Jamie Beaumont - Academia.edu (original) (raw)

Uploads

Papers by Jamie Beaumont

Research paper thumbnail of Epigenetic potentiation of somatostatin-2 by guadecitabine in neuroendocrine neoplasias as a novel method to allow delivery of peptide receptor radiotherapy

European Journal of Cancer

Research paper thumbnail of BCR Unresponsiveness and 13q14 Duplication Underpin Spontaneous Disease Regression in Chronic Lymphocytic Leukemia

Research paper thumbnail of Abstract 5398: Apelinergic signalling in hepatocellular carcinoma (HCC): A new therapeutic treatment option

Cancer Research

HCC is the third most frequent cancer-related death worldwide and incidence continues to rise. Mo... more HCC is the third most frequent cancer-related death worldwide and incidence continues to rise. Most patients presenting with advanced stage disease where their treatment goal is palliation, emphasizing the requirement for new treatment options. HCC is characterized by arterialization of its blood supply deemed pathognomonic for its development. We investigated the neoangiogenic peptide apelin as a driver of carcinogenesis in HCC followed by the efficacy of novel apelin antagonists as a therapeutic strategy in-vitro. Firstly, meta-analysis conducted through the TCGA database showed that apelin is significantly upregulated in liver cancer compared to healthy tissue and this correlated with a worse mean overall survival. Additionally, enzyme-linked immunosorbent assay (ELISA) of patient serum samples corroborated that apelin concentration significantly increases from healthy liver to cirrhosis and then further through tumorigenesis. In-vitro studies across multiple hepatocyte cell line...

Research paper thumbnail of Schnapsideen in der Spirituosensteuergesetzgebung : Verfassungsrechtliche Überlegungen zur beabsichtigten steuerlichen Privilegierung der inländischen Spirituosenherstellung

Research paper thumbnail of Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma

British Journal of Cancer

BACKGROUND: Aberrant activation of Axl is implicated in the progression of hepatocellular carcino... more BACKGROUND: Aberrant activation of Axl is implicated in the progression of hepatocellular carcinoma (HCC). We explored the biologic significance and preclinical efficacy of Axl inhibition as a therapeutic strategy in sorafenib-naive and resistant HCC. METHODS: We evaluated Axl expression in sorafenib-naive and resistant (SR) clones of epithelial (HuH7) and mesenchymal origin (SKHep-1) using antibody arrays and confirmed tissue expression. We tested the effect of Axl inhibition with RNA-interference and pharmacologically with R428 on a number of phenotypic assays. RESULTS: Axl mRNA overexpression in cell lines (n = 28) and RNA-seq tissue datasets (n = 373) correlated with epithelial-tomesenchymal transition (EMT). Axl was overexpressed in HCC compared to cirrhosis and normal liver. We confirmed sorafenib resistance to be associated with EMT and enhanced motility in both HuH7-SR and SKHep-1-SR cells documenting a 4-fold increase in Axl phosphorylation as an adaptive feature of chronic sorafenib treatment in SKHep-1-SR cells. Axl inhibition reduced motility and enhanced sensitivity to sorafenib in SKHep-1SR cells. In patients treated with sorafenib (n = 40), circulating Axl levels correlated with shorter survival. CONCLUSIONS: Suppression of Axl-dependent signalling influences the transformed phenotype in HCC cells and contributes to adaptive resistance to sorafenib, providing a pre-clinical rationale for the development of Axl inhibitors as a measure to overcome sorafenib resistance.

Research paper thumbnail of Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma

British Journal of Cancer

BACKGROUND: Aberrant activation of Axl is implicated in the progression of hepatocellular carcino... more BACKGROUND: Aberrant activation of Axl is implicated in the progression of hepatocellular carcinoma (HCC). We explored the biologic significance and preclinical efficacy of Axl inhibition as a therapeutic strategy in sorafenib-naive and resistant HCC. METHODS: We evaluated Axl expression in sorafenib-naive and resistant (SR) clones of epithelial (HuH7) and mesenchymal origin (SKHep-1) using antibody arrays and confirmed tissue expression. We tested the effect of Axl inhibition with RNA-interference and pharmacologically with R428 on a number of phenotypic assays. RESULTS: Axl mRNA overexpression in cell lines (n = 28) and RNA-seq tissue datasets (n = 373) correlated with epithelial-tomesenchymal transition (EMT). Axl was overexpressed in HCC compared to cirrhosis and normal liver. We confirmed sorafenib resistance to be associated with EMT and enhanced motility in both HuH7-SR and SKHep-1-SR cells documenting a 4-fold increase in Axl phosphorylation as an adaptive feature of chronic sorafenib treatment in SKHep-1-SR cells. Axl inhibition reduced motility and enhanced sensitivity to sorafenib in SKHep-1SR cells. In patients treated with sorafenib (n = 40), circulating Axl levels correlated with shorter survival. CONCLUSIONS: Suppression of Axl-dependent signalling influences the transformed phenotype in HCC cells and contributes to adaptive resistance to sorafenib, providing a pre-clinical rationale for the development of Axl inhibitors as a measure to overcome sorafenib resistance.

Research paper thumbnail of Epigenetic potentiation of somatostatin-2 by guadecitabine in neuroendocrine neoplasias as a novel method to allow delivery of peptide receptor radiotherapy

European Journal of Cancer

Research paper thumbnail of BCR Unresponsiveness and 13q14 Duplication Underpin Spontaneous Disease Regression in Chronic Lymphocytic Leukemia

Research paper thumbnail of Abstract 5398: Apelinergic signalling in hepatocellular carcinoma (HCC): A new therapeutic treatment option

Cancer Research

HCC is the third most frequent cancer-related death worldwide and incidence continues to rise. Mo... more HCC is the third most frequent cancer-related death worldwide and incidence continues to rise. Most patients presenting with advanced stage disease where their treatment goal is palliation, emphasizing the requirement for new treatment options. HCC is characterized by arterialization of its blood supply deemed pathognomonic for its development. We investigated the neoangiogenic peptide apelin as a driver of carcinogenesis in HCC followed by the efficacy of novel apelin antagonists as a therapeutic strategy in-vitro. Firstly, meta-analysis conducted through the TCGA database showed that apelin is significantly upregulated in liver cancer compared to healthy tissue and this correlated with a worse mean overall survival. Additionally, enzyme-linked immunosorbent assay (ELISA) of patient serum samples corroborated that apelin concentration significantly increases from healthy liver to cirrhosis and then further through tumorigenesis. In-vitro studies across multiple hepatocyte cell line...

Research paper thumbnail of Schnapsideen in der Spirituosensteuergesetzgebung : Verfassungsrechtliche Überlegungen zur beabsichtigten steuerlichen Privilegierung der inländischen Spirituosenherstellung

Research paper thumbnail of Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma

British Journal of Cancer

BACKGROUND: Aberrant activation of Axl is implicated in the progression of hepatocellular carcino... more BACKGROUND: Aberrant activation of Axl is implicated in the progression of hepatocellular carcinoma (HCC). We explored the biologic significance and preclinical efficacy of Axl inhibition as a therapeutic strategy in sorafenib-naive and resistant HCC. METHODS: We evaluated Axl expression in sorafenib-naive and resistant (SR) clones of epithelial (HuH7) and mesenchymal origin (SKHep-1) using antibody arrays and confirmed tissue expression. We tested the effect of Axl inhibition with RNA-interference and pharmacologically with R428 on a number of phenotypic assays. RESULTS: Axl mRNA overexpression in cell lines (n = 28) and RNA-seq tissue datasets (n = 373) correlated with epithelial-tomesenchymal transition (EMT). Axl was overexpressed in HCC compared to cirrhosis and normal liver. We confirmed sorafenib resistance to be associated with EMT and enhanced motility in both HuH7-SR and SKHep-1-SR cells documenting a 4-fold increase in Axl phosphorylation as an adaptive feature of chronic sorafenib treatment in SKHep-1-SR cells. Axl inhibition reduced motility and enhanced sensitivity to sorafenib in SKHep-1SR cells. In patients treated with sorafenib (n = 40), circulating Axl levels correlated with shorter survival. CONCLUSIONS: Suppression of Axl-dependent signalling influences the transformed phenotype in HCC cells and contributes to adaptive resistance to sorafenib, providing a pre-clinical rationale for the development of Axl inhibitors as a measure to overcome sorafenib resistance.

Research paper thumbnail of Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma

British Journal of Cancer

BACKGROUND: Aberrant activation of Axl is implicated in the progression of hepatocellular carcino... more BACKGROUND: Aberrant activation of Axl is implicated in the progression of hepatocellular carcinoma (HCC). We explored the biologic significance and preclinical efficacy of Axl inhibition as a therapeutic strategy in sorafenib-naive and resistant HCC. METHODS: We evaluated Axl expression in sorafenib-naive and resistant (SR) clones of epithelial (HuH7) and mesenchymal origin (SKHep-1) using antibody arrays and confirmed tissue expression. We tested the effect of Axl inhibition with RNA-interference and pharmacologically with R428 on a number of phenotypic assays. RESULTS: Axl mRNA overexpression in cell lines (n = 28) and RNA-seq tissue datasets (n = 373) correlated with epithelial-tomesenchymal transition (EMT). Axl was overexpressed in HCC compared to cirrhosis and normal liver. We confirmed sorafenib resistance to be associated with EMT and enhanced motility in both HuH7-SR and SKHep-1-SR cells documenting a 4-fold increase in Axl phosphorylation as an adaptive feature of chronic sorafenib treatment in SKHep-1-SR cells. Axl inhibition reduced motility and enhanced sensitivity to sorafenib in SKHep-1SR cells. In patients treated with sorafenib (n = 40), circulating Axl levels correlated with shorter survival. CONCLUSIONS: Suppression of Axl-dependent signalling influences the transformed phenotype in HCC cells and contributes to adaptive resistance to sorafenib, providing a pre-clinical rationale for the development of Axl inhibitors as a measure to overcome sorafenib resistance.

Log In