Abstract:A cell population with stem cell like characteristics is thought to underlie treatment resistance and local recurrence in glioma. In this work we investigate the role of the DNA repair protein RAD51 in these cells and the impact of inhibiting homologous recombination repair on radiation resistance in vitro and in vivo.
We used a model of inducible differentiation of patient derived glioma cells to investigate repair protein levels, repair foci formation and kinetics in clonogenic, stem-like popu… Show more
“…Depending on the availability of the building blocks, the cinnamide analogues (B) were also constructed by Heck coupling of the corresponding aromatic bromide with acrylamide C. After introducing motif 1 as an amine through amide coupling (D to E), the intermediates were cyclized under mild dehydration conditions with iodine and hexamethyldisilazine 18 to give the desired quinazolinone products (F). In this way, one series of compounds incorporated alkyl and cycloalkyl substituents (1)(2)(3)(4)(5)(6)(7)(8), and another series contained substituted aromatics with a variable spacer -(CH 2 )n-(n =0-2, 9-27). The latter series was designed to optimally target residues F195 and Y191 through piinteractions.…”
Section: Ar T Ic Le In F O Abstractmentioning
confidence: 99%
“…Upregulation of RAD51 is reported in several cancers, including triplenegative breast cancer (TNBC) 2 , glioblastoma 3 , prostate cancer 4 , and is a mechanism by which these tumors acquire resistance to therapies. HR-defective cells are significantly more sensitive to ionizing irradiation and DNA damaging chemotherapeutics 1 .…”
Abbreviations: BRAC2, breast cancer type 2 susceptibility protein; GFP, green fluorescent protein; HR, homologous recombination; HTS, high throughput screening.
“…Depending on the availability of the building blocks, the cinnamide analogues (B) were also constructed by Heck coupling of the corresponding aromatic bromide with acrylamide C. After introducing motif 1 as an amine through amide coupling (D to E), the intermediates were cyclized under mild dehydration conditions with iodine and hexamethyldisilazine 18 to give the desired quinazolinone products (F). In this way, one series of compounds incorporated alkyl and cycloalkyl substituents (1)(2)(3)(4)(5)(6)(7)(8), and another series contained substituted aromatics with a variable spacer -(CH 2 )n-(n =0-2, 9-27). The latter series was designed to optimally target residues F195 and Y191 through piinteractions.…”
Section: Ar T Ic Le In F O Abstractmentioning
confidence: 99%
“…Upregulation of RAD51 is reported in several cancers, including triplenegative breast cancer (TNBC) 2 , glioblastoma 3 , prostate cancer 4 , and is a mechanism by which these tumors acquire resistance to therapies. HR-defective cells are significantly more sensitive to ionizing irradiation and DNA damaging chemotherapeutics 1 .…”
Abbreviations: BRAC2, breast cancer type 2 susceptibility protein; GFP, green fluorescent protein; HR, homologous recombination; HTS, high throughput screening.
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