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Erschienen in: Journal of Neuro-Oncology 2/2010

01.11.2010 | Clinical Study - Patient Study

Inverse association of PPARγ agonists use and high grade glioma development

verfasst von: Christian Grommes, Devon S. Conway, Amer Alshekhlee, Jill S. Barnholtz-Sloan

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2010

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Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have antineoplastic effects on gliomas in cell lines and animal models. In a retrospective chart review, we assessed the influence of PPARγ agonists on the odds of having a high grade glioma. We reviewed patients with a diagnosis of anaplastic astrocytoma and glioblastoma multiforme (GBM) between 1999 and 2008. Patients with hip fractures served as the control group. Multivariable unconditional logistic regression models were used to calculate the odds of diabetic hip fracture patients using a PPARγ agonist at time of diagnosis as compared to diabetic glioma patients. In addition, survival analysis was performed for all GBM patients. We identified 1602 hip fracture patients and 302 high grade glioma patients, 15 and 16% were diabetics, respectively. PPARγ agonists were used by 20% of diabetic hip fracture patients and by 6% of high grade glioma patients (chi-square P-value = 0.02) with an odds ratio of 4.081 (95% CI: 1.119–14.881). In addition, there was no difference in survival for diabetic patients with GBM compared to non-diabetic patients with GBM. The prevalence of PPARγ agonist use was lower in the diabetic high grade glioma group when compared to diabetic hip fracture patients. These findings suggest that diabetic high grade glioma patients are not given PPARγ agonists as often as diabetic hip fracture patients even though these drugs are considered standard of care and should be equally distributed throughout both groups. This indicates a possible anti-neoplastic effect of PPARγ agonists in gliomas.
Literatur
1.
Zurück zum Zitat Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK (2002) The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61:215–225 (discussion 226-219)PubMed Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK (2002) The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61:215–225 (discussion 226-219)PubMed
2.
Zurück zum Zitat Nieder C, Grosu AL, Astner S, Molls M (2005) Treatment of unresectable glioblastoma multiforme. Anticancer Res 25:4605–4610PubMed Nieder C, Grosu AL, Astner S, Molls M (2005) Treatment of unresectable glioblastoma multiforme. Anticancer Res 25:4605–4610PubMed
3.
Zurück zum Zitat Reardon DA, Rich JN, Friedman HS, Bigner DD (2006) Recent advances in the treatment of malignant astrocytoma. J Clin Oncol 24:1253–1265CrossRefPubMed Reardon DA, Rich JN, Friedman HS, Bigner DD (2006) Recent advances in the treatment of malignant astrocytoma. J Clin Oncol 24:1253–1265CrossRefPubMed
4.
Zurück zum Zitat Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed
5.
Zurück zum Zitat Wilson S, Bergsma D (2000) Orphan G-protein coupled receptors: novel drug targets for the pharmaceutical industry. Drug Des Discov 17:105–114PubMed Wilson S, Bergsma D (2000) Orphan G-protein coupled receptors: novel drug targets for the pharmaceutical industry. Drug Des Discov 17:105–114PubMed
6.
Zurück zum Zitat Lemberger T, Desvergne B, Wahli W (1996) Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology. Annu Rev Cell Dev Biol 12:335–363CrossRefPubMed Lemberger T, Desvergne B, Wahli W (1996) Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology. Annu Rev Cell Dev Biol 12:335–363CrossRefPubMed
7.
Zurück zum Zitat Grommes C, Landreth GE, Heneka MT (2004) Antineoplastic effects of peroxisome proliferator-activated receptor gamma agonists. Lancet Oncol 5:419–429CrossRefPubMed Grommes C, Landreth GE, Heneka MT (2004) Antineoplastic effects of peroxisome proliferator-activated receptor gamma agonists. Lancet Oncol 5:419–429CrossRefPubMed
8.
Zurück zum Zitat Zander T, Kraus JA, Grommes C, Schlegel U, Feinstein D, Klockgether T, Landreth G, Koenigsknecht J, Heneka MT (2002) Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARgamma. J Neurochem 81:1052–1060CrossRefPubMed Zander T, Kraus JA, Grommes C, Schlegel U, Feinstein D, Klockgether T, Landreth G, Koenigsknecht J, Heneka MT (2002) Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARgamma. J Neurochem 81:1052–1060CrossRefPubMed
9.
Zurück zum Zitat Grommes C, Landreth GE, Schlegel U, Heneka MT (2005) The nonthiazolidinedione tyrosine-based peroxisome proliferator-activated receptor gamma ligand GW7845 induces apoptosis and limits migration and invasion of rat and human glioma cells. J Pharmacol Exp Ther 313:806–813CrossRefPubMed Grommes C, Landreth GE, Schlegel U, Heneka MT (2005) The nonthiazolidinedione tyrosine-based peroxisome proliferator-activated receptor gamma ligand GW7845 induces apoptosis and limits migration and invasion of rat and human glioma cells. J Pharmacol Exp Ther 313:806–813CrossRefPubMed
10.
Zurück zum Zitat Grommes C, Landreth GE, Sastre M, Beck M, Feinstein DL, Jacobs AH, Schlegel U, Heneka MT (2006) Inhibition of in vivo glioma growth and invasion by peroxisome proliferator-activated receptor gamma agonist treatment. Mol Pharmacol 70:1524–1533CrossRefPubMed Grommes C, Landreth GE, Sastre M, Beck M, Feinstein DL, Jacobs AH, Schlegel U, Heneka MT (2006) Inhibition of in vivo glioma growth and invasion by peroxisome proliferator-activated receptor gamma agonist treatment. Mol Pharmacol 70:1524–1533CrossRefPubMed
11.
Zurück zum Zitat Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRef Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRef
12.
Zurück zum Zitat Cox DR (1972) Regression models and life-tables. J R Stat Soc B 30:248–275 Cox DR (1972) Regression models and life-tables. J R Stat Soc B 30:248–275
13.
Zurück zum Zitat SAS (2003) Statistical analysis software, version 9.1. SAS Institute, Cary SAS (2003) Statistical analysis software, version 9.1. SAS Institute, Cary
14.
Zurück zum Zitat Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB (2009) Incidence and mortality of hip fractures in the United States. JAMA 302:1573–1579CrossRefPubMed Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB (2009) Incidence and mortality of hip fractures in the United States. JAMA 302:1573–1579CrossRefPubMed
15.
Zurück zum Zitat Jemal A, Clegg LX, Ward E, Ries LA, Wu X, Jamison PM, Wingo PA, Howe HL, Anderson RN, Edwards BK (2004) Annual report to the nation on the status of cancer, 1975–2001, with a special feature regarding survival. Cancer 101:3–27CrossRefPubMed Jemal A, Clegg LX, Ward E, Ries LA, Wu X, Jamison PM, Wingo PA, Howe HL, Anderson RN, Edwards BK (2004) Annual report to the nation on the status of cancer, 1975–2001, with a special feature regarding survival. Cancer 101:3–27CrossRefPubMed
16.
Zurück zum Zitat Meier C, Kraenzlin ME, Bodmer M, Jick SS, Jick H, Meier CR (2008) Use of thiazolidinediones and fracture risk. Arch Intern Med 168:820–825CrossRefPubMed Meier C, Kraenzlin ME, Bodmer M, Jick SS, Jick H, Meier CR (2008) Use of thiazolidinediones and fracture risk. Arch Intern Med 168:820–825CrossRefPubMed
17.
Zurück zum Zitat Loke YK, Singh S, Furberg CD (2009) Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ 180:32–39PubMed Loke YK, Singh S, Furberg CD (2009) Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ 180:32–39PubMed
18.
Zurück zum Zitat Dormuth CR, Carney G, Carleton B, Bassett K, Wright JM (2009) Thiazolidinediones and fractures in men and women. Arch Intern Med 169:1395–1402CrossRefPubMed Dormuth CR, Carney G, Carleton B, Bassett K, Wright JM (2009) Thiazolidinediones and fractures in men and women. Arch Intern Med 169:1395–1402CrossRefPubMed
19.
Zurück zum Zitat Kahn SE, Zinman B, Lachin JM, Haffner SM, Herman WH, Holman RR, Kravitz BG, Yu D, Heise MA, Aftring RP, Viberti G (2008) Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care 31:845–851CrossRefPubMed Kahn SE, Zinman B, Lachin JM, Haffner SM, Herman WH, Holman RR, Kravitz BG, Yu D, Heise MA, Aftring RP, Viberti G (2008) Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care 31:845–851CrossRefPubMed
20.
Zurück zum Zitat Balakumar P, Rose M, Ganti SS, Krishan P, Singh M (2007) PPAR dual agonists: are they opening Pandora’s Box? Pharmacol Res 56:91–98CrossRefPubMed Balakumar P, Rose M, Ganti SS, Krishan P, Singh M (2007) PPAR dual agonists: are they opening Pandora’s Box? Pharmacol Res 56:91–98CrossRefPubMed
21.
Zurück zum Zitat Berge K, Tronstad KJ, Flindt EN, Rasmussen TH, Madsen L, Kristiansen K, Berge RK (2001) Tetradecylthioacetic acid inhibits growth of rat glioma cells ex vivo and in vivo via PPAR-dependent and PPAR-independent pathways. Carcinogenesis 22:1747–1755CrossRefPubMed Berge K, Tronstad KJ, Flindt EN, Rasmussen TH, Madsen L, Kristiansen K, Berge RK (2001) Tetradecylthioacetic acid inhibits growth of rat glioma cells ex vivo and in vivo via PPAR-dependent and PPAR-independent pathways. Carcinogenesis 22:1747–1755CrossRefPubMed
22.
Zurück zum Zitat Kato M, Nagaya T, Fujieda M, Saito K, Yoshida J, Seo H (2002) Expression of PPARgamma and its ligand-dependent growth inhibition in human brain tumor cell lines. Jpn J Cancer Res 93:660–666PubMed Kato M, Nagaya T, Fujieda M, Saito K, Yoshida J, Seo H (2002) Expression of PPARgamma and its ligand-dependent growth inhibition in human brain tumor cell lines. Jpn J Cancer Res 93:660–666PubMed
23.
Zurück zum Zitat Hau P, Kunz-Schughart L, Bogdahn U, Baumgart U, Hirschmann B, Weimann E, Muhleisen H, Ruemmele P, Steinbrecher A, Reichle A (2007) Low-dose chemotherapy in combination with COX-2 inhibitors and PPAR-gamma agonists in recurrent high-grade gliomas—a phase II study. Oncology 73:21–25CrossRefPubMed Hau P, Kunz-Schughart L, Bogdahn U, Baumgart U, Hirschmann B, Weimann E, Muhleisen H, Ruemmele P, Steinbrecher A, Reichle A (2007) Low-dose chemotherapy in combination with COX-2 inhibitors and PPAR-gamma agonists in recurrent high-grade gliomas—a phase II study. Oncology 73:21–25CrossRefPubMed
24.
Zurück zum Zitat Reichle A, Bross K, Vogt T, Bataille F, Wild P, Berand A, Krause SW, Andreesen R (2004) Pioglitazone and rofecoxib combined with angiostatically scheduled trofosfamide in the treatment of far-advanced melanoma and soft tissue sarcoma. Cancer 101:2247–2256CrossRefPubMed Reichle A, Bross K, Vogt T, Bataille F, Wild P, Berand A, Krause SW, Andreesen R (2004) Pioglitazone and rofecoxib combined with angiostatically scheduled trofosfamide in the treatment of far-advanced melanoma and soft tissue sarcoma. Cancer 101:2247–2256CrossRefPubMed
25.
Zurück zum Zitat Reichle A, Vogt T, Coras B, Terheyden P, Neuber K, Trefzer U, Schultz E, Berand A, Brocker EB, Landthaler M, Andreesen R (2007) Targeted combined anti-inflammatory and angiostatic therapy in advanced melanoma: a randomized phase II trial. Melanoma Res 17:360–364CrossRefPubMed Reichle A, Vogt T, Coras B, Terheyden P, Neuber K, Trefzer U, Schultz E, Berand A, Brocker EB, Landthaler M, Andreesen R (2007) Targeted combined anti-inflammatory and angiostatic therapy in advanced melanoma: a randomized phase II trial. Melanoma Res 17:360–364CrossRefPubMed
26.
Zurück zum Zitat Govindarajan R, Ratnasinghe L, Simmons DL, Siegel ER, Midathada MV, Kim L, Kim PJ, Owens RJ, Lang NP (2007) Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes. J Clin Oncol 25:1476–1481CrossRefPubMed Govindarajan R, Ratnasinghe L, Simmons DL, Siegel ER, Midathada MV, Kim L, Kim PJ, Owens RJ, Lang NP (2007) Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes. J Clin Oncol 25:1476–1481CrossRefPubMed
27.
Zurück zum Zitat Koro C, Barrett S, Qizilbash N (2007) Cancer risks in thiazolidinedione users compared to other anti-diabetic agents. Pharmacoepidemiol Drug Saf 16:485–492CrossRefPubMed Koro C, Barrett S, Qizilbash N (2007) Cancer risks in thiazolidinedione users compared to other anti-diabetic agents. Pharmacoepidemiol Drug Saf 16:485–492CrossRefPubMed
28.
Zurück zum Zitat Ramos-Nino ME, MacLean CD, Littenberg B (2007) Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System. BMC Med 5:17 Ramos-Nino ME, MacLean CD, Littenberg B (2007) Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System. BMC Med 5:17
Metadaten
Titel
Inverse association of PPARγ agonists use and high grade glioma development
verfasst von
Christian Grommes
Devon S. Conway
Amer Alshekhlee
Jill S. Barnholtz-Sloan
Publikationsdatum
01.11.2010
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 2/2010
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-010-0185-x

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