Effect of peroxisome proliferator-activated receptor γ agonist, rosiglitazone, on dedifferentiated thyroid cancers

Philips, Jean-Christophe; Petite, C.; Willi, Jean-Pierre; Buchegger, Franz; Meier, Christoph A.

doi:10.1097/00006231-200412000-00005

Cited by 53 publications

(27 citation statements)

References 7 publications

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“…Activation of PPARg isoforms elicits both anti-neoplastic (Grommes et al 2004, Garcia-Bates et al 2008) and anti-inflammatory effects (Antonelli et al 2006) in several types of mammalian cells. Recently, it has been shown that agonists of PPARg induce apoptosis and exert antiproliferative effects on human papillary carcinoma cells (Ohta et al 2001), prevent distant metastasis of BHP18-21 tumors in nude mice in vivo (Ohta et al 2001), and induce redifferentiation in thyroid cancer cell lines (Klopper et al 2004, Philips et al 2004, Frohlich et al 2005, Park et al 2005, Aiello et al 2006, demonstrating effective therapeutic agents for the treatment of patients with thyroid cancer that fail to respond to traditional treatments (Klopper et al 2004, Philips et al 2004, Frohlich et al 2005, Park et al 2005. Moreover, the expression of PPARg gene and protein were examined in five human anaplastic cancer cell lines (Hayashi et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of secretion of CXC α-chemokine CXCL10 in papillary thyroid cancer: modulation by peroxisome proliferator-activated receptor-γ agonists

Antonelli

Ferrari

Fallahi

et al. 2009

Endocrine-Related Cancer

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In papillary thyroid carcinomas (PTCs), oncogenes activate a transcriptional program including the upregulation of CXCL10 chemokine, which stimulates proliferation and invasion. Furthermore, peroxisome proliferator-activated receptor-g (PPARg) activators thiazolidinediones (TZDs) modulate CXCL10 secretion in normal thyroid follicular cells (TFC), and inhibit PTC growth. Until now, no study has evaluated the effect of cytokines on CXCL10 secretion in PTCs, nor the effect of PPARg activation. The combined effects of interferon g (IFNg) and tumor necrosis factor a (TNFa) stimulation on CXCL10 secretion in primary cells from PTCs and TFC were tested. Furthermore, the effect of PPARg activation by TZDs, on CXCL10 secretion and proliferation in these cell types was studied. In primary cultures of TFC and PTCs CXCL10 production was absent under basal conditions; a similar dose-dependent secretion of CXCL10 was induced by IFNg in both cell types. TNFa alone induced a slight but significant CXCL10 secretion only in PTCs. The stimulation with IFNgCTNFa induced a synergistic CXCL10 release in both cell types; however, a secretion more than ten times higher was induced in PTCs. Treatment of TFC with TZDs dose-dependently suppressed IFNgCTNFainduced CXCL10 release, while TZDs stimulated CXCL10 secretion in PTCs. A significant antiproliferative effect by TZDs was observed only in PTCs. In conclusion, a dysregulation of CXCL10 secretion has been shown in PTCs. In fact, a CXCL10 secretion more than ten times higher has been induced by IFNgCTNFa in PTCs with respect to TFC. Moreover, TZDs inhibited CXCL10 secretion in TFC and stimulated it in PTCs. The effect of TZDs on CXCL10 was unrelated to the significant antiproliferative effect in PTCs.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of secretion of CXC α-chemokine CXCL10 in papillary thyroid cancer: modulation by peroxisome proliferator-activated receptor-γ agonists

Antonelli

Ferrari

Fallahi

et al. 2009

Endocrine-Related Cancer

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“…(14), that elicit both anti-neoplastic (14) and antiinflammatory effects (15) in several types of mammalian cells. Recently, it has been shown that TZD exert anti-proliferative effects on human papillary carcinoma cells (16), and it has been proposed that PPARg agonists may be effective for the treatment of patients with thyroid cancer that fails to respond to traditional treatments (17)(18)(19)(20). Moreover, it has been shown that TZD inhibited cell proliferation and down-regulated the invasive potential in five continuous human anaplastic cancer cell lines (21).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the sensitivity to chemotherapeutics or thiazolidinediones of primary anaplastic thyroid cancer cells obtained by fine-needle aspiration

Antonelli

Ferrari²,

Fallahi³

et al. 2008

European Journal of Endocrinology

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Objective: Anaplastic thyroid cancer (ATC) is often unoperable and chemotherapy and radiotherapy are the main treatments. Until now 'primary ATC cell cultures' (ANA) have been developed from surgical biopsies. The possibility to obtain ANA from fine-needle aspiration (FNA-ANA) and to test their sensitivity to different drugs could increase the effectiveness of treatments and avoid unnecessary surgical procedures. Design: To obtain FNA-ANA from six ATC patients before undergoing surgery and to evaluate the chemosensitivity of FNA-ANA to chemotherapeutic agents and thiazolidinediones (TZD). Methods and results: FNA-ANA from the six ATC patients were cultured in RPMI 1640 and propagated in DMEM. Chemosensitivity was evaluated by inhibiting the proliferation with increasing concentrations of five different chemotherapeutic agents (bleomycin, cisplatin, gemcitabine, etoposide, and carboplatin) or TZD (rosiglitazone). Chemotherapeutic agents significantly inhibited (P!0.0001) FNA-ANA proliferation, such as TZD (P!0.001); etoposide was the most effective in reducing cell growth. Another ANA culture for each patient was obtained from a biopsy specimen; the results for the chemosensitivity tests were similar to those obtained with FNA-ANA. The V600E BRAF mutation was observed in two ATC patients; the inhibition of proliferation by drugs was similar in tumors with or without V600E BRAF mutation. Conclusions: Our study demonstrates 1) the possibility to obtain FNA-ANA, and opens the way to the use of FNA-ANA to test the chemosensitivity to different drugs (chemotherapeutic agents or TZD; and possibly the radiosensitivity) in each patient, avoiding unnecessary surgical procedures and the administration of inactive chemotherapeutics; and 2) that etoposide is highly effective in reducing ATC cell growth in vitro.European Journal of Endocrinology 159 283-291

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“…PPARg was believed to act as a tumor suppressor in tumors of prostate, breast and colon by inducing apoptosis (Koeffler 2003, Philips et al 2004, Kim et al 2007). Yet TR4's roles in PCa progression can be either as an enhancer of PCa metastasis or as an suppressor of PCa development.…”

Section: Cancermentioning

confidence: 99%

“…PPARg-mediated apoptosis and cell differentiation have been found to be beneficial in the chemotherapy of different types of cancers including prostate, breast, and colon (Koeffler 2003, Philips et al 2004, Kim et al 2007. Moderate anticancer activities of PPARg ligands with minimal toxicities have been observed in patients with liposarcomas and PCa, possibly due to decreased expression of cyclin D1 and increased expression of p21waf1 (Wang et al 2001, Lyles et al 2009).…”

Section: Cancermentioning

confidence: 99%

Differential roles of PPARγ vs TR4 in prostate cancer and metabolic diseases

Liu

Lin

et al. 2014

Endocrine-Related Cancer

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Peroxisome proliferator-activated receptor g (PPARg, NR1C3) and testicular receptor 4 nuclear receptor (TR4, NR2C2) are two members of the nuclear receptor (NR) superfamily that can be activated by several similar ligands/activators including polyunsaturated fatty acid metabolites, such as 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatetraenoic acid, as well as some anti-diabetic drugs such as thiazolidinediones (TZDs). However, the consequences of the transactivation of these ligands/activators via these two NRs are different, with at least three distinct phenotypes. First, activation of PPARg increases insulin sensitivity yet activation of TR4 decreases insulin sensitivity. Second, PPARg attenuates atherosclerosis but TR4 might increase the risk of atherosclerosis. Third, PPARg suppresses prostate cancer (PCa) development and TR4 suppresses prostate carcinogenesis yet promotes PCa metastasis. Importantly, the deregulation of either PPARg or TR4 in PCa alone might then alter the other receptor's influences on PCa progression. Knocking out PPARg altered the ability of TR4 to promote prostate carcinogenesis and knocking down TR4 also resulted in TZD treatment promoting PCa development, indicating that both PPARg and TR4 might coordinate with each other to regulate PCa initiation, and the loss of either one of them might switch the other one from a tumor suppressor to a tumor promoter. These results indicate that further and detailed studies of both receptors at the same time in the same cells/organs may help us to better dissect their distinct physiological roles and develop better drug(s) with fewer side effects to battle PPARg-and TR4-related diseases including tumor and cardiovascular diseases as well as metabolic disorders.

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Effect of peroxisome proliferator-activated receptor γ agonist, rosiglitazone, on dedifferentiated thyroid cancers

Cited by 53 publications

References 7 publications

Dysregulation of secretion of CXC α-chemokine CXCL10 in papillary thyroid cancer: modulation by peroxisome proliferator-activated receptor-γ agonists

Dysregulation of secretion of CXC α-chemokine CXCL10 in papillary thyroid cancer: modulation by peroxisome proliferator-activated receptor-γ agonists

Evaluation of the sensitivity to chemotherapeutics or thiazolidinediones of primary anaplastic thyroid cancer cells obtained by fine-needle aspiration

Differential roles of PPARγ vs TR4 in prostate cancer and metabolic diseases

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