研究業績：酵素補充療法｜千葉大学病院未来開拓センター

酵素補充療法

Tamaki A, Kuroda M, Yonaha K, Ishiki Y, Uehara M, Nakayama Y, Honma KI, Chinen R, Uema T, Okamoto S, Miyoshi J, Kirinashizawa M, Sato K, Aohara T, Yamamoto M, Maezawa Y, Yokote K, Masuzaki H. A Rare Case of Autoimmune-Mediated Lecithin:Cholesterol Acyltransferase Insufficiency Manifesting as the Acute Onset of Extremely Hypo-High-Density Lipoprotein-Cholesterolemia and Spontaneous Improvement: A Case Report with a Review of the Literature. J Atheroscler Thromb. 2024 Dec 10. doi: 10.5551/jat.65298. Epub ahead of print. PMID: 39662947. 2024 in press.
Miyata M, Kuroda M, Miyoshi J, Kirinashizawa M, Nagasawa R, Yamamoto M, Akasaki Y, Utatsu K, Maezawa Y, Yokote K, Ohishi M. Novel pathogenic variant in the LCAT gene in a compound heterozygous patient with fish-eye disease and a mild phenotype. J Clin Lipidol. 2025 Jan-Feb;19(1):125-133. doi: 10.1016/j.jacl.2024.09.013. Epub 2024 Oct 2. PMID: 39537502.
黒田正幸、斯波真理子. LCAT欠損症．希少疾病ライブラリ（企画・制作ケアネット）　2024/09/12
Teranaka R, Fujimoto H, Masuda T, Kuroda M, Aoyagi Y, Nagashima T, Takada M, Sakakibara J, Yamada H, Yamamoto H, Kubota Y, Ohtsuka M. Ex vivo dual gene therapy using human adipocytes secreting anti-HER2 antibody on HER2-positive xenograft tumor models. Breast Cancer. 2023 Nov;30(6):1018-1027. doi:10.1007/s12282-023-01497-8. Epub 2023 Aug 23. PMID: 37612442.

黒田正幸、横手幸太郎. 家族性LCAT 欠損症を対象としたex vivo 脂肪細胞遺伝子治療遺伝子治療開発研究ハンドブック第2版、第1章Ex vivo遺伝子治療、第3節、脂肪細胞を標的とするex vivo 遺伝子治療、p290-p296、株式会社エヌ・ティー・エス、発行日2023/4/30

Aso M, Yamamoto TT, Kuroda M, Wada J, Kubota Y, Ishikawa K, Maezawa Y, Teramoto N, Tawada A, Asada S, Aoyagi Y, Kirinashizawa M, Onitake A, Matsumura Y, Yasunaga K, Konno S, Nishino K, Yamamoto M, Miyoshi J, Kobayashi N, Tanio M, Ikeuchi T, Igari H, Mitsukawa N, Hanaoka H, Yokote K, Saito Y.(2022) First-in-human autologous implantation of genetically modified adipocytes expressing LCAT for the treatment of familial LCAT deficiency. Heliyon, 2022 e11271 DOI:10.1016/j.heliyon.2022.e11271
Kuroda M, Hori M, Maezawa Y, Kubota Y, Mitsukawa N, Shiko Y, Ozawa Y, Kawasaki Y, Saito Y, Hanaoka H, Yokote K. LCAT-trial-24 weeks: Protocol for a clinical study to evaluate the safety of regenerative medicine and gene therapy by the autologous transplantation of human lecithin:cholesterol acyltransferase gene-transduced human pre-adipocytes. Contemp Clin Trials Commun. 2022 Jun 9;28:100946. DOI:
10.1016/j.conctc.2022.100946
Takeda T, Ide T, Okuda D, Kuroda M, Asada S, Kirinashizawa M, Yamamoto M, Miyoshi J, Yokote K, Mizutani N. A novel homozygous frameshift mutation in the APOA1 gene associated with marked high-density lipoprotein deficiency. J Clin Lipidol. 2022 Jul-Aug;16(4):423-433.
DOI:10.1016/j.jacl.2022.06.001
Kubota Y, Nagano H, Kosaka K, Ogata H, Nakayama A, Yokoyama M, Murata K, Akita S, Kuriyama M, Furuyama N, Kuroda M, Tanaka T, Mitsukawa N. Epigenetic modifications underlie the differential adipogenic potential of preadipocytes derived from human subcutaneous fat tissue. Am J Physiol Cell Physiol. 2021 Sep 1;321(3):C596-C606.
DOI:10.1152/ajpcell.00387.2020

Kuroda M, Bujo H, Yokote K, Murano T, Yamaguchi T, Ogura M, Ikewaki K, Koseki M, Takeuchi Y, Nakatsuka A, Hori M, Matsuki K, Miida T, Yokoyama S, Wada J, Harada-Shiba M. Current Status of Familial LCAT Deficiency in Japan. J Atheroscler Thromb. 2021 Jul 1;28(7):679-691.
doi:10.5551/jat.RV17051

Yamamuro D, Yamazaki H, Osuga JI, Okada K, Wakabayashi T, Takei A, Takei S, Takahashi M, Nagashima S, Holleboom AG, Kuroda M, Bujo H, Ishibashi S. Esterification of 4β-hydroxycholesterol and other oxysterols in human plasma occurs independently of LCAT. J Lipid Res. 2020 Sep;61(9):1287-1299.
doi:10.1194/jlr.RA119000512
Masuda T, Fujimoto H, Teranaka R, Kuroda M, Aoyagi Y, Nagashima T, Sangai T, Takada M, Nakagawa A, Kubota Y, Yokote K, Ohtsuka M. Anti-HER2 antibody therapy using gene-transduced adipocytes for HER2-positive breast cancer. Breast Cancer Res Treat. 2020 Apr;180(3):625-634.
doi:10.1007/s10549-020-05581-x
Sasahara Y, Kubota Y, Kosaka K, Adachi N, Yamaji Y, Nagano H, Akita S, Kuroda M, Tanaka T, Bujo H, Mitsukawa N. Adipose-Derived Stem Cells and Ceiling Culture-Derived Preadipocytes Cultured from Subcutaneous Fat Tissue Differ in Their Epigenetic Characteristics and Osteogenic Potential. Plast Reconstr Surg. 2019 Sep;144(3):644-655.
DOI:10.1097/PRS.0000000000005913
黒田正幸、横手幸太郎. 家族性LCAT欠損症の過去・現在・未来. The Lipid, 2019, 30; 71-78.
Ishibashi R, Takemoto M, Tsurutani Y, Kuroda M, Ogawa M, Wakabayashi H, Uesugi N, Nagata M, Imai N, Hattori A, Sakamoto K, Kitamoto T, Maezawa Y, Narita I, Hiroi S, Furuta A, Miida T, Yokote K. (2018) Immune-mediated acquired lecithin-cholesterol acyltransferase deficiency: A case report and literature review. J Clin Lipidol. 12, 888-897.
Kuroda M, Saito Y, Aso M, Yokote K. (2018) A novel approach to the treatment of plasma protein deficiency: Ex vivo-manipulated adipocytes for sustained secretion oftherapeutic proteins. Chem. Pharm. Bull. 66, 217-224.
Baba Y, Kaneko H, Takemoto M, Ide K, Haga Y, Kanda T, Akita S, Kubota Y, Kuroda M, Kitagawa Y, Yokote K. (2017) Case of lipoatrophic diabetes induced by juvenile dermatomyositis.J Diabetes Investig. 2017 Sep 12. doi: 10.1111/jdi.12745.
黒田正幸、横手幸太郎. 内分泌代謝分野における遺伝子治療の現状と課題．糖尿病と遺伝－患者さんからの質問に的確にこたえるために．糖尿病診療マスター、医学書院、2017年7月15日発行
黒田正幸、横手幸太郎．角膜混濁・蛋白尿にHDL低下があれば千葉大学発　世界に先駆けた難病治療研究－家族性LCAT欠損症の難病指定と再生医療研究の開始－．千葉県医師会雑誌、2017; 69(1): 36-39.
Tanino A, Okura T, Nagao T, Kukida M, Enomoto D, Miyoshi K, Higaki J, Kuroda M, Bujo H. (2016) A case of acquired lecithin:cholesterol acyltransferase deficiency with sarcoidosis that remitted spontaneously. CEN Case Rep. 5, 1-5.
黒田正幸、武城英明、齋藤康、横手幸太郎. 遺伝的酵素欠損症に対する遺伝子・細胞治療. 内分泌疾患のtrends & topics 2016. 月刊Mebio. メジカルレビュー社、2016.33.75-82.
黒田正幸、横手幸太郎. 遺伝子導入脂肪細胞の移植による持続的酵素補充療法-家族性LCAT 欠損症を対象とした治療法開発と難治性疾患への応用展開-,再生医療等製品の開発と実用化展望第16章; p123-130、シーエムシー出版、2016年6月発行
黒田正幸、武城英明、麻生雅是、齋藤康、横手幸太郎. 疾患治療用タンパク質分泌加工脂肪細胞の創薬開発と難病治療. 薬学雑誌-Symposium Review- 2016, 136; 705-709.
Kosaka K, Kubota Y, Adachi N, Akita S, Sasahara Y, Kira T, Kuroda M, Mitsukawa N, Bujo H, and Satoh K. (2016) Human adipocytes from the subcutaneous superficial layer have greater adipogenic potential and lower PPAR-γ DNA methylation levels than deep layer adipocytes. Am. J. Physiol. Cell Physiol. 311, C322-329.
Adachi N, Kubota Y, Kosaka K, Akita S, Sasahara Y, Kira T, Kuroda M, Mitsukawa N, Bujo H, Satoh K. (2015) Low-dose radiation pretreatment improves survival of human ceiling culture-derived proliferative adipocytes (ccdPAs) under hypoxia via HIF-1 alpha and MMP-2 induction. Biochem Biophys Res Commun. 463, 1176-1183.
Fujisaki K, Fujimoto H, Sangai T, Nagashima T, Sakakibara M, Shiina N, Kuroda M, Aoyagi Y, Miyazaki M. (2015) Cancer-mediated adipose reversion promotes cancer cell migration via IL-6 and MCP-1. Breast Cancer Res Treat. 150: 255-263
瀬川茉莉、星　明彦、成瀬紘也、黒田正幸、武城英明、宇川義一. (2015) Valosin-containing protein (VCP) 遺伝子変異を認めた家族性筋萎縮性側索硬化症の1例臨床神経学. 55, 914-920.
黒田正幸、横手幸太郎. リポ蛋白受容体, 高LDL-C血症・低HDL-C血症-診断と治療のABC 101-、最新医学別冊、最新医学社、2015/1/15発行
黒田正幸、武城英明. 脂質異常症の遺伝子細胞治療－LCAT欠損症患者への新規治療法の開発－, Annual Review 2015 糖尿病・代謝・内分泌、中外医学社、2015, 128-132
黒田正幸、武城英明. LCAT欠損症の診断と治療, 腎と透析（特集、腎のたまり病）、東京医学社、2014, 77; 226-230.
Kuroda M, Holleboom AG, Stroes E, Asada S, Aoyagi Y, Kamata K, Yamashita S, Ishibashi S, Saito Y, Bujo H. Lipoprotein subfractions highly associated with renal damage in familial LCAT deficiency Arterioscler Thromb Vasc Biol. 2014; 34(8), 1756-1762.
Naito S, Kamata M, Furuya M, Hayashi M, Kuroda M, Bujo H, Kamata K. Amelioration of circulating lipoprotein profile and proteinuria in a patient with LCAT deficiency due to a novel mutation (Cys74Tyr) in the lid region of LCAT under a fat-restricted diet and ARB treatment. Atherosclerosis. 2013; 228, 193-197.
Ogita M, Miyauchi K, Dohi T, Tsuboi S, Miyazaki T, Yokoyama T, Yokoyama K, Shimada K, Kurata T, Jiang M, Bujo H, Daida H. Increased circulating soluble LR11 in patients with acute coronary syndrome. Clin Chim Acta. 2013; 415: 191-194.
Fukaya Y, Kuroda M, Aoyagi Y, Asada S, Kubota Y, Okamoto Y, Nakayama T, Saito Y, Satoh K, and Bujo H. Platelet-rich plasma inhibits the apoptosis of highly adipogenic homogeneous preadipocytes in an in vitro culture system. Exp Mol Med. 2012; 44: 330-339.
Takahashi M, Bujo H, Shiba T, Jiang M, Maeno T, Shirai K. Enhanced circulating soluble LR11 in patients with diabetic retinopathy. Am J Ophthalmol. 2012; 154: 187-192.
Sakai S, Nakaseko C, Takeuchi M, Ohwada C, Shimizu N, Tsukamoto S, Kawaguchi T, Jiang M, Sato Y, Ebinuma H, Yokote K, Iwama A, Fukamachi I, Schneider WJ, Saito Y, and Bujo H. Circulating soluble LR11/SorLA levels are highly increased and ameliorated by chemotherapy in acute leukemias. Clin Chim Acta. 2012; 413: 1542-1548.
Harada-Shiba M, Arai H, Okamura T, Yokote K, Oikawa S, Nohara A, Okada T, Ohta T, Bujo H, Watanabe M, Wakatsuki A, Yamashita S. Multicenter study to determine the diagnosis criteria of heterozygous familial hypercholesterolemia in Japan. J Atheroscler Thromb. 2012; 19: 1019-1026.
Harada-Shiba M, Arai H, Oikawa S, Ohta T, Okada T, Okamura T, Nohara A, Bujo H, Yokote K, Wakatsuki A, Ishibashi S, Yamashita S. Guidelines for the management of familial hypercholesterolemia. J Atheroscler Thromb. 2012; 19: 1043-1060.
Fukaya Y, Kuroda M, Aoyagi Y, Asada S, Kubota Y, Okamoto Y, Nakayama T, Saito Y, Satoh K, Bujo H. Platelet-rich plasma inhibits the apoptosis of highly adipogenic homogeneous preadipocytes in an in vitro culture system. Exp Mol Med. 2012; 44(5): 330-339
Aoyagi Y, Kuroda M, Asada S, Tanaka S, Konno S, Tanio M, Aso M, Okamoto Y, Nakayama T, Saito Y, Bujo H. Fibrin glue is a candidate scaffold for long-term therapeutic protein expression in spontaneously differentiated adipocytes in vitro. Exp Cell Res. 2012; 318(1): 8-15.
Katayama A, Wada J, Usui-Kataoka H, Yamasaki H, Teshigawara S, Terami T, Inoue K, Kanzaki M, Murakami K, Nakatsuka A, Sugiyama H, Koide N, Bujo H, Makino H. Two novel mutations of lecithin:cholesterol acyltransferase (LCAT) gene and the influence of APOE genotypes on clinical manifestations. NDT Plus. 2011;4:299-302
Kuroda M, Bujo H, Aso M, and Saito Y. Adipocytes as a vehicle for ex vivo gene
therapy: Novel replacement therapy for diabetes and other metabolic diseases. J Diabetes Invest. 2011; 2: 333-340.
Aoyagi Y, Kuroda M, Asada S, Bujo H, Tanaka S, Konno S, Tanio M, Ishii I, Aso M, and Saito Y. Fibrin glue increases the cell survival and the transduced gene product secretion of the ceiling culture-derived adipocytes transplanted in mice. Exp Mol Med. 2011; 43: 161-7.
Asada S, Kuroda M, Aoyagi Y, Fukaya Y, Tanaka S, Konno S, Tanio M, Aso M, Okamoto Y, Nakayama T, Saito Y, and Bujo H. Ceiling culture-derived proliferative adipocytes retain high adipogenic potential suitable for use as a vehicle for gene transduction therapy. Am J Physiol Cell Physiol. 2011; 301: C181-C185.
Asada S, Kuroda M, Aoyagi Y, Bujo H, Tanaka S, Konno S, Tanio M, Ishii I, Aso M, and Saito Y. Disturbed apolipoprotein A-I-containing lipoproteins in fish-eye disease are improved by the lecithin:cholesterol acyltransferase produced by gene-transduced adipocytes in vitro. Mol Genet Metab. 2011; 102: 229-31.
Kuroda M, Aoyagi Y, Asada S, Bujo H, Tanaka S, Konno S, Tanio M, Ishii I, Machida K, Matsumoto F, Satoh K, Aso M, Saito Y. Ceiling culture-derived proliferative adipocytes are a possible delivery vehicle for enzyme replacement therapy in lecithin:cholesterol acyltransferase deficiency. The Open Gene Ther J. 2011; 4: 1-10.
Nakata Z, Nagae M, Yasui N, Bujo H, Nogi T, and Takagi J. Crystallization and preliminary crystallographic analysis of human LR11 Vps10p domain. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011; 67(Pt 1): 129-32.
Ikeuchi T, Hirayama S, Miida T, Fukamachi I, Tokutake T, Ebinuma H, Takubo K, Kaneko H, Kasuga K, Kakita A, Takahashi H, Bujo H, Saito Y, Nishizawa M. Increased Levels of Soluble LR11 in Cerebrospinal Fluid of Alzheimer Disease. Demen Geriat Cognit Disord. 2010; 30 :28-32.
Takahashi M, Bujo H, Jiang M, Noike H, Saito Y, Shirai K. Enhanced circulating soluble LR11 in patients with coronary organic stenosis. Atherosclerosis. 2010; 210: 581-4.
Unoki-Kubota H, Yamagishi SI, Takeuchi M, Bujo H, Saito Y. Pyridoxamine, an Inhibitor of Advanced Glycation End Product (AGE) Formation Ameliorates Insulin Resistance in Obese, Type 2 Diabetic Mice. Protein Pept Lett. 2010; 17: 1177-81.
Unoki-Kubota H, Yamagishi S, Takeuchi M, Bujo H, Saito Y. Pyridoxamine, an inhibitor of advanced glycation end product (AGE) formation ameliorates insulin resistance in obese, type 2 diabetic mice. Protein Pept Lett. 2010; 17: 1177-81.
Matsuo M, Ebinuma H, Fukamachi I, Jiang M, Bujo H, Saito Y. Development of an Immunoassay for the Quantification of Soluble LR11, a Circulating Marker of Atherosclerosis. Clin Chem. 2009; 55: 1801-8.
Neff Y, Bujo H, Miyashita Y, Uchida D, Ban T, Tashiro T, Yamazaki K, Ishikawa K, Tokuyama T, Jiang M, Kawamura T, Saito, Y. The potential role of patient awareness regarding one's own medical data in the management of lifestyle-related. Chiba Medical Journal. 2009; 85: 125-34.
Tashiro J, Miyazaki O, Nakamura Y, Miyazaki A, Fukamachi I, Bujo H, and Saito Y. Plasma Preβ1-HDL level is elevated in unstable angina pectoris. Atherosclerosis. 2009; 204: 595-600.
Jiang M, Bujo H, Ohwaki K, Unoki H, Yamazaki H, Kanaki T, Shibasaki M, Azuma K, Harigaya K, Schnerider W J, Saito Y. AngII - stimulated migration of vascular SMC is dependent on LR11. J Clin Invest. 2008; 118: 2733-46.
Kawamura T, Murakami K, Bujo H, Unoki H, Jiang M, Nakayama T, Saito Y. Matrix metalloproteinase-3 enhances the free fatty acids-induced VEGF expression in adipocytes through toll-like receptor 2. Exp Biol Med. 2008; 283: 1213-21.
Kuramochi D, Unoki H, Bujo H, Kubota Y, Jiang M, Rikihisa N, Udagawa A, Yoshimoto S, Ichinose M, Saito Y. Matrix metalloproteinase 2 improves the transplanted adipocyte survival in mice. Eur J Clin Invest. 2008; 38: 752-9.
Yamashita S, Bujo H, Arai H, Harada-Shiba M, Matsui S, Fukushima M, Saito Y, Kita T, Matsuzawa, Y. Long-term probucol treatment prevents secondary cardiovascular events: a cohort study of patients with heterozygous familial hypercholesterolemia in Japan. J Atheroscler Thromb. 2008; 15: 292-303.