Hobnail Papillary Thyroid Carcinoma, A Systematic Review and Meta-Analysis.

Although papillary thyroid carcinoma (PTC) is considered to have an excellent prognosis, some recently identified more aggressive variants show reduced overall survival rates. Hobnail PTC (HPTC) was newly recognized as one of these aggressive forms, affecting recurrence, metastasis, and overall survival rates. Herein, we performed a systematic review and meta-analysis of studies including cases or case series with patients with HPTC. Furthermore, we included our individual case series consisting of six patients. The pooled mortality rate in the cohort, consisting of 290 patients, was 3.57 (95% CI 1.67−7.65) per 100 person/years. No sex differences could be observed concerning mortality (p = 0.62), but older age and tumor size significantly affected mortality (p = 0.004 and p = 0.02, respectively). The percentage of hobnail cells did not affect mortality (p = 0.97), neither did the presence of BRAF mutations. Classical characteristics such as the presence of extrathyroidal extension (p = 0.001), distant metastases (p < 0.001), and lymph node metastases (p < 0.001) all had a significant impact on mortality. Thus, HPTC appears to correlate with worse overall survival, and all PTC cases should be carefully assessed for this variant.

From the Argonauts Mythological Sailors to the Argonautes RNA-Silencing Navigators: Their Emerging Roles in Human-Cell Pathologies.

Regulation of gene expression has emerged as a fundamental element of transcript homeostasis. Key effectors in this process are the Argonautes (AGOs), highly specialized RNA-binding proteins (RBPs) that form complexes, such as the RNA-Induced Silencing Complex (RISC). AGOs dictate post-transcriptional gene-silencing by directly loading small RNAs and repressing their mRNA targets through small RNA-sequence complementarity. The four human highly-conserved family-members (AGO1, AGO2, AGO3, and AGO4) demonstrate multi-faceted and versatile roles in transcriptome's stability, plasticity, and functionality. The post-translational modifications of AGOs in critical amino acid residues, the nucleotide polymorphisms and mutations, and the deregulation of expression and interactions are tightly associated with aberrant activities, which are observed in a wide spectrum of pathologies. Through constantly accumulating information, the AGOs' fundamental engagement in multiple human diseases has recently emerged. The present review examines new insights into AGO-driven pathology and AGO-deregulation patterns in a variety of diseases such as in viral infections and propagations, autoimmune diseases, cancers, metabolic deficiencies, neuronal disorders, and human infertility. Altogether, AGO seems to be a crucial contributor to pathogenesis and its targeting may serve as a novel and powerful therapeutic tool for the successful management of diverse human diseases in the clinic.

Total and high-molecular-weight adiponectin in breast cancer: in vitro and in vivo studies.

BACKGROUND: Obesity is a major risk factor for breast cancer. We hypothesized that obesity-induced decreases in total and/or high-molecular-weight (HMW) adiponectin levels may underlie this association. METHODS: We measured serum total and HMW adiponectin in a hospital-based case-control study of 74 female breast cancer patients and 76 controls. In parallel, expression of adiponectin and its receptors AdipoR1/R2 were measured in tissue samples using RT-PCR, and protein expression of AdipoR1/R2 was localized and quantified using immunohistochemistry. Finally, we documented AdipoR1/R2 expression in several breast cancer cell lines and studied adiponectin signaling and the effect of adiponectin on proliferation in the T47D breast cancer cell line in vitro. RESULTS: Women with the highest adiponectin levels had a 65% reduced risk of breast cancer (P = 0.04). This association became stronger after adjustment for age, body mass index, and hormonal and reproductive factors (P = 0.02). Modeling HMW instead of total adiponectin produced similar results and did not offer any additional predictive value. Breast cancer cells expressed AdipoR1/R2 but not adiponectin. Expression of AdipoR1, but not AdipoR2, was higher in tumor tissue than both adjacent and control tissues. Exposure of T47D cells to adiponectin significantly inhibited the percentage of viable cells to 86% and proliferation to 66% but had no effect on apoptosis. These effects were associated with activation of ERK1/2 but not AMP-activated protein kinase or p38MAPK. CONCLUSION: These studies suggest that adiponectin may act as a biomarker of carcinogenesis and may constitute a molecular link between obesity and breast cancer.