Abstract

Cytological examination is widely used as a diagnostic tool because of the ease of collecting cells from the involved area. However, the diagnostic yield of cytological examination is unsatisfactory; the reasons include sampling error, poorly prepared samples, small numbers of malignant cells, and low grades of cellular atypia. In this study, we focused on the high infectivity of adenovirus towards epithelial cells and applied the luciferase- expressing adenoviral vector to a new cancer cell detection tool. In addition, adenoviral infectivity was enhanced by modifying viral fiber proteins. The sensitivity of the diagnostic tool was tested using the NCI-H1299 lung cancer cell line, and validated in body fluid samples from cancer patients with a variety of etiology. Results showed that the adenovirus efficiently transfected NCI-H1299 with high sensitivity. Only 10 cancer cells were sufficient for detection of luciferase signals. In body fluid samples, the adenovirus confirmed the diagnosis for malignant and benign cancer, but not in non-epithelial cell derived samples. This study provides proof-of-concept for a more reliable and sensitive diagnostic tool for epithelium-derived cancer.

Highlights

  • The diagnosis of malignant disease is made by cytological or histological examination of clinical samples obtained from patients

  • We focused on the high infectivity of adenovirus towards epithelial cells and applied the luciferaseexpressing adenoviral vector to a new cancer cell detection tool

  • Histological examination requires a certain amount of tissue, and using an invasive procedure to obtain this type of sample is inevitable

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Summary

Introduction

The diagnosis of malignant disease is made by cytological or histological examination of clinical samples obtained from patients. Cytological examination only requires small clinical samples collected by non-invasive techniques, including body fluids, lavage of targeted area, and needle aspiration of lymph nodes This approach is commonly used in the case of poorly conditioned patients unable to tolerate invasive procedures. Additional immunostaining or other specific staining improves the diagnostic yield to some extent, though the promptness of diagnosis is adversely impaired (Kuenen-Boumeester et al, 1996 ; Porcel et al, 2004; Lee and Chang, 2005; Shitrit et al, 2005; Westfall et al, 2010 ; Su et al, 2011) Methods such as fluorescence in situ hybridization analysis, image analysis cytometry, and PCR, are more sensitive than standard cytologic studies (Fieglure, 2005; Holloway et al, 2006; Sriram et al, 2011). We focused on effective gene transduction into cancer cells by an adenoviral vector and conceived of

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