Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many factors, such as interleukin 1, TGF alpha, tumor necrosis factor alpha and beta, and PGs, have been implicated in etiological roles in HHM (Martin and Mundy, 1987). Much interest in the past has also centered upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and were found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the NH2 terminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support of this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have a similar intron--exon organization as the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have enabled detailed structure-function studies that have identified NH 2-terminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in a subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP have added to our understanding of the mechanisms of hypercalcemia and may contribute to the understanding of other metabolic bone diseases, such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in normal cell physiology.
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PMID:Parathyroid hormone-related protein: isolation, molecular cloning, and mechanism of action. 268 46

Studies of humoral hypercalcemia of malignancy (HHM) have provided evidence that tumors produce a protein that acts through the parathyroid (PTH) receptor but is immunologically distinct from PTH. We have recently purified and cloned a parathyroid hormone-related protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino-terminal residues are identical with human PTH, although antisera directed to the amino-terminus of PTHrP do not recognize PTH. The striking homology with PTH about the amino-terminal region is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone. A 34-amino acid synthetic peptide, PTHrP(1-34) was 2-4 times more potent than bovine or human PTH(1-34) in bioassays promoting the formation of cAMP and plasminogen activity in osteogenic sarcoma cells and activation of adenylate cyclase in chick kidney membranes. Like PTH, PTHrP peptides of less than 30 residues from the amino-terminus showed substantially reduced activity. PTHrP(1-34) was also more potent than hPTH(1-34) in stimulating cAMP and phosphate excretion and reducing calcium excretion in the isolated perfused rat kidney. Immunohistochemical localization of PTHrP was consistently demonstrated in squamous cell carcinomas. In normal tissues PTHrP has been immunohistochemically localized in keratinocytes and PTHrP-like activity has been extracted from ovine placenta and fetal ovine parathyroids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Humoral hypercalcemia of malignancy. 269 18

Copper, zinc, magnesium, calcium and iron were measured in serum and lung tissue - tumor mass and histologically nonneoplastic tissue - from lung cancer patients and compared with serum concentrations in healthy subjects and control lung tissue obtained from patients with nonmalignant lung disease. Lung cancer patients showed a significant increase in serum Cu and Cu/Zn ratio levels and decrease in serum Zn and Fe concentrations. These findings were correlated with TNM stage of the disease, but not with histologic type of tumor. Malignant lung tissue showed a higher level of Cu, Ca, Mg, and Cu/Zn ratio and lower Zn level than that found in control samples, as well as an increase in Cu, Mg and Cu/Zn ratio concentrations with regard to histologically nonneoplastic tissue samples from the same patient. Tissue concentration of trace metals was not significantly influenced either by histologic type of tumor or clinical TNM stage. Significant correlation coefficients between serum and tissue trace metal levels were not found.
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PMID:Serum and tissue trace metal levels in lung cancer. 274 65

A 3-hour single intravenous infusion of aminohydroxypropylidene diphosphonate (APD) 45 mg was given to 25 patients with malignant hypercalcemia. There were seven patients with breast cancer, eight with lung cancer, and ten with a variety of other cancers. Twenty-four patients responded to a single APD 45 mg infusion, 18 of whom (75%) had falls in plasma calcium to below the upper limit of normal (less than or equal to 2.75 mmol/l). Of 15 patients who had severe hypercalcemia, i.e., plasma calcium levels greater than 3.5 mmol/l, 14 responded and 9 (60%) achieved normocalcemia. Five patients developed hypocalcemia. One patient with lung cancer developed spontaneously reversible acute dyspnea after APD which was considered to be an idiosyncratic drug reaction. Single short-duration infusions of APD 45 mg are very effective in correcting malignant hypercalcemia in the majority of patients and are particularly suitable for patients with pre-APD plasma calcium levels greater than 3.5 mmol/l, who are less likely to develop hypocalcemia.
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PMID:Single high-dose (45 mg) infusions of aminohydroxypropylidene diphosphonate for severe malignant hypercalcemia. 276 28

In 121 proven cases of intracranial metastases, lung cancer was as high as 48 per cent. Multiple lesions were noted (67.8%) in almost every type of organ source. Brain parenchyma (80.3%), predominantly supratentorium was the major site of metastases. The minority was observed in leptomeninge, cranial bone and subgaleal tissue. Subarachnoid seeding tumors along CSF pathways spread mainly from pineal neoplasms; a few cases from lung and choriocarcinoma. Extensive brain edema occurred in metastases from almost every type of primary organ source. Calcification exhibited 5.8 per cent and their origins were lung and breast. Bleeding tumors were noted in 10.7 per cent mainly from choriocarcinoma, a few from lung and GI. Hyperdense tumors occurred in 86.8 per cent on noncontrast scans. Almost all tumors (95.2%) showed contrast enhancement, predominantly ring-shaped lesions. Their organ sources were GI, lung and breast. A few patterns of enhancement were homogeneous and heterogeneous. Non-enhanced lesion were noted in 4.8 per cent mainly due to the high density of calcium and blood inside the tumors. Apart from seeding, calcified and bleeding tumors, the CT findings were not specific for various types of metastases.
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PMID:CT findings of brain metastases. 279 20

To examine the biochemical basis for growth factor-induced responses in human lung cancer cells, we used the quin2 technique to study the effect of the amphibian peptide bombesin and its congeners including mammalian gastrin-releasing peptide (GRP) on the intracellular free calcium level [Ca2+]i in small cell lung cancer cell lines. In five of eleven cell lines tested, Tyr4-bombesin or GRP elicited a rapid and transient increase in [Ca2+]i. The response was seen with as little as 1 nM ligand, was not affected by membrane depolarization, and derived in part from internal calcium stores. Desensitization to a second addition of active bombesin congeners occurs subsequent to initial addition of Tyr4-bombesin. Structure-activity analysis showed the carboxyl-terminal octapeptide was the active portion of the peptide. Analogs in which the carboxyl terminus was oxidized or deamidated were inactive. Ranatensin, litorin, alytesin, and GRP, but not physalaemin, were as active as Tyr4-bombesin. A monoclonal antibody to the carboxyl terminus of bombesin selectively blocked the increased [Ca2+]i elicited by Tyr4-bombesin. These studies suggest that bombesin congeners can act on some small cell lung cancer cell lines by a pathway utilizing increased [Ca2+]i.
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PMID:Bombesin-related peptides induce calcium mobilization in a subset of human small cell lung cancer cell lines. 282 95

The sensitivity of 7 human non-small cell lung cancer cell lines to each of 7 cytotoxic drugs was determined. None of the cell lines used in these experiments had been previously exposed to cytotoxic drugs in vitro. A pattern of cross-resistance (P less than 0.05) between the drugs adriamycin (ADR), vincristine (VC) and etoposide (VP16) was noted similar to that seen in other models. The calcium antagonist verapamil (6.6 microM) was shown to increase sensitivity (up to 29-fold) to ADR, VC or VP16 in 5 cell lines. For 2 of the cell lines (A549 and WIL) 2.2 microM verapamil increased VP16 cytotoxicity (up to 4-fold). Drug accumulation studies in 2 cell lines (A549 and SK-MES-1) showed that 6.6 microM verapamil increased intracellular levels of VC up to 4-fold with the greatest increase seen in the cell line (SK-MES-1) for which verapamil produced the greatest increase in cytotoxicity (10-fold). For ADR and VP16 increases in drug accumulation were smaller (up to 1.6-fold). Our data support a potential clinical role for verapamil in overcoming cytotoxic drug resistance in human lung cancer.
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PMID:Circumvention of drug resistance in human non-small cell lung cancer in vitro by verapamil. 282 48

The controversial prognostic significance of serum calcitonin in small-cell lung cancer (SCC) prompted this retrospective study relating serum levels to (1) stage of disease [limited disease (LD) vs. extensive disease (ED)], (2) imaging studies of metastases to bone, liver, and brain, and (3) survival. Of the 127 previously untreated patients with SCC presenting from 1979 to 1984, calcitonin levels could be compared to the stage of the disease in 69 patients (25 LD and 44 ED) and to various staging procedures including 99mTc methylene diphosphonate bone scans (63 patients), 99mTc sulfur colloid liver-spleen scans (64 patients), computed tomography of the head (63 patients) and serum calcium (61 patients). 71% (49/69) of patients had elevated calcitonin of whom 65% (32/49) had ED. 29% (20/69) had normal levels of whom 60% (12/20) had ED. 40% (18/45) of patients with raised calcitonin had liver metastases. 100% (19/19) with normal calcitonin had no liver involvement. Two patients with hypercalcemia and increased calcitonin had extensive bony metastases. The survival experiences of patients with normal and elevated serum calcitonin levels were analyzed. No significant differences were found within each stage or in the group overall. The positive correlation of serum calcitonin to liver metastases was statistically significant. No such relationship could be demonstrated with stage of disease, bone metastases, brain metastases, or survival.
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PMID:Imaging studies and the prognostic value of serum calcitonin in staging small-cell lung cancer. 283 15

This describes a retrospective study in which 88 lung cancer patients and 137 district-matched controls were interviewed concerning the effects of diet on lung cancer risk among Hong Kong Chinese women who never smoked tobacco. Those in the lowest tertile of consuming fresh fruit or fresh fish had statistically significant adjusted relative risks (RRs) of 2.4 and 2.8, respectively. The protective effects of diet, i.e., higher consumption of leafy green vegetables, carrots, tofu, fresh fruit, and fresh fish, were confined mostly to those with adenocarcinoma or large cell tumors. Only fresh fruit was found to positively, and smoked meats to negatively, affect the risk of squamous or small cell tumors. Foods high in vitamin C, retinol, and calcium seemed to exert larger effects. Subjects from larger households were shown to be more frequent consumers of fresh vegetables, fruit, and fish. Because the lifetime weighted household size could be used as a surrogate index of past dietary quality, when it was combined with current dietary intakes of fresh fruit, the RR increased as either factor decreased in a dose-response manner. The adjusted RR was 5.8 at the lowest level. Further testing of the validity of the lifetime weighted household size as an index of past dietary quality is needed.
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PMID:Dietary habits and lung cancer risk among Chinese females in Hong Kong who never smoked. 284 51

We have produced adriamycin (ADM)-resistant variants of the human lung cancer cell lines NCI-H69 (small cell), MOR (adenocarcinoma) and COR-L23 (large cell) but have failed to produce resistant variants of two other small cell lines. In each case, the derivation protocol took 7-9 months and included a period of drug-free growth. All three resistant lines show reduced cellular content of ADM after 1 h exposure when compared with their controls. During prolonged incubation of control and resistant NCI-H69 cells in 0.4 microgram ml-1 ADM, the ADM content of resistant cells was 6-7 times lower than that of control cells. The ratio of ADM doses to suppress growth of the two lines, however, was in the range of 40-200X. The ADM-resistant variant of NCI-H69 was also resistant to vincristine, colchicine, VP16, mitozantrone, 4' epiadriamycin and 4' deoxyadriamycin, somewhat resistant to melphalan but not resistant to aclacinomycin A, bleomycin of CCNU. The resistance to ADM could be partially overcome by the use of verapamil, an inhibitor of calcium transport.
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PMID:Derivation and preliminary characterisation of adriamycin resistant lines of human lung cancer cells. 301 Oct 54


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