Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bombesin-like peptides (BN-LP) are involved in the regulation of many important functions, including sensory transmission, regulation of central autonomic pathways, thermoregulation, pituitary, gastric and pancreatic secretion, food intake and satiety. They also stimulate cellular proliferation in a developmental and tissue-specific manner. Their role in pathogenesis appears to be related to their properties as growth factors, especially in the lung, where BN-LP can induce growth of normal and neoplastic epithelial cells. The formulated hypothesis of autocrine control of small cell lung cancer growth by BN-LP will be tested using specific synthetic bombesin antagonists.
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PMID:Bombesin-like peptides as growth factors. 254 48

Pretreatment serum neuron specific enolase (NSE) and plasma bombesin/gastrin releasing peptide (BN/GRP) were measured in 92 lung cancer patients and 17 controls. The mean level of NSE (p less than 0.001) and BN/GRP (p less than 0.05) was significantly raised in patients with small cell lung cancer (SCLC, n = 62) compared to non-SCLC (n = 30) and controls. The mean concentration of NSE in extensive SCLC was significantly greater (p less than 0.005) than in limited stage but with a substantial overlap of values. Forty-seven out of 62 SCLC patients had at least one of the two markers raised (sensitivity 76%, specificity 83%), 44 had raised NSE (sensitivity 71%, specificity 89%) but only 24 had BN/GRP raised (sensitivity 42%, specificity 91%). At restaging, 16 of 19 patients with SCLC responsive to chemotherapy showed a significant fall of NSE; on the other hand, BN/GRP fell significantly in only 3 patients, remaining unchanged in the majority of responding patients. In conclusion, the combined determination of NSE and BN/GRP in SCLC, at diagnosis and during the follow-up, was not found to be superior to NSE determination alone.
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PMID:Combined measurements of neuron specific enolase and bombesin/gastrin releasing peptide in lung cancer. 255 76

The tumor stem cell clonogenic assay was utilized to investigate the autocrine growth response of small cell lung cancer (SCLC) to bombesin (BN) and beta-endorphin (beta-E). Mycoplasma contamination was detected in the human SCLC cell line NCl-H345 by a nucleic acid hybridization assay which detects mycoplasma ribosomal RNA. Clonogenic assays of mycoplasma (+) cells were compared to assays of the same cell line following treatment for mycoplasma. Concentrations of beta-E ranging from 0.1nM to 25nM or BN (0.1nM-100nM) were added to cells, media and agarose and applied to prepared base layers. Following incubation for 12-14 days at 37 degrees C, the degree of clonal growth stimulation was determined by colony counts greater than or equal to 42 mu. The non-infected cell population grew in the presence of 25nM BN up to 69% over control growth. The infected cells, however, did not grow more than 27% above control. In the presence of 10nM beta-E, colony counts of non-infected cells exceeded the control values by up to 187% whereas the mycoplasma (+) colonies did not grow more than 20% over the control values. These results indicate a marked reduction in the response of SCLC cell lines to the peptides BN and beta-E when infected with mycoplasma. Since infecting mycoplasma typically adhere to cellular membranes, these adherent mycoplasma may interfere with membrane receptors or alter signal transduction, thus, inhibiting the development of the autocrine response.
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PMID:The effect of mycoplasma on the autocrine stimulation of human small cell lung cancer in vitro by bombesin and beta-endorphin. 255 67

Although the normal function of pulmonary neuroendocrine (PNE) cells containing bioactive peptides is poorly understood, various pulmonary diseases are associated with hyperplasia of these cells, and they also may be progenitors for small cell lung cancer in humans. In this study we have investigated the effects of subchronic cigarette smoke exposure in the hamster on the PNE cells and their peptide content. Daily exposure to standard research cigarette smoke for as long as 90 days led to progressively higher levels of serum calcitonin (iCT) as well as higher lung tissue iCT and the gastrin releasing-like peptides or mammalian bombesin (MB). Subsequent to a 30-day period during which there was no further exposure to smoke, serum levels returned to control levels, but the lung levels of both iCT and MB remained higher than control levels. Also, after the 90 days of exposure, immunocytochemistry revealed an increase in the number of iCT-containing PNE cells. This increase in the number of PNE cells correlated well with the increased iCT content of the lung tissue. We conclude that subchronic cigarette smoke exposure causes an increase in pulmonary levels of iCT and MB, which may be linked to the observed proliferative response of the PNE cells.
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PMID:Stimulation of hamster pulmonary neuroendocrine cells and associated peptides by repeated exposure to cigarette smoke. 276 80

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

Bombesin-like peptides are found in many different human tumors and are thought to function as an autocrine growth factor for small cell lung cancer in humans. In this study, a human small cell lung carcinoma (NCI-H69) was s.c. implanted bilaterally into the flanks of 12 nude mice. The mice were randomized and divided into two groups and given either bombesin (20 micrograms/kg) or saline i.p. 3 times a day. Tumor areas were measured twice weekly for 6 wk. At sacrifice, the tumors and normal pancreas were excised, weighed, and assayed for DNA, RNA, and protein content. Significant stimulation of tumor growth was observed at weeks 4, 5, and 6. Tumor weight at sacrifice was significantly elevated (77%) above the control, as was DNA content (78%). Bombesin significantly increased the weight (42%), DNA (48%), and protein (61%) contents of the normal mouse pancreas. We conclude that bombesin may act as an autocrine growth factor, or indirectly through the release of other growth factors, on human small cell lung carcinoma.
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PMID:Effects of bombesin on growth of human small cell lung carcinoma in vivo. 283 Sep 65

Gastrin releasing peptide (GRP) is a peptide hormone containing 27 amino acids which is structurally analogous to the amphibian peptide bombesin. GRP serves a variety of physiological functions and has been implicated in the pathophysiology of small cell lung cancer. Previous work has demonstrated that the modified C terminus of GRP, N-acetyl-GRP-20-27, exerts full agonist activity in a variety of assay systems. However, no systematic comparison of binding of GRP fragments to its receptor and mitogenic potency has been reported. To investigate whether smaller GRP fragments could bind to the GRP receptor without stimulating mitogenesis, we performed binding inhibition and thymidine uptake assays with Swiss 3T3 fibroblasts. These studies were facilitated by the development of a novel tritiated GRP-based radioligand, [3H-Phe15] GRP-15-27, which exhibits enhanced chemical stability compared to iodinated GRP derivatives. We examined a series of C-terminal GRP fragments, from the pentapeptide to the octapeptide, with both N-acetyl and free amine moieties at the N terminus. N-Acetylated derivatives were more potent than their primary amine counterparts in both assays. Deletion of N-terminal residues from GRP-20-27 resulted in significant loss of potency in both assays: the EC50 values of N-acetyl-GRP-21-27 were 10(2)-fold higher than N-acetyl-GRP-20-27, those of N-acetyl-GRP-22-27 were 10(4)-fold higher, and N-acetyl-GRP-23-27 showed minimal activity at concentrations below 100 microM. These results suggest that 1) both His20 and Trp21 play an important role in binding of GRP to the receptor, and 2) for this series of N-terminal deletions, binding to the receptor and mitogenic activity are tightly coupled.
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PMID:Minimal ligand analysis of gastrin releasing peptide. Receptor binding and mitogenesis. 283 60

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.
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PMID:Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects. 283 87

Progress achieved in the understanding of small cell lung cancer (SCLC) include: the establishment and characterization of cell lines with the identification of a variant type with poor prognosis; the use of non-specific biochemical markers such as neuron specific enolase (NSE) and calcitonin; the generation of monoclonal antibodies (MoAbs) directed against SCLC antigens; growth factors including GRP and IGF. GRP or human bombesin produced by the tumor cells favours their own growths; in cytogenetics, with the observation of a characteristic chromosomal abnormality: the deletion of the short arm of chromosome 3 (3p 14-23). The region deleted is currently under study to identify the genes potentially involved in the oncogenesis of SCLC. the activation of several oncogenes: C-myc, N-myc, L-myc, Myb, Raf-1. The amplification of C-myc favors the tumor cell progression and is related to a bad prognosis. This biological approach has confirmed the neuroendocrine origin of these tumor cells (as a result of protein studies of the cytoskeleton and of MoAbs); it has allowed the use of tumor markers in the diagnosis and work-up of SCLC and the consideration of new therapeutic approaches. Current studies concern the deletion of 3p- and the integration of the cytogenetic data, growth factors and oncogenes in a coherent model of the genesis of SCLC.
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PMID:[Recent progress in the biology of small cell bronchial carcinoma]. 284 57

In Swiss 3T3 fibroblasts, antibodies which recognize a phosphotyrosine residue (P-Tyr antibodies) identify a 115-kDa cell surface protein (p115) that becomes phosphorylated on tyrosine as a response to bombesin stimulation of quiescent cells. The extent of phosphorylation is dose-dependent and correlates with the mitogenic effect induced by bombesin, measured by [3H]thymidine incorporation. Tyrosine phosphorylation of p115 is detectable minutes after addition of bombesin and precedes the activation of c-fos and c-myc gene transcription. Immunocomplexes of phosphorylated p115 with P-Tyr antibodies bind 125I-labeled [Tyr4]bombesin in a specific and saturable manner and display an associated tyrosine protein kinase activity enhanced by bombesin. P-Tyr antibodies also recognize a protein of 115 kDa, phosphorylated at tyrosine, in four human SCLC lines producing bombesin but not in a non-producer "variant" line. Phosphorylation of SCLC p115 does not require the addition of exogenous bombesin. As in the case of the p115 immunoprecipitated from mouse fibroblasts, the SCLC p115 is phosphorylated in an immunocomplex kinase assay. These observations are in agreement with the hypothesis of autocrine activation of bombesin receptors in human small cell lung carcinoma cells.
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PMID:A tyrosine protein kinase activated by bombesin in normal fibroblasts and small cell carcinomas. 285 93


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