Role of Peroxisome Proliferator‐Activated Receptor Gamma and Its Ligands in the Treatment of Hematological Malignancies

García-Bates, Tatiana M.; Lehmann, Geniece M.; Simpson-Haidaris, Patricia J.; Bernstein, Steven H.; Sime, Patricia J.; Phipps, Richard P.

doi:10.1155/2008/834612

Cited by 27 publications

(32 citation statements)

References 211 publications

(267 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…PPARγ affects normal and malignant B cell differentiation and proliferation (21, 33). Considering that B cells from PPARγ-deficient mice produced less IgG upon activation, we investigated if there were any differences in cell proliferation.…”

Section: Resultsmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor γ B Cell-Specific–Deficient Mice Have an Impaired Antibody Response

Ramon

Bancos

Thatcher

et al. 2012

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. PPARγ, a ligand activated transcription factor, has important anti-inflammatory and anti-proliferative functions and it has been associated with diseases including diabetes, scarring and atherosclerosis among others. PPARγ is expressed in most bone marrow derived cells and influences their function. PPARγ ligands can stimulate human B cell differentiation and promote antibody production. A knowledge gap is that the role of PPARγ in B cells under physiological conditions is not known. We developed a new B cell-specific PPARγ (B-PPARγ) knockout mouse and explored the role of PPARγ during both the primary and secondary immune response. Here, we show that PPARγ deficiency in B cells decreases germinal center B cells and plasma cell development as well as the levels of circulating antigen-specific antibodies during a primary challenge. Inability to generate germinal center B cells and plasma cells is correlated to decreased MHC class II expression and decreased Bcl-6 and Blimp-1 levels. Furthermore, B-PPARγ-deficient mice have an impaired memory response, characterized by low titers of antigen-specific antibodies and low numbers of antigen-experienced antibody-secreting cells. However, B-PPARγ-deficient mice have no differences in B cell population distribution within neither primary nor secondary lymphoid organs during development. This is the first report to show under physiological conditions that PPARγ expression in B cells is required for an efficient B cell-mediated immune response as it regulates B cell differentiation and antibody production.

show abstract

“…It has been reported that PPARg activation inhibits cell growth [31] and causes differentiation and apoptosis in a variety of cancer cell types [32]. Activation of PPARg has been shown to change mitochondrial membrane permeability resulted in the induction of cellular apoptosis [32].…”

Section: Discussionmentioning

confidence: 99%

PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b

Luo

Wang

et al. 2015

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Role of Peroxisome Proliferator‐Activated Receptor Gamma and Its Ligands in the Treatment of Hematological Malignancies

Cited by 27 publications

References 211 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

Peroxisome Proliferator-Activated Receptor γ B Cell-Specific–Deficient Mice Have an Impaired Antibody Response

PPARγ inhibits ovarian cancer cells proliferation through upregulation of miR-125b

Contact Info

Product

Resources

About