Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Renin-Angiotensin-Aldosterone System.

Sodium-glucose cotransporters inhibitors (SGLT2-i) and GLP-1 receptor agonists (GLP1-RA) are glucose-lowering drugs that are proved to reduce the cardiovascular (CV) risk in type 2 diabetes mellitus (T2DM). In this process, the renin-angiotensin-aldosterone system (RAAS) is assumed to play a role. The inhibition of SGLT2 improves hyperglycemia hampering urinary reabsorption of glucose and inducing glycosuria.

Correction to: Malignant struma ovarii: next-generation sequencing of six cases revealed Nras, Braf, and Jak3 mutations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Malignant struma ovarii: next-generation sequencing of six cases revealed Nras, Braf, and Jak3 mutations.

Purpose: Struma ovarii (SO) is a highly specialized ovarian teratoma, consisting of thyroid tissue. Rarely, carcinomas histologically identical to their thyroid counterparts may occur, and are comprehensively defined as malignant struma ovarii (MSO). Their optimal management is controversial, and the molecular profile of the malignant counterpart in the ovary is incompletely known.

Histone deacetylase inhibition modulates E-cadherin expression and suppresses migration and invasion of anaplastic thyroid cancer cells.

Context: Anaplastic thyroid cancer cells are characterized by a mesenchymal phenotype, as revealed by spindle-shaped cells and absent or reduced levels of E-cadherin. Epigenetic silencing is considered one of the leading mechanisms of E-cadherin impairment, which causes the acquisition of the invasive and metastatic phenotype of anaplastic thyroid cancer.

Objectives: In this study we investigated the effects of histone deacetylase inhibition on E-cadherin expression, cell motility, and invasion in anaplastic thyroid cancer cell cultures.

Cytotoxic activity of the histone deacetylase inhibitor panobinostat (LBH589) in anaplastic thyroid cancer in vitro and in vivo.

Anaplastic thyroid carcinoma (ATC) has a rapidly fatal clinical course, being resistant to multimodal treatments. Microtubules, α/β tubulin heterodimers, are crucial in cell signaling, division and mitosis and are among the most successful targets for anticancer therapy. Panobinostat (LBH589) is a potent deacetylase inhibitor acting both on histones and nonhistonic proteins, including α-tubulin.

Emerging molecular therapies of advanced thyroid cancer.

Advanced thyroid cancer refers to thyroid tumors which are resistant to conventional therapies and do not respond to radioiodine and comprises metastatic or recurrent differentiated cancers, poorly differentiated and anaplastic tumors. Progress in the knowledge of genetic/epigenetic alterations in thyroid cancer cells is rapidly offering several opportunities to develop new drugs directed to specific targets. Drugs currently proposed for molecular therapy include: (a) monoclonal antibodies; (b) kinase inhibitors; (c) anti-angiogenetic drugs; (d) proteasome inhibitors; (e) retinoic acid and PPAR-gamma ligands; (f) radionuclide therapy; (g) epigenetic drugs (deacetylase inhibitors and demethylating agents).

Effects of the histone deacetylase inhibitor valproic acid on the sensitivity of anaplastic thyroid cancer cell lines to imatinib.

New therapeutic approaches are mandatory for anaplastic thyroid cancer. We investigated the ability of a new combined treatment using valproic acid (VPA), the only clinically available histone deacetylase inhibitor, and the tyrosine-kinase inhibitor imatinib mesylate to control the cell growth of anaplastic thyroid cancer cell lines. We showed that treatment with imatinib alone is unable to affect the cell growth of anaplastic thyroid cancer cells, whereas in ARO cells, the combined treatment resulted in a cytostatic effect, with clinically achievable doses of imatinib and VPA.

Valproic acid enhances tubulin acetylation and apoptotic activity of paclitaxel on anaplastic thyroid cancer cell lines.

The introduction of paclitaxel into multimodal therapy for anaplastic thyroid carcinoma has failed to improve overall survival. Toxicity rules out the high doses required, especially in older patients. The search for strategies to enhance paclitaxel antineoplastic activity and reduce its side effects is thus advisable.

Valproic acid, a histone deacetylase inhibitor, enhances sensitivity to doxorubicin in anaplastic thyroid cancer cells.

Multimodality treatments (i.e. surgery, chemotherapy, and radiotherapy) are recommended for anaplastic thyroid carcinoma (ATC), an extremely lethal human cancer, but to date there is little evidence that such approaches improve survival rates.

Valproic acid induces apoptosis and cell cycle arrest in poorly differentiated thyroid cancer cells.

Poorly differentiated thyroid carcinoma is an aggressive human cancer that is resistant to conventional therapy. Histone deacetylase inhibitors are a promising class of drugs, acting as antiproliferative agents by promoting differentiation, as well as inducing apoptosis and cell cycle arrest. Valproic acid (VPA), a class I selective histone deacetylase inhibitor widely used as an anticonvulsant, promotes differentiation in poorly differentiated thyroid cancer cells by inducing Na(+)/I(-) symporter and increasing iodine uptake.