アルドステロン合成細胞(APC)を探して：高血圧症臓器障害の新たな機序の解明

2015 Fiscal Year Annual Research Report

• Project/Area Number: 15H04711
• Research Institution: Tohoku University
• Principal Investigator: 笹野 公伸 東北大学, 医学(系)研究科(研究院), 教授 (50187142)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 副腎 / ステロイド / アルドステロン / 免疫組織化学 / 高血圧 / 病理学

Outline of Annual Research Achievements

生前にステロイド投与歴がなく内分泌異常も明らかではない日本人剖検例94例（平均年齢39.5歳、男50例、女44例）の副腎パラフィン組織に対して、アルドステロン合成酵素であるAldosterone synthase (CYP11B2)の発現動態を免疫組織化学的に検討した。具体的には、アルドステロン合成が行なわれている副腎皮質球状層細胞の発現細胞数、面積を画像解析により評価した。
その結果、検討した多くの症例ではCYP11B2陽性細胞は球状層全体に観察されるのではなく、クラスター状に散見された。以上から、アルドステロン合成は球状層で瀰漫性には行なわれてはおらず、局所／結節性に合成が行われている事をはじめて証明した。
更に、このCYP11B2陽性細胞の発現度や分布に男女差はないものの、加齢に伴い結節様の副腎皮質細胞は面積、数共に増加していた。加えて、これらの合成細胞における様々なカルシウムチャネルおよびビタミンD受容体の発現動態も検討し、同じ球状層細胞の中でのアルドステロン合成能の有無はカルシウム代謝と密接に関係している事が示された。現在、アルドステロン産生合成に関するepigeneticな変化を検討する為に合成に密接に関係するmirco RNAの同定も行っている。また、既に最近アルドステロン産生腺腫(APA)で報告されている各種イオンチャネル(KCNJ5、ATP1A1、ATP2B3、CACNA1Dなど)の体細胞変異の有無との関連についても検討していく予定である。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Ⅰ. 剖検で得られた正常副腎及び手術検体で得られたAPA症例でAPCを同定する。: 剖検例では解析を一応達成し、APA症例では現在UMN, IHAなどの非腫瘍性原発性アルドステロン症との関係を含めて解析を進めている
Ⅱ. これらAPCにおけるアルドステロン合成動態の詳細をその制御機構を含めて明らかにする。：カルシウムチャネル関係のタンパク質発現動態との関係を検討した。培養細胞でアルドステロン合成と関係がある可能性があるmicroRNAを現在同定しているところである。
Ⅲ. 正常副腎皮質、APAでのAPCの病態意義を種々の臨床病理学的因子と相関させて解明する。：正常副腎皮質では加齢との相関を示し、血圧とは有意の相関はない事を認めた。　APAでは現在検討中である。
Ⅳ. 得られた結果が高血圧症やPAの新しい診断・治療方法の開発に結びつけられる可能性を模索する：現在検討中である

Strategy for Future Research Activity

1. 正常副腎皮質球状層でアルドステロンを合成している細胞とそうでない細胞間で、現在種々のアルドステロン合成の病態での関与が提唱されているカルシウムチャネルに関係するsomatic DNA mutationsが認められるのかどうかを、CYP11B2陽性のアルドステロン合成細胞、陰性の球状層細胞を顕微鏡下で単離し検討する。
2. 同様に培養細胞でアルドステロン合成に関係する事が同定されたmicroRNAが発現しているのかどうかを、CYP11B2陽性のアルドステロン合成細胞、陰性の球状層細胞を顕微鏡下で単離し検討する。
3. 上記の１、２の検討を APAのAPCCで行う。
4. 正常副腎皮質球状層でアルドステロンを合成している細胞、特に局所的に合成を行っているAPCCが原発性アルドステロン症とどのような関係があるのかを腫瘍性病変であるAPAばかりではなく非腫瘍性病変であるUMN, IHA等と比較検討を行い総合的に検索を進める。

Research Products

• [Journal Article] Androgen and breast cancer: an update. (2016)
  • Author(s): McNamara KM, Sasano H.
  • Journal Title: Curr Opin Endocrinol Diabetes Obes. Volume: 23 Pages: 249-256
  • DOI: 10.1097/MED.0000000000000251.
  • Peer Reviewed / Open Access
• [Journal Article] Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas. (2016)
  • Author(s): Takagi M, Miki Y, Miyashita M, Hata S, Yoda T, Hirakawa H, Sagara Y, Rai Y, Ohi Y, Tamaki K, Ishida T, Suzuki T, Ouchi N, Sasano H.
  • Journal Title: Breast Cancer Res Treat. Volume: 156 Pages: 45-55
  • DOI: 10.1007/s10549-016-3739-6.
  • Peer Reviewed / Open Access
• [Journal Article] Acute Exacerbation of Idiopathic Pulmonary Fibrosis Following Treatment for Cushing's Syndrome. (2016)
  • Author(s): Ohara N, Kaneko M, Sato K, Usuda H, Tanaka J, Maekawa T, Sasano H, Katakami H, Kaneko K, Kamoi K.
  • Journal Title: Intern Med. Volume: 55 Pages: 389-394
  • DOI: 10.2169/internalmedicine.55.5566.
  • Peer Reviewed / Open Access
• [Journal Article] Renal Resistive Index Predicts Postoperative Blood Pressure Outcome in Primary Aldosteronism. (2016)
  • Author(s): Iwakura Y, Ito S, Morimoto R, Kudo M, Ono Y, Nezu M, Takase K, Seiji K, Ishidoya S, Arai Y, Funamizu Y, Miki T, Nakamura Y, Sasano H, Satoh F.
  • Journal Title: Hypertension. Volume: 67 Pages: 654-660
  • DOI: 10.1161/HYPERTENSIONAHA.115.05924.
  • Peer Reviewed / Open Access
• [Journal Article] Cushing Syndrome Due to ACTH-Secreting Pheochromocytoma, Aggravated by Glucocorticoid-Driven Positive-Feedback Loop. (2016)
  • Author(s): Sakuma I, Higuchi S, Fujimoto M, Takiguchi T, Nakayama A, Tamura A, Kohno T, Komai E, Shiga A, Nagano H, Hashimoto N, Suzuki S, Mayama T, Koide H, Ono K, Sasano H, Tatsuno I, Yokote K, Tanaka T.
  • Journal Title: J Clin Endocrinol Metab. Volume: 101 Pages: 841-846
  • DOI: 10.1210/jc.2015-2855.
  • Peer Reviewed / Open Access
• [Journal Article] 5th International ACC Symposium: An Outlook to Current and Future Research on the Biology of Adrenocortical Carcinoma: Diagnostic and Therapeutic Applications. (2016)
  • Author(s): Lalli E, Sasano H.
  • Journal Title: Horm Cancer. Volume: 7 Pages: 44-48
  • DOI: 10.1007/s12672-015-0240-3.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Recommendations for description and validation for antibodies for research use. (2016)
  • Author(s): Rizner TL, Sasano H, Choi MH, Odermatt A, Adamski J.
  • Journal Title: J Steroid Biochem Mol Biol. Volume: 156 Pages: 40-42
  • DOI: 10.1016/j.jsbmb.2015.11.021.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and Steroidogenic characteristics of Aldosterone-producing Adenomas with ATPase or CACNA1D gene mutations. (2016)
  • Author(s): Kitamoto T, Suematsu S, Yamazaki Y, Nakamura Y, Sasano H, Matsuzawa Y, Saito J, Omura M, Nishikawa T.
  • Journal Title: J Clin Endocrinol Metab. Volume: 101 Pages: 494-503
  • DOI: 10.1210/jc.2015-3284.
  • Peer Reviewed / Open Access
• [Journal Article] Intratumoral heterogeneity of steroidogenesis in aldosterone-producing adenoma revealed by intensive double- and triple-immunostaining for CYP11B2/B1 and CYP17. (2016)
  • Author(s): Nakamura Y, Kitada M, Satoh F, Maekawa T, Morimoto R, Yamazaki Y, Ise K, Gomez-Sanchez CE, Ito S, Arai Y, Dezawa M, Sasano H.
  • Journal Title: Mol Cell Endocrinol. Volume: 442 Pages: 57-63
  • DOI: 10.1016/j.mce.2015.11.014.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Extraordinarily high aldosterone, 901.0 ng/dL, in a patient with primary aldosteronism: an insight into the underlying mechanism. (2016)
  • Author(s): Okubo Y, Sato Y, Nakasone Y, Shirotori K, Oguchi K, Matsushita T, Nishikawa T, Yamazaki Y, Sasano H, Komtasu M, Yamauchi K, Aizawa T.
  • Journal Title: Endocr J. Volume: 63 Pages: 127-133
  • DOI: 10.1507/endocrj.EJ15-0398.
  • Peer Reviewed / Open Access
• [Journal Article] A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery. (2016)
  • Author(s): Morimoto R, Satani N, Iwakura Y, Ono Y, Kudo M, Nezu M, Omata K, Tezuka Y, Seiji K, Ota H, Kawasaki Y, Ishidoya S, Nakamura Y, Arai Y, Takase K, Sasano H, Ito S, Satoh F.
  • Journal Title: J Hum Hypertens. Volume: 30 Pages: 379-385
  • DOI: 10.1038/jhh.2015.100.
  • Peer Reviewed / Open Access
• [Journal Article] The Role of Androgen under Normal and Pathological Conditions in SebaceousGlands: The Possibility of Target Therapy. (2016)
  • Author(s): Azmahani A, Nakamura Y, McNamara KM, Sasano H.
  • Journal Title: Curr Mol Pharmacol. Volume: 9 Pages: 311-319
  • DOI: 10.2174/1874467208666150710120217
  • Peer Reviewed / Open Access
• [Journal Article] A Calcitonin Non-producing Neuroendocrine Tumor of the Thyroid Gland. (2016)
  • Author(s): Kasajima A, Cameselle-Teijeiro J, Loidi L, Takahashi Y, Nakashima N, Sato S, Fujishima F, Watanabe M, Nakazawa T, Naganuma H, Kondo T, Kato R, Sasano H.
  • Journal Title: Endocr Pathol. Volume: - Pages: -
  • Peer Reviewed
• [Journal Article] Triple Negative Breast Cancer Chemosensitivity and Chemoresistance: Current Advances in Biomarkers Indentification. (2016)
  • Author(s): Guestini F, McNamara KM, Ishida T, Sasano H.
  • Journal Title: Expert Opin Ther Targets. Volume: - Pages: -
  • Peer Reviewed
• [Journal Article] Reply to comments to "Letter to the Editor: comment on Azmahani et al. steroidogenic enzymes, their related transcription factors and nuclear receptors in human sebaceous glands under normal and pathological conditions". (2016)
  • Author(s): Azmahani A, Nakamura Y, Felizola SJ, Ozawa Y, Ise K, Inoue T, McNamara KM, Doi M, Okamura H, Zouboulis CC, Aiba S, Sasano H.
  • Journal Title: J Steroid Biochem Mol Biol. Volume: 155（Pt A) Pages: 178-180
  • DOI: 10.1016/j.jsbmb.2015.09.028.
  • Peer Reviewed / Open Access
• [Journal Article] Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors. (2015)
  • Author(s): Pilon C, Rebellato A, Urbanet R, Guzzardo V, Cappellesso R, Sasano H, Fassina A, Fallo F.
  • Journal Title: Int J Endocrinol. Volume: 2015 Pages: 375349
  • DOI: 10.1155/2015/375349.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Androgen receptor, androgen-producing enzymes and their transcription factors in extramammary Paget disease. (2015)
  • Author(s): Azmahani A, Nakamura Y, Ozawa Y, McNamara KM, Fujimura T, Haga T, Hashimoto A, Aiba S, Sasano H.
  • Journal Title: Hum Pathol. Volume: 46(11) Pages: 1662-1669
  • DOI: 10.1016/j.humpath.2015.07.007.
  • Peer Reviewed / Open Access
• [Journal Article] Abnormal expression of miR-1 in breast carcinoma as a potent prognostic factor. (2015)
  • Author(s): Minemura H, Takagi K, Miki Y, Shibahara Y, Nakagawa S, Ebata A, Watanabe M, Ishida T, Sasano H, Suzuki T.
  • Journal Title: Cancer Sci. Volume: 106(11) Pages: 1642-1650
  • DOI: 10.1111/cas.12808.
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of proline, glutamic acid, leucine rich protein 1 (PELP1) in triple-negative breast cancer: a retrospective study on 129 cases. (2015)
  • Author(s): Zhang Y, Dai J, McNamara KM, Bai B, Shi M, Chan MS, Liu M, Sasano H, Wang X, Li X, Liu L, Ma Y, Cao S, Xing Y, Zhao B, Song Y, Wang L.
  • Journal Title: BMC Cancer. Volume: 15 Pages: 699
  • DOI: 10.1186/s12885-015-1694-y.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intracrine steroid production and mammalian target of rapamycin pathways in pulmonary lymphangioleiomyomatosis. (2015)
  • Author(s): Adachi K, Miki Y, Saito R, Hata S, Yamauchi M, Mikami Y, Okada Y, Seyama K, Kondo T, Sasano H.
  • Journal Title: Hum Pathol. Volume: 46(11) Pages: 1685-1693
  • DOI: 10.1016/j.humpath.2015.02.019.
  • Peer Reviewed / Open Access
• [Journal Article] Beyond the C18 frontier: Androgen and glucocorticoid metabolism in breast cancer tissues: The role of non-typical steroid hormones in breast cancer development and progression. (2015)
  • Author(s): McNamara KM, Sasano H.
  • Journal Title: Steroids. Volume: 103 Pages: 115-122
  • DOI: 10.1016/j.steroids.2015.05.008.
  • Peer Reviewed / Open Access
• [Journal Article] GERMLINE DELETION OF ARMC5 IN FAMILIAL PRIMARY MACRONODULAR ADRENAL HYPERPLASIA. (2015)
  • Author(s): Suzuki S, Tatsuno I, Oohara E, Nakayama A, Komai E, Shiga A, Kono T, Takiguchi T, Higuchi S, Sakuma I, Nagano H, Hashimoto N, Mayama T, Koide H, Sasano H, Nakatani Y, Imamoto T, Ichikawa T, Yokote K, Tanaka T.
  • Journal Title: Endocr Pract. Volume: 21(10) Pages: 1152-1160
  • DOI: 10.4158/EP15756.OR.
  • Peer Reviewed
• [Journal Article] PROGRESS IN PRIMARY ALDOSTERONISM:Is there a role for segmental adrenal venous sampling and adrenal sparing surgery in patients with primary aldosteronism? (2015)
  • Author(s): Satoh F, Morimoto R, Seiji K, Satani N, Ota H, Iwakura Y, Ono Y, Kud, M, Nezu M, Omata K, Tezuka Y, Kawasaki Y, Ishidoya S, Arai Y, Takase K, Nakamura Y, McNamara K, Sasano H, Ito S.
  • Journal Title: Eur J Endocrinol. Volume: 173(4) Pages: 465-477
  • DOI: 10.1530/EJE-14-1161.
  • Peer Reviewed / Open Access
• [Journal Article] Sinonasal yolk sac (Endodermal sinus) tumor in an adult female - A case report and review of the literature. (2015)
  • Author(s): Mei X, Xia Y, Sasano H, Gao H.
  • Journal Title: APMIS. Volume: 123（9） Pages: 810-814
  • DOI: 10.1111/apm.12409.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic significance of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple-negative breast cancer: a retrospective multicenter study. (2015)
  • Author(s): Miyashita M, Sasano H, Tamaki K, Hirakawa H, Takahashi Y, Nakagawa S, Watanabe G, Tada H, Suzuki A, Ohuchi N, Ishida T.
  • Journal Title: Breast Cancer Res. Volume: 17(1) Pages: 124
  • DOI: 10.1186/s13058-015-0632-x.
  • Peer Reviewed / Open Access
• [Journal Article] 11β-Prostaglandin F2α, a bioactive metabolite catalyzed by AKR1C3, stimulates Prostaglandin F receptor and induces Slug expression in breast cancer. (2015)
  • Author(s): Yoda T, Kikuchi K, Miki Y, Onodera Y, Hata S, Takagi K, Nakamura Y, Hirakawa H, Ishida T, Suzuki T, Ohuchi N, Sasano H, McNamara KM.
  • Journal Title: Mol Cell Endocrinol. Volume: 413 Pages: 236-247
  • DOI: 10.1016/j.mce.2015.07.008.
  • Peer Reviewed / Open Access
• [Journal Article] Surgical resection and chemoradiotherapy for metachronous pulmonary metastasis of basaloid squamous cell carcinoma of the oesophagus. (2015)
  • Author(s): Ishida H, Nakano T, Fujishima F, Kamei T, Taniyama Y, Sakurai T, Sato C, Fukutomi T, Kamiya K, Ozawa Y, Sasano H, Ohuchi N.
  • Journal Title: Int J Surg Case Rep. Volume: 17 Pages: 151-154
  • DOI: 10.1016/j.ijscr.2015.11.013.
  • Peer Reviewed / Open Access
• [Journal Article] Aldosterone biosynthesis in the human adrenal cortex and associated disorders. (2015)
  • Author(s): Nakamura Y, Yamazaki Y, Konosu-Fukaya S, Ise K, Satoh F, Sasano H.
  • Journal Title: J Steroid Biochem Mol Biol. Volume: 153 Pages: 57-62
  • DOI: 10.1016/j.jsbmb.2015.05.008.
  • Peer Reviewed / Open Access
• [Journal Article] Immunolocalization of thymidylate synthase as a favorable prognostic marker in estrogen receptor-positive breast carcinoma. (2015)
  • Author(s): Takagi K, Miki Y, Nakamura Y, Hirakawa H, Kakugawa Y, Amano G, Watanabe M, Ishida T, Sasano H, Suzuki T.
  • Journal Title: Histol Histopathol. Volume: 30（10） Pages: 1223-1232
  • DOI: 10.14670/HH-11-619.
  • Peer Reviewed
• [Journal Article] Pathology diagnosis of pancreatic neuroendocrine tumors. (2015)
  • Author(s): Kasajima A, Yazdani S, Sasano H.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 22（8） Pages: 586-593
  • DOI: 10.1002/jhbp.208.
  • Peer Reviewed / Open Access
• [Journal Article] KLF15 in breast cancer: a novel tumor suppressor? (2015)
  • Author(s): Yoda T, McNamara KM, Miki Y, Onodera Y, Takagi K, Nakamura Y, Ishida T, Suzuki T, Ohuchi N, Sasano H.
  • Journal Title: Cell Oncol (Dordr). Volume: 38（3） Pages: 227-235
  • DOI: 10.1007/s13402-015-0226-8.
  • Peer Reviewed
• [Journal Article] Pre-B Lymphocyte Protein 3 (VPREB3) Expression in the Adrenal Cortex:Precedent for non-Immunological Roles in Normal and Neoplastic Human Tissues. (2015)
  • Author(s): Felizola SJ, Katsu K, Ise K, Nakamura Y, Arai Y, Satoh F, Sasano H.
  • Journal Title: Endocr Pathol. Volume: 26（2） Pages: 119-128
  • DOI: 10.1007/s12022-015-9366-7.
  • Peer Reviewed / Open Access
• [Journal Article] Practical approaches for evaluating adrenal toxicity in nonclinical safety assessment. (2015)
  • Author(s): Inomata A, Sasano H.
  • Journal Title: J Toxicol Pathol. Volume: 28（3） Pages: 125-132
  • DOI: 10.1293/tox.2015-0025.
  • Peer Reviewed / Open Access
• [Journal Article] Hypoelectrolytic isoosmotic solution for infusion prevents saline-induced ultrastuructural artifacts of renal biopsy specimens. (2015)
  • Author(s): Nakamura Y, McNamara KM, Onodera S, Kitamoto Y, Kisu K, Shibahara Y, Kurosu A, Sasano H, Sato H, Joh K.
  • Journal Title: Pathol Int. Volume: 65（7） Pages: 374-378
  • DOI: 10.1111/pin.12302.
  • Peer Reviewed / Open Access
• [Journal Article] Adrenocortical Carcinoma: Review of the Pathologic Features, Production of Adrenal Steroids, and Molecular Pathogenesis. (2015)
  • Author(s): Nakamura Y, Yamazaki Y, Felizola SJ, Ise K, Morimoto R, Satoh F, Arai Y, Sasano H.
  • Journal Title: Endocrinol Metab Clin North Am. Volume: 44（2） Pages: 399-410
  • DOI: 10.1016/j.ecl.2015.02.007.
  • Peer Reviewed
• [Journal Article] 8D.02: PERIPHERAL PLASMA 18-OXOCORTISOL CAN DISCRIMINATE UNILATERAL ADENOMA FROM BILATERAL DISEASES IN PRIMARY ALDOSTERONISM PATIENTS. (2015)
  • Author(s): Satoh F, Morimoto R, Ono Y, Iwakura Y, Omata K, Kudo M, Tkase K, Seiji K, Gomez-Sanchez C, Rainey W, Nakamura Y, Sasano H, Ito S.
  • Journal Title: J Hypertens Volume: 33 Suppl 1 Pages: e113
  • DOI: 10.1097/01.hjh.0000467656.46285.fb.
  • Peer Reviewed / Open Access
• [Journal Article] 8D.04: CLINICAL BENEFITS OF ADMINISTERING SUPER-SELECTIVE SEGMENTAL ADRENAL VENOUS SAMPLING AND PERFORMING ADRENAL SPARING SURGERY IN THE PATIENTS WITH PRIMARY ALDOSTERONISM. (2015)
  • Author(s): Satoh F, Morimoto R, Ono Y, Iwakura Y, Omata K, Kudo M, Satani N, Ota H, Seiji K, Takase K, Nakamura Y, Sasano H, Ito S.
  • Journal Title: J Hypertens. Volume: 33 Suppl 1 Pages: e114
  • DOI: 10.1097/01.hjh.0000467658.23414.b0.
  • Peer Reviewed / Open Access
• [Journal Article] c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target. (2015)
  • Author(s): Ozawa Y, Nakamura Y, Fujishima F, Felizola SJ, Takeda K, Okamoto H, Ito K, Ishida H, Konno T, Kamei T, Miyata G, Ohuchi N, Sasano H.
  • Journal Title: BMC Cancer. Volume: 15 Pages: 451
  • DOI: 10.1186/s12885-015-1450-3.
  • Peer Reviewed / Open Access
• [Journal Article] Modified autonomic regulation in mice mutated in the β4 subunit of the lh/lh calcium channel. (2015)
  • Author(s): Murakami M, Suzuki T, Wu TW, Kuwasako K, Takahashi E, Watanabe H, Murakami AM, Miyoshi I, Yanagisawa T, Sasano H, Ono K, Ohba T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 461（2） Pages: 200-205
  • DOI: 10.1016/j.bbrc.2015.03.112.
  • Peer Reviewed / Open Access
• [Journal Article] Progesterone Receptor Isoforms A and B in Pancreatic Neuroendocrine Tumor. (2015)
  • Author(s): Yazdani S, Kasajima A, Ogata H, Felizola SJ, Nakamura Y, Onodera Y, Motoi F, Unno M, Watanabe M, Sasano H.
  • Journal Title: Neuroendocrinology. Volume: 101（4） Pages: 309-320
  • DOI: 10.1159/000381455.
  • Peer Reviewed / Open Access
• [Journal Article] Measurement of peripheral plasma 18-oxocortisol can discriminate unilateral adenoma from bilateral diseases in patients with primary aldosteronism. (2015)
  • Author(s): Satoh F, Morimoto R, Ono Y, Iwakura Y, Omata K, Kudo M, Takase K, Seiji K, Sasamoto H, Honma S, Okuyama M, Yamashita K, Gomez-Sanchez CE, Rainey WE, Arai Y, Sasano H, Nakamura Y, Ito S.
  • Journal Title: Hypertension. Volume: 65（5） Pages: 1096-1102
  • DOI: 10.1161/HYPERTENSIONAHA.114.04453.
  • Peer Reviewed / Open Access
• [Journal Article] Anterior gradient 2 is correlated with EGFR mutation in lung adenocarcinoma tissues. (2015)
  • Author(s): Narumi S, Miki Y, Hata S, Ebina M, Saito M, Mori K, Kobayashi M, Suzuki T, Iwabuchi E, Sato I, Maemondo M, Endo C, Inoue A, Kondo T, Yamada-Okabe H, Ichinose M, Sasano H.
  • Journal Title: Int J Biol Markers. Volume: 30(2) Pages: e234-e242
  • DOI: 10.5301/jbm.5000131.
  • Peer Reviewed
• [Journal Article] Androgen receptor and enzymes in lymph node metastasis and cancer reoccurrence in triple-negative breast cancer (2015)
  • Author(s): McNamara KM, Yoda T, Miki Y, Nakamura Y, Suzuki T, Nemoto N, Miyashita M, Nishimura R, Arima N, Tamaki K, Ishida T, Ohuchi N, Sasano H.
  • Journal Title: Int J Biol Markers. Volume: 30(2) Pages: e184-e189
  • DOI: 10.5301/jbm.5000132.
  • Peer Reviewed
• [Journal Article] G-cell hyperplasia of the stomach induces ECL-cell proliferation in the pyloric glands in a paracrinal manner. (2015)
  • Author(s): Kasajima A, Fujishima F, Morikawa T, Kawasaki S, Konosu-Fukaya S, Shibahara Y, Nakamura T, Yoshikawa T, Iijima K, Koike T, Watanabe M, Shibata C, Sasano H.
  • Journal Title: Pathol Int. Volume: 65（5） Pages: 259-263
  • DOI: 10.1111/pin.12276.
  • Peer Reviewed / Open Access
• [Journal Article] Personalization of loco-regional care for primary breast cancer patients (part 1). (2015)
  • Author(s): Toi M, Winer EP, Benson JR, Inamoto T, Forbes JF, von Minckwitz G, Robertson JF, Grobmyer SR, Jatoi I, Sasano H, Kunkler I, Ho AY, Yamauchi C, Chow LW, Huang CS, Han W, Noguchi S, Pegram MD, Yamauchi H, Lee ES, Larionov AA, Bevilacqua JL, Yoshimura M, Sugie T, Yamauchi A, Krop IE, Noh DY, Klimberg VS.
  • Journal Title: Future Oncol. Volume: 11（9） Pages: 1297-1300
  • DOI: 10.2217/fon.15.65
  • Peer Reviewed / Open Access
• [Journal Article] Personalization of loco-regional care for primary breast cancer patients (part 2). (2015)
  • Author(s): Toi M, Winer EP, Benson JR, Inamoto T, Forbes JF, von Minckwitz G, Robertson JF, Grobmyer SR, Jatoi I, Sasano H, Kunkler I, Ho AY, Yamauchi C, Chow LW, Huang CS, Han W, Noguchi S, Pegram MD, Yamauchi H, Lee ES, Larionov AA, Bevilacqua JL, Yoshimura M, Sugie T, Yamauchi A, Krop IE, Noh DY, Klimberg VS.
  • Journal Title: Future Oncol. Volume: 11（9） Pages: 1301-1305
  • DOI: 10.2217/fon.15.66
  • Peer Reviewed / Open Access
• [Journal Article] Precise preoperative localization of prostate cancer employing 12-core needle biopsy with a tissue-marking method for effective surgical strategy. (2015)
  • Author(s): Sato S, Watanabe M, Taniuchi S, Kasajima A, Mitsuzuka K, Nakamura Y, Fujishima F, Arai Y, Sasano H.
  • Journal Title: Tohoku J Exp Med. Volume: 236（1） Pages: 55-61
  • DOI: 10.1620/tjem.236.55
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of subtype classification in metastatic lymph nodes of breast cancer patients undergoing neoadjuvant chemotherapy. (2015)
  • Author(s): Nemoto N, Shibahara Y, Tada H, Uchida K, McNamara KM, Chan MS, Watanabe M, Tamaki K, Miyashita M, Miki Y, Gonda K, Ishida T, Ohuchi N, Sasano H.
  • Journal Title: Int J Biol Markers. Volume: 30(2) Pages: e174-e183
  • DOI: 10.5301/jbm.5000128.
  • Peer Reviewed
• [Journal Article] Decreased Expression of ARID1A Contributes to Infiltrative Growth of Esophageal Squamous Cell Carcinoma. (2015)
  • Author(s): Ozawa Y, Nakamura Y, Fujishima F, Felizola SJ, Takeda K, Okamoto H, Ito K, Ishida H, Konno T, Kamei T, Ohuchi N, Sasano H.
  • Journal Title: Tohoku J Exp Med. Volume: 235（3） Pages: 185-191
  • DOI: 10.1620/tjem.235.185.
  • Peer Reviewed / Open Access
• [Journal Article] Murine double minute 2 predicts response of advanced esophageal squamous cell carcinoma to definitive chemoradiotherapy. (2015)
  • Author(s): Okamoto H, Fujishima F, Kamei T, Nakamura Y, Ozawa Y, Miyata G, Nakano T, Katsura K, Abe S, Taniyama Y, Sakurai T, Teshima J, Hikage M, Sasano H, Ohuchi N.
  • Journal Title: BMC Cancer. Volume: 15 Pages: 208
  • DOI: 10.1186/s12885-015-1222-0.
  • Peer Reviewed / Open Access
• [Journal Article] 18F-FDG-PET-positive adrenal tumour. (2015)
  • Author(s): Kakita-Kobayashi M, Usui T, Sasano H, Shimatsu A.
  • Journal Title: BMJ Case Rep. Volume: - Pages: -
  • DOI: 10.1136/bcr-2015-209379.
  • Peer Reviewed / Open Access
• [Journal Article] OX40 ligand expressed in glioblastoma modulates adaptive immunity depending on the microenvironment: a clue for successful immunotherapy. (2015)
  • Author(s): Shibahara I, Saito R, Zhang R, Chonan M, Shoji T, Kanamori M, Sonoda Y, Kumabe T, Kanehira M, Kikuchi T, So T, Watanabe T, Takahashi H, Iwabuchi E, Tanaka Y, Shibahara Y, Sasano H, Ishii N, Tominaga T.
  • Journal Title: Mol Cancer. Volume: 14（1） Pages: 41
  • DOI: 10.1186/s12943-015-0307-3.
  • Peer Reviewed / Open Access
• [Journal Article] The significance of combined CK5/6 and p63 immunohistochemistry in predicting the risks of subsequent carcinoma development in intraductal papilloma of the breast. (2015)
  • Author(s): Yang Y, Suzuki K, Abe E, Li C, Uno M, Akiyama F, Yamauchi H, Kikuchi M, Ohde S, Deshpande G, Shibahara Y, Nakamura Y, Sasano H.
  • Journal Title: Pathol Int. Volume: 65(2) Pages: 81-88
  • DOI: 10.1111/pin.12248.
  • Peer Reviewed / Open Access
• [Journal Article] Inhibits p53 in Human Breast Adipose Stromal Cells: A Novel Mechanism for the Regulation of Aromatase in Obesity and Breast Cancer. (2015)
  • Author(s): Wang X, Docanto MM, Sasano H.
  • Journal Title: Cancer Res. Volume: 75(4) Pages: 645-655
  • DOI: 10.1158/0008-5472.CAN-14-2164.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A case of Cushing's syndrome due to bilateral cortisol-secreting adenomas with unilateral DHEAS oversecretion. (2015)
  • Author(s): Monno S, Tachikawa T, Maekawa T, Sasano H.
  • Journal Title: Endocr J. Volume: 62（3） Pages: 283-288
  • DOI: 10.1507/endocrj.EJ14-0552.
  • Peer Reviewed / Open Access
• [Journal Article] 3β -hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma. (2015)
  • Author(s): Konosu-Fukaya S, Nakamura Y, Satoh F, Felizola SJ, Maekawa T, Ono Y, Morimoto R, Ise K, Takeda KI, Katsu K, Fujishima F, Kasajima A, Watanabe M, Arai Y, Gomez-Sanchez EP, Gomez-Sanchez CE, Doi M, Okamura H, Sasano H.
  • Journal Title: Mol Cell Endocrinol. Volume: 408 Pages: 205-212
  • DOI: 10.1016/j.mce.2014.10.008.
  • Peer Reviewed / Open Access
• [Presentation] NOVEL CLASSIFICATION OF NEOPLASTIC AND NON-NEOPLASTIC PRIMARY ALDOSTERONISM (2016)
  • Author(s): Hironobu Sasano
  • Organizer: 41st International Aldosterone Conference
  • Place of Presentation: ボストン（アメリカ合衆国)
  • Year and Date: 2016-03-30 – 2016-03-31
  • Int'l Joint Research
• [Presentation] ヒト副腎皮質 (2016)
  • Author(s): 笹野公伸
  • Organizer: 第23回日本ステロイドホルモン学会学術集会
  • Place of Presentation: 倉敷市芸文館（岡山県倉敷市）
  • Year and Date: 2016-01-15 – 2016-01-15
• [Presentation] Estrogen, Obesity and Breast Cance (2015)
  • Author(s): Hironobu Sasano
  • Organizer: 2015 ANNUAL Carol M. Baldwin Breast Cancer Research Lecture
  • Place of Presentation: シラキュース（アメリカ合衆国)
  • Year and Date: 2015-12-03 – 2015-12-03
  • Int'l Joint Research
• [Presentation] 原発性アルドステロン症における組織学的新分類の提唱 (2015)
  • Author(s): 山﨑有人、中村保宏、伊勢和恵、尾股慧、小野美澄、森本玲、佐藤文俊
  • Organizer: 第19回特定非営利活動法人東北内分泌研究会/第31回日本内分泌学会東北地方会
  • Place of Presentation: リンクモア平安閣市民ホール（青森県青森市）
  • Year and Date: 2015-10-31 – 2015-10-31
• [Presentation] アルドステロン産生腺腫におけるmicroRNAの網羅的発現解析：KCNJ5体細胞変異との関連性の検討 (2015)
  • Author(s): 山﨑有人、中村保宏、菊池久美、端秀子、伊勢和恵、森本玲、佐藤文俊、笹野公伸
  • Organizer: 第19回日本内分泌病理学会学術総会
  • Place of Presentation: アバンセ（佐賀県佐賀市）
  • Year and Date: 2015-10-24 – 2015-10-25
• [Presentation] 副腎皮質癌の治療標的因子 (2015)
  • Author(s): 笹野公伸
  • Organizer: 第27回日本内分泌外科学会総会
  • Place of Presentation: アバンセ（佐賀県佐賀市）
  • Year and Date: 2015-10-24 – 2015-10-25
• [Presentation] アルドステロン過剰の副腎皮質球状層は過形成から腫瘍へ移行するのか？ (2015)
  • Author(s): 笹野公伸、中村保宏、尾股慧、北脇優子、小野美澄、山﨑有人、佐藤文俊
  • Organizer: 第19回日本内分泌病理学会学術総会
  • Place of Presentation: アバンセ（佐賀県佐賀市）
  • Year and Date: 2015-10-24 – 2015-10-25
• [Presentation] Pathology of CT negative primary aldosteronism at post B2 era (2015)
  • Author(s): Hironobu Sasano
  • Organizer: tumor board
  • Place of Presentation: アナーバー（アメリカ合衆国)
  • Year and Date: 2015-10-13 – 2015-10-13
  • Invited
• [Presentation] 副腎性高血圧の病理update (2015)
  • Author(s): 笹野公伸
  • Organizer: 第38回日本高血圧学会総会
  • Place of Presentation: 愛媛県県民文化会館（愛媛県松山市）
  • Year and Date: 2015-10-09 – 2015-10-11
• [Presentation] Update on adrenal cortical tumours (2015)
  • Author(s): Hironobu Sasano
  • Organizer: The 9th Asia Pacific IAP Congress: APIAP 2015
  • Place of Presentation: ブリスベン（オーストラリア）
  • Year and Date: 2015-06-04 – 2015-06-07
  • Int'l Joint Research
• [Presentation] 内分泌外科医が知っておくべきアルドステロン合成/分泌の新知見 (2015)
  • Author(s): 笹野公伸、中村保宏、山﨑有人、佐藤文俊
  • Organizer: 第27回日本内分泌外科学会総会
  • Place of Presentation: コラッセふくしま（福島県福島市）
  • Year and Date: 2015-05-28 – 2015-05-29
• [Presentation] 副腎皮質癌の治療標的因子 (2015)
  • Author(s): 笹野公伸
  • Organizer: 第27回日本内分泌外科学会総会
  • Place of Presentation: コラッセふくしま（福島県福島市）
  • Year and Date: 2015-05-28 – 2015-05-29
• [Presentation] Dissecting hormone production and secretion in primary aldosteronism (2015)
  • Author(s): Hironobu Sasano
  • Organizer: 2015 Seoul International Congress of Endocrinology and Metabolism in conjunction with - 34th Annual Meeting of Korean Endocrine Society
  • Place of Presentation: ソウル(韓国)
  • Year and Date: 2015-04-30 – 2015-05-03
  • Int'l Joint Research
• [Presentation] 非外分泌腫瘍-神経内分泌腫瘍を中心に- (2015)
  • Author(s): 笠島敦子、藤島史喜、笹野公伸
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-30 – 2015-05-02
• [Presentation] 副腎皮質癌におけるKi67標識率の解析：eye ball versus image analysis (2015)
  • Author(s): 山﨑有人、中村保宏、笠島敦子、藤島史喜、前川尚志、緑川早苗、沖隆、馬場聡、佐藤文俊、笹野公伸
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-30 – 2015-05-02
• [Presentation] 副腎の内分泌病理学の臨床内分泌学への貢献 (2015)
  • Author(s): 笹野公伸
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: ホテルニューオータニ東京（東京都千代田区）
  • Year and Date: 2015-04-23 – 2015-04-25