Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo
Dasatinib is a targeted cancer therapy, while programmed death ligand 1 (PD-L1) inhibitors are a form of immune checkpoint therapy used to treat various types of cancers. Several studies showed the potential efficacy of these drugs in the management of triple-negative breast cancer- an aggressive su...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , |
| التنسيق: | article |
| منشور في: |
2020
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| الموضوعات: | |
| الوصول للمادة أونلاين: | http://dx.doi.org/10.1016/j.biopha.2020.111134 https://www.sciencedirect.com/science/article/pii/S0753332220313275 http://hdl.handle.net/10576/17228 |
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| _version_ | 1857415084518670336 |
|---|---|
| author | Maha, Al-Asmakh |
| author2 | Bawadi, Hiba Hamdan, Munia Gupta, Ishita Kheraldine, Hadeel Jabeen, Ayesha Rizeq, Balsam Al Moustafa, Ala-Eddin |
| author2_role | author author author author author author author |
| author_facet | Maha, Al-Asmakh Bawadi, Hiba Hamdan, Munia Gupta, Ishita Kheraldine, Hadeel Jabeen, Ayesha Rizeq, Balsam Al Moustafa, Ala-Eddin |
| author_role | author |
| dc.creator.none.fl_str_mv | Maha, Al-Asmakh Bawadi, Hiba Hamdan, Munia Gupta, Ishita Kheraldine, Hadeel Jabeen, Ayesha Rizeq, Balsam Al Moustafa, Ala-Eddin |
| dc.date.none.fl_str_mv | 2020-12-21T10:49:44Z 2021-02-28 |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://dx.doi.org/10.1016/j.biopha.2020.111134 Maha Al-Asmakh, Hiba Bawadi, Munia Hamdan, Ishita Gupta, Hadeel Kheraldine, Ayesha Jabeen, Balsam Rizeq, Ala-Eddin Al Moustafa, Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo, Biomedicine & Pharmacotherapy, Volume 134, 2021, 111134, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2020.111134. 07533322 https://www.sciencedirect.com/science/article/pii/S0753332220313275 http://hdl.handle.net/10576/17228 134 |
| dc.language.none.fl_str_mv | en |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Dasatinib PD-L/PD-L1 Embryo Angiogenesis Chorioallantoic membrane Toxicity |
| dc.title.none.fl_str_mv | Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Dasatinib is a targeted cancer therapy, while programmed death ligand 1 (PD-L1) inhibitors are a form of immune checkpoint therapy used to treat various types of cancers. Several studies showed the potential efficacy of these drugs in the management of triple-negative breast cancer- an aggressive subtype of breast cancer, which can develop during pregnancy. Nevertheless, side effects of Dasatinib (DA) and PD-L1 drugs during pregnancy, especially in the early stages of embryogenesis are not explored yet. The aim of this study is to assess the individual and combined toxicity of DA and PD-L1 inhibitors during the early stages of embryogenesis and to evaluate their effect(s) on angiogenesis using the chorioallantoic membrane (CAM) model of the embryo. Our results show that embryos die at greater rates after exposure to DA and PD-L1 inhibitors as compared to their matched controls. Moreover, treatment with these drugs significantly inhibits angiogenesis of the CAM. To further elucidate key regulator genes of embryotoxicity induced by the actions of PD-L1 and DA, an RT-PCR analysis was performed for seven target genes that regulate cell proliferation, angiogenesis, and survival (ATF3, FOXA2, MAPRE2, RIPK1, INHBA, SERPINA4, and VEGFC). Our data revealed that these genes are significantly deregulated in the brain, heart, and liver tissues of exposed embryos, compared to matched control tissues. Nevertheless, further studies are necessary to evaluate the effects of these anti breast cancer drugs and elucidate their role during pregnancy. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | qu_e63659041878fd7ca4f21b170eeaade8 |
| identifier_str_mv | Maha Al-Asmakh, Hiba Bawadi, Munia Hamdan, Ishita Gupta, Hadeel Kheraldine, Ayesha Jabeen, Balsam Rizeq, Ala-Eddin Al Moustafa, Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo, Biomedicine & Pharmacotherapy, Volume 134, 2021, 111134, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2020.111134. 07533322 134 |
| language_invalid_str_mv | en |
| network_acronym_str | qu |
| network_name_str | Qatar University repository |
| oai_identifier_str | oai:qspace.qu.edu.qa:10576/17228 |
| publishDate | 2020 |
| publisher.none.fl_str_mv | Elsevier |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| spelling | Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryoMaha, Al-AsmakhBawadi, HibaHamdan, MuniaGupta, IshitaKheraldine, HadeelJabeen, AyeshaRizeq, BalsamAl Moustafa, Ala-EddinDasatinibPD-L/PD-L1EmbryoAngiogenesisChorioallantoic membraneToxicityDasatinib is a targeted cancer therapy, while programmed death ligand 1 (PD-L1) inhibitors are a form of immune checkpoint therapy used to treat various types of cancers. Several studies showed the potential efficacy of these drugs in the management of triple-negative breast cancer- an aggressive subtype of breast cancer, which can develop during pregnancy. Nevertheless, side effects of Dasatinib (DA) and PD-L1 drugs during pregnancy, especially in the early stages of embryogenesis are not explored yet. The aim of this study is to assess the individual and combined toxicity of DA and PD-L1 inhibitors during the early stages of embryogenesis and to evaluate their effect(s) on angiogenesis using the chorioallantoic membrane (CAM) model of the embryo. Our results show that embryos die at greater rates after exposure to DA and PD-L1 inhibitors as compared to their matched controls. Moreover, treatment with these drugs significantly inhibits angiogenesis of the CAM. To further elucidate key regulator genes of embryotoxicity induced by the actions of PD-L1 and DA, an RT-PCR analysis was performed for seven target genes that regulate cell proliferation, angiogenesis, and survival (ATF3, FOXA2, MAPRE2, RIPK1, INHBA, SERPINA4, and VEGFC). Our data revealed that these genes are significantly deregulated in the brain, heart, and liver tissues of exposed embryos, compared to matched control tissues. Nevertheless, further studies are necessary to evaluate the effects of these anti breast cancer drugs and elucidate their role during pregnancy.Elsevier2020-12-21T10:49:44Z2021-02-28Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1016/j.biopha.2020.111134Maha Al-Asmakh, Hiba Bawadi, Munia Hamdan, Ishita Gupta, Hadeel Kheraldine, Ayesha Jabeen, Balsam Rizeq, Ala-Eddin Al Moustafa, Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo, Biomedicine & Pharmacotherapy, Volume 134, 2021, 111134, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2020.111134.07533322https://www.sciencedirect.com/science/article/pii/S0753332220313275http://hdl.handle.net/10576/17228134enhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:qspace.qu.edu.qa:10576/172282024-07-23T11:23:12Z |
| spellingShingle | Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo Maha, Al-Asmakh Dasatinib PD-L/PD-L1 Embryo Angiogenesis Chorioallantoic membrane Toxicity |
| status_str | publishedVersion |
| title | Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo |
| title_full | Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo |
| title_fullStr | Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo |
| title_full_unstemmed | Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo |
| title_short | Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo |
| title_sort | Dasatinib and PD-L1 inhibitors provoke toxicity and inhibit angiogenesis in the embryo |
| topic | Dasatinib PD-L/PD-L1 Embryo Angiogenesis Chorioallantoic membrane Toxicity |
| url | http://dx.doi.org/10.1016/j.biopha.2020.111134 https://www.sciencedirect.com/science/article/pii/S0753332220313275 http://hdl.handle.net/10576/17228 |