Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy
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 trea...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/16/3973 |
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| author | Nicole Chmielewski-Stivers Benoit Petit Jonathan Ollivier Virginie Monceau Pelagia Tsoutsou Ana Quintela Pousa Xiaomeng Lin Charles Limoli Marie-Catherine Vozenin |
| author_facet | Nicole Chmielewski-Stivers Benoit Petit Jonathan Ollivier Virginie Monceau Pelagia Tsoutsou Ana Quintela Pousa Xiaomeng Lin Charles Limoli Marie-Catherine Vozenin |
| author_sort | Nicole Chmielewski-Stivers |
| collection | DOAJ |
| description | 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, <i>rhoB-</i>deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones, including estrogen. In females, <i>RhoB</i> deficiency and advanced age had no impact on neurocognitive impairment induced by paclitaxel but enhanced cardiac sensitivity to radiotherapy. Conversely, <i>rhoB-</i>deficiency protected males from radiation toxicity. In sum, <i>RhoB</i> 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. |
| first_indexed | 2024-03-10T08:57:23Z |
| format | Article |
| id | doaj.art-4c4274f0d88240778aea142590a73c2e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:57:23Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4c4274f0d88240778aea142590a73c2e2023-11-22T07:01:55ZengMDPI AGCancers2072-66942021-08-011316397310.3390/cancers13163973Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac RadiotherapyNicole Chmielewski-Stivers0Benoit Petit1Jonathan Ollivier2Virginie Monceau3Pelagia Tsoutsou4Ana Quintela Pousa5Xiaomeng Lin6Charles Limoli7Marie-Catherine Vozenin8Department of Radiation Oncology, University of California at Irvine, Irvine, CA 92697, USALaboratory of Radiation Oncology, Radiation Oncology Service, Department of Oncology, CHUV, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, SwitzerlandLaboratory of Radiation Oncology, Radiation Oncology Service, Department of Oncology, CHUV, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, SwitzerlandInstitut de Radioprotection et de Sureté Nucléaire (IRSN), 92260 Fontenay aux Roses, FranceLaboratory of Radiation Oncology, Radiation Oncology Service, Department of Oncology, CHUV, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, SwitzerlandLaboratory of Radiation Oncology, Radiation Oncology Service, Department of Oncology, CHUV, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, SwitzerlandDepartment of Radiation Oncology, University of California at Irvine, Irvine, CA 92697, USADepartment of Radiation Oncology, University of California at Irvine, Irvine, CA 92697, USALaboratory of Radiation Oncology, Radiation Oncology Service, Department of Oncology, CHUV, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, SwitzerlandThe 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, <i>rhoB-</i>deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones, including estrogen. In females, <i>RhoB</i> deficiency and advanced age had no impact on neurocognitive impairment induced by paclitaxel but enhanced cardiac sensitivity to radiotherapy. Conversely, <i>rhoB-</i>deficiency protected males from radiation toxicity. In sum, <i>RhoB</i> 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.https://www.mdpi.com/2072-6694/13/16/3973cancer treatmentchemotherapyradiotherapycardiotoxicityneurotoxicitysex |
| spellingShingle | Nicole Chmielewski-Stivers Benoit Petit Jonathan Ollivier Virginie Monceau Pelagia Tsoutsou Ana Quintela Pousa Xiaomeng Lin Charles Limoli Marie-Catherine Vozenin Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy Cancers cancer treatment chemotherapy radiotherapy cardiotoxicity neurotoxicity sex |
| title | Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy |
| title_full | Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy |
| title_fullStr | Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy |
| title_full_unstemmed | Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy |
| title_short | Sex-Specific Differences in Toxicity Following Systemic Paclitaxel Treatment and Localized Cardiac Radiotherapy |
| title_sort | sex specific differences in toxicity following systemic paclitaxel treatment and localized cardiac radiotherapy |
| topic | cancer treatment chemotherapy radiotherapy cardiotoxicity neurotoxicity sex |
| url | https://www.mdpi.com/2072-6694/13/16/3973 |
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