Faculty Profiles - MATSUKAWA Akihiro

Papers - MATSUKAWA Akihiro

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Overexpression of SOCS3 Attenuates Tracheal Allograft Rejection in the Early Phase After Murine Heterotopic Tracheal Transplantation by the Inhibition of Th1 Response Reviewed

K. Mesaki, S. Sugimoto, H. Watanabe, M. Fujisawa, T. Yoshimura, T. Kurosaki, S. Otani, M. Yamane, S. Toyooka, A. Matsukawa, T. Oto

The Journal of Heart and Lung Transplantation 37 ( 4 ) 2018.4

miRNA-133a-5p Inhibits the Expression of Osteoblast Differentiation-Associated Markers by Targeting the 3' UTR of RUNX2. Reviewed International journal

Wei Zhang, Yonggang Wu, Yasuyuki Shiozaki, Yoshihisa Sugimoto, Tomoyuki Takigawa, Masato Tanaka, Akihiro Matsukawa, Toshifumi Ozaki

DNA and cell biology 37 ( 3 ) 199 - 209 2018.3

Language：English Publishing type：Research paper (scientific journal)

Recent studies have recognized the involvement of microRNAs (miRNAs) in the development of osteoporosis, which regulate the balance between osteogenesis and osteoclasis. In this study, we investigated the regulation by miRNA-133a-5p on the osteoblast differentiation-associated markers in the mouse osteoblast-like MC3T3-E1 cells by RUNX2. First, we manipulated the miRNA-133a level in the MC3T3-E1 cells with 20 or 40 nM miR-133a-5p mimics, miR-133a-5p inhibitor, or scramble miRNA. Then, we quantified with real-time polymerase chain reaction (qRT-PCR) the expression of Collagen I, osteocalcin (OCN), and osteopontin (OPN) in the miR-133a-5p-manipulated MC3T3-E1 cells. And the confocal microscopy was also utilized to confirm the regulation by miR-133a-5p on the expression of the three molecules. We also investigated the extracellular matrix (ECM) mineralization and the alkaline phosphatase (ALP) activity in the miR-133a-5p-manipulated MC3T3-E1 cells. In addition, we explored the possible targeting by miR-133a-5p on RUNX2, which was a well-recognized promoter to osteoblast differentiation, with luciferase reporter, qRT-PCR, and Western blotting assay. Results demonstrated that the miRNA-133a-5p mimics markedly reduced, whereas the miRNA-133a-5p inhibitor significantly promoted the expression of Collagen I, OCN, and OPN, the ECM mineralization, and the ALP activity in MC3T3-E1 cells. The alignment analysis demonstrated a high homology between miRNA-133a-5p and the 3' UTR of RUNX2. Moreover, the luciferase reporter assay demonstrated that miRNA-133a-5p targeted the 3' UTR of RUNX2, and inhibited the expression of RUNX2 in both mRNA and protein levels. In conclusion, we identified the inhibition by miRNA-133a-5p to the expression of osteoblast differentiation markers, to the ECM mineralization, and to the ALP activity in MC3T3-E1 cells, by targeting the 3' UTR of RUNX2. Our study suggests that miRNA-133a-5p might be an important target to inhibit osteoblast differentiation in osteoporosis.

DOI： 10.1089/dna.2017.3936

ラット脊椎固定モデルにおけるrhBMP2添加リン酸化プルランフィルムの有用性の検討

宇川諒, 塩崎泰之, 村岡聡介, 吉田晶, 瀧川朋亨, 三澤治夫, 尾崎敏文, 松川昭博

Journal of Spine Research 9 ( 3 ) 542 - 542 2018.3

Spred2 Deficiency Exacerbates D-Galactosamine/Lipopolysaccharide -induced Acute Liver Injury in Mice via Increased Production of TNFα. Reviewed International journal

Xu Yang, Masayoshi Fujisawa, Teizo Yoshimura, Toshiaki Ohara, Miwa Sato, Megumi Mino, Thar Htet San, Tong Gao, Steven L Kunkel, Akihiro Matsukawa

Scientific reports 8 ( 1 ) 188 2018.1

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Acute liver injury (ALI) is characterized by hepatocyte damage and inflammation. In the present study, we examined whether the absence of Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, influences ALI induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS). Compared to wild-type mice, Spred2-/- mice developed exacerbated liver injury represented by enhanced hepatocyte damage and inflammation. Enhanced ERK activation was observed in Spred2-/--livers, and the MEK/ERK inhibitor U0126 ameliorated ALI. Hepatic tumour necrosis factor α (TNFα) and interleukin (IL)-1β levels were increased in Spred-2-/--livers, and the neutralization of TNFα dramatically ameliorated ALI, which was associated with decreased levels of endogenous TNFα and IL-1β. When mice were challenged with D-GalN and TNFα, much severer ALI was observed in Spred2-/- mice with significant increases in endogenous TNFα and IL-1β in the livers. Immunohistochemically, Kupffer cells were found to produce TNFα, and isolated Kupffer cells from Spred2-/- mice produced significantly higher levels of TNFα than those from wild-type mice after LPS stimulation, which was significantly decreased by U0126. These results suggest that Spred2 negatively regulates D-GalN/LPS-induced ALI under the control of TNFα in Kupffer cells. Spred2 may present a therapeutic target for the treatment of ALI.

DOI： 10.1038/s41598-017-18380-0

Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin- furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord Injury. Reviewed International journal

Yamane K, Mazaki T, Shiozaki Y, Yoshida A, Shinohara K, Nakamura M, Yoshida Y, Zhou D, Kitajima T, Tanaka M, Ito Y, Ozaki T, Matsukawa A

Scientific reports 8 ( 1 ) 917 2018.1

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

The treatment of spinal cord injury (SCI) is currently a significant challenge. Hepatocyte growth factor (HGF) is a multipotent neurotrophic and neuroregenerative factor that can be beneficial for the treatment of SCI. However, immobilized HGF targeted to extracellular matrix may be more effective than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF remained in the spinal cord for 7 days after a single administration, while unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA) hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single administration of CBD-HGF enhanced recovery from spinal cord compression injury compared with HGF, as determined by motor recovery, and electrophysiological and immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. These results suggest that engineered CBD-HGF has superior therapeutic effects than naïve HGF. CBD-HGF combined with hydrogel scaffold may be promising for the treatment of serious SCI.

DOI： 10.1038/s41598-018-19316-y

Ovarian stromal cells as a source of cancer-associated fibroblasts in human epithelial ovarian cancer: A histopathological study. Reviewed International journal

Masayoshi Fujisawa, Aye Moh-Moh-Aung, Zheng Zeng, Teizo Yoshimura, Yoji Wani, Akihiro Matsukawa

PloS one 13 ( 10 ) e0205494 2018

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Fibroblasts are a major component of cancer tissue and known to contribute to cancer progression. However, it remains unknown whether they are derived from local fibroblasts or of other origin. This study was designed to identify the contribution of local stromal cells to cancer stroma in human epithelial ovarian cancer. Seventy-six cases of surgically resected primary ovarian carcinoma (48 cases confined to the ovaries and 28 cases with distant metastases) and 17 cases of secondary ovarian tumor (e.g. colon cancer metastasized to the ovary) were enrolled in this study. The tissues were immunostained for forkhead box protein L2 (FOXL2), a transcription factor crucial for ovarian development and function, and markers for cancer-associated fibroblasts (CAFs) and inflammatory cells. Under normal condition, FOXL2 expression was restricted to ovarian stromal cells and some other types of cells in female genital tracts and never found in other sites of the body. FOXL2-positive cells were found in all primary and secondary tumors in the ovary, and were the dominant stromal cells in most cases. In contrast, only a few FOXL2-positive cells were found in peritoneal seeding sites of four serous carcinoma cases, and all the other tumors at extraovarian sites had no FOXL2-positive cells. FOXL2-positive cells in the ovarian lesion variably expressed CAFs markers, such as alpha-smooth muscle actin and fibroblast activating protein, as determined by double immunostaining. Background inflammation, but not histological subtype or origin of the neoplasm seemed to correlate with the proportion of FOXL2-positive cells. These results suggest that ovarian stromal cells are the main source of cancer stroma in the ovary but do not seem to move to distant sites via circulation together with tumor cells. Our results also support the hypothesis that cancer-associated fibroblasts may originate locally, which was previously demonstrated using animal models.

DOI： 10.1371/journal.pone.0205494

Iron depletion is a novel therapeutic strategy to target cancer stem cells. Reviewed International journal

Takayuki Ninomiya, Toshiaki Ohara, Kazuhiro Noma, Yuki Katsura, Ryoichi Katsube, Hajime Kashima, Takuya Kato, Yasuko Tomono, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Fumiaki Kimura, Ling Chen, Tomonari Kasai, Masaharu Seno, Akihiro Matsukawa, Toshiyoshi Fujiwara

Oncotarget 8 ( 58 ) 98405 - 98416 2017.11

Language：English Publishing type：Research paper (scientific journal)

Adequate iron levels are essential for human health. However, iron overload can act as catalyst for the formation of free radicals, which may cause cancer. Cancer stem cells (CSCs), which maintain the hallmark stem cell characteristics of self-renewal and differentiation capacity, have been proposed as a driving force of tumorigenesis and metastases. In the present study, we investigated the role of iron in the proliferation and stemness of CSCs, using the miPS-LLCcm cell model. Although the anti-cancer agents fluorouracil and cisplatin suppressed the proliferation of miPS-LLCcm cells, these drugs did not alter the expression of stemness markers, including Nanog, SOX2, c-Myc, Oct3/4 and Klf4. In contrast, iron depletion by the iron chelators deferasirox and deferoxamine suppressed the proliferation of miPS-LLCcm cells and the expression of stemness markers. In an allograft model, deferasirox inhibited the growth of miPS-LLCcm implants, which was associated with decreased expression of Nanog and Sox2. Altogether, iron appears to be crucial for the proliferation and maintenance of stemness of CSCs, and iron depletion may be a novel therapeutic strategy to target CSCs.

DOI： 10.18632/oncotarget.21846

Corrigendum: Induction of monocyte chemoattractant proteins in macrophages via the production of Granulocyte/Macrophage Colony-Stimulating Factor By Breast Cancer Cells [Front Immunol, 7, (2016) (2)] DOI:10.3389/fimmu.2016.00002 Reviewed

Teizo Yoshimura, Tomozumi Imamichi, Jonathan M. Weiss, Miwa Sato, Liangzhu Li, Akihiro Matsukawa, Ji Ming Wang

Frontiers in Immunology 8 2017.11

Spred2-deficiecy Protects Mice from Polymicrobial Septic Peritonitis by Enhancing Inflammation and Bacterial Clearance Reviewed International journal

Junya Itakura, Miwa Sato, Toshihiro Ito, Megumi Mino, Soichiro Fushimi, Sakuma Takahashi, Teizo Yoshimura, Akihiro Matsukawa

SCIENTIFIC REPORTS 7 ( 1 ) 12833 2017.10

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Sepsis is an infection-induced systemic inflammatory syndrome and a major cause of death for critically ill patients. Here, we examined whether the absence of Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, influences host defense against polymicrobial sepsis (PMS) induced by cecal ligation and puncture (CLP). Compared to wildtype mice, Spred2(-)/(-) mice exhibited higher survival rates with increased level of leukocyte infiltration and local chemokine production and reduced plasma and peritoneal bacterial loads after CLP. The MEK inhibitor U0126 significantly reduced LPS-induced chemokine production by Spred2(-)/(-) resident macrophages in vitro, and decreased CLP-induced leukocyte infiltration in vivo. Spred2(-)/(-)resident macrophages, but not neutrophils or elicited macrophages, exhibited increased phagocytic activity. Interestingly, surface expression of complement receptor 1/2 (CR1/2) was increased in Spred2(-)/(-) resident macrophages in response to lipopolysaccharide in a manner dependent on the ERK/MAPK pathway, and blocking CR1/2 in vivo resulted in reduced leukocyte infiltration and increased bacterial loads after CLP. Taken together, our results indicate that Spred2-deficiency protects mice from PMS via increased activation of the ERK/MAPK pathway and subsequent increase in innate immune responses. Thus, inhibiting Spred2 may present a novel means to prevent the development of PMS.

DOI： 10.1038/s41598-017-13204-7

The STAT4/MLL1 Epigenetic Axis Regulates the Antimicrobial Functions of Murine Macrophages Reviewed International journal

William F. Carson, Karen A. Cavassani, Elyara M. Soares, Soichiro Hirai, Nicolai A. Kittan, Matthew A. Schaller, Melissa M. Scola, Amrita Joshi, Akihiro Matsukawa, David M. Aronoff, Craig N. Johnson, Yali Dou, Katherine A. Gallagher, Steven L. Kunkel

JOURNAL OF IMMUNOLOGY 199 ( 5 ) 1865 - 1874 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC IMMUNOLOGISTS

Macrophages are critical immune cells for the clearance of microbial pathogens and cellular debris from peripheral tissues. Macrophage inflammatory responses are governed by gene expression patterns, and these patterns are often subject to epigenetic control. Chromatin modifications, such as histone methylation, regulate gene accessibility in macrophages, and macrophage polarization is governed in part by the expression and function of chromatin-modifying enzymes. The histone methyltransferase mixed-lineage leukemia 1 (MLL1) preferentially modifies lysine residue 4 on the unstructured protein tail of histone H3. MLL1 expression and function have been shown to be governed by signal transduction pathways that are activated by inflammatory stimuli, such as NF-kappa B. Therefore, we sought to investigate the role of MLL1 in mediating macrophage inflammatory responses. Bone marrow-derived macrophages from mice with a targeted MLL1 gene knockout (Lys2-Cre(+/-) MLL1(fx/fx)) exhibited decreased proinflammatory gene expression with concurrent decreases in activating histone methylation. However, MLL1-deficient macrophages also exhibited increased phagocytic and bacterial killing activity in vitro. RNA profiling of MLL1-knockout macrophages identified numerous genes involved with inflammatory responses whose expression was altered in response to TLR ligands or proinflammatory cytokines, including STAT4. STAT4-dependent cytokines, such as type I IFNs were able to drive MLL1 expression in macrophages, and MLL1-knockout macrophages exhibited decreased activating histone methylation in the STAT4 promoter. These results implicate an important role for MLL1-dependent epigenetic regulation of macrophage antimicrobial functions.

DOI： 10.4049/jimmunol.1601272

多糖複合体を担体とした抗菌薬伝達システムの開発

渡邉典行, 吉田晶, 田中雅人, 松川昭博, 尾崎敏文

日本整形外科学会雑誌 91 ( 8 ) S1661 - S1661 2017.8

Molecular Subtypes of Breast Cancers from Myanmar Women: A Study of 91 Cases at Two Pathology Centers Reviewed International journal

Thar Htet San, Masayoshi Fujisawa, Soichiro Fushimi, Lamin Soe, Ngu Wah Min, Teizo Yoshimura, Toshiaki Ohara, Myint Myint Yee, Shinsuke Oda, Akihiro Matsukawa

Asian Pacific journal of cancer prevention : APJCP 18 ( 6 ) 1617 - 1621 2017.6

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Background: Breast cancer is the most common cancer in Myanmar women. Revealing the hormonal receptor
status, human epidermal growth factor receptor 2 (HER2) and Ki-67 expression is useful for estimating patient
prognosis as well as determination of treatment strategy. However, immunohistochemical features and classification of
molecular subtypes in breast cancers from Myanmar remain unknown. Methods: The clinicopathological features of
91 breast cancers from Myanmar women were examined. Immunohistochemistry was performed on tissue specimens
with antibodies to estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki-67, cytokeratin (CK)5/6 and CK14.
Immunohistochemistry-based molecular subtyping was conducted. Results: Breast cancers in Myanmar women were
relatively large, high grade with frequent metastatic lymph nodes. Of the 91 patients, tumors with ER positive, PgR
positive, and HER2 positive were 57.1%, 37.4%, and 28.6%, respectively. The most prevalent subtype was luminal B
(HER2-) (39.6%), followed by HER2 (22.0%), triple negative (TN)-basal-like (12.1%), luminal A (11.0%), TN-null
(8.8%) and luminal B (HER2+) (6.6%). The mean Ki-67 expression of 91 cases was 33.9% (33.9% ± 19.2%) and the
median was 28% (range; 4%-90%). The mean Ki-67 expression of luminal A, luminal B, HER2 and TN-basal-like/
null was 7%, 30%, 40%, and 57%/43%, respectively. A higher Ki-67 expression significantly correlated with a higher
grade, larger size and higher stage of malignancy. Conclusions: We, for the first time, investigated the histopathological
features of breast cancers from Myanmar women. Myanmar breast cancers appeared to be aggressive in nature, as
evidenced by high frequency of poor-prognosis subtypes with high level of Ki-67 expression.

DOI： 10.22034/APJCP.2017.18.6.1617

Low prevalence of human mammary tumor virus (HMTV) in breast cancer patients from Myanmar Reviewed International journal

Thar Htet San, Masayoshi Fujisawa, Soichiro Fushimi, Teizo Yoshimura, Toshiaki Ohara, Lamin Soe, Ngu Wah Min, Ohnmar Kyaw, Xu Yang, Akihiro Matsukawa

INFECTIOUS AGENTS AND CANCER 12 ( 1 ) 60 - 66 2017.4

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: Human mammary tumor virus (HMTV) is 90-95% homologous to mouse mammary tumor virus (MMTV), one of the causal agents of murine mammary tumors. HMTV (MMTV-like) sequences were reported to be present in human breast cancers from several populations with a prevalence range of 0-78%; however, the prevalence of HMTV in breast cancers from Myanmar remains unknown.
Methods: Fifty-eight breast cancer samples from Myanmar women were examined in this study. DNA was isolated from formalin-fixed paraffin-embedded specimens, and HMTV envelope sequences were detected by semi-nested PCR. The sequence of the PCR products was also confirmed.
Results: Only 1.7% (1 of 58) of the breast cancers were positive for HMTV, and the sequence of PCR products was 98.9% identical to the reference HMTV sequence (GenBank accession No. AF243039). The tumor with HMTV was grade III invasive ductal carcinoma, 7.0 cm in size with lymph node metastasis (T3, N1, M0).
Conclusions: We, for the first time, investigated the presence of HMTV in Myanmar breast cancer patients. In accordance with other Asian studies, the prevalence of HMTV in Myanmar was quite low, supporting the hypothesis that Asian breast cancers have different etiologies than in Western countries, where HMTV is more prevalent.

DOI： 10.1186/s13027-017-0130-0

緑内障手術のサイエンス - 濾過手術とサイトカインを中心に

井上俊洋, 谷原秀信, 布田龍佑, 福島美紀子, 伊藤康裕, 川路隆博, 岩尾圭一郎, 高橋枝里, 藤本智和, 井上みゆき, 岩尾美奈子, 笠岡奈々子, 原竜平, 正林耕平, 榮木大輔, 大平さおり, 後藤章子, 小島祥, 芳賀彰, 黒田詩子, 中島圭一, 平川沙織, 福島亜矢子, 松村理世, 徳永瞳, 川畑和幸, 北村文香, 西澤麻保, 二口亜希子, 松本桃佳, 吉村長久, 亀田隆範, 吉田晃敏, 川井基史, 川井尚子, 木下茂, 上田真由美, 古賀彩加, 稲谷大, 瀧原祐史, 本庄恵, 石井優, 菊田順一, 古家雅之, 松川昭博, 猿渡淳二, 田賀哲也, 鹿川哲史

日本眼科学会雑誌 121 ( 3 ) 314 - 335 2017

Language：Japanese Publisher：(公財)日本眼科学会

緑内障に対する手術治療は流出路再建術,濾過手術,毛様体破壊/凝固術に大別される.理想的な効果と安全性を兼ね備えた術式はないが,その中で眼圧下降効果は濾過手術が優るといえる.濾過手術の一種である線維柱帯切除術は最も標準的な緑内障手術の一つであり,優れた眼圧下降効果を有する一方で,術後に過剰な創傷治癒に伴って眼圧コントロール不良となる症例が一定数存在し,重篤な術中・術後合併症もまれではない.したがって,緑内障手術成績のさらなる改善は緑内障診療において重要な命題であり,本総説では,この命題に取り組むべく,我々が多面的に行ってきた臨床研究および基礎研究について紹介し,その成果と新しい試みについて論じた.まず,臨床成績の解析から,白内障手術の既往および施行が線維柱帯切除術の手術成績に一定の影響を与えることが明らかとなった.また硝子体手術既往眼,緑内障手術既往眼は手術既往なしと比較して,ぶどう膜炎に伴う緑内障,血管新生緑内障,家族性アミロイドポリニューロパチーに伴う緑内障は一般的に原発開放隅角緑内障と比較して線維柱帯切除術の成績が不良であった.これらの危険因子は眼内環境に変化を及ぼし,その結果,線維柱帯切除術の創傷治癒に影響が及び,最終的に眼圧コントロールが不良となったと考えられる.次に,背景因子が眼内環境に及ぼした変化に焦点を当て,房水サイトカインに着目して解析を行った.白内障手術既往眼では術後1年以上経過してもinterleukin(IL)-6,IL-8,monocyte chemoattractant protein(MCP)-1などの炎症性サイトカインの濃度が高値であった.これらのサイトカイン濃度は互いに正の相関があるとともに,ぶどう膜炎に伴う緑内障や血管新生緑内障でさらに高値であり,複合的に創傷治癒に影響を与えていることが示唆された.このうち房水内MCP-1は線維柱帯切除術術後成績に影響を与える因子と確認された.さらに,眼内の環境変化が濾過胞に与える影響を詳細に観察するために,我々は三次元光干渉断層計を用いた定量的な濾過胞解析を行った.三次元的な解析によって線維柱帯切除術術後の強膜弁縁における開口部を同定し,術中所見からこれが濾過胞への房水流出路となっていることを確認した.前向き研究によって,この開口部の幅は時間経過とともに狭くなり将来的な眼圧コントロールに関係することが示唆されるとともに,房水内MCP-1濃度と相関していることが明らかとなった.最後に,線維柱帯切除術術後の創傷治癒機転を細胞レベルで理解するために,マクロファージと結膜線維芽細胞を用いた細胞生物学的な実験を行った.創傷治癒機転において,マクロファージなどの関与によって線維芽細胞が筋線維芽細胞化することが重要であることが分かっている.この変化をROCK阻害薬やエピジェネティック薬が抑制することを見出した.また,2光子顕微鏡を用いた生体イメージングにより,手術によって結膜下の炎症細胞の動態は大きく影響を受けることが確認された.眼内環境の病的シフトをリスクの低い状態に近づけることを目的とした抗MCP-1治療やレセプターであるCCR2の阻害薬は,緑内障手術成績改善の試みの新たな糸口となる可能性を秘めていると考えられた.(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01049&link_issn=&doc_id=20170316410005&doc_link_id=%2Fdz1nigan%2F2017%2F012103%2F005%2F0314-0335%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz1nigan%2F2017%2F012103%2F005%2F0314-0335%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Tumor-Associated Macrophages in the Development of 4-Nitroquinoline-1-Oxide-Induced Tongue Squamous Cell Carcinoma in a Mouse Model Reviewed International journal

Kentaro Miki, Yorihisa Orita, Yuka Gion, Soshi Takao, Kyotaro Ohno, Mai Takeuchi, Toshihiro Ito, Akira Minoura, Tomoyasu Tachibana, Hidenori Marunaka, Takuma Makino, Akihiro Matsukawa, Kazunori Nishizaki, Tadashi Yoshino, Yasuharu Sato

ONCOLOGY 93 ( 3 ) 204 - 212 2017

Language：English Publishing type：Research paper (scientific journal) Publisher：KARGER

Objective: We aimed to determine the distribution of tumor-associated macrophages (TAMs) in the development of tongue squamous cell carcinoma (SCC) and to elucidate the role of TAMs in the progression of tongue SCC. Methods: The expression of the macrophage markers nitric oxide synthase, Retnla, and mannose receptor 1 in the development of tongue SCC was longitudinally observed using real-time quantitative polymerase chain reaction. Additionally, an immunohistochemical study using an anti-mannose receptor (MR) antibody was performed. Results: The numbers of both of M1 and M2 macrophages in the tongues of mice treated with 4-nitroquinoline-1-oxide (4NQO) were significantly lower compared with those of normal tongues. The cyclo-oxygenase-2 (COX-2) inhibitor did not prevent cancer progression and did not affect the total number of macrophages in the tongues of 4NQO-treated mice. In the immunohistochemical studies, MR staining was observed in lymphangio-endothelium in the subepithelial area of the tongues. The staining intensity of the MR was significantly stronger in the 4NQO-treated mice compared with that in control mice and 4NQO-treated mice treated with the COX-2 inhibitor. Conclusion: TAMs may not contribute to the development of 4NQO-induced tongue SCC. MR expression is associated with the progression of 4NQO-induced tongue SCC. (C) 2017 S. Karger AG, Basel

DOI： 10.1159/000477301

多忙生嚢胞性変化を呈した輪状細管を伴う性策腫瘍（SCAT）の一例

太田陽子, 伏見聡一郎, 堀田真智子, タテサン, 内野かおり, 藤澤真義, 和仁洋治, 松川昭博

診断病理 34 ( 3 ) 231 - 235 2017

Language：Japanese Publisher：(一社)日本病理学会

多房化した肉眼形態を示し、術前診断が困難であったsex cord tumor with annular tubules(SCTAT)の1例を経験したので報告する。症例は月経不順でホルモン治療中の20代女性。増大傾向の右卵巣腫瘍を指摘され、臨床的には境界悪性ないし悪性の粘液性腫瘍が疑われ手術が行われた。腫瘍は多房性嚢胞性、肥厚した壁の部分には腫瘍細胞の輪状細管を含む胞巣を認めた。免疫染色ではinhibin-αとFOXL2が陽性、遺伝子解析ではFOXL2(C134W)変異はなく、SCTATと診断した。(著者抄録)

前頭葉に発生し，てんかん原性を示した髄膜腫合併髄膜血管腫症の1例

河原明奈, 伏見聡一郎, 板倉淳哉, 藤澤真義, 小林勝弘, 林裕美子, 伊達勲, 上利崇, 柳井広之, 松川昭博

診断病理 34 ( 1 ) 46 - 50 2017

Language：Japanese Publisher：(一社)日本病理学会

17歳、男性。てんかん発作を幼少期より繰り返していた。3歳時の頭部CTでは病変を指摘されなかったが、13歳時に左中前頭回の脳表に石灰化を伴う病変を認めた。発作頻度が増したため、17歳時に病変とその直下のてんかん焦点を含む左前頭葉部分切除術が施行された。脳表側では砂粒体と渦巻き状に紡錘形細胞が認められ、移行性髄膜腫であった。大脳側では血管が網目状に増生し、血管周囲には髄膜皮細胞が取り巻く髄膜血管腫症であった。症状や画像の経過より髄膜血管腫症が先行し、その後髄膜腫が合併したと考えられた。(著者抄録)

Internationalization of medical education

Matsukawa Akihiro

Okayama Igakkai Zasshi (Journal of Okayama Medical Association) 129 ( 3 ) 195 - 197 2017

超音波内視鏡下穿刺吸引術(EUS-FNA)で得られたgangliocytic paragangliomaの細胞像の検討

河合穂高, 伏見聡一郎, 板倉淳哉, 井上博文, 藤井昌江, 武部祐一郎, 松川昭博

日本臨床細胞学会雑誌 55 ( 6 ) 376 - 381 2016.11

Language：Japanese Publisher：(公社)日本臨床細胞学会

背景:Gangliocytic paraganglioma(GP)は、十二指腸乳頭部に好発するまれな腫瘍で、主として粘膜下に存在するため、生検による確定診断は困難なことが多い。EUS-FNAは術前診断の有効な方法として期待されるが、その報告は少ない。症例:60歳代、男性。タール便を主訴に上部消化管内視鏡が施行された。生検では十二指腸粘膜のみしか得られなかった。EUS-FNA検体では、細顆粒状クロマチンを有する短紡錘形〜類円形の核をもつ紡錘形細胞に加え、少数ながら核小体の目立つ大型細胞も認められた。多彩な細胞像を呈し、核所見などから神経内分泌系の腫瘍が疑われた。膵十二指腸切除検体では十二指腸乳頭部の近傍に粘膜下腫瘍が認められた。組織学的に腫瘍は、Zellballen配列をとる上皮様細胞、明瞭な核小体をもつ神経節細胞様細胞、束状の紡錘形細胞(支持細胞)の3成分から構成されていた。最終的にGPと病理診断された。結論:EUS-FNA検体では必ずしも3成分の細胞が採取されない可能性がある。しかし、3成分の細胞が正しく採取され、さらにセルブロックの免疫組織化学的検討を加えれば、診断は可能と思われた。(著者抄録)

DOI： 10.5795/jjscc.55.376

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J01209&link_issn=&doc_id=20170214130003&doc_link_id=10.5795%2Fjjscc.55.376&url=https%3A%2F%2Fdoi.org%2F10.5795%2Fjjscc.55.376&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation Reviewed International journal

Sakuma Takahashi, Teizo Yoshimura, Takahiro Ohkura, Masayoshi Fujisawa, Soichiro Fushimi, Toshihiro Ito, Junya Itakura, Sakiko Hiraoka, Hiroyuki Okada, Kazuhide Yamamoto, Akihiro Matsukawa

SCIENTIFIC REPORTS 6 37531 2016.11

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Rapid and adequate mucosal healing is important for a remission of ulcerative colitis (UC) patients. Here, we examined whether Spred2, a member of the Sprouty-related EVH1-domain-containing proteins that inhibit the Ras/Raf/ERK pathway, plays a role in colonic mucosal homeostasis and inflammation by using Spred2 knockout (KO) mice. We first detected increased epithelial cell proliferation and cadherin 1 expression in the colon of naive Spred2 KO mice compared to wild-type mice. Interestingly, Spred2 KO mice were resistant to dextran sulfate sodium (DSS)-induced acute colitis as indicated by lower levels of body weight loss and disease activity index. Histologically, epithelial cell injury and inflammation were milder in the colonic mucosa of Spred2 KO mice on day 3 and almost undetectable by day 8. Experiments with bone chimeric mice indicated that Spred2 deficiency in non-hematopoietic cells was responsible for the reduced sensitivity to DSS. Finally, Spred2 KO mice developed significantly fewer tumors in response to azoxymethane plus DSS. Taken together, our results demonstrate, for the first time, that Spred2 plays an important role in the regulation of colonic epithelial cell proliferation and inflammation by potentially down-regulating the activation of ERK. Thus, Spred2 may be a new therapeutic target for the treatment of UC.

DOI： 10.1038/srep37531

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