Hironobu Sasano

Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

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Publications (950)3356.58 Total impact

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    ABSTRACT: Background: Aldosterone-producing adrenocortical carcinoma is a rare malignancy, which is usually diagnosed by histopathological examination of the excised tumor. In inoperable cases, aldosterone-producing ACC diagnosed by immunohistochemical staining of the metastatic tumor for Cytochrome P450 (CYP) 11β has not previously been reported and even in that case staining for adrenocortical-specific adrenal 4 binding protein/steroidogenic factor1 (Ad4BP/SF1) and steroidogenic enzymes has not been reported. Case presentation: We report the case of a 67-year-old Japanese woman with aldosterone-producing adrenocortical carcinoma. Laboratory findings showed severe hypopotassemia. Endocrinological examination revealed an increased plasma aldosterone concentration and suppressed plasma renin activity. Plasma dehydroepiandrosterone sulfate (DHEA-S) was elevated. Diurnal variation in serum cortisol was lost and administration of 1 mg and 8 mg dexamethasone did not suppress serum cortisol levels. From the 24-h urine collection sample, urine aldosterone and urine cortisol levels were greatly increased. Therefore, autonomous excess production was observed for the three adrenal cortex hormones. Abdominal computed tomography and magnetic resonance imaging showed a right adrenal tumor and a huge liver tumor. Adrenocortical carcinoma with metastatic liver cancer was strongly suggested, however surgery could not be considered due to stage IV disease: the liver tumor was too large and cardiac ultrasonography indicated that her cardiac function was poor. Therefore, a liver biopsy was taken to properly determine the diagnosis. Immunohistochemical stains for Ad4BP/SF1 and steroidogenic enzymes were positive. Ad4BP/SF-1 was originally identified as a steroidogenic, tissue-specific transcription factor implicated in the expression of the steroidogenic CYP gene encoding cytochrome P450s. Hence we could diagnose the patient as having adrenocortical carcinoma with metastatic liver cancer. Conclusion: This rare case had severe hypopotassemia accompanied with not only increased cortisol and DHEA-S but also aldosterone. We reached the diagnosis of adrenocortical carcinoma with metastatic liver cancer based on positive immunohistochemical staining of Ad4BP/SF1 in the liver biopsy specimen. We have reported the first case of aldosterone-producing adrenocortical carcinoma diagnosed solely by immunohistochemical staining for adrenocortical-specific Ad4BP/SF1 and steroidogenic enzymes in a metastatic liver tumor.
    No preview · Article · Dec 2016 · BMC Endocrine Disorders
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    ABSTRACT: Nucleobindin 2 (NUCB2) is a multifunctional protein containing several functional domains, and associated with wide variety of biological process such as food intake and energy homeostasis. Recently, NUCB2 has been implicated in not only normal human tissues but also some kinds of human malignancies. However, its clinical and/or biological significance has largely remained unknown in endometrial carcinomas. We therefore immunolocalized NUCB2 protein in 87 endometrial carcinoma tissues and examined its clinical significance. NUCB2 immunoreactivity was detected in 19 out of 87 (22%) of endometrial carcinoma cases examined, and positively correlated with Ki67 labeling index, while there was no significant correlation between NUCB2 and stage, histological grade, and progesterone receptor status. Furthermore, NUCB2 immunoreactivity was significantly correlated with increased risk of recurrence and worse clinical outcome regardless of stage or histological grade. Subsequent multivariate analyses did reveal that NUCB2 immunoreactivity was an independent prognostic factor for both disease-free survival and endometrial cancer specific survival. In vitro experiments demonstrated that knockdown of NUCB2 using specific siRNA for NUCB2 significantly impaired cell proliferation and migration of the endometrial carcinoma cell lines, Ishikawa and Sawano cells, and that nesfatin-1 treatment significantly promoted cell proliferation and migration in Ishikawa cells. These findings possibly suggested that NUCB2 and/or nesfatin-1 had pivotal roles in the progression of endometrial carcinomas. Immunohistochemical NUCB2 status may therefore serve as a potent biomarker for endometrial carcinomas.
    No preview · Article · Feb 2016 · Endocrine Journal

  • No preview · Article · Jan 2016 · Hypertension
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    ABSTRACT: Introduction: Basaloid squamous cell carcinoma of the oesophagus (BSCCE) is a relatively rare variant of oesophageal malignancy. There are no established treatment strategies for pulmonary metastases of BSCCE. Presentation of case: A 72-year-old man underwent oesophagectomy and subsequently received a pathological diagnosis of stage IIIA (T3N1M0) BSCCE according to Union for International Cancer Control. One year and 5 months later, he underwent partial resection of the right lung because of metastasis of the BSCCE. One year and 6 months after the pulmonary resection, recurrence in the right lung was observed. The patient was treated with concurrent chemoradiotherapy using cisplatin and 5-fluorouracil, and the lesion completely disappeared. The patient is doing well without recurrence 5 years after chemoradiotherapy. Discussion: In our case, the recurrent lesion in the right lung was observed after the pulmonary resection. It is difficult to determine whether the recurrent lesion is solitary or multiple and whether it is a local or pleural metastasis. Therefore, surgical indication must be decided carefully. Systemic chemotherapy or radiotherapy is useful to treat BSCCE metastasis, however, appropriate, but which agents and their regimens are appropriate is not clear. Concurrent chemotherapy using cisplatin and 5-fluorouracil and radiotherapy for pulmonary BSCCE metastases may provide curative therapy and should be considered. Conclusion: This report describes a case of recurrent pulmonary metastasis after pulmonary resection of BSCCE metastasis, successfully treated by concurrent chemotherapy and radiotherapy. Further studies are required to establish the indications and efficacy of these therapeutic approaches.
    Full-text · Article · Dec 2015 · International Journal of Surgery Case Reports
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    ABSTRACT: We previously showed a decreased expression of vitamin D receptor (VDR) mRNA/protein in a small group of adrenocortical carcinoma (ACC) tissues, suggesting the loss of a protective role of VDR against malignant cell growth in this cancer type. Downregulation of VDR gene expression may result from epigenetics events, that is, methylation of cytosine nucleotide of CpG islands in VDR gene promoter. We analyzed methylation of CpG sites in the VDR gene promoter in normal adrenals and adrenocortical tumor samples. Methylation of CpG-rich 5′ regions was assessed by bisulfite sequencing PCR using bisulfite-treated DNA from archival microdissected paraffin-embedded adrenocortical tissues. Three normal adrenals and 23 various adrenocortical tumor samples (15 adenomas and 8 carcinomas) were studied. Methylation in the promoter region of VDR gene was found in 3/8 ACCs, while no VDR gene methylation was observed in normal adrenals and adrenocortical adenomas. VDR mRNA and protein levels were lower in ACCs than in benign tumors, and VDR immunostaining was weak or negative in ACCs, including all 3 methylated tissue samples. The association between VDR gene promoter methylation and reduced VDR gene expression is not a rare event in ACC, suggesting that VDR epigenetic inactivation may have a role in adrenocortical carcinogenesis.
    Preview · Article · Dec 2015 · International Journal of Endocrinology
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    ABSTRACT: Invasive ductal and lobular carcinomas (IDC and ILC) are the two most common histological types of breast cancer, and have been considered to develop from terminal duct lobular unit but their molecular, pathological, and clinical features are markedly different between them. These differences could be due to different mechanisms of carcinogenesis and tumor microenvironment, especially cancer-associated fibroblasts (CAFs) but little has been explored in this aspect. Therefore, in this study, we evaluated the status of angiogenesis, maturation of intratumoral microvessels, and proliferation of CAFs using immunohistochemistry and PCR array analysis to explore the differences of tumor microenvironment between ILC and IDC. We studied grade- and age-matched, luminal-like ILC and IDC. We immunolocalized CD34 and αSMA for an evaluation of CAFs and CD31, Vasohibin-1, a specific marker of proliferative endothelial cells and nestin, a marker of pericytes for studying the status of proliferation and maturation of intratumoral microvessel. We also performed PCR array analysis to evaluate angiogenic factors in tumor stromal components. The number of CAFs, microvessel density, and vasohibin-1/CD31 positive ratio were all significantly higher in ILC than IDC but nestin immunoreactivity in intratumoral microvessel was significantly lower in ILC. These results did indicate that proliferation of CAFs and endothelial cells was more pronounced in ILC than IDC but newly formed microvessels were less mature than those in IDC. PCR array analysis also revealed that IGF-1 expression was higher in ILC than IDC. This is the first study to demonstrate the differences of tumor microenvironment including CAFs and proliferation and maturation of intratumoral vessels between ILC and IDC.
    No preview · Article · Dec 2015 · Breast Cancer Research and Treatment
  • Enzo Lalli · Hironobu Sasano
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    ABSTRACT: Groundbreaking progress has been recently made in elucidating the signaling pathways that are altered in adrenocortical carcinoma (ACC), an endocrine malignancy that still has an unfavorable prognosis, and in understanding its genomic structure. These advances need now to be translated to create cellular and animal models more relevant to human disease in order to develop new and more effective diagnostic procedures and targeted therapies against this deadly malignancy.
    No preview · Article · Dec 2015 · Hormones and Cancer
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    ABSTRACT: Background Triple-negative breast cancer (TNBC) is associated with an aggressive clinical course due to the lack of therapeutic targets. Therefore, identifying reliable prognostic biomarkers and novel therapeutic targets for patients with TNBC is required. Proline, glutamic acid, leucine rich protein 1 (PELP1) is a novel steroidal receptor co-regulator, functioning as an oncogene and its expression is maintained in estrogen receptor (ER) negative breast cancers. PELP1 has been proposed as a prognostic biomarker in hormone-related cancers, including luminal-type breast cancers, but its significance in TNBC has not been studied. Methods PELP1 immunoreactivity was evaluated using immunohistochemistry in 129 patients with TNBC. Results were correlated with clinicopathological variables including patient’s age, tumor size, lymph node stage, tumor grade, clinical stage, histological type, Ki-67 LI, as well as clinical outcome of the patients, including disease-free survival (DFS) and overall survival (OS). Results PELP1 was localized predominantly in the nuclei of carcinoma cells in TNBC. With the exception of a positive correlation between PELP1 protein expression and lymph node stage (p = 0.027), no significant associations between PELP1 protein expression and other clinicopathological variables, including DFS and OS, were found. However, when PELP1 and Ki-67 LI were grouped together, we found that patients in the PELP1/Ki-67 double high group (n = 48) demonstrated significantly reduced DFS (p = 0.005, log rank test) and OS (p = 0.002, log rank test) than others (n = 81). Multivariable analysis supported PELP1/Ki-67 double high expression as an independent prognostic factor in patients with TNBC, with an adjusted hazard ratio of 2.020 for recurrence (95 % CL, 1.022–3.990; p = 0.043) and of 2.380 for death (95 % CL, 1.138–4.978; p = 0.021). Conclusions We found that evaluating both PELP1 and Ki-67 expression in TNBC could enhance the prognostic sensitivity of the two biomarkers. Therefore, we propose that PELP1/Ki-67 double high expression in tumors is an independent prognostic factor for predicting a poor outcome for patients with TNBC.
    Preview · Article · Dec 2015 · BMC Cancer
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    ABSTRACT: Introduction: Triple negative breast cancer (TNBC) is a heterogeneous clinicopathological entity constituting approximately 15-20% of all breast cancer (BC) patients. It shows high recurrence rate and poor prognosis. At this juncture, because of the lack of specific targeted therapies available and the development in patients of resistance to some therapeutic agents, clinical and translational settings have gained importance over the past decades. Areas covered: The development of novel, safe and effective alternatives for the treatment of TNBC are in high demand. Therefore, this review aims to summarize the state of the art of TNBC, its current therapies and potential therapeutic targets. In particular, focus is put on recent advances regarding the identification of emerging biomarkers as prognostic and/or predictive markers, including surrogate markers for molecular tumor subtyping and identifying potential responders to new therapies. Expert opinion: Effective development of informative markers could constitute an important armamentarium tool for identifying appropriate therapies to challenge the aggressiveness of TNBC.
    No preview · Article · Nov 2015 · Expert Opinion on Therapeutic Targets
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    ABSTRACT: Object: This comparative study clarified the clinical characteristics and in vitro steroidogenic activities of aldosterone-producing adenomas (APAs) harboring ATPase or CACNA1D gene mutations. Design and patients: Genetic testing was performed on 159 unilateral APAs. Somatic ATPase and CACNA1D gene mutations were analyzed in 42 APA tissues without KCNJ5 gene mutations. Results: ATP1A1, ATP2B3, and CACNA1D mutations were detected in 1, 4, and 4 patients, respectively. Compared with patients without KCNJ5, ATPase, or CACNA1D mutations (wild type), ATPase mutations tended to have more severe hyperaldosteronism and smaller tumors; those with CACNA1D mutations had clinical characteristics and tumor sizes similar to those with wild-type genes. APAs with ATPase mutations were composed mainly of compact eosinophilic tumor cells, whereas CACNA1D mutations resulted in predominantly clear tumor cells. Aldosterone production in APA cells with ATP2B3 mutations were more responsive to (Bt)2cAMP, whereas those with CACNA1D mutations were more responsive to adrenocorticotropic hormone than the wild-type cells. Conclusion: APAs with ATPase mutations demonstrated a potentially severe primary aldosteronism phenotype, whereas those with CACNA1D mutations displayed characteristics similar to wild-type APAs. The status of stimulated aldosterone production was also different according to the cell types, suggesting that the regulatory effects of adrenocorticotropic hormone on aldosterone synthesis could possibly vary according to the intracellular signaling involved in hormone production.
    No preview · Article · Nov 2015 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: A 43-yr-old hypertensive male was admitted due to hypokalemia (1.8 mEq/L) and renal dysfunction (eGFR, 20.0 mL/min/1.73 m(2)). His plasma aldosterone was 901.0 ng/dL, plasma renin activity 5.7 ng/mL/hr, and aldosterone/renin activity ratio 158. Angiotensin II (AII) was 0.7 pg/mL, ACTH <1.0 pg/mL, and cortisol 21.6 μg/dL. Liquid chromatography-tandem mass spectrometry analysis showed that aldosterone (104 times the control) as well as its precursors were significantly elevated in the patient's plasma. A left adrenal (4-cm-diameter) tumor with (131)I-Adosterol(®) uptake was found and removed. Four days later, plasma aldosterone and renin activity had dropped to 7.73 ng/dL and 1.6 ng/mL/hr, respectively. However, they rose to 24.0 ng/dL and 10.9 ng/mL/hr, respectively, by Day 102. Nevertheless, magnetic resonance angiography found no evidence of a renovascular lesion. The tumor was a benign adrenocortical adenoma composed predominantly of clear cells positive for 17α-hydroxylase, [hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerases], and aldosterone synthase. A quantitative real-time polymerase chain reaction analysis of the tumor cells revealed that expression of the gene encoding aldosterone synthase was 85 times the control level. In addition, the tumor cells harbored G151R mutation of the inward rectifying potassium channel subfamily j, member 5 gene. The striking overexpression of aldosterone synthase by the tumor cells was considered the primary mechanism for the extravagant overproduction of aldosterone in this case. This overexpression may have resulted from integration of signals from AII and forced membrane depolarization due to the potassium channel mutation.
    Preview · Article · Nov 2015 · Endocrine Journal
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    ABSTRACT: Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl(-1) and aldosterone renin activity ratio of 90.2 (ng dl(-1) per ng ml(-1 )h(-1)), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl(-1) confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production.Journal of Human Hypertension advance online publication, 5 November 2015; doi:10.1038/jhh.2015.100.
    No preview · Article · Nov 2015 · Journal of human hypertension
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    ABSTRACT: Introduction: Cytochrome P450 11B2 (CYP11B2) plays a pivotal role in aldosterone synthesis, while cytochrome P450 11B1 (CYP11B1) and cytochrome P450 17A1 (CYP17) are involved in cortisol synthesis in normal human adrenal glands. However, their detailed distribution in aldosterone-producing adenoma (APA) remains incompletely settled. Materials and methods: We examined the status of CYP11B1/CYP11B2 and CYP11B2/CYP17A1 expressions in 27 APA (double staining) cases and 21 APA (triple staining) cases by using immunofluorescence staining and semi-quantitative evaluation. Results: Tumor cells co-expressing CYP11B1/B2 (hybrid cell type A), CYP11B2/17 (hybrid cell type B), CYP11B1/17 (hybrid cell type C), and CYP11B1/B2/17 (triple-positive cells) were identified. The area and cell number of these cells were relatively small, but size of individual hybrid cells were different between three hybrid cell types (A/B/C) and triple-positive cells. Conclusion: The presence of hybrid cells indicated the marked intratumoral heterogeneity of steroidogenesis in APAs, particularly in those producing glucocorticoids and mineralocorticoids.
    No preview · Article · Nov 2015 · Molecular and Cellular Endocrinology
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    Full-text · Article · Oct 2015 · The Journal of steroid biochemistry and molecular biology
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    ABSTRACT: Extramammary Paget disease (EMPD) has been known to frequently express androgen receptor (AR). Therefore, androgens could play roles in the biological behavior of Paget cells. 5α-Reductase (5α-red) types 1 and 2 and 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5) are pivotal in situ regulators of androgen production in androgen-responsive tissues including androgen-dependent neoplasms. Therefore, in this study, we immunolocalized AR, androgen-producing enzymes, and their transcription factors to assess the state of in situ androgen production and actions and its correlation of invasiveness in EMPD. We studied 51 cases of EMPD with known clinicopathological status. AR, 5α-red1, 17β-HSD5, and β-catenin immunoreactivity was evaluated by using the modified H-score method while cyclin D1, p53, forkhead box protein P1, and a proliferation marker, Ki-67, were quantified using labeling index. The mean scores of AR, 5α-red1, and 17β-HSD5 in invasive EMPD were all significantly higher than noninvasive EMPD (P < .0001). Ki-67 labeling index as well as the cyclin D1 score was also significantly higher in invasive than noninvasive lesions of EMPD. These results demonstrated that androgen receptor and androgen-producing enzymes were both associated with cell cycle regulation and subsequently the invasiveness of EMPD lesions and could also indicate those above as potential markers of invasive potentials in EMPD.
    Full-text · Article · Sep 2015 · Human pathology
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    ABSTRACT: Introduction: The status of tumor-infiltrating lymphocytes (TILs) has been recently proposed to predict clinical outcome of patients with breast cancer. We therefore studied the prognostic significance of CD8(+) TILs and FOXP3(+) TILs in residual tumors after neoadjuvant chemotherapy (NAC) and the alterations in these parameters before and after NAC in patients with triple-negative breast cancer (TNBC). Methods: One hundred thirty-one TNBC patients who received NAC at three institutions were examined. CD8(+) TIL and FOXP3(+) TIL in residual tumors and biopsy specimens were evaluated by double-staining immunohistochemistry. The CD8(+) TIL and FOXP3(+) TIL status of the residual tumors was assessed, and the rates of their changes before and after NAC were calculated. Results: TNBC patients with high CD8(+) TIL levels or a high CD8/FOXP3 ratio in residual tumors had significantly better recurrence-free survival (RFS) and breast cancer-specific survival (BCSS) than patients with low values of these parameters. In multivariate analyses, CD8(+) TIL exhibited strong prognostic significance for RFS, with a hazard ratio (HR) of 3.09 (95 % confidence interval (CI) 1.537-6.614, P=0.0013). The CD8/FOXP3 ratio was also significantly correlated with RFS (HR=2.07, 95 % CI 1.029-4.436, P=0.0412). TNBC with larger residual tumor size and positive lymph node status, which are known prognostic factors, was independently associated with worse RFS (P=0.0064 and P=0.0015, respectively). High CD8(+) TIL levels were a markedly powerful indicator of improved BCSS, with an HR of 3.59 (95 % CI 1.499-9.581, P=0.0036). Nodal status was also associated with BCSS (P=0.0024). TNBC with a high rate of CD8(+) TIL changes was associated with significantly better RFS compared with the low group (P=0.011). Higher rates of changes in the CD8/FOXP3 ratio were significantly correlated with both better RFS and BCSS compared with lower rates (P=0.011 and P=0.023, respectively). Conclusions: This is the first study to demonstrate that high CD8(+) TIL and a high CD8/FOXP3 ratio in residual tumors and increment of these parameters following NAC and accurately predict improved prognosis in TNBC patients with non-pathological complete response following NAC. These parameters could serve as a surrogate one for adjuvant treatment in patients with residual disease in the neoadjuvant setting.
    Full-text · Article · Sep 2015 · Breast cancer research: BCR
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    ABSTRACT: Metastatic breast cancer still remains a highly lethal disease, and it is very important to evaluate biomarkers associated with the distant metastasis. MicroRNAs (miRNAs) are small non-protein coding RNAs and regulate various cellular functions. Recent investigations have demonstrated importance of some miRNAs in breast cancer, but the significance has still remained largely unclear in a great majority of miRNAs in breast cancer metastasis. Therefore, in this study, we first examined expression profiles of miRNAs in stage IV breast carcinoma tissues comparing stages I-III cases by miRNA PCR array, and identified miR-1 as a miRNA which was the most associated with the distant metastasis. However, miR-1 has not yet been examined in breast carcinoma tissue, and its significance remains unknown. Therefore, we further examined miR-1 expression in breast carcinoma using in situ hybridization (ISH). miR-1 was localized in carcinoma cells in 20% of breast carcinoma cases, but it was negligible in non-neoplastic mammary glands or stroma. miR-1 ISH status was significantly associated with stage, pathological T factor, lymph node metastasis, distant metastasis, histological grade, estrogen receptor, progesterone receptor and Ki-67 in breast carcinoma. Moreover, the miR-1 status was demonstrated an independent worse prognostic factor for both disease-free and breast cancer-specific survival by multivariate analysis. These findings suggest that abnormal miR-1 expression is associated with an aggressive phenotype of breast carcinoma and miR-1 status is a potent prognostic factor in human breast cancer patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Sep 2015 · Cancer Science
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    ABSTRACT: Lymphangioleiomyomatosis (LAM) is a rare, potentially fatal disease primarily affecting young women. Estrogens enhance cell proliferation and progression of the tumor. Clinical trials using molecularly targeted agents such as endocrine manipulation and mammalian target of rapamycin (mTOR) inhibitors are in progress, but the status of these molecules, including aromatase and mTOR, has not been explored in LAM tissue. We first examined immunoreactivity for sex steroid receptors (estrogen receptor [ER] α, ERβ, progesterone receptor, androgen receptor), sex steroid-synthesizing enzymes (aromatase, steroid sulfatase, 17β-hydroxysteroid dehydrogenase 1, 5α-reductases), apoptotic suppression factor (Bcl-2), and factors involved in the mTOR signaling pathway in 30 pulmonary LAM tissues. Immunoreactivity for ERα, ERβ, progesterone receptor, aromatase, and Bcl-2 was significantly more abundant in epithelioid cells, whereas the status of androgen receptor, 5α-reductases, and phospho-mTOR signaling was not different in epithelioid and spindle-shaped LAM cells. We further examined the correlation among H scores of these markers using hierarchical clustering analysis. The results indicated that LAM tumors can be further classified into "aromatase" and "mTOR" groups on the basis of the patterns of immunoreactivity, and the 2 types could benefit from different modes of therapy. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jul 2015 · Human pathology
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    ABSTRACT: Adrenal venous sampling (AVS) is critical to determine the subtype of primary aldosteronism (PA). "Central" AVS, that is, the collection of effluents from bilateral adrenal central veins, sometimes does not allow differentiation between bilateral aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism (IHA). To establish the best treatment course, we have developed "segmental AVS"; that is, we collect effluents from the tributaries of central veins to determine the intra-adrenal sources of aldosterone overproduction. We then evaluated the clinical utility of this novel approach in the diagnosis and treatment of PA. We performed central and/or segmental AVS in 297 PA patients, and assessed the accuracy of diagnosis based on the results of central (n=138, 46.5%) and segmental AVS (n=159, 53.5%) by comparison with those of clinicopathological evaluation of resected specimens. Segmental AVS demonstrated both elevated and attenuated secretion of aldosterone from APA and non-tumorous segments, respectively, in patients with bilateral APA and recurrent APA. These findings were completely confirmed by detailed histopathological examination after surgery. Segmental AVS, but not central AVS, also served to identify APA located distal from the central vein. Compared to central AVS, segmental AVS served to identify APA in some patients and its use should expand the pool of patients eligible for adrenal sparing surgery through the identification of unaffected segments, despite the fact that segmental AVS requires more expertise and time. Especially, this new technique could enormously benefit patients with bilateral or recurrent APA because of the preservation of non-tumorous glandular tissue.
    No preview · Article · Jul 2015 · European Journal of Endocrinology
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    ABSTRACT: The androgen receptor plays a pivotal role in the sebaceous glands. Its primary function is to stimulate cell proliferation and differentiation in the sebaceous and is association with acne. Previous studies have demonstrated expression of AR and steroidogenic enzymes in normal sebaceous glands and in all sebaceous disorders present evidence that androgen receptor may be a sensitive marker of sebaceous differentiation. It has been previously suggested that AR and steroidogenic enzymes immunohistochemistry may be useful particularly in identifying poorly sebaceous carcinoma. This review will provide an overview of the AR functions in the sebaceous glands and discussion of the therapeutic targets in acne and carcinoma.
    No preview · Article · Jul 2015 · Current Molecular Pharmacology

Publication Stats

23k Citations
3,356.58 Total Impact Points


  • 2015
    • Peter MacCallum Cancer Centre
      Melbourne, Victoria, Australia
  • 1986-2015
    • Tohoku University
      • • Department of Pathology
      • • Division of Internal Medicine
      Sendai-shi, Miyagi, Japan
  • 2014
    • St. Luke's International Hospital
      • Department of Radiology
      Edo, Tōkyō, Japan
  • 2013
    • Sendai National College of Technology
      Sendai, Kagoshima, Japan
    • Kyoto University
      • Division of Pharmaceutical Sciences
      Kioto, Kyōto, Japan
  • 1989-2013
    • University of Texas Southwestern Medical Center
      • • Department of Obstetrics and Gynecology
      • • Department of Biochemistry
      Dallas, Texas, United States
  • 2010
    • Fudan University
      Shanghai, Shanghai Shi, China
  • 2004-2007
    • Sendai University
      Sendai, Kagoshima, Japan
  • 2005
    • The Jikei University School of Medicine
      • Department of Pathology
      Edo, Tōkyō, Japan
  • 2000-2003
    • University of Illinois at Chicago
      • • Department of Obstetrics and Gynecology (Chicago)
      • • Department of Obstetrics and Gynecology (Peoria)
      Chicago, Illinois, United States
  • 2002
    • Matsunami General Hospital
      Gihu, Gifu, Japan
  • 2001
    • Hyogo Prefectural Amagasaki Hospital
      Amagasaki, Hyōgo, Japan
    • Hokkaido University of Education
      Sapporo, Hokkaidō, Japan
  • 1994-2000
    • Fujita Health University
      • Department of Molecular Genetics
      Nagoya, Aichi, Japan
    • Yokohama Rosai Hospital
      Yokohama, Kanagawa, Japan
  • 1998-1999
    • University of Toronto
      • Saint Michael's Hospital
      Toronto, Ontario, Canada
    • Hamamatsu University School Of Medicine
      Hamamatu, Shizuoka, Japan
  • 1997
    • Sendai City Hospital
      Sendai, Kagoshima, Japan
  • 1995
    • Kyushu University
      • Graduate School of Medical Sciences
      Hukuoka, Fukuoka, Japan
  • 1991-1993
    • Kitasato University
      • Graduate School of Fisheries Sciences
      Edo, Tōkyō, Japan
  • 1988-1991
    • George Washington University
      • Department of Pathology
      Washington, Washington, D.C., United States
  • 1985-1988
    • Cornell University
      • Department of Pediatrics
      Итак, New York, United States