative chemotherapy at Hiroshima Memorial Hospital. The effects of 37 factors, including perioperative inflammatory, nutritional, and tumor status, on the persistence of postoperative chemotherapy were analyzed. Results: In univariate analysis of preoperative factors, age, carbohydrate antigen 19-9, platelet-to-neutrophil ratio, Onodera's prognostic nutritional index (PNI), controlling nutritional status score, and nutritional risk screening (NRS-2002) score were significantly associated with the duration of postoperative chemotherapy. In multivariate analysis of preoperative factors, age (≥74 years) was an independent factor for a shorter duration of postoperative chemotherapy (hazard ratio [HR], 5.24; 95% confidence interval [CI], 2.19–12.96; P<0.01). In univariate analysis of factors before postoperative chemotherapy, intraoperative blood loss, perioperative weight loss rate, postoperative performance status, PNI, albumin-to-bilirubin index, and NRS-2002 score were significantly associated with the duration of postoperative chemotherapy. In multivariate analysis of factors before postoperative therapy, age (≥74 years) (HR, 5.75; 95% CI, 1.90–19.49; P<0.01) and PNI (<39) (HR, 3.29; 95% CI, 1.26–8.56; P=0.02) were independent factors for a shorter duration of postoperative chemotherapy. Conclusions: Age and PNI are useful predictors of postoperative chemotherapy intolerance after total gastrectomy and may determine the treatment strategy and timing of chemotherapy initiation.

Valsalva Aneurysm Filled with Thrombi Mimicking a Cardiac Tumor

Yasuharu Lee,Naoki Mori,Daisuke Nakamura,Takahiro Yoshimura,Masayuki Taniike,Nobuhiko Makino,Hiroyasu Kato,Yasuyuki Egami,Ryu Shutta,Jun Tanouchi,Yoshio Yamada,Masami Nishino 대한심장학회 2012 Korean Circulation Journal Vol.42 No.12

A Valsalva aneurysm filled with thrombi can be difficult to diagnose, because it mimics a cardiac tumor. Both cardiac magnetic resonance imaging (MRI) and transesophageal echocardiogram (TEE) were performed on a patient who showed a low-echoic mass located between the atrial septum and the non-coronary sinus. Based on MRI findings allowing tissue characterization and the accurate location of the mass and the TEE findings of an irregular surface of the mass and a partial defect in the edge of the non-coronary sinus, we diagnosed the mass as a thrombosed Valsalva aneurysm that had perforated the inter-atrial septum. The operative findings coincided with the preoperative di-agnosis. Both MRI and TEE are useful for diagnosing this condition.

Variation of Oxygen Nonstoichiometry of Porous $La_{0.6}Ca_{0.4}MnO_{3-{\delta}}$ SOFC-Cathode under Polarization

Mizusaki, Junichiro,Harita, Hideki,Mori, Naoya,Dokiya, Masayuki,Tagawa, Hiroaki The Korean Ceramic Society 2000 The Korean journal of ceramics Vol.6 No.2

At the porous $La_{0.6}Ca_{0.4}MnO_{3-{\delta}}$(LCM)/YSZ electrodes of solid oxide fuel cells (SOFC), the electrochemical redox reaction of oxygen proceeds via the triple boundary (TPB) of gas/LCM/YSZ. The surface diffusion of adsorbed oxygen on LCM has been proposed as the rate determining process, assuming the gradient of oxygen chemical potential from the outer surface of porous layer to TPB. Along with the formation of this gradient, oxygen nonstoichiometry in the bulk of LCM may varies. In this paper, an electrochemical technique was described precisely to determine the variation of oxygen content in LCM of porous LCM/YSZ under polarization. It was shown that the oxygen potential in LCM layer under large cathodic polarization is much lower than that in the gas phase, being determined from the electrode potential and Nernst equation.

Aglycone specificity of <i>Escherichia coli</i>α‐xylosidase investigated by transxylosylation

Kang, Min‐,Sun,Okuyama, Masayuki,Yaoi, Katsuro,Mitsuishi, Yasushi,Kim, Young‐,Min,Mori, Haruhide,Kim, Doman,Kimura, Atsuo BLACKWELL 2007 FEBS JOURNAL Vol.274 No.23

<P>The specificity of the aglycone‐binding site of <I>Escherichia coli</I>α‐xylosidase (YicI), which belongs to glycoside hydrolase family 31, was characterized by examining the enzyme's transxylosylation‐catalyzing property. Acceptor specificity and regioselectivity were investigated using various sugars as acceptor substrates and α‐xylosyl fluoride as the donor substrate. Comparison of the rate of formation of the glycosyl–enzyme intermediate and the transfer product yield using various acceptor substrates showed that glucose is the best complementary acceptor at the aglycone‐binding site. YicI preferred aldopyranosyl sugars with an equatorial 4‐OH as the acceptor substrate, such as glucose, mannose, and allose, resulting in transfer products. This observation suggests that 4‐OH in the acceptor sugar ring made an essential contribution to transxylosylation catalysis. Fructose was also acceptable in the aglycone‐binding site, producing two regioisomer transfer products. The percentage yields of transxylosylation products from glucose, mannose, fructose, and allose were 57, 44, 27, and 21%, respectively. The disaccharide transfer products formed by YicI, α‐<SMALL>d</SMALL>‐Xyl<I>p</I>‐(1→6)‐<SMALL>d</SMALL>‐Man<I>p</I>, α‐<SMALL>d</SMALL>‐Xyl<I>p</I>‐(1→6)‐<SMALL>d</SMALL>‐Fru<I>f</I>, and α‐<SMALL>d</SMALL>‐Xyl<I>p</I>‐(1→3)‐<SMALL>d</SMALL>‐Fru<I>p</I>, are novel oligosaccharides that have not been reported previously. In the transxylosylation to cello‐oligosaccharides, YicI transferred a xylosyl moiety exclusively to a nonreducing terminal glucose residue by α‐1,6‐xylosidic linkages. Of the transxylosylation products, α‐<SMALL>d</SMALL>‐Xyl<I>p</I>‐(1→6)‐<SMALL>d</SMALL>‐Man<I>p</I> and α‐<SMALL>d</SMALL>‐Xyl<I>p</I>‐(1→6)‐<SMALL>d</SMALL>‐Fru<I>f</I> inhibited intestinal α‐glucosidases.</P>

Molecular Cloning of cDNA for Trehalase from the European Honeybee, <i>Apis mellifera</i> L., and Its Heterologous Expression in <i>Pichia pastoris</i>

LEE, Jin-Ha,SAITO, Saori,MORI, Haruhide,NISHIMOTO, Mamoru,OKUYAMA, Masayuki,KIM, Doman,WONGCHAWALIT, Jintanart,KIMURA, Atsuo,CHIBA, Seiya Japan Society for Bioscience, Biotechnology, and A 2007 Bioscience, Biotechnology, and Biochemistry Vol.71 No.9

<P>cDNA encoding the bound type trehalase of the European honeybee was cloned. The cDNA (3,001 bp) contained the long 5′ untranslated region (UTR) of 869 bp, and the 3′ UTR of 251 bp including a poly(A) tail, and the open reading frame of 1,881 bp consisting of 626 amino acid residues. The <I>M</I><SUB>r</SUB> of the mature enzyme comprised of 591 amino acids, excluded a signal sequence of 35 amino acid residues, was 69,177. Six peptide sequences analyzed were all found in the deduced amino acid sequence. The amino acid sequence exhibited high identity with trehalases belonging to glycoside hydrolase family 37. A putative transmembrane region similar to trehalase-2 of the silkworm was found in the C-terminal amino acid sequence. Recombinant enzyme of the trehalase was expressed in the methylotrophic yeast <I>Pichia pastoris</I> as host, and displayed properties identical to those of the native enzyme except for higher sugar chain contents. This is the first report of heterologous expression of insect trehalase.</P>

Truncation of N- and C-terminal regions of Streptococcus mutans dextranase enhances catalytic activity

Kim, Young-Min,Shimizu, Ryoko,Nakai, Hiroyuki,Mori, Haruhide,Okuyama, Masayuki,Kang, Min-Sun,Fujimoto, Zui,Funane, Kazumi,Kim, Doman,Kimura, Atsuo Springer-Verlag 2011 Applied microbiology and biotechnology Vol.91 No.2

Regulation of Major Histocompatibility (MHC) Class Ⅱ Human Leukocyte Antigen-DRα Gene Expression in Thyrocytes by Single Strand Binding Protein-1, a Transcription Factor That Also Regulates Thyrotropin Receptor and MHC Class I Gene Expression

BALDUCCI-SILANO, PINA L.,SUZUKI, KOICHI,OHTA, MASANORI,SAITO, JUN,OHMORI, MASAYUKI,MONTANI, VALERIA,NAPOLITANO, GIORGIO,SHONG, MINHO,TANIGUCHI, SHIN-ICHI,PIETRARELLI, MICHELE,LAVARONI, STEFANO,MORI, A 충남대학교 생물공학연구소 1999 생물공학연구지 Vol.7 No.-

The single strand binding protein (SSBP-1) is a positive regulator of TSH receptor gene expression and binds to an element with a GXXXXG motif. The S box of the mouse major histocompatibility classⅡ gene has multiple GXXXXG motifs and can also bind SSBP-1. The S box is one of four highly conserved elements on the 5'-flanking region of classⅡ genes that are necessary for interferon-γ (IFNγ) to overcome the normally suppressed state of the gene and induce aberrant classⅡ expression. In this report we show that SSBP-1, when overexpressed in FRTL-5 thyroid cells, is a positive regulator of human leukocyte antigen (HLA)-DRα classⅡ gene expression, as is IFNγ or the classⅡ trans-activator (CIITA). This is evidenced by increased exogenous promoter activity, increased endogenous RNA levels, and increased endogenous antigen expression after transfecting full-length SSBP-1 complementary DNA together with a HLA-DRα promoter-reporter gene chimera into TSH-treated FRTL-5 thyroid cells whose endogenous SSBP-1 levels are low. IFNγ reverses the ability of TSH to decrease endogenous SSBP-1 RNA levels. Also, whereas SSBP-1 transfection does not cause any increase in IFNγ-induced exogenous promoter activity, transfection of SSBP-1 and CIITA additively increases endogenous classⅡ RNA levels to levels measured in cells treated with IFNγ. Further, competition studies show that SSBP-1 binding is necessary for formation of the double strand protein/DNA complexes that are seen in electrophoretic mobility shift assays when the classⅡ 5'-flanking region is incubated with extracts from IFNγ-treated FRTL-5 cells and that have been previously associated with IFNγ-induced aberrant classⅡ expression. These data suggest that SSBP-1 is involved in the action of IFNγ to overcome the normally suppressed state of the classⅡ gene; it functions together with CIITA, whose expression is independently increased by IFNγ. The effect of SSBP-1 as a positive regulator of classⅡ promoter activity is lost in cells maintained without TSH, in which endogenous SSBP-1 RNA levels are already high in the absence of aberrant classⅡ gene expression. These data suggest that high levels of endogenous SSBP-1 are insufficient to cause aberrant classⅡ expression, but, rather, TSH or IFNγ treatment additionally modulates the cell, albeit differently, such that transfected or endogenous SSBP-1, respectively, can express its positive regulatory activity. The effect of TSH is consistent with reports indicating that TSH enhances the ability of IFNγ to increase classⅡ gene expression despite the fact IFNγ increases endogenous SSBP-1 to only the same levels as in cells untreated with TSH. Finally, the effect of SSBP-1 as a positive regulator is lost when GXXXXG motifs, which exist on both the coding and noncoding strands of the S box, are mutated. Consistent with this, mutation and oligonucleotide competition studies show that GXXXXG motifs are necessary for either strand of the S box to bind protein/DNA complexes containing SSBP-1 in FRTL-5 cell extracts or to bind to recombinant SSBP-1. They also suggest that the SSBP-1-binding sites on either strand of the HLA-DRα S box are functionally distinct. We conclude from these data that the positive regulatory action of SSBP-1 on classⅡ gene expression involves GXXXXG motifs on each strand of the highly conserved S box of the classⅡ 5'-flanking region. As SSBP-1 is modulated by IFNγ and is involved in classⅠ and TSH receptor as well as classⅡ gene expression in FRTL-5 cells, the sum of the data supports the hypotheses that common transcription factors regulate all three genes, and their altered activities may contribute to the development of autoimmunity. (Endocrinology 139: 2300-2313, 1998)

Clinicopathologic features, treatment, prognosis and prognostic factors of neuroendocrine carcinoma of the endometrium: a retrospective analysis of 42 cases from the Kansai Clinical Oncology Group/Intergroup study in Japan

Harunobu Matsumoto,Mototsugu Shimokawa,Kaei Nasu,Ayumi Shikama,Takaya Shiozaki,Masayuki Futagami,Kentaro Kai,Hiroaki Nagano,Taisuke Mori,Mitsutake Yano,Norihiro Sugino,Etsuko Fujimoto,Norihito Yoshiok 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.6

Objective: We conducted a retrospective, multi-institutional, collaborative study to accumulate cases of neuroendocrine carcinoma of the endometrium, to clarify its clinicopathologic features, treatment, prognosis and prognostic factors to collate findings to establish future individualized treatment regimens. To our knowledge, this is the largest case study and the first study to statistically analyze the prognosis of this disease. Methods: At medical institutions participating in the Kansai Clinical Oncology Group/Intergroup, cases diagnosed at a central pathologic review as neuroendocrine carcinoma of the endometrium between 1995 and 2014 were enrolled. We retrospectively analyzed the clinicopathologic features, treatment, prognosis and prognostic factors of this disease. Results: A total of 65 cases were registered from 18 medical institutions in Japan. Of these, 42 (64.6%) cases were diagnosed as neuroendocrine carcinoma of the endometrium based on the central pathological review and thus included in the study. Advanced International Federation of Gynecology and Obstetrics stages (stage III and IV) and pure type small cell neuroendocrine carcinoma cases had a significantly worse prognosis. Upon multivariate analysis, only histologic subtypes and surgery were significant prognostic factors. Pure type cases had a significantly worse prognosis compared to mixed type cases and complete surgery cases had a significantly better prognosis compared to cases with no or incomplete surgery. Conclusion: Our findings suggest that complete surgery improves the prognosis of neuroendocrine carcinoma of the endometrium. Even among cases with advanced disease stages, if complete surgery is expected to be achieved, clinicians should consider curative surgery to improve the prognosis of neuroendocrine carcinoma of the endometrium.