Electrochemotherapy of radioresistant head and neck squamous cell carcinoma cells and tumor xenografts.
Oncol Rep
; 41(3): 1658-1668, 2019 Mar.
Article
em En
| MEDLINE
| ID: mdl-30628709
ABSTRACT
Electrochemotherapy is an established local ablative method used for the treatment of different tumor types, including tumors of the head and neck area. Clinical studies have demonstrated a lower response rate of tumors that recur in preirradiated area. The aim of the present study was to explore the response of experimentally induced radioresistant cells and tumors to electrochemotherapy with cisplatin or bleomycin. The radioresistant cells (FaDuRR) were established by fractionated irradiation of parental human squamous cell carcinoma cell line, FaDu. We compared the 2 cell lines in response to chemotherapy and electrochemotherapy with cisplatin or bleomycin in vitro and in vivo. Using specific mass spectrometrybased analytical methods we determined the difference in the uptake of chemotherapeutics in tumors after electrochemotherapy. Additionally, we compared the capacity of the cells to repair DNA doublestrand breaks (DSB) after exposure to the drugs used in electrochemotherapy with the γH2AX foci resolution determined by immunofluorescence microscopy. Our results indicate radio and cisplatin crossresistance, confirmed with the lower response rate of radioresistant tumors after electrochemotherapy with cisplatin. On the other hand, the sensitivity to electrochemotherapy with bleomycin was similar in both cell lines and tumors. While the uptake of chemotherapeutics after electrochemotherapy was comparable in both tumor models, there was a difference between the cell lines in capacity to repair DNA DSBthe radioresistant cells had a lower level of DSB and faster DNA repair rate after exposure to both, cisplatin or bleomycin. Due to the higher complete response rate after electrochemotherapy with bleomycin than with cisplatin, we conclude that the results favor bleomycinover cisplatinbased electrochemotherapy for treatment of radioresistant tumors and/or tumors that regrow after radiotherapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Eletroquimioterapia
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Carcinoma de Células Escamosas de Cabeça e Pescoço
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Neoplasias de Cabeça e Pescoço
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Recidiva Local de Neoplasia
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Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article