Endocrine Abstracts

Background: Anaplastic thyroid-carcinomas (ATC) and a subset of papillary (PTC) and follicular (FTC) thyroid carcinomas behave aggressively showing metastatic spread and radio-resistance. Both the PI3K and HIF pathways are associated with aggressiveness and metastasis in thyroid carcinoma.Aims: To assess if the PI3K/HIF pathways contribute to radio-resistance and assess the effect of PI3K/HIF inhibition on radio-sensitivity and metastatic behaviour of th...

Intratumoural hypoxia is associated with aggressive and metastatic phenotypes with poor prognosis. The transcription factor HIF-1α is a key regulator of hypoxia-mediated gene expression that is documented to promote tumour growth and metastasis in a wide range of cancers. However its role in the development of thyroid carcinomas is relatively unknown. We have previously shown that HIF-1α is highly active in a range of thyroid cancer cell lines with highest activity o...

Background: Intratumoural hypoxia is associated with an aggressive and metastatic phenotype and poor prognosis. The transcription factor Hypoxia-inducible Factor-1α (HIF-1α) is a key regulator of hypoxia, inducing the expression of genes which promote tumour cell survival, such as carbonic-anhydrase IX (CA-IX) playing a role in cell adhesion, pH regulation and dedifferentiation of the tumours. Here we investigated whether there is cross talk between the HIF-1 and Wnt...

Background: Tissue hypoxia is a hallmark of rapidly proliferating tumours which most frequently adapt and prosper under low oxygen tension. The transcription factor, HIF-1α, is mediating these effects and induces target genes involved in survival, invasion and resistance to drugs and radiation. No data are available on the functional regulation of HIF-1α in thyroid carcinoma cells.Methods: Using thyroid carcinoma cells derived from papillary (N...

Small cell lung cancer (SCLC) is distinguished by its neuroendocrine phenotype and secretion of hormone biomarkers. Tumours initially respond well to therapy but almost invariably relapse with a therapy-resistant phenotype. We have previously described pro-opiomelanocortin (POMC) as a potential biomarker of SCLC. In this study, we investigated how POMC acts as a biomarker of tumour response to treatment.SCLC cells (DMS 79) were injected subcutaneously in...

The transcription factor HIF-1α regulates hypoxia-mediated gene expression which promotes tumour growth, metastasis and desensitisation to chemo-and radiotherapy. HIF-1 is functional in a range of thyroid-carcinoma cells and is regulated by hypoxia and the PI3K and MAPK-signalling pathways.We aimed to determine if HIF-1 and PI3K were important in the development of a metastatic phenotype and play a role in desensitisation to radiotherapy in thyroid ...

Context: HIF-1α is frequently upregulated in many tumour types and has been shown to be critical for radio- and chemosensitivity in pre-clinical studies. However the regulation and function of HIF-1α is unknown in thyroid carcinomas.Objectives: Here, we evaluated basal expression and regulation of HIF-1α and target genes in primary thyroid carcinomas and in thyroid cancer cell lines (NPA, FTC-133, ARO).Design and out...

Small cell lung cancer (SCLC) is highly aggressive with a particularly poor prognosis. This is due to tumours quickly metastasising and developing chemoresistance. SCLC tumours possess neuroendocrine properties in that they secrete prohormones such as pro-opiomelanocortin (POMC) and pro-gastrin releasing peptide (pro-GRP). These can be detected in the circulation and therefore have potential as biomarkers for prognosis and relapse. The aims of this study are; i) develop a mode...