calcitonin and Lung-Neoplasms

An in vitro cultured monolayer system of alveolar epithelial cells was used as a model to investigate the transport pathway peptides or proteins, salmon calcitonin (sCT), insulin (INS), recombinant hirudin (rHAV2), and recombinant human growth hormone (rhGH), in pulmonary epithelium in vivo.. Human lung adenocarcinoma A549 cells formed continuous monolayers with growing polycarbonate filters of Transwell plate. Transport studies of macromolecules in the monolayer system were carried out after 6 days in culture. The transport of peptides or proteins with MW 3,400 - 22,000 was studied in cultured human lung adenocarcinoma A549 cell monolayers at different conditions.. The results showed that the apparent permeability coefficients (Papp) of these macromolecules across A549 cell monolayers ranged from 2 x 10(-6) to 5 x 10(-6) cm x s(-1) and exhibited good inverse correlation with molecule weight. No concentration, direction and temperature dependence were observed in the permeation of sCT, INS and rHAV2. While the Papp of rhGH in the BA direction (2.25 x 10(-6) cm x s(-1)) was significantly less than that in the reverse direction. The Papp values of rhGH were concentration and temperature independent in the AB direction.. These findings suggest that the hydrophilic peptides and proteins, salmon calcitonin, insulin, recombinant hirudin, and recombinant human growth hormone used in this study, appeared to penetrate the A549 cell monolayers via a paracellular pathway by passive diffusion mechanism.

Topics: Adenocarcinoma; Biological Transport; Calcitonin; Cell Line, Tumor; Epithelial Cells; Hirudins; Human Growth Hormone; Humans; Insulin; Lung Neoplasms; Peptides; Permeability; Proteins; Pulmonary Alveoli

Transcriptional regulation of the human parathyroid hormone-related protein (PTHrP) gene by calcitonin was examined in a lung cancer line (BEN cells). Northern analysis demonstrated that calcitonin caused a rapid 4.5-fold elevation in PTHrP mRNA. Transient transfection of a construct containing 1119 base pairs of the human PTHrP gene 5' to the ATG start site of translation, fused to the CAT reporter sequence, was used to demonstrate a five-fold increase in transcription by calcitonin. Similar increases were also observed when transfected cells were exposed to a number of cAMP agonists including forskolin, as well as isobutyl-methylxanthine. A putative cAMP responsive element (5'-TGACTTCA-3') present within exon 4 was placed upstream of the heterologous SV40 promoter. Expression of this construct was elevated 4.5-fold in response to calcitonin and 7-fold in response to forskolin. Similar responses to calcitonin occurred with a smaller construct (pZMR30) containing 530 bp of sequence upstream of the ATG start site. Thus we postulate that calcitonin acts at least partially via cAMP through this element in exon 4 of the human PTHrP gene.

Topics: 1-Methyl-3-isobutylxanthine; Base Sequence; Bucladesine; Calcitonin; Colforsin; Cyclic AMP; Gene Expression Regulation, Neoplastic; Humans; Ionomycin; Lung Neoplasms; Molecular Sequence Data; Neoplasm Proteins; Parathyroid Hormone-Related Protein; Protein Biosynthesis; Proteins; Recombinant Fusion Proteins; Regulatory Sequences, Nucleic Acid; RNA, Messenger; RNA, Neoplasm; Second Messenger Systems; Transcription, Genetic; Tumor Cells, Cultured

Serum bone Gla protein (BGP) and alkaline phosphatase (AP) activity were compared for the assessment of skeletal status in 11 normal pregnant women, 12 normal women on days 3 and 13 of the menstrual cycle, five postmenopausal women before and after 1 month of treatment with ethinyl estradiol (20 micrograms/day), five patients with cancer and hypercalcemia during treatment with calcitonin, and one patient with Paget disease during treatment with Plicamycin. BGP and AP correlated with each other only in the pregnant women. In all other circumstances, there was no correlation between these two serum osteoblast products. Furthermore, there were conditions in which the two measurements became discordant. These studies demonstrate that BGP and AP commonly are dissociated when used as measurements of skeletal status. Although both are osteoblast products, BGP and AP probably reflect different aspects of osteoblast differentiation and function.

Topics: Adult; Alkaline Phosphatase; Calcitonin; Carcinoma, Squamous Cell; Ethinyl Estradiol; Female; Humans; Hypercalcemia; Lung Neoplasms; Middle Aged; Multiple Myeloma; Osteocalcin; Postmenopause; Pregnancy

Topics: Biomarkers, Tumor; Calcitonin; Carcinoma, Bronchogenic; Humans; Lung Neoplasms; Predictive Value of Tests; Reference Values

The analgesic effect of salmon calcitonin (Calcitonina-Sandoz) was evaluated in an open study of thirty-four patients with bone metastases of a lung cancer. Two different administration protocols were used: eighteen subjects received sCT 400 IU/day for three consecutive days, while the remaining sixteen were given sCT 200 IU/day for six consecutive days. In both protocols salmon calcitonin was diluted in saline and infused intravenously in one hour. Bone, visceral and neuritic pain were evaluated by means of Huskisson's visual analog scale and Keele's pain scale. The analgesic efficacy of salmon calcitonin was also evaluated on the basis of daily consumption of analgesic drugs. Salmon calcitonin proved of extreme efficacy in the treatment of intractable pain from advanced malignancy. A higher and earlier analgesic activity was observed with sCT at the 400 IU daily dosage.

Topics: Bone Neoplasms; Calcitonin; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pain, Intractable

Topics: Calcitonin; Carcinoma, Small Cell; Cell Line; Humans; Lung Neoplasms