Beyond peroxisome proliferator-activated receptor gamma signaling: the multi-facets of the antitumor effect of thiazolidinediones.

Abstract:

:Certain members of the thiazolidinedione (TZD) family of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, such as troglitazone and ciglitazone, exhibit antitumor activities; however, the underlying mechanism remains inconclusive. Substantial evidence suggests that the antiproliferative effect of these TZD members in cancer cells is independent of PPARgamma activation. To discern the role of PPARgamma in the antitumor effects of TZDs, we have synthesized PPARgamma-inactive TZD analogs which, although devoid of PPARgamma activity, retain the ability to induce apoptosis with a potency equal to that of their parental TZDs in cancer cell lines with varying PPARgamma expression status. Mechanistic studies from this and other laboratories have further suggested that troglitazone and ciglitazone mediate antiproliferative effects through a complexity of PPARgamma-independent mechanisms. Evidence indicates that troglitazone and ciglitazone block BH3 domain-mediated interactions between the anti apoptotic Bcl-2 (B-cell leukemia/lymphoma 2) members Bcl-2/Bcl-xL and proapoptotic Bcl-2 members. Moreover, these TZDs facilitate the degradation of cyclin D1 and caspase-8-related FADD-like IL-l-converting enzyme (FLICE)-inhibitory protein through proteasome-mediated proteolysis, and down-regulate the gene expression of prostate-specific antigen gene expression by inhibiting androgen activation of the androgen response elements in the promoter region. More importantly, dissociation of the effects of TZDs on apoptosis from their original pharmacological activity (i.e. PPARgamma activation) provides a molecular basis for the exploitation of these compounds to develop different types of molecularly targeted anticancer agents. These TZD-derived novel therapeutic agents, alone or in combination with other anticancer drugs, have translational relevance in fostering effective strategies for cancer treatment.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Weng JR,Chen CY,Pinzone JJ,Ringel MD,Chen CS

doi

10.1677/erc.1.01182

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

401-13

issue

2

eissn

1351-0088

issn

1479-6821

pii

13/2/401

journal_volume

13

pub_type

杂志文章,评审
  • Src family kinase activity regulates adhesion, spreading and migration of pancreatic endocrine tumour cells.

    abstract::Pancreatic endocrine tumours (PETs) are rare and 'indolent' neoplasms that usually develop metastatic lesions and exhibit poor response to standard medical treatments. Few studies have investigated pathways responsible for PET cell growth and invasion and no alternative therapeutic strategies have been proposed. In a ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/erc.1.01318

    authors: Di Florio A,Capurso G,Milione M,Panzuto F,Geremia R,Delle Fave G,Sette C

    更新日期:2007-03-01 00:00:00

  • Increased expression of both insulin receptor substrates 1 and 2 confers increased sensitivity to IGF-1 stimulated cell migration.

    abstract::Insulin-like growth factors (IGFs) are thought to promote tumour progression and metastasis in part by stimulating cell migration. Insulin receptor substrate-1 (IRS-1) and IRS-2 are multisite docking proteins positioned immediately downstream from the type I IGF and insulin receptors. IRS-2 but not IRS-1 has been repo...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-08-0216

    authors: de Blaquière GE,May FE,Westley BR

    更新日期:2009-06-01 00:00:00

  • p300 is upregulated by docetaxel and is a target in chemoresistant prostate cancer.

    abstract::Administration of the microtubule inhibitor docetaxel is a common treatment for metastatic castration-resistant prostate cancer (mCRPC) and results in prolonged patient overall survival. Usually, after a short period of time chemotherapy resistance emerges and there is urgent need to find new therapeutic targets to ov...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-19-0488

    authors: Gruber M,Ferrone L,Puhr M,Santer FR,Furlan T,Eder IE,Sampson N,Schäfer G,Handle F,Culig Z

    更新日期:2020-03-01 00:00:00

  • Support of a bi-faceted role of estrogen receptor β (ERβ) in ERα-positive breast cancer cells.

    abstract::The expression of estrogen receptor α (ERα) in breast cancer identifies patients most likely to respond to endocrine treatment. The second ER, ERβ, is also expressed in breast tumors, but its function and therapeutic potential need further study. Although in vitro studies have established that ERβ opposes transcriptio...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-13-0444

    authors: Jonsson P,Katchy A,Williams C

    更新日期:2014-01-30 00:00:00

  • A multi-gene approach to differentiate papillary thyroid carcinoma from benign lesions: gene selection using support vector machines with bootstrapping.

    abstract::Selection of novel molecular markers is an important goal of cancer genomics studies. The aim of our analysis was to apply the multivariate bioinformatical tools to rank the genes - potential markers of papillary thyroid cancer (PTC) according to their diagnostic usefulness. We also assessed the accuracy of benign/mal...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-06-0048

    authors: Fujarewicz K,Jarzab M,Eszlinger M,Krohn K,Paschke R,Oczko-Wojciechowska M,Wiench M,Kukulska A,Jarzab B,Swierniak A

    更新日期:2007-09-01 00:00:00

  • Role of carbonic anhydrase IX expression in prediction of the efficacy and outcome of primary epirubicin/tamoxifen therapy for breast cancer.

    abstract::The purpose of this study is to investigate the role of carbonic anhydrase IX (CAIX) expression in predicting the response to epirubicin and disease-free survival (DFS) in breast cancer patients enrolled in a single institution trial of primary anthracycline and tamoxifen therapy. CAIX expression was assessed in 183 p...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/erc.1.01216

    authors: Generali D,Fox SB,Berruti A,Brizzi MP,Campo L,Bonardi S,Wigfield SM,Bruzzi P,Bersiga A,Allevi G,Milani M,Aguggini S,Dogliotti L,Bottini A,Harris AL

    更新日期:2006-09-01 00:00:00

  • Identification of a paired box gene 8-peroxisome proliferator-activated receptor gamma (PAX8-PPARgamma) rearrangement mosaicism in a patient with an autonomous functioning follicular thyroid carcinoma bearing an activating mutation in the TSH receptor.

    abstract::Our main objective was to search for mutations in candidate genes and for paired box gene 8-peroxisome proliferator-activated receptor gamma (PAX8-PPARgamma) rearrangement in a well-differentiated angioinvasive follicular thyroid carcinoma (FTC) causing hyperthyroidism. DNA and RNA were extracted from the patient's th...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-09-0069

    authors: Lado-Abeal J,Celestino R,Bravo SB,Garcia-Rendueles ME,de la Calzada J,Castro I,Castro P,Espadinha C,Palos F,Soares P,Alvarez CV,Sobrinho-Simões M,Cameselle-Teijeiro J

    更新日期:2010-06-03 00:00:00

  • SAHA-induced loss of tumor suppressor Pten gene promotes thyroid carcinogenesis in a mouse model.

    abstract::Thyroid cancer is on the rise. Novel approaches are needed to improve the outcome of patients with recurrent and advanced metastatic thyroid cancers. FDA approval of suberoylanilide hydroxamic acid (SAHA; vorinostat), an inhibitor of histone deacetylase, for the treatment of hematological malignancies led to the clini...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-16-0103

    authors: Zhu X,Kim DW,Zhao L,Willingham MC,Cheng SY

    更新日期:2016-07-01 00:00:00

  • Genetically defined mouse models that mimic natural aspects of human prostate cancer development.

    abstract::This review is focused on mouse models for prostate cancer that have been designed on the basis of genetic alterations that are frequently found in human prostate cancer. It begins with an analysis of the similarities and differences in the gross and microscopic anatomy of the mouse and human prostate glands, and exte...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1677/erc.0.0110225

    authors: Roy-Burman P,Wu H,Powell WC,Hagenkord J,Cohen MB

    更新日期:2004-06-01 00:00:00

  • Uncontrolled insulin secretion from a childhood pancreatic beta-cell adenoma is not due to the functional loss of ATP-sensitive potassium channels.

    abstract::We report the case of an 8-year-old child who presented with severe hyperinsulinaemic hypoglycaemia due to a pancreatic islet cell adenoma. In vivo, there was no beneficial response to the hyperglycaemia-inducing agent diazoxide and as a consequence the child underwent a subtotal pancreatectomy. In vitro studies of ad...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/erc.0.0090221

    authors: Hussain K,Cosgrove KE,Shepherd RM,Chapman JC,Swift SM,Smith VV,Kassem SA,Glaser B,Lindley KJ,Aynsley-Green A,Dunne MJ

    更新日期:2002-12-01 00:00:00

  • Tropomyosin receptor kinase: a novel target in screened neuroendocrine tumors.

    abstract::Tropomyosin receptor kinase (Trk) inhibitors are investigated as a novel targeted therapy in various cancers. We investigated the in vitro effects of the pan-Trk inhibitor GNF-5837 in human neuroendocrine tumor (NET) cells. The human neuroendocrine pancreatic BON1, bronchopulmonary NCI-H727 and ileal GOT1 cell lines w...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-17-0201

    authors: Aristizabal Prada ET,Heinzle V,Knösel T,Nölting S,Spöttl G,Maurer J,Spitzweg C,Angele M,Schmidt N,Beuschlein F,Stalla GK,Blaser R,Kuhn KA,Auernhammer CJ

    更新日期:2018-05-01 00:00:00

  • Overexpression of ERBB-2 was more frequently detected in malignant than benign pheochromocytomas by multiplex ligation-dependent probe amplification and immunohistochemistry.

    abstract::To analyze the genetic alterations of pheochromocytomas and evaluate the difference among malignant, extra-adrenal, and benign pheochromocytomas. Forty-three tumor samples were tested for genetic changes using multiplex ligation-dependent probe amplification. Among them, 39 samples were available for protein expressio...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-07-0188

    authors: Yuan W,Wang W,Cui B,Su T,Ge Y,Jiang L,Zhou W,Ning G

    更新日期:2008-03-01 00:00:00

  • mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors.

    abstract::Medical therapy of pancreatic neuroendocrine tumors (P-NET) may take advantage of Everolimus treatment. However, the extent of therapeutic response cannot be predicted. This study was aimed to identify the possible predictive markers of response to Everolimus in P-NET. We found that Everolimus reduced the cell viabili...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-16-0329

    authors: Falletta S,Partelli S,Rubini C,Nann D,Doria A,Marinoni I,Polenta V,Di Pasquale C,Degli Uberti E,Perren A,Falconi M,Zatelli MC

    更新日期:2016-11-01 00:00:00

  • Oestrogen receptor 1 mRNA is a prognostic factor in ovarian cancer patients treated with neo-adjuvant chemotherapy: determination by array and kinetic PCR in fresh tissue biopsies.

    abstract::Oestrogen receptors (ESRs) regulate the growth and differentiation of normal ovarian epithelia. However, to date their role as biomarkers in the clinical setting of ovarian cancer remains unclear. In view of potential endocrine treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer in the cont...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-08-0342

    authors: Zamagni C,Wirtz RM,De Iaco P,Rosati M,Veltrup E,Rosati F,Capizzi E,Cacciari N,Alboni C,Bernardi A,Massari F,Quercia S,D'Errico Grigioni A,Dietel M,Sehouli J,Denkert C,Martoni AA

    更新日期:2009-12-01 00:00:00

  • Distinctive functions of p160 steroid receptor coactivators in proliferation of an estrogen-independent, tamoxifen-resistant breast cancer cell line.

    abstract::Elevated expression of steroid receptor coactivator-3 (SRC-3), a member of the p160 family of nuclear receptor coactivators, has been implicated in tamoxifen resistance of breast tumors while the involvement of the two other members of this family, SRC-1 and SRC-2, is less well characterized. In this study, using smal...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1677/ERC-09-0285

    authors: Karmakar S,Foster EA,Blackmore JK,Smith CL

    更新日期:2010-12-21 00:00:00

  • Androgen receptor signaling in castration-resistant prostate cancer: a lesson in persistence.

    abstract::The androgen receptor (AR) signaling axis drives all stages of prostate cancer, including the lethal, drug-resistant form of the disease termed castration-resistant prostate cancer (CRPC), which arises after failure of androgen deprivation therapy (ADT). Persistent AR activity in spite of ADT and the second-generation...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-16-0422

    authors: Coutinho I,Day TK,Tilley WD,Selth LA

    更新日期:2016-12-01 00:00:00

  • A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors.

    abstract::The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-17-0196

    authors: Dumanski JP,Rasi C,Björklund P,Davies H,Ali AS,Grönberg M,Welin S,Sorbye H,Grønbæk H,Cunningham JL,Forsberg LA,Lind L,Ingelsson E,Stålberg P,Hellman P,Tiensuu Janson E

    更新日期:2017-08-01 00:00:00

  • Autophagy and thyroid carcinogenesis: genetic and epigenetic links.

    abstract::Thyroid cancer is the most common cancer of the endocrine system and is responsible for the majority of deaths from endocrine malignancies. Although a large proportion of thyroid cancers belong to well differentiated histologic subtypes, which in general show a good prognosis after surgery and radioiodine ablation, th...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-13-0271

    authors: Morani F,Titone R,Pagano L,Galetto A,Alabiso O,Aimaretti G,Isidoro C

    更新日期:2013-12-16 00:00:00

  • Metabolomics signatures of a subset of RET variants according to their oncogenic risk level.

    abstract::Thirty percent of medullary thyroid carcinomas (MTCs) are related to dominant germline pathogenic variants in the RET proto-oncogene. According to their aggressiveness, these pathogenic variants are classified in three risk levels: 'moderate', 'high' and 'highest'. The present study compares the metabolomics profiles ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-18-0314

    authors: Veyrat-Durebex C,Bouzamondo N,Le Mao M,Chao de la Barca JM,Bris C,Dieu X,Simard G,Gadras C,Tessier L,Drui D,Borson-Chazot F,Barlier A,Reynier P,Prunier-Mirebeau D

    更新日期:2019-03-01 00:00:00

  • Overview of tyrosine kinase inhibitors in clinical breast cancer.

    abstract::Studies of cell models and profiling of clinical breast cancer material to reveal the mechanisms of resistance to anti-oestrogen therapy, and to tamoxifen in particular, have reported that this phenomenon can be associated with increased expression and signalling through erbB Type 1 growth factor receptors, notably th...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1677/erc.1.01059

    authors: Agrawal A,Gutteridge E,Gee JM,Nicholson RI,Robertson JF

    更新日期:2005-07-01 00:00:00

  • Metabolite analysis-aided diagnosis of papillary thyroid cancer.

    abstract::Thyroid cancer is the most frequent endocrine tumor with a growing incidence worldwide. However, common diagnostic strategy for thyroid cancer classification is hardly to make a proper diagnosis in some cases. To assist classical approach, this study used metabolomics to screen and validate biomarkers from serum and u...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-19-0344

    authors: Chen J,Hu Q,Hou H,Wang S,Zhang Y,Luo Y,Chen H,Deng H,Zhu H,Zhang L,Liu H,Wang A,Liu Y

    更新日期:2019-12-01 00:00:00

  • Acquired resistance to aromatase inhibitors: where we stand!

    abstract::Aromatase inhibitors (AIs) are one of the principal therapeutic approaches for estrogen receptor-positive (ER+) breast cancer in postmenopausal women. They block estrogen biosynthesis through aromatase inhibition, thus preventing tumour progression. Besides the therapeutic success of the third-generation AIs, acquired...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-17-0425

    authors: Augusto TV,Correia-da-Silva G,Rodrigues CMP,Teixeira N,Amaral C

    更新日期:2018-05-01 00:00:00

  • DUSP6/MKP3 is overexpressed in papillary and poorly differentiated thyroid carcinoma and contributes to neoplastic properties of thyroid cancer cells.

    abstract::Thyroid carcinomas derived from follicular cells comprise papillary thyroid carcinoma (PTC), follicular thyroid carcinoma, poorly differentiated thyroid carcinoma (PDTC) and undifferentiated anaplastic thyroid carcinoma (ATC). PTC, the most frequent thyroid carcinoma histotype, is associated with gene rearrangements t...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-12-0078

    authors: Degl'Innocenti D,Romeo P,Tarantino E,Sensi M,Cassinelli G,Catalano V,Lanzi C,Perrone F,Pilotti S,Seregni E,Pierotti MA,Greco A,Borrello MG

    更新日期:2013-01-21 00:00:00

  • Overcoming oncogene addiction in breast and prostate cancers: a comparative mechanistic overview.

    abstract::Prostate cancer (PCa) and breast cancer (BCa) are both hormone-dependent cancers that require the androgen receptor (AR) and estrogen receptor (ER, ESR1) for growth and proliferation, respectively. Endocrine therapies that target these nuclear receptors (NRs) provide significant clinical benefit for metastatic patient...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-20-0272

    authors: Blatt EB,Kopplin N,Kumar S,Mu P,Conzen SD,Raj GV

    更新日期:2020-12-01 00:00:00

  • Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study.

    abstract::In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1...

    journal_title:Endocrine-related cancer

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1530/ERC-15-0490

    authors: Caplin ME,Pavel M,Ćwikła JB,Phan AT,Raderer M,Sedláčková E,Cadiot G,Wolin EM,Capdevila J,Wall L,Rindi G,Langley A,Martinez S,Gomez-Panzani E,Ruszniewski P,CLARINET Investigators.

    更新日期:2016-03-01 00:00:00

  • Phase III trial of chemotherapy using 5-fluorouracil and streptozotocin compared with interferon alpha for advanced carcinoid tumors: FNCLCC-FFCD 9710.

    abstract::The aim of this randomized multicenter phase III trial was to compare chemotherapy and interferon (IFN) in patients with metastatic carcinoid tumors. Patients with documented progressive, unresectable, metastatic carcinoid tumors were randomized between 5-fluorouracil plus streptozotocin (day 1-5) and recombinant IFN-...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1677/ERC-09-0104

    authors: Dahan L,Bonnetain F,Rougier P,Raoul JL,Gamelin E,Etienne PL,Cadiot G,Mitry E,Smith D,Cvitkovic F,Coudert B,Ricard F,Bedenne L,Seitz JF,Fédération Francophone de Cancérologie Digestive (FFCD).,Digestive Tumors Group of the F

    更新日期:2009-12-01 00:00:00

  • Inhibition of Notch signaling attenuates pituitary adenoma growth in Nude mice.

    abstract::Preclinical and clinical studies support that Notch signaling may play an important oncogenic role in cancer, but there is scarce information for pituitary tumors. We therefore undertook a functional study to evaluate Notch participation in pituitary adenoma growth. Tumors generated in Nude mice by subcutaneous GH3 so...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-18-0337

    authors: Zubeldía-Brenner L,De Winne C,Perrone S,Rodríguez-Seguí SA,Willems C,Ornstein AM,Lacau-Mengido I,Vankelecom H,Cristina C,Becu-Villalobos D

    更新日期:2019-01-01 00:00:00

  • Potentiated anti-tumor effects of BETi by MEKi in anaplastic thyroid cancer.

    abstract::Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited treatment options. We explored novel treatment modalities by targeting epigenetic modifications using inhibitors of BET (e.g. BRD4) activity. We evaluated the efficacy in the treatment of ATC of a novel BET inhibitor, PLX51107 (PLX), currently in...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-19-0107

    authors: Zhu X,Park S,Lee WK,Cheng SY

    更新日期:2019-09-01 00:00:00

  • FOXO factors and breast cancer: outfoxing endocrine resistance.

    abstract::The majority of metastatic breast cancers cannot be cured and present a major public health problem worldwide. Approximately 70% of breast cancers express the estrogen receptor, and endocrine-based therapies have significantly improved patient outcomes. However, the development of endocrine resistance is extremely com...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审

    doi:10.1530/ERC-15-0461

    authors: Bullock M

    更新日期:2016-02-01 00:00:00

  • MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma.

    abstract::Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章

    doi:10.1530/ERC-15-0162

    authors: Romitti M,Wajner SM,Ceolin L,Ferreira CV,Ribeiro RV,Rohenkohl HC,Weber Sde S,Lopez PL,Fuziwara CS,Kimura ET,Maia AL

    更新日期:2016-03-01 00:00:00