bromochloroacetic-acid and Radiation-Pneumonitis

Cytokeratin 19 fragment (CYFRA 21-1) level in serum have already been documented as a useful tumor marker for lung cancer. In the present study, we hypothesized that CYFRA 21-1 increases in the sera of patients with radiation pneumonitis, resulting from epithelial cell damage. We measured CYFRA 21-1 in the sera of patients with radiation pneumonitis and evaluated the correlation between CYFRA 21-1 level and severity of radiation pneumonitis as well as clinical course. We studied 16 patients diagnosed with radiation pneumonitis associated with primary lung cancer. CYFRA 21-1 levels in the sera of patients with diffuse radiation pneumonitis (n = 6) significantly increased compared to normal smokers (n = 10) or patients with local radiation pneumonitis (n = 10). CYFRA 21-1 values in sera changed according to the progression or improvement of the diffuse radiation pneumonitis. An immunohistochemical study using pulmonary tissues obtained from autopsied patients with radiation pneumonitis demonstrated that the hyaline membrane and proliferating type II pneumocytes were strongly stained by the anti-human cytokeratin 19 antibody. Our data demonstrated that CYFRA 21-1 was increased in patients with diffuse radiation pneumonitis. Since CYFRA 21-1 is widely used as a tumor marker for lung cancer, this evidence should be noted especially in irradiated patients.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Radiation Pneumonitis; Treatment Outcome

We studied the relationship between type II pneumocytes number and alveolar septal thickness during different time after sublethal whole-thorax irradiation of rats and we investigated the influence of pentoxifylline (TNF-alpha inhibitor).. Wistar rats were exposed to 15 Gy thoracic irradiation and pentoxifylline (35 mg/kg) twice a week. Lungs were examined histologically and immunohistochemically at intervals ranging from 1-12 weeks and alveolar septal thickness, number of type II pneumocytes (identified by immunoreactivity for cytokeratin 18), and neutrophile granulocytes were counted.. Significant increase of alveolar septal thickness and type II pneumocytes depletion 3 weeks after irradiation were found. Correlation of these markers was r = -0.759. Pentoxifylline significantly inhibits increased alveolar septal thickness without the influence on type II pneumocytes number. Neutrophil penetration started 5 weeks after irradiation in non-treated animals, 8 weeks after irradiation in PTX-treated rats.. We suggest that pneumocytes depletion is linked to increased vascular permeability, and pentoxifylline therapy does not influence on pneumocytes kinetics after irradiation.

Topics: Animals; Immunohistochemistry; Keratins; Lung; Male; Pentoxifylline; Pulmonary Alveoli; Radiation Pneumonitis; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Vasodilator Agents

Two cases of bilateral radiation pneumonitis associated with unilateral thoracic irradiation against lung cancer are described. Both patients died of respiratory failure and autopsy was performed. Histologically, bilateral diffuse alveolar damage was demonstrated in both cases, associated with marked organization of hyaline membrane in one case (case 1). In addition, numerous hyperplastic type II pneumocytes which strongly expressed cytokeratins 8, 18 and 19 were observed. In both patients' sera, antibodies against cytokeratin 8, 18 and 19 were demonstrated by a Western immunoblot. The possible association between autoantibodies to cytokeratins and diffuse alveolar damage observed in patients with bilateral radiation pneumonitis are discussed.

Topics: Adenocarcinoma; Aged; Autoantibodies; Blotting, Western; Fatal Outcome; Humans; Keratins; Lung Neoplasms; Male; Pulmonary Alveoli; Radiation Pneumonitis; Sarcoma, Small Cell

The degree of immunoreactive connexin43 (C x 43) in rat lung was evaluated during the development of radiation-induced pulmonary fibrosis in rat by a double immunofluorescence technique using polyclonal antisera to Cx43 and monoclonal antibodies to cytokeratins on cryostat sections. In normal rat lungs, Cx43 was detected in pneumocytes type II and I, in large blood vessel endothelia, in peribronchial smooth muscle cells, and in some peribronchial and perivascular interstitial cells. As early as 1 week after irradiation, enhanced immunoreactivity for Cx43 in the epithelial cells was detected. In severely injured lungs (about 3 months after irradiation), Cx43 was found also in the cytoplasm of type II pneumocytes. These findings were confirmed by western blot data. Western blot analysis also revealed increased phosphorylation of Cx43. It remains to be investigated whether the increased content of Cx43 in irradiated rat lung may be due to an enhanced number of gap junctions between type I and II alveolar epithelial cells.

Topics: Actins; Animals; Blotting, Western; Connexin 43; Epithelium; Fluorescent Antibody Technique, Indirect; Keratins; Lung; Pulmonary Alveoli; Radiation Pneumonitis; Rats; Rats, Inbred F344; Up-Regulation