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DIVERSet JAG compounds inhibit topoisomerase II and are effective against adult and pediatric high-grade gliomas

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DIVERSet JAG compounds inhibit topoisomerase II and are effective against adult and pediatric high-grade gliomas. / Howarth, Alison; Simms, Claire; Kerai, Nitesh; Allen, Olivia; Mihajluk, Karina; Madureira, Patricia A.; Sokratous, Giannis; Cragg, Simon; Lee, Sang Y.; Morley, Andy D.; Keyoumars, Ashkan; Cox, Paul A.; Pilkington, Geoffrey J.; Hill, Richard.

In: Translational Oncology, Vol. 12, No. 10, 01.10.2019, p. 1375-1385.

Research output: Contribution to journalArticle

Harvard

Howarth, A, Simms, C, Kerai, N, Allen, O, Mihajluk, K, Madureira, PA, Sokratous, G, Cragg, S, Lee, SY, Morley, AD, Keyoumars, A, Cox, PA, Pilkington, GJ & Hill, R 2019, 'DIVERSet JAG compounds inhibit topoisomerase II and are effective against adult and pediatric high-grade gliomas', Translational Oncology, vol. 12, no. 10, pp. 1375-1385. https://doi.org/10.1016/j.tranon.2019.07.007

APA

Howarth, A., Simms, C., Kerai, N., Allen, O., Mihajluk, K., Madureira, P. A., ... Hill, R. (2019). DIVERSet JAG compounds inhibit topoisomerase II and are effective against adult and pediatric high-grade gliomas. Translational Oncology, 12(10), 1375-1385. https://doi.org/10.1016/j.tranon.2019.07.007

Vancouver

Author

Howarth, Alison ; Simms, Claire ; Kerai, Nitesh ; Allen, Olivia ; Mihajluk, Karina ; Madureira, Patricia A. ; Sokratous, Giannis ; Cragg, Simon ; Lee, Sang Y. ; Morley, Andy D. ; Keyoumars, Ashkan ; Cox, Paul A. ; Pilkington, Geoffrey J. ; Hill, Richard. / DIVERSet JAG compounds inhibit topoisomerase II and are effective against adult and pediatric high-grade gliomas. In: Translational Oncology. 2019 ; Vol. 12, No. 10. pp. 1375-1385.

Bibtex

@article{4a9953e415b846cb8c26539a9905c9e8,
title = "DIVERSet JAG compounds inhibit topoisomerase II and are effective against adult and pediatric high-grade gliomas",
abstract = "High-grade gliomas (HGGs) are aggressive primary brain tumors with local invasive growth and poor clinical prognosis in both adult and pediatric patients. Clinical response is compounded by resistance to standard frontline antineoplastic agents, an absence of novel therapeutics, and poor in vitro models to evaluate these. We screened a range of recently identified anticancer compounds in conventional adult, pediatric, and new biopsy-derived HGG models. These in vitro lines showed a range of sensitivity to standard chemotherapeutics, with varying expression levels of the prognostic markers hypoxia-induced factor (HIF) 1α and p53. Our evaluation of lead DIVERSet library compounds identified that JAG-6A, a compound that was significantly more potent than temozolomide or etoposide, was effective against HGG models in two-dimensional and three-dimensional systems; mediated this response by the potent inhibition of topoisomerase Iiα; remained effective under normoxic and hypoxic conditions; and displayed limited toxicity to non-neoplastic astrocytes. These data suggest that JAG-6A could be an alternative topoisomerase IIα inhibitor and used for the treatment of HGG.",
author = "Alison Howarth and Claire Simms and Nitesh Kerai and Olivia Allen and Karina Mihajluk and Madureira, {Patricia A.} and Giannis Sokratous and Simon Cragg and Lee, {Sang Y.} and Morley, {Andy D.} and Ashkan Keyoumars and Cox, {Paul A.} and Pilkington, {Geoffrey J.} and Richard Hill",
year = "2019",
month = "10",
day = "1",
doi = "10.1016/j.tranon.2019.07.007",
language = "English",
volume = "12",
pages = "1375--1385",
journal = "Translational Oncology",
issn = "1936-5233",
publisher = "Neoplasia Press",
number = "10",

}

RIS

TY - JOUR

T1 - DIVERSet JAG compounds inhibit topoisomerase II and are effective against adult and pediatric high-grade gliomas

AU - Howarth, Alison

AU - Simms, Claire

AU - Kerai, Nitesh

AU - Allen, Olivia

AU - Mihajluk, Karina

AU - Madureira, Patricia A.

AU - Sokratous, Giannis

AU - Cragg, Simon

AU - Lee, Sang Y.

AU - Morley, Andy D.

AU - Keyoumars, Ashkan

AU - Cox, Paul A.

AU - Pilkington, Geoffrey J.

AU - Hill, Richard

PY - 2019/10/1

Y1 - 2019/10/1

N2 - High-grade gliomas (HGGs) are aggressive primary brain tumors with local invasive growth and poor clinical prognosis in both adult and pediatric patients. Clinical response is compounded by resistance to standard frontline antineoplastic agents, an absence of novel therapeutics, and poor in vitro models to evaluate these. We screened a range of recently identified anticancer compounds in conventional adult, pediatric, and new biopsy-derived HGG models. These in vitro lines showed a range of sensitivity to standard chemotherapeutics, with varying expression levels of the prognostic markers hypoxia-induced factor (HIF) 1α and p53. Our evaluation of lead DIVERSet library compounds identified that JAG-6A, a compound that was significantly more potent than temozolomide or etoposide, was effective against HGG models in two-dimensional and three-dimensional systems; mediated this response by the potent inhibition of topoisomerase Iiα; remained effective under normoxic and hypoxic conditions; and displayed limited toxicity to non-neoplastic astrocytes. These data suggest that JAG-6A could be an alternative topoisomerase IIα inhibitor and used for the treatment of HGG.

AB - High-grade gliomas (HGGs) are aggressive primary brain tumors with local invasive growth and poor clinical prognosis in both adult and pediatric patients. Clinical response is compounded by resistance to standard frontline antineoplastic agents, an absence of novel therapeutics, and poor in vitro models to evaluate these. We screened a range of recently identified anticancer compounds in conventional adult, pediatric, and new biopsy-derived HGG models. These in vitro lines showed a range of sensitivity to standard chemotherapeutics, with varying expression levels of the prognostic markers hypoxia-induced factor (HIF) 1α and p53. Our evaluation of lead DIVERSet library compounds identified that JAG-6A, a compound that was significantly more potent than temozolomide or etoposide, was effective against HGG models in two-dimensional and three-dimensional systems; mediated this response by the potent inhibition of topoisomerase Iiα; remained effective under normoxic and hypoxic conditions; and displayed limited toxicity to non-neoplastic astrocytes. These data suggest that JAG-6A could be an alternative topoisomerase IIα inhibitor and used for the treatment of HGG.

U2 - 10.1016/j.tranon.2019.07.007

DO - 10.1016/j.tranon.2019.07.007

M3 - Article

VL - 12

SP - 1375

EP - 1385

JO - Translational Oncology

JF - Translational Oncology

SN - 1936-5233

IS - 10

ER -

ID: 15114371