Hisako Inoue

Saiseikai Fukuoka General Hospital

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Recent advances in the treatment strategy for AAV improved outcomes with intensive GC tapering

International Journal of Rheumatic Diseases (2023)

Nobuyuki Ono Tatsuya Kai Yukiko Takeyama Yasushi Inoue Naoyasu Ueda

Abstract Objective To evaluate trends in results of care and management for antineutrophil cytoplasmic antibodies (ANCA)‐associated vasculitis (AAV). Methods We employed multicenter cohort data collected during 2011–2021, recruiting 43 patients with granulomatosis with polyangiitis (GPA) and 91 with microscopic polyangiitis (MPA). According to the median registration date of September 2015, patients have split into two groups: an early group and a late group (both of them, n = 67). To prevent bias, a propensity score according to numerous baseline characteristics variables was calculated; 50 matching members of each group were statistically extracted. Their treatments and clinical outcomes were examined at 6, 12, and 24 months after initial remission therapy. Results Statistics demonstrated that the baseline characteristics were similar. The late group used rituximab (RTX) more often for both remission induction and maintenance therapy, compared with the early group. The mean daily PSL doses of the late group were significantly lower than those of early group at each time point. The late group discontinued PSL 14.0% at 12 months and 23.3% at 24 months. Despite their intensive glucocorticoids (GC) tapering, the remission rates and the relapse rates were significantly fairer in the late group. The Vasculitis Damage Index (VDI) and VDI due to GC at each time point were lower in the late group, and those differences had become wider over time. Conclusion Recent developments in AAV treatment have allowed efficient remission and prevention of relapses, which in turn enabled extensive GC tapering causing fewer sequelae.

Granulomatosis with polyangiitis

Tapering

Microscopic polyangiitis

10.1111/1756-185x.15009

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Effect of disease activity and corticosteroids on serum levels of soluble endothelial cell protein C receptor in patients with systemic lupus erythematosus

Modern Rheumatology (2008)

Syuichi Koarada Naoko Tsuneyoshi Yoshio Haruta Yoshifumi Tada Mio Mitamura

To assess the effects of disease activity of systemic lupus erythematosus (SLE) and high-dose corticosteroids on endothelial injuries, the significance of soluble endothelial cell protein C receptor (sEPCR) and soluble thrombomodulin (sTM) was analyzed. Serum levels of sEPCR and sTM were measured by enzyme-linked immunosorbent assay (ELISA) cross-sectionally in 97 SLE patients, 49 patients with other rheumatic diseases and 22 normal subjects. The changes in these levels upon corticosteroid treatment were also analyzed in 41 patients. The levels of sEPCR and sTM were both higher in SLE and other rheumatic disease patients than in normal subjects. When low-dose corticosteroids were used, both the level of sEPCR and the ratio of positive tests for sEPCR were significantly higher in active SLE patients than in inactive patients [median 2.30 ng/ml (range 0.00-147.10 ng/ml) vs 0.00 ng/ml (0.00-58.90 ng/ml) and 53.5 vs 13.0%, respectively] (P < 0.005). Moreover, the ratio of positive tests for sEPCR was higher after corticosteroid treatment in 9 of 19 (47.3%) SLE patients compared to other rheumatic diseases (3/22; 13.6%). Although the mean level of sTM was significantly higher in active SLE patients than in inactive patients, the ratio of positive tests for sTM was not affected by disease activity or corticosteroids. In conclusion, the positive test for sEPCR is a more sensitive biomarker than that for sTM in reflecting endothelial injuries caused by active disease and often by corticosteroids in SLE.

10.1007/s10165-008-0143-z

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Additional file 1: Figure S1. of Cooperation of Sox4 with β-catenin/p300 complex in transcriptional regulation of the Slug gene during divergent sarcomatous differentiation in uterine carcinosarcoma

Hisako Inoue Hiroyuki Takahashi Miki Hashimura Koji Eshima Masashi Akiya

Slug

Carcinosarcoma

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A Case of Microscopic Polyangiitis and Giant Cell Arteritis after Influenza Vaccination

Japanese Journal of Clinical Immunology (2011)

Mai Konishi Syuichi Koarada Ken Yamaguchi Satoko Tashiro Sachiko Soejima

症例は67歳女性.主訴は頭痛,四肢の小結節・紅斑.近医にて慢性腎不全・高脂血症を治療中であったが,インフルエンザワクチン接種を行った.接種2週間後,微熱,頭痛が出現し,CRP高値,MPO-ANCA陽性,腎機能障害,側頭部の圧痛,四肢の紅斑を指摘され,紹介受診となった.紅斑の組織像で動脈周囲に炎症細胞浸潤,フィブリノイド壊死を認め,側頭動脈の組織では炎症細胞浸潤と巨細胞を伴う血管炎を認めた.CTで両肺に多発する斑状影を認め,肺胞出血または間質性肺炎と考えられた.顕微鏡的多発血管炎(mPA)と側頭動脈炎(GCA)の合併と診断し,副腎ステロイドによる治療を開始した.CRP, MPO-ANCAの陰性化を認め,腎機能も改善した.その後,日和見感染症を併発し死亡され剖検がなされた.剖検では,半月対形成性糸球体病変が証明された.本例はインフルエンザ・ワクチン接種を契機として2つの血管炎が同時に発症しており,組織学的に巨細胞性血管炎と微小血管炎が証明された世界初の報告である.血管炎症候群に共通する発症機序を示唆する貴重な症例と考えられた.

Microscopic polyangiitis

Granulomatosis with polyangiitis

10.2177/jsci.34.154

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Citations (12)

Cooperation of Sox4 with β-catenin/p300 complex in transcriptional regulation of the Slug gene during divergent sarcomatous differentiation in uterine carcinosarcoma

BMC Cancer (2016)

Hisako Inoue Hiroyuki Takahashi Miki Hashimura Koji Eshima Masashi Akiya

Uterine carcinosarcoma (UCS) represents a true example of cancer associated with epithelial-mesenchymal transition (EMT), which exhibits cancer stem cell (CSC)-like traits. Both Sox and β-catenin signal transductions play key roles in the regulation of EMT/CSC properties, but little is known about their involvement in UCS tumorigenesis. Herein, we focused on the functional roles of the Sox/β-catenin pathway in UCSs. EMT/CSC tests and transfection experiments were carried out using three endometrial carcinoma (Em Ca) cell lines. Immunohistochemical investigation was also applied for a total of 32 UCSs. Em Ca cells cultured in STK2, a serum-free medium for mesenchymal stem cells, underwent changes in morphology toward an EMT appearance through downregulation of E-cadherin, along with upregulation of Slug, known as a target gene of β-catenin. The cells also showed CSC properties with an increase in the aldehyde dehydrogenase (ALDH) 1high activity population and spheroid formation, as well as upregulation of Sox4, Sox7, and Sox9. Of these Sox factors, overexpression of Sox4 dramatically led to transactivation of the Slug promoter, and the effects were further enhanced by cotransfection of Sox7 or Sox9. Sox4 was also able to promote β-catenin-mediated transcription of the Slug gene through formation of transcriptional complexes with β-catenin and p300, independent of TCF4 status. In clinical samples, both nuclear β-catenin and Slug scores were significantly higher in the sarcomatous elements as compared to carcinomatous components in UCSs, and were positively correlated with Sox4, Sox7, and Sox9 scores. These findings suggested that Sox4, as well as Sox7 and Sox9, may contribute to regulation of EMT/CSC properties to promote development of sarcomatous components in UCSs through transcriptional regulation of the Slug gene by cooperating with the β-catenin/p300 signal pathway.

Slug

Beta-catenin

10.1186/s12885-016-2090-y

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Citations (37)

[A Case of Synchronous Diffuse Large B-Cell Lymphoma of the Right Breast and Invasive Ductal Carcinoma of the Left Breast].

PubMed (2019)

Tomoki Fujii Nobuhiro Ohno Tomoharu Matsui Naruhiko Sahara Satomi Yoneyama

A woman in her early 60s noticed bilateral breast masses and visited a different hospital. Core needle biopsy showed diffuse large B-cell lymphoma of the right breast and invasive ductal carcinoma of the left breast. After referral to our department, PET-CT was performed. Compared with mild fluorodeoxyglucose accumulation in left breast cancer(BC), highly accumulated lesions were found on the right breast, left anterior chest wall, nasopharynx, and tonsil. The right breast lesion was the largest with a diameter of 30mm and was considered the primary lesion of malignant lymphoma(ML). The ML was classified as stage Ⅳ, pathologically proven with erythema of the left breast and nasopharynx. Three courses of R-CHOP were performed. However, due to suspicion of heart failure, chemotherapy was changed to R-CEOP(non-anthracycline-containing regimen)and 3 courses were additionally performed. The therapeutic effect of R-Chemo for ML was CR. Left BC showed a tendency of shrinkage. After intrathecal administration of anticancer drugs to prevent infiltration of ML into the central nervous system and preoperative endocrine therapy with aromatase inhibitor, left lumpectomy and sentinel lymph node biopsy were performed. BC was classified as clinical stage ⅠA and had an estrogen receptor score of 3b. Postoperative whole breast radiotherapy was completed, and the planned internal use of exemestane was more than 5 years. With multidisciplinary therapy, 3.5 years had passed since the initial treatment without recurrence.

Lumpectomy

Exemestane

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Citations (1)

Cigarette smoking, CYP1A1 MspI and GSTM1 genotypes, and colorectal adenomas.

PubMed (2000)

Hisako Inoue Chikako Kiyohara Tomomi Marugame Sachiko Shinomiya Emiko Tsuji

Cigarette smoking has been related to increased risk of colorectal adenomas, but the underlying mechanisms are unknown. Genetic polymorphisms are known for enzymes involved in the activation of polycyclic aromatic hydrocarbons and other tobacco-related carcinogens. Polycyclic aromatic hydrocarbons are activated by cytochrome P4501A1 (CYP1A1) and detoxified by glutathione S-transferases. We investigated the relation of CYP1A1 MspI and GSTM1 genotypes to the risk of colorectal adenomas with special reference to interaction with cigarette smoking among 205 cases of colorectal adenomas and 220 controls with normal total colonoscopy in a male Japanese population. Cigarette smoking was strongly associated with increased risk of colorectal adenomas. Overall, neither the CYP1A1 MspI genotype nor the GSTM1 genotype was related to colorectal adenomas. A significant trend for increased risk of colorectal adenomas associated with smoking was observed for each of the CYP1A1 MspI genotypes, and the increasing trends did not differ by MspI genotype. The positive association between smoking and colorectal adenomas did not vary much with GSTM1 genotypes. Among former and current smokers, adenoma risk did not differ according to the combination of CYP1A1 MspI and GSTM1 genotypes. CYP1A1 MspI and GSTM1 genotypes do not seem to modify the risk of colorectal adenomas associated with cigarette smoking.

Colorectal adenoma

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Citations (48)

Pulmonary blastoma. Comparison between its epithelial components and fetal bronchial epithelium.

PubMed (1992)

Hisako Inoue K. Kasai Jun Shinada Hirokuni Yoshimura T Kameya

Three cases of pulmonary blastoma exhibiting biphasic epithelial and stromal patterns, and a case of fetal lung-type adenocarcinoma, were examined by immunohistochemistry and electron microscopy (EM) and compared with fetal bronchial epithelium in order to explore the multidirectional differentiation of their epithelial components. The glandular cells of all four tumors resembled fetal bronchial epithelial cells in the pseudoglandular stage. Neuroendocrine (NE) cells were also present; they were argyrophilic and expressed pan-NE markers, neurosecretory granules and peptide hormones. The neural cell adhesion molecule (NCAM) was strongly expressed on the cell membranes of glandular cells, as in the case of proximal bronchial epithelial cells at the pseudoglandular stage in fetal lung. Sialosylated Lewis X was also expressed, indicating that the epithelial cells were possibly of endodermal origin. Two of the four cases showed considerable immunoreactivity for alpha-fetoprotein (AFP). The epithelial cells of pulmonary blastomas may occasionally de-differentiate into cells functionally resembling fetal hepatic, foregut and yolk sac cells expressing AFP. Tumor examination by immunohistochemistry and EM suggested that the glandular cells of the tumors may differentiate to some extent like those of fetal large bronchi at the pseudoglandular stage, but there was concordance and discordance in the expression of neuroendocrine and oncofetal markers between blastomatous tumors and fetal bronchial epithelium.

Pulmonary Blastoma

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Citations (13)

Transcriptional upregulation of HIF-1α by NF-κB/p65 and its associations with β-catenin/p300 complexes in endometrial carcinoma cells

Laboratory Investigation (2013)

Tsutomu Yoshida Miki Hashimura Toshihide Mastumoto Yuki Tazo Hisako Inoue

Hypoxia

10.1038/labinvest.2013.111

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Citations (53)

Rituximab maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis in Japan

Figshare (2020)

Yukiko Takeyama Nobuyuki Ono Yuri Shirahama Yasushi Inoue Atsushi Tanaka

We examined the efficacy and safety of rituximab (RTX) maintenance therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan. We conducted a retrospective study using a multi-center cohort database of vasculitis patients. All maintenance treatment courses were divided into three groups: a RTX group, a group treated with other immunosuppressant drugs (IS) and a group receiving glucocorticoid monotherapy (GC). The primary endpoint was the comparison of relapse-free survival after 1 year. We also analyzed the occurrence of severe adverse events (SAEs) to assess safety. We included 123 courses of 107 patients (RTX n = 14, IS n = 64, GC n = 45). Twelve of 14 in the RTX group patients were diagnosed with granulomatosis with polyangiitis (GPA). The relapse-free survival of RTX maintenance therapy was comparable to that in the other groups (p = .122). After 1 year of treatment, the RTX group was administered lower steroid doses and one-third of them could withdraw corticosteroid. The overall incidence of SAE was 0.54/patient-year in the RTX group, 0.39/patient-year in the IS group and 0.34/patient-year in the GC group. RTX maintenance therapy could be effective and safe in Japanese GPA patients.

Maintenance therapy

ANCA-Associated Vasculitis

10.6084/m9.figshare.12850811

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