Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-2 has been shown to stimulate cortisol secretion in man. Owing to its immunosuppressive properties, an increase in cortisol levels during interleukin-2 cancer immunotherapy could potentially counteract induced activation of the antitumor immune response. Few data are available about cortisol secretion secondary to prolonged interleukin-2 administration. To investigate the problem, we evaluated cortisol circadian rhythms in 7 consecutive metastatic small cell lung cancer patients who received interleukin-2 subcutaneously for 4 weeks (daily dose: 6 x 10(6) x IU/m2). Venous blood samples were drawn at 8.00 a.m., 4.00 p.m. and 12.00 p.m., before interleukin-2, and after each week until the end of the cycle. Beta-endorphin levels were also measured on the same samples. Four patients were evaluated during a second interleukin-2 cycle. Mean cortisol levels increased during interleukin-2 therapy, but were significantly higher than those seen in basal conditions after the first week of treatment. Moreover, cortisol peaks observed during the second cycle of therapy were not significantly different from those seen during the first cycle. Mean beta-endorphin levels increased in response to interleukin-2 administration, but the increase did not reach statistical significance. The early cortisol rise progressively decreased as treatment continued. This suggests that the interleukin-2-induced cortisol rise has no relevant clinical importance in antagonizing the activation of an effective antitumor immune response during cancer immunotherapy with interleukin-2.
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PMID:Effect of prolonged subcutaneous administration of interleukin-2 on the circadian rhythms of cortisol and beta-endorphin in advanced small cell lung cancer patients. 166 67

Beta-endorphin-like immunoreactivity (beta-ELIR) blood levels in control subjects and in patients with different carcinoma and non-Hodgkin's lymphoma tumor types, were found within the same range, with the exception of one carcinoma type. This pertained to a group of patients with small cell lung cancer who had a significantly higher median beta-ELIR level compared to controls. This finding, and the fact that proopiomelanocortin expression is enhanced in tissues of this cancer type, suggest that the latter might secrete elevated beta-ELIR amounts into the blood of the affected patients.
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PMID:Beta-endorphin-like immunoreactivity: assessment of blood levels in patients with tumors of different origin. 180 94

The authors report a patient with ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) resulting from small cell lung cancer. Treatment with ketoconazole (KCZ) resulted in significant suppression of serum cortisol levels. The authors confirmed KCZ to be a useful adjunct in the treatment of Cushing's syndrome.
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PMID:The use of ketoconazole in ectopic adrenocorticotropic hormone syndrome. 184 77

The molecular forms of ACTH secreted by established human small cell lung cancer (SCLC) cells and primary cultures derived from a bronchial carcinoid tumour, a pituitary adenoma and hyperplastic pituitary tissue have been characterized by Sephadex G-75 chromatography and quantified with two novel immunoradiometric assays for ACTH and ACTH precursor peptides. Pro-opiomelanocortin (POMC; Mr 31,000) and pro-ACTH (Mr 22,000) were secreted by all cell types. No smaller peptides were identified in the culture media from SCLC and bronchial carcinoid cells, implying a deficiency in the enzymes and/or intracellular organelles required for extensive POMC processing. A more heterogeneous profile of ACTH-containing peptides was produced by cells of pituitary origin, indicating more extensive proteolytic processing of POMC. However, the major peptide secreted by cells from a large aggressive pituitary adenoma was unprocessed POMC (Mr 31,000). These results suggest that both lung and pituitary cells in vitro retain their in-vivo pattern of POMC processing and provide valuable models in which to study the regulation of ACTH synthesis and secretion.
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PMID:Comparison of ACTH and ACTH precursor peptides secreted by human pituitary and lung tumour cells in vitro. 215 69

A panel of 18 well characterised human small cell lung cancer (SCLC) cell lines was assessed for the production of adrenocorticotrophin (ACTH) and its precursor peptides, pro-opiomelanocortin (POMC) and pro-ACTH. These precursor peptides were measured directly using a novel two-site immunoradiometric assay (IRMA) based on monoclonal antibodies, in conjunction with a similar IRMA for ACTH 1-39. Significant concentrations of ACTH precursors were secreted by 10 of the 18 cell lines (56%). The low levels of ACTH immunoreactivity detected in seven cell lines could be accounted for by the known cross-reactivity of precursors in the ACTH IRMA. This suggests there is little, if any, processing of ACTH precursors to ACTH. Cell pellet extracts contained undetectable or low levels of ACTH precursors and ACTH, indicating that these peptides are not stored intracellularly. During the growth of the SCLC cells in vitro ACTH precursors accumulated progressively in the culture medium. Thus the combination of a direct assay for the ACTH precursors and the panel of SCLC cell lines provides a valuable in vitro model for the expression of POMC in human tumours.
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PMID:Small cell lung cancer cell lines secrete predominantly ACTH precursor peptides not ACTH. 255 86

We describe the characteristics of pro-opiomelanocortin (POMC) mRNA synthesized by a human small cell lung cancer (SCLC) cell line that secretes a peptide immunoreactive with antibodies to the POMC-derived component, adrenocorticotropin. While no alteration in restriction endonuclease pattern or structure was found for the SCLC-derived pomc gene vs. the previously described human pomc gene cloned from a fetal liver library, Northern-blot analysis of SCLC RNA using pomc-derived probes showed a hybridizing transcript more than 300 nucleotides longer than POMC mRNA isolated from human pituitaries, as well as a pomc-gene-hybridizing mRNA the same length as pituitary-derived transcripts. 5' end mapping and primer extension analyses showed that the novel mRNA species is initiated at a site 371 bp upstream from the 5' end identified for pituitary-derived POMC mRNA. We conclude that synthesis of POMC transcripts occurs from an ordinarily quiescent promoter in the SCLC cell line we have studied, as well as from the pomc promoter normally used in pituitary cells.
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PMID:Initiation of pro-opiomelanocortin mRNA from a normally quiescent promoter in a human small cell lung cancer cell line. 255 57

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

An unusual tumor of the skin was removed from the thigh of a 52-year-old white male. By light microscopy, the tumor was composed of intermediate and small cells in sheets and clusters. Ultrastructural study of the tumor cells showed numerous dense core granules and dendritic cell processes as well as intermediate filaments and cell junctions frequently within the same cells. Most of the tumor cells were stained intensely by antibodies to neurone-specific enolase (NSE), a marker of cells of the central and peripheral nervous system. The neuropeptides met-enkephalin and vasoactive intestinal peptide (VIP) were also found in tumor cells. Immunohistochemistry furthermore demonstrated cytokeratin. Both the ultrastructural appearance and keratin content of this tumor set it apart from conventional Merkel cell (or trabecular) carcinoma of the skin in a manner analogous to bipartite (i.e., epidermoid and small cell) carcinoma of lung. The production of neuropeptides simultaneously with the production of keratin establishes this as a bipartite skin tumor (i.e., ectodermal and neuroectodermal phenotype). We suggest that at least some primary neuroendocrine tumors of the skin arise from multipotential ectodermal cells not of neural crest origin, as has been proposed for small cell carcinoma of lung.
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PMID:Neuroendocrine carcinoma of skin with simultaneous cytokeratin expression. 620 92

The mechanism of ectopic adrenocorticotrophic hormone (ACTH) secretion was examined by studies on the effects of corticotropin-releasing hormone (CRH), dexamethasone, interleukin (IL)-1 beta and 2, somatostatin, calcium ionophore A23187, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 8-bromo-cAMP on pro-opiomelanocortin (POMC) expression and ACTH secretion from a human small cell lung cancer cell line COR-L103. None of these agents except TPA and A23187 had any effect on ACTH secretion from the cell line in short (0-8 hrs) or long term (1-4 days) cultures. In long term cultures, 1-100 nM TPA stimulated ACTH secretion dose-dependently, whereas 500nM A23187 inhibited ACTH secretion completely. When the cells were incubated with 10nM TPA plus 500 nM A23187, the inhibitory action of A23187 on ACTH secretion was suppressed by TPA. These results suggest that the mechanisms of ACTH secretion by COR-L103 cells and normal pituitary cells are different.
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PMID:Calcium ionophore A23187 inhibits ACTH secretion from a human small cell lung cancer cell line, COR-L103. 785 71

We describe a patient with Cushing's syndrome and metastatic small cell lung cancer. The plasma ACTH concentrations were markedly elevated (91.6 pmol/L), and the AM cortisol did not suppress by > 50% overnight after administration of 8 mg dexamethasone, both consistent with the ectopic ACTH syndrome. Immunohistochemical studies of a single metastatic tumor specimen, however, demonstrated an absence of ACTH and yet an abundance of corticotropin-releasing hormone (CRH). In addition, radioimmunoassay of the patient's plasma demonstrated persistently elevated CRH concentrations. The majority of the plasma CRH immunoreactivity exhibited the same chromatographic mobility as synthetic r/h CRH (1-41) on HPLC. Failure to evaluate the tumor tissue for the presence of ACTH and/or CRH would have led to the erroneous conclusion that this patient's Cushing's syndrome resulted from paraneoplastic ACTH production. We conclude that immunoassay of plasma for both ACTH and CRH and, perhaps, immunostaining of tumor samples are required to distinguish between the ectopic ACTH and CRH syndromes.
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PMID:Corticotropin-releasing hormone production by a small cell carcinoma in a patient with ACTH-dependent Cushing's syndrome. 793 Mar 90


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