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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spike electrogenesis, local depolarizing and hyperpolarizing responses, spontaneous rhythmic firing, and alternating resting potentials were measured in cells from a continuously cultured small cell carcinoma of the lung. Spike generation was blocked by MnCl2. In view of this evidence for calcium-spike electrogenesis and previous evidence of secretory activity in these cells, this cell line (DMS 53) can provide a model for the study of excitation-secretion behavior in human neoplastic cells.
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PMID:Calcium spike electrogenesis and other electrical activity in continuously cultured small cell carcinoma of the lung. 626 14

The bronchial Kulchitsky cells are scattered specific cells which lie close to the basement membrane of the bronchi and bronchioles. Electron microscopy reveals that they contain electron-dense granules similar to that seen in cells with a known endocrine function. In addition, experimentally induced degranulation of the K cell suggestive of a secretory process, and the likelihood that these cells are precursors of small cell lung carcinoma (which often elaborates humoral substances) has led to the postulate that this bronchial cell serves a humoral role of either a paracrine or endocrine nature. We have found that the bronchial K cell of man contains a calcitonin-like polypeptide which, immunologically and chemically, is not dissimilar to the hormone produced by the C cells of human thyroid. This finding may help explain the persistence of serum immunoreactive calcitonin (iCT) after total thyroidectomy, the fact that thyroidectomized man does not manifest any profound alteration of calcium metabolism, and why small cell cancer of the lung is frequently associated with hypercalcitonemia. In addition, the finding of K cell hyperplasia in chronic bronchitis and emphysema may explain the occurrence of hypercalcitonemia in patients with these diseases and some lung cancers of cell types other than the small cell variety. Further studies are needed to elucidate the role of K cell iCT, and to determine what other hormones might also be elaborated by this diffuse system of bronchial cells.
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PMID:Hypothesis: the bronchial Kulchitsky (K) cell as a source of humoral biologic activity. 627 May 16

Seventeen patients with small cell carcinoma of the lung (SCCL) refractory to at least one combination chemotherapy regimen were treated with a high-dose methotrexate (HDMTX) program consisting of 1500 mg/m2 of MTX by iv infusion at a constant rate over 30 hrs following a priming dose of 50 mg/m2 of MTX iv. Administration of calcium leucovorin was begun at the end of the infusion. Treatment was repeated every 2 weeks. No complete or partial responses were observed, and the median time to tumor progression was 4 weeks. Hematologic toxicity was much more severe than anticipated, with five patients having thrombocytopenic bleeding requiring platelet transfusions. This HDMTX regimen was both ineffective and unexpectedly toxic in our heavily pretreated patients with SCCL. Literature review discloses little evidence that HDMTX programs have superior activity to standard doses of MTX in this disease.
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PMID:Lack of efficacy of high-dose methotrexate by 30-hour infusion in patients with progressive small cell carcinoma of the lung. 628 53

Although small cell carcinoma of the lung has a high incidence of skeletal metastasis and is frequently associated with paraneoplastic syndromes, it is only rarely associated with hypercalcemia. Similarly, the more unusual small cell carcinoma of the pancreas has not been associated with hypercalcemia. The authors describe the first such patient with small cell carcinoma of the pancreas and hypercalcemia. Comprehensive metabolic measurements (fasting calcium excretion, renal phosphorus threshold, 1,25 dihydroxyvitamin D, 25 hydroxyvitamin D levels, nephrogenous cyclic AMP and immunoreactive PTH levels) suggest that although bone metastases were present, the hypercalcemia may have been caused in part by humoral mechanisms.
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PMID:Hypercalcemia in small cell carcinoma of the pancreas. 632 Oct 9

We have established a model for malignancy-associated humoral hypercalcemia (MAHH) in athymic mice, utilizing a human squamous cell lung carcinoma. In the present studies, we evaluated cis-platinum (DDP), a cytotoxic agent known to produce hypomagnesemia, and occasionally hypocalcemia, in the treatment of MAHH. Upon development of significant hypercalcemia, defined as serum calcium (Ca) greater than or equal to 11.5 mg/dl, tumor-bearing mice received either normal saline (NS) alone (1.5 ml/day, i.p.), or NS + DDP. The DDP was given as a single dose of 6 micrograms/g body weight i.p. Serum Ca was determined on day 6 in surviving mice (6 of 10 survived in the NS-alone group; 7 of 10 survived in the NS + DDP group). Serum Ca (mean +/- SE) decreased from 14.3 +/- 0.46 to a nadir of 12.7 +/- 0.33 mg/dl in the NS-alone group, and from 13.5 +/- 0.46 to a nadir of 10.4 +/- 0.48 mg/dl in the NS + DDP group. Nadir serum Ca levels were significantly lower in the NS + DDP group (P = 0.003). Three of 7 surviving NS + DDP mice achieved normocalcemia, whereas none of the NS-alone animals became normocalcemic. Tumor volumes increased in all animals. There was no change in the serum Ca in 5 tumor-free mice treated with NS + DDP. There were no significant differences in serum magnesium levels among groups of control mice, tumor-free mice treated with NS + DDP, tumor-bearing mice treated with NS + DDP, and tumor-bearing mice treated with NS-alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cis-platinum treatment for malignancy-associated humoral hypercalcemia in an athymic mouse model. 644 29

Recently we reported a low calcium (110 microM) serum-free medium (LHC-1) for clonal growth of normal human bronchial epithelial (NHBE) cells. NHBE cells within colonies are small (mean surface area = 1,250 mu2) rarely migratory, have few tonofilaments, and multiply with an average population doubling time of 28 h. We have also noted that adding small amounts of blood-derived serum to LHC-1 medium (as little as 2%) significantly decreased the clonal growth rate. We have now found that the growth inhibiting effect of serum is due to the induction of squamous (terminal) differentiation. Serum quickly increases the size of the cells (mean surface area = 4,900 mu2). In addition, the cells acquire numerous desmosomal junctions and an extensive network of keratin bundles. In contrast, human lung carcinoma cells multiply rapidly at clonal density in LHC-1 medium containing as much as 8% serum. Although high concentrations of calcium ions in the medium are known to induce squamous differentiation of epidermal keratinocytes in the absence of serum, high levels of Ca2+ (up to 1,000 microM) increased the number of desmosomal junctions, but did not significantly affect the clonal growth rate or size of the NHBE cells. However, high concentrations of calcium (above 450 microM) were found to potentiate serum differentiation-inducing activity. On the other hand, cholera toxin (10 ng/ml) inhibited the differentiation-inducing activity of serum. These results show that squamous differentiation of NHBE cells can be induced by serum and the potency of these serum factors can be modulated. In addition, the data show that lung carcinoma cells differ from their normal counterparts by not undergoing differentiation in the presence of serum.
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PMID:Induction of squamous differentiation of normal human bronchial epithelial cells by small amounts of serum. 669 33

Cultured cell lines LL, B16, C26, and C38 established from mouse solid tumors of Lewis lung carcinoma, B16 melanoma, and colon adenocarcinomas 26 and 38, respectively, showed inherently different resistance to vincristine (VCR) in vitro. The inherent resistance to VCR of these cell lines was related to the ability of the cells to accumulate VCR. Verapamil, a calcium antagonist with coronary vasodilator activity, enhanced the cytotoxicity of VCR against these cell lines depending upon their susceptibility to VCR. C26 cells, the most resistant, became the most susceptible to VCR with a nontoxic dose of verapamil. A 12-fold increase in VCR cytotoxicity occurred. Only a 2.5-fold increase in VCR cytotoxicity was observed for B16 cells, the most sensitive cells. VCR cytotoxicity against each cell line reached almost the same level by verapamil (2.2 to 6.6 microM). Thus, the inherent resistance to VCR among the tumor lines was circumvented. Verapamil enhanced the cellular accumulation of VCR. A 3- to 4-fold increase in cellular VCR occurred in C26 cells, while approximately a 2-fold increase was observed for B16 and LL cells. A similar rate of enhancement was observed for both bound and free VCR, indicating that verapamil does not enhance the affinity of VCR to tubulin. Verapamil inhibited the outward transport of VCR from the cells. The most prominent inhibition was observed for C26 cells. Circumvention of inherent resistance of tumor cells to VCR by verapamil could be attained through an enhanced cellular accumulation of VCR in each of the tumor cells. The enhancement of VCR cytotoxicity and circumvention of inherent VCR resistance by verapamil could be explained by the cellular concentration of VCR, and also it might be related to the extent of VCR binding to tubulin in the cell. The chemotherapeutic effect of VCR is significantly enhanced by verapamil in colon adenocarcinoma 26-bearing mice.
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PMID:Promotion by verapamil of vincristine responsiveness in tumor cell lines inherently resistant to the drug. 684 94

A human epithelial cell line, WISH, and a mouse cell line, LB6-uPAR, transfected with the human urokinase receptor (uPAR), both expressed high affinity uPAR but undetectable levels of urokinase (uPA). In two independent assays, binding of exogenous pro-uPA produced an up to threefold enhancement of migration. The migration was time and concentration dependent and did not involve extracellular proteolysis. This biologic response suggested that uPAR can trigger an intracellular signal. Since this receptor is a glycosyl-phosphatidylinositol-linked protein, we postulated that it must do so by interacting with other proteins, among which, by analogy to other systems, would be a kinase. To test this hypothesis, we carried out a solid phase capture of uPAR from WISH cell lysates using either antibodies against uPAR or pro-uPA adsorbed to plastic wells, followed by in vitro phosphorylation of the immobilized proteins. SDS-PAGE and autoradiography revealed two phosphorylated protein bands of 47 and 55 kD. Both proteins were phosphorylated on serine residues. Partial sequence of the two proteins showed a 100% homology to cytokeratin 18 (CK18) and 8 (CK8), respectively. A similar pattern of phosphorylation was obtained with lysates from A459 cells, a lung carcinoma, but not HL60, LB6-uPAR or HEp3 cell lysates, suggesting that the identified multiprotein uPAR-complex may be specific for simple epithelia. Moreover, immunocapture with antibody to another glycosyl-phosphatidylinositol-linked protein, CD55, which is highly expressed in WISH cells, was ineffective. The kinase was tentatively identified as protein kinase C, because it was inhibited by an analogue of staurosporine more specific for PKC and not by a PKA or tyrosine kinase inhibitors. The kinase was tentatively identified as PKC epsilon because of its resistance to PMA down-modulation, independence of Ca2+ for activity, and reaction with a specific anti-PKC epsilon antibody in Western blots. Cell fractionation into cytosolic and particulate fractions revealed that all four proteins, the kinase, uPAR, CK18, and CK8, were present in the particulate fraction. In vivo, CK8, and to a lesser degree CK18, were found to be phosphorylated on serine residues. Occupation of uPAR elicited a time-dependent increase in the phosphorylation intensity of CK8, a cell shape change and a redistribution of the cytokeratin filaments. These results strongly suggest that uPAR serves not only as an anchor for uPA but participates in a signal transduction pathway resulting in a pronounced biological response.
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PMID:Induction of cell migration by pro-urokinase binding to its receptor: possible mechanism for signal transduction in human epithelial cells. 751 43

The 30-residue human neuropeptide, galanin, was shown to bind to rat insulinoma RINm5F cells and to inhibit glyceraldehyde-stimulated insulin secretion from these cells in a manner quantitatively similar to that of porcine galanin. Neither human nor porcine galanin stimulated Ca2+ mobilization in cultured human small cell lung carcinoma cells. Sedimentation equilibrium analysis of human galanin showed that it was strictly monomeric in aqueous solution, indicating that the peptide interacts with its receptor(s) as a monomer. The monomeric nature of the peptide makes it especially suitable for structural studies using NMR. Nuclear Overhauser enhancement spectroscopy experiments performed on galanin dissolved in aqueous solution (150 mM KCl, pH 4) at both 33 and 3 degrees C indicate that certain regions of the peptide are capable of adopting detectable levels of short-range structure in rapid equilibrium with random coil. At 33 degrees C, the short-range structures include a nascent helix spanning residues 3-11 which incorporates a hydrophobic core from residues 6-11. Residues 14-18 and 22-30 display sequential NH-NH and C beta H-NH connectivities, indicating that these regions of the peptide adopt nonrandom conformations by significantly populating the alpha-region of conformational space. However, no medium-range dipolar connectivities indicative of nascent helix or turn conformations were observed. At 3 degrees C, almost all residues significantly populate the alpha-region of conformational space, and the nascent helix between residues 3 and 11, with its hydrophobic core, is retained.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structural and biochemical studies of human galanin: NMR evidence for nascent helical structures in aqueous solution. 753 69

P-type channels, a recently described form of voltage-gated calcium channels, are found in many central and peripheral neurons. In the present study, a partial cDNA clone sharing extensive nucleotide identity with a putative P-type voltage-gated calcium channel alpha 1 subunit was isolated from a small-cell lung carcinoma (SCLC) cell line. Anti-peptide antibodies generated to a unique acidic stretch in the IVS5-S6 linker region of the putative SCLC P-type channel reacted specifically with a SCLC fusion protein produced in bacteria and with a cell surface molecule in SCLC cells. Calcium currents in SCLC cells, measured by whole-cell patch clamp, were inhibited by these antibodies and by the P-type channel-specific toxin omega-agatoxin IVA. The inhibitory effects of the antibody and the toxin were not additive, consistent with their proposed action on the same type of channel. These results provide evidence for the expression of P-type calcium channels by SCLC cells. The expression of neuron-related molecules by these cells is of particular interest because small-cell lung carcinoma is frequently associated with paraneoplastic disorders affecting the nervous system.
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PMID:Expression and antibody inhibition of P-type calcium channels in human small-cell lung carcinoma cells. 782 33


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