Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782465349698977792 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5095795 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT voloshintali alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT munstermijal alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT blattroni alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT shteingauzanna alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT robertspaulc alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT schmelzevam alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT giladimoshe alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT schneidermanrosas alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT zeevieinav alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT poratyaara alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT bomzonzeev alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT urmannoa alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT itzhakiaviran alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT cahalshay alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT kirsoneilond alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT weinberguri alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo AT paltiyoram alternatingelectricfieldsttfieldsincombinationwithpaclitaxelaretherapeuticallyeffectiveagainstovariancancercellsinvitroandinvivo |