研究者詳細 - 小山内　誠

論文 - 小山内　誠

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Establishment and characterization of the novel myxofibrosarcoma cell line, SMU-MFS

Naoya Nakahashi, Makoto Emori, Kohichi Takada, Yasutaka Murahashi, Junya Shimizu, Kazuyuki Murase, Tomohide Tsukahara, Shintaro Sugita, Akira Takasawa, Kousuke Iba, Atsushi Teramoto, Makoto Osanai

Human Cell ( Springer Science and Business Media LLC ) 38 ( 1 ) 2024年12月

DOI

Multilayered proteomics reveals that JAM-A promotes breast cancer progression via regulation of amino acid transporter LAT1.

Kazufumi Magara, Akira Takasawa, Kumi Takasawa, Tomoyuki Aoyama, Misaki Ota, Daisuke Kyuno, Yusuke Ono, Taro Murakami, Soh Yamamoto, Yuna Nakamori, Naoya Nakahashi, Goro Kutomi, Ichiro Takemasa, Tadashi Hasegawa, Makoto Osanai

Cancer science 2024年06月 [国際誌]

Recent studies have shown that transmembrane-type tight junction proteins are upregulated in various cancers compared with their levels in normal tissues and are involved in cancer progression, suggesting that they are potential therapeutic targets. Here, we demonstrated the expression profile and a novel role of junctional adhesion molecule-A (JAM-A) in breast cancer. Immunohistochemistry of surgical specimens showed that JAM-A was highly expressed from carcinoma in situ lesions, as in other adenocarcinomas, with higher expression in invasive carcinomas. High expression of JAM-A contributed to malignant aspects such as lymph node metastasis and lymphatic involvement positivity. In breast cancer cells, JAM-A expression status affects malignant potentials including proliferation and migration. Multilayered proteomics revealed that JAM-A interacts with the amino acid transporter LAT1 in breast cancer cells. JAM-A regulates the expression of LAT1 and interacts with it on the whole cell membrane, leading to enhanced amino acid uptake to promote tumor growth. Double high expression of JAM-A and LAT1 predicts poor prognosis in patients with breast cancer. Of note, an antibody against an extracellular domain of JAM-A suppressed the proliferation of breast cancer cells. Our findings indicate the possibility of JAM-A-targeted therapy ideally combined with LAT1-targeted therapy as a new therapeutic strategy against breast cancer.

DOI PubMed

Vitamin D-metabolizing enzyme CYP24A1 affects oncogenic behaviors of oral squamous cell carcinoma and its prognostic implication.

Yuna Nakamori, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Naoya Nakahashi, Shohei Sekiguchi, Kei Tsuchihashi, Akihiro Miyazaki, Makoto Osanai

Medical molecular morphology 2024年05月 [国内誌]

Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy.

DOI PubMed

MPNSTで異常発現するPVRはがん悪性化に寄与し,治療標的となりうる

中橋尚也, 江森誠人, 高澤久美, 太田未咲, 真柄和史, 小野祐輔, 及能大輔, 杉田真太朗, 長谷川匡, 小山内誠, 高澤啓

日本整形外科学会雑誌 ( (公社)日本整形外科学会 ) 98 ( 2 ) S194 - S194 2024年03月

膵癌の進展におけるClaudin-1の機能(The role of Claudin-1 in Pancreatic Cancer)

浅野日南英, 及能大輔, 奥村礼央菜, 真柄和史, 小野佑輔, 高澤久美, 高澤啓, 小山内誠

日本病理学会会誌 ( (一社)日本病理学会 ) 113 ( 1 ) 474 - 474 2024年02月

乳癌患者における癌幹細胞マーカーに対する血中自己抗体価と術後予後の相関(Autoantibodies against breast cancer stem cells are associated with a poor prognosis in patients)

奥村礼央菜, 及能大輔, 水江由佳, 廣橋良彦, 浅野日南英, 真柄和史, 小野佑輔, 小山内誠

日本病理学会会誌 ( (一社)日本病理学会 ) 113 ( 1 ) 475 - 475 2024年02月

胎盤FFPE組織を用いた比較プロテオーム解析による妊娠高血圧症候群のバイオマーカー探索(Biomarker analysis of hypertensive disorders of pregnancy by proteomics from placental FFPE tissues)

太田未咲, 高澤啓, 高澤久美, 真柄和史, 小野佑輔, 及能大輔, 杉田真太朗, 長谷川匡, 小山内誠

日本病理学会会誌 ( (一社)日本病理学会 ) 113 ( 1 ) 328 - 328 2024年02月

Common pathological findings in the heart in COVID-19-related sudden death cases: An autopsy case series.

Daisuke Kyuno, Masatoshi Tateno, Yusuke Ono, Kazufumi Magara, Kumi Takasawa, Akira Takasawa, Makoto Osanai

Heliyon 9 ( 10 ) e20564 2023年10月 [国際誌]

BACKGROUND: Cardiomyopathy is a leading cause of sudden out-of-hospital death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. Such unexpected COVID-19-related cardiomyopathies are challenging to diagnose as specific pathological findings are not always identified. CASE SUMMARY: We reported the autopsy findings of two cases of sudden death due to COVID-19-related cardiomyopathies. In one case, death occurred after SARS-CoV-2 infection, while in the other, after COVID-19 vaccination. We found common pathological findings in both hearts: decreased staining intensity with special stains, loss of rhabdomeres, and multivacuolation in cardiomyocytes without inflammatory cell infiltration. The remaining organs showed no findings that could have contributed to the deaths. CONCLUSION: In cases of sudden death after SARS-CoV-2 infection or COVID-19 vaccination, the decreased staining intensity with special stains may aid the diagnosis of sudden death due to COVID-19-related cardiomyopathy, even when H&E staining shows few findings.

DOI PubMed

癌幹細胞マーカーに対する自己抗体を利用した乳癌患者の予後予測(Prediction of Prognosis in Breast Cancer Patients Using Autoantibodies to Cancer Stem Cell Markers)

及能大輔, 廣橋良彦, 和田朝香, 島宏彰, 九冨五郎, 真柄和史, 高澤久美, 高澤啓, 竹政伊知朗, 小山内誠

日本癌学会総会記事 ( (一社)日本癌学会 ) 82回 2116 - 2116 2023年09月

癌幹細胞マーカーに対する自己抗体を利用した乳癌患者の予後予測(Prediction of Prognosis in Breast Cancer Patients Using Autoantibodies to Cancer Stem Cell Markers)

及能大輔, 廣橋良彦, 和田朝香, 島宏彰, 九冨五郎, 真柄和史, 高澤久美, 高澤啓, 竹政伊知朗, 小山内誠

日本癌学会総会記事 ( (一社)日本癌学会 ) 82回 2116 - 2116 2023年09月

Emerging roles of transmembrane-type tight junction proteins in cancers.

Akira Takasawa, Kumi Takasawa, Masaki Murata, Makoto Osanai, Norimasa Sawada

Pathology international 73 ( 8 ) 331 - 340 2023年08月 [国際誌]

Tight junctions (TJs) are the most apical components of the cell-cell adhesion machinery in epithelial and endothelial cells and they play essential roles in homeostasis. Recent studies have revealed that aberrant expression of tight junction proteins (TJPs) is frequently observed in various type of cancers. Here we review cancer-associated aberrant expression of TJPs with focus on transmembrane-type TJPs including claudins, junctional adhesion molecule-A (JAM-A), and occludin. Some transmembrane-type TJPs are upregulated at the early neoplastic stage and their expression persists during dedifferentiation. Aberrant expression of TJPs contributes to proliferation, invasion, and dysregulated signaling of cancer cells. In addition to an increase in their expression level, their localization is altered from a TJ-restricted pattern to distribution throughout the whole cell membrane, making them suitable as therapeutic targets. Extracellular domains of transmembrane-type TJPs can be approached by target drugs not only from the lumen side (apical side) but also from the extracellular matrix side (basal side), including blood vessels. Aberrantly expressed TJPs are potential useful diagnostic markers as well as therapeutic targets for cancers.

DOI PubMed

MPNSTにおけるPVR発現の意義

中橋尚也, 高澤啓, 江森誠人, 高澤久美, 太田未咲, 真柄和史, 小野佑輔, 及能大輔, 杉田真太朗, 長谷川匡, 小山内誠

日本整形外科学会雑誌 ( (公社)日本整形外科学会 ) 97 ( 8 ) S1975 - S1975 2023年08月

Establishment and characterization of a novel dedifferentiated chondrosarcoma cell line, SMU-DDCS, harboring an IDH1 mutation

Makoto Emori, Naoya Nakahashi, Akira Takasawa, Kenji Murata, Yasutaka Murahashi, Junya Shimizu, Tomohide Tsukahara, Shintaro Sugita, Kohichi Takada, Tadashi Hasegawa, Makoto Osanai, Kosuke Iba

Human Cell ( Springer Science and Business Media LLC ) 2023年07月

DOI

A novel approach to diagnosing crystal-storing histiocytosis: utility of scanning electron microscopy for formalin-fixed paraffin-embedded tissue specimens.

Kazufumi Magara, Akira Takasawa, Keisuke Kikuchi, Taro Sugawara, Taro Murakami, Daisuke Kyuno, Yusuke Ono, Kumi Takasawa, Yasunao Numata, Shigeru Sasaki, Hiroshi Nakase, Tadashi Hasegawa, Makoto Osanai

Medical molecular morphology 2023年07月 [国内誌]

Crystal-storing histiocytosis (CSH) is a rare disorder that shows infiltration of histiocytes with an aberrant cytoplasmic accumulation of crystalline structures and is often accompanied by lymphoproliferative-plasma cell disorders (LP-PCD) as background diseases. The diagnosis of CSH requires identification of crystalline structures that accumulate in the infiltrating histiocytes, which may be challenging by optical microscopy alone. In this case report, we describe an atypical course of systemic CSH with multifocal fibrosclerosis of an unknown background disease that was diagnosed by ultrastructural observation, including transmission electron microscopy (TEM) and scanning electron microscopy (SEM), in pathological autopsy. In addition, crystalline structures were successfully identified by scanning electron microscopic observations using formalin-fixed and paraffin-embedded (FFPE) tissue from biopsy specimens taken before death. Since CSH was identified by SEM in a tiny biopsy specimen, observation of histiocytic infiltrative lesions by SEM using FFPE tissue may lead to early detection of and initiation of treatment for CSH.

DOI PubMed

Suppression of the vitamin D metabolizing enzyme CYP24A1 provides increased sensitivity to chemotherapeutic drugs in breast cancer.

Sakura Kamiya, Yuna Nakamori, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Makoto Osanai

Oncology reports 49 ( 5 ) 2023年05月 [国際誌]

Vitamin D is an essential nutrient for the human body not only for the metabolism of calcium but also for homeostasis. Vitamin D contributes to cell fate decisions, including cell proliferation, differentiation and viability. Accumulated epidemiological data suggest a relationship between vitamin D deficiency and carcinogenesis in numerous organs. Furthermore, it is known that the expression of the vitamin D metabolizing enzyme, cytochrome P450 family 24 subtype A1 (CYP24A1), is increased in different types of human malignancy including breast carcinoma. However, the pathological relevance of elevated CYP24A1 expression level requires further clarification. In the present study, it was demonstrated that CYP24A1 promoted the oncogenic property of breast carcinoma cells. Consistent with previous reports, it was demonstrated that the expression of CYP24A1 was elevated in invasive breast carcinoma and significantly decreased the overall survival of patients with invasive breast carcinoma. Importantly, suppression of CYP24A1 expression significantly enhanced cell death sensitivity to two anticancer drugs with pharmacologically different modes of action, cisplatin and gefitinib. The results of the present study suggest the possibility of CYP24A1‑inhibiting therapy as a novel therapy in breast cancer with overexpression of CYP24A1.

DOI PubMed

Elevated expression of endocan in the development of cervical squamous neoplasia of the uterus.

Midori Sato, Ayano Inoue, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Makoto Osanai

Medical molecular morphology 2023年04月 [国内誌]

Accumulated evidence has shown that endocan, which was originally called endothelial cell-specific molecule-1, is an attractive prognostic factor in a variety of cancers. However, the relevance of endocan expression in human malignancies remains to be clarified. In the present study, the expression of endocan in cervical squamous neoplasia of the uterus, including low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), as well as in invasive squamous cell carcinoma was examined by immunohistochemistry. Endocan was not sufficiently expressed in the normal cervical epithelium. Endocan expression was present in LSIL cases but was limited to basal and parabasal areas of the cells. HSIL cases exhibited strong expression of endocan with widely distributed expression toward the epithelial surface. In contrast, further strong expression of endocan was not observed in patients with invasive carcinoma. This study is the first study showing increased expression of endocan in precancerous dysplastic lesions and malignancy of the cervix. The data suggest that a high expression level of endocan potentially contributes to the development of cervical squamous neoplasia of the uterus.

DOI PubMed

レチノイン酸代謝酵素CYP26A1の異常発現は、舌癌の悪性化に関与する

桑原未羽, 黒田睦喜, 小野佑輔, 高澤啓, 仲盛優菜, 及能大輔, 真柄和史, 青山智志, 高澤久美, 小山内誠

日本病理学会会誌 ( (一社)日本病理学会 ) 112 ( 1 ) 386 - 386 2023年03月

舌扁平上皮がんで異常高発現するPVRはがん悪性化に寄与する

永井佐和, 高澤啓, 永井美佐, 小野佑輔, 真柄和史, 青山智志, 及能大輔, 高澤久美, 村田雅樹, 小山内誠

日本病理学会会誌 ( (一社)日本病理学会 ) 112 ( 1 ) 382 - 383 2023年03月

MPNSTにおけるPVR発現の意義

中橋尚也, 高澤啓, 高澤久美, 太田未咲, 真柄和史, 小野祐輔, 及能大輔, 杉田真太朗, 長谷川匡, 小山内誠

日本病理学会会誌 ( (一社)日本病理学会 ) 112 ( 1 ) 346 - 346 2023年03月

乳がんにおけるタイト結合関連タンパク質LSRの膜型エストロゲン受容体GPR30を介した発現調節とその意義

太田未咲, 高澤啓, 高澤久美, 青山智志, 小野祐輔, 及能大輔, 小山内誠, 長谷川匡

日本病理学会会誌 ( (一社)日本病理学会 ) 112 ( 1 ) 303 - 303 2023年03月

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