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Chemotherapy and chemoprevention by thiazolidinediones.

Fröhlich E, Wahl R - Biomed Res Int (2015)

Bottom Line: Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ).The results of chemopreventive effects of TZDs are also considered.Effects are cell-, species-, and compound-specific and concentration-dependent.

View Article: PubMed Central - PubMed

Affiliation: Internal Medicine, Department of Endocrinology, Metabolism, Nephrology and Clinical Chemistry, Department IV, University of Tuebingen, Otfried-Muellerstrasse 10, 72076 Tuebingen, Germany ; Center for Medical Research, Medical University of Graz, Stiftingtalstraße 24, 8010 Graz, Austria.

ABSTRACT
Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ). Troglitazone, rosiglitazone, and pioglitazone have been approved for treatment of diabetes mellitus type II. All three compounds, together with the first TZD ciglitazone, also showed an antitumor effect in preclinical studies and a beneficial effect in some clinical trials. This review summarizes hypotheses on the role of PPARγ in tumors, on cellular targets of TZDs, antitumor effects of monotherapy and of TZDs in combination with other compounds, with a focus on their role in the treatment of differentiated thyroid carcinoma. The results of chemopreventive effects of TZDs are also considered. Existing data suggest that the action of TZDs is highly complex and that actions do not correlate with cellular PPARγ expression status. Effects are cell-, species-, and compound-specific and concentration-dependent. Data from human trials suggest the efficacy of TZDs as monotherapy in prostate cancer and glioma and as chemopreventive agent in colon, lung, and breast cancer. TZDs in combination with other therapies might increase antitumor effects in thyroid cancer, soft tissue sarcoma, and melanoma.

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Related in: MedlinePlus

Overview of treatment options for DTC. Scheme of thyroid tumor (upper left) and scintigraphy with 123Iodide showing lack of uptake in the lower part of the right lobe (upper right).
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fig3: Overview of treatment options for DTC. Scheme of thyroid tumor (upper left) and scintigraphy with 123Iodide showing lack of uptake in the lower part of the right lobe (upper right).

Mentions: Thyroid cancer incidence in the United States has increased in the last thirty years not only apparently because of enhanced detection but probably also as a true increase [95]. DTC is the most common type of thyroid carcinoma, mainly in the form of papillary thyroid carcinoma, accounting for 80–90% of all thyroid cancer cases. The second-most common form of DTC is follicular thyroid cancer with 10–15% incidence. The prognosis of DTC is generally good, with a 10-year survival rate of 85% [96]. A total of 10–20% of patients develops distant metastases [97]. In this group, the 10-year survival rate drops to 40%. Recurrence in DTC, however, occurs in up to a third of patients and only 30% of patients with distant metastases respond to radioiodine (RAI) therapy with complete remission [98, 99]. First-line treatment of DTC is by total or near total removal of the thyroid and if necessary lymph node dissection (Figure 3). This is generally followed by RAI treatment for thyroid remnant ablation and elimination of metastases. In case of insufficient efficacy of this treatment, doxorubicin is initiated [100]. Because doxorubicin treatment is not highly efficient, it is expected that, in the future, differentiating therapies will play a prominent role in cancer treatment. Redifferentiating compounds include retinoids, histone deacetylase inhibitors, DNA methyltransferase inhibitors, and TZDs. Somatostatin analogues such as 68Ga-DOTATOC are additional options for RAI-negative thyroid cancer [101].


Chemotherapy and chemoprevention by thiazolidinediones.

Fröhlich E, Wahl R - Biomed Res Int (2015)

Overview of treatment options for DTC. Scheme of thyroid tumor (upper left) and scintigraphy with 123Iodide showing lack of uptake in the lower part of the right lobe (upper right).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383438&req=5

fig3: Overview of treatment options for DTC. Scheme of thyroid tumor (upper left) and scintigraphy with 123Iodide showing lack of uptake in the lower part of the right lobe (upper right).
Mentions: Thyroid cancer incidence in the United States has increased in the last thirty years not only apparently because of enhanced detection but probably also as a true increase [95]. DTC is the most common type of thyroid carcinoma, mainly in the form of papillary thyroid carcinoma, accounting for 80–90% of all thyroid cancer cases. The second-most common form of DTC is follicular thyroid cancer with 10–15% incidence. The prognosis of DTC is generally good, with a 10-year survival rate of 85% [96]. A total of 10–20% of patients develops distant metastases [97]. In this group, the 10-year survival rate drops to 40%. Recurrence in DTC, however, occurs in up to a third of patients and only 30% of patients with distant metastases respond to radioiodine (RAI) therapy with complete remission [98, 99]. First-line treatment of DTC is by total or near total removal of the thyroid and if necessary lymph node dissection (Figure 3). This is generally followed by RAI treatment for thyroid remnant ablation and elimination of metastases. In case of insufficient efficacy of this treatment, doxorubicin is initiated [100]. Because doxorubicin treatment is not highly efficient, it is expected that, in the future, differentiating therapies will play a prominent role in cancer treatment. Redifferentiating compounds include retinoids, histone deacetylase inhibitors, DNA methyltransferase inhibitors, and TZDs. Somatostatin analogues such as 68Ga-DOTATOC are additional options for RAI-negative thyroid cancer [101].

Bottom Line: Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ).The results of chemopreventive effects of TZDs are also considered.Effects are cell-, species-, and compound-specific and concentration-dependent.

View Article: PubMed Central - PubMed

Affiliation: Internal Medicine, Department of Endocrinology, Metabolism, Nephrology and Clinical Chemistry, Department IV, University of Tuebingen, Otfried-Muellerstrasse 10, 72076 Tuebingen, Germany ; Center for Medical Research, Medical University of Graz, Stiftingtalstraße 24, 8010 Graz, Austria.

ABSTRACT
Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ). Troglitazone, rosiglitazone, and pioglitazone have been approved for treatment of diabetes mellitus type II. All three compounds, together with the first TZD ciglitazone, also showed an antitumor effect in preclinical studies and a beneficial effect in some clinical trials. This review summarizes hypotheses on the role of PPARγ in tumors, on cellular targets of TZDs, antitumor effects of monotherapy and of TZDs in combination with other compounds, with a focus on their role in the treatment of differentiated thyroid carcinoma. The results of chemopreventive effects of TZDs are also considered. Existing data suggest that the action of TZDs is highly complex and that actions do not correlate with cellular PPARγ expression status. Effects are cell-, species-, and compound-specific and concentration-dependent. Data from human trials suggest the efficacy of TZDs as monotherapy in prostate cancer and glioma and as chemopreventive agent in colon, lung, and breast cancer. TZDs in combination with other therapies might increase antitumor effects in thyroid cancer, soft tissue sarcoma, and melanoma.

Show MeSH
Related in: MedlinePlus