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


: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.


Endocr Relat Cancer


Endocrine-related cancer


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




Has Abstract


2006-06-01 00:00:00














  • Sporadic hypercalcitoninemia: clinical and therapeutic consequences.

    abstract::'Calcitonin screening' is not accepted as the standard of care in daily practice. The clinical and surgical consequences of 'calcitonin screening' in a series of patients with mildly elevated basal calcitonin and pentagastrin stimulated calcitonin levels are presented. 260 patients with elevated basal (>10 pg/ml) and ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Scheuba C,Kaserer K,Moritz A,Drosten R,Vierhapper H,Bieglmayer C,Haas OA,Niederle B

    更新日期:2009-03-01 00:00:00

  • Factors regulating the growth of metastatic cancer in bone.

    abstract::Metastatic tumor cells can interfere directly with the function of bone cells involved in normal bone remodeling or indirectly by influencing the behavior of hematopoietic, stromal and other cells in bone marrow that interact with bone cells. Recent studies of metastatic cancer have revealed that tumor cells interact ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Boyce BF,Yoneda T,Guise TA

    更新日期:1999-09-01 00:00:00

  • Role of chromosomal instability in cancer progression.

    abstract::Cancer cells often display chromosomal instability (CIN), a defect that involves loss or rearrangement of the cell's genetic material - chromosomes - during cell division. This process results in the generation of aneuploidy, a deviation from the haploid number of chromosomes, and structural alterations of chromosomes...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: McClelland SE

    更新日期:2017-09-01 00:00:00

  • Clinical aspects of cell death in breast cancer: the polyamine pathway as a new target for treatment.

    abstract::Because intracellular polyamines have a critical role in cell proliferation and death pathways, the polyamine metabolic pathway represents a potential target for intervention in cancers. A number of polyamine analogues have been identified that downregulate polyamine synthesis and enhance polyamine catabolism, thereby...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Davidson NE,Hahm HA,McCloskey DE,Woster PM,Casero RA Jr

    更新日期:1999-03-01 00:00:00

  • Rationale for the development of alternative forms of androgen deprivation therapy.

    abstract::With few exceptions, the almost 30,000 prostate cancer deaths annually in the United States are due to failure of androgen deprivation therapy. Androgen deprivation therapy prevents ligand-activation of the androgen receptor. Despite initial remission after androgen deprivation therapy, prostate cancer almost invariab...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Kumari S,Senapati D,Heemers HV

    更新日期:2017-08-01 00:00:00

  • MAPK- and AKT-activated thyroid cancers are sensitive to group I PAK inhibition.

    abstract::The number of individuals who succumb to thyroid cancer has been increasing and those who are refractory to standard care have limited therapeutic options, highlighting the importance of developing new treatments for patients with aggressive forms of the disease. Mutational activation of MAPK signaling, through BRAF a...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Knippler CM,Saji M,Rajan N,Porter K,La Perle KMD,Ringel MD

    更新日期:2019-08-01 00:00:00

  • MINDIN secretion by prostate tumors induces premetastatic changes in bone via β-catenin.

    abstract::Bone metastases are common in advanced prostate cancer patients, but mechanisms by which specific pro-metastatic skeletal niches are formed before tumor cell homing are unclear. We aimed to analyze the effects of proteins secreted by primary prostate tumors on the bone microenvironment before the settlement and propag...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Ardura JA,Álvarez-Carrión L,Gutiérrez-Rojas I,Friedman PA,Gortázar AR,Alonso V

    更新日期:2020-07-01 00:00:00

  • Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma.

    abstract::Ten to fifteen percent of fine-needle aspiration biopsy (FNAB) of thyroid nodules are indeterminate. Galectin-3 (Gal-3) and the oncogene BRAFV600E are markers of malignancy useful to improve FNAB accuracy. The objective of this study was to determine whether the combined analysis of Gal-3 and BRAFV600E expression in t...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Sapio MR,Guerra A,Posca D,Limone PP,Deandrea M,Motta M,Troncone G,Caleo A,Vallefuoco P,Rossi G,Fenzi G,Vitale M

    更新日期:2007-12-01 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


    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

  • Differential expression of microRNAs in human parathyroid carcinomas compared with normal parathyroid tissue.

    abstract::Parathyroid carcinoma (PaC) is a rare cause of primary hyperparathyroidism. Though the loss of the oncosuppressor CDC73/HRPT2 gene product, parafibromin, has been involved in the hyperparathyroidism-jaw tumor syndrome and in a consistent set of sporadic PaCs, parathyroid carcinogenesis remains obscure. MicroRNAs are a...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Corbetta S,Vaira V,Guarnieri V,Scillitani A,Eller-Vainicher C,Ferrero S,Vicentini L,Chiodini I,Bisceglia M,Beck-Peccoz P,Bosari S,Spada A

    更新日期:2010-02-18 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


    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

  • HES5 silencing is an early and recurrent change in prostate tumourigenesis.

    abstract::Prostate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation prof...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Massie CE,Spiteri I,Ross-Adams H,Luxton H,Kay J,Whitaker HC,Dunning MJ,Lamb AD,Ramos-Montoya A,Brewer DS,Cooper CS,Eeles R,UK Prostate ICGC Group.,Warren AY,Tavaré S,Neal DE,Lynch AG

    更新日期:2015-04-01 00:00:00

  • Role of hypoxia-inducible factor-1alpha as a cancer therapy target.

    abstract::Hypoxia occurs in solid tumours due to a mismatch between tumour growth and angiogenesis. Hypoxia in solid tumours is associated with an aggressive phenotype and resistance to radiation therapy and chemotherapy leading to poor patient prognosis. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, which is ac...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Patiar S,Harris AL

    更新日期:2006-12-01 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


    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

  • Obesity and cancer: mechanistic insights from transdisciplinary studies.

    abstract::Obesity is associated with a range of health outcomes that are of clinical and public health significance, including cancer. Herein, we summarize epidemiologic and preclinical evidence for an association between obesity and increased risk of breast and prostate cancer incidence and mortality. Moreover, we describe dat...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Allott EH,Hursting SD

    更新日期:2015-12-01 00:00:00

  • The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R.

    abstract::Imatinib mesylate (IM), a small molecule that is a selective inhibitor of the ABL, platelet derived growth factor receptor (PDGFR-R) and stem cell ligand receptor (c-kit) tyrosine kinases (TK). IM was also found to inhibit the TK activity of BCR/ABL fusion protein produced in chronic myelogenous leukemia, with marked ...

    journal_title:Endocrine-related cancer

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Gross DJ,Munter G,Bitan M,Siegal T,Gabizon A,Weitzen R,Merimsky O,Ackerstein A,Salmon A,Sella A,Slavin S,Israel Glivec in Solid Tumors Study Group.

    更新日期:2006-06-01 00:00:00

  • Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

    abstract::Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-Pa...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Krauss T,Ferrara AM,Links TP,Wellner U,Bancos I,Kvachenyuk A,Villar Gómez de Las Heras K,Yukina MY,Petrov R,Bullivant G,von Duecker L,Jadhav S,Ploeckinger U,Welin S,Schalin-Jäntti C,Gimm O,Pfeifer M,Ngeow J,Hasse-Laza

    更新日期:2018-09-01 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


    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


    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

  • Body fatness as a cause of cancer: epidemiologic clues to biologic mechanisms.

    abstract::Carrying excess body fat is a leading cause of cancer. Epidemiologic evidence gives strong clues about the mechanisms that link excess adiposity to risk for several cancer sites. For postmenopausal breast cancer and endometrial cancer, the hyper-estrogenic state that is induced by excess body fatness is the likely cau...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Byers T,Sedjo RL

    更新日期:2015-06-01 00:00:00

  • Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity.

    abstract::Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not wel...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Imam S,Paparodis R,Sharma D,Jaume JC

    更新日期:2014-06-01 00:00:00

  • TRAP1 regulates cell cycle and apoptosis in thyroid carcinoma cells.

    abstract::Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a heat shock protein 90 (HSP90) molecular chaperone upregulated in several human malignancies and involved in protection from apoptosis and drug resistance, cell cycle progression, cell metabolism and quality control of specific client proteins. TRAP1 role...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Palladino G,Notarangelo T,Pannone G,Piscazzi A,Lamacchia O,Sisinni L,Spagnoletti G,Toti P,Santoro A,Storto G,Bufo P,Cignarelli M,Esposito F,Landriscina M

    更新日期:2016-09-01 00:00:00

  • Notch1 pathway in adrenocortical carcinomas: correlations with clinical outcome.

    abstract::Previous SNP array analyses have revealed genomic alterations of the Notch pathway as being the most frequent abnormality in adrenocortical tumors (ACTs). The aim of the present study was to evaluate the expression of components of Notch signaling in ACTs and to correlate them with clinical outcome. The mRNA expressio...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Ronchi CL,Sbiera S,Altieri B,Steinhauer S,Wild V,Bekteshi M,Kroiss M,Fassnacht M,Allolio B

    更新日期:2015-08-01 00:00:00

  • The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers.

    abstract::Breast and prostate cancer are the most well-characterized cancers of the type that have their development and growth controlled by the endocrine system. These cancers are the leading causes of cancer death in women and men, respectively, in the United States. Being hormone-dependent tumors, antihormone therapies usua...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Rau KM,Kang HY,Cha TL,Miller SA,Hung MC

    更新日期:2005-09-01 00:00:00

  • Prognostic factors of papillary and follicular thyroid cancer: differences in an iodine-replete endemic goiter region.

    abstract::Papillary (PTC) and follicular thyroid carcinoma (FTC) are known as differentiated thyroid carcinoma (DTC). Nevertheless, according to the UICC/AJCC (TNM) classification PTC and FTC are frequently analyzed as one cancer. The aim of this study is to show differences in outcome and specific prognostic factors in an iodi...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Passler C,Scheuba C,Prager G,Kaczirek K,Kaserer K,Zettinig G,Niederle B

    更新日期:2004-03-01 00:00:00

  • Overexpression of the natural antisense hypoxia-inducible factor-1alpha transcript is associated with malignant pheochromocytoma/paraganglioma.

    abstract::Paragangliomas (PGLs) have widely different metastastic potentials. Two different types of PGLs can be defined by expression profiling. Cluster 1 PGLs exhibit VHL and/or succinate dehydrogenase (SDH) mutations and a pseudohypoxic phenotype. RET and neurofibromatosis type 1 (NF1) mutations occur in cluster 2 tumors cha...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章


    authors: Span PN,Rao JU,Oude Ophuis SB,Lenders JW,Sweep FC,Wesseling P,Kusters B,van Nederveen FH,de Krijger RR,Hermus AR,Timmers HJ

    更新日期:2011-04-28 00:00:00

  • Progress in breast cancer chemoprevention.

    abstract::Over the past years there have been significant advances in breast cancer treatment and early detection. For the first time, a decrease in cancer mortality has been observed. Recently, much progress has been made in the understanding of carcinogenesis partly due to available new technologies to detect early molecular ...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Arun B,Hortobagyi GN

    更新日期:2002-03-01 00:00:00

  • Mouse models of transforming growth factor beta impact in breast development and cancer.

    abstract::It is now recognized that transforming growth factor beta (TGF-beta) is an important factor that regulates normal breast development as well as breast cancer. Genetically engineered mouse models have been used to determine the role and mechanism of TGF-beta action in normal development and diseases of the breast. Usin...

    journal_title:Endocrine-related cancer

    pub_type: 杂志文章,评审


    authors: Serra R,Crowley MR

    更新日期:2005-12-01 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


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

    更新日期:2020-12-01 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


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

    更新日期:2005-07-01 00:00:00