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Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo

Long‐term survival rates for advanced ovarian cancer patients have not changed appreciably over the past four decades; therefore, development of new, effective treatment modalities remains a high priority. Tumor Treating Fields (TTFields), a clinically active anticancer modality utilize low‐intensit...

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Autores principales: Voloshin, Tali, Munster, Mijal, Blatt, Roni, Shteingauz, Anna, Roberts, Paul C., Schmelz, Eva M., Giladi, Moshe, Schneiderman, Rosa S., Zeevi, Einav, Porat, Yaara, Bomzon, Ze'ev, Urman, Noa, Itzhaki, Aviran, Cahal, Shay, Kirson, Eilon D., Weinberg, Uri, Palti, Yoram
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095795/
https://www.ncbi.nlm.nih.gov/pubmed/27561100
http://dx.doi.org/10.1002/ijc.30406
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author Voloshin, Tali
Munster, Mijal
Blatt, Roni
Shteingauz, Anna
Roberts, Paul C.
Schmelz, Eva M.
Giladi, Moshe
Schneiderman, Rosa S.
Zeevi, Einav
Porat, Yaara
Bomzon, Ze'ev
Urman, Noa
Itzhaki, Aviran
Cahal, Shay
Kirson, Eilon D.
Weinberg, Uri
Palti, Yoram
author_facet Voloshin, Tali
Munster, Mijal
Blatt, Roni
Shteingauz, Anna
Roberts, Paul C.
Schmelz, Eva M.
Giladi, Moshe
Schneiderman, Rosa S.
Zeevi, Einav
Porat, Yaara
Bomzon, Ze'ev
Urman, Noa
Itzhaki, Aviran
Cahal, Shay
Kirson, Eilon D.
Weinberg, Uri
Palti, Yoram
author_sort Voloshin, Tali
collection PubMed
description Long‐term survival rates for advanced ovarian cancer patients have not changed appreciably over the past four decades; therefore, development of new, effective treatment modalities remains a high priority. Tumor Treating Fields (TTFields), a clinically active anticancer modality utilize low‐intensity, intermediate frequency, alternating electric fields. The goal of this study was to evaluate the efficacy of combining TTFields with paclitaxel against ovarian cancer cells in vitro and in vivo. In vitro application of TTFields on human ovarian cancer cell lines led to a significant reduction in cell counts as compared to untreated cells. The effect was found to be frequency and intensity dependent. Further reduction in the number of viable cells was achieved when TTFields treatment was combined with paclitaxel. The in vivo effect of the combined treatment was tested in mice orthotopically implanted with MOSE‐L(TICv) cells. In this model, combined treatment led to a significant reduction in tumor luminescence and in tumor weight as compared to untreated mice. The feasibility of effective local delivery of TTFields to the human abdomen was examined using finite element mesh simulations performed using the Sim4life software. These simulations demonstrated that electric fields intensities inside and in the vicinity of the ovaries of a realistic human computational phantom are about 1 and 2 V/cm pk‐pk, respectively, which is within the range of intensities required for TTFields effect. These results suggest that prospective clinical investigation of the combination of TTFields and paclitaxel is warranted.
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spelling pubmed-50957952016-11-09 Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo Voloshin, Tali Munster, Mijal Blatt, Roni Shteingauz, Anna Roberts, Paul C. Schmelz, Eva M. Giladi, Moshe Schneiderman, Rosa S. Zeevi, Einav Porat, Yaara Bomzon, Ze'ev Urman, Noa Itzhaki, Aviran Cahal, Shay Kirson, Eilon D. Weinberg, Uri Palti, Yoram Int J Cancer Cancer Therapy and Prevention Long‐term survival rates for advanced ovarian cancer patients have not changed appreciably over the past four decades; therefore, development of new, effective treatment modalities remains a high priority. Tumor Treating Fields (TTFields), a clinically active anticancer modality utilize low‐intensity, intermediate frequency, alternating electric fields. The goal of this study was to evaluate the efficacy of combining TTFields with paclitaxel against ovarian cancer cells in vitro and in vivo. In vitro application of TTFields on human ovarian cancer cell lines led to a significant reduction in cell counts as compared to untreated cells. The effect was found to be frequency and intensity dependent. Further reduction in the number of viable cells was achieved when TTFields treatment was combined with paclitaxel. The in vivo effect of the combined treatment was tested in mice orthotopically implanted with MOSE‐L(TICv) cells. In this model, combined treatment led to a significant reduction in tumor luminescence and in tumor weight as compared to untreated mice. The feasibility of effective local delivery of TTFields to the human abdomen was examined using finite element mesh simulations performed using the Sim4life software. These simulations demonstrated that electric fields intensities inside and in the vicinity of the ovaries of a realistic human computational phantom are about 1 and 2 V/cm pk‐pk, respectively, which is within the range of intensities required for TTFields effect. These results suggest that prospective clinical investigation of the combination of TTFields and paclitaxel is warranted. John Wiley and Sons Inc. 2016-09-19 2016-12-15 /pmc/articles/PMC5095795/ /pubmed/27561100 http://dx.doi.org/10.1002/ijc.30406 Text en © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Cancer Therapy and Prevention
Voloshin, Tali
Munster, Mijal
Blatt, Roni
Shteingauz, Anna
Roberts, Paul C.
Schmelz, Eva M.
Giladi, Moshe
Schneiderman, Rosa S.
Zeevi, Einav
Porat, Yaara
Bomzon, Ze'ev
Urman, Noa
Itzhaki, Aviran
Cahal, Shay
Kirson, Eilon D.
Weinberg, Uri
Palti, Yoram
Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo
title Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo
title_full Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo
title_fullStr Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo
title_full_unstemmed Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo
title_short Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo
title_sort alternating electric fields (ttfields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo
topic Cancer Therapy and Prevention
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095795/
https://www.ncbi.nlm.nih.gov/pubmed/27561100
http://dx.doi.org/10.1002/ijc.30406
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