Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy.

Details

Ressource 1Download: 34439129_BIB_EC36C22A988A.pdf (4203.94 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_EC36C22A988A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy.
Journal
Cancers
Author(s)
Chmielewski-Stivers N., Petit B., Ollivier J., Monceau V., Tsoutsou P., Quintela Pousa A., Lin X., Limoli C., Vozenin M.C.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
06/08/2021
Peer-reviewed
Oui
Volume
13
Number
16
Pages
3973
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female wild-type (WT) mice were treated with paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB-deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones, including estrogen. In females, RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by paclitaxel but enhanced cardiac sensitivity to radiotherapy. Conversely, rhoB-deficiency protected males from radiation toxicity. In sum, RhoB was identified as a molecular determinant driving estrogen-dependent cardioprotection in female mice, whereas neuroprotection was not sex hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.
Keywords
cancer treatment, cardiotoxicity, chemotherapy, neurotoxicity, radiotherapy, rhoB, sex
Pubmed
Web of science
Open Access
Yes
Create date
03/09/2021 18:12
Last modification date
12/01/2022 7:14
Usage data