Search

Anaplastic thyroid carcinoma (ATC) is the most aggressive malignancy in thyroid cancers. Resistance to current therapies is still a challenge. MicroRNAs are a class of small non-coding RNAs, regulating gene expression. MiR-21 is an oncomiR that is overexpressed in nearly all cancers including ATC. Accumulating evidence suggested that miR-21 has a role in cancer stemness state, apoptosis, cell cycle progression, and differentiation. Therefore, we evaluated the application of Off-miR-21 to sequester the microRNA for therapeutic purposes on ATC cell lines. In this study, C643 and SW1736 were transducted by hsa-miR-21 antagomir (Off-miR-21). PTEN gene expression was performed as a known target of miR-21. Stemness state in cancer stem cells (CSCs) was evaluated by the changes of CSC biomarkers including Oct-4 and ABCG2. Apoptosis was assessed by PDCD4 and Mcl-1 gene expression and flow cytometry. Sodium/iodide symporter ( NIS) and thyroglobulin ( TG) were measured as ATC differentiation markers. In addition, cell cycle progression was investigated via the alterations of p21 gene expression and flow cytometry. Specific downregulation of miR-21 induced the differentiation and apoptosis in C643 and SW1736. Inversely, the treatment inhibited stemness state and cell cycle progression. Knockdown of miR-21 significantly increased the expression of PDCD4, p21, NIS, and TG while leading to decreased expression of Oct-4, ABCG2, and Mcl-1.Taken together, the results suggest that miR-21, as an oncomiR, has a role not only in stemness state but also in tumor growth, differentiation, and apoptosis. Hence, suppression of miR-21 could pave the way for ATC therapy. [ABSTRACT FROM AUTHOR]

The Distinction between malignant and benign pheochromocytoma has always been a diagnostic challenge over the last decades. To date, the only reliable criterion is metastasis. The aim of the present study was to investigate the possible expression of pituitary-tumor transforming gene (PTTG1) and retinoblastoma (Rb) in benign and malignant pheochromocytoma. Paraffin blocks of 44 and 11 patients diagnosed with benign and malignant pheochromocytoma were collected. Parameters such as sex, age, tumor size, necrosis, and histological features were compared between the benign and malignant groups as well as immunohistochemical labeling using specific antibodies. PTTG1 showed negative expression in all (44) benign and 9 out of 11 (81.8%) malignant tumors with only 2 out of 11 (18.2%) malignant tumors showed positive reactivity for PTTG1 (P: 0.037) with spindle cell histological pattern in both of them (P: 0.013). Although Rb expression in malignant tumors (81.8%) was slightly more than the benign ones (52.3%), no statistically significant correlation was observed (P: 0.087). These results suggest that PTTG1 immunostaining may play a key role in distinguishing between benign and malignant phaeochromocytoma. However, larger studies are necessary to confirm the outcomes of the present study. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) has been identified as a histone deacetylase inhibitor, inducing differentiation in transformed cells. However, no study has shown the effect of VPA in the redifferentiation induction and stemness of anaplastic thyroid. Themain objective of this study was to evaluate the efficacy of VPA as a differentiation therapy agent in human thyroid cancer based on its effect on stemness and differentiation process. Indications for differentiation of 8305C and B-CPAP cell lines following VPA treatment were obtained by analyzing cell proliferation rate, morphological changes, adherent-dependent colony formation, and Hoechst 33342 staining. The expressions of stemness, differentiation, and aggressiveness specific marker genes were measured by quantitative RT-PCR. VPA treatment effectively showed growth inhibition in both cell lines. The high nuclear-cytoplasmic (N : C) ratio of8305C cells markedly decreased and treated cells became more epithelial-like. Treated cells showed stronger Hoechst 33342 fluorescence compared with control cells. The hTERT and OCT-4 reduction was paralleled with adherent-dependent colony formation decrement in both cell lines. VPA effectively induced NIS and TTF-1 in anaplastic cells, it whereas showed no clear pattern in papillary cell line. VPA treatment also resulted in the reduction of MMP-2 and MMP-9. These finding suggest that VPA could redifferentiate the anaplastic thyroid cancer cells. [ABSTRACT FROM AUTHOR]

Objective: In this study we aimed to determine the prevalence of cardiac malformations in fetuses of Iranian diabetic mothers with pre-gestational and gestational diabetes mellitus (GDM) and to find the patterns of different cardiac malformations. Methods: One-hundred and seventy diabetic pregnant women (68 preGDM and 102 GDM) (mean age: 32.17±4.8 years) and 85 healthy controls (mean age: 31.35±4.55 years) were recruited from September 2008 to July 2012. Fetal echocardiography was performed to assess cardiac malformation. In order to study major factors that may affect the results, a complete history was obtained. Findings: Fetal echocardiography was performed at mean gestational age of 24.7±5.4 and 20.27±3.9 weeks in diabetic patients and control group, respectively. Fifteen (8.8%) fetuses of diabetic mothers were detected to have cardiac malformations compared with 1 (1.17%) fetus in control group (OR: 8.13, 95%CI: 1.1-62.61, P-value=0.02). Hypertrophic cardiomyopathy noted as the most common cardiac malformation occurred in 6 out of 15 (40%) fetuses, and was found significantly more common in pre-GDM compared to GDM group (7.4% vs 1%, P-value =0.04). Despite the higher incidence of cardiac malformation in pre-GDM compared to GDM group, the difference was not significant. Further, no significant association was observed between the variables including; parity, diabetic regimen, parents' consanguinity, maternal history of hypertension or hypothyroidism and occurring cardiac malformations (P-value >0.05). Conclusion: In this study we detected cardiac malformations in 8.8% of our diabetic referrals. The result of the present study shows that screening diabetic mothers for fetal cardiac malformations could be beneficial. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid carcinoma (ATC) is the most aggressive malignancy in thyroid cancers. Resistance to current therapies is still a challenge. MicroRNAs are a class of small non-coding RNAs, regulating gene expression. MiR-21 is an oncomiR that is overexpressed in nearly all cancers including ATC. Accumulating evidence suggested that miR-21 has a role in cancer stemness state, apoptosis, cell cycle progression, and differentiation. Therefore, we evaluated the application of Off-miR-21 to sequester the microRNA for therapeutic purposes on ATC cell lines. In this study, C643 and SW1736 were transducted by hsa-miR-21 antagomir (Off-miR-21). PTEN gene expression was performed as a known target of miR-21. Stemness state in cancer stem cells (CSCs) was evaluated by the changes of CSC biomarkers including Oct-4 and ABCG2. Apoptosis was assessed by PDCD4 and Mcl-1 gene expression and flow cytometry. Sodium/iodide symporter (NIS) and thyroglobulin (TG) were measured as ATC differentiation markers. In addition, cell cycle progression was investigated via the alterations of p21 gene expression and flow cytometry. Specific downregulation of miR-21 induced the differentiation and apoptosis in C643 and SW1736. Inversely, the treatment inhibited stemness state and cell cycle progression. Knockdown of miR-21 significantly increased the expression of PDCD4, p21, NIS, and TG while leading to decreased expression of Oct-4, ABCG2, and Mcl-1.Taken together, the results suggest that miR-21, as an oncomiR, has a role not only in stemness state but also in tumor growth, differentiation, and apoptosis. Hence, suppression of miR-21 could pave the way for ATC therapy.

In this study, we evaluated the immunohistochemical expression and the possible advantages of Ki67 antigen, c-erbB-2, and c-kit proto-oncogenes in the differentiation between benign and malignant pheochromocytomas. Paraffin-embedded tissue blocks from 44 benign (35 adrenal and 9 extra-adrenal) and 11 malignant (9 adrenal and 2 extra-adrenal) cases of pheochromocytoma were selected for immunohistochemical staining using antibodies against Ki67, c-erbB-2, and c-kit antigens. We investigated the relationship between the expression of these antigens and age, gender, tumor size, histologic patterns and necrosis, as well as tumor behavior. The risk of malignancy was higher when tumor size was increased. We found out that more uncommon tissue patterns, such as small cell and spindle cell patterns, are mostly indicators of malignancy. There was a statistically significant relationship between Ki67- and c-erbB-2-positive staining of the tumor cells and the malignant behavior of the pheochromocytomas (p-value=0.000), while cytoplasmic c-kit staining did not show any correlation with tumor malignancy (p-value=0.087). We concluded that tumor size and the histomorphologic patterns (spindle cell and small round cell) are significantly associated with tumor behavior. In addition, Ki67 positivity and c-erbB-2 expression can be used as immunohistochemical markers for predicting the malignant behavior of pheochromocytoma., ((c) 2010 Elsevier GmbH. All rights reserved.)

Pituitary adenomas without clinically active hypersecretion are summarized under the term non-functioning pituitary adenoma (NFPA). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties. By using immunohistochemical methods we will have new insight into the nature and pathogenesis of these tumours. Ki-67 is a nuclear antigen detected by the monoclonal antibody MIB-1 and its labelling index (LI) is considered a marker of normal and abnormal cell proliferation. The aim of this study was to investigate the possible role of immunohistochemistry and MIB1-LI determination in NFPAs to predict tumoural behaviour and better management. In this clinicopathological study, 85 cases of NFPAs were analysed immunohistochemically. MIB1-LI was also determined in studied cases. Clinical presentation, treatment and follow-up data were also reviewed and the correlation between clinical and pathologic findings was established. Eighteen adenomas (21.2%) were immunoreactive to one or two adenohypophysial hormones of which 4 GH positive adenomas had aggressive behaviour (2 significant juxtasellar extensions and 2 recurrences). MIB-1 LI was more than 5% in only 5 cases including 2 invasive adenomas but with no evidence of recurrence. No significant statistical difference between clinical presentations in immunoreactive and non-immunoreactive NFPAs was observed except for unilateral temporal hemianopia which was more common in immunoreactive adenomas (P=0.022). NFPAs comprise several pathologically different types of tumours, some of which are potentially hormone producing, but some defects in hormone secretion or production of biologically inactive or insufficient amount of hormone may be the culprit in the lack of evidence of rising serum hormone levels. MIB-1 LI may be indicative of invasiveness but not a predictor of recurrence. Silent somatotropinomas may have more aggressive behaviour in comparison with other NFPAs.

Follicular thyroid carcinoma with metastasis rarely presents with clinical picture of spinal cord compression. This report describes a 53 years old patient with follicular thyroid carcinoma who presented with paraplegia and urinary incontinence. Magnetic resonance imaging (MRI) of neck revealed a mass with destruction of C5 and extension to C6. Histopathology study demonstrated metastatic carcinoma of thyroid.