Thyroid neoplasia is frequently associated with rearranged during transfection (RET) proto-oncogene mutations that cause hyperactivation of RET kinase activity. Selective inhibition of RET-mediated signaling should lead to an efficacious therapy. SU5416 is a potent inhibitor of vascular endothelial cell growth factor receptor, c-Kit, and FLT-3 receptor tyrosine kinases presently used in clinica...

Thyroid epithelial cells frequently express one or more members of the rearranged during transfection/papillary thyroid carcinoma (RET/PTC) fusion oncogene family during early stages of cancer, and fusion gene transcripts have been found in inflammatory conditions of the thyroid such as the autoimmune disease, Hashimoto's thyroiditis. Because these oncogenes encode chimeric proteins, novel RET/...

Papillary thyroid cancer (PTC) is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF linear molecular signaling cascade is known to mediate PTC pathogenesis. However,...

The relationship between cancer and inflammation is well known since 1863 when Rudolf Virchow, following the observation of leukocytes in neoplastic tissues, hypothesized that chronic inflammation could contribute to the tumorigenic process. In the following decades, several lines of evidence suggested a strong association between chronic inflammation and increased susceptibility to neoplastic ...

RET alterations are recognized as key oncogenic drivers in different cancer types, including non-small cell lung (NSCLC). Multikinase inhibitors (MKIs) with anti-RET activities resulted variable efficacy significant toxicities because of low target specificity. Selective kinase inhibitors, such pralsetinib and selepercatinib, demonstrated high favorable tolerability advanced RET-rearranged NSCL...

The main regulating systems of thyroid growth are the mitogen-activated protein kinase (MAPK) signaling pathway and the cAMP signaling pathway. Thyroid papillary carcinoma frequently involves mutations in BRAF or RET/PTC without overlap, which are expected to constitutively activate MAPK signaling. On the other hand, it has been reported that cAMP signaling acts in an inhibitory manner on the p...

Papillary Thyroid Carcinoma (PTC) is the most frequent thyroid cancer. Although several PTC-specific miRNA profiles have been reported, only few upregulated miRNAs are broadly recognized, while less consistent data are available about downregulated miRNAs. In this study we investigated miRNA deregulation in PTC by miRNA microarray, analysis of a public dataset from The Cancer Genome Atlas (TCGA...

Irregularity in the nuclear shape, with extensive folds and invaginations of the nuclear membrane (NM), remain the basic diagnostic feature of papillary thyroid carcinoma (PTC). The biological reasons for these irregularities are obscure, but evidence has been presented that they might be linked to RET÷PTC gene translocation. In the present study, we have investigated the hypothesis that the NM...

Rearranged during transfection (RET) rearrangements occur in 1% to 2% of lung adenocarcinomas as well other malignancies and are now established targets for tyrosine kinase inhibitors. We developed three novel RET fusion–positive (RET+) patient–derived cancer cell lines, CUTO22 [kinesin 5B (KIF5B)–RET fusion], CUTO32 (KIF5B-RET fusion), CUTO42 (e...