神戸大学附属図書館デジタルアーカイブ
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https://hdl.handle.net/20.500.14094/90008429
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2024-05-23
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90008429 (fulltext)
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メタデータID
90008429
アクセス権
open access
出版タイプ
Version of Record
タイトル
Aggressive Cushing's Disease: Molecular Pathology and Its Therapeutic Approach
著者
Yamamoto, Masaaki ; Nakao, Takahiro ; Ogawa, Wataru ; Fukuoka, Hidenori
著者ID
A2522
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=8f5d3ac259d263b9520e17560c007669
著者名
Yamamoto, Masaaki
山本, 雅昭
ヤマモト, マサアキ
所属機関名
医学部附属病院
著者名
Nakao, Takahiro
著者ID
A1358
研究者ID
1000040294219
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=38228987a3a438c8520e17560c007669
著者名
Ogawa, Wataru
小川, 渉
オガワ, ワタル
所属機関名
医学研究科
著者ID
A1463
研究者ID
1000080622068
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=7a6e73f7fe330695520e17560c007669
著者名
Fukuoka, Hidenori
福岡, 秀規
フクオカ, ヒデノリ
所属機関名
医学部附属病院
収録物名
Frontiers in Endocrinology
巻(号)
12
ページ
650791
出版者
Frontiers Media
刊行日
2021-06-16
公開日
2021-07-13
抄録
Cushing's disease is a syndromic pathological condition caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (ACTHomas) mediated by hypercortisolemia. It may have a severe clinical course, including infection, psychiatric disorders, hypercoagulability, and metabolic abnormalities, despite the generally small, nonaggressive nature of the tumors. Up to 20% of ACTHomas show aggressive behavior, which is related to poor surgical outcomes, postsurgical recurrence, serious clinical course, and high mortality. Although several gene variants have been identified in both germline and somatic changes in Cushing's disease, the pathophysiology of aggressive ACTHomas is poorly understood. In this review, we focused on the aggressiveness of ACTHomas, its pathology, the current status of medical therapy, and future prospects. Crooke's cell adenoma (CCA), Nelson syndrome, and corticotroph pituitary carcinoma are representative refractory pituitary tumors that secrete superphysiological ACTH. Although clinically asymptomatic, silent corticotroph adenoma is an aggressive ACTH-producing pituitary adenoma. In this review, we summarize the current understanding of the pathophysiology of aggressive ACTHomas, including these tumors, from a molecular point of view based on genetic, pathological, and experimental evidence. The treatment of aggressive ACTHomas is clinically challenging and usually resistant to standard treatment, including surgery, radiotherapy, and established medical therapy (e.g., pasireotide and cabergoline). Temozolomide is the most prescribed pharmaceutical treatment for these tumors. Reports have shown that several treatments for patients with refractory ACTHomas include chemotherapy, such as cyclohexyl-chloroethyl-nitrosourea combined with 5-fluorouracil, or targeted therapies against several molecules including vascular endothelial growth factor receptor, cytotoxic T lymphocyte antigen 4, programmed cell death protein 1 (PD-1), and ligand for PD-1. Genetic and experimental evidence indicates that some possible therapeutic candidates are expected, such as epidermal growth factor receptor tyrosine kinase inhibitor, cyclin-dependent kinase inhibitor, and BRAF inhibitor. The development of novel treatment options for aggressive ACTHomas is an emerging task.
キーワード
Cushing's disease (CD)
aggressiveness
physiology
pathology
medical treatment/surgical treatment
targeted therapy
カテゴリ
医学研究科
医学部附属病院
学術雑誌論文
権利
© 2021 Yamamoto, Nakao, Ogawa and Fukuoka.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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資源タイプ
journal article
言語
English (英語)
eISSN
1664-2392
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関連情報
DOI
https://doi.org/10.3389/fendo.2021.650791
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