ポロソームに焦点をあてた分泌機構抑制による機能性下垂体腺腫の新しい治療法の確立

• 研究課題/領域番号: 20591723
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 脳神経外科学
• 研究機関: 帝京大学
• 研究代表者: 松野 彰 帝京大学, 医学部, 教授 (00242058)
• 連携研究者: 水谷 晃子 帝京平成大学, 健康メディカル学部, 助教 (80465252)
• 研究期間 (年度): 2008 – 2010
• 研究課題ステータス: 完了 (2010年度)
• 配分額: 4,550千円 (直接経費: 3,500千円、間接経費: 1,050千円); 2010年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円); 2009年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円); 2008年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
• キーワード: 下垂体細胞 / 成長ホルモン / ポロソーム / 分泌機構 / 細胞内輸送 / VAMP / fodrin / porosome / GH / pituitary cell / siRNA / GH3 cell / AtT-20 cell / EYFP-GH

研究概要

蛍光タンパクと成長ホルモンとの融合蛋白の遺伝子を発現する、ラット下垂体培養細胞において、ポロソームの存在を確認した。ついで、ポロソームの分泌顆粒側の構成因子であるVAMPと介在分子であるfodrinについて、これらが成長ホルモンの分泌において必須であることを明らかにした。これらの分子の抑制が、成長ホルモンの分泌抑制をおこすこと、ひいては成長ホルモン産生下垂体腺腫の新たな治療方法となりうると考えられた。

研究成果

• [雑誌論文] Skull base metastasis from follicular thyroid carcinoma: A report of two cases. (2010)
  • 著者名/発表者名: Matsuno A, Katakami H, Okazaki R, Yamada S, Sasaki M, Nakaguchi H, Yamada SM, Hoya K, Murakami M, Yamazaki K, Ishida Y, Iwasaki H, Kuyama J, Kakudo K
  • 雑誌名: Neurol Med Chir (Tokyo) 50 ページ: 421-425
  • 査読あり
• [雑誌論文] Small cell carcinoma originating from the cavernous sinus. (2010)
  • 著者名/発表者名: Nakaguchi H, Matsuno A, Miyawaki S, Murakami M, Yamada M, Yamazaki K, Ishida Y
  • 雑誌名: Acta Neurochir 152 ページ: 493-500
  • 査読あり
• [雑誌論文] the International FIPA consortium : Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families. (2010)
  • 著者名/発表者名: Igreja S, Chahal1 HS, King P, Bolger GB, Srirangalingam U, Guasti L, Chapple JP, Gueorguiev M, Guegan K, Stals K, Khoo B, Kumar AV, Ellard S, Grossman AB, Korbonits M
  • 雑誌名: Hum Mutat 31 ページ: 1-11
  • 査読あり
• [雑誌論文] SIRT1 regulates thyroid-stimulating hormone release by enhancing PIP5Kγ activity through deacetylation of specific lysine residues in mammals. (2010)
  • 著者名/発表者名: Asai-Akieda S, Zaima N, Ikegami K, Kahyo T, Yao I, Hatanaka T, Iemura S, Sugiyama R, Yokozeki T, Eishi Y, Koike M, Ikeda K, Chiba T, Yamaza H, Shimokawa I, Song SY,Matsuno A, Mizutani A, Sawabe M, Chao MV, Tanaka M, Kanaho Y, Natsume T, Sugimura H, Date Y, McBurney MW, Konioshi Y, Guarente L, Setou M
  • 雑誌名: PLoS One 5
  • 査読あり
• [雑誌論文] A rare association of ruptured left middle cerebral artery aneurysm and dextrocardia with situs inversus totalis. (2010)
  • 著者名/発表者名: Matsuno A, Miyawaki S, Yamada S, Ide F, Yamada SM, Nakaguchi H, Hoya K, Murakami M, Takeuchi M, Sugaya M
  • 雑誌名: Ir J Med Sci Sep 25(Epub ahead of print)
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• [雑誌論文] Current trends in the treatment of malignant pituitary tumors. (2010)
  • 著者名/発表者名: Matsuno A, Murakami M, Mizutani A, Nakaguchi H, Yamada SM, Hoya K, Ide F, Yamada S, Onda Y, Takeuchi M, Okinaga H
  • 雑誌名: Current Trends in Endocrinology 4 ページ: 1-7
  • 査読あり
• [雑誌論文] Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families (2010)
  • 著者名/発表者名: Igreja S, ら
  • 雑誌名: Hum Mutat 巻: 31 ページ: 1-11
  • 査読あり
• [雑誌論文] SIRT1 regulates thyroid-stimulating hormone release by enhancing PIP5Kγ activity through deacetylation of specific lysine residues in mammals (2010)
  • 著者名/発表者名: Asai-Akieda S, ら
  • 雑誌名: PLoS One 巻: 5
  • 査読あり
• [雑誌論文] Current trends in the treatment of malignant pituitary tumors (2010)
  • 著者名/発表者名: Matsuno A, ら
  • 雑誌名: Current Trends in Endocrinology 2010, 4 : 1-7 巻: 4 ページ: 1-7
  • 査読あり
• [雑誌論文] Oral administration of cilnidipine to patients with hypertensive intracerebral hemorrhage in an acute stage : significance and role of an N-type calcium channel blocker. (2009)
  • 著者名/発表者名: Matsuno A, Ide F, Tanaka H, Asano S, Miyawaki S, Uno T, Tanaka J, Nakaguchi H, Sasaki M, Murakami M, Fuke N
  • 雑誌名: Ir J Med Sci 178 ページ: 419-422
  • 査読あり
• [雑誌論文] Preoperative elevated serum growth hormone is preventive of osteopenia in postsurgical patients with pituitary somatotroph adenomas : comparison with clinically non-functioning adenomas. (2009)
  • 著者名/発表者名: Sasaki M, Okazaki R, Inoue D, Nakashima M, Ide F, Nakaguchi H, Yamada SM, Hoya K, Murakami M, Mizutani A, Okinaga H, Matsuno A
  • 雑誌名: Endocrinologist 19 ページ: 208-210
  • 査読あり
• [雑誌論文] Analyses of factors influencing the acute effect of octreotide in growth hormone-secreting adenomas. (2009)
  • 著者名/発表者名: Nakashima M, Takano K, Matsuno A
  • 雑誌名: Endocr J 56 ページ: 295-304
  • NAID: 10026913199
  • 査読あり
• [雑誌論文] Molecular pathogenesis and functional analysis of pituitary adenoma. (2009)
  • 著者名/発表者名: Matsuno A, Mizutani A, Takekoshi S, Osamura RY, Sanno N, Teramoto A, Ide F, Yamada S, Sasaki M, Nakaguchi H, Yamada SM, Hoya K, Murakami M, Okinaga H
  • 雑誌名: Current Trends in Neurology 3 ページ: 69-73
  • 査読あり
• [雑誌論文] Oral administration of cilnidipine to patients with hypertensive intracerebral hemorrhage in anacute stage : significance and role_of an N-type calcium channel blocker (2009)
  • 著者名/発表者名: Matsuno A, Ide F, Tanaka H, Asano S, Miyawaki S, Uno T, Tanaka, J, Nakaguchi H, Sasaki M, Murakami M, Fuke N
  • 雑誌名: Ir J Med Sci 178 ページ: 419-422
  • 査読あり
• [雑誌論文] Preoperative elevated serum growth hormone is preventive of osteonenia in postsurgical patients with pituitary somatotroph adenomas : comparison with clinically non-functioning adenomas (2009)
  • 著者名/発表者名: Sasaki M, Okazaki R, Inoue D, Nakashima, M, Ide F, Nakaguchi H, Yamada SM, Hoya K, Murakami M, Mizutani A, Okinaga H, Matsuno A
  • 雑誌名: Endocrinologist 19 ページ: 208-210
  • 査読あり
• [雑誌論文] Analyses of factors_influencing the acute effect of octreotide in growth hormone-secreting adenomas (2009)
  • 著者名/発表者名: Nakashima M, Takano K, Matsuno A
  • 雑誌名: Endocr J 56 ページ: 295-304
  • 査読あり
• [雑誌論文] Disappearance of gadolinium enhancement in a chemoresistant astrocytoma of the tectum after high dose interferon beta. (2008)
  • 著者名/発表者名: Matsuno A, Fujimaki T, Mizutani A, Ide F, Tanaka H, Asano S, Miyawaki S, Uno T, Tanaka J, Nakaguchi H, Sasaki M, Murakami M, Yamazaki K, Ishida Y
  • 雑誌名: Tumori 94 ページ: 853-855
  • 査読あり
• [雑誌論文] Effective combined medical treatment with octreotide long acting release (Sandostatin LAR) and cabergoline for an extremely rare pituitary somatotroph adenoma producing growth hormone-releasing hormone (2008)
  • 著者名/発表者名: Matsuno A, Katakami H, Okazaki R, Mizutani A, Osamura RY, Miyawaki S, Uno T, Ide F, Asano S, Tanaka J, Nakaguchi H, Sasaki M, Murakami M, Yamazaki K, Ishida Y, Okinaga H, Teramoto A
  • 雑誌名: Endocrinologist 18 ページ: 266-269
  • 査読あり
• [雑誌論文] Co-transfection of EYFP-GH and ECFP-rab3B in an experimental pituitary GH3 cell: a role of rab3B in secretion of GH through porosome. (2008)
  • 著者名/発表者名: Matsuno A, Itoh J, Mizutani A, Takekoshi S, Osamura RY, Okinaga H, Ide F, Miyawaki S, Uno T, Asano S, Tanaka J, Nakaguchi H, Sasaki M, Murakami M
  • 雑誌名: Folia Histochem Cytobiol 46 ページ: 419-421
  • 査読あり
• [雑誌論文] Prediction of the incidence of spontaneous intracerebral hemorrhage from meteorological data. (2008)
  • 著者名/発表者名: Nakaguchi H, Matsuno A, Teraoka A
  • 雑誌名: Int J Biometeorol 52 ページ: 323-329
  • 査読あり
• [雑誌論文] The role of the AIP gene in familial and sporadic pituitary adenomas. (2008)
  • 著者名/発表者名: Leontiou CA, Gueorguiev M, van der Spuy J, Quinton R, Lolli F, Hassan S, Chahal HS, Igreja SC, Jordan S, Rowe J, Stolbrink M, Christian HC, Wray J, Bishop-Bailey D, Berney DM, Wass JAH, Popovic V, Ribeiro-Oliveira Jr. A, Gadelha MR, Monson JP, Davis JR, Clayton RN, Yoshimoto K, Iwata T, Matsuno A, Eguchi K, Musat M, Peters G, Bolger G, Chapple JP, Frohman LA, Grossman AB, Korbonits M
  • 雑誌名: J Clin Endocrinol Metab 93 ページ: 2390-2401
  • 査読あり
• [雑誌論文] Co-transfection of EYFP-GH and ECFP-rab3B in an experimental pituitary GH3 cell : a role of rab3B in secretion of GH through porosome (2008)
  • 著者名/発表者名: Matsuno A, et al.
  • 雑誌名: Folia Histochem Cytobiol 46 ページ: 419-421
  • 査読あり
• [雑誌論文] Effective combined medical treatment with octreotide long acting release (Sandostatin LAR) and cabergoline for an extremely rare pituitary somatotroph adenoma producing growth hormone-releasing hormone (2008)
  • 著者名/発表者名: Matsuno A, et al.
  • 雑誌名: Endocrinologist 18 ページ: 266-269
  • 査読あり
• [雑誌論文] The role of the AIP gene in familial and sporadic pituitary adenomas (2008)
  • 著者名/発表者名: Leontiou CA, et al.
  • 雑誌名: J Clin Endocrinol Metab 93 ページ: 2390-2401
  • 査読あり
• [雑誌論文] Disappearance of gadolinium enhancement in a chemoresistant astrocytoma of the tectum after high dose interferon β (2008)
  • 著者名/発表者名: Matsuno A, et al.
  • 雑誌名: Tumori 2008 94 ページ: 853-855
  • 査読あり
• [雑誌論文] Functional molecular morphology of anterior pituitary cells, from hormone production to intracellular transport and secretion.
  • 著者名/発表者名: Matsuno A, Mizutani A, Okinaga H, Takano K, Yamada S, Yamada SM, Nakaguchi H, Hoya K, Murakami M, Takeuchi M, Sugaya M, Itoh J, Takekoshi S, Osamura RY
  • 雑誌名: Med Mol Morphol (in press)
  • NAID: 10029036664
  • 査読あり
• [雑誌論文] A mechanism of aquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma
  • 著者名/発表者名: Murakami M, Mizutani A, Asano S, Katakami H, Ozawa Y, Yamazaki K, Ishida Y, Takano K, Okinaga H, Matsuno A
  • 雑誌名: Neurosurgery (in press)
  • 査読あり
• [雑誌論文] Combination therapy with rituximab and temozolomide for recurrent and refractory primary central nervous system lymphoma.
  • 著者名/発表者名: Murakami M, Fujimaki T, Asano S, Nakaguchi H, Yamada SM, Hoya K, Yamazaki K, Ishida Y, Matsuno A
  • 雑誌名: Yonsei Med J (in press)
  • 査読あり
• [雑誌論文] Abnormal dynamics of growth hormone after thyrotropin-releasing hormone loading test, gonadotropin-releasing hormone loading test, and oral glucose tolerance test in mixed gonadal dysgenesis with a pituitary lesion.
  • 著者名/発表者名: Matsuno A, Yamada S, Yamada SM, Nakaguchi H, Hoya K, Murakami M
  • 雑誌名: International Journal of Case Reports and Images (in press)
  • 査読あり
• [学会発表] 下垂体細胞における下垂体ホルモンmRNAと蛋白の細胞内発現と細胞内動態、分泌機構の可視化 (2010)
  • 著者名/発表者名: 松野彰
  • 学会等名: 第42回日本臨床分子形態学会
  • 発表場所: 三島
  • 年月日: 2010-09-25
• [学会発表] Microsurgery and neuroendoscopic surgery of pituitary tumors with medical and pathological studies. (2010)
  • 著者名/発表者名: Matsuno A
  • 学会等名: The 4th International Neurosurgical Conference
  • 発表場所: Harbin, China
  • 年月日: 2010-07-17
• [学会発表] Microsurgery and neuroendoscopic surgery of pituitary tumors with medical and pathological studies (2010)
  • 著者名/発表者名: Matsuno A
  • 学会等名: The 4^<th> International Neurosurgical Conference
  • 発表場所: Harbin, China
  • 年月日: 2010-07-17
• [学会発表] Temozolomide treatment of malignant pituitary tumors. (2010)
  • 著者名/発表者名: Matsuno A, Murakami M, Mizutani A, Nakaguchi H, Yamada SM, Hoya K
  • 学会等名: The 8th China-Japan Friendship Neurosurgical Symposium
  • 発表場所: Chengdu, China
  • 年月日: 2010-06-18
• [学会発表] A case of subarachnoid with pituitary apoplexy caused by idiopathic pachymeningitis. (2010)
  • 著者名/発表者名: Yamada SM, Yamada S, Onda Y, Nakaguchi H, Murakami M, Hoya K, Matsuno A, Nakayama H
  • 学会等名: The 8th China-Japan Friendship Neurosurgical Symposium
  • 発表場所: Chengdu, China
  • 年月日: 2010-06-18
• [学会発表] Temozolomide treatment of malignant pituitary tumors. (2010)
  • 著者名/発表者名: Matsuno A, Murakami M, Mizutani A, Yamada S, Onda Y, Nakaguchi H, Yamada SM, Hoya K, Okinaga H
  • 学会等名: The 2nd Russian-Japanese Neurosurgical Symposium
  • 発表場所: Yamanashi
  • 年月日: 2010-05-10
• [学会発表] Differential diagnosis of adrenocorticotropin (ACTH) insufficiency by a novel ultrasensitive EIA. (2010)
  • 著者名/発表者名: Katakami H, Hashida S, Matsuno A, Miyamura N, Usui T, Yamada S, Nishikawa T
  • 学会等名: ICE2010
  • 発表場所: Kyoto, Japan
  • 年月日: 2010-03-27
• [学会発表] Effectiveness and ineffectiveness of temozolomide for atypical prolactinoma and prolactin-producing pituitary carcinoma. (2010)
  • 著者名/発表者名: Matsuno A, Mizutani A, Yamada S, Onda Y, Nakaguchi H, Yamada SM, Hoya K, Murakami M, Okinaga H, Ishibashi S
  • 学会等名: Joint Neurosurgical Convention 2010
  • 発表場所: Hawaii, USA
  • 年月日: 2010-01-24
• [学会発表] Temozolomide is not effective for recurrent pituitary carcinoma transformed from atypical adenoma. (2010)
  • 著者名/発表者名: Matsuno A, Murakami M, Mizutani A, Asano S, Ishida Y, Okinaga H
  • 学会等名: 21^<st> Annual Meeting of Asaia-Pacific Endocrine Conference
  • 発表場所: Taipei, Taiwan
  • 年月日: 2010-01-10
• [学会発表] Temozolomide is not effective for recurrent pituitary carcinoma transformed from atypical adenoma. (2009)
  • 著者名/発表者名: Matsuno A, Murakami M, Mizutani A, Asano S, Yamazaki K, Ishida Y, Okinaga H
  • 学会等名: The 9th China-Japan Joint Seminar on Histochemistry and Cytochemistry
  • 発表場所: 南寧、中国
  • 年月日: 2009-11-05
• [学会発表] Temozolomide is not effective for recurrent pituitary carcinoma transformed from atypical a denoma (2009)
  • 著者名/発表者名: Matsuno A, Murakami M, Mizutani, A, Asano S, Ishida Y, Yamazaki K, Okinaga H
  • 学会等名: The 9th China-Japan Joint Seminar on Histochemistry and Cytochemistry
  • 発表場所: Nannng, China
  • 年月日: 2009-11-05
• [学会発表] Temozolomide is not effective for recurrent pituitary carcinoma transformed from atypical adenoma. (2009)
  • 著者名/発表者名: Matsuno A, Murakami M, Mizutani A, Asano S, Ishida Y, Okinaga H
  • 学会等名: The 11th International Pituitary Pathology Society (IPPS) Meeting
  • 発表場所: Awaji, Japan
  • 年月日: 2009-10-19
• [学会発表] Temozolomide is not effective for recurrent pituitary carcinoma transformed from atypical adenoma (2009)
  • 著者名/発表者名: Matsuno A, Murakami M, Mizutani, A, Asano S, Ishida Y, Okinaga H
  • 学会等名: The 11th International Pituitary Pathology Society (IPPS) Meeting
  • 発表場所: Awaji, Japan
  • 年月日: 2009-10-19
• [学会発表] Intravenous rituximab combined with temozolomide as a second line therapy for CD20 positive primary central nervous system malignant lymphoma. (2009)
  • 著者名/発表者名: Matsuno A, Murakami M, Nakaguchi H, Sasaki M, Uno T, Ide F, Tanaka H, Fujimaki T
  • 学会等名: The 3rd Quadrennial Meeting of the World Federation of Neuro-Oncology, jointly with The 6th Meeting of the Asian Society for Neuro-Oncology
  • 発表場所: Yokohama, Japan
  • 年月日: 2009-05-14
• [学会発表] Ectopic acromegaly due to extracranial GHRH-producing tumors in Japan : Prevalence and clinical features. (2009)
  • 著者名/発表者名: Katakami H, Genga S, Kawa S, Fujii S, Okajima T, Ishikwa E, , Nishina Y, Sugihara H, Kurita M, Hizuka N, Yamada S, Matsuno A, Hashida S
  • 学会等名: The 11th International Pituitary Congress
  • 発表場所: Washinton D.C., U.S.A.
• [学会発表] In situ hybridization with quantum dot detection and confocal scanning microscopy for three-dimensional visualization of protein and mRNA : comparison with electron microscopic in situ hybridization. (2008)
  • 著者名/発表者名: Matsuno A
  • 学会等名: The 13th Congress of the International Federation of Societies for Histochemistry and Cytochemistry
  • 発表場所: Gdansk, Poland
  • 年月日: 2008-08-27
• [学会発表] In situ hybridization with quantum dot detection and confocal scanning microscopy for three-dimensional visualization of protein and mRNA : comparison with electron microscopic in situ hybridization (2008)
  • 著者名/発表者名: Matsuno A
  • 学会等名: The 13th Congress of the International Federation of Societies for Histochemistry and Cytochemistry
  • 発表場所: Gdansk, Poland
  • 年月日: 2008-08-27
• [学会発表] Contribution of factors influencing the acute effect of octreotide in GH-secreting adenomas. (2008)
  • 著者名/発表者名: Matsuno A, Nakashima M, Takano K, Yasufuku-Takano J, Mizutani A, Osamura RY, Takei M, Tahara S, Teramoto A, Yamada M, Yamazaki K, Ishida Y, Katakami H, Ide F, Miyawaki S, Uno T, Tanaka J, Asano S, Nakaguchi H, Sasaki M, Murakami M
  • 学会等名: 19th Annual Meeting of Asaia-Pacific Endocrine Conference
  • 発表場所: Shzhou, China
  • 年月日: 2008-01-13
• [図書] Progress in Laser and Electro-Optics Research. (2010)
  • 著者名/発表者名: Matsuno A, Mizutani A, Itoh J, Utsunomiya H, Takekoshi S, Osamura RY
  • 出版者: Nova Science Publishers, Inc.
• [図書] Antisense Elements (Genetics) Research Focus. (2008)
  • 著者名/発表者名: Matsuno A
  • 出版者: Nova Science Publishers, Inc.
• [図書] Quantum Dots : Research, Technology and Applications. (2008)
  • 著者名/発表者名: Matsuno A, Mizutani A, Takekoshi S, Osamura RY, Itoh J, Ide F, Miyawaki S, Uno T, Asano S, Tanaka J, Nakaguchi H, Sasaki M, Murakami M, Okinaga H
  • 出版者: Nova Science Publishers, Inc.
• [図書] New Research on Neurosecretory Systems. (2008)
  • 著者名/発表者名: Matsuno A, Mizutani A, Takekoshi S, Osamura RY, Itoh J, Takano K, Ide F, Miyawaki S, Uno T, Asano S, Tanaka J, Nakaguchi H, Sasaki M, Murakami M, Okinaga H
  • 出版者: Nova Science Publishers, Inc.