Quantitative Evaluation of Hormesis in Breast Cancer Using Histoculture Drug Response Assay

Purpose: Hormesis is a phenomenon of growth stimulation at low doses and inhibition at higher doses. In cancer treatment, little is known about how hormesis affects cancer cell proliferation. We evaluated the hormetic dose–response relationship of paclitaxel using surgically resected breast cancer s...

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Main Authors: Yuka Aoishi, Tatsuya Yoshimasu, Shoji Oura, Mitsumasa Kawago, Yoshimitsu Hirai, Miwako Miyasaka, Takuya Ohashi, Yoshiharu Nishimura
Format: Article
Language:English
Published: SAGE Publishing 2019-12-01
Series:Dose-Response
Online Access:https://doi.org/10.1177/1559325819896183
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author Yuka Aoishi
Tatsuya Yoshimasu
Shoji Oura
Mitsumasa Kawago
Yoshimitsu Hirai
Miwako Miyasaka
Takuya Ohashi
Yoshiharu Nishimura
author_facet Yuka Aoishi
Tatsuya Yoshimasu
Shoji Oura
Mitsumasa Kawago
Yoshimitsu Hirai
Miwako Miyasaka
Takuya Ohashi
Yoshiharu Nishimura
author_sort Yuka Aoishi
collection DOAJ
description Purpose: Hormesis is a phenomenon of growth stimulation at low doses and inhibition at higher doses. In cancer treatment, little is known about how hormesis affects cancer cell proliferation. We evaluated the hormetic dose–response relationship of paclitaxel using surgically resected breast cancer specimens on the basis of histoculture drug response assay (HDRA). Methods: We used surgically resected fresh tumor specimens from 22 patients with breast cancer: 17 invasive ductal, 3 mucinous, and 2 other “special-type” cancers. All patients were female, ranging in age between 40 and 86 (median 60) years. Small pieces of viable cancer tissue were placed on collagen gel and cultured for 7 days with paclitaxel. Inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose–response curve. Results: Hormesis was observed in 9 of the 22 cases; ED 50 of cytotoxic effect was significantly higher ( P = .0036) in hormesis (H) group (44.6 ± 4.2 µg/mL) than in nonhormesis (N) group (26.7 ± 3.5 μg/mL). Conclusion: We evaluated hormesis in breast cancer tissue using HDRA for the first time although previously confirmed in cultured cells. Hormesis seems to occur in patients undergoing treatment with anticancer agents, especially in a metastatic setting. Meanwhile, tumor growth may be stimulated in patients who are resistant to paclitaxel.
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spelling doaj.art-50be8ed1a59b4ae2bbbe0211d4f9b78f2022-12-21T23:51:33ZengSAGE PublishingDose-Response1559-32582019-12-011710.1177/1559325819896183Quantitative Evaluation of Hormesis in Breast Cancer Using Histoculture Drug Response AssayYuka Aoishi0Tatsuya Yoshimasu1Shoji Oura2Mitsumasa Kawago3Yoshimitsu Hirai4Miwako Miyasaka5Takuya Ohashi6Yoshiharu Nishimura7 Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, JapanPurpose: Hormesis is a phenomenon of growth stimulation at low doses and inhibition at higher doses. In cancer treatment, little is known about how hormesis affects cancer cell proliferation. We evaluated the hormetic dose–response relationship of paclitaxel using surgically resected breast cancer specimens on the basis of histoculture drug response assay (HDRA). Methods: We used surgically resected fresh tumor specimens from 22 patients with breast cancer: 17 invasive ductal, 3 mucinous, and 2 other “special-type” cancers. All patients were female, ranging in age between 40 and 86 (median 60) years. Small pieces of viable cancer tissue were placed on collagen gel and cultured for 7 days with paclitaxel. Inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose–response curve. Results: Hormesis was observed in 9 of the 22 cases; ED 50 of cytotoxic effect was significantly higher ( P = .0036) in hormesis (H) group (44.6 ± 4.2 µg/mL) than in nonhormesis (N) group (26.7 ± 3.5 μg/mL). Conclusion: We evaluated hormesis in breast cancer tissue using HDRA for the first time although previously confirmed in cultured cells. Hormesis seems to occur in patients undergoing treatment with anticancer agents, especially in a metastatic setting. Meanwhile, tumor growth may be stimulated in patients who are resistant to paclitaxel.https://doi.org/10.1177/1559325819896183
spellingShingle Yuka Aoishi
Tatsuya Yoshimasu
Shoji Oura
Mitsumasa Kawago
Yoshimitsu Hirai
Miwako Miyasaka
Takuya Ohashi
Yoshiharu Nishimura
Quantitative Evaluation of Hormesis in Breast Cancer Using Histoculture Drug Response Assay
Dose-Response
title Quantitative Evaluation of Hormesis in Breast Cancer Using Histoculture Drug Response Assay
title_full Quantitative Evaluation of Hormesis in Breast Cancer Using Histoculture Drug Response Assay
title_fullStr Quantitative Evaluation of Hormesis in Breast Cancer Using Histoculture Drug Response Assay
title_full_unstemmed Quantitative Evaluation of Hormesis in Breast Cancer Using Histoculture Drug Response Assay
title_short Quantitative Evaluation of Hormesis in Breast Cancer Using Histoculture Drug Response Assay
title_sort quantitative evaluation of hormesis in breast cancer using histoculture drug response assay
url https://doi.org/10.1177/1559325819896183
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