Early lung cancer detection project: Evaluation of 5, 10, 15, 20 tetrakis (4-carboxyphenyl) porphine (H(sub 2)TCPP). Final report

摘要

The author evaluated a synthetic porphyrin, 5, 10, 15, 20 tetrakis (4- carboxyphenyl) porphene (H(sub 2)TCPP) as a marker of carcinogenesis. H(sub 2) TCPP was compared with two other carcinogenesis markers evaluated in the laboratory for their ability to detect exfoliated sputum cells undergoing transformation to lung cancer. In the present project the authors first established optimal conditions for cultured neoplastic and non-neoplastic (sputum) cells to take up H(sub 2)TCPP. This was accomplished using spectrofluorimetry and video-enhanced fluorescent microscopy to maximize H(sub 2)TCPP auto-fluorescence across a matrix of substrate conditions, including; reagent concentration, incubation time, temperature, and pH. The second aim was to validate H(sub 2)TCPP on clinical material obtained from subjects monitored in advance of clinical cancer and link those marker results with subsequent histologic confirmation of disease. This was accomplished by applying H(sub 2) TCPP to sputum specimens archived by the Frost Center at Johns Hopkins which maintains a record of the clinical course and long-term follow-up for the patients from whom the specimens were obtained. The authors have used fluorescent immunostaining and flow cytometry to compare uptake of these cytoplasmic Mabs to that of a potential new marker of carcinogenesis, 5, 10, 15, 20 tetrakis (4 carboxyphenyl) porphene (H(sub 2)TCPP). The nuclear uptake of H(sub 2)TCPP was compared to a standard quantitative fluorescent DNA marker (7- AAD).