Pituitary adenomas producing almost exclusively growth hormones (GH) have been ultrastructurally classified into two distinct types: densely granulated somatotroph (DG) adenomas and sparsely granulated (SG) adenomas. Fibrous body (FB), an intracytoplasmic globular aggregation of cytokeratin (CK) filaments, is a hallmark of SG adenomas. Under light microscope, FB could be identified by CK immunohistochemistry as a dot-pattern immunoreaction versus a perinuclear pattern for cells without FB. However, it has been noted that numerous adenomas contain mixed populations of the two patterns. To clarify clinicopathological characteristics of the adenomas with mixed populations ("intermediate type" adenomas) and to confirm clinicopathological differences between strictly defined DG-type and SG-type adenomas, we performed this study on 104 GH cell adenomas. Having segregated "intermediate-type" adenomas (26 cases), we found significant differences between typical DG-type (47 cases) and SG-type adenomas (31 cases); SG-type adenomas had younger ages (44 vs. 50), higher frequency of macroadenomas (86% vs. 58%), invasiveness (65% vs. 38%), advanced grades (3 or 4) in Knosp's classification (50% vs. 24%), and weaker immunoreaction for GH, beta-TSH, alpha-subunit, E-cadherin, and beta-catenin. Clinicopathological characteristics of "intermediate-type" adenomas were identical to those of DG-type adenomas. These findings confirm that SG-type adenoma is a distinct section of GH cell adenomas with special properties and biological behavior, and suggest that intermediate-phenotype adenomas are enrolled in DG-type adenomas. Special properties and biological behavior of SG-type adenomas may appear after the majority of tumor cells possess a fully developed fibrous body.

High-mobility group A2 is highly expressed during embryogenesis and in various benign and malignant tumors. Recent studies report that high-mobility group A2 is negatively regulated by the let-7 microRNAs (miRNAs) family in vitro. The development of pituitary adenomas in high-mobility group A2 transgenic mice showed that high-mobility group A2 may be involved in pituitary tumorigenesis. However, no studies have investigated the clinical significance of high-mobility group A2 and its relationship to the let-7 miRNA family in human pituitary adenomas. Using immunohistochemistry, we analyzed high-mobility group A2 expression with respect to various clinicopathologic factors in 98 pituitary adenomas. Overexpression of high-mobility group A2 was observed in 39% (38/98) of pituitary adenomas compared with normal adenohypophysial tissue and was frequently found in adenomas including prolactin (PRL), adrenocorticotrophic hormone, or follicle-stimulating hormone/luteinizing hormone and in null cell adenomas, but relatively rare in growth hormone (GH) and mixed GH/PRL adenomas. High-mobility group A2 expression was significantly associated with tumor invasion (Po0.05) and was significantly higher in grade IV than in grades I, II, and III adenomas (Po0.05). High levels of high-mobility group A2 expression were more frequently observed in macroadenomas than in microadenomas (Po0.05). High levels of high-mobility group A2 expression also significantly correlated with the proliferation marker Ki-67 (Po0.0001). Real-time quantitative RT-PCR analysis was carried out to evaluate the expression of let-7 in 55 pituitary adenomas. Subsequently, decreased expression of let-7 was confirmed in 23 of 55 (42%) adenomas and was correlated with high-grade tumors (Po0.05). An inverse correlation between let-7 and highmobility group A2 expression was evident (R ¼ À0.33, Po0.05). These findings support a causal link between let-7 and high-mobility group A2 whereby loss of let-7 expression induces high-mobility group A2 upregulation that represents an important mechanism in pituitary tumorigenesis and progression.

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The molecular pathogenesis of gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) remains to be elucidated. Highmobility group A (HMGA) proteins play important roles in the regulation of transcription, differentiation, and neoplastic transformation. In this study, the expression of HMGA1 and HMGA2 was studied in 55 GEP NETs. Overexpression of HMGA1 and 2 was frequently detected in GEP NETs compared with normal tissues. Nuclear immunostaining of HMGA1 and 2 was observed in GEP NETs (38 of 55, 69%; 40 of 55, 73%, respectively). High-mobility group A2 expression increased from well-differentiated NET (WNET) to well-differentiated neuroendocrine carcinoma (WNEC) and poorly differentiated NEC (PNEC) (Po0.005) and showed the highest level in stage IV tumours (Po0.01). In WNECs, the expression of HMGA1 and 2 was significantly higher in metastatic tumours than those without metastasis (Po0.05). Gastroenteropancreatic NETs in foregut showed the highest level of HMGA1 and 2 expressions. MIB-1 labelling index (MIB-1 LI) correlated with HMGA1 and 2 overexpression (R ¼ 0.28, Po0.05; R ¼ 0.434, Po0.001; respectively) and progressively increased from WNETs to WNECs and PNECs (Po0.001). Let-7 expression was addressed in 6 normal organs, 30 tumour samples, and 24 tumour margin non-tumour tissues. Compared with normal tissues, let-7 downregulation was frequent in NETs (19 of 30, 63%). Higher expression of HMGA1 and 2 was frequently observed in tumours with let-7 significant reduction (53, 42%, respectively). The reverse correlation could be detected between HMGA1 and let-7 (Po0.05). Our findings suggested that HMGA1 and 2 overexpression and let-7 downregulation might relate to pathogenesis of GEP NETs.

BackgroundGaro Hills represents one of earliest human habitation in Bangladesh preserving its ancient cultures due to the geographic location. It is situated in the most northern part of Durgapur sub-district having border with Meghalaya of India. Durgapur is rich in ethnic diversity with Garo and Hajong as the major ethnic groups along with Bangalee settlers from the mainstream population. Thus the ethnomedicinal practice in Garo Hills is considered rich as it encompasses three different groups. Present survey was undertaken to compile the medicinal plant usage among the various communities of the Garo Hills.MethodsThe ethnomedicinal data was collected through open and focussed group discussions, and personal interviews using semi-structured questionnaire. A total of 185 people were interviewed, including the three community people and their traditional health practitioners (THPs). The usage of the plants were further analysed and are presented as use value (UV), informant consensus factor (ICF) and fidelity level (FL).ResultsA total of 71 plants from 46 families and 64 genera were documented during our survey. Gastrointestinal disorders represented the major ailment category with the use of 36 plant species followed by dermatological problems (25 species). The ICF ranged from 0.90 to 0.99, with an average value of 0.96. Leaves (41) were the principle source of medication followed by fruits (27). Trees (33) were the major plant type used in the ethnobotanical practice. A total of 25 plants showed high FL (70.91 to 100 %) with 12 plants showing maximum FL (100 %). A number of the plants appear to have unique ethnomedicinal uses.ConclusionPresent investigation revealed a rich traditional practice in the studied region, which provides primary health care to the local community. This compilation of the ethnobotanical knowledge can help researchers to identify the uses of various medicinal plants that have a long history of use.