mitopodozide and Lung-Neoplasms

Surfactant protein B (SP-B) is essential for the maintenance of biophysical properties and physiological function of pulmonary surfactant. Tumor necrosis factor-alpha (TNF-alpha), an important mediator of lung inflammation, inhibits surfactant phospholipid and surfactant protein synthesis in the lung. In the present study, we investigated the TNF-alpha inhibition of rabbit SP-B promoter activity in a human lung adenocarcinoma cell line (NCI-H441). Deletion experiments indicated that the TNF-alpha response elements are located within -236 bp of SP-B 5'-flanking DNA. The TNF-alpha response region contained binding sites for nuclear factor-kappa B (NF-kappa B), Sp1/Sp3, thyroid transcription factor (TTF)-1, and hepatocyte nuclear factor (HNF)-3 transcription factors. Inhibitors of NF-kappa B activation such as dexamethasone and N-tosyl-L-phenylalanine chloromethyl ketone and mutation of the NF-kappa B element did not reverse TNF-alpha inhibition of SP-B promoter, indicating that TNF-alpha inhibition of SP-B promoter activity occurs independently of NF-kappa B activation. TNF-alpha treatment decreased the binding activities of TTF-1 and HNF-3 elements without altering the nuclear levels of TTF-1 and HNF-3 alpha proteins. Pretreatment of cells with okadaic acid reversed TNF-alpha inhibition of SP-B promoter activity. Taken together these data indicated that in NCI-H441 cells 1) TNF-alpha inhibition of SP-B promoter activity may be caused by decreased binding activities of TTF-1 and HNF-3 elements, 2) the decreased binding activities of TTF-1 and HNF-3 alpha are not due to decreased nuclear levels of the proteins, and 3) okadaic acid-sensitive phosphatases may be involved in mediating TNF-alpha inhibition of SP-B promoter activity.

Topics: Adenocarcinoma; Animals; Cell Line; Cell Nucleus; Cytosol; DNA-Binding Proteins; Gene Expression Regulation; Hepatocyte Nuclear Factor 3-alpha; Humans; Lung Neoplasms; Mutagenesis, Site-Directed; NF-kappa B; Nuclear Proteins; Podophyllin; Podophyllotoxin; Promoter Regions, Genetic; Proteolipids; Pulmonary Surfactants; Rabbits; Thyroid Nuclear Factor 1; Transcription Factors; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Concentration of orosomucoid, pregnancy associated alpha 2-glycoprotein (alpha 2-PAG), Schwangerschaftsprotein 1 (SP1), placental specific-tissue protein 10 (PP10), placental specific-tissue protein 12 (PP12), alpha 1-Fetoprotein (AFP) were estimated in serum samples of 83 patients with lung cancer of stages II-IV. The proteins were determined by means of the single radial immunodiffusion, the rocket immunoelectrophoresis, the radioimmunoassay and the enzymeimmunoassay. Orosomucoid, PP12 and AFP serum concentrations of the cancer group compared with those of the control group, were increased significantly. Orosomucoid (control group: means = 0.828 g/l; s = 0.301; tumour group: mean = 2.16 g/l; s = 0.862); PP12 (control group: mean = 54.08 micrograms/l; s = 61.70; tumour group: mean = 122.52 micrograms/l; s = 131.16); AFP (control group: mean = 3.05 micrograms/l; s = 3.76; Tumour group: means = 8.29 micrograms/l; s = 17.75). alpha 2-PAG was found only in 37 cases of the tumour group; SP1 in 22 cases. PP10 (control group: mean = 2.25 micrograms/l; s = 0.866; tumour group: mean = 2.503 micrograms/l, s = 1.508). On condition that 2 tested parameters at least were estimated in the pathological range the sensitivity amounted to 0.64 and the specificity to 0.92.

Topics: Aged; alpha-Fetoproteins; Carcinoma, Bronchogenic; Female; Glycoproteins; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Proteins; Lung Neoplasms; Male; Middle Aged; Orosomucoid; Podophyllin; Podophyllotoxin; Pregnancy Proteins

Two patients with lung metastases are presented who were submitted to a combined low-dose radiotherapy and adriamycin monotherapy with good palliative results. The mode of action as well as the experimental examination results are discussed. The ineffectiveness of single low-dose chemotherapy is demonstrated by the non-response of lung metastases beyond the irradiation fields (heart block, diaphragm). Both patients were resistant to chemotherapy.

Topics: Adenocarcinoma; Aged; Carcinoma; Cobalt Radioisotopes; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Hysterectomy; Lung Neoplasms; Male; Methotrexate; Middle Aged; Podophyllin; Podophyllotoxin; Radioisotope Teletherapy; Uterine Neoplasms