INHIBITION OF IFN-γ PRODUCTION BY SOLUBLE FACTORS DERIVED FROM ORAL CANCER CELLS

The streptococcal antitumor agent OK-432 is commonly used as an immunopotentiator for immunotherapy in various types of malignant tumors including oral cancer. It has been demonstrated that OK-432 elicits an antitumor effect by stimulating immunocompetent cells, thereby inducing multiple cytokines including interferon (IFN)-γ, interleukin (IL)-2 and IL-12. Serum concentrations of IFN-γ in patients with oral cancer were examined 24 h after administration of OK-432. Serum concentrations of IFN-γ in patients with advanced cancer were significantly lower than those in patients with early cancer. These results suggested that some soluble factors produced by cancer cells may inhibit IFN-γ production with OK-432. Thus, in the present study, an in vitro simulation model was established for the immune status of patients with oral cancer by adding conditioned medium (CM) derived from oral cancer cell lines into a culture of peripheral blood mononuclear cells (PBMCs) derived from a healthy volunteer. We investigated whether soluble factors derived from oral cancer cells affected IFN-γ production from PBMCs following stimulation with OK-432. PBMCs stimulated with OK-432 produced a large amount of IFN-γ; however, both IFN-γ production and cytotoxic activity from PBMCs induced by OK-432 were inhibited by the addition of CM in a dose-dependent manner. In order to examine these inhibitory effects against IFN-γ production, the contribution of inhibitory cytokines such as IL-4, IL-6, IL-10, transforming growth factor-β and vascular endothelial growth factor was investigated. However, neutralization of these inhibitory cytokines did not recover IFN-γ production inhibited by CM. These results indicated that unknown molecules may inhibit IFN-γ production from PBMCs following stimulation with OK-432

Immunohistochemical detection of a specific receptor for lipocalin2 (solute carrier family 22 member 17, SLC22A17) and its prognostic significance in endometrial carcinoma

Background: We previously reported the overexpression of lipocalin2 (LCN2), a 25 kDa secretory protein involved in iron-transportation, in endometrial carcinoma and its possible contribution to endometrial carcinogenesis. Recently, a specific receptor for LCN2, solute carrier family 22 member 17 (SLC22A17), was identified. The present study was undertaken to investigate the expression of SLC22A17 in endometrial carcinoma. Methods: The expression of the SLC22A17 and LCN2 proteins was examined immunohistochemically using 69 cases of endometrial carcinoma and adjacent normal endometrial tissues. Immunoreactivity was evaluated according to the percentage of positive cells and described as a positivity index (PI, full score 100). Results: The expression of SLC22A17 was negligible in normal endometria, but positive staining for SLC22A17 (PI 1) was observed in 35 cases of endometrial carcinoma. The PI for SLC22A17 was significantly higher in cases with histological grade 3 (P < 0.0005), advanced FIGO stage (P=0.002), deep myometrial invasion (P=0.029), positive lymph-vascular space invasion (P = 0.029), positive intraperitoneal cytology (P = 0.020) and adnexal metastasis (P= 0.029). The expression of SLC22A17 and LCN2 was positively correlated with a significant difference (P= 0.002), and the patients who overexpressed both SLC22A17 and LCN2 showed poorer survival than those without the expression of SLC22A17 or LCN2 (P= 0.002). Moreover, the overexpression of both SLC22A17 and LCN2 was indicated to be an independent prognostic factor by multivariable analysis. Conclusions: These results suggested that SLC22A17, in cooperation with LCN2, to be involved in the acquisition of aggressive behavior among endometrial carcinoma cells.ArticleEXPERIMENTAL AND MOLECULAR PATHOLOGY. 91(2):563-568 (2011)journal articl

戦後小津安二郎直筆資料群からたどる映画成立過程研究

早大学位記番号:新7693早稲田大

『箱入り娘』から『晩春』へ

Director Yasujiro Ozu’s Late Spring (1949) has been referred to as Ozu’s perfect work. As the title was credited on the film, it was borrowed from Kazuo Hirotsu’s short story, Chichi to Musume. However, as Ozu clearly stated, the conclusion in the film is different to Hirotsu’s story. If so, what are the main themes of Late Spring? Compared to Hirotsu’s short story and Ozu’s other work, this study examines the main themes of Late Spring.First, one of the themes in Late Spring develops around the expression of the “lie.” In Hirotsu’s story, readers are made aware of the father’s “lie,” and his motive is described in detail. While a novel may communicate its characters’ inner discourse through narration or a narrator, it is impossible for a film to do the same without the support of a voice-over or subtitles. However, without resorting to any of these techniques, Late Spring deliberately withholds the truth from its audience. The final scene where the father confesses that he had “lied” to his daughter is far more powerful than just a final revelation. The facial expression of Chishu Ryu, who portrays the father, when he first “lied” is also worth noting. Presenting a stern face without a twitch or a smile, he simply answers “un” when his daughter asks him if he was really getting remarried. Chishu Ryu’s “expressionless face” is instrumental to the success of this film.Second, in Ozu’s works before Late Spring, the pattern of developing a “lie” theme can also be seen in Hakoiri-Musume (1935). Here, we can see the same pattern of deception in the girl’s “lie.” Worthy of attention here is Kogo Noda, the screenwriter, who had participated in both films. Late Spring was their first collaboration in 14 years since Hakoiri-Musume, after which, they continued to co-write film scripts.In this way, we can see the themes of Late Spring based on and borrowed from Kazuo Hirotsu’s short story; however, Ozu and Noda created an additional “lie” theme in Late Spring.論

Infection of RANKL-Primed RAW-D Macrophages with Porphyromonas gingivalis Promotes Osteoclastogenesis in a TNF-α-Independent Manner

Infection of macrophages with bacteria induces the production of pro-inflammatory cytokines including TNF-α. TNF-α directly stimulates osteoclast differentiation from bone marrow macrophages in vitro as well as indirectly via osteoblasts. Recently, it was reported that bacterial components such as LPS inhibited RANKL-induced osteoclastogenesis in early stages, but promoted osteoclast differentiation in late stages. However, the contribution to osteoclast differentiation of TNF-α produced by infected macrophages remains unclear. We show here that Porphyromonas gingivalis, one of the major pathogens in periodontitis, directly promotes osteoclastogenesis from RANKL-primed RAW-D (subclone of RAW264) mouse macrophages, and we show that TNF-α is not involved in the stimulatory effect on osteoclastogenesis. P. gingivalis infection of RANKL-primed RAW-D macrophages markedly stimulated osteoclastogenesis in a RANKL-independent manner. In the presence of the TLR4 inhibitor, polymyxin B, infection of RANKL-primed RAW-D cells with P. gingivalis also induced osteoclastogenesis, indicating that TLR4 is not involved. Infection of RAW-D cells with P. gingivalis stimulated the production of TNF-α, whereas the production of TNF-α by similarly infected RANKL-primed RAW-D cells was markedly down-regulated. In addition, infection of RANKL-primed macrophages with P. gingivalis induced osteoclastogenesis in the presence of neutralizing antibody against TNF-α. Inhibitors of NFATc1 and p38MAPK, but not of NF-κB signaling, significantly suppressed P. gingivalis-induced osteoclastogenesis from RANKL-primed macrophages. Moreover, re-treatment of RANKL-primed macrophages with RANKL stimulated osteoclastogenesis in the presence or absence of P. gingivalis infection, whereas re-treatment of RANKL-primed macrophages with TNF-α did not enhance osteoclastogenesis in the presence of live P. gingivalis. Thus, P. gingivalis infection of RANKL-primed macrophages promoted osteoclastogenesis in a TNF-α independent manner, and RANKL but not TNF-α was effective in inducing osteoclastogenesis from RANKL-primed RAW-D cells in the presence of P. gingivalis

Immunohistochemical expression of keratan sulfate: a possible diagnostic marker for carcinomas of the female genital tract

Aims The authors previously reported the expression of keratan sulfate (KS), a glycosaminoglycan, in the epithelium of normal and neoplastic endometria. The aim of this study was to evaluate its potential use as a diagnostic marker, and the expression of KS was investigated in other human epithelial tissues. Methods Expression was examined immunohistochemically using 102 samples of normal epithelia and 110 samples of carcinomas from the female genital tract (FGT; cervix, endometrium, ovary, fallopian tube), digestive organs (gastrointestinal tract, pancreas, liver), urinary tract, lung, mammary gland, thyroid and mesothelium. Results In normal tissues, KS was consistently detected in the FGT and ectopic endometrium (25/26), but was not found in the digestive organs (1/42) and urinary tract (0/6), and was only partly detected in the lung (7/10), mammary gland (3/9) and thyroid (4/4). In malignant tissues, KS was consistently observed in carcinomas of the endometrium, ovary and fallopian tube (29/32), and was partly detected in carcinomas of the lung, mammary gland, thyroid, pancreas and mesothelium, but was absent in carcinomas of the gastrointestinal tract (0/17), liver (0/5) and urinary tract (0/11). Among carcinomas of the FGT, digestive organs and urinary tract, KS positivity suggested the possibility of FGT carcinomas, with 79.5% (31/39) sensitivity and 92.9% (39/42) specificity. Conclusions KS is a potentially useful marker for the supportive diagnosis of the primary site of metastatic carcinomas or unknown primary carcinomas, especially in the abdominal cavity.ArticleJOURNAL OF CLINICAL PATHOLOGY. 64(12):1058-1063 (2011)journal articl

キノウテキ ヒキノウテキ ジコ チュウモク ノ ジゾク ト フアン ヨクウツ ノ カンレン

The purpose of this study was to examine the relationships among functional and dysfunctional self-focused attention, namely, self-reflection and rumination, and anxiety and depression. A survey was administered to 226 undergraduate students on self-rumination, self-reflection, self-focused attention, anxiety, and depression. The analysis showed that partial correlation between self-rumination and anxiety was significant while controlling for depression, same as self-focused attention and anxiety. Regression analysis revealed that self-focused attention predicted anxiety and depression. Results of this study showed that self-focused attention had a stronger association with anxiety. This study suggested that self-focused attention influences mental health regardless of motives, such as self-rumination and self-reflection. Future analysis needs to examine interventions in characteristics of self-focused attention

Inverse correlation between Skp2 and p27(Kip1) in normal endometrium and endometrial carcinoma

Copyright (c) 2010 Taylor & Francis. This is an electronic version of an article published in "GYNECOLOGICAL ENDOCRINOLOGY, Volume 26, Issue 3, pages 220-229 (2010)". GYNECOLOGICAL ENDOCRINOLOGY is available online at: https://doi.org/10.3109/09513590903215482Cyclin-dependent-kinase (cdk) inhibitor, p27<SUKip1</SU (p27), has been shown to participate in progestin-induced growth suppression of normal endometrial glands. To analyse the molecular mechanisms regulating p27 protein, we examined immunohistochemical expression of the SCF<SUSkp2</SU (Skp1-Cullin-F-box protein) complex factors, i.e. Skp1, Cul1 and Skp2, and compared them with that of p27, steroid receptors and Ki-67. In normal endometrial glands, the expression of Skp2 was observed in the proliferative phase, whereas that of p27 was observed in the secretory phase. Cultured normal endometrial glandular cells showed that progesterone induced the down-regulation of Skp2 along with up-regulation of p27. In endometrial carcinomas, the inverse topological correlation between Skp2 and p27 was evident in 39/66 (59%) cases, and the expression of Skp2 showed a strong correlation with Ki-67. These findings suggest that the expression of SCF<SUSkp2</SU complex changes during the menstrual cycle in normal endometrium and the SCF<SUSkp2</SU ubiquitin-proteasome pathway may also work in endometrial carcinomas.</.ArticleGYNECOLOGICAL ENDOCRINOLOGY. 26(3):220-229 (2010)journal articl

Effectiveness of Newly Developed Water-Equivalent Mouthpiece during External Beam Radiotherapy for Oral Cancer

The objective of this study was to research the effectiveness of newly developed water-equivalent mouthpiece during external beam radiotherapy for oral cancer. In external beam radiotherapy for cancer of the tongue, floor of the mouth, and lower gingiva, it is possible to prescribe a low dose to the upper gingiva and hard palate at an open mouth position using a mouthpiece. However, the inhomogeneity correction resulting from the air cavity and the mobility of the tongue produced by an open mouth position should be considered. Therefore, a new mouthpiece was designed to be fixed by the dental arch, and the air cavity of the mouth can be filled with water-equivalent material. In 30 patients with previously treated oral cancer, the simulated homogeneity index of the calculated water-equivalent mouthpiece by a treatment-planning system was significantly better than that of a conventional mouthpiece (p = 0.004). This new mouthpiece facilitates excellent dose distribution while attaining immobilization of the tongue in patients with oral cancer

A Case of Vaginal Varices that Caused Massive Bleeding after Vaginal Delivery

Article信州医学雑誌 64(1):35-39 (2016)journal articl