論文 - 小山内　誠

乳がんにおけるタイト結合分子JAM-Aの役割

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

日本病理学会会誌 ( (一社)日本病理学会 )  112 ( 1 ) 240 - 240  2023年03月

膵臓がんで高発現する解糖系酵素ALDOAはがん悪性化に関与する

永井 美佐, 高澤 啓, 永井 佐和, 小野 佑輔, 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 )  112 ( 1 ) 378 - 378  2023年03月

子宮頸部腺癌で異所性高発現するclaudin-6はがん悪性化に寄与する

高澤 啓, 伊藤 祐衣, 高澤 久美, 村上 太朗, 太田 未咲, 青山 智志, 小野 祐輔, 及能 大輔, 小山内 誠

日本病理学会会誌 ( (一社)日本病理学会 )  112 ( 1 ) 255 - 255  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

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

膵臓がんで高発現する解糖系酵素ALDOAはがん悪性化に関与する

永井 美佐, 高澤 啓, 永井 佐和, 小野 佑輔, 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 )  112 ( 1 ) 378 - 378  2023年03月

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

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

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

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

子宮頸部腺癌で異所性高発現するclaudin-6はがん悪性化に寄与する

高澤 啓, 伊藤 祐衣, 高澤 久美, 村上 太朗, 太田 未咲, 青山 智志, 小野 祐輔, 及能 大輔, 小山内 誠

日本病理学会会誌 ( (一社)日本病理学会 )  112 ( 1 ) 255 - 255  2023年03月

乳がんにおけるタイト結合分子JAM-Aの役割

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

日本病理学会会誌 ( (一社)日本病理学会 )  112 ( 1 ) 240 - 240  2023年03月

Invasive pulmonary aspergillosis with candidiasis: usefulness of molecular and ultrastructural morphological analysis on FFPE tissue for invasive fungal infections.

Yusaku Kubota, Akira Takasawa, Yusuke Ono, Tomoyuki Aoyama, Kumi Takasawa, Akinori Tada, Kazufumi Magara, Taro Murakami, Fuminori Daimon, Soh Yamamoto, Shota Sato, Yutaro Hiratsuka, Daisuke Kyuno, Makoto Osanai

Medical molecular morphology   56 ( 2 ) 1 - 8  2023年02月  [国内誌]

　概要を見る

Invasive pulmonary aspergillosis (IPA) is one of the most frequent forms of invasive fungal infections (IFI); however, it is often difficult to identify the pathogenic fungal species and to select appropriate treatments for patients with IFI including IPA. Here, we describe the detailed pathophysiology of an autopsy case of severe respiratory failure due to IPA with candidiasis. The patient developed severe respiratory failure after influenza infection and died, and the autopsy revealed a mixed disease of IPA with candidiasis. In this study, in addition to the routine pathological examination, we further examined formalin-fixed paraffin-embedded (FFPE) tissues by scanning electron microscopy (SEM) and partial genomic DNA sequencing. Although optical microscopy alone was insufficient to identify the pathogenic organisms, SEM clearly depicted the characteristic morphology of Aspergillus sp. and Candida sp. as closely overlapping in a nested fashion, providing evidence of mixed infection of both fungal species in a focal site. The technique using FFPE tissue in combination with ultrastructural observation by SEM, elemental analysis by SEM-EDX, and DNA sequencing is promising for analyzing the pathophysiology of IFI.

DOI PubMed

Vitamin D metabolism in cancer: potential feasibility of vitamin D metabolism blocking therapy.

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

Medical molecular morphology   56 ( 2 ) 85 - 93  2023年02月  [国内誌]

　概要を見る

In this review, we discuss the possibility of the vitamin D metabolizing enzyme CYP24A1 being a therapeutic target for various tumors including breast, colorectal and prostate tumors. Given the pleiotropic cellular activity of vitamin D, its deficiency impairs its physiological function in target cells and results in various pathologies including cancer. In addition, accumulated data have shown that elevated expression of CYP24A1 promotes carcinogenesis in various cancer subtypes by decreasing the bioavailability of vitamin D metabolites. Thus, we propose the potential feasibility of vitamin D metabolism-blocking therapy in various types of human malignancies that express constitutive CYP24A1.

DOI PubMed

Retinoic acid metabolism in cancer: potential feasibility of retinoic acid metabolism blocking therapy.

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

Medical molecular morphology   56 ( 1 ) 1 - 10  2023年01月  [国内誌]

　概要を見る

Retinoic acid (RA) is an active metabolite of vitamin A, which is an essential signaling molecule involved in cell fate decisions, such as differentiation, proliferation, and apoptosis, in a wide variety of cell types. Accumulated data have demonstrated that expression of RA-metabolizing enzymes, CYP26A1, B1, and C1 (cytochrome P450, family 26A1, B1, and C1, respectively), protects cells and tissues from exposure to RA through restriction of RA access to transcriptional machinery by converting RA to rapidly excreted derivatives. CYP26 enzymes play similar but separate roles in limiting the consequences of fluctuations in nutritional vitamin A. Recently, we found that RA depletion caused by expression of CYP26A1 promotes malignant behaviors of tumor cells derived from various tissues, implicating CYP26A1 as a candidate oncogene. We also showed that the expression levels of CYP26 enzymes are elevated in various types of cancer. We have provided evidence for oncogenic and cell survival properties of CYP26 enzymes, indicating that these molecules are possible therapeutic targets for CYP26-expressing malignancies.

DOI PubMed

Serum amyloid A1 recruits neutrophils to the invasive front of T1 colorectal cancers.

Ayano Yoshido, Gota Sudo, Akira Takasawa, Hironori Aoki, Hiroshi Kitajima, Eiichiro Yamamoto, Takeshi Niinuma, Taku Harada, Toshiyuki Kubo, Hajime Sasaki, Kazuya Ishiguro, Akira Yorozu, Masahiro Kai, Akio Katanuma, Hiro-O Yamano, Makoto Osanai, Hiroshi Nakase, Hiromu Suzuki

Journal of gastroenterology and hepatology    2022年11月  [国際誌]

　概要を見る

BACKGROUND AND AIM: The tumor microenvironment plays an essential role in the development and progression of colorectal cancer (CRC). We recently reported that crosstalk between CRC cells and tumor-associated macrophages (TAMs) via serum amyloid A1 (SAA1) promotes invasion by T1 CRCs. In the present study, we aimed to clarify the role of neutrophils in early CRCs. METHODS: Immunohistochemical analysis of CD66b, chemokine CXC motif ligand 8 (CXCL8 or interleukin-8, IL-8) and matrix metalloproteinase-9 (MMP-9) was performed using primary T1 CRCs (n = 49). The HL-60 human promyelocytic leukemia cell line and THP-1 human monocytic leukemia cell line were used to obtain neutrophil-like and macrophage-like cells, respectively. Boyden chamber assays were used to analyze cell migration and invasion, and quantitative RT-PCR was used to analyze gene expression. RESULTS: Immunohistochemical analysis revealed accumulation of neutrophils at the SAA1-positive invasive front of T1 CRCs. Experiments using HL-60 cells suggested that treatment with SAA1 induced neutrophil migration and expression of CXCL8 and MMP-9 in neutrophils and that neutrophils promote CRC cell migration and invasion. Immunohistochemistry confirmed accumulation of CXCL8- or MMP-9-positive neutrophils at the SAA1-positive invasive front of T1 CRCs. Moreover, co-culture experiments using CRC, THP-1 and HL-60 cells suggested that CRC cells activated by macrophages upregulate CXCL8 and MMP-9 in neutrophils. CONCLUSIONS: Our results suggest that interplay between macrophages and CRC cells leads to recruitment of neutrophils to the invasive front of T1 CRCs and that SAA1 secreted by CRC cells activate neutrophils to promote invasion.

DOI PubMed

CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma.

Akira Yorozu, Shohei Sekiguchi, Akira Takasawa, Fumika Okazaki, Takeshi Niinuma, Hiroshi Kitajima, Eiichiro Yamamoto, Masahiro Kai, Mutsumi Toyota, Yui Hatanaka, Koyo Nishiyama, Kazuhiro Ogi, Hironari Dehari, Kazufumi Obata, Makoto Kurose, Atsushi Kondo, Makoto Osanai, Akihiro Miyazaki, Kenichi Takano, Hiromu Suzuki

Cancer medicine   12 ( 5 ) 5953 - 5963  2022年10月  [国際誌]

　概要を見る

BACKGROUND: The CXCL12/CXCR4 axis plays a pivotal role in the progression of various malignancies, including oral squamous cell carcinoma (OSCC). In this study, we aimed to clarify the biological and clinical significance of CXCL12 in the tumor microenvironment of OSCCs. METHODS: Publicly available single-cell RNA-sequencing (RNA-seq) datasets were used to analyze CXCL12 expression in head and neck squamous cell carcinomas (HNSCC). Immunohistochemical analysis of CXCL12, α-smooth muscle antigen (α-SMA), fibroblast activation protein (FAP) and CD8 was performed in a series of 47 surgically resected primary tongue OSCCs. Human skeletal muscle cells were co-cultured with or without OSCC cells, after which CXCL12 expression was analyzed using quantitative reverse-transcription PCR. RESULTS: Analysis of the RNA-seq data suggested CXCL12 is abundantly expressed in stromal cells within HNSCC tissue. Immunohistochemical analysis showed that in grade 1 primary OSCCs, CXCL12 is expressed in both tumor cells and muscle cells. By contrast, grade 3 tumors were characterized by disruption of muscle structure and reduced CXCL12 expression. Quantitative analysis of CXCL12-positive areas within tumors revealed that reduced CXCL12 expression correlated with poorer overall survival. Levels of CXCL12 expression tended to inversely correlate α-SMA expression and positively correlate with infiltration by CD8+ lymphocytes, though these relations did not reach statistical significance. CXCL12 was significantly upregulated in muscle cells co-cultured with OSCC cells. CONCLUSION: Our results suggest that tongue OSCC cells activate CXCL12 expression in muscle cells, which may contribute to tumor progression. However, CXCL12 is reduced in advanced OSCCs due to muscle tissue destruction.

DOI PubMed

COVID-19-associated disseminated mucormycosis: An autopsy case report.

Daisuke Kyuno, Terufumi Kubo, Mitsuhiro Tsujiwaki, Shintaro Sugita, Michiko Hosaka, Hazuki Ito, Keisuke Harada, Akira Takasawa, Yusaku Kubota, Kumi Takasawa, Yusuke Ono, Kazufumi Magara, Eichi Narimatsu, Tadashi Hasegawa, Makoto Osanai

World journal of clinical cases   10 ( 28 ) 10358 - 10365  2022年10月  [国際誌]

　概要を見る

BACKGROUND: Reports of mucormycosis, an infectious disease that commonly affects immunocompromised individuals, have increased during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Disseminated mucormycosis associated with COVID-19 is rare but fatal and is characterized by an aggressive clinical course and delayed diagnosis. Our report documents a case of disseminated mucormycosis after COVID-19 infection. This is a rare pathological autopsy report on COVID-19-associated mucormycosis. CASE SUMMARY: A 58-year-old man was transferred to our hospital with severe COVID-19 pneumonia. During treatment for acute respiratory distress syndrome, he developed intra-abdominal bleeding that required a right hemicolectomy and ileostomy for hemostasis. The ileostoma and surgical wound developed necrosis followed by sepsis and multi-organ failure, which led to death. An autopsy revealed multiple thrombi associated with Rhizopus oryzae infection, which led to the necrosis of multiple infected organs. CONCLUSION: Early suspicion and diagnosis followed by treatment are keys to better outcomes of mucormycosis in patients with severe COVID-19.

DOI PubMed