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Cancer During Pregnancy: The Role of Vascular Toxicity in Chemotherapy-Induced Placental Toxicity

Breast cancer is diagnosed in ~0.3% of pregnant women. Studies that have addressed gestational and neonatal outcomes of chemotherapy during pregnancy have demonstrated increased gestational complications including preeclampsia and intrauterine growth retardation. We hypothesized that anthracycline-i...

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Autores principales: Bar-Joseph, Hadas, Peccatori, Fedro Alessandro, Goshen-Lago, Tal, Cribiù, Fulvia Milena, Scarfone, Giovanna, Miller, Irit, Nemerovsky, Luba, Levi, Mattan, Shalgi, Ruth, Ben-Aharon, Irit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281110/
https://www.ncbi.nlm.nih.gov/pubmed/32443608
http://dx.doi.org/10.3390/cancers12051277
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author Bar-Joseph, Hadas
Peccatori, Fedro Alessandro
Goshen-Lago, Tal
Cribiù, Fulvia Milena
Scarfone, Giovanna
Miller, Irit
Nemerovsky, Luba
Levi, Mattan
Shalgi, Ruth
Ben-Aharon, Irit
author_facet Bar-Joseph, Hadas
Peccatori, Fedro Alessandro
Goshen-Lago, Tal
Cribiù, Fulvia Milena
Scarfone, Giovanna
Miller, Irit
Nemerovsky, Luba
Levi, Mattan
Shalgi, Ruth
Ben-Aharon, Irit
author_sort Bar-Joseph, Hadas
collection PubMed
description Breast cancer is diagnosed in ~0.3% of pregnant women. Studies that have addressed gestational and neonatal outcomes of chemotherapy during pregnancy have demonstrated increased gestational complications including preeclampsia and intrauterine growth retardation. We hypothesized that anthracycline-induced gestational complications could be derived from direct toxicity on the placenta vasculature. Pregnant ICR mice (day E12.5) were treated with doxorubicin (DXR; 8 mg/kg) or saline, while their umbilical cord blood flow was imaged by pulse-wave (PW) Doppler. Mice were euthanized on day E18.5, and their embryos and placentae were collected for further analysis. Unlike control mice, the DXR-treated mice presented an acute change in the umbilical cord’s blood flow parameters (velocity time integral and heart rate interval), reduced embryos’ weight, reduced placenta efficiency, and modulation in vascular-related pathways of treated placenta proteomics. Apoptosis and proliferation were also enhanced, as demonstrated by TUNEL and proliferating cell nuclear antigen (PCNA) analysis. We further examined the placentae of patients treated with epirubicin (EPI), who had been diagnosed with breast cancer during pregnancy (weeks 27–35). The immunohistochemistry of the EPI-treated human placentae showed enhanced proliferation and apoptosis as compared with matched chemo-naïve placentae, as well as reduced neovascularization (CD34). Our findings suggest that anthracycline-induced vascular insult promotes placental toxicity, and could point to potential agents designated to offset the damage and to reduce gestational complications in pregnant cancer patients.
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spelling pubmed-72811102020-06-15 Cancer During Pregnancy: The Role of Vascular Toxicity in Chemotherapy-Induced Placental Toxicity Bar-Joseph, Hadas Peccatori, Fedro Alessandro Goshen-Lago, Tal Cribiù, Fulvia Milena Scarfone, Giovanna Miller, Irit Nemerovsky, Luba Levi, Mattan Shalgi, Ruth Ben-Aharon, Irit Cancers (Basel) Article Breast cancer is diagnosed in ~0.3% of pregnant women. Studies that have addressed gestational and neonatal outcomes of chemotherapy during pregnancy have demonstrated increased gestational complications including preeclampsia and intrauterine growth retardation. We hypothesized that anthracycline-induced gestational complications could be derived from direct toxicity on the placenta vasculature. Pregnant ICR mice (day E12.5) were treated with doxorubicin (DXR; 8 mg/kg) or saline, while their umbilical cord blood flow was imaged by pulse-wave (PW) Doppler. Mice were euthanized on day E18.5, and their embryos and placentae were collected for further analysis. Unlike control mice, the DXR-treated mice presented an acute change in the umbilical cord’s blood flow parameters (velocity time integral and heart rate interval), reduced embryos’ weight, reduced placenta efficiency, and modulation in vascular-related pathways of treated placenta proteomics. Apoptosis and proliferation were also enhanced, as demonstrated by TUNEL and proliferating cell nuclear antigen (PCNA) analysis. We further examined the placentae of patients treated with epirubicin (EPI), who had been diagnosed with breast cancer during pregnancy (weeks 27–35). The immunohistochemistry of the EPI-treated human placentae showed enhanced proliferation and apoptosis as compared with matched chemo-naïve placentae, as well as reduced neovascularization (CD34). Our findings suggest that anthracycline-induced vascular insult promotes placental toxicity, and could point to potential agents designated to offset the damage and to reduce gestational complications in pregnant cancer patients. MDPI 2020-05-18 /pmc/articles/PMC7281110/ /pubmed/32443608 http://dx.doi.org/10.3390/cancers12051277 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bar-Joseph, Hadas
Peccatori, Fedro Alessandro
Goshen-Lago, Tal
Cribiù, Fulvia Milena
Scarfone, Giovanna
Miller, Irit
Nemerovsky, Luba
Levi, Mattan
Shalgi, Ruth
Ben-Aharon, Irit
Cancer During Pregnancy: The Role of Vascular Toxicity in Chemotherapy-Induced Placental Toxicity
title Cancer During Pregnancy: The Role of Vascular Toxicity in Chemotherapy-Induced Placental Toxicity
title_full Cancer During Pregnancy: The Role of Vascular Toxicity in Chemotherapy-Induced Placental Toxicity
title_fullStr Cancer During Pregnancy: The Role of Vascular Toxicity in Chemotherapy-Induced Placental Toxicity
title_full_unstemmed Cancer During Pregnancy: The Role of Vascular Toxicity in Chemotherapy-Induced Placental Toxicity
title_short Cancer During Pregnancy: The Role of Vascular Toxicity in Chemotherapy-Induced Placental Toxicity
title_sort cancer during pregnancy: the role of vascular toxicity in chemotherapy-induced placental toxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281110/
https://www.ncbi.nlm.nih.gov/pubmed/32443608
http://dx.doi.org/10.3390/cancers12051277
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