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 Cancerjournal_title
Endocrine-related cancerauthors
Weng JR,Chen CY,Pinzone JJ,Ringel MD,Chen CSdoi
10.1677/erc.1.01182subject
Has Abstractpub_date
2006-06-01 00:00:00pages
401-13issue
2eissn
1351-0088issn
1479-6821pii
13/2/401journal_volume
13pub_type
杂志文章,评审abstract::Na(+)/I(-) symporter (NIS)-mediated radioiodide uptake (RAIU) serves as the basis for targeted ablation of thyroid cancer remnants. However, many patients with thyroid cancer have reduced NIS expression/function and hence do not benefit from radioiodine therapy. microRNA (miR) has emerged as a promising therapeutic ta...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0439
更新日期:2015-02-01 00:00:00
abstract::Patients suffering from the neurofibromatosis type 1 syndrome, which is caused by germline mutations in the NF1 gene, have a tiny but not negligible risk of developing pheochromocytomas. It is, therefore, of interest that the NF1 gene has recently been revealed to carry somatic, inactivating mutations in a total of 35...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0046
更新日期:2013-07-04 00:00:00
abstract::The aim of this study was to explore the pharmacological response to 4-hydroxy-tamoxifen (OH-Tam) and to estradiol (E2) in three cell lines: MVLN, a human breast carcinoma cell line derived from MCF-7, and two MVLN-derived OH-Tam-resistant (OTR) cell lines, called CL6.8 and CL6.32. The OH-Tam response in the OTR cells...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.00899
更新日期:2005-03-01 00:00:00
abstract::The anaplastic lymphoma kinase (ALK) gene is frequently rearranged in various types of cancer and is highly responsive to targeted therapeutics. We developed a system to detect rearrangement of ALK in a large group of Korean thyroid cancer patients. We screened 474 malignant or benign thyroid tumor cases to identify A...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0467
更新日期:2015-02-01 00:00:00
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
doi:10.1677/erc.0.0060069
更新日期:1999-03-01 00:00:00
abstract::Resveratrol is a naturally occurring polyphenol that provides a number of anti-aging health benefits including improved metabolism, cardioprotection, and cancer prevention. Much of the work on resveratrol and cancer comes from in vitro studies looking at resveratrol actions on cancer cells and pathways. There are, how...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-13-0171
更新日期:2014-05-06 00:00:00
abstract::Although targeted therapy, including inhibitors of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor, being developed for carcinoids arised from the gastrointestinal tract, treatment for locally advanced or metastatic bronchial carcinoids (BCs) remains lacking. Traditional cytotoxic chemother...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-10-0290
更新日期:2011-04-28 00:00:00
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
更新日期:2020-03-01 00:00:00
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
更新日期:2004-06-01 00:00:00
abstract::Neuroendocrine neoplasms (NENs) are a relatively rare group of heterogeneous tumours originating from neuroendocrine cells found throughout the body. Pancreatic NENs (PanNENs) are the second most common pancreatic malignancy accounting for 1-3% of all neoplasms developing in the pancreas. Despite having a low backgrou...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-19-0175
更新日期:2019-08-01 00:00:00
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
doi:10.1530/ERC-17-0121
更新日期:2017-08-01 00:00:00
abstract::There is a trend of increasing prevalence of neuroendocrine tumors (NETs), and the inherited multiple endocrine neoplasia type 1 (MEN1) syndrome serves as a genetic model to investigate how NETs develop and the underlying mechanisms. Menin, encoded by the MEN1 gene, at least partly acts as a scaffold protein by intera...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-17-0298
更新日期:2017-10-01 00:00:00
abstract::Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,随机对照试验
doi:10.1530/ERC-12-0229
更新日期:2013-02-18 00:00:00
abstract::Although anatomic imaging to assess the precise localization of pheochromocytomas/paragangliomas (PHEOs/PGLs) is unavoidable before any surgical intervention on these tumors, functional imaging is becoming an inseparable portion of the imaging algorithm for these tumors. This review article presents applications of th...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-15-0175
更新日期:2015-08-01 00:00:00
abstract::Long-term culture of MCF-7 wild-type (wt) cells in steroid-depleted medium (LTED) results in hypersensitivity to oestradiol (E2) coinciding with elevated levels of ERalpha and enhanced growth factor signalling. In this study, we aimed to compare the effects of the pure anti-oestrogen ICI 182,780 (ICI) with the competi...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.00905
更新日期:2005-12-01 00:00:00
abstract::Resistance to chemotherapy is a critical issue in the management of breast cancer patients. The nature of clinical drug resistance is likely to be multifactorial. However, in the last decade considerable attention has been dedicated to the role played by membrane transporter proteins belonging to the ATP binding casse...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0100043
更新日期:2003-03-01 00:00:00
abstract::Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized M...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0104
更新日期:2016-06-01 00:00:00
abstract::Autotaxin is a secreted enzyme that converts extracellular lysophosphatidylcholine to lysophosphatidate (LPA). In cancers, LPA increases tumour growth, metastasis and chemoresistance by activating six G-protein coupled receptors. We examined >200 human thyroid biopsies. Autotaxin expression in metastatic deposits and ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-15-0045
更新日期:2015-08-01 00:00:00
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
doi:10.1530/ERC-15-0400
更新日期:2015-12-01 00:00:00
abstract::Cancers of the reproductive tract account for 12% of all malignancies in women. As previous studies have shown that oestrogen metabolites can cause apoptosis, we characterised the effect of oestrogen and oestrogen metabolites on non-cancerous and cancerous human endometrial cells. Herein, we demonstrate that 2-methoxy...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-07-0008
更新日期:2007-06-01 00:00:00
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
更新日期:2013-12-16 00:00:00
abstract::We have reported a high prevalence of hypothyroidism in the cutaneous melanoma population, suggesting that the pathologic hormonal environment of hypothyroidism promotes melanoma growth. The objective of this study was to test the hypothesis that TSH, which circulates at elevated levels in hypothyroid individuals, sti...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.01239
更新日期:2006-12-01 00:00:00
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
doi:10.1677/erc.1.01124
更新日期:2006-06-01 00:00:00
abstract::This study was designed to address whether simultaneous primary chemo-hormonal therapy provides additional activity compared with chemotherapy alone in breast cancer patients with operable or locally advanced disease. Between January 1997 and January 2002, 211 consecutive patients with T2-4, N0-1, M0 breast cancer wer...
journal_title:Endocrine-related cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1677/erc.1.00945
更新日期:2005-06-01 00:00:00
abstract::Deprivation of estrogen causes breast tumors in women to adapt and develop enhanced sensitivity to this steroid. Accordingly, women relapsing after treatment with oophorectomy, which substantially lowers estradiol for a prolonged period, respond secondarily to aromatase inhibitors with tumor regression. We have utiliz...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.01018
更新日期:2005-07-01 00:00:00
abstract::Carcinoid syndrome (CS) is a debilitating disease caused by functional neuroendocrine tumors. Several treatment options are available to alleviate the hormonal symptoms, but their relative efficacy is unknown. Online databases were searched for publications on the treatment of CS symptoms. Independent reviewers assess...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,meta分析
doi:10.1530/ERC-18-0495
更新日期:2019-03-01 00:00:00
abstract::We studied the psychological performance and the quality of life in patients with differentiated thyroid carcinoma, either during treatment with chronic suppressive doses of levothyroxine, or during the withdrawal of levothyroxine needed to perform whole-body scanning with radioactive iodine, with those of appropriate...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.0.0100601
更新日期:2003-12-01 00:00:00
abstract::CD74, the invariant chain of major histocompatibility complex class II, is also a receptor for macrophage migration inhibitory factor (MIF). CD74 and MIF have been associated with tumor progression and metastasis in hematologic and solid tumors. In this study, we found that 60 and 65% of papillary thyroid cancers were...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0269
更新日期:2015-04-01 00:00:00
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
doi:10.1530/ERC-13-0436
更新日期:2014-06-01 00:00:00
abstract::Malignant growth of small-cell lung carcinoma is promoted by various neuroendocrine autocrine/paracrine loops. Therefore, to interfere with this mitogenic process, it is crucial to elucidate the mechanisms involved. It is known that the oxytocin (OT) and vasopressin (VP) genes, normally transcriptionally restricted in...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.00803
更新日期:2004-12-01 00:00:00