Abstract:
:Dedifferentiation of follicular cells is a central event in resistance to radioactive iodine and patient mortality in papillary thyroid carcinoma (PTC). We reveal that platelet derived growth factor receptor alpha (PDGFRα) specifically drives dedifferentiation in PTC by disrupting the transcriptional activity of thyroid transcription factor-1 (TTF1). PDGFRα activation dephosphorylates TTF1 consequently shifting the localization of this transcription factor from the nucleus to the cytoplasm. TTF1 is required for follicular cell development and disrupting its function abrogates thyroglobulin production and sodium iodide transport. PDGFRα also promotes a more invasive and migratory cell phenotype with a dramatic increase in xenograft tumor formation. In patient tumors we confirm that nuclear TTF1 expression is inversely proportional to PDGFRα levels. Patients exhibiting PDGFRα at time of diagnosis are three times more likely to exhibit nodal metastases and are 18 times more likely to recur within 5years than those patients lacking PDGFRα expression. Moreover, high levels of PDGFRα and low levels of nuclear TTF1 predict resistance to radioactive iodine therapy. We demonstrate in SCID xenografts that focused PDGFRα blockade restores iodide transport and decreases tumor burden by >50%. Focused PDGFRα inhibitors, combined with radioactive iodine, represent an additional avenue for treating patients with aggressive variants of PTC.
journal_name
EBioMedicinejournal_title
EBioMedicineauthors
Lopez-Campistrous A,Adewuyi EE,Benesch MGK,Ko YM,Lai R,Thiesen A,Dewald J,Wang P,Chu K,Ghosh S,Williams DC,Vos LJ,Brindley DN,McMullen TPWdoi
10.1016/j.ebiom.2016.09.007subject
Has Abstractpub_date
2016-10-01 00:00:00pages
86-97issn
2352-3964pii
S2352-3964(16)30414-5journal_volume
12pub_type
杂志文章相关文献
EBioMedicine文献大全abstract::Chronic kidney disease (CKD) is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G0/G1 switch 2 (G0s2) ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif) ligand 2 (Ccl2) was increased in response to p65 activa...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2016.10.008
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma. METHODS:The Apcmin/+ mice gavage with phosphate-buffere...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.09.021
更新日期:2019-10-01 00:00:00
abstract::Metabolites have emerged as the quintessential effectors mediating the impact of the commensal microbiome on human physiology, both locally at the sites of microbial colonization and systemically. The endocrine activity of the microbiome and its involvement in a multitude of complex diseases has made microbiome-modula...
journal_title:EBioMedicine
pub_type: 杂志文章,评审
doi:10.1016/j.ebiom.2019.05.063
更新日期:2019-06-01 00:00:00
abstract::Clear cell renal cell carcinoma (ccRCC) is the most lethal neoplasm of the urologic system. Clinical therapeutic effect varies greatly between individual ccRCC patients, so there is an urgent need to develop prognostic molecular biomarkers to help clinicians identify patients in need of early aggressive management. In...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2016.12.003
更新日期:2017-02-01 00:00:00
abstract:BACKGROUND:Individuals of low socioeconomic status experience a disproportionate burden of chronic conditions; however it is unclear whether chronic condition burden affects survival differently across socioeconomic strata. METHODS:This retrospective cohort study used health administrative data from all residents of O...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2015.11.018
更新日期:2015-11-18 00:00:00
abstract::Compelling evidence shows that fine particulate matters (PMs) from air pollution penetrate lower airways and are associated with adverse health effects even within concentrations below those recommended by the WHO. A paper reported a dose-dependent link between carbon content in alveolar macrophages (assessed only by ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2015.10.012
更新日期:2015-10-09 00:00:00
abstract::Cardiovascular diseases (CVDs) are the leading cause of death and a major cause of disability globally. Transcription factor EB (TFEB), as a member of the microphthalmia transcription factor (MITF) family, has been demonstrated to be a master regulator of autophagy and lysosomal biogenesis. Emerging studies suggest th...
journal_title:EBioMedicine
pub_type: 杂志文章,评审
doi:10.1016/j.ebiom.2020.103207
更新日期:2021-01-01 00:00:00
abstract::A central pathogenic event of Alzheimer's disease (AD) is the accumulation of the Aβ42 peptide, which is generated from amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. We have developed a class of soluble 2-aminothiazole γ-secretase modulators (SGSMs) that preferentially decreases Aβ42 levels. H...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.08.028
更新日期:2017-10-01 00:00:00
abstract:BACKGROUND:Angiogenesis improves reperfusion to the ischaemic tissue after vascular obstruction. The underlying molecular mechanisms of post-ischaemic angiogenesis are not clear. FAM3A belongs to the family with sequence similarity 3 (FAM3) genes, but its biological function in endothelial cells in regards to vascular ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.03.038
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.103129
更新日期:2020-12-01 00:00:00
abstract::Despite substantial declines in mortality following myocardial infarction (MI), subsequent left ventricular remodeling (LVRm) remains a significant long-term complication. Extracellular small non-coding RNAs (exRNAs) have been associated with cardiac inflammation and fibrosis and we hypothesized that they are associat...
journal_title:EBioMedicine
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ebiom.2018.05.013
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:BM32, a grass pollen allergy vaccine containing four recombinant fusion proteins consisting of hepatitis B-derived PreS and hypoallergenic peptides from the major timothy grass pollen allergens adsorbed on aluminium hydroxide has been shown to be safe and to improve clinical symptoms of grass pollen allergy ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.11.006
更新日期:2019-12-01 00:00:00
abstract::Prostate cancer (PCa) is the most commonly diagnosed cancer in males in the Western world. Although prostate-specific antigen (PSA) has been widely used as a biomarker for PCa diagnosis, its results can be controversial. Therefore, new biomarkers are needed to enhance the clinical management of PCa. From publicly avai...
journal_title:EBioMedicine
pub_type: 杂志文章,meta分析
doi:10.1016/j.ebiom.2018.05.010
更新日期:2018-06-01 00:00:00
abstract::Trauma experienced during surgery can contribute to the development of a systemic inflammatory response that can cause multi-organ dysfunction or even failure. Post-surgical neuroinflammation is a documented phenomenon that results in synaptic impairment, neuronal dysfunction and death, and impaired neurogenesis. Vari...
journal_title:EBioMedicine
pub_type: 杂志文章,评审
doi:10.1016/j.ebiom.2018.10.021
更新日期:2018-11-01 00:00:00
abstract::Inter-individual variability has been a major hurdle to optimize disease management. Precision medicine holds promise for improving health and healthcare via tailor-made therapeutic strategies. Herein, we outline the paradigm of "pharmacometabolomics-aided pharmacogenomics" in autoimmune diseases. We envisage merging ...
journal_title:EBioMedicine
pub_type: 杂志文章,评审
doi:10.1016/j.ebiom.2016.02.001
更新日期:2016-02-02 00:00:00
abstract:BACKGROUND:While PARP inhibitors and CDK4/6 inhibitors, the two classes of FDA-approved agents, have shown promising clinical benefits, there is an urgent need to develop new therapeutic strategies to improve clinical response. Meanwhile, extending the utility of these inhibitors beyond their respective molecularly def...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.03.027
更新日期:2019-05-01 00:00:00
abstract::Mesenchymal stem cell (MSC)-derived exosomes have diverse functions in regulating wound healing and inflammation; however, the molecular mechanism of human umbilical cord MSC (hUCMSC)-derived exosomes in regulating burn-induced inflammation is not well understood. We found that burn injury significantly increased the ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2016.04.030
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:Clozapine is the most effective drug for treatment-resistant schizophrenia, but its use is limited by toxicity. Because ethnicity has been reported to affect clozapine metabolism, we compared its steady state pharmacokinetics in New Zealand Maori and European patients. METHODS:Clozapine and norclozapine ste...
journal_title:EBioMedicine
pub_type: 临床试验,杂志文章
doi:10.1016/j.ebiom.2017.11.030
更新日期:2018-01-01 00:00:00
abstract::Detecting circulating tumor cells (CTCs) has proven valuable for evaluating the prognosis of cancer patients and for studying the mechanisms of treatment resistance. Owing to the lack of universal and specific tumor markers for neuroblastoma (NB), in this prospective study, we adopted an EpCAM-independent method to de...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2018.08.005
更新日期:2018-09-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) shows remarkable propensity to metastasize. This predilection to escape from the primary tumor is driven by paracrine and autocrine mechanisms that guide cancer cells through a multi-step process concluding with colonization in distant tissues. Although cell-intrinsic features s...
journal_title:EBioMedicine
pub_type: 杂志文章,评审
doi:10.1016/j.ebiom.2020.102662
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND:Cancer of unknown primary (CUP), representing approximately 3-5% of all malignancies, is defined as metastatic cancer where a primary site of origin cannot be found despite a standard diagnostic workup. Because knowledge of a patient's primary cancer remains fundamental to their treatment, CUP patients are s...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.103030
更新日期:2020-11-01 00:00:00
abstract::Although psychotropic drugs act on neurons and glial cells, how glia respond, and whether glial responses are involved in therapeutic effects are poorly understood. Here, we show that fluoxetine (FLX), an anti-depressant, mediates its anti-depressive effect by increasing the gliotransmission of ATP. FLX increased ATP ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2018.05.036
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Recurrent mutations in the promoter of the telomerase reverse transcriptase (TERT) gene (C228T and C250T) detected in tumours and cells shed into urine of urothelial cancer (UC) patients are putative biomarkers for UC detection and monitoring. However, the possibility of detecting these mutations in cell-fre...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.05.004
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:Robust prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is important for developing individualized treatment plans. This study was conducted to develop and validate a clinically feasible prognostic classifier based on transcriptome-wide gene expression profiles. METHO...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.102805
更新日期:2020-11-01 00:00:00
abstract::Environmental exposure early in development plays a role in susceptibility to disease in later life. Here, we demonstrate that prolonged febrile seizures induced by exposure of rat pups to a hyperthermic environment enhance seizure susceptibility not only in these hyperthermia-treated rats but also in their future off...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.02.006
更新日期:2017-03-01 00:00:00
abstract::Cancer cells frequently up-regulate DNA replication and repair proteins such as the multifunctional DNA2 nuclease/helicase, counteracting DNA damage due to replication stress and promoting survival. Therefore, we hypothesized that blocking both DNA replication and repair by inhibiting the bifunctional DNA2 could be a ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2016.02.043
更新日期:2016-04-01 00:00:00
abstract::The emergence and prevalence of antibiotic-resistant bacteria are an increasing cause of death worldwide, resulting in a global 'call to action' to avoid receding into an era lacking effective antibiotics. Despite the urgency, the healthcare industry still relies on a single in vitro bioassay to determine antibiotic e...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.05.026
更新日期:2017-06-01 00:00:00
abstract::The nascent field of 'Nutritional Psychiatry' offers much promise for addressing the large disease burden associated with mental disorders. A consistent evidence base from the observational literature confirms that the quality of individuals' diets is related to their risk for common mental disorders, such as depressi...
journal_title:EBioMedicine
pub_type: 杂志文章,评审
doi:10.1016/j.ebiom.2017.02.020
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND:Besides long-term trans-differentiation into neural cells, benefits of stem cell therapy (SCT) in ischemic stroke may include secretion of protective factors, which partly reflects extracellular vesicle (EVs) released by stem cell. However, the mechanism(s) by which stem cells/EVs limit stroke injury have ye...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.103161
更新日期:2021-01-01 00:00:00
abstract::The identification of SYK as a molecular target in B-lineage leukemia/lymphoma cells prompted the development of SYK inhibitors as a new class of anti-cancer drug candidates. Here we report that induction of the SYK gene expression in human cells causes a significant down-regulation of evolutionarily conserved genes a...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2014.10.019
更新日期:2014-11-01 00:00:00