Alexei Doudkine | PubMed Health

PubMed2003

In vitro model for studying malignancy associated changes.

Malignancy associated changes (MAC) can be defined as subtle morphological and physiologic changes that are found in ostensibly normal cells of patients harboring malignant disease. It has been postulated that MAC have a potential to become a useful tool in detection, diagnosis and prognosis of malignant diseases. An in vitro cell culture model system was designed to study interactions between non-small cell lung cancer (NSCLC) and the normal bronchial epithelium of the human respiratory tract in vivo to see if the MAC-like phenomenon can be detected in such a system. In this study we examined changes in nuclear features of normal human bronchial epithelial cells (NHBE) when they were co-cultured with cells derived from a lung cancer cell line NCI-H460. Using discriminant function analysis, nuclear features were determined which allow maximal discrimination between normal cells incubated with or without cancerous cells. Our results demonstrate that MAC appear to be specific to changes induced by malignancy, and that these changes differ from those induced by growth factors in the serum. This study provides evidence in support to the hypothesis that MAC are induced by a soluble factor(s) released by malignant cells. Colour figure can be viewed on http://www.esacp.org/acp/2003/25-2/sun.htm

Bronchi↗

PubMed2002

Increase of sensitivity of sputum cytology using high-resolution image cytometry: field study results.

Lung cancer remains the leading cause of cancer deaths in the developed world. There is no widely accepted method to screen for this cancer. The most commonly used method remains conventional sputum cytology, but this method is hampered by low sensitivity. We tested the hypothesis that sensitivity of sputum cytology for early lung cancer can be greatly improved by using image analysis of sputum cells, at a modest reduction of specificity. The study was double-blinded and used sputum samples from subjects with well-characterized clinical diagnoses. There were 177 cancers, 98 dysplasias, and 558 normals. The study samples were separated into two independent sets: training set and test set. Sputum samples were collected prospectively from subjects with a high probability of having lung cancer. Seven institutions from five countries participated in the study. All subjects had complete clinical diagnoses which included, as a minimum, negative chest x-rays for all negative cancers, while all cancers had confirmed tissue pathology. Samples were prepared according to the Saccomanno method. For conventional cytology, slides were stained using Papanicolaou stain. For image analysis, slides were stained using a DNA-specific (Feulgen-Thionin) stain. An automated, high-resolution image cytometer was used for measurements. At 90% specificity, sensitivity of 60% can be achieved for adenocarcinoma, compared to only 14% sensitivity of conventional cytology (at 99% specificity). Similarly, 45% sensitivity at 90% specificity can be reached for stages 0 and I lung cancer, compared to only 14% (at 99% specificity) using conventional cytology.Cytometry combined with conventional cytology shows an increase in sensitivity to early-stage cancer and to adenocarcinomas compared to conventional cytology alone. While the results are encouraging, the sensitivity to detect early lung cancer should be further improved to 70-80% at 90-95% specificity before this test can be considered for screening of high-risk individuals for lung cancer. Cytometry (Clin. Cytometry) 50:168-176, 2002.

Double-Blind Method↗