論文 - 小山内　誠

膵癌患者の予後と癌進展におけるJAM-Aの役割(Junctional Adhesion Molecule-A may play a role in the progression of pancreatic cancer)

及能 大輔, 高澤 啓, 高澤 久美, 真柄 和史, 小山内 誠

日本癌学会総会記事 ( (一社)日本癌学会 )  81回   J - 2053  2022年09月

タイト結合分子JAM-Aの異常高発現が乳がんの悪性化に関与する(Elevated expression of JAM-A contributes malignant progression of breast cancer)

真柄 和史, 高澤 啓, 高澤 久美, 及能 大輔, 小山内 誠

日本癌学会総会記事 ( (一社)日本癌学会 )  81回   P - 3247  2022年09月

Pathological classification of desmoplastic reaction is prognostic factor in cervical adenocarcinoma.

Taishi Akimoto, Akira Takasawa, Kumi Takasawa, Tomoyuki Aoyama, Motoki Matsuura, Masato Tamate, Masahiro Iwasaki, Shutaro Habata, Taro Murakami, Makoto Osanai, Tsuyoshi Saito

Medical molecular morphology   55 ( 4 ) 275 - 282  2022年07月  [国内誌]

　概要を見る

Desmoplastic reaction (DR) and inflammation are significant pathological manifestations of tumorigenesis in several cancers. However, the correlation between these stromal reactions and cervical adenocarcinoma has been poorly documented. This investigation elucidated whether DR is a prognostic indicator in early cervical adenocarcinoma patients. Fifty-nine patients with early stage cervical adenocarcinoma (stages I/II) were included in the study. DR was divided into three groups, mature, intermediate, and immature, based on the presence of myxoid stroma and hyalinized keloid-like collagen. Inflammatory cell responses were classified as mild, moderate, and severe. Those stromal reactions were separately evaluated in the invasion front stroma and intratumoral stroma. In both the intratumor and invasion front stroma, intermediate/immature DR was correlated with tumor size, T stage, N stage, lymphovascular invasion, and parametrial infiltration (p < 0.001 to p < 0.05). In addition, in the intratumoral stroma, intermediate/immature DR led to short relapse-free survival and overall survival (p < 0.001). In the invasion front stroma, inflammatory cell responses were associated with DR immaturity and FIGO stage (p < 0.01). These results suggest that the classification of DR maturity is a potential prognostic biomarker in early stage cervical adenocarcinoma patients. DR can be evaluated by routine H&E staining without immunohistochemistry, making it convenient and economical in clinical practice.

DOI PubMed

免疫チェックポイント阻害薬による偽増悪および免疫関連有害事象を併発した肺多形癌の一剖検例

多田 聡法, 真柄 和史, 高澤 啓, 久保田 雄策, 小野 佑輔, 及能 大輔, 高澤 久美, 廣橋 良彦, 小山内 誠

日本病理学会会誌 ( (一社)日本病理学会 )  111 ( 1 ) 357 - 358  2022年03月

両側肺の壊死組織周囲への黒色色素、シュウ酸カルシウム結晶の沈着をともなった深在性真菌症の一剖検例

久保田 雄策, 小野 佑輔, 高澤 啓, 多田 聡法, 真柄 和史, 青山 智志, 及能 大輔, 高澤 久美, 小山内 誠

日本病理学会会誌 ( (一社)日本病理学会 )  111 ( 1 ) 357 - 357  2022年03月

舌扁平上皮癌におけるPVR発現とその意義

永井 佐和, 高澤 啓, 永井 美佐, 仲盛 優菜, 小野 佑輔, 真柄 和史, 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 )  111 ( 1 ) 354 - 354  2022年03月

膵臓癌におけるALDOA発現とその意義

永井 美佐, 小野 佑輔, 高澤 啓, 永井 佐和, 真柄 和史, 青山 智志, 及能 大輔, 高澤 久美, 小山内 誠

日本病理学会会誌 ( (一社)日本病理学会 )  111 ( 1 ) 352 - 352  2022年03月

膵癌におけるJAM-Aの機能

及能 大輔, 高澤 啓, 高澤 久美, 小野 佑輔, 真柄 和史, 仲盛 優菜, 小山内 誠

日本病理学会会誌 ( (一社)日本病理学会 )  111 ( 1 ) 239 - 239  2022年03月

タイト結合蛋白質Claudin-1は細胞接着、微絨毛形成を制御する

高澤 啓, 高澤 久美, 青山 智志, 村上 太朗, 真柄 和史, 小野 佑輔, 及能 大輔, 小山内 誠

日本病理学会会誌 ( (一社)日本病理学会 )  111 ( 1 ) 249 - 249  2022年03月

ビタミンD代謝酵素CYP24A1の発現様式は口腔扁平上皮がんにおける予後規定因子である

仲盛 優菜, 紙谷 咲良, 真柄 和史, 小野 佑輔, 及能 大輔, 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 )  111 ( 1 ) 278 - 279  2022年03月

乳がんにおいてJAM-Aの異常高発現が悪性化に関与する

真柄 和史, 高澤 啓, 高澤 久美, 小野 佑輔, 及能 大輔, 小山内 誠

日本病理学会会誌 ( (一社)日本病理学会 )  111 ( 1 ) 284 - 284  2022年03月

レチノイン酸代謝酵素CYP26A1の異常発現は、膵癌細胞の悪性形質の促進に関与する

井上 彩乃, 小野 佑輔, 高澤 啓, 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 )  111 ( 1 ) 351 - 352  2022年03月

ビタミンD代謝酵素CYP24A1は乳癌に対する新規治療標的である

紙谷 咲良, 仲盛 優菜, 真柄 和史, 小野 佑輔, 及能 大輔, 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 )  111 ( 1 ) 354 - 354  2022年03月

Aberrant expression of claudin-6 contributes to malignant potentials and drug resistance of cervical adenocarcinoma.

Yui Ito, Akira Takasawa, Kumi Takasawa, Taro Murakami, Taishi Akimoto, Daisuke Kyuno, Yuka Kawata, Kodai Shano, Kurara Kirisawa, Misaki Ota, Tomoyuki Aoyama, Masaki Murata, Kotaro Sugimoto, Hideki Chiba, Tsuyoshi Saito, Makoto Osanai

Cancer science   113 ( 4 ) 1519 - 1530  2022年01月  [査読有り]  [国際誌]

　概要を見る

Recent studies have revealed that aberrant expression of tight junction (TJ) proteins is a hallmark of various solid tumors and it is recognized as a useful therapeutic target. Claudin-6 (CLDN6), a member of the family of TJ transmembrane proteins, is an ideal therapeutic target because it is not expressed in human adult normal tissues. In this study, we found that CLDN6 is highly expressed in uterine cervical adenocarcinoma and that high CLDN6 expression was correlated with lymph node metastasis and lymphovascular infiltration and was an independent prognostic factor. Shotgun proteome analysis revealed that cell-cell adhesion-related proteins and drug metabolism-associated proteins (aldo-keto reductase (AKR) family proteins) were significantly increased in CLDN6-overexpressing cells. Furthermore, overexpression of CLDN6 enhanced cell-cell adhesion properties and attenuated sensitivity to anticancer drugs including doxorubicin, daunorubicin and cisplatin. Taken together, the results indicate that aberrant expression of CLDN6 enhances malignant potentials and drug resistance of cervical adenocarcinoma, possibly due to increased cell-cell adhesion properties and drug metabolism. Our findings provide an insight into a new therapeutic strategy, a CLDN6-targeting therapy, against cervical adenocarcinoma.

DOI PubMed

Claudin-18.2 as a therapeutic target in cancers: cumulative findings from basic research and clinical trials.

Daisuke Kyuno, Akira Takasawa, Kumi Takasawa, Yusuke Ono, Tomoyuki Aoyama, Kazufumi Magara, Yuna Nakamori, Ichiro Takemasa, Makoto Osanai

Tissue barriers   10 ( 1 ) 1967080 - 1967080  2022年01月  [国際誌]

　概要を見る

Claudins are major components of tight junctions that maintain cell polarity and intercellular adhesion. The dynamics of claudins in cancer cells have attracted attention as a therapeutic target. During carcinogenesis, claudin expression is generally downregulated; however, overexpression of claudin-18.2 has been observed in several types of cancers. Upregulated and mislocalized claudin-18.2 expression in cancer cells has been suggested as a therapeutic target. Research on claudin-18.2 has revealed its involvement in carcinogenesis. Clinical trials using zolbetuximab, a monoclonal antibody targeting claudin-18.2, for patients with advanced cancer yielded positive results with few high-grade adverse events; thus, it is expected to be a novel and effective therapeutic. Here, we review current insights into the role that claudin-18.2 plays in basic cancer research and clinical applications. A better understanding of these roles will facilitate the development of new treatment strategies for cancer patients with poor prognoses.

DOI PubMed

Claudin 6 is associated with a short survival and a short recurrent free interval in non-small cell lung carcinoma.

Ylermi Soini, Risto Pirinen, Kumi Takasawa, Makoto Osanai, Akira Takasawa

Polish journal of pathology : official journal of the Polish Society of Pathologists   73 ( 1 ) 1 - 5  2022年  [国際誌]

　概要を見る

We investigated the expression of claudin 6 in non-small-cell lung carcinomas (NSCLC) by immunohistochemistry. Samples of 164 patients with NSCLC were studied by immunohistochemistry. Claudin 6 was expressed in 42 % of cases. Its expression was significantly more frequent in adeno- than in squamous cell carcinoma (p = 0.002). There was no association between the TNM status and claudin 6 expression. Claudin 6 associated with a poor prognosis of the patients and with a short recurrence-free interval (p = 0.002, p < 0.001). The association with survival had independent prognostic value (p = 0.011). The results show that claudin 6 can be regarded as a marker of poor prognosis in lung cancer. This is different to some other cancers, such as breast and cervical carcinoma suggesting that claudin 6 probably induces other cellular pathways in neoplastic lung cells than in those tumors. In lung cancer, adenocarcinomas were most abundantly positive indicating a higher linkage of claudin 6 to glandular differentiation.

DOI PubMed

悪性末梢神経鞘腫のFFPE組織標本を用いた新規バイオマーカー探索の試み

車野 晃大, 高澤 啓, 伊藤 祐衣, 桐澤 くらら, 青山 智志, 小野 祐輔, 高澤 久美, 及能 大輔, 小山内 誠

日本病理学会会誌 ( (一社)日本病理学会 )  110 ( 2 ) 71 - 71  2021年10月

頭頸部扁平上皮がんの腫瘍微小環境におけるAEBP1の解析

関口 翔平, 萬 顕, 山本 英一郎, 新沼 猛, 高澤 啓, 須藤 豪太, 小池 和茂, 畠中 柚衣, 吉戸 文乃, 北嶋 洋志, 甲斐 正広, 小山内 誠, 高野 賢一, 宮崎 晃亘, 鈴木 拓

日本癌学会総会記事 ( (一社)日本癌学会 )  80回   [J14 - 5]  2021年09月

活性化マクロファージはIL-1β-SAA1 axisを介して早期大腸がんの浸潤を促進する

須藤 豪太, 山本 英一郎, 青木 敬則, 高澤 啓, 新沼 猛, 久保 俊之, 萬 顕, 吉戸 文乃, 北嶋 洋志, 甲斐 正広, 小山内 誠, 仲瀬 裕志, 鈴木 拓

日本癌学会総会記事 ( (一社)日本癌学会 )  80回   [P14 - 3]  2021年09月

蛍光標識単球を用いた肝区域の可視化技術の開発

及能 大輔, 高澤 啓, 高澤 久美, 小野 佑輔, 真柄 和史, 仲盛 優菜, 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 )  80回   [P14 - 3]  2021年09月