Abstract:
:Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-up. We have previously demonstrated overactivation of the SHH pathway in both human and mouse ACP. Here, we show that this activation is ligand dependent and induced by the expression of SHH protein in a small proportion of tumour cells. We investigate the functional relevance of SHH signalling in ACP through MRI-guided preclinical studies using an ACP mouse model. Treatment with vismodegib, a clinically approved SHH pathway inhibitor, results in a significant reduction in median survival due to premature development of highly proliferative and vascularised undifferentiated tumours. Reinforcing the mouse data, SHH pathway inhibition in human ACP leads to a significant increase in tumour cell proliferation both ex vivo, in explant cultures, and in vivo, in a patient-derived xenograft model. Together, our results demonstrate a protumourigenic effect of vismodegib-mediated SHH pathway inhibition in ACP.
journal_name
Endocr Relat Cancerjournal_title
Endocrine-related cancerauthors
Carreno G,Boult JKR,Apps J,Gonzalez-Meljem JM,Haston S,Guiho R,Stache C,Danielson LS,Koers A,Smith LM,Virasami A,Panousopoulos L,Buchfelder M,Jacques TS,Chesler L,Robinson SP,Martinez-Barbera JPdoi
10.1530/ERC-18-0538subject
Has Abstractpub_date
2019-03-01 00:00:00pages
355-366issue
3eissn
1351-0088issn
1479-6821pii
ERC-18-0538.R1journal_volume
26pub_type
杂志文章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
doi:10.1677/erc.0.0090015
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journal_title:Endocrine-related cancer
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doi:10.1677/ERC-08-0002
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-11-0379
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abstract::It has been proposed that knowledge of estrogen receptor beta (ER-beta) expression may refine estrogen receptor alpha (ER-alpha) predictivity of response to endocrine therapy. We challenged this hypothesis in ER-alpha-positive breast cancers subjected to preoperative antiestrogen treatment. Forty-seven elderly (> or =...
journal_title:Endocrine-related cancer
pub_type: 临床试验,杂志文章
doi:10.1677/erc.1.00822
更新日期:2004-12-01 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
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,多中心研究,随机对照试验
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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
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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-10-0290
更新日期:2011-04-28 00:00:00
abstract::Quantitative reverse transcription-polymerase chain reaction (RT-PCR) used to detect minor changes in specific mRNA concentrations may be associated with poor reproducibility. Stringent quality control is therefore essential at each step of the protocol, including the PCR procedure. We performed inter-laboratory quali...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.00808
更新日期:2004-09-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/ERC-08-0266
更新日期:2009-06-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-19-0095
更新日期:2020-02-01 00:00:00
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
更新日期:2014-01-30 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-19-0372
更新日期:2020-06-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-19-0175
更新日期:2019-08-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.01216
更新日期:2006-09-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-20-0136
更新日期:2020-10-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-18-0509
更新日期:2019-04-01 00:00:00
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
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更新日期:2006-12-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
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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
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
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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
abstract::The tumour microenvironment is known to be acidic due to high glycolytic rates of tumour cells. Monocarboxylate transporters (MCTs) play a role in extracellular acidification, which is widely known to be involved in tumour progression. Recently, we have described the upregulation of MCT1 in breast carcinomas and its a...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
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更新日期:2013-12-16 00:00:00
abstract::The etiology and pathogenesis of renal cell carcinoma (RCC) are only partially understood. Key findings in hereditary RCC, which may be site specific or a component of a syndrome, have contributed to our current understanding. Important heritable syndromes of RCC are those associated with pheochromocytoma, especially ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-11-0324
更新日期:2012-05-03 00:00:00
abstract::The aim of this systematic review is to study the features of cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) by analysing the 129 documented cases in the English literature. The disease occurred almost exclusively in women. The median age of presentation for CMV-PTC was 24 years. Slightly over hal...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-17-0014
更新日期:2017-04-01 00:00:00
abstract::Somatostatin-producing neuroendocrine tumors (SOM-NETs) of the duodenum and pancreas appear to be heterogeneous. To determine their clinicopathological profiles, respective data were analyzed on a series of 82 duodenal and 541 pancreatic NETs. In addition, the clinical records of 821 patients with duodenal or pancreat...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,多中心研究
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abstract::Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumors were coupled with in...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.0.0100601
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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
pub_type: 杂志文章,评审
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