Hironobu Sasano

Tohoku University, Miyagi, Japan

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Publications (918)3230.07 Total impact

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    ABSTRACT: Adrenocortical carcinoma (ACC) is a malignant neoplasm often associated with an aggressive biological behavior. The histologic differentiation between ACC and adrenocortical adenoma (ACA) is largely determined by employing the Weiss criteria, although this classification may not apply to all the cases. Additionally, various genomic features of ACC could be an auxiliary mode to establish the diagnosis of ACC. Most ACC cases are hormonally functional, and immunohistochemical analysis of steroidogenic enzymes has provided pivotal information as to the analysis of intratumoral production of corticosteroids. This article summarizes the current status of the histopathological diagnosis, molecular pathogenesis, and hormonal features of ACC. Copyright © 2015 Elsevier Inc. All rights reserved.
    Endocrinology & Metabolism Clinics of North America 06/2015; 44(2):399-410. DOI:10.1016/j.ecl.2015.02.007 · 2.86 Impact Factor
  • Keely May McNamara, Hironobu Sasano
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    ABSTRACT: Breast cancer's hormonal dependence is well known and has been so for a long time. However in the last two decades great advances have been made in understanding the local metabolism of steroids within tissue. In the form of aromatase inhibition this is already one of the mainstays of breast cancer therapy. This review aims to summarise briefly what is known in terms of the metabolism of C18 steroids but perhaps more importantly to touch on the new developments regarding the importance of the metabolism of androgens and glucocorticoids in breast tissue. It is our hope that this review should provide the reader with a "birds eye view" of the current state of knowledge regarding localised steroid metabolism in the breast. Copyright © 2015. Published by Elsevier Inc.
    Steroids 06/2015; DOI:10.1016/j.steroids.2015.05.008 · 2.72 Impact Factor
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    ABSTRACT: Aldosterone is one of the mineralocorticoids synthesized and secreted by the adrenal glands, and it plays pivotal roles in regulating extracellular fluid volume and blood pressure. Autonomous excessive aldosterone secretion resulting from adrenocortical diseases is known as primary aldosteronism, and it constitutes one of the most frequent causes of secondary hypertension. Therefore, it is important to understand the molecular mechanisms of aldosterone synthesis in both normal and pathological adrenal tissues. Various factors have been suggested to be involved in regulation of aldosterone biosynthesis, and several adrenocortical cell lines have been developed for use as in vitro models of adrenal aldosterone-producing cells, for analysis of the underlying molecular mechanisms. In this review, we summarize the available reports on the regulation of aldosterone biosynthesis in the normal adrenal cortex, in associated disorders, and in in vitro models. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Journal of steroid biochemistry and molecular biology 06/2015; DOI:10.1016/j.jsbmb.2015.05.008 · 4.05 Impact Factor
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    ABSTRACT: BACKGROUND: c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. METHODS: The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. RESULTS: Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. CONCLUSIONS: The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.
    BMC Cancer 06/2015; 15(1):451. DOI:10.1186/s12885-015-1450-3 · 3.32 Impact Factor
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    ABSTRACT: Adrenal venous sampling (AVS) has been well known to play pivotal roles in clinical differential diagnosis of unilateral aldosterone producing adenoma (APA) from bilateral idiopathic hyperaldosteronism (IHA). However, it is also true that a central vein AVS or c-AVS which collects the blood from right and left central adrenal veins can by no means discriminate bilateral APA from BHA. There have been no published studies reporting the reliable clinical differential diagnosis between bilateral APA and IHA, especially IHA cases with bilateral non-functioning adenomas (NFA), which has been considered practically impossible in clinical differential diagnosis. As an attempt to this clinical dilemma, segmental AVS (S-AVS), which could evaluate segmental effluents from adrenal tributary veins, has been recently developed. We have performed S-AVS in these patients above following C-AVS, via the insertion of a microcatheter in up to three intra-adrenal first-degree tributary veins on bilateral adrenals. S-AVS did enable us to evaluate the intra-adrenal localization of corticosteroidogenesis. These data did indicate that S-AVS should be performed in the PA patients who had increased aldosterone levels in bilateral central vein and demonstrated space occupying lesions in the bilateral adrenals in order to avoid bilateral adrenalectomy or long lasting medical treatment toward persistent PA. In addition to the situations above, we have administere S-AVS to the following patients; those who had clinically suspected APA but not sufficiently high lateralization indexes according to the results of C-AVS, very young ones with higher clinical probability of recurrence and those who could benefit from partial adrenalectomy by demonstrating the sites of specific steroidogenesis. However, it is also entirely true that S-AVS is more expensive, time-consuming and labor-intensive compared to C-AVS.(Figure is included in full-text article.)The angiography during S-AVS (A, B), the coronal CT image (C), and the data in external iliac vein (EIV), each central vein (1, 4) and each tributary vein (2, 3, 5, 6) of 66 year-old male patient with bilateral APAs. We should carefully select the candidate patients who should undergo S-AVS, which will give a benefit to themselves by demonstrating intra-adrenal steroidogenesis for a safer preserving adrenalectomy.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e114. DOI:10.1097/01.hjh.0000467658.23414.b0 · 4.22 Impact Factor
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    ABSTRACT: ABSTRACT Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the second of a two part conference scene, consensus recommendations for radiation treatment, primary systemic therapies and management of genetic predisposition are reported and focus on the following topics: influence of both clinical response to PST and stage at presentation on recommendations for postmastectomy radiotherapy; use of regional nodal irradiation in selected node-positive patients and those with adverse pathological factors; extent of surgical resection following downstaging of tumors with PST; use of preoperative hormonal therapy in premenopausal women with larger, node-negative luminal A-like tumors and managing increasing demands for contralateral prophylactic mastectomy in patients with a unilateral sporadic breast cancer.
    Future Oncology 05/2015; 11(9):1301-5. DOI:10.2217/fon.15.66 · 2.61 Impact Factor
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    ABSTRACT: ABSTRACT Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the first of a two part conference scene, consensus recommendations for axillary management are presented and focus on the following topics: indications for completion axillary lymph node dissection in primary surgical patients with ≤2 macrometastases or any sentinel nodal deposits after PST; the timing of sentinel lymph node biopsy in the context of PST; use of axillary irradiation as a component of primary treatment plans and the role of intraoperative node assessment in the post-Z0011 era.
    Future Oncology 05/2015; 11(9):1297-300. DOI:10.2217/fon.15.65 · 2.61 Impact Factor
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    ABSTRACT: Artifacts in the process of specimen preparation are frequent in ultrastructural evaluation of renal biopsy. We hypothesized that the common practice of wrapping kidney biopsy specimens in saline-soaked gauze to prevent the drying of the specimens could be the major factor of artifacts. In this study, whole kidneys from two male Sprague-Dawley rats were used. Before fixation, fresh small cubes of kidney tissue were macerated in saline (Saline group) or hypoelectrolytic isoosmotic solution for infusion (HISI group) (Sorita T3 or SOLDEM 3A) for 10 or 30 min. Then, the specimens were processed by 1% OsO4 in 0.1 M phosphate buffer (pH 7.4) and embedded by EPON 812 for ultramicroscopic analysis. In the Saline group, ultrastructural examination revealed swollen podocyte, swollen capillary protuberance of the mesangium into the glomerular capillary loop, tubular cells with swollen mitochondria and microvilli, and the smooth muscle cells in the arteriolar wall with marked vacuolar degeneration were detected after 10 min maceration in saline and these findings become more pronounced after 30 min maceration. However, in the HISI group, these artifacts were not identified or limited within 30 min. It is postulated that HISI solution could prevent the artifacts, and be used for soaking and wrapping instead of physiologic saline solution. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
    Pathology International 04/2015; DOI:10.1111/pin.12302 · 1.59 Impact Factor
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    ABSTRACT: Genetic analyses have revealed an important association between P/Q-type calcium channel activities and hereditary neurological disorders. The P/Q-type channels are composed principally of heterologous multimeric subunits including CaV2.1 and CaVβ4. Of these, the β4 subunit is thought to play a significant role in channel physiology, because a mouse line mutant in that subunit (the lethargic mouse: lh) exhibits a severe ataxic phenotype. The aim of the present study was to elucidate the physiological importance of the β4 subunit. ECG analysis showed that the T wave was high in 8-week-old lh mutants; this may be associated with hyperkalemia. Upon pharmacological ECG analysis, 2-3-week-old lh mutants exhibited reduced responses to a β-blocker and a muscarinic receptor antagonist. Analysis of heart rate variability revealed that the R-R interval was unstable in lh mutants and that both the low- and high-frequency components had increased in extent, indicating that the tonus of both the sympathetic and parasympathetic nervous systems was modified. Thus, our present study revealed that the β4 subunit played a significant role in regulation of sympathetic and parasympathetic nerve activities. Copyright © 2015 Elsevier Inc. All rights reserved.
    Biochemical and Biophysical Research Communications 04/2015; 461(2). DOI:10.1016/j.bbrc.2015.03.112 · 2.28 Impact Factor
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    ABSTRACT: Thymidylate synthase (TS) is an enzyme involved in DNA synthesis, and it is a target for 5-fluorouracil. Previous studies have demonstrated that TS is a potent estrogen-induced gene in breast carcinoma cells, suggesting the importance of TS in estrogen-receptor (ER)-positive breast carcinoma. TS immunolocalization has been reported previously, but the clinicopathological significance of TS in ER-positive breast carcinoma still remains unclear. We immunolocalized TS in 178 breast carcinoma tissues in total, and examined its significance according to the ER-status. TS status was positive in 58% of ER-positive ductal carcinoma in situ (DCIS) cases, and it was significantly associated with the Ki-67 and progesterone receptor (PR). Moreover, in ER-positive DCIS patients who received aromatase inhibitor (AI) before surgery, TS immunoreactivity was significantly decreased after AI treatment. In ER-positive invasive ductal carcinoma (IDC) cases, TS status was significantly associated with PR, and it turned out an independent favorable prognostic factor for recurrence of the patients by multivariate analysis. On the other hand, TS status was positively correlated with pathological T factor in ER-negative IDC cases, and tended to have a worse prognosis for disease-free survival of the patients. These results suggest that TS expression is mainly regulated by estrogen in ER-positive breast carcinoma and is associated with estrogen-mediated proliferation. TS status is a favorable prognostic factor in ER-positive IDC patients, which is different from the ER-negative cases.
    Histology and histopathology 04/2015; DOI:10.14670/HH-11-619 · 2.24 Impact Factor
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    ABSTRACT: Krüppel-like factor 15 (KLF15) is a transcription factor that is involved in various biological processes, including cellular proliferation, differentiation and death. In addition, KLF15 has recently been implicated in the development of several human malignancies, including breast cancer. In vitro breast cancer studies have pointed at a putative role in the regulation of cell proliferation. As yet, however, KLF15 expression analyses in primary human breast cancers have not been reported. Here, we set out to investigate the clinical and biological significance of KLF15 expression in human breast cancers. KLF15 expression was evaluated by immunohistochemistry in 54 primary invasive ductal breast carcinomas, and its status was correlated with various clinicopathological parameters. We also assessed KLF15 expression in vitro in 4 breast cancer-derived cell lines using Western blotting, and examined the effects of exogenous KLF15 expression on cell cycle progression using flow cytometry. Concomitant (changes in) p21, p27 and TOPO2A expression levels were examined using real-time RT-PCR and immunocytochemistry, respectively. In ~90 % of the primary breast carcinoma tissues tested, KLF15 was found to be expressed and localized in either the cytoplasm, the nucleus or both. Predominant nuclear immunoreactivity was found to be associated with clinicopathological factors predicting a better clinical outcome (i.e., ER positive, HER2 negative, low grade, low Ki-67 expression). The breast cancer-derived cell lines tested showed a low KLF15 expression with a predominant cytoplasmic localization. Subsequent exogenous KLF15 over-expression resulted in a predominant nuclear localization and a concomitant decreased cellular proliferation and an arrest at the G0/G1 phase of the cell cycle. In addition, we found that nuclear KLF15 expression results in up-regulation of p21, a pivotal suppressor of the G1 to S phase transition of the cell cycle. Our results indicate that nuclear KLF15 expression suppresses breast cancer cell proliferation at least partially through p21 up-regulation and subsequent cell cycle arrest. This is a first study addressing the role of KLF15 in breast cancer development.
    04/2015; 38(3). DOI:10.1007/s13402-015-0226-8
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    ABSTRACT: New molecular markers related to prognosis and/or clinical outcome have been extensively studied in breast cancer. In particular, microRNA (miRNA) has attracted the interest of both basic and clinical investigators as one of the promising molecular markers of breast cancer patients. MiRNAs are a class of short noncoding RNAs that regulate mRNAs at posttranscriptional level and are deregulated in various human malignancies. Previous studies have reported that miRNAs were stably conserved in 10% formalin-fixed paraffin-embedded tissues without significant degradation, in contrast to more fragile RNA. Therefore, in this study, we examined 21 surgical breast cancer specimens using the Human Cancer microRNA PCR Array system (QIAGEN) to explore potential molecular targets of miRNAs. Profiling of miRNA expression in archival materials demonstrated that a group of deregulated miRNAs was associated with clinicopathological parameters of the patients, such as Ki-67, HER2, ER and PR. For instance, an abundant expression of multiple let-7 miRNA family, also known as tumor suppressor, was detected in low Ki-67 and HER2 groups. Elevated expression of 8 miRNAs overlapped between Ki-67+/HER2+/ER+/PR+ groups, including several known oncogenic miRNAs such as miR-148b, miR-15b, miR-200c, miR-150, miR-191, miR-96, miR-25 and miR-21. These results all indicated that when analyzing miRNAs in surgical pathology specimens of breast cancer as a biomarker, they should be examined as a cluster through miRNA profiling, rather than relying on the analysis of a single miRNA.
    The International journal of biological markers 04/2015; 30(2). DOI:10.5301/jbm.5000141 · 1.36 Impact Factor
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    ABSTRACT: The pre-B lymphocyte protein 3 (VPREB3) is expressed during B-cell differentiation and in subsets of mature B-lymphocytes and is mainly found in bone marrow and lymphoid tissue germinative centers. So far, its function in B-cells remains to be clarified. The mRNA of VPREB3 was previously detected in aldosterone-producing adenomas (APA), however further information about this protein in human adrenocortical cells and tissues is currently unavailable. Therefore, in the present study we for the first time investigate the protein expression of VPREB3 in human adrenocortical tissues. In addition, we approach the previously suggested similarities in expression patterns of aldosterone-producing cells and Purkinje neurons. Immunohistochemical analysis of VPREB3 was performed in 13 non-pathological adrenals (NA), 6 adrenal glands with idiopathic hyperaldosteronism (IHA), 18 APA, 5 cortisol-producing adenomas (CPA) and 5 non-pathological human cerebellum specimens. The mRNA levels of VPREB3, steroidogenic-enzymes and other aldosterone biosynthesis markers were detected in 53 APA samples using real-time RT-PCR (qPCR) and compared to the clinical data of APA patients. In our results, the VPREB3 protein was diffusely detected in APA, partially or weakly detected in CPA, and immunolocalized in the zona glomerulosa of NA and IHA, as well as in the cytoplasm of cerebellar Purkinje cells. In APA, VPREB3 mRNA levels were significantly correlated to plasma aldosterone (P=0.026; R=0.30), KCNJ5 mutations (P=0.0061; mutated 34:19 wild-type), CYP11B2 (P<0.0001; R=0.65), Purkinje cell protein 4 (PCP4; P<0.0001; R=0.53) and voltage-dependent calcium channels CaV1.3 (P=0.023; R=0.31) and CaV3.2 (P=0.0019; R=0.42). Based on our data, we hypothesize a possible role for VPREB3 in aldosterone biosynthesis, and present ideas for future functional studies.
    Endocrine Pathology 04/2015; DOI:10.1007/s12022-015-9366-7 · 1.64 Impact Factor
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    ABSTRACT: Background Definitive chemoradiotherapy (dCRT) has recently become one of the most effective therapies for the treatment of esophageal squamous cell carcinoma (ESCC). However, it is also true this treatment has not been effective in all patients. Therefore, it is very important to evaluate the surrogate marker of dCRT in order to improve clinical outcomes of patients with ESCC. On the other hand, our previous study had suggested that murine double minute 2 (MDM2) and p16 were associated with chemoradioresistance in ESCC. Methods We selected pretreatment biopsy specimens of ESCC patients from our prospective clinical study on dCRT. Seventy-nine cases histologically diagnosed as ESCC were used. We immunohistochemically investigated these specimens using antibodies against MDM2, p53, p16, and Ki-67. Results The patients included 68 males and 11 females with a mean age of 63.3 years. The number of patients in each clinical stage was as follows: 22 in c-Stage I; 17 in c-Stage II; and 40 in c-Stage III. cT, cN, and cStage were significantly more advanced in the Failure group (including patients with persistent and recurrent disease after dCRT) than in the complete response (CR) group (patients with persistent CR after dCRT). The clinical stage inversely correlated with the CR rate and the rescue rate after failure. The overall survival rate was significantly worse in the patients with advanced cT, cN, and cStage levels, and in the Failure group. MDM2 positivity was significantly higher in the Failure group than in the CR group in cStageIII (P = 0.014). The number of patients with an absence of p16 immunoreactivity was significantly higher in the Failure group than in the CR group in cStageIII (P = 0.010) but not in cStageI or cStageII. Moreover, the overall survival with a Ki-67 ≥ 33.7% was significantly better than that with <33.7% for patients in cStageIII (P = 0.024). Conclusions The results of this study suggested that MDM2 and p16 are predictive markers for chemoradioresistance in cStageIII ESCC and Ki-67 is a prognostic marker following dCRT in cStageIII ESCC. These issues could contribute to the formulation of treatment strategy for patients with advanced ESCC.
    BMC Cancer 03/2015; 15(1). DOI:10.1186/s12885-015-1222-0 · 3.32 Impact Factor
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    ABSTRACT: Adrenal venous sampling is currently the only reliable method to distinguish unilateral from bilateral diseases in primary aldosteronism. In this study, we attempted to determine whether peripheral plasma levels of 18-oxocortisol (18oxoF) and 18-hydroxycortisol could contribute to the clinical differentiation between aldosteronoma and bilateral hyperaldosteronism in 234 patients with primary aldosteronism, including computed tomography (CT)-detectable aldosteronoma (n=113) and bilateral hyperaldosteronism (n=121), all of whom underwent CT and adrenal venous sampling. All aldosteronomas were surgically resected and the accuracy of diagnosis was clinically and histopathologically confirmed. 18oxoF and 18-hydroxycortisol were measured using liquid chromatography tandem mass spectrometry. Receiver operating characteristic analysis of 18oxoF discrimination of adenoma from hyperplasia demonstrated sensitivity/specificity of 0.83/0.99 at a cut-off value of 4.7 ng/dL, compared with that based on 18-hydroxycortisol (sensitivity/specificity: 0.62/0.96). 18oxoF levels above 6.1 ng/dL or of aldosterone >32.7 ng/dL were found in 95 of 113 patients with aldosteronoma (84%) but in none of 121 bilateral hyperaldosteronism, 30 of whom harbored CT-detectable unilateral nonfunctioning nodules in their adrenals. In addition, 18oxoF levels below 1.2 ng/dL, the lowest in aldosteronoma, were found 52 of the 121 (43%) patients with bilateral hyperaldosteronism. Further analysis of 27 patients with CT-undetectable micro aldosteronomas revealed that 8 of these 27 patients had CT-detectable contralateral adrenal nodules, the highest values of 18oxoF and aldosterone were 4.8 and 24.5 ng/dL, respectively, both below their cut-off levels indicated above. The peripheral plasma 18oxoF concentrations served not only to differentiate aldosteronoma but also could serve to avoid unnecessary surgery for nonfunctioning adrenocortical nodules concurrent with hyperplasia or microadenoma. © 2015 American Heart Association, Inc.
    Hypertension 03/2015; 65(5). DOI:10.1161/HYPERTENSIONAHA.114.04453 · 7.63 Impact Factor
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    ABSTRACT: Pancreatic neuroendocrine tumor (PNET) has been reported to express progesterone receptor (PR) and its expression is demonstrated as a favorable prognostic factor in these patients. We examined the status of PR isoforms, PRA and PRB, in human PNET cell line and their association with cell proliferation of the tumor cells which is closely related to the clinical outcome of PNET patients. Quantitative RT-PCR and cell proliferation assay was performed following the treatment of the cells with progesterone and RU486 as PR antagonist in nontransfected and PRA transfected cells of NET cell line, QGP-1 which expressed PRB in its native state. PRA, PRB and cyclin D1 (CCND1) were immunolocalized in 87 PNET cases and the results were compared with clinicopathological parameters. CCND1, c-Fos and c-Jun mRNA were all significantly increased by the treatment with progesterone in QGP-1 cell line with PRB expression than PRA transfected cells (p = 0.02, p = 0.007, p = 0.001; respectively). The proliferative activity of QGP-1 with PRB expression, was also significantly stimulated by the administration of progesterone (p = 0.008). PRA immunoreactivity was significantly decreased in higher grade PNET (p = 0.04) whereas CCND1 significantly elevated in higher grade PNET (p = 0.035). Results of our present study demonstrated that PRA could play an inhibitory role in cell proliferation of PNET possibly through inhibiting PRB mediated signals under the presence of progesterone, which could result in decreased CCND1 expression. In addition, the status of PRA in tumor cells could be the prognostic factor in PNET. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 03/2015; Online first. DOI:10.1159/000381455 · 4.93 Impact Factor
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    ABSTRACT: A 36-year-old woman presented with a history of sudden back pain. A CT scan showed a retroperitoneal mass (60×38 mm) in the vicinity of the superior pole of the left kidney (figure 1A). She had no apparent signs of Cushing's syndrome. General examination, including complete blood count, blood chemistry, chest X-ray and ECG were all unremarkable. Endocrinological examination, including basal adrenocorticotropic hormone and cortisol levels, was also unremarkable. MRI was performed to characterise …
    Case Reports 03/2015; 2015(mar06 1). DOI:10.1136/bcr-2015-209379
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    ABSTRACT: An inhibitory mechanism toward gastrin hypersecretion is significantly different between G-cell hyperplasia and gastrinoma despite the common clinical manifestations; hypergastrinemia and its related persistent gastric ulcers. We recenlty studied the G-cell, d-cell and ECL-cell density in a case of G-cell hyperplasia. The 70-year-old patient has been treated for persistent gastric ulcers with a markedly increased plasma gastrin (5600 pg/mL). The stomach was surgically resected because of the obstruction associated with ulcer scars. The number of G-cells in the pyloric glands was quantified on the surgical specimens and G-cell hyperplasia was histolopathologically identified. Immunostainig of histidine decarboxylate revealed the presence of ECL-cell hyperplasia in the pyloric glands and its density was significantly and positively correlated with G-cell density. Somatostatin immunoreactive cells (d-cells) increased in their number in the oxyntic glands. These results all indicated that hypersecretion of gastrin in G-cell hyperplasia could induce ECL-cell proliferation in a paracrinal manner. In addition, relatively non-prominent endocrinological features in the G-cell hyperplasia compared to gastrinoma could be also related to the paracrinal somatostatin inhibitory effects upon ECL-cells in the pyloric glands. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.
    Pathology International 03/2015; 65(5). DOI:10.1111/pin.12276 · 1.59 Impact Factor
  • Hironobu Sasano, Samaneh Yazdani, Atsuko Kasajima
    Nippon rinsho. Japanese journal of clinical medicine 03/2015; 73 Suppl 3:321-6.
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    ABSTRACT: We report a rare case of lymphangitis carcinomatosa in a 66-year-old man with a relatively long survival of 18 months following chemotherapy.The patient initially presented with dyspnea and lower abdominal pain.Subsequent colonoscopy detected adenocarcinoma of the descending colon, and computed tomography(CT)demonstrated indications of lymphangitis carcinomatosa of the lung.Therefore, the patient was diagnosed with pulmonary metastasis due to colon cancer and administered chemotherapy.The performance status(PS)of patients with lymphangitis carcinomatosa is usually dismal.This patient's PS was also poor, but dyspnea markedly improved following chemotherapy, and a subsequent CT revealed disappearance of radiological findings of lymphangitis carcinomatosa.However, subsequent immunocytochemistry analysis using the cell transfer method in bronchoalveolar lavage fluid specimens revealed diffuse positivity for cytokeratin(CK)7, while the colon carcinoma was negative for CK7.The difference in CK7 immunoreactivity between the bronchoalveolar lavage fluid and biopsy specimen of the colon indicated that the lymphangitis carcinomatosa in this patient could be reasonably postulated to be caused by a synchronous primary pulmonary adenocarcinoma with intestinal differentiation.However, an autopsy could not be performed to test this hypothesis.
    Gan to kagaku ryoho. Cancer & chemotherapy 03/2015; 42(3):371-374.

Publication Stats

18k Citations
3,230.07 Total Impact Points


  • 1997–2015
    • Tohoku University
      • • Department of Pathology
      • • Division of Internal Medicine
      Miyagi, Japan
  • 2013
    • Kyoto University
      • Division of Pharmaceutical Sciences
      Kioto, Kyōto, Japan
    • Sendai National College of Technology
      Sendai, Kagoshima, Japan
    • Fudan University
      • Department of Obstetrics and Gynecology
      Shanghai, Shanghai Shi, China
  • 1998–2013
    • University of Texas Southwestern Medical Center
      • • Department of Obstetrics and Gynecology
      • • Division of Reproductive Endocrinology and Infertility
      Dallas, Texas, United States
    • Hamamatsu University School Of Medicine
      Hamamatu, Shizuoka, Japan
    • Hyogo Prefectural Amagasaki Hospital
      Amagasaki, Hyōgo, Japan
  • 2012
    • St. Luke's International Hospital
      Edo, Tōkyō, Japan
  • 1999–2012
    • Yokohama Rosai Hospital
      Yokohama, Kanagawa, Japan
    • University of Toronto
      • Saint Michael's Hospital
      Toronto, Ontario, Canada
  • 2011
    • Mitsubishi Nagoya Hospital
      Nagoya, Aichi, Japan
  • 2009
    • The University of Hong Kong
      • Department of Pathology
      Hong Kong, Hong Kong
  • 2003–2009
    • Hirosaki University
      • Department of Endocrinology and Metabolism
      Khirosaki, Aomori Prefecture, Japan
    • University of Illinois at Chicago
      • Department of Obstetrics and Gynecology (Chicago)
      Chicago, Illinois, United States
    • Baker IDI Heart and Diabetes Institute
      Melbourne, Victoria, Australia
    • Akita University
      Akita, Akita, Japan
  • 2008
    • Georgia Health Sciences University
      • Department of Physiology
      Augusta, GA, United States
    • Akita University Hospital
      Akita, Akita, Japan
  • 2004–2008
    • The Jikei University School of Medicine
      • • Department of Internal Medicine H
      • • Department of Pathology
      Tokyo, Tokyo-to, Japan
    • Northwestern University
      • Department of Obstetrics and Gynecology
      Evanston, IL, United States
    • Kumamoto University
      • Department of Obstetrics and Gynecology
      Kumamoto, Kumamoto, Japan
  • 2007
    • Novartis
      Bâle, Basel-City, Switzerland
  • 2004–2007
    • Sendai University
      Sendai, Kagoshima, Japan
  • 2001–2006
    • Fukushima Medical University
      • Department of Obstetrics and Gynecology
      Hukusima, Fukushima, Japan
  • 2005
    • Prince Henry's Institute
      Melbourne, Victoria, Australia
    • Sendai Orthopaedic Hospital
      Sendai, Kagoshima, Japan
  • 1996–2003
    • Keio University
      Edo, Tōkyō, Japan
    • University of Oulu
      • Department of Clinical Chemistry
      Uleoborg, Northern Ostrobothnia, Finland
    • Nippon Kayaku Co., Ltd.
      Edo, Tōkyō, Japan
    • Hokkaido University Hospital
      Sapporo, Hokkaidō, Japan
  • 2002
    • Aomori Prefectural Central Hospital
      Aomori, Aomori Prefecture, Japan
  • 1996–2001
    • Fujita Health University
      Nagoya, Aichi, Japan
  • 2000
    • Fukuoka University
      • Department of Internal Medicine
      Hukuoka, Fukuoka, Japan
  • 1995
    • University of California, Davis
      Davis, California, United States
    • Kyushu University
      • Department of Molecular Biology
      Hukuoka, Fukuoka, Japan
  • 1988–1990
    • George Washington University
      • Department of Pathology
      Washington, Washington, D.C., United States
  • 1985–1988
    • Cornell University
      • Department of Pediatrics
      Итак, New York, United States