rosiglitazone new england journal of medicine

In particular, rosiglitazone (RGZ), the TZD with the highest affinity for the receptor, has been demonstrated to interfere with cancer growth by blocking cell proliferation/migration and to induce cell differentiation/apoptosis in the ACC cell line H295R ( Very few studies have been conducted on TZD effects in adrenal cancer. Although the antitumor action of TZDs (due to their anti-proliferative, anti-angiogenic, and anti-inflammatory effects) have been well documented in in vitro and animal studies, the results which have emerged from the few clinical trials are still quite controversial (īurton et al. The peroxisome proliferator-activated receptor (PPAR)-γ is a ligand-activated transcription factor, its thiazolidinedione (TZD) ligands, used in type 2 diabetes therapy, have been shown to exert additional anticancer effects in several solid tumors ( Thus, the development of new efficacious and less toxic drugs, specific for ACC, to be eventually combined with mitotane ( However, its effects are mainly due to its adrenocortical cytotoxicity. 2007), and its combination with other chemotherapic drugs has led to variable results (īerruti et al. Mitotane is the only pharmacological adjuvant treatment available for ACC in advanced disease ( The lack of a specific and effective medical regimen is due to the poor knowledge of the mechanisms underlying malignant tumor transformation and progression. Prognosis depends on the tumor stage at surgery – mean survival rate at 5 years is 16–38% (Īllolio & Fassnacht 2006) however, metastatic disease reduces survival to <10% (įassnacht et al. At present, early diagnosis followed by total surgical tumor resection is the only valuable option for ACC cure. Our findings support and expand the role of RGZ in controlling ACC proliferation and angiogenesis in vivo and in vitro.Īdrenocortical carcinoma (ACC) is a rare (1:4×10 6 annual estimated incidence) and aggressive endocrine tumor with a poor prognosis, generally characterized by a limited response to radio/chemotherapy (Īllolio & Fassnacht 2006). The same inhibitory effects were confirmed in in vitro RGZ-treated H295R. Quantitative real-time RT-PCR demonstrated a significant reduction in the expression of angiogenic (VEGF), vascular (CD31), proliferation (BMI-1), and anti-apoptotic (Bcl-2) genes in RGZ versus control group tumors. Tumor immunohistochemistry showed that Ki-67 was reduced in RGZ versus control group. Tumor histological evaluation revealed characteristics of invasiveness, richness in small vessels and mitotic figures in control group, while RGZ group tumors presented non infiltrating borders, few vessels, and many apoptotic bodies.

After 31 days of treatment, mice were killed and tumor analyzed. A significant reduction of tumor growth in RGZ versus control (control) group was observed and was already maximal following 17 day treatment (1−T/C=75.4% (43.7–93.8%)). When the tumor size reached 5 mm, animals were allocated to 5 mg/kg RGZ- or water-treated groups. injection of human ACC H295R cells in athymic mice. We evaluated for the first time the in vivo effect of rosiglitazone (RGZ), an anti-diabetic drug with in vitro anti-tumor properties, on ACC proliferation in a xenograft model obtained by s.c. Research on potential drugs able to specifically interfere with tumor proliferation is essential to develop more efficacious therapies. The lack of a specific and effective medical treatment is due to the poor knowledge of the mechanisms underlying tumor growth. Adrenocortical carcinoma (ACC) is a rare aggressive tumor with a poor prognosis.

Rosiglitazone new england journal of medicine