ORCID Profile
0000-0002-0945-5496
Current Organisation
University of Oxford
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Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526882.V1
Abstract: S2. E0771 mcoEltd1 tumours have increased vessel and M2 macrophage markers.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526882
Abstract: S2. E0771 mcoEltd1 tumours have increased vessel and M2 macrophage markers.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526861
Abstract: Supplementary Figure and Table Legends
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526876.V1
Abstract: S4. Eltd1 expressing tumour cells proliferate in the presence of endothelial cells and modifies their secretome.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526864
Abstract: S8. Tumour vascular ADGRL4/ELTD1 is differentially expressed between primary breast cancer and regional node metastases and expression correlates with improved relapse free survival (RFS).
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526855.V1
Abstract: Supplementary Table 2. Patient characteristics from (A) the primary breast cancer core biopsy study and (B) the primary breast cancer and regional node metastasis study.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526885
Abstract: S1. Expression of mcoEltd1 in E0771 cells does not affect cell growth or invasion.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526879
Abstract: S3. Expression of mcoEltd1 in 4T1 cells does not affect cell growth in vitro but increases tumour growth and metastasis.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526858
Abstract: Supplementary Table 1. QPCR primer sequences
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.C.6545234.V1
Abstract: Abstract ELTD1/ADGRL4 expression is increased in the vasculature of a number of tumor types and this correlates with a good prognosis. Expression has also been reported in some tumor cells with high expression correlating with a good prognosis in hepatocellular carcinoma (HCC) and a poor prognosis in glioblastoma. Here we show that 35% of primary human breast tumors stain positively for ELTD1, with 9% having high expression that correlates with improved relapse-free survival. Using immunocompetent, syngeneic mouse breast cancer models we found that tumors expressing recombinant murine Eltd1 grew faster than controls, with an enhanced ability to metastasize and promote systemic immune effects. The Eltd1-expressing tumors had larger and better perfused vessels and tumor–endothelial cell interaction led to the release of proangiogenic and immune-modulating factors. M2-like macrophages increased in the stroma along with expression of programmed death-ligand 1 (PD-L1) on tumor and immune cells, to create an immunosuppressive microenvironment that allowed Eltd1-regulated tumor growth in the presence of an NY-ESO-1–specific immune response. Eltd1-positive tumors also responded better to chemotherapy which could explain the relationship to a good prognosis observed in primary human cases. Thus, ELTD1 expression may enhance delivery of therapeutic antibodies to reverse the immunosuppression and increase response to chemotherapy and radiotherapy in this subset of tumors. ELTD1 may be useful as a selection marker for such therapies. Implications: ELTD1 expression in mouse breast tumors creates an immunosuppressive microenvironment and increases vessel size and perfusion. Its expression may enhance the delivery of therapies targeting the immune system. /
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526873.V1
Abstract: S5. Representative flow cytometry dot plots indicating the gating strategy for identification of myeloid and lymphoid populations and PD-L1.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526855
Abstract: Supplementary Table 2. Patient characteristics from (A) the primary breast cancer core biopsy study and (B) the primary breast cancer and regional node metastasis study.
Publisher: American Association for Cancer Research (AACR)
Date: 03-2008
DOI: 10.1158/1078-0432.CCR-07-1755
Abstract: Purpose: MicroRNA (miRNA) expression alterations have been described in cancer. Many cancers are characterized by areas of hypoxia, enhanced hypoxia-inducible factor (HIF) levels, and increased expression of hypoxically regulated genes, all of which correlate with patient outcome. We examined hypoxia-induced miRNA expression changes to identify markers of survival in breast cancer. Experimental Design: We used microarrays to analyze miRNA expression changes induced by hypoxia in MCF7 breast cancer cell lines and validated results by quantitative-PCR (Q-PCR). Small interfering RNA against HIF-1α and HIF-2α, and RCC4 cells transfected with the von Hippel-Lindau (VHL) protein were used to investigate HIF dependency of miRNA expression. miRNA Q-PCR assays were done on 219 early breast cancer s les with long-term follow-up. Correlation of expression with clinical variables was done using Pearson and Spearman's rank tests, univariate, and Cox multivariate analysis. Results: hsa-miR-210 induction was the most significant change under hypoxia by microarray analysis (3.4-fold, P & 0.001). hsa-miR-210 expression changes were validated by Q-PCR and detected in other cancer cell lines. Using small interfering RNAs and RCC4 cells transfected with VHL, we showed that the regulation by hypoxia of hsa-miR-210 was mediated by the HIF-1α/VHL transcriptional system but not HIF-2α. hsa-miR-210 expression levels in breast cancer s les correlated directly with a hypoxia score based on the expression of 99 genes. hsa-miR-210 expression levels showed an inverse correlation with disease-free and overall survival, significant in both univariate and multivariate analyses. Conclusions: We show that hsa-miR-210 overexpression is induced by hypoxia in a HIF-1α– and VHL-dependent fashion and its expression levels in breast cancer s les are an independent prognostic factor.
Publisher: American Association for Cancer Research (AACR)
Date: 13-09-2011
DOI: 10.1158/0008-5472.CAN-11-1704
Abstract: Resistance to VEGF inhibitors is emerging as a major clinical problem. Notch signaling has been implicated in tumor angiogenesis. Therefore, to investigate mechanisms of resistance to angiogenesis inhibitors, we transduced human glioblastoma cells with retroviruses encoding Notch delta-like ligand 4 (DLL4), grew them as tumor xenografts and then treated the murine hosts with the VEGF-A inhibitor bevacizumab. We found that DLL4-mediated tumor resistance to bevacizumab in vivo. The large vessels induced by DLL4-Notch signaling increased tumor blood supply and were insensitive to bevacizumab. However, blockade of Notch signaling by dibenzazepine, a γ-secretase inhibitor, disrupted the large vessels and abolished the tumor resistance. Multiple molecular mechanisms of resistance were shown, including decreased levels of hypoxia-induced VEGF and increased levels of the VEGF receptor VEGFR1 in the tumor stroma, decreased levels of VEGFR2 in large blood vessels, and reduced levels of VEGFR3 overall. DLL4-expressing tumors were also resistant to a VEGFR targeting multikinase inhibitor. We also observed activation of other pathways of tumor resistance driven by DLL4-Notch signaling, including the FGF2-FGFR and EphB4-EprinB2 pathways, the inhibition of which reversed tumor resistance partially. Taken together, our findings show the importance of classifying mechanisms involved in angiogenesis in tumors, and how combination therapy to block DLL4-Notch signaling may enhance the efficacy of VEGF inhibitors, particularly in DLL4-upregulated tumors, and thus provide a rational base for the development of novel strategies to overcome antiangiogenic resistance in the clinic. Cancer Res 71(18) 6073–83. ©2011 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2021
DOI: 10.1158/1541-7786.MCR-21-0171
Abstract: ELTD1 expression in mouse breast tumors creates an immunosuppressive microenvironment and increases vessel size and perfusion. Its expression may enhance the delivery of therapies targeting the immune system.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526867.V1
Abstract: S7. Mice with Eltd1 expressing tumours have less specific T CD8+ cells raised against the tumour NY-ESO-1 antigen.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526861.V1
Abstract: Supplementary Figure and Table Legends
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526858.V1
Abstract: Supplementary Table 1. QPCR primer sequences
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526885.V1
Abstract: S1. Expression of mcoEltd1 in E0771 cells does not affect cell growth or invasion.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526879.V1
Abstract: S3. Expression of mcoEltd1 in 4T1 cells does not affect cell growth in vitro but increases tumour growth and metastasis.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526870
Abstract: S6. Eltd1 increases myeloid accumulation in the spleen.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526876
Abstract: S4. Eltd1 expressing tumour cells proliferate in the presence of endothelial cells and modifies their secretome.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526873
Abstract: S5. Representative flow cytometry dot plots indicating the gating strategy for identification of myeloid and lymphoid populations and PD-L1.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526870.V1
Abstract: S6. Eltd1 increases myeloid accumulation in the spleen.
Publisher: Springer Science and Business Media LLC
Date: 10-2008
DOI: 10.1038/NATURE07362
Publisher: American Association for Cancer Research (AACR)
Date: 30-08-2011
DOI: 10.1158/0008-5472.CAN-11-0489
Abstract: microRNA expression profiling plays an emerging role in cancer classification and identification of therapeutic strategies. In this study, we have evaluated the benefits of a joint microRNA–mRNA analysis in breast cancer. Matched mRNA and microRNA global expression profiling was conducted in a well-annotated cohort of 207 cases with complete 10-year follow-up. Penalized Cox regression including microRNA expression, mRNA expression, and clinical covariates was used to identify microRNAs associated with distant relapse-free survival (DRFS) that provide independent prognostic information, and are not simply surrogates of previously identified prognostic covariates. Penalized regression was chosen to prevent overfitting. Furthermore, microRNA–mRNA relationships were explored by global expression analysis, and exploited to validate results in several published cohorts (n = 592 with DRFS, n = 1,050 with recurrence-free survival). Four microRNAs were independently associated with DRFS in estrogen receptor (ER)-positive (3 novel and 1 known miR-128a) and 6 in ER-negative (5 novel and 1 known miR-210) cases. Of the latter, miR-342, -27b, and -150 were prognostic also in triple receptor-negative tumors. Coordinated expression of predicted target genes and prognostic microRNAs strengthened these results, most significantly for miR-210, -128a, and -27b, whose targets were prognostic in meta-analysis of several cohorts. In addition, miR-210 and -128a showed coordinated expression with their cognate pri-microRNAs, which were themselves prognostic in independent cohorts. Our integrated microRNA–mRNA global profiling approach has identified microRNAs independently associated with prognosis in breast cancer. Furthermore, it has validated known and predicted microRNA–target interactions, and elucidated their association with key pathways that could represent novel therapeutic targets. Cancer Res 71(17) 5635–45. ©2011 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.C.6545234
Abstract: Abstract ELTD1/ADGRL4 expression is increased in the vasculature of a number of tumor types and this correlates with a good prognosis. Expression has also been reported in some tumor cells with high expression correlating with a good prognosis in hepatocellular carcinoma (HCC) and a poor prognosis in glioblastoma. Here we show that 35% of primary human breast tumors stain positively for ELTD1, with 9% having high expression that correlates with improved relapse-free survival. Using immunocompetent, syngeneic mouse breast cancer models we found that tumors expressing recombinant murine Eltd1 grew faster than controls, with an enhanced ability to metastasize and promote systemic immune effects. The Eltd1-expressing tumors had larger and better perfused vessels and tumor–endothelial cell interaction led to the release of proangiogenic and immune-modulating factors. M2-like macrophages increased in the stroma along with expression of programmed death-ligand 1 (PD-L1) on tumor and immune cells, to create an immunosuppressive microenvironment that allowed Eltd1-regulated tumor growth in the presence of an NY-ESO-1–specific immune response. Eltd1-positive tumors also responded better to chemotherapy which could explain the relationship to a good prognosis observed in primary human cases. Thus, ELTD1 expression may enhance delivery of therapeutic antibodies to reverse the immunosuppression and increase response to chemotherapy and radiotherapy in this subset of tumors. ELTD1 may be useful as a selection marker for such therapies. Implications: ELTD1 expression in mouse breast tumors creates an immunosuppressive microenvironment and increases vessel size and perfusion. Its expression may enhance the delivery of therapies targeting the immune system. /
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526867
Abstract: S7. Mice with Eltd1 expressing tumours have less specific T CD8+ cells raised against the tumour NY-ESO-1 antigen.
Publisher: EMBO
Date: 28-07-2020
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/1541-7786.22526864.V1
Abstract: S8. Tumour vascular ADGRL4/ELTD1 is differentially expressed between primary breast cancer and regional node metastases and expression correlates with improved relapse free survival (RFS).
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Helen Sheldon.