Increased staining for phospho-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies.

Background: The development of non-small cell lung carcinoma proceeds through a series of well-defined pathological steps before the appearance of invasive lung carcinoma. The molecular changes that correspond with pathology changes are not well defined and identification of the molecular events may provide clues on the progression of intraepithelial neoplasia in the lung, as well as suggest potential targets for chemoprevention. The acquisition of anti-apoptotic signals is critical for the survival of cancer cells but the pathways involved are incompletely characterized in developing intra-epithelial neoplasia (IEN).

Nuclear morphometry as a biomarker for bronchial intraepithelial neoplasia: correlation with genetic damage and cancer development.

Background: Bronchial carcinomas are preceded by epithelial morphologic changes. The variation in interpretation of these grades of intraepithelial neoplasia makes it difficult to determine its natural history and utility of histopathology as a surrogate endpoint biomarker. The objective of this study was to quantitate morphologic changes of intraepitherlial neoplasia and validate its utility through correlation with histopathology, allelic loss, and cancer development.

A randomized phase IIb trial of pulmicort turbuhaler (budesonide) in people with dysplasia of the bronchial epithelium.

Purpose: Preclinical studies suggest that inhaled budesonide may be an effective chemopreventive agent for lung cancer. We conducted a phase IIb study to determine the effects of inhaled budesonide in smokers with bronchial dysplasia.

Experimental Design: A total of 112 smokers with more than or equal to one site of bronchial dysplasia > 1.

Surrogate end-point biomarker analysis in a retinol chemoprevention trial in current and former smokers with bronchial dysplasia.

Epidemiological studies suggested that vitamin A may be protective against lung cancer, however, recent chemoprevention trials with beta-carotene, a precursor of vitamin A, demonstrated enhancement of lung carcinogenesis among smokers. Whether vitamin A is beneficial or harmful in chemoprevention of lung cancer in smokers has not been resolved. This study was designed to determine the effect of retinol alone in current and former smokers using bronchial dysplasia, nuclear morphometry and retinoic acid receptor-beta (RAR-beta) mRNA expression as surrogate end-point biomarkers (SEBs).

Key issues in lung cancer chemoprevention trials of new agents.

Lung cancer is a major health problem world-wide. Former heavy smokers retain a significant risk for lung cancer after smoking cessation. With a large population of current and former smokers at risk, an alternative cancer control strategy such as chemoprevention needs to be developed to reduce lung cancer mortality especially for smokers who have followed medical advice to give up smoking.

Lung cancer screening: a different paradigm.

Thoracic computed tomography (CT) is a sensitive method for detecting early lung cancer but has a high false-positive rate and is not sensitive for detecting central preinvasive and microinvasive cancer. Our hypothesis was that automated quantitative image cytometry (AQC) of sputum cells as the first screening method may improve detection rate by identifying individuals at highest risk for lung cancer. A total of 561 volunteer current or former smokers 50 years of age or older, with a smoking history of more than or equal to 30 pack/years, were studied.

A randomized phase IIb trial of anethole dithiolethione in smokers with bronchial dysplasia.

Background: Results from preclinical studies have suggested that the organosulfur compound anethole dithiolethione (ADT) may be an effective chemopreventive agent for lung cancer. We conducted a phase IIb study to determine the effects of ADT in smokers with bronchial dysplasia.

Methods: One hundred twelve current and former smokers with a smoking history of at least 30 pack-years and at least one site of bronchial dysplasia identified by an autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive placebo or ADT at 25 mg orally thrice daily for 6 months.