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Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome (2022)
Journal Article
Sueca-Comes, M., Rusu, E. C., Grabowska, A. M., & Bates, D. O. (2022). Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome. Pharmacological Reviews, 74(4), 1136-1145. https://doi.org/10.1124/pharmrev.121.000410

The number of cancer drugs is increasing as new chemical entities are developed to target molecules, often protein kinases, driving cancer progression. In 2009, Fedorov et al. identified that of the protein kinases in the human kinome, most of the fo... Read More about Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome.

Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts (2022)
Journal Article
Sharpe, B. P., Hayden, A., Manousopoulou, A., Cowie, A., Walker, R. C., Harrington, J., …Underwood, T. J. (2022). Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts. Cell Reports Medicine, 3(6), Article 100541. https://doi.org/10.1016/j.xcrm.2022.100541

The chemotherapy resistance of esophageal adenocarcinomas (EACs) is underpinned by cancer cell extrinsic mechanisms of the tumor microenvironment (TME). We demonstrate that, by targeting the tumor-promoting functions of the predominant TME cell type,... Read More about Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts.

Apoptosis in Cancer Cells Is Induced by Alternative Splicing of hnRNPA2/B1 Through Splicing of Bcl-x, a Mechanism that Can Be Stimulated by an Extract of the South African Medicinal Plant, Cotyledon orbiculata (2020)
Journal Article
Makhafola, T. J., Mbele, M., Yacqub-Usman, K., Hendren, A., Haigh, D. B., Blackley, Z., …Dlamini, Z. (2020). Apoptosis in Cancer Cells Is Induced by Alternative Splicing of hnRNPA2/B1 Through Splicing of Bcl-x, a Mechanism that Can Be Stimulated by an Extract of the South African Medicinal Plant, Cotyledon orbiculata. Frontiers in Oncology, 10, Article 547392. https://doi.org/10.3389/fonc.2020.547392

Alternative splicing is deregulated in cancer and alternatively spliced products can be linked to cancer hallmarks. Targeting alternative splicing could offer novel effective cancer treatments. We investigated the effects of the crude extract of a So... Read More about Apoptosis in Cancer Cells Is Induced by Alternative Splicing of hnRNPA2/B1 Through Splicing of Bcl-x, a Mechanism that Can Be Stimulated by an Extract of the South African Medicinal Plant, Cotyledon orbiculata.

Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells (2020)
Journal Article
Boonsri, B., Yacqub-Usman, K., Thintharua, P., Myint, K. Z., Sae-Lao, T., Collier, P., …Wongprasert, K. (2020). Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells. Cancer Research and Treatment, 53(2), 457-470. https://doi.org/10.4143/crt.2020.585

Purpose The potential of members of the epidermal growth factor receptor (ErbB) family as drug targets in cholangiocarcinoma (CCA) has not been extensively addressed. Although phase III clinical trials showed no survival benefits of erlotinib in pati... Read More about Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells.

Non?invasive measurement of retinal permeability in a diabetic rat model (2020)
Journal Article
Whatmore, J. L., Allen, C. L., Malhi, N. K., Whatmore, J. D., Bates, D. O., & Arkill, K. P. (2020). Non?invasive measurement of retinal permeability in a diabetic rat model. Microcirculation, 27(6), https://doi.org/10.1111/micc.12623

Objective: The gold standard for measuring blood-retinal barrier permeability is the Evans blue assay. However, this technique has limitations in vivo, including non-specific tissue binding and toxicity. This study describes a non-toxic, high through... Read More about Non?invasive measurement of retinal permeability in a diabetic rat model.

Blocking endothelial apoptosis revascularises the retina in a model of ischemic retinopathy (2020)
Journal Article
Grant, Z. L., Whitehead, L., Wong, V. H. Y., He, Z., Yan, R. Y., Miles, A. R., …Coultas, L. (2020). Blocking endothelial apoptosis revascularises the retina in a model of ischemic retinopathy. Journal of Clinical Investigation, 130(8), 4235-4251. https://doi.org/10.1172/jci127668

Aberrant, neovascular retinal blood vessel growth is a vision-threatening complication in ischemic retinal diseases. It is driven by retinal hypoxia frequently caused by capillary nonperfusion and endothelial cell (EC) loss. We investigated the role... Read More about Blocking endothelial apoptosis revascularises the retina in a model of ischemic retinopathy.

Local microvascular leakage promotes trafficking of activated neutrophils to remote organs (2020)
Journal Article
Owen-Woods, C., Joulia, R., Barkaway, A., Rolas, L., Ma, B., Nottebaum, A. F., …Nourshargh, S. (2020). Local microvascular leakage promotes trafficking of activated neutrophils to remote organs. Journal of Clinical Investigation, 130(5), 2301-2318. https://doi.org/10.1172/JCI133661

Copyright: © 2020, Owen-Woods et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. Increased microvascular permeability to plasma proteins and neutrophil emigration are hallmar... Read More about Local microvascular leakage promotes trafficking of activated neutrophils to remote organs.

Activation of Notch signalling by soluble Dll4 decreases vascular permeability via a cAMP/PKA-dependent pathway (2019)
Journal Article
Boardman, R., Pang, V., Malhi, N., Lynch, A. P., Leach, L., Benest, A. V., …Machado, M. J. (2019). Activation of Notch signalling by soluble Dll4 decreases vascular permeability via a cAMP/PKA-dependent pathway. AJP - Heart and Circulatory Physiology, 316(5), H1065-H1075. https://doi.org/10.1152/ajpheart.00610.2018

© 2019 the American Physiological Society. The Notch ligand delta-like ligand 4 (Dll4), upregulated by VEGF, is a key regulator of vessel morphogenesis and function, controlling tip and stalk cell selection during sprouting angiogenesis. Inhibition o... Read More about Activation of Notch signalling by soluble Dll4 decreases vascular permeability via a cAMP/PKA-dependent pathway.

Enhanced notch signaling modulates unproductive revascularization in response to nitric oxide-angiopoietin signaling in a mouse model of peripheral ischemia (2019)
Journal Article
Machado, M. J., Boardman, R., Riu, F., Emanueli, C., Benest, A. V., & Bates, D. O. (2019). Enhanced notch signaling modulates unproductive revascularization in response to nitric oxide-angiopoietin signaling in a mouse model of peripheral ischemia. Microcirculation, 26(6), https://doi.org/10.1111/micc.12549

Introduction Arteriolargenesis can be induced by concomitant stimulation of nitric Oxide (NO)?Angiopoietin receptor (Tie)?Vascular Endothelial Growth Factor (VEGF) signaling in the rat mesentery angiogenesis assay. We hypothesized that the same comb... Read More about Enhanced notch signaling modulates unproductive revascularization in response to nitric oxide-angiopoietin signaling in a mouse model of peripheral ischemia.

An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance (2019)
Journal Article
Li, N., Babaei-Jadidi, R., Lorenzi, F., Spencer-Dene, B., Clarke, P., Domingo, E., …Nateri, A. S. (2019). An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance. Oncogenesis, 8, Article 13. https://doi.org/10.1038/s41389-019-0125-3

Colorectal cancer (CRC) patients develop recurrence after chemotherapy owing to the survival of stem cell-like cells referred to as cancer stem-like cells (CSCs). The origin of CSCs is linked to the epithelial–mesenchymal transition (EMT) process. Cu... Read More about An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance.

SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4 (2018)
Journal Article
Tzelepis, K., De Braekeleer, E., Aspris, D., Barbieri, I., Vijayabaskar, M. S., Liu, W., …Vassiliou, G. S. (2018). SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4. Nature Communications, 9(1), https://doi.org/10.1038/s41467-018-07620-0

We recently identified the splicing kinase gene SRPK1 as a genetic vulnerability of acute myeloid leukemia (AML). Here, we show that genetic or pharmacological inhibition of SRPK1 leads to cell cycle arrest, leukemic cell differentiation and prolonge... Read More about SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4.

VEGFC Reduces Glomerular Albumin Permeability and Protects Against Alterations in VEGF Receptor Expression in Diabetic Nephropathy (2018)
Journal Article
Onions, K. L., Gamez, M., Buckner, N. R., Baker, S. L., Betteridge, K. B., Desideri, S., …Foster, R. R. (2019). VEGFC Reduces Glomerular Albumin Permeability and Protects Against Alterations in VEGF Receptor Expression in Diabetic Nephropathy. Diabetes, 68(1), 172-187. https://doi.org/10.2337/db18-0045

Elevated levels of vascular endothelial growth factor (VEGF) A are thought to cause glomerular endothelial cell (GEnC) dysfunction and albuminuria in diabetic nephropathy. We hypothesized that VEGFC could counteract these effects of VEGFA to protect... Read More about VEGFC Reduces Glomerular Albumin Permeability and Protects Against Alterations in VEGF Receptor Expression in Diabetic Nephropathy.

BDNF (Brain-Derived Neurotrophic Factor) Promotes Embryonic Stem Cells Differentiation to Endothelial Cells Via a Molecular Pathway, Including MicroRNA-214, EZH2 (Enhancer of Zeste Homolog 2), and eNOS (Endothelial Nitric Oxide Synthase) (2018)
Journal Article
Descamps, B., Saif, J., Benest, A. V., Biglino, G., Bates, D. O., Chamorro-Jorganes, A., & Emanueli, C. (2018). BDNF (Brain-Derived Neurotrophic Factor) Promotes Embryonic Stem Cells Differentiation to Endothelial Cells Via a Molecular Pathway, Including MicroRNA-214, EZH2 (Enhancer of Zeste Homolog 2), and eNOS (Endothelial Nitric Oxide Synthase). Arteriosclerosis, Thrombosis, and Vascular Biology, 38(9), 2117-2125. doi:10.1161/atvbaha.118.311400

Novel haemodynamic structures in the human glomerulus (2018)
Journal Article
Neal, C., Arkill, K., Bell, J., Betteridge, K., Bates, D., Winlove, C., …Harper, S. (in press). Novel haemodynamic structures in the human glomerulus. AJP - Renal Physiology, https://doi.org/10.1152/ajprenal.00566.2017

To investigate human glomerular structure under conditions of physiological perfusion we have analysed fresh and perfusion fixed normal human glomeruli at physiological hydrostatic and oncotic pressures using serial resin section reconstruction, conf... Read More about Novel haemodynamic structures in the human glomerulus.

Diabetes-induced microvascular complications at the level of the spinal cord: a contributing factor in diabetic neuropathic pain (2018)
Journal Article
Ved, N., Da Vitoria Lobo, M., Bestall, S. M., Vidueira, C., Beazley-Long, N., Ballmer-Hofer, K., …Hulse, R. P. (2018). Diabetes-induced microvascular complications at the level of the spinal cord: a contributing factor in diabetic neuropathic pain. Journal of Physiology, 596(16), 3675-3693. https://doi.org/10.1113/JP275067

Abnormalities of neurovascular interactions within the central nervous system of diabetic patients is associated with the onset of many neurological disease states. However, to date, the link between the neurovascular network within the spinal cord a... Read More about Diabetes-induced microvascular complications at the level of the spinal cord: a contributing factor in diabetic neuropathic pain.

Vascular endothelial growth factor-A165b restores normal glomerular water permeability in a diphtheria-toxin mouse model of glomerular injury (2018)
Journal Article
Stevens, M., Neal, C. R., Salmon, A. H., Bates, D. O., Harper, S. J., & Oltean, S. (in press). Vascular endothelial growth factor-A165b restores normal glomerular water permeability in a diphtheria-toxin mouse model of glomerular injury. Nephron, https://doi.org/10.1159/000485664

BACKGROUND/AIMS:Genetic cell ablation using the human diphtheria toxin receptor (hDTR) is a new strategy used for analysing cellular function. Diphtheria toxin (DT) is a cytotoxic protein that leaves mouse cells relatively unaffected, but upon bindin... Read More about Vascular endothelial growth factor-A165b restores normal glomerular water permeability in a diphtheria-toxin mouse model of glomerular injury.

Effects of hypoxia and hyperoxia on the differential expression of VEGF-A isoforms and receptors in Idiopathic Pulmonary Fibrosis (IPF) (2018)
Journal Article
Barratt, S. L., Blythe, T., Ourradi, K., Jarrett, C., Welsh, G. I., Bates, D. O., & Millar, A. B. (in press). Effects of hypoxia and hyperoxia on the differential expression of VEGF-A isoforms and receptors in Idiopathic Pulmonary Fibrosis (IPF). Respiratory Research, 19, https://doi.org/10.1186/s12931-017-0711-x

Dysregulation of VEGF-A bioavailability has been implicated in the development of lung injury/fibrosis, exemplified by Idiopathic Pulmonary Fibrosis (IPF). VEGF-A is a target of the hypoxic response via its translational regulation by HIF-1?. The rol... Read More about Effects of hypoxia and hyperoxia on the differential expression of VEGF-A isoforms and receptors in Idiopathic Pulmonary Fibrosis (IPF).

Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-A165a, VEGF-A165b, PIGF and VE-cadherin (2017)
Journal Article
Pang, V., Bates, D. O., & Leach, L. (2017). Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-A165a, VEGF-A165b, PIGF and VE-cadherin. Clinical Science, 131(23), 2763-2775. https://doi.org/10.1042/CS20171252

The human placenta nourishes and protects the developing fetus whilst influencing maternal physiology for fetal advantage. It expresses several members of the VEGF family including the pro-angiogenic/pro-permeability VEGF-A165a isoform, the anti-angi... Read More about Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-A165a, VEGF-A165b, PIGF and VE-cadherin.

Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells (2017)
Journal Article
Sae-Lao, T., Luplertlop, N., Janvilisri, T., Tohtong, R., Bates, D. O., & Wongprasert, K. (2017). Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells. Phytomedicine, 36, https://doi.org/10.1016/j.phymed.2017.09.014

BACKGROUND: Seaweeds have a long history of use in Asian countries as functional foods, medicinal herbs, and the treatment of cancer. Polysaccharides from various seaweeds have shown anti-tumor activity. Cholangiocarcinoma (CCA), often with metastati... Read More about Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells.

Differential expression of VEGF-Axxx isoforms is critical for development of pulmonary fibrosis (2017)
Journal Article
Barratt, S. L., Blythe, T., Jarrett, C., Ourradi, K., Shelley-Fraser, G., Day, M. J., …Millar, A. B. (2017). Differential expression of VEGF-Axxx isoforms is critical for development of pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine, 196(4), https://doi.org/10.1164/rccm.201603-0568OC

RATIONALE Fibrosis after lung injury is related to poor outcome, and idiopathic pulmonary fibrosis (IPF) can be regarded as an exemplar. Vascular endothelial growth factor (VEGF)-A has been implicated in this context, but there are conflicting rep... Read More about Differential expression of VEGF-Axxx isoforms is critical for development of pulmonary fibrosis.