Hironobu Sasano

Tohoku University, Japan

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Publications (863)2990.94 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Assessment of the microvessel density (MVD) may yield important information leading to an effective antiangiogenic treatment for hepatocellular carcinoma (HCC). The intratumoral MVD of 136 HCC patients was retrospectively evaluated using CD34. The correlation between the MVD and clinicopathological findings was assessed. In addition, the prognostic factors influencing the two-year disease-free survival (DFS) and overall survival (OS) were analyzed. The MVD of each tumor size group (<2, 2-5 and >5 cm) was 196±51, 181±63 and 147±69 (P=0.004). The MVD of each histological grade (well-, moderately- and poorly-differentiated) was 200±56, 184±61 and 114±55 (P<0.001). The optimum cut-off values of the MVD for the two-year DFS and OS were 118.3 and 112.7, respectively. For the two-year DFS, high tumor marker levels[AFP>100 ng/ml and PIVKA-II>100 mAU/ml] (P=0.016 and P=0.008), poorly-differentiated HCC (P=0.005), a high Ki-67 index [>20 %] (P=0.006), a large tumor size [>5 cm] (P<0.001), vascular invasion (P<0.001), high TNM stage [III/IV] (P<0.001) and a low MVD (P<0.001) were the significant unfavorable prognostic factors. For the OS, a high Ki-67 index (P=0.009), a large tumor size (P=0.005), vascular invasion (P=0.003), high TNM stage (P<0.001) and a low MVD (P<0.001) were the significant risk factors for death. By the multivariate analysis, a low MVD was identified as an independent predictor of the two-year DFS (P=0.032, hazard ratio: 0.513, 95% confidence interval: 0.279-0.943) as well as the OS (P=0.011, hazard ratio: 0.415, 95% confidence interval: 0.210-0.820). A low MVD can be used to predict an unfavorable prognosis in HCC patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Hepatology Research 01/2015; · 2.07 Impact Factor
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    ABSTRACT: Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor, progesterone receptor and HER2. TNBCs are a diverse subgroup, but one promising marker and therapeutic target of this breast cancer is the androgen receptor (AR). Previously we demonstrated that AR and cognate intracrine pathways are associated with decreased proliferation in invasive ductal carcinoma with their decrease also detected between organ-confined and invasive diseases. Therefore, in this study, we examined the status of AR and androgen-producing enzymes during the process of metastasis to lymph nodes and cancer recurrence. We studied 2 series of patients with TNBC, one from Kumamoto University Hospital composed of 16 matched cases of primary and locally or distal recurrences and the other from Tohoku University Hospital examining 46 lymph node metastasis from 23 patients. In addition to studying concordance in AR expression, we also examined the interactions between AR and Ki-67 labeling index and AR and site of distal metastasis. In both series, AR status was concordant between primary and recurrent/metastatic disease, but coordinated expression of AR and androgenic enzymes was lost during the process. The inverse association between AR and Ki-67, previously reported in invasive ductal carcinoma (IDC), was markedly potentiated in both lymph node and recurrent cancers. In addition, AR expression appeared to have little effect on visceral metastasis but was associated directly with bone metastasis and inversely with brain metastasis. The results of our present study demonstrated that AR remained in the majority of metastatic samples from AR-positive primary TNBCs and that AR manipulation could be exploited in the metastatic settings of TNBC.
    The International journal of biological markers 12/2014; · 1.36 Impact Factor
  • Noriko Nemoto, Yukiko Shibahara, Hiroshi Tada, Keiko Uchida, Keely M McNamara, Monica S M Chan, Mika Watanabe, Kentaro Tamaki, Minoru Miyashita, Yasuhiro Miki, Kohsuke Gonda, Takanori Ishida, Noriaki Ohuchi, Hironobu Sasano
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    ABSTRACT: Neoadjuvant chemotherapy has been increasingly utilized in the treatment of breast cancer patients. However, there are no established surrogate markers predicting the response to subsequent adjuvant therapy and clinical outcome of patients. In particular, whether primary or lymph nodes metastasis should be evaluated for these analyses has remained unknown. Therefore, in this study, we first evaluated the differences in biomarkers between primary and metastatic cancer tissues in the patients undergoing neoadjuvant chemotherapy. We then correlated the findings with the clinical outcomes of these patients. We examined 49 patients receiving neoadjuvant chemotherapy and subsequent surgery with lymph node metastasis. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) and Ki-67 were all immunohistochemically evaluated in core needle biopsy samples from primary and metastatic tumors following chemotherapy. No statistically significant differences in these markers were detected between the primary tumor and metastatic lymph nodes following therapy, but the Ki-67 labeling index was significantly higher in metastatic lymph nodes than in primary tumor (p = 0.017). The patients associated with luminal A type carcinoma in their lymph nodes following chemotherapy demonstrated significantly better clinical outcomes (disease-free survival: p = 0.0045, overall survival: p = 0.0006) than those who were not. These data indicate that subtype classification following chemotherapy, in the metastatic lymph nodes rather than primary tumor could predict long-term outcomes of patients undergoing neoadjuvant chemotherapy.
    The International journal of biological markers 12/2014; · 1.36 Impact Factor
  • Hironobu Sasano, Atsuko Kasajima
    12/2014; 111(12):2280-5.
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    ABSTRACT: The anti-tumor immune response was recently reported to play a critical role in the chemotherapeutic sensitivity of breast cancer. Therefore, we investigated the correlation between CD8+ and FOXP3+ tumor-infiltrating lymphocytes and the pathological complete response (pCR) following neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), in conjunction with neoangiogenesis, basal and proliferation markers. CD8+ and FOXP3+ lymphocytes were assessed in biopsy specimens by double-staining immunohistochemistry, in combination with immunostaining of vasohibin-1, CD31, EGFR, CK5/6, and Ki-67. Earlier age, pre-menopausal status, smaller tumor size, and high Ki-67 were significantly associated with pCR, as in high CD8+, high CD8+/FOXP3+ ratio, and low vasohibin-1 positive ratio. Multivariate analysis did reveal that a high CD8+/FOXP3+ ratio was a strong predictor of pCR with an odds ratio of 5.32 (P = 0.005). High Ki-67 was also significantly associated with pCR (P = 0.002). TNBCs with a high CD8+/FOXP3+ ratio and high Ki-67 had the highest pCR rate (70 %) following NAC. However, the pCR rate of the patients with low CD8+/FOXP3+ ratio and low Ki-67 was only 5 %. The pCR rates of a high CD8+/FOXP3+ ratio and low Ki-67 patients and those with a low CD8+/FOXP3+ ratio and high Ki-67 were 24 and 21 %, respectively. TNBCs with a high CD8+/FOXP3+ ratio were more sensitive to anthracycline and taxane-based chemotherapeutic regimens, and the CD8+/FOXP3+ ratio in conjunction with Ki-67 could predict pCR following NAC in TNBC. This predictor may represent a new surrogate for testing the efficacy of investigational agents in the neoadjuvant setting.
    Breast Cancer Research and Treatment 11/2014; · 4.47 Impact Factor
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    ABSTRACT: The activating transcription factor 3 (ATF3) is a member of the cAMP-responsive element-binding (CREB) protein family of transcription factors. ATF3 is expressed in H295R human adrenocortical carcinoma cells and considered a rapid-responder gene to angiotensin-II stimulation. However, the functions of ATF3 in human adrenocortical tissues have remained unknown. In this study, we analyzed the localization and possible regulatory mechanisms of ATF3 in human adrenocortical cells and tissues. The expression levels of ATF3 mRNA were analyzed in 66 aldosterone-producing adenomas (APA) and 14 cortisol-producing adenomas (CPA) using real-time RT-PCR. To localize the ATF3 protein, we performed immunohistochemical analysis in 20 non-pathological adrenal glands, 9 adrenal glands with idiopathic hyperaldosteronism (IHA), 20 APA, and 5 CPA using a mouse monoclonal antibody against human ATF3. We showed that ATF3 mRNA levels were higher in APA compared to CPA (P = 0.0053). ATF3 was immunolocalized to the zona glomerulosa of non-pathological adrenal glands and adrenal glands with IHA, and diffusely detected in the tumor cells of APA and CPA. Subsequently, H295R cells were treated for 6 h with each inhibitor of Src kinase (SRC), PKC, JAK2, and calcium-dependent calmodulin kinase-II (CaMKII) in the presence or absence of angiotensin-II. The expression levels of ATF3 mRNA were increased by angiotensin-II (about 3.5-fold induction), but the magnitude of the induction was significantly decreased in the presence of an inhibitor for SRC (PP2) or CaMKII (KN93). These results suggest that ATF3 is a downstream target of SRC and CaMKII signaling, and may be involved in adrenocortical aldosterone synthesis.
    The Tohoku Journal of Experimental Medicine 11/2014; 234:249-254. · 1.37 Impact Factor
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    ABSTRACT: It has become important to evaluate the possible involvement of 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) and 2 (HSD3B2) isoforms in aldosterone-producing adenoma (APA). In this study, we studied 67 and 100 APA cases using real-time quantitative PCR (qPCR) and immunohistochemistry, respectively. Results of qPCR analysis demonstrated that HSD3B2 mRNA was significantly more abundant than HSD3B1 mRNA (P<0.0001), but only HSD3B1 significantly correlated with CYP11B2 (aldosterone synthase) (P<0.0001) and plasma aldosterone concentration (PAC) of the patients (P<0.0001). Results of immunohistochemistry subsequently revealed that HSD3B2 immunoreactivity was detected in the great majority of APA but a significant correlation was also detected between HSD3B1 and CYP11B2 (P<0.0001). In KCNJ5 mutated APA, CYP11B2 (P<0.0001) and HSD3B1 (P=0.011) were significantly higher than wild type APA. These results suggest that HSD3B1 is involved in aldosterone production, despite its lower levels of expression compared to HSD3B2, and also possibly associated withKCNJ5mutation in APA.
    Molecular and Cellular Endocrinology 10/2014; In Press(Online first). · 4.24 Impact Factor
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    ABSTRACT: Usually, benign tumors are not associated with an increased F-18 fluorodeoxyglucose (F-18 FDG) uptake on positron emission tomography (PET), although some exceptions have been reported in adrenal neoplasms. We present a rare case of adrenocortical oncocytoma associated with markedly increased FDG uptake, demonstrating a maximum standardized uptake value of 46.8. Histological examination demonstrated diffuse proliferation of tumor cells with eosinophilic and granular cytoplasm that were diffusely immunopositive for mitochondria and glucose transport protein 1, with focal and weak immunopositivity for 3β-hydroxysteroid dehydrogenase. Ultrastructural examination also revealed abundant mitochondria in the tumor cells. The tumor was diagnosed as adrenocortical oncocytoma and was considered benign according to Lin-Weiss-Bisceglia criteria. Diagnosis of adrenocortical oncocytoma can pose difficulties during both preoperative radiological and postoperative histopathological investigations.
    Endocrine Pathology 10/2014; · 1.64 Impact Factor
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    ABSTRACT: The great majority of the cases clinically diagnosed as primary aldosteronism (PA) have been caused by aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). The differential diagnosis of both subtypes of PA is important due to the different therapeutic modes but clinically it is sometimes difficult. It is also important to understand the morphological features of these two subtypes with special emphasis upon differences of the status for aldosterone biosynthesis. In the last decade, molecular mechanisms of PA including the aberrant expression of G-protein coupled receptors (GPCRs), key regulators of the intracellular calcium signaling pathway and somatic mutations of ion channels, have been revealed and our understanding of the molecular pathways involved in excessive aldosterone production has been markedly advanced. In addition, newly developed monoclonal antibodies specific to the isoform of adrenal steroidogenic enzymes have demonstrated the novel profiles of adrenal steroidogenesis in PA. These novel findings indicate that the molecular mechanisms on the onset and pathophysiology of PA are more complicated than previously considered and further clarification of clinical relevance of these findings is required at this juncture.
    Pathology International 10/2014; · 1.59 Impact Factor
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    ABSTRACT: It is important to identify the sites of aldosterone biosynthesis in the adrenal glands, especially those involved in primary aldosteronism (PA). CYP11B2 catalyzes the last step of aldosterone biosynthesis but its close similarity to CYP11B1 has made it difficult to generate specific antibodies that distinguish between these two highly homologous cytochromes. We have recently produced specific monoclonal antibodies against CYP11B2. In addition, we have also produced the specific antibodies against 3BHSD 1/2, which is also the pivotal step in aldosterone biosynthesis. In 3BHSD, type 1 is the predominant form in idiopathic hyperaldosteronism (IHA) with diffuse glomerulosa hyperplasia but type 2 dominant in aldosterone producing adenoma (APA). Many of micro APA expressed 3BHSD2 and CYP11B2 with the absence of c17 and CYP11B1, which could explain the cause of hyperaldosteronism despite the small size of the lesions. In addition, many of the adrenals manifesting PA without discernible lesions demonstrated multiple clusters or nodules of cortical cells demonstrating the similar enzyme expression patterns as in micro APA. These results indicated that UMN or unilateral multiple nodules cases resulting in APA are much higher than previously considered.
    Pathology 10/2014; 46 Suppl 2:S14. · 2.62 Impact Factor
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    ABSTRACT: Adrenocortical carcinoma is a rare malignancy. Medical treatment including op'DDD or mitotane with or without platinum-based cytotoxic chemotherapy is frequently administered to the patients in an adjuvant setting following surgery or in advanced disease, because of aggressive clinical behavior in some cases. Potential roles of pathologists in determining the clinical algorithm of medical therapy are histopathological confirmation of adrenocortical carcinoma, both malignant features using the criteria of Weiss and adrenocortical origin applying immunohistochemistry of steroid factor-1 (SF-1); providing the relevant pathological information to determine the precise pathological stage in individual patients; and providing the accurate Ki67 labeling index of the patients. There are no established pathological surrogate markers for response to mitotane or op' DDD therapy available at this juncture but as in other malignancies, Ki67 LI could provide information as to the potential clinical response to platinum-based cytotoxic chemotherapy. Epidermal growth factor receptor (EGFR) is significantly overexpressed in adrenocortical carcinoma but the absence of gene mutations could limit the therapeutic application of anti-EGFR antibody and/or EGFR tyrosine kinase inhibitor in the patients.
    Endocrine Pathology 09/2014; · 1.64 Impact Factor
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    ABSTRACT: Corticotropin-releasing hormone (CRH), a major regulator of the stress response, regulates various biological functions through its interaction with CRH receptors 1 (CRHR1) and 2 (CRHR2). CRH, CRHR1, and CRHR2 have recently been reported in several types of carcinoma, but the significance of these proteins has remained largely unknown in human endometrial carcinoma.
    International Journal of Gynecological Cancer 09/2014; · 1.95 Impact Factor
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    ABSTRACT: TSH is the important regulator of thyroid function but detailed molecular mechanisms have not been clarified. We first generated the iodine deficient (ID) rat in which goiter is induced by accelerated endogenous TSH secretion. The result of microarray analysis demonstrated markedly increased levels of adrenomedullin 2/intermedin (AM2/IMD) expression in the ID rat thyroid. AM2/IMD is a potent vasodilator. AM2/IMD mRNA expression was induced by TSH in a rat thyroid follicular cell line FRTL-5. Immunohistochemical analysis in human normal and Graves' disease thyroid revealed that AM2/IMD immunoreactivity was detected in follicular cells and more pronounced in Graves' disease. These results indicated that TSH induced AM2/IMD expression in the rat thyroid gland and it could locally work as a potent vasodilator, resulting in the expansion of thyroid inter-follicular capillaries. AM2/IMD could also contribute to facilitate thyroid hormone synthesis possibly via vasodilation effects and/or cAMP stimulating effects in the human thyroid gland.
    Molecular and Cellular Endocrinology 09/2014; · 4.24 Impact Factor
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    ABSTRACT: Invasive lobular carcinoma (ILC) accounts for approximately 10% of all breast carcinomas and is characterized by higher levels of androgen receptor (AR) compared to invasive ductal carcinoma (IDC). Despite this potentially androgen responsive environment the combined importance of AR and androgen metabolism in non-neoplastic lobules and lobular carcinoma remains unknown. Therefore, in this study, we evaluated the status of pivotal androgen-producing enzymes, 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5) and 5α-reductase type 1 (5αRed1), in 178 cases of ILC and surrounding histologically non-neoplastic lobular tissue using immunohistochemistry. AR prevalence was higher but androgenic enzymes lower in ILC than non-neoplastic lobules. In ILC cases the status of 5αRed1 and 17βHSD5 was inversely correlated with tumor size (p = 0.0053) and nuclear grade (p = 0.0440), and significantly associated with better overall survival of the patients (p = 0.0059). Based on these findings, we hypothesized that androgen signaling could act as a tumor suppressor. As previous studies suggested that androgens might partially act by increasing levels of the estrogen inactivating enzyme 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) in IDC tissues, this was reasonably considered a potential mechanism of androgen actions. Significantly positive correlation was detected between the status of androgenic enzymes and 17βHSD2 (p < 0.0001) and intratumoral 17βHSD2 was inversely correlated with tumor size in ILC (p = 0.0075). These correlations suggest one protective mode of androgen action could be through modulation of estrogen metabolism. Results of our present study indicated that androgen producing enzymes could play pivotal protective roles in AR-enriched ILC cases.This article is protected by copyright. All rights reserved.
    Cancer Science 09/2014; · 3.53 Impact Factor
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    ABSTRACT: Aromatase inhibitors (AI) are commonly used to treat postmenopausal estrogen-receptor (ER)-positive breast carcinoma. However, resistance to AI is sometimes acquired, and the molecular mechanisms underlying such resistance are largely unclear. Recent studies suggest that AI treatment increases androgen activity during estrogen deprivation in breast carcinoma, but the role of the androgen receptor (AR) in breast carcinoma is still a matter of controversy. The purpose of this study is to examine the potential correlation between the AR- and AI-resistant breast carcinoma. To this end, we performed immunohistochemical analysis of 21 pairs of primary breast carcinoma and corresponding AI-resistant recurrent tissue samples and established two stable variant cell lines from ER-positive T-47D breast carcinoma cell line as AI-resistance models and used them in in vitro experiments. Immunohistochemical analysis demonstrated that the expression of prostate-specific antigen (PSA) and Ki-67 were significantly higher and ER and progesterone receptor (PR) were lower in recurrent lesions compared to the corresponding primary lesions. Variant cell lines overexpressed AR and PSA and exhibited neither growth response to estrogen nor expression of ER. Androgen markedly induced the proliferation of these cell lines. In addition, the expression profile of androgen-induced genes was markedly different between variant and parental cell lines as determined by microarray analysis. These results suggest that in some cases of ER-positive breast carcinoma, tumor cells possibly change from ER-dependent to AR-dependent, rendering them resistant to AI. AR inhibitors may thus be effective in a selectd group of patients.
    The Journal of Steroid Biochemistry and Molecular Biology 08/2014; · 4.05 Impact Factor
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    ABSTRACT: Calcium channel blockers can efficiently be used in the treatment of primary aldosteronism (PA) related hypertension, but details on the localization of calcium channels (CCs) in the human adrenal and its disorders, including PA, have remained unclear. Therefore, in this study we analyzed the known α subunits of L-, N-, and T-type CCs in 74 adrenocortical aldosterone-producing adenomas (APA) and 16 cortisol-producing adenomas (CPA) using quantitative RT-PCR (qPCR). We also examined the status of L-(CaV1.2, CaV1.3), N-(CaV2.2) and T-(CaV3.2) CC subunits in five non-pathological adrenals (NA), five idiopathic hyperaldosteronism (IHA) cases, and 50 APA using immunohistochemistry. After qPCR evaluation, only CaV1.2, CaV1.3, CaV2.2, and CaV3.2 mRNA levels could be detected in APA and CPA. Among those, only CaV3.2 mRNA levels were significantly correlated with plasma aldosterone levels (P=0.0031), CYP11B2 expression levels (P<0.0001) and the presence of KCNJ5 mutations (P=0.0019) in APA. The immunolocalization of CCs in NA and IHA was detected in the zona glomerulosa (ZG), with a predominance of CaV3.2 in APA. These findings suggest that different types of CC can be involved in calcium-related aldosterone biosynthesis.
    The Journal of Steroid Biochemistry and Molecular Biology 08/2014; pii: S0960-0760(14):00191-5. · 4.05 Impact Factor
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    ABSTRACT: The sebaceous gland is a major site of steroid synthesis in human skin, but details of the status of steroidogenic enzymes and their regulation in human sebaceous glands under normal and pathological conditions have rarely been reported. Therefore, in this study, we examined the status of steroidogenic enzymes, sex steroid receptors and transcription factors in human sebaceous glands under normal and pathological conditions to explore their possible roles in in situ steroid production in human skin. Immunohistochemical analysis was performed in a total of 59 human skin specimens, including 22 normal human sebaceous glands, 12 with sebaceous nevus, 12 with sebaceous gland hyperplasia, 3 with sebaceoma and 10 with sebaceous carcinoma. Immortalised human SZ95 sebocytes were treated with forskolin or vehicle for 3h, 6h, 12h or 24h, and the mRNA levels of steroidogenic enzymes were evaluated at each time point using quantitative RT-PCR (qPCR). The results of immunohistochemistry demonstrated the immunoreactivity of 3β-HSD1, CYP11A1, StAR, 17β-HSD5, CYP17A1, 5α-red1, PRB, AR and NGFI-B in normal human sebaceous gland, with lower levels of expression in pathological sebaceous glands. The results of the in vitro study also indicated that the expression levels of 3β-HSD1, CYP11A1, StAR, 5α-red1 and NGFI-B were elevated by forskolin. 3β-HSD1 and other steroidogenic enzymes were expressed in sebaceous glands resulting in in situ androgen and progesterone synthesis and their functions.
    The Journal of Steroid Biochemistry and Molecular Biology 07/2014; pii: S0960-0760(14):00134-4. · 4.05 Impact Factor
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    ABSTRACT: Title (in Japanese): 副腎腫瘍の病理診断 Authors: 笹野公伸 、サウロJ.A.フェリゾラ 、 中村保宏 Affiliation: Tohoku University Graduate School of Medicine Department of Pathology ( 東北大学大学院医学系研究科医科学専攻病理学講座病理診断学分野 ) Journal title (in Japanese): 臨床泌尿器科
    Japanese Journal of Clinical Urology 07/2014; 68(8):570-574.
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    ABSTRACT: CYP11B1 and CYP11B2 play pivotal roles in adrenocorticosteroids synthesis. We performed semi-quantitative immunohistochemical analysis of these proteins in adrenals from patients with primary aldosteronism using novel monoclonal antibodies. Clusters of cortical cells positive for CYP11B2 were detected in the zona glomerulosa (ZG) of normal adrenal gland (NA), idiopathic hyperaldosteronism (IHA) and the adjacent adrenal of aldosterone-producing adenoma (APA). In APA, heterogenous immunolocalization of CYP11B2 and diffuse immunoreactivity of CYP11B1 were detected in tumor cells, respectively. The relative immunoreactivity of CYP11B2 in the ZG of adjacent adrenal of APA was significantly lower than that of NA, IHA and APA tumor cells, suggestive of suppressed aldosterone biosynthesis in these cells. These findings did indicate the regulatory mechanisms of aldosterone biosynthesis were different between normal/hyperplastic and neoplastic aldosterone-producing cells in human adrenals. CYP11B2 immunoreactivity in the ZG could also serve as a potential immunohistochemical marker differentiating morphologically hyperplastic ZG of IHA and APA adjacent adrenal.
    Molecular and Cellular Endocrinology 07/2014; 392(1-2):73-79. · 4.24 Impact Factor
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    ABSTRACT: While the clinical benefit of androgen-based therapeutics in breast cancer has been known since the 1940s, we have only recently begun to fully understand the mechanisms of androgen action in breast cancer. Androgen signalling pathways can have either beneficial or deleterious effects in breast cancer depending on the breast cancer subtype and intracellular context. This review discusses our current knowledge of androgen signalling in breast cancer, including the relationship between serum androgens and breast cancer risk, the prognostic significance of androgen receptor (AR) expression in different breast cancer subtypes and the downstream molecular pathways mediating androgen action in breast cancer cells. Intracrine androgen metabolism is also discussed, and proposed as a potential mechanism that may explain some of the reported differences regarding dichotomous androgen actions in breast cancers. A better understanding of AR signalling in this disease is critical given the current resurgence in interest in utilising contemporary AR directed therapies for breast cancer and the need for biomarkers that will accurately predict clinical response.
    Endocrine Related Cancer 06/2014; · 5.26 Impact Factor

Publication Stats

15k Citations
2,990.94 Total Impact Points


  • 1987–2014
    • Tohoku University
      • • Department of Pathology
      • • Division of Internal Medicine
  • 2013
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
    • Fudan University
      Shanghai, Shanghai Shi, China
    • Naha-Nishi Clinic
      Okinawa, Okinawa, Japan
  • 2008–2013
    • Kyoto University
      • • Department of Breast Surgery
      • • Department of Medicine and Clinical Science
      Kioto, Kyōto, Japan
    • Washington University in St. Louis
      • Alvin J. Siteman Cancer Center
      Saint Louis, MO, United States
  • 2005–2013
    • Prince Henry's Institute
      Melbourne, Victoria, Australia
    • Sendai Orthopaedic Hospital
      Sendai, Kagoshima, Japan
  • 2012
    • Akershus universitetssykehus
      Kristiania (historical), Oslo County, Norway
    • University of Toyama
      • Faculty of Medicine
      Тояма, Toyama, Japan
  • 1993–2012
    • Yokohama Rosai Hospital
      Yokohama, Kanagawa, Japan
  • 2011
    • Mitsubishi Nagoya Hospital
      Nagoya, Aichi, Japan
  • 2008–2011
    • Georgia Health Sciences University
      • Department of Physiology
      Augusta, GA, United States
  • 2009–2010
    • Hirosaki University
      • Department of Endocrinology and Metabolism
      Khirosaki, Aomori Prefecture, Japan
    • University of Bergen
      • Institute of Medicine
      Bergen, Hordaland Fylke, Norway
    • The University of Hong Kong
      • Department of Pathology
      Hong Kong, Hong Kong
  • 2004–2009
    • The University of Tokyo
      • Department of Reproductive, Developmental and Aging Sciences
      Tokyo, Tokyo-to, Japan
    • Sendai University
      Sendai, Kagoshima, Japan
    • University of Hamamatsu
      Hamamatu, Shizuoka, Japan
  • 2005–2008
    • The Jikei University School of Medicine
      • • Department of Internal Medicine H
      • • Department of Pathology
      Tokyo, Tokyo-to, Japan
  • 2004–2008
    • Northwestern University
      • • Feinberg School of Medicine
      • • Department of Obstetrics and Gynecology
      Evanston, IL, United States
  • 2003–2008
    • Akita University Hospital
      Akita, Akita, Japan
    • Tazuke Kofukai Medical Research Institute, Kitano Hospital
      Ōsaka, Ōsaka, Japan
  • 2004–2006
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
  • 1998–2005
    • University of Texas Southwestern Medical Center
      • • Department of Obstetrics and Gynecology
      • • Division of Reproductive Endocrinology and Infertility
      Dallas, TX, United States
    • Tsukuba Research Institute
      Edo, Tōkyō, Japan
    • Hyogo Prefectural Amagasaki Hospital
      Amagasaki, Hyōgo, Japan
  • 2002–2003
    • Aomori Prefectural Central Hospital
      Aomori, Aomori Prefecture, Japan
  • 2000–2003
    • University of Illinois at Chicago
      • Department of Obstetrics and Gynecology (Chicago)
      Chicago, Illinois, United States
  • 1999–2001
    • Fukushima Medical University
      • Division of Medicine
      Hukusima, Fukushima, Japan
    • University of Toronto
      Toronto, Ontario, Canada
  • 1997
    • Nagasaki University Hospital
      Nagasaki, Nagasaki, Japan
  • 1996
    • Alfred Hospital
      Melbourne, Victoria, Australia
    • Keio University
      Edo, Tōkyō, Japan
    • Hokkaido University Hospital
      Sapporo, Hokkaidō, Japan
  • 1994
    • Fujita Health University
      Nagoya, Aichi, Japan
  • 1988–1991
    • George Washington University
      • Department of Pathology
      Washington, D. C., DC, United States