A Case of Hashimoto's Thyroiditis with Multiple Drug Resistance and High Expression of Efflux Transporters.

Context: Hashimoto's thyroiditis is the most common cause of hypothyroidism. Patients usually respond well to oral synthetic thyroxine (levothyroxine); however, for unknown reasons some individuals present with treatment-resistant Hashimoto thyroiditis. In cases of cancer and certain infectious diseases, the ATP binding cassette (ABC) transporters have been implicated in multidrug resistance, and we hypothesized and investigated a role of ABC transporters in drug-resistant Hashimoto's thyroiditis.

Pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome.

Solitary fibrous tumors occasionally present with hypoglycemia because of the excessive release of insulin-like growth factor II. We report the first case of pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome. An 82-year-old Japanese man presented with lower limb edema, uncontrolled hypertension, hypokalemia, and baseline hypercortisolism.

Expression of steroidogenic enzymes and their transcription factors in cortisol-producing adrenocortical adenomas: immunohistochemical analysis and quantitative real-time polymerase chain reaction studies.

Adrenal Cushing syndrome (CS) is caused by the overproduction of cortisol in adrenocortical tumors including adrenal cortisol-producing adenoma (CPA). In CS, steroidogenic enzymes such as 17α-hydroxylase/17, 20-lase (CYP17A1), 3β-hydroxysteroid dehydrogenase (HSD3B), and 11β-hydroxylase (CYP11B1) are abundantly expressed in tumor cells. In addition, several transcriptional factors have been reported to play pivotal roles in the regulation of these enzymes in CPA, but their correlations with those enzymes above have still remained largely unknown.

Adrenocortical carcinoma: review of the pathologic features, production of adrenal steroids, and molecular pathogenesis.

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.

c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

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.

Pre-B Lymphocyte Protein 3 (VPREB3) Expression in the Adrenal Cortex: Precedent for non-Immunological Roles in Normal and Neoplastic Human Tissues.

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 messenger RNA (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.

Progesterone Receptor Isoforms A and B in Pancreatic Neuroendocrine Tumor.

Background: Pancreatic neuroendocrine tumors (PNETs) have been reported to express progesterone receptor (PR), and its expression has been demonstrated to be a favorable prognostic factor in these patients. We examined the status of the PR isoforms PRA and PRB in the 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.

Methods: Quantitative RT-PCR and cell proliferation assays were performed following treatment with progesterone and RU-486 as a PR antagonist in nontransfected and PRA-transfected cells of the NET cell line QGP-1, which expresses PRB in its native state.

Decreased expression of ARID1A contributes to infiltrative growth of esophageal squamous cell carcinoma.

The clinical outcome for esophageal squamous cell carcinoma (ESCC) patients is often poor because of the invasive nature of this tumor type. AT-rich interactive domain 1A (ARID1A) functions as a tumor suppressor, and its gene mutation has been reported in various human malignancies. ARID1A is a non-catalytic subunit of the SWItch/Sucrose Non Fermentable (SWI/SNF) chromatin-remodeling complex that regulates gene transcription.

3β-Hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma.

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.

Activating transcription factor 3 (ATF3) in the human adrenal cortex: its possible involvement in aldosterone biosynthesis.

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.

Dissecting the molecular pathways of primary aldosteronism.

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.

Voltage-gated calcium channels in the human adrenal and primary aldosteronism.

Calcium channel blockers can efficiently be used in the treatment of primary aldosteronism (PA) related hypertension, but details on the localization of calcium channel (CC) 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.

Steroidogenic enzymes, their related transcription factors and nuclear receptors in human sebaceous glands under normal and pathological conditions.

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.

Different expression of 11β-hydroxylase and aldosterone synthase between aldosterone-producing microadenomas and macroadenomas.

Aldosterone-producing adenoma is a major subtype of primary aldosteronism. The number of cases of these adenomas, which are below the detection limit of computed tomography but diagnosed by adrenal venous sampling, has recently been increasing. However, the pathophysiology of these adenomas, especially those manifesting clinically overt hyperaldosteronism despite their small size, remains unknown.

Adrenal CYP11B1/2 expression in primary aldosteronism: immunohistochemical analysis using novel monoclonal antibodies.

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).

3βHSD and CYB5A double positive adrenocortical cells during adrenal development/aging.

Androstenedione is a common precursor of sex steroids produced and secreted in the human adrenal gland and produced by 3β-hydroxysteroid dehydrogenase (3βHSD), 17β-hydroxylase/17,20-lyase (CYP17) and cytochrome b5 (CYB5A). 3βHSD is expressed in the zona glomerulosa (ZG) and fasciculata (ZF), CYP17 in the ZF and zona reticularis (ZR) and CYB5A in the ZR, respectively. We previously demonstrated the presence of cortical parenchymal cells co-expressing 3βHSD and CYB5A with hybrid features of both ZF and ZR in human adrenal cortex and hypothesized that these cells may play an important role in androstenedione production in human adrenal gland.

Correlation of tumor-infiltrative lymphocyte subtypes alteration with neoangiogenesis before and after neoadjuvant chemotherapy treatment in breast cancer patients.

The two most important factors in tumor-stromal interactions are tumor-infiltrating lymphocytes (TIL) and neoangiogenesis (NAng). While changes of these parameters in responders of neoadjuvant chemotherapy (NCTx) have been reported, their correlation with pathological response in breast cancer (BC) patients treated with NCTx have not been described. We therefore evaluated alterations of the TIL subtypes ratio and alterations of NAng using the vasohibin-1-positive ratio (VPR) in BC patients during the course of NCTx.

GATA6, SF1, NGFIB and DAX1 in the remodeled subcapsular zones in primary aldosteronism.

The majority of the cases diagnosed as primary aldosteronism (PA) are caused by aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). Histopathologically, both IHA and adjacent adrenal glands of APA demonstrate remodeled subcapsular zone (RSZ) but these zones in two disorders are markedly different in terms of steroidogenesis. 3β-Hydroxysteroid dehydrogenase/Δ⁵-Δ⁴ isomerase (3β-HSD) expression has been known to be activated synergistically by GATA6 and SF1, and repressed by DAX1 through abolishing the activation.

Intercellular adhesion molecule 1/2 and E-selectin in plasma cell mastitis: immunohistochemical study of 35 cases.

Plasma cell mastitis (PCM) is one of the most frequently encountered inflammatory diseases of the nonlactating breast. Histologically, PCM is characterized by infiltration of relatively abundant plasma cells into the mammary ducts. Its pathogenesis has remained unknown.

PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues.

Purkinje cell protein 4 (PCP4) is a calmodulin (CaM)-binding protein that accelerates calcium association and dissociation with CaM. It has been previously detected in aldosterone-producing adenomas (APA), but details on its expression and function in adrenocortical tissues have remained unknown. Therefore, we performed the immunohistochemical analysis of PCP4 in the following tissues: normal adrenal (NA; n=15), APA (n=15), cortisol-producing adenomas (n=15), and idiopathic hyperaldosteronism cases (IHA; n=5).

Metallothionein-3 (MT-3) in the human adrenal cortex and its disorders.

Metallothionein-3 (MT-3) is an intracellular, low molecular weight protein mainly distributed in the central nervous system but also in various peripheral organs and several types of human neoplasms. However, details of MT-3 expression have not been examined in human adrenal cortex and its disorders. The mRNA levels of MT-3 were first evaluated by quantitative RT-PCR (qPCR) in adrenocortical aldosterone-producing adenoma (APA: 11) and cortisol-producing adenoma (CPA: 14).

Changes of tumor infiltrating lymphocyte subtypes before and after neoadjuvant endocrine therapy in estrogen receptor-positive breast cancer patients--an immunohistochemical study of Cd8+ and Foxp3+ using double immunostaining with correlation to the pathobiological response of the patients.

Tumor-stromal interactions involve continuous crosstalk and interactions among different cell types and play pivotal roles in tumorigenesis, tumor development, disease progression, subsequent metastasis, and also tumor response to therapeutic agents. Tumor infiltrating lymphocytes (TILs) are important components of these tumor-stromal interactions. Specific TIL subtypes are known to be involved in the clinical course of individual patients.

Estrogen-related receptor α in normal adrenal cortex and adrenocortical tumors: involvement in development and oncogenesis.

Aims: The nuclear hormone receptor estrogen-related receptor α (ERRα) regulates the activation of mitochondrial genes in various human tissues, but its role in the adrenal gland and its disorders has not been defined. Therefore, we examined ERRα expression in both normal adrenal cortex (NAC) and adrenocortical tumor (ACT) in order to study the possible correlation of ERRα with adrenal development and tumor development.

Methods: Human adrenal specimens (non-pathological fetal n=7; non-pathological post-birth n=40; aldosterone producing adenoma (APA) n=11; cortisol producing adenoma (CPA) n=11; adrenocortical carcinoma (ACC) n=8) were immunohistochemically examined in this study.

Cyclin D1 (CCND1) expression is involved in estrogen receptor beta (ERβ) in human prostate cancer.

Background: Estrogen receptor beta (ERβ) has been demonstrated to be expressed in prostate carcinoma cells and estrogen signals through ERβ to act as a tumor suppressor in prostate cancer patients. ERβ is thought to regulate the cell cycle of prostate carcinoma cells by controlling the expression of cell cycle regulators including cyclin D1 (CCND1). This interaction is of particular interest as CCND1 has been implicated in the development of prostate cancer.