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

Four surface antigens previously recognized only in macrophages are present on human small cell lung carcinoma cells and tumors. Cancerous cells may arise from macrophage precursors in bone marrow, and these precursors migrate to lung to participate in the repair of damaged tissue produced by continuous heavy smoking. The characteristic presence of neuropeptides such as bombesin in small cell carcinoma, when considered along with these findings, presents new possibilities for the role of such peptides in nervous, endocrine, and immune system function.
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PMID:Small cell carcinoma of the lung: macrophage-specific antigens suggest hemopoietic stem cell origin. 608 38

Three established cell lines derived from human small cell carcinoma of the lung, and known to produce significant amounts of peptide hormones were used to evaluate the regulation of hormone secretion by cholinergic agonists. In two of the cell lines (DMS 53, DMS 153) acetylcholine chloride, bethanechol chloride, and carbamylcholine at the concentrations of 10(-3)M to 10(-5)M stimulated secretion of bombesin and calcitonin as measured by RIA. The third cell line, DMS 406, was not significantly stimulated. Inhibition of induced stimulation by the cholinergic antagonist atropine, but not hexamethonium, indicated the presence of muscarinic rather than the nicotinic type of cholinergic receptors on the stimulatable cells. These receptors appear to mediate hormone secretion comparably to normal endocrine cells.
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PMID:Bombesin and calcitonin secretion by pulmonary carcinoma is modulated by cholinergic receptors. 613 24

Vasoactive intestinal peptide (VIP), leucine-enkephalin (Leu-Enk), dynorphin (Dyn), neurotensin (NT) and substance P (SP) were measured by radioimmunoassay in lung and bronchoalveolar lavage (BAL) fluids of sham operated control rats and rats exposed to asbestos (5 and 10 mg, single intratracheal injections) for 3 and 6 months. Among these peptides, VIP, Leu-Enk and Dyn were the most abundant with 6 to 25 pmoles per g of lung tissue as compared with 0.95 to 1.2 pmoles per g for the other neuropeptides. In the presence of asbestos, VIP levels were selectively increased up to 2.7 times in lung tissue and 4.3 times in BAL fluids. On high pressure liquid chromatography (HPLC), the immunoreactive VIP coeluted with synthetic VIP. It is concluded that this selective increase may be involved in the pathogenesis of asbestos-related diseases. Exposure to asbestos causes chronic inflammatory reactions in the lung which may lead to fibrosis (1) and increase the incidence of pleuropulmonary cancers (2). Little is known concerning the biochemical changes responsible for the deleterious effects of asbestos on pulmonary functions. Previous studies have documented the vast complexity and diversity of lung biochemistry including its ability to metabolize lipids, inactivate certain enzymes and produce physiologically active amines (3-6). Recently, the lung has been recognized as an important source of peptidergic substances. VIP and SP were reported to be localized in nerve terminals of the main airways and in axons of the parasympathetic conducts (7-11). Other neuropeptides including bombesin (12, 13), calcitonin (13, 14) and Leu-Enk (13) were also detected in the lung. However, these latter peptides were mainly confined to diffuse granule-containing cells also known as APUD cells (amine precursor uptake and decarboxylation cells) (15). The role of these neuropeptides in normal lung function and in pulmonary diseases is unknown. However, it has recently been demonstrated that APUD cells proliferate in the rat lung following asbestos inhalation (16) and lung exposure to carcinogens (17, 18). In addition, Moody et al. (19) and Sorenson et al. (20) have observed high levels of bombesin in human cell lines derived from small-cell lung carcinoma. It was then of particular interest to verify if lung exposure to asbestos can induce some changes in the levels of various neuropeptides. In the present study, we report that VIP is significantly increased in the lungs and BAL fluids of rats exposed to asbestos while no significant change in the levels of Leu-Enk, Dyn, NT and SP is observed.
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PMID:Asbestos-related increase in pulmonary levels of vasoactive intestinal peptide (VIP). 619 89

A series of continuous cell lines of human small cell carcinoma of the lung (SCCL) have been evaluated for the production of bombesin (BN). In early established cultures BN was detected in the medium of 9 out of 11 cell lines and in 6 out of 7 cell homogenates examined. Levels in the medium were frequently higher in cultures of later passages compared to earlier passages of the same line and low levels developed in the two previously negative cell lines. Plasma concentrations were greater than 80 pmol/l in 2 out of 27 (7%) randomly selected patients with SCCL. A culture (DMS 406) established from the tumor of a patient with the highest plasma level (1240 pmol/l) was the highest producer in vitro. The results indicate that BN, which has been demonstrated immunocytochemically to be present in normal bronchial mucosal cells, is frequently produced by SCCL in vitro but elevated plasma levels are infrequently found in patients with this neoplasm.
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PMID:Bombesin production by human small cell carcinoma of the lung. 628 85

High intracellular levels of BN-like peptides are present in tumors and cell lines of small cell carcinoma of the lung (SCCL) as well as the putative precursor cells of this tumor, the pulmonary endocrine cell. In cell line NCI-H209 the density of bombesin-like peptides was 8.9 +/- 1.1 pmol/mg total protein. Gel filtration chromatography of an extract of these cells revealed one major peak of immunoreactivity which coeluted with synthetic bombesin (1620 daltons). Also, high pressure liquid chromatography revealed one major peak of immunoreactivity was present which eluted before synthetic peptide. Therefore, SCCL bombesin-like peptides may be of similar size but are more hydrophilic than synthetic peptide. Cells maintained in culture continuously release bombesin-like peptides into the growth medium. Also, high concentrations of K+ stimulated the secretion of immunoreactive bombesin from cell lines in a Ca++-dependent manner. These SCCL bombesin-like peptides may function as important regulatory agents in the malignant lung.
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PMID:Bombesin-like peptides in small cell lung cancer: biochemical characterization and secretion from a cell line. 629 91

A new tumor cell line, designated SU-CCS-1, was established from the malignant pleural effusion of a 16-year-old Caucasian girl with clear cell sarcoma. Morphological studies at the light- and electron-microscopic levels revealed similar features between the SU-CCS-1 cells and the primary tumor. Ultrastructural and cytochemical techniques showed that both the SU-CCS-1 cell line and the original tumor were amelanotic in nature. The malignant derivation of the SU-CCS-1 cell line was demonstrated by intracranial and s.c. heterotransplantation in the nude, athymic mouse and by cytogenetic analysis which showed that the cell line had a hypodiploid chromosome number and several karyotypic abnormalities. Live-cell radioimmunoassay procedures using a large panel of monoclonal antibodies directed against tumor-associated antigens revealed that, phenotypically, SU-CCS-1 closely resembled melanoma tumor cell lines. Immunological assays for the detection of neuroendocrine-associated peptides, hormones, and enzymes revealed that, like melanoma, the SU-CCS-1 cell line was actively producing alpha-melanotropin, S-100 antigen, and nerve growth factor. A notable difference between these tumor types was the capacity of SU-CCS-1 to produce bombesin, an active neuropeptide whose synthesis has been found in cell lines from patients with small cell carcinoma of the lung. From these studies, we concluded that the SU-CCS-1 cell line is phenotypically similar to melanoma, yet displays unique characteristics which distinguishes it from other sarcomas. The availability of an established clear cell sarcoma cell line will greatly facilitate further studies aimed at uncovering the histogenesis of this rare cancer.
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PMID:Use of a newly established human cell line (SU-CCS-1) to demonstrate the relationship of clear cell sarcoma to malignant melanoma. 636 60

In order to estimate the value of immunohistochemical identification of neuroendocrine (NE) differentiation markers in non-small cell lung carcinomas (NSCLCs), we investigated the expression of five neuroendocrine and neural differentiation-related antigens in 51 NSCLCs. Additionally, 20 epithelial lung tumors with NE differentiation [15 carcinoids and five small cell lung carcinomas (SCLCs)] and 61 epithelial tumors of various other origin (breast, prostate, colon and head-neck carcinomas) were studied. An indirect two-stage immunoperoxidase method was performed in formalin-fixed and paraffin-embedded tissue specimens, by using commercially available monoclonal antibodies. These antibodies are directed against neuron-specific enolase (NSE), chromogranin-A and Leu-7 which are general markers of NE differentiation, bombesin, which is a specific NE secretory product and neurofilament triplet protein (NFTP), an intermediate filament protein of neuronal differentiation. All five markers demonstrated a positive immunoreactivity in NSCLCs, equally distributed to all three histologic subtypes, ranging from 16 to 47% of the cases (NSE 47%, bombesin 21.5%, Leu-7 21.5%, chromogranin-A 18% and NFTP 16%). Most of the carcinoids and SCLCs expressed multiple or all NE markers. The other four epithelial tumors showed a positive immunoreactivity for bombesin, Leu-7 and NFTP, ranging from 11 to 40% of the cases. Chromogranin-A was not expressed in any of these tumors, whereas NSE was demonstrated only in 17% of breast carcinomas. The following remarks can be drawn from this study: (1) some NSCLCs showed immunophenotypic NE differentiation; (2) among all the markers used, NSE was the most sensitive (sensitivity, 100%) and chromogranin-A the most specific (specificity, 100%); and (3) NSE and chromogranin-A appear to be the most valuable and useful indicators of probable neuroendocrine differentiation in lung epithelial tumors.
Lung Cancer 1994 Dec
PMID:The value of neuroendocrine markers in non-small cell lung cancer: a comparative immunohistopathologic study. 753 40

The bombesin-like peptides can function as autocrine growth factors in lung cancer and candidate tumor suppressor genes on chromosomes 3 and 9 play important roles in lung cancer. Bombesin-like peptides can function as mitogens for normal bronchial epithelial cells and lung cancer cell lines. The monoclonal antibody directed against gastrin releasing peptide and bombesin, 2A11, can inhibit the growth of small cell lung cancer in vitro and in vivo and intravenous administration has induced a clinical remission in a patient with relapsed small cell lung cancer. The loss of a portion of one of the two short arms of chromosome 3 (3p) is identified in nearly 100% of tumor cell lines and tumors from patients with small cell lung cancer. Introduction of chromosome 3 into tumor cell lines suppresses their tumorigenicity in athymic nude mice, one of the characteristics of the cancer phenotype. Both copies of the candidate tumor suppressor gene on chromosome 9, CDKN2, are deleted in approximately one-fourth of lung cancer cell lines examined and the protein product of CDKN2, p16 is undetectable in one-third of the lung cancer cell lines studied. The CDKN2 gene is inactivated more commonly in non-small cell lung cancer than small cell lung cancer while the retinoblastoma gene is inactivated more commonly in small cell lung cancer than non-small cell lung cancer. It appears that a single defect in this cell cycle pathway is necessary for unregulated growth in lung cancer and current evidence suggests these defects differ between small cell and non-small cell lung cancer.
Lung Cancer 1995 Jun
PMID:Biology of small cell lung cancer. 755 56

Bombesin-related peptides (BRP) are present in the lung during foetal life and are mitogenic for normal bronchial epithelial cells, pulmonary fibroblasts, and small-cell lung carcinoma cell lines. Increased levels of BRP have been described in the adult lung of cigarette smokers and in smoking related lung diseases. BRP have also been involved in the network of neuroimmune interactions, having been shown to modulate the phagocytic function of monocytes and alveolar macrophages. BRP have recently been shown to modulate the release of procoagulant activity (PCA) by human monocytes and alveolar macrophages after a 24 h culture. The aim of this study was to evaluate the effect of bombesin on cell-associated PCA of alveolar macrophages (AMs) obtained from asymptomatic subjects. In basal conditions, AMs were found to possess a low procoagulant activity, that was not affected by their preincubation (4 h at 37 degrees C) with phorbol myristate acetate (1 microgram-mL-1). On the contrary, endotoxin (lipopolysaccharide (LPS)) induced a significant increase of procoagulant activity of macrophages when used at a concentration of 1 microgram.mL-1, in the same experimental conditions; whilst a lower (1 ng.mL-1) concentration of LPS nonsignificantly enhanced cell-associated PCA. Treatment of AMs with synthetic bombesin (BN) alone (10(-6) to 10(-10) M) did not enhance cell-associated PCA, whilst a significant effect was seen when BN was added to the lower concentration of LPS (BN 10(-6) M+LPS 1 ng.mL-1: 12.6 U.10(-6) cells; LPS alone 1 ng.mL-1: 7.8 U.10(-6) cells).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro effect of bombesin-related peptides on the procoagulant activity of alveolar macrophages. 766 87

Various pseudononapeptide bombesin (BN)-(6-14) antagonists with a reduced peptide bond (CH2-NH) between positions 13 and 14 can suppress the mitogenic activity of BN or gastrin-releasing peptide in 3T3 fibroblast cells and small cell lung carcinoma. In the search for more potent BN antagonists, 10 modified nonapeptide BN antagonists containing N-terminal D-Phe, D-Cpa, and D- or L-Tpi and C-terminal Leu-psi(CH2-N)-Tac-NH2, Leu-psi(CH2-N)-MeTac-NH2, or Leu-psi(CH2-N)-Me2Tac-NH2 have been synthesized by incubating [13 psi 14,CH2-NH,Cys14]BN-(6-14) or [13 psi 14-CH2-NH,Pen14]BN-(6-14) with formaldehyde or acetaldehyde (Cpa = 4-chlorophenylalanine, Tac = thiazolidine-4-carboxylic acid, Tpi = 2,3,4,9-tetrahydro-1H- pyrido[3,4-b]indol-3-carboxylic acid, and Pen = penicillamine). The biological activities of these compounds were then evaluated. [D-Phe6,13 psi 14,CH2-N,Tac14]BN-(6-14) (RC-3950-II) and [D-Phe6,13 psi 14,CH2-N,Me2Tac14]BN-(6-14) (RC-3985-II) exhibited greater potency in inhibition of 125I-labeled [Tyr4]BN binding to Swiss 3T3 cells than their parent compounds [D-Phe6,13 psi 14,CH2-NH,Cys14]BN-(6-14) (RC-3950-I) and [D-Phe6,13 psi 14,CH2-NH,Pen14]BN-(6-14) (RC-3985-I). The order of binding affinities of these compounds was as follows: [13 psi 14,CH2-N,Tac14]BN-(6-14) > [13 psi 14,CH2-N,Me2Tac14]BN-(6-14) > [13 psi 14,CH2-N,MeTac14]BN-(6-14). In most cases, the analogs with C-terminal Leu-psi(CH2-N)-Tac-NH2 were also more potent growth inhibitors of 3T3 cells than compounds containing C-terminal Leu-psi(CH2-N)-Me2Tac-NH2 or Leu-psi(CH2-N)-MeTac-NH2. The best BN antagonists of this series, RC-3950-II and [D-Cpa6,13 psi 14,CH2-N,Tac14]BN- (6-14) (RC-3925-II), inhibited gastrin-releasing peptide-stimulated growth of Swiss 3T3 cells with IC50 values of 1 nM and 6 nM, respectively. Since antagonists of this class inhibit growth of various tumors in animal cancer models, some of them may have clinical applications.
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PMID:Potent bombesin antagonists with C-terminal Leu-psi(CH2-N)-Tac-NH2 or its derivatives. 780 97


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