研究の概要
消化管に発生する間葉系腫瘍であるGastrointestinal stromal tumor (GIST)の発生機序や起源細胞についての研究を行い、GISTの治療に関わる研究も行ってきた。最近では、GISTのさらなる病態解析や治療に対する耐性機構の解明などの研究を分子病理学的に進めている。また、動脈硬化や大動脈瘤などの循環器疾患に関する病理学的研究や肺癌、軟部腫瘍、血液疾患の研究なども行っている。様々な臨床症例についての病理学的検索・考察に関する症例報告も行っている。
主な内容
1.GISTの病態・治療に関する研究:多発性GIST家系のモデルとなるノックインマウス(germlineにc-kit遺伝子の機能獲得性突然変異を導入)を作製し、カハールの介在細胞の過形成からGIST発生に至るメカニズムを検討している。また、GISTにみられる様々なタイプのc-kitおよびPDGFRA遺伝子変異の特性や分子標的薬イマチニブに耐性を示すGISTの耐性メカニズムについての研究も進めている。(2003年までのGISTに関する研究経過の詳細を見る場合はここをクリックして下さい)
2.循環器疾患に関する病理学的研究:冠動脈および頸動脈にみられる粥状硬化の性状と心筋梗塞・脳梗塞との関連につき臨床病理学的なアプローチでの研究を行っている。また、これまでの血管平滑筋細胞の多様性に関する研究を基礎に、様々なフェノタイプを示す平滑筋細胞と大動脈瘤の形成との関係や大動脈瘤に見られる平滑筋細胞のアポトーシスの機序、各種心血管疾患における小胞体ストレス関連分子の役割についての研究も進めている。
<教室主導で行われた最近の論文発表(2015年~)>
●英文
Ikeo
K, Matsuda I, Hirota S. EBV-positive bile duct carcinoma associated with
ulcerative colitis. Intern Med.
2023 In press
Sano D, Kihara T, Yuan
J, Kimura N, Ohkouchi M, Hashikura Y, Ohkubo S, Hirota S. Characterization of
cell line with dedifferentiated GIST‐like features established from cecal GIST
of familial GIST model mice. Pathol Int.
in press
Kihara T, Kuwahara R,
Kusunoki K, Minagawa T, Horio Y, Uchino M, Ikeuchi H, Hirota S. Rectal carcinoma with dual differentiation toward
enteroblastic and neuroendocrine features arising in a patient with ulcerative
colitis: a case report.
Yuan J, Kihara T, Kimura N, Yamasaki T, Yoshida M, Isozaki K, Ito A, Hirota S. CADM1 promotes adhesion to vascular endothelial cells and transendothelial migration in cultured GIST cells. Oncol Lett. 23:86, 2022.
Yoshiyasu
K, Kono H, Hojo Y, Ishida
Y, Tamura A, Nakai K, Oshima T, Miwa H, Shinohara H, Hirota S. A
minute primary gastric synovial sarcoma with ulcer: a case report. Diagn Pathol. 16:115, 2021. (case
report)
Nambu N, Yamasaki
T, Nakagomi N, Kumamoto T, Nakamura T, Tamura A, Tomita T, Miwa H, Shinohara H,
Hirota S. A case of ectopic pancreas of the stomach accompanied by intraductal
papillary mucinous neoplasm with GNAS mutation. World J Surg Oncol. 19:309,
2021.
(case report)
Kihara
T, Yuan J, Watabe T, Kitajima K, Kimura N, Ohkouchi M, Hashikura Y, Ohkubo S, Takahashi T, Hirota S. Pimitespib is effective on cecal GIST in a
mouse model of familial GISTs with KIT-Asp820Tyr mutation through KIT signaling
inhibition. Exp Mol Pathol.
23:104692, 2021.
Torii Y,
Sano D, Ikeuchi H, Hida N, Hirota
S. Use
of segmental colorectal lavage cytology during surveillance colonoscopy for
detecting dysplastic and cancer cells in patients with ulcerative colitis. Int J Clin Exp Pathol. 13:2035-2040, 2020.
Matsuda I, Nakamura J, Ohkouchi M,
Torii Y, Futani H, Tsukamoto Y, Hirota
S.
Kawakami
R, Imanaka T, Ishihara M, Kihara T, Fujii K, Hirota S, Hao H. Protruding
in-stent mass after bioresorbable polymer sirolimus-eluting stent: ex vivo
intravascular images and histopathology. Circ
J. 82:932-933, 2018. (case report)
Tsuchida
Y, Tsukamoto Y, Futani H, Kumanishi S, Watanabe T, Kajimoto N, Matsuo S,
Yoshiya S, Hirota S. A rare case of
low-grade fibromyxoid sarcoma with ossification which was radiologically
detected as apparent calcification and histopathologically proven. Human Pathology:
Case Reports. 12:24-28, 2018. (case report)
Fujino A, Hao H, Shimodai S,
Kawakami R, Matsuo K, Yasumura Y, Higuchi Y, Tsujimoto M, Ueda Y, Hirota S. Atherosclerotic
plaque component as a risk for distal embolization during percutaneous coronary
intervention; pathological assessment of tissue obtained by distal protection
device. Circ J.
82:2292-2298, 2018.
Kawakami
R, Hao H, Tsuchida YA, Fujino A, Imanaka
T, Saita T, Fujii K, Ishihara M, Hirota
S. Neoatherosclerosis
after paclitaxel-eluting stent implantation: ex vivo intravascular image and
histopathology. Pathol
Int. 67:53-55, 2017. (case
report)
Tsukamoto
Y, Futani H, Yoshiya S,
Watanabe T, Kihara T, Matsuo S, Hirota S. Primary undifferentiated small
round cell sarcoma of the deep abdominal wall with a novel variant of t(10;19)
CIC-DUX4 gene fusion. Pathol Res Pract. 213:1315-1321,
2017. (case report)
Nambu N, Tsukamoto Y, Tsuji H, Watanabe T, Shigehara R, Kakibuchi
M, Morii E, Hirota S. Invasive ductal carcinoma ex pleomorphic adenoma of the
lacrimal gland - a long term follow-up case - Human Pathology: Case Reports. 10:81-84,
2017. (case report)
Tsukamoto Y, Imakita M, Nishitani A, Ito T,
Izukura M, Hirota S. Pancreatic
desmoid-type fibromatosis with beta-catenin gene mutation - report of a case
and review of the literature. Pathol Res
Pract. 212:484-489, 2016. (case
report)
Fujino A, Hao H, Kawakami R, Tsuchida YA, Fujii K, Hirota S. Ex vivo optical frequency domain imaging and
histopathology of malapposed drug eluting stent in coronary artery. Pathol Int. 66:354-355,
2016. (case report)
Fujino A,
Hao H, Kawakami R, Tsuchida YA, Imanaka T, Saita T, Fujii K, Ishihara M, Hirota S. Ulcerated
plaque of coronary artery: insights from ex vivo images of optical frequency
domain imaging and histopathology. Pathol Int.
66:643-644, 2016. (case report)
Matsuda
I, Yamamoto A, Shimizu Y, Matsuo S, Ohsawa M, Hirota S.
CD31 is a surrogate marker for blastic plasmacytoid dendritic
cell neoplasm: a case of a hematologic skin tumor immunohistochemically false
negative for CD45. Int J Clin Exp
Pathol. 9:7622-7628, 2016. (case
report)
Matsuda
I, Sugihara N, Yunokizaki H, Abe T, Hirota S. A case of immunohistochemical
false positive staining caused by incompatibility between a CD4 antibody and an
autostainer. Int J Clin Exp Pathol. 8:1019-1024,
2015. (case report)
Fujino A,
Hao H, Kajimoto N, Kawakami R, Imanaka T, Fujii K, Abe T, Ishihara M, Hirota S.
Restenosis after drug-eluting
stent implantation in a patient with polycythemia vera: optical coherence
tomography and pathological findings. JACC Cardiovasc Interv. 8:e111-112,
2015. (case report)
Ide Y,
Tsukamoto Y, Ito T, Watanabe T, Nakagawa N,
Haneda T, Nagai M, Yamanishi K, Hirota S. Penile pseudomyogenic
hemangioendothelioma/epithelioid sarcoma-like hemangioendothelioma with a novel
pattern of SERPINE1-FOSB fusion detected by RT-PCR - report of a case. Pathol Res Pract. 211:415-420, 2015. (case report)
Kawakami
R, Hao H, Kimura N, Komatsu S, Kodama K, Hirota S.
Pathological evaluation of
massive left atrial calcification 35 years after mitral-aortic valve
replacement. J Cardiol Cases. 11:44-47,
2015. (case report)
Fujino A,
Hao H, Kawakami R, Fujii K, Imanaka T, Ishihara M, Tsuchida Y, Hirota S. Is
optical frequency domain imaging a promising modality for diagnosis of erosion?
Pathol Int. 65:617-618, 2015. (case report)
Matsuda I, Tsuchida Y, Toyoshima F,
Tozawa K, Ikehara H, Ohda Y, Hori K, Ohtsuka Y, Watari J, Miwa H, Hirota S. Occurrence of colon tumors in a 16-year-old Japanese boy after
hematopoietic stem cell transplantation for Diamond Blackfan anemia at age of
4: a case report.
Int J Clin Exp Pathol. 8:5938-5943,
2015. (case report)
Kawakami R, Hao H, Takagi Y, Fujino A,
Tsuchida YA, Imanaka T, Fujii K, Hirota
S. Drug-eluting stent implantation on calcified nodule:
ex vivo intravascular images and histopathology. JACC
Cardiovasc Interv. 8:e127-128, 2015. (case report)
Kajimoto N, Tsukamoto Y, Hao H, Watanabe T, Tsubamoto H,
Kuribayashi K, Kamiya H, Shibata E, Nakano T, Hirota S. Uterine
metastasis of lung adenocarcinoma revealed by the same epidermal growth factor
receptor mutation in both lung and endometrial biopsies. Cancer Treat Comm.
4:134-137,
2015. (case report)
Matsuda
I, Kan K, Doi S, Motoki Y, Onodera M, Hirota S.
A case of gastric cancer with heterogeneous components of EB
virus (+)/TP53 (+) and EB virus (-)/TP53 (-). Int J Clin Exp Pathol. 8:11766-11771, 2015. (case report)
Kajimoto
N, Nakai N, Ohkouchi M, Hashikura Y, Liu-Kimura N-N, Isozaki K, Hirota S.
Characterization of various types of mast cells derived from model mice of
familial gastrointestinal stromal tumors with KIT-Asp818Tyr mutation. Int J Clin Exp Pathol. 8:11970-11982,
2015.
●和文
糸山雅子,中村純子,佐藤元,石田圭子,榎本利香,鳥居良貴,石川恵理,井出良浩,渡邊隆弘,廣田誠一.オンサイト迅速細胞診における湿固定簡易ギムザ染色の有用性.日本臨床細胞学会雑誌60-3: 141-149, 2021.
石田誠実,中西昂弘,鳥居良貴,廣田誠一.マイクロチューブを利用した細胞浮遊状態での免疫細胞化学染色法の検討.日本臨床細胞学会雑誌59-5: 248-250, 2020.
石川恵理, 木原多佳子, 毛利武士, 貴田紘太, 塚本吉胤, 廣田誠一. β-catenin (CTNNB1) 遺伝子変異検索が確定診断に有用であった Glomangiopericytoma の一例. 診断病理.
37-2, 278-282,2020.(症例報告)
鳥居洋祐, 大西崇文, 長友忠相, 佐藤元, 中村純子, 鳥居良貴, 森井英一, 廣田誠一. 施行者間差の少ないグロコット染色法の工夫 - クロム酸アンモニウム銀法における菌体ごとの至適時間の検討 -. 医学検査 67(2):221-227, 2018.
<最近の教室内の学位取得状況>
佐野太亮2022年
(学位論文名)
Sano D, Kihara T, Yuan J, Kimura N, Ohkouchi M, Hashikura Y, Ohkubo S, Hirota
S. Characterization of cell line with dedifferentiated GIST‐like features
established from cecal GIST of familial GIST model mice. Pathol Int. in press
木原多佳子2021年
(学位論文名)
Kihara
T, Yuan J, Watabe T, Kitajima K, Kimura N, Ohkouchi M, Hashikura Y, Ohkubo S, Takahashi T, Hirota S. Pimitespib is effective on cecal GIST in a
mouse model of familial GISTs with KIT-Asp820Tyr mutation through KIT signaling
inhibition. Exp
Mol Pathol. 23:104692, 2021.
袁嘉茵2021年
(学位論文名)
Yuan J,
Kihara T, Kimura N, Hashikura Y, Ohkouchi M, Isozaki K, Takahashi T, Nishida T,
Ito A, Hirota S. Differential expression of CADM1 in
gastrointestinal stromal tumors of different sites and with different gene
abnormalities. Pathol
Oncol Res. 27:602008, 2021.
川上りか2018年
(学位論文名)
Kawakami R, Hao H, Imanaka T, Shibuya M, Ueda Y,
Tsujimoto M, Ishibashi-Ueda H, Hirota S. Initial pathological responses of
second-generation everolimus-eluting stents implantation in Japanese coronary
arteries: Comparison with first-generation sirolimus-eluting stents. J Cardiol. 71:452-457, 2018.
藤野明子2018年
(学位論文名)
Fujino A, Hao H, Shimodai S,
Kawakami R, Matsuo K, Yasumura Y, Higuchi Y, Tsujimoto M, Ueda Y, Hirota S. Atherosclerotic
plaque component as a risk for distal embolization during percutaneous coronary
intervention; pathological assessment of tissue obtained by distal protection
device. Circ J.
82:2292-2298, 2018.
渡邊隆弘2018年
(学位論文名)
Watanabe T, Hida AI, Inoue N, Imamura M, Fujimoto Y, Akazawa K, Hirota S, Miyoshi Y. Abundant tumor infiltrating lymphocytes after primary systemic chemotherapy
predicts poor prognosis in estrogen receptor-positive/HER2-negative breast
cancers. Breast Cancer Res Treat. 168:135-145, 2018.
中村佳子2017年
(学位論文名)
Nakamura K, Nonaka S, Nakajima T, Yachida T, Abe S, Sakamoto T, Suzuki
H, Yoshinaga S, Oda I, Matsuda T, Sekine S, Kanemitsu Y, Katai H, Saito
Y, Hirota S. Clinical outcomes of gastric polyps and
neoplasms in patients with familial adenomatous polyposis. Endosc
Int Open. 5:E137-E145,
2017.
梶本仙子2016年
(学位論文名)
Kajimoto N, Nakai N, Ohkouchi M, Hashikura Y, Liu-Kimura N-N, Isozaki K,
Hirota S. Characterization of various types of mast cells derived from
model mice of familial gastrointestinal stromal tumors with KIT-Asp818Tyr
mutation. Int J Clin Exp Pathol. 8:11970-11982,
2015.
劉寧寧2013年
(学位論文名)
Liu
N-N, Ohkouchi M, Hashikura Y, Kajimoto N, Matsuda I, Isozaki K, Toh Y,
Takahashi T, Nishida T, Hirota S. Extracellular domain c-kit gene mutation of duplication of Ser501Ala502 found in
gastrointestinal stromal tumors is more imatinib- and nilotinib-sensitive than
that of duplication of Ala502Tyr503. Lab
Invest. 93:502-507, 2013.
中井真由美2012年
(学位論文名)
Nakai M,
Hashikura Y, Ohkouchi M, Yamamura M, Akiyama T, Shiba K, Kajimoto N, Tsukamoto
Y, Hao H, Isozaki K, Hirai T, Hirota S. Characterization of novel germline c-kit gene mutation, KIT-Tyr553Cys,
observed in a family with multiple gastrointestinal stromal tumors. Lab Invest. 92:451-457, 2012.
造住誠孝2012年
(学位論文名)
Zozumi M, Nakai M, Ito T, Matsuda I, Hao H, Tsukamoto
Y, Hirota S. New double embedding
technique for specimens of endoscopic submucosal dissection using agarose: comparison with other media. J Clin Pathol. 63:904-909, 2010.