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J Cancer 2014; 5(5):344-350. doi:10.7150/jca.9021

Research Paper

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

Wolfgang Hohenforst-Schmidt¹, Paul Zarogoulidis^2✉, Bernd Linsmeier³, Ioannis Kioumis², Qiang Li⁴, Haidong Huang⁴, Despoina Sachpatzidou⁵, Sofia Lampaki², John Organtzis², Kalliopi Domvri², Leonidas Sakkas⁶, George A. Zachariadis⁷, Konstantinos N. Archontas⁷, Anastasios Kallianos⁸, Aggeliki Rapti⁸, Lonny Yarmus⁹, Konstantinos Zarogoulidis², Johannes Brachmann¹

1. II Medical Department, ``Coburg`` Regional Clinic, University of Wuerzburg, Coburg, Germany
2. Pulmonary Department-Oncology Unit, ``G. Papanikolaou`` General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
3. Department of Thoracic Surgery, Medinos Clinic Sonneberg, Sonneberg, Germany
4. Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, China
5. Experimental Animal Laboratory, ``Theiagenio`` Anticancer Hospital, Thessaloniki, Greece
6. Pathology Department, ``G. Papanikolaou`` General Hospital, Thessaloniki, Greece
7. Laboratory of Analytical Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece
8. Pulmonary Department, ``Sotiria`` Hospital of Chest Diseases, Athens, Greece
9. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, U.S.A.

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.

Keywords: ATP, ABC10, lung cancer, gene therapy, chemotherapy, aerosol.