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Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo

Chemotherapy resistant high grade serous ovarian cancer remains a clinically intractable disease with a high rate of mortality. We tested a novel glycosylated antitumor ether lipid called l-Rham to assess the in vitro and in vivo efficacy on high grade serous ovarian cancer cell lines and patient sa...

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Autores principales: Nachtigal, Mark W, Musaphir, Paris, Dhiman, Shiv, Altman, Alon D, Schweizer, Frank, Arthur, Gilbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379490/
https://www.ncbi.nlm.nih.gov/pubmed/34416424
http://dx.doi.org/10.1016/j.tranon.2021.101203
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author Nachtigal, Mark W
Musaphir, Paris
Dhiman, Shiv
Altman, Alon D
Schweizer, Frank
Arthur, Gilbert
author_facet Nachtigal, Mark W
Musaphir, Paris
Dhiman, Shiv
Altman, Alon D
Schweizer, Frank
Arthur, Gilbert
author_sort Nachtigal, Mark W
collection PubMed
description Chemotherapy resistant high grade serous ovarian cancer remains a clinically intractable disease with a high rate of mortality. We tested a novel glycosylated antitumor ether lipid called l-Rham to assess the in vitro and in vivo efficacy on high grade serous ovarian cancer cell lines and patient samples. l-Rham effectively kills high grade serous ovarian cancer cells grown as 2D or 3D cultures in a dose and time dependent manner. l-Rham efficacy was tested in vivo in a chicken allantoic membrane/COV362 xenograft model, where l-Rham activity was as effective as paclitaxel in reducing tumor weight and metastasis. The efficacy of l-Rham to reduce OVCAR3 tumor xenografts in NRG mice was assessed in low and high tumor burden models. l-Rham effectively reduced tumor formation in the low tumor burden group, and blocked ascites formation in low and high tumor burden animals. l-Rham demonstrates efficacy against OVCAR3 tumor and ascites formation in vivo in NRG mice, laying the foundation for further development of this drug class for the treatment of high grade serous ovarian cancer patients.
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spelling pubmed-83794902021-09-02 Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo Nachtigal, Mark W Musaphir, Paris Dhiman, Shiv Altman, Alon D Schweizer, Frank Arthur, Gilbert Transl Oncol Original Research Chemotherapy resistant high grade serous ovarian cancer remains a clinically intractable disease with a high rate of mortality. We tested a novel glycosylated antitumor ether lipid called l-Rham to assess the in vitro and in vivo efficacy on high grade serous ovarian cancer cell lines and patient samples. l-Rham effectively kills high grade serous ovarian cancer cells grown as 2D or 3D cultures in a dose and time dependent manner. l-Rham efficacy was tested in vivo in a chicken allantoic membrane/COV362 xenograft model, where l-Rham activity was as effective as paclitaxel in reducing tumor weight and metastasis. The efficacy of l-Rham to reduce OVCAR3 tumor xenografts in NRG mice was assessed in low and high tumor burden models. l-Rham effectively reduced tumor formation in the low tumor burden group, and blocked ascites formation in low and high tumor burden animals. l-Rham demonstrates efficacy against OVCAR3 tumor and ascites formation in vivo in NRG mice, laying the foundation for further development of this drug class for the treatment of high grade serous ovarian cancer patients. Neoplasia Press 2021-08-17 /pmc/articles/PMC8379490/ /pubmed/34416424 http://dx.doi.org/10.1016/j.tranon.2021.101203 Text en © 2021 Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Nachtigal, Mark W
Musaphir, Paris
Dhiman, Shiv
Altman, Alon D
Schweizer, Frank
Arthur, Gilbert
Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo
title Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo
title_full Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo
title_fullStr Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo
title_full_unstemmed Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo
title_short Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo
title_sort cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379490/
https://www.ncbi.nlm.nih.gov/pubmed/34416424
http://dx.doi.org/10.1016/j.tranon.2021.101203
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