beta-endorphin and Lung-Neoplasms

Topics: Adenocarcinoma; Amine Oxidase (Copper-Containing); APUD Cells; beta-Endorphin; Calcitonin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cell Line; Dopa Decarboxylase; Endorphins; Humans; Lung Neoplasms

Topics: Adult; Aged; Anesthesia, General; beta-Endorphin; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Cytokines; Female; Hemodynamics; Humans; Inflammation Mediators; Lung Neoplasms; Male; Malondialdehyde; Middle Aged; Neoplasm Staging; Neurosecretory Systems; Time Factors; Treatment Outcome; Visual Analog Scale

To explore the therapeutic effect and mechanism of Aitongping capsule (ATP) in treating cancerous pain.. Sixty cancer patients were randomly divided into two groups, 30 patients in the treated group took ATP and 30 patients in the control group took diclofenac, 1 week of treatment was applied. The relevant clinical conditions of cancerous pain, the content of plasma beta-endorphin (beta-EP) and c-AMP, hemorheological index, improuement of life quality of patients, occurrence rate of adverse reaction were observed before and after treatment.. The total effective rate in the treated group and in the control group was 90.0 % and 83.3%, respectively, difference between them showed no significance. However, there were significant difference between the two groups in such aspects as the degree of pain relieving, the decrease of pain episodes, the shortening persistent time of pain and the initiation time of analgesic action and prolonged analgesic duration, the decrease of tenderness and percussion pain, the increase of plasma beta-EP content and the decrease of cAMP (P< 0.05 or P< 0.01). The evidences also showed that it was better in improving quality of life, ameliorating hemorheologic indexes and reducing incidence of adverse reaction in the treated group than in the control group (P <0.05 or P <0.01).. ATP has affirmative effect on cancerous pain, its analgesic effect may be associated with the increasing of plasma beta-EP content, decreasing of cAMP level and ameliorating of hemorheologic indexes.

Topics: beta-Endorphin; Capsules; Cyclic AMP; Drugs, Chinese Herbal; Female; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Pain; Phytotherapy; Quality of Life

In order to investigate the role of acupuncture in the regulation of cellular immune function, the changes of T lymphocyte subsets (CD3+, CD4+, CD8+), soluble interleukin-2 receptor (SIL-2 R) and beta-endorphine (beta-EP) in the peripheral blood of patients with malignant tumors before and after acupuncture were observed with double blind method. Forty patients were divided randomly into two groups, 20 for each. One group treated with acupuncture and the other one for control. Results showed that acupuncture has the effect of enhancing the cellular immunity of patient with malignant tumor. Acupuncture treatment could increase the percentage of T lymphocyte subsets CD3+, CD4+ and the CD4+/CD8+ ratio (P < 0.01) and the level of beta-EP, as well as decrease the level of SIL-2 R (P < 0.01). The correlation analysis of the three criteria showed there was a positive correlation between beta-EP and T lymphocyte subsets and a negative correlation between beta-EP and SIL-2 R, there was also a negative correlation between T lymphocyte subsets and SIL-2 R. Based on these results, a discussion on the acupuncture immunomodulation network was conducted in this article in order to explore the possible mechanism of acupuncture on immunomodulation.

Topics: Acupuncture Therapy; Adult; Aged; beta-Endorphin; CD4-CD8 Ratio; Double-Blind Method; Esophageal Neoplasms; Female; Humans; Lung Neoplasms; Male; Middle Aged; Receptors, Interleukin-2; T-Lymphocyte Subsets

A large number of lung cancers contains and releases a variety of neuropeptides such as adrenocorticotropic hormone (ACTH) and beta-endorphin (beta-EP). Although the plasma levels of these peptides have been extensively investigated as possible markers that may help in the early diagnosis of the disease, the data collected have shown their limited clinical usefulness. The present study was undertaken to evaluate whether corticotropin-releasing hormone (CRH), ACTH or beta-EP levels in the bronchoalveolar lavage (BAL) fluid of patients with lung cancer might have been more helpful. To accomplish this, bronchial lavages were carried out in 25 patients affected by lung cancer (17 squamous carcinomas, 4 adenocarcinomas, 2 small cell carcinomas, and 2 not classified) and 18 controls. After centrifugation, BAL fluid was extracted using cartridges of SepPak C-18 and CRH, ACTH and beta-EP levels were measured by radioimmunoassay. CRH and ACTH BAL levels in patients with lung cancer were not significantly different from those of controls. beta-EP concentrations in the BAL fluid were about 200-fold higher than those of ACTH and showed a downward trend (p = 0.08, Mann-Whitney test) in patients with cancer. No histologic tumor type was associated with particularly elevated levels of any of the peptides measured, not even the two patients with small cell carcinoma, a tumor type which tends to release higher peptide levels. Therefore we conclude that measurements of CRH, ACTH and/or beta-EP in the BAL fluid are not useful diagnostic tumor markers of lung cancer.

Topics: Adrenocorticotropic Hormone; Aged; Aged, 80 and over; beta-Endorphin; Biomarkers, Tumor; Bronchoalveolar Lavage Fluid; Corticotropin-Releasing Hormone; Female; Hormones; Humans; Lung Neoplasms; Male; Middle Aged; Peptides; Radioimmunoassay

In order to investigate the role of acupuncture in the regulation of cellular immune function, we observed acupuncture therapy affecting the levels of T lymphocytes subgroup (CD3+, CD4+, CD8+), soluble interleukin-2 receptor (SIL-2R) and beta-endorphin (beta-EP) in the peripheral blood of patients with malignant tumors. Here was used the random-gioland method, the patients were divided into a group treated by acupuncture (acup. group, 20 cases) and a control group (20 cases). The acup. group was treated using points PC6, LI4, ST36, RN4 and location of symptomatic points bilaterally, one treatment of 30 min daily for 10 days. The results showed that there were increased levels of CD3+, CD4+ percentage, CD4+/CD8+ ratio and radioimmunoassay of beta-EP in blood plasma, a decreased level of SIL-2R after acup. The statistical significance was found to be remarkable (P < 0.01), so has a notable difference, the correlation analysis indicated: (1) there was a positive correlation between beta-EP and T-lymphocytes subgroups; (2) a negative correlation between beta-Bp and SIL-2R, so did it between T subgroups and SIL-2R. Our results showed that beta-EP enhanced immune function of patients by increased T lymphocyte subgroups, reduced SIL-2R, and this action of beta-EP may be mediated by opioid receptor. The above mentioned results prevented evidence that there was an adjusting-network of immune in the body, through this way, acup. therapy can heighten the cellular immune function of patients, providing a beneficial effect in anti-cancer treatment.

Topics: Acupuncture Therapy; Adult; Aged; beta-Endorphin; CD4-CD8 Ratio; Esophageal Neoplasms; Female; Humans; Immunity, Cellular; Lung Neoplasms; Male; Middle Aged; Receptors, Interleukin-2; T-Lymphocyte Subsets

Ectopic ACTH-producing tumors preferentially secrete biologically inactive ACTH precursors and ACTH-related fragments. DMS-79 is known to secrete unprocessed high-molecular-weight (HMW) form ACTH. To determine whether prohormone convertase (PC) 1/3 is involved in the abnormal processing of proopiomelanocortin (POMC), we studied whether PC1/3 and 2 genes are expressed in DMS-79, and whether overexpression of PC1/3 gene affects POMC processing pattern. Steady-state mRNA levels of PC1/3 and 2 were determined by real-time RT-PCR. Molecular weights of ACTH-related peptides were determined by chromatographical analyses coupled with ACTH and beta-endorphin (beta-END) radioimmunoassays. PC1/3 gene was transfected into DMS-79 by retrovirus transduction using pMX-IP vector encoding PC1/3 cDNA. The steady-state mRNA levels of PC1/3 and 2 in DMS-79 were lower than those in ACTH-secreting and nonfunctioning pituitary tumors. DMS-79 predominantly secreted HMW form with both ACTH and beta-END immunoreactivities by size-exclusion chromatography. After purification by immunoaffinity chromatography with anti-ACTH antibody, the apparent molecular weight of HMW form ACTH was estimated to be 16 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver staining. After retroviral transfection of PC1/3 cDNA into DMS-79 and puromycin selection, PC1/3 stably-expressing cell line (DMS-79T) secreted two immunoreactive ACTH components, a major one coeluting with ACTH(1-39) and a minor one as a HMW form as well as two beta- END immunoreactive components coeluting with beta-lipotropic hormone and beta-END, respectively. Thus, we have established PC1/3 stably-expressing cell line (DMS-79T) capable of proteolytically processing ACTH precursor molecule(s) into mature ACTH and beta-END.

Topics: Adenoma; Adrenocorticotropic Hormone; beta-Endorphin; Cell Line, Tumor; Electrophoresis, Polyacrylamide Gel; Gene Expression; Humans; Lung Neoplasms; Molecular Weight; Pituitary Neoplasms; Pro-Opiomelanocortin; Proprotein Convertase 1; Proprotein Convertase 2; Retroviridae; RNA, Messenger; Small Cell Lung Carcinoma; Transfection

The small cell lung carcinoma cell line U-1690 bound beta-endorphin via nonopioid binding sites also recognized by the C-terminal part of this opioid peptide Lys-Lys-Gly-Glu, but not by opiate alkaloids such as naloxone and morphine or other opioid peptides. The beta-endorphin binding did not affect the production of cAMP, but was enhanced by dexamethasone pretreatment. The beta-endorphin-stimulated proliferation of U-1690 cells was inhibited by Lys-Lys-Gly-Glu and increased by dexamethasone pretreatment. The cells also produce beta-endorphin, suggesting an autocrine mechanism.

Topics: Amino Acid Sequence; beta-Endorphin; Binding Sites; Carcinoma, Small Cell; Cell Division; Cyclic AMP; Humans; Lung Neoplasms; Molecular Sequence Data; Narcotics

Previous reports have demonstrated that beta-endorphin stimulates the clonal growth of human small cell lung carcinoma (SCLC) cell lines. In this study, the human SCLC lines, NCI-H69, NCI-H345, and NCI-N417, were observed to be highly-enriched in saturable, high-affinity binding sites which are labeled by [125I]beta-endorphin. In contrast to conventional opioid receptors, [125I]beta-endorphin SCLC binding was insensitive to naloxone and other mu, delta, or kappa opioid ligands. Further analysis of the NCI-H69 cells demonstrated that specific (naloxone-insensitive) binding was dependent on receptor concentration, reversible, sensitive to sodium ion, but insensitive to the GTP analogue, Gpp(NH)p. These results suggest a role for naloxone-insensitive beta-endorphin in modulating SCLC metabolism.

Topics: Animals; beta-Endorphin; Binding Sites; Binding, Competitive; Carcinoma, Small Cell; Cell Membrane; Humans; Iodine Radioisotopes; Lung Neoplasms; Naloxone; Prosencephalon; Rats; Receptors, Opioid; Sensitivity and Specificity; Tumor Cells, Cultured

The endogenous opioid beta-endorphin, a derivative of proopiomelanocortin, stimulates the growth of cloned human small cell lung carcinoma. The present hypothesis states that mutations of the retinoblastoma gene (a tumor suppressor gene) associated to the malignant transformation of bronchial cells would trigger a cascade of biomolecular events leading to 'de novo' proopiomelanocortin expression in small cell lung carcinoma.

Topics: ACTH Syndrome, Ectopic; beta-Endorphin; Carcinoma, Small Cell; Cushing Syndrome; Female; Gene Expression Regulation, Neoplastic; Genes, fos; Genes, Retinoblastoma; Hormones, Ectopic; Humans; Lung Neoplasms; Models, Biological; Neoplasm Proteins; Pro-Opiomelanocortin; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-fos; Retinoblastoma Protein

Neuroendocrine tumours of the lung may be associated with the ectopic adrenocorticotrophin (ACTH) syndrome and may synthesize and secrete ACTH-related peptides in the absence of the syndrome. However, immunocytochemical analysis may not confirm these biochemical findings, particularly in small cell carcinoma, which is poorly granulated. To investigate further the morphological evidence for expression of the pro-opiomelanocortin (POMC) gene in neuroendocrine lung tumours, we have examined a series of 46 small cell carcinomas and 13 carcinoid tumours of the lung by in situ hybridization for POMC mRNA using a digoxigenin-labelled oligoprobe. We have compared the findings with the immunocytochemical detection of ACTH and beta-endorphin. In situ hybridization was positive in 15 of 46 small cell carcinomas (33 per cent) and in 8 of 13 carcinoid tumours (62 per cent). Immunocytochemical staining was positive in only one carcinoid tumour. These in situ hybridization studies have corroborated biochemical data indicating POMC gene expression in a high proportion of lung neuroendocrine tumours. This suggests that the low levels of expression detected by immunocytochemistry may be due to low levels of hormone storage. Multivariate analysis showed a weak negative association between POMC expression and survival in small cell carcinomas, although this did not reach statistical significance.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; beta-Endorphin; Carcinoid Tumor; Carcinoma, Small Cell; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Lung Neoplasms; Male; Middle Aged; Pro-Opiomelanocortin; RNA, Messenger

We measured plasma corticotropin-releasing hormone (CRH), ACTH, beta-endorphin (beta-EP), and cortisol levels as possible tumor markers in a sequence of 103, randomly selected, patients with lung cancer but without the ectopic Cushing's syndrome and in 72 age- and sex-matched controls. Plasma CRH levels of cancer patients were similar to those of controls both in patients sampled in the morning or in the afternoon. On the other hand, plasma ACTH levels of cancer patients were significantly higher than control patients both in the morning and in the afternoon and showed a preserved circadian rhythm. However, about 35% of cancer patients sampled in the morning and about 60% of those sampled in the afternoon had ACTH levels within the 95% confidence interval (CI) of controls. Also plasma beta-EP levels were more elevated in cancer patients than controls in the morning but about 33% of them and about 80% of those sampled in the afternoon had beta-EP levels within the 95% CI of controls. Despite the higher plasma ACTH levels, cancer patients had cortisol plasma levels similar to controls with preserved circadian rhythm. In conclusion, although mean plasma ACTH and beta-EP were higher in patients affected by lung cancer, their measurements, as well as those of CRH, have practically no diagnostic value. Perhaps measurement of ACTH levels in the bronchial lavage may be more helpful.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; beta-Endorphin; Biomarkers, Tumor; Circadian Rhythm; Corticotropin-Releasing Hormone; Humans; Hydrocortisone; Lung Neoplasms; Middle Aged

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.

Topics: beta-Endorphin; Carcinoma, Small Cell; Circadian Rhythm; Female; Humans; Hydrocortisone; Injections, Subcutaneous; Interleukin-2; Lung Neoplasms; Male; Middle Aged

Melatonin, the most important indole hormone produced by the pineal gland, appears to inhibit tumor growth; moreover, altered melatonin secretion has been reported in cancer patients. Despite these data, the possible use of melatonin in human neoplasms remains to be established. The aim of this clinical trial was to evaluate the therapeutic, immunological and endocrine effects of melatonin in patients with metastatic solid tumor, who did not respond to standard therapies. The study was carried out on 14 cancer patients (colon, six; lung, three; pancreas, two; liver, two; stomach, one). Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m., followed by a maintenance period in an oral dose of 10 mg daily in patients who had a remission, stable disease or an improvement in PS. Before and after the first 2 months of therapy, GH, somatomedin-C, beta-endorphin, melatonin blood levels and lymphocyte subpopulations were evaluated. A partial response was achieved in one case with cancer of the pancreas, with a duration of 18+ months; moreover, six patients had stable disease, while the other eight progressed. An evident improvement in PS was obtained in 8/14 patients. In patients who did not progress, T4/T8 mean ratio was significantly higher after than before melatonin therapy, while it decreased in patients who progressed. On the contrary, hormonal levels were not affected by melatonin administration. This study would suggest that melatonin may be of value in untreatable metastatic cancer patients, particularly in improving their PS and quality of life; moreover, based on its effects on the immune system, melatonin could be tested in association with other antitumor treatments.

Topics: Adenocarcinoma; Aged; B-Lymphocytes; beta-Endorphin; Female; Growth Hormone; Humans; Insulin-Like Growth Factor I; Leukocyte Count; Liver Neoplasms; Lung Neoplasms; Male; Melatonin; Middle Aged; T-Lymphocytes

Topics: beta-Endorphin; Bombesin; Carcinoma, Small Cell; Cell Line; Clone Cells; Humans; Lung Neoplasms; Neurotensin

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.

Topics: beta-Endorphin; Bombesin; Carcinoma, Small Cell; Dose-Response Relationship, Drug; Humans; Lung Neoplasms; Mycoplasma; Tumor Cells, Cultured; Tumor Stem Cell Assay

Recent studies showed that both the pineal gland and the endogenous opioid system are involved in the modulation of the immune system and in the regulation of tumor growth. Moreover, a relationship between pineal and opioid system has been demonstrated. In order get an overall view of the psychoneuroendocrine interactions in cancer patients, the levels of melatonin, the most important pineal hormone, and of beta-endorphin have been measured on blood samples collected during the morning. The study was carried out on 54 patients, 42 healthy subjects, and in 34 patients having illnesses other than cancer. Breast cancer, lung carcinoma, and colorectum cancer were the three neoplasms detected in the patients investigated. Growth hormone (GH), somatomedin-C and prolactin (PRL) levels were also determined. beta-endorphin levels were found to be substantially within the normal range in patients with cancer, whereas those of melatonin were raised in several cases. The beta-endorphin/melatonin ratio was higher than 2 in normal subjects, in non-neoplastic patients and in most cancer patients without metastases, whereas this ratio was lower than 2 in almost all patients in a metastatic stage of the disease. Neither melatonin levels nor those of beta-endorphin appeared to be significantly correlated with GH, somatomedin-C, and PRL concentrations. The low beta-endorphin/melatonin ratio observed in metastatic patients suggests the presence of an unbalanced relation between the pineal and the opioid system in those subjects. Therefore, an anomalous relationship between pineal function and opioid activity might play a role in the clinical course of neoplastic disease.

Topics: Adult; beta-Endorphin; Breast Neoplasms; Colonic Neoplasms; Endorphins; Female; Growth Hormone; Humans; Insulin-Like Growth Factor I; Lung Neoplasms; Male; Melatonin; Middle Aged; Neoplasms; Pineal Gland; Prolactin; Rectal Neoplasms

Endogenous opioid peptides have been seen to play a role in regulating immunity and tumor growth. This study was carried out to investigate opioid activity in human cancer. We evaluated by radioimmunoassay beta-endorphin plasma levels on blood samples collected at 9.00 a.m. from 121 cancer patients and 42 healthy subjects. In 22 cancer patients and in 12 controls, beta-endorphin circadian rhythm was also investigated. Finally, in 14 cancer patients and in 10 controls GH, PRL, FSH, LH and cortisol serum levels were measured after the administration of a metenkephalin analogue, FK 33-824 (0.3 mg i.v.). No significant differences were seen in beta-endorphin mean levels between cancer patients and normal subjects. Moreover, no differences were found between patients with or without metastases, nor between those with or without chronic pain. beta-Endorphin circadian rhythm appeared to be altered in 16/22 cancer patients, and anomalous hormonal responses to FK 33-824 were seen in 13/14 patients. This study shows an altered opioid activity in human neoplasms, whose clinical significance remains to be determined.

Topics: Adult; Aged; beta-Endorphin; Breast Neoplasms; Circadian Rhythm; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Female; Gastrointestinal Neoplasms; Humans; Hydrocortisone; Lung Neoplasms; Male; Middle Aged; Pituitary Hormones, Anterior; Radioimmunoassay

Two human small cell carcinoma cell lines were assayed for total opioid and beta-endorphin-like immunoreactivity. Small cell carcinoma cell line NCI-H146 contained approximately 1.1 pmol/mg protein of total opioid immunoreactivity. This material was similar in size and immunoreactive determinants to C-terminally modified beta-endorphin. Small cell carcinoma cell line NCI-H187 contained approximately 0.2 pmol/mg protein total opioid immunoreactivity, which was of low molecular weight. NCI-H187 also contained approximately 1.2 pmol/mg protein of material similar in size and immunoreactive determinants to beta-lipotropin. The two small cell carcinoma cell lines were also examined for opioid receptors with the use of [3H]-etorphine as ligand. Both cell lines contained between 50 and 100 fmol/mg protein of specific, saturable, high-affinity opioid receptor binding sites. Together, these findings suggest a possible autocrine role for opioids in small cell carcinoma of the lung.

Topics: beta-Endorphin; Carcinoma, Small Cell; Cell Line; Endorphins; Etorphine; Humans; Lung Neoplasms; Receptors, Opioid

ACTH responses to corticotropin-releasing hormone (CRH) were studied in three patients with the ectopic ACTH syndrome caused by lung cancer. Plasma ACTH responded to synthetic CRH in two of three patients. Tumor tissues obtained from these two patients contained CRH and ACTH. In one patient, tumor ACTH secretion was stimulated by CRH in vitro. Tumor CRH was immunologically, chromatographically, and biologically similar to hypothalamic CRH. In addition, multiple forms of immunoreactive beta-endorphin were present in plasma and the tumor extracts. From these results, we conclude that some patients with the ectopic ACTH syndrome have tumors that produce both ACTH and CRH and that CRH can stimulate ACTH secretion by such tumors. Other patients with the ectopic ACTH syndrome do not have ACTH responses to CRH. Therefore, procedures other than CRH testing are needed to differentiate patients with Cushing's syndrome due to ectopic ACTH/CRH production from those with Cushing's disease, since the latter also usually have ACTH responses to CRH.

Topics: ACTH Syndrome, Ectopic; Aged; beta-Endorphin; Carcinoma, Small Cell; Corticotropin-Releasing Hormone; Endorphins; Humans; In Vitro Techniques; Lung Neoplasms; Male; Middle Aged; Paraneoplastic Endocrine Syndromes; Radioimmunoassay

Electrical stimulation of the periaqueductal gray of the rat's midbrain analgesia leads to an increase in the number of artificial pulmonary metastases from the Walker 256 tumor. In an effort to investigate the influence of the pain suppression system and its associated peptides on this phenomenon, we activated the pain suppression system directly from the Nucleus of the Raphe Magnus, a non-opioid subsystem. After inducing analgesia by direct injection of beta-endorphin on the Nucleus of the Raphe Magnus, we noted an increase in the number of artificial pulmonary metastases. This result could be blocked by pretreatment with naloxone. If the Nucleus of the Raphe Magnus was activated by electrical stimulation sufficient to induce analgesia, the metastatic effect was still present but markedly attenuated.

Topics: Animals; beta-Endorphin; Brain Stem; Carcinoma 256, Walker; Endorphins; Female; Lung Neoplasms; Neoplasm Metastasis; Neoplasms, Experimental; Pain; Periaqueductal Gray; Raphe Nuclei; Rats; Rats, Inbred Strains

Topics: Adrenocorticotropic Hormone; Antigens, Neoplasm; beta-Endorphin; Blood Proteins; Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Chorionic Gonadotropin; Endorphins; Humans; Lung Neoplasms; Neoplasm Staging; Paraneoplastic Syndromes

We have previously determined that the cell surface protein phenotype distinguishes human small cell lung carcinoma (SCC), a neoplasm with endocrine properties, from non-SCC in culture. We now demonstrate that cloned cell cultures of human large cell undifferentiated lung carcinoma, established directly from a patient with mixed SCC and non-SCC, simultaneously express surface proteins characteristic of SCC and non-SCC lung cancer cells. Hence, SCC and a form of large cell carcinoma appear linked through a continuum of differentiation events that: (i) may explain clinically important transitions that occur between the major types of human lung cancer and (ii) provide evidence for a common cellular origin of endocrine and nonendocrine cells in the bronchial mucosa.

Topics: Amine Oxidase (Copper-Containing); beta-Endorphin; Calcitonin; Cell Differentiation; Cell Line; Cell Membrane; Clone Cells; Dopa Decarboxylase; Electrophoresis, Polyacrylamide Gel; Endorphins; Humans; Lung Neoplasms; Membrane Proteins

A rare case of metastatic lung cancer from the tonsil associated with ectopic ACTH, beta-LPH and beta-endorphin production was presented. A year ater the tonsillectomy and lymphadenectomy, the patient had metastatic lung cancer. Three years later he died. Brown pigmentation remained evident for a month before his death. Both ACTH and cortisol levels were high in the plasma. ACTH, beta-LPH and beta-endorphin were found in the tissue extracts (squamous cell carcinoma).

Topics: ACTH Syndrome, Ectopic; Adrenocorticotropic Hormone; beta-Endorphin; beta-Lipotropin; Carcinoma, Squamous Cell; Endorphins; Hormones, Ectopic; Humans; Lung Neoplasms; Male; Tonsillar Neoplasms

We report the history, laboratory findings, and studies performed on a 27-yr-old patient with a metastatic parasellar adenoma of the pituitary and Cushing's syndrome. She developed intense hyperpigmentation and extraordinarily high ACTH levels after bilateral adrenalectomy in 1974. With the exception of marked hyperpigmentation, she did well on glucocorticoid replacement therapy until August 1979, when multiple hepatic nodules were observed during a cholecystectomy. Histological studies and immunoperoxidase staining indicated that these lesions were pituitary tumor metastases. What were presumed to be metastatic lesions also developed in lungs and bone. This combination of liver, bone, and lung metastases from primary pituitary tumors has not previously been reported. Immunoreactive plasma ACTH concentrations were as high as 230,000 pg/ml. Similarly, high levels of plasma immunoreactive beta MSH and immunoreactive beta-endorphin were found. High doses of glucocorticoids reduced the concentration of ACTH to one seventh to one tenth the basal level. The sensitivity of plasma ACTH to exogenous steroid administration strongly suggests that an intact intracellular mechanism for negative feedback control of ACTH secretion persisted within the tumor cells. The rapid rise in ACTH and related peptides and the development of metastases after adrenalectomy suggest that both the secretory capacity and the oncogenic potential of the parasellar tumor were chronically inhibited by glucocorticoid hormones.

Topics: Adenoma; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Bone Neoplasms; Dexamethasone; Endorphins; Female; Humans; Hydrocortisone; Liver Neoplasms; Lung Neoplasms; Melanocyte-Stimulating Hormones; Pituitary Neoplasms

Human ACTH-producing tumor and plasma have been examined by gel filtration and ion exchange chromatography to detect the possible presence of reported multiple forms of immunoreactive beta-endorphin (I-EP) Ion exchange chromatography of I-EP obtained from gel filtration showed four components of I-EP [two major peaks in the positions of EP-(1-31) and EP-(1-27) and two minor peaks in the positions of N-acetyl EP-(1-31) and N-acetyl EP-(1-27)] in two ectopic ACTH-producing lung cancers, and two components of I-EP [the major peak in the position of EP-(1-31) and minor peak in the position of N-acetyl EP-(1-31) in an ectopic ACTH-producing thyroid cancer. Only a single peak in the position of EP-(1-31) was present in plasma from a patient with Nelson's sindrome and a patient with Addison's disease, in the pituitary adenomas from six patients with Cushing's disease, and in the nontumorous pituitary tissues from a patient with Cushing's disease and a patient with acromegaly. These data suggest that the posttranslational processing of EP in human pituitary is different from that in the ectopic ACTH-producing tumor.

Topics: Addison Disease; Adenoma; Adrenocorticotropic Hormone; beta-Endorphin; Chromatography, Gel; Chromatography, Ion Exchange; Cushing Syndrome; Endorphins; Humans; Lung Neoplasms; Nelson Syndrome; Pituitary Gland; Pituitary Neoplasms; Radioimmunoassay; Thyroid Neoplasms

beta-Endorphin, a pituitary morphino-mimetic peptide, was identified in a culture medium derived from a human corticotropic adenoma. Secretion products from cultured human cells derived from a small-cell carcinoma of the lung were shown to contain a high molecular weight precursor analagous to pro-opiocortin: this molecule is a polypeptide of the order of 28,000 daltons the enzymatic processing of which leads to the coordinated and simultaneous release of different peptide fragments: ACTH, beta- and gamma-lipotropins, beta-endorphin, fragment 16 K and gamma 3-MSH. All these peptides have been identified in human plasma, and pituitary and non-pituitary tumor extracts. Their plasma concentrations vary in a parallel manner, beta-endorphin and a peptide very similar to beta-MSH have been detected in human hypothalamus.

Topics: Adenoma; Adrenocorticotropic Hormone; beta-Endorphin; beta-Lipotropin; Endorphins; Humans; Hypothalamus; Lung Neoplasms; Pituitary Gland; Pituitary Hormones, Anterior; Pituitary Neoplasms; Pro-Opiomelanocortin; Protein Precursors

The association of hormonal syndrome and APUD (amine precursor uptake, decarboxylase) features with small cell carcinoma of the lung (SCC) has suggested that SCC has a separate cell origin from other major forms of lung cancer. Recently, however, both SCC and non-SCC lung cancers have been found to contain small polypeptide hormones and APUD enzymes. The present study quantitates, in 50 samples of human lung cancer tissue, relationships among the 4 major types of lung cancer and endocrine-related properties. Among 4 parameters measured (dopa decarboxylase, histaminase, beta-endorphin, and calcitonin), no single marker clearly separated SCC from non-SCC lung cancer. The high activity of dopa decarboxylase (the "D" in "APUD") best separated SCC from non-SCC, but significant overlap existed even for this critical APUD property. In fact, 2 adenocarcinomas had among the highest concentrations of dopa decarboxylase, histaminase, and calcitonin of any tumor tissue studied. The simultaneous appearance of high levels of 2 or more markers favored SCC. This was quantitated by deriving an index unit based upon the product of the values for the 4 markers in each lesion. This index separated all SCC from all non-SCC lung carcinomas, with the exception of the above 2 adenocarcinomas. Endocrine-related properties thus occur throughout the spectrum of human lung cancer. Biochemical differences between the major histopathological types are quantitative rather than qualitative and probably reflect the fact that the major forms of lung cancer represent a continuum of differentiation within a common cell lineage which includes both SCC and non-SCC lung tumors.

Topics: Adenocarcinoma; Amine Oxidase (Copper-Containing); APUD Cells; Aromatic-L-Amino-Acid Decarboxylases; beta-Endorphin; Calcitonin; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Dopa Decarboxylase; Endorphins; Humans; Lung Neoplasms