Show simple item record

dc.contributor.advisorYarnold J
dc.contributor.authorNimalasena, S
dc.contributor.editorYarnold, J
dc.date.accessioned2022-10-26T09:48:08Z
dc.date.available2022-10-26T09:48:08Z
dc.date.issued2022-10-18
dc.identifier.citation2022en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5551
dc.description.abstractIntroduction In the early 2000s, Japanese colleagues reported sensitisation of normal and tumour cell lines to cytotoxic doses of ionising radiation (IR) by low concentrations of hydrogen peroxide (H2O2), research that prompted clinical studies testing intratumoural (IT) injections of 0.5% H2O2 in 1% sodium hyaluronate gel during radiotherapy in patients with inoperable breast cancer. Five-year local control rates were substantially higher than expected from the radiotherapy dose intensities used, with no additional late adverse effects. Methods Using the radioresistant cell lines HCT116 and HN5, the effect of H2O2 + IR was investigated in 2D clonogenic survival and 3D spheroid growth assays. A dual hypoxia marker technique was used to capture the effect of IT H2O2 in murine xenografts. In paralleL, a phase I clinical trial of IT H2O2 + radiotherapy was conducted in 12 patients with breast cancer to evaluate safety and cute toxicity. Results 2D clonogenic assays did not confirm sensitisation of HCT116 or HN5 under normoxic conditions. Growth inhibition was demonstrated in HCT116 spheroids treated with H2O2 + IR, compared with H2O2/IR alone. Xenograft tumours injected with H2O2 + sodium hyaluronate exhibited a reduction in hypoxia staining compared to baseline. A significant difference in pimonidazole versus CCI-103F staining was demonstrated in H2O2-injected tumours (p0=02), with no significant difference in the control groups. The phase I clinical trial confirmed safety with no additional toxicity compared to RT alone. Conclusion 3D spheroid results are in keeping with clinical reports of enhancement of radiation effect by H2O2. Reoxygenation by IT H2O2 may be an important mechanism by which tumour response is enhanced for therapeutic gain, and which has implications for scheduling of H2O2 relative to radiotherapy in the clinical setting. If this method of increasing oxygen delivery to tumours is confirmed to be successful, it has potential to be utilised in several other tumour types.
dc.language.isoengen_US
dc.publisherInstitute of Cancer Research (University Of London)en_US
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserveden_US
dc.titleInvestigation of the effects of hydrogen peroxide in combination with ionising radiation in canceren_US
dc.typeThesis or Dissertation
dcterms.accessRightsPublic
dc.date.updated2022-10-26T09:46:59Z
rioxxterms.versionAOen_US
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserveden_US
rioxxterms.licenseref.startdate2022-10-18
rioxxterms.typeThesisen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
icr.researchteamTargeted Therapyen_US
dc.contributor.icrauthorNimalasena, Samantha
uketdterms.institutionInstitute of Cancer Research
uketdterms.qualificationlevelDoctoral
uketdterms.qualificationnameM.D.Res
icr.provenanceDeposited by Mr Barry Jenkins (impersonating Dr Samantha Nimalasena) on 2022-10-26. Deposit type is initial. No. of files: 1. Files: MD(Res)_Nimalasena_S.pdf
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameM.D.Res


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record