Abstract:
:The thyroid hormones T3 and T4 have emerged as pro-angiogenic hormones with important implications for cancer management. Endogenous circulating hormone levels may help stimulate cancer progression and limit the effectiveness of anticancer therapy, though clinical data remain inconclusive. The capacity of thyroid hormones to modulate angiogenesis is mediated through non-canonical mechanisms initiated at the cell surface receptor integrin αvβ3. This integrin is predominantly expressed on tumour cells, proliferating endothelial cells and tumour stroma-associated cells, emphasising its potential relevance in angiogenesis and tumour biology. Thyroid hormone/integrin αvβ3 signalling results in the activation of intracellular pathways that are commonly associated with angiogenesis and are mediated through classical pro-angiogenic molecules such as vascular endothelial growth factor. The naturally occurring T4 analogue tetrac blocks the pro-angiogenic actions of thyroid hormones at the integrin receptor, in addition to agonist-independent anti-angiogenic effects. Tetrac reduces endothelial cell proliferation, migration and tube formation through a reduction in the transcription of vascular growth factors/growth factor receptors, hypoxia-inducible factor-1α, pro-angiogenic cytokines and a number of other pro-angiogenic genes, while at the same time stimulating the expression of endogenous angiogenesis inhibitors. It further modulates vascular growth factor activity by disrupting the crosstalk between integrin αvβ3 and adjacent growth factor receptors. Moreover, tetrac disrupts thyroid hormone-stimulated tumour recruitment, differentiation and the pro-angiogenic signalling of tumour stroma-associated mesenchymal stem cells. Tetrac affects tumour-associated angiogenesis via multiple mechanisms and interferes with other cancer cell survival pathways. In conjunction with its low toxicity and high tissue selectivity, tetrac is a promising candidate for clinical application.
journal_name
Endocr Relat Cancerjournal_title
Endocrine-related cancerauthors
Schmohl KA,Nelson PJ,Spitzweg Cdoi
10.1530/ERC-19-0058subject
Has Abstractpub_date
2019-06-01 00:00:00pages
R287-R304issue
6eissn
1351-0088issn
1479-6821pii
ERC-19-0058journal_volume
26pub_type
杂志文章,评审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
更新日期:2009-12-01 00:00:00
abstract::Platinum-based therapy remains the cornerstone for cancer therapy; however, its efficacy varies. The role of lipoprotein receptor-mediated lipid entry for cancer development has been reported. Yet, the roles and mechanism of the low-density lipoprotein receptor (LDLR) in chemo-sensitivities are unknown. In the current...
journal_title:Endocrine-related cancer
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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
更新日期:2007-09-01 00:00:00
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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
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0227
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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::Resistance to anoikis (matrix deprivation-induced apoptosis) is a critical component of the metastatic cascade. Molecular mechanisms underlying resistance to anoikis have not been reported in thyroid cancer cells. For an in vitro model of anoikis, we cultured follicular, papillary, and anaplastic thyroid cancer cell l...
journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
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更新日期:2003-12-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
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更新日期:2017-08-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0444
更新日期:2014-01-30 00:00:00
abstract::A splice variant of the human gene HER2, lacking exon-16 (DeltaHER2) which encodes a small extracellular region, has been described. This altered receptor forms disulfide bond-stabilized homodimers. We report here that the DeltaHER2 splice variant represents about 9% of the HER2 mRNA obtained from most of the 46 breas...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.01047
更新日期:2006-03-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-15-0042
更新日期:2015-08-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0132
更新日期:2013-12-16 00:00:00
abstract::Combined clinical and laboratory investigations of multiple endocrine neoplasia type 1 (MEN1) have resulted in an increased understanding of this disorder which may be inherited as an autosomal dominant condition. Defining the features of each disease manifestation in MEN1 has improved patient management and treatment...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0060449
更新日期:1999-12-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-08-0059
更新日期:2009-03-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-19-0344
更新日期:2019-12-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-09-0321
更新日期:2010-05-18 00:00:00
abstract::Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized in man by parathyroid, pancreatic, pituitary and adrenal tumours. The MEN1 gene encodes a 610-amino acid protein (menin) which is a tumour suppressor. To investigate the in vivo role of menin, we developed a mouse model, by dele...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-09-0082
更新日期:2009-12-01 00:00:00
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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
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
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更新日期:1999-06-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-17-0442
更新日期:2018-03-01 00:00:00
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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abstract::Non-functioning pituitary adenomas, recently alternatively termed pituitary neuroendocrine tumours (NFpitNETs), are mostly benign neoplasms that are not associated with a hormonal hypersecretory syndrome. The clinical spectrum of NFpitNETs varies from completely asymptomatic to the development of panhypopituitarism an...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
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更新日期:2020-10-01 00:00:00
abstract::Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the...
journal_title:Endocrine-related cancer
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更新日期:2018-08-01 00:00:00
abstract::The imprinted gene, neuronatin (NNAT), is one of the most abundant transcripts in the pituitary and is thought to be involved in the development and maturation of this gland. In a recent whole-genome approach, exploiting a pituitary tumour cell line, we identified hypermethylation associated loss of NNAT. In this repo...
journal_title:Endocrine-related cancer
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doi:10.1677/ERC-09-0008
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abstract::Obesity increases both the risk and mortality associated with many types of cancer including that of the breast. In mice, obesity increases both incidence of spontaneous tumors and burden of transplanted tumors. Our findings identify leptin, an adipose secreted cytokine, in promoting increased mammary tumor burden in ...
journal_title:Endocrine-related cancer
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更新日期:2011-07-11 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
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abstract::Genetic alteration is the driving force for thyroid tumorigenesis and progression, based upon which novel approaches to the management of thyroid cancer can be developed. A recent important genetic finding in thyroid cancer is the oncogenic T1799A transversion mutation of BRAF (the gene for the B-type Raf kinase, BRAF...
journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0254
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