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Enhancement of Aerosol Cisplatin Chemotherapy with Gene Therapy Expressing ABC10 protein in Respiratory System.

Journal of Cancer (2014-04-12)
Wolfgang Hohenforst-Schmidt, Paul Zarogoulidis, Bernd Linsmeier, Ioannis Kioumis, Qiang Li, Haidong Huang, Despoina Sachpatzidou, Sofia Lampaki, John Organtzis, Kalliopi Domvri, Leonidas Sakkas, George A Zachariadis, Konstantinos N Archontas, Anastasios Kallianos, Aggeliki Rapti, Lonny Yarmus, Konstantinos Zarogoulidis, Johannes Brachmann
ABSTRACT

Inhaled therapy for lung cancer is a local form of treatment. Currently inhaled non-specific cytotoxic agents have been evaluated as a future treatment for local disease control and distant metastasis control. There are few information regarding the influence of local transporters and gene expression of the respiratory epithelium to the absorption of administered drugs. In the current work we used adenoviral-type 5(dE1/E3) (Cytomegalovirus promoter) with human ABCA10 transgene (Ad-h-ABCA10) purchased from Vector Labs(®) in order to investigate whether gene therapy can be used as a pre-treatment to enhance the efficiency of inhaled cisplatin. We included the following groups to our work: a) control, b) aerosol vector, c) aerosol vector plus cisplatin, d) aerosol cisplatin, e) intratumoral cisplatin administration, f) intratumoral vector plus cisplatin administration. The results indicate that the aerosol cisplatin group had a long term survival with the intratumoral cisplatin group following. The enhancement of the ABCA family locally to the respiratory system prior to the aerosol cisplatin administration can be used safely and efficiently. Future treatment design of local therapies should include the investigation of local transporters and genes.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
cis-Diammineplatinum(II) dichloride, crystalline
Sigma-Aldrich
trans-Platinum(II)diammine dichloride
Cisplatin, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
cis-Diamineplatinum(II) dichloride, ≥99.9% trace metals basis
Cisplatin impurity A, European Pharmacopoeia (EP) Reference Standard
USP
Transplatin, United States Pharmacopeia (USP) Reference Standard