beta-endorphin and Adenocarcinoma

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

The opioids beta-endorphin and the dynorphins belong to two separate families of endogenous opioid peptides (EOP). They are produced not only in the central nervous system but also in nonneural tissues where, as it appears, they act locally via paracrine mechanisms. These opioids have been shown to be produced at multiple sites along the mammalian reproductive tract including the intrauterine cavity. The aim of the present work was to find out if the well differentiated human endometrial cell line of Ishikawa, which has been shown to be a good in vitro model for the study of the effects of steroid hormones on human epithelial endometrium, expresses these two EOP. Northern blot hybridization of RNA from these cells showed the presence of a 1.2-kb POMC and a 2.4-kb PDYN transcript. Radioimmunoassay and gel filtration chromatography characterization of the immunoreactive (IR) opioid peptides present in the culture media showed the presence of IR-beta-endorphin and IR-dynorphins. The apparent molecular weight of IR-beta-endorphin was that of authentic beta-endorphin while the bulk of the IR-dynorphin had an apparent molecular weight of 8 kd. The secretion of both opioids could be increased by KCl-induced depolarization. Estrogen and glucocorticoids decreased, in a dose- and time-dependent manner, the secretion of beta-endorphin from the Ishikawa cells while progesterone and dihydrotestosterone did not have a statistically significant effect. The antiprogestin-antiglucocorticoid RU486 acted as an agonist, i.e., it diminished beta-endorphin secretion possibly via glucocorticoid receptors. On the other hand, the secretion of dynorphins was not affected by any of the steroids tested while LHRH, the inducer of gonadotropins and anterior pituitary dynorphins secretion, provoked a time- and dose-dependent increase of their secretion without affecting that of beta-endorphin. These data suggest that the regulation of endometrial opioids production is type-specific. Thus, it is possible that each type of endometrial opioid participates in different local homeostatic loops and exerts distinct paracrine effects.

Topics: Adenocarcinoma; Animals; beta-Endorphin; Blotting, Northern; Dexamethasone; Dynorphins; Endometrial Neoplasms; Estradiol; Female; Hormones; Humans; Male; Mifepristone; Potassium Chloride; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tamoxifen; Tumor Cells, Cultured

Topics: Adenocarcinoma; Adrenocorticotropic Hormone; Anesthesia, Endotracheal; Anesthesia, Epidural; beta-Endorphin; Chronic Disease; Enkephalin, Leucine; Humans; Insulinoma; Intraoperative Care; Pain, Postoperative; Pancreatic Neoplasms; Pancreatitis; Postoperative Care; Stress, Physiological

Maharishi-4 (M-4), an ayurvedic food supplement, was tested for anticarcinogenic and anticancer properties against 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats. The 6% M-4-supplemented diet protected DMBA-induced carcinogenesis by reducing both tumor incidence and multiplicity during initiation and promotion phases. The control animals who developed tumors when supplemented with M-4 diet for four weeks showed tumor regression in 60% of cases. There was no significant difference in the food intake or weight gain in rats who were on M-4-supplemented diet compared to control group. Possible mechanisms of action of M-4 are discussed.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; beta-Endorphin; Enkephalin, Methionine; Estradiol; Female; Hypothalamus; Mammary Neoplasms, Experimental; Medicine, Ayurvedic; Pituitary Gland; Plants, Medicinal; Prolactin; Rats; Rats, Inbred Strains

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

beta-Endorphin-like immunoreactivity was detected in the mucosa and muscle layer of normal colon, adenocarcinomas derived from the colon mucosa, and colon polyps which were histologically confirmed to be adenoma without a focus of carcinoma or with in situ carcinoma. The contents of beta-endorphin-like immunoreactivity in adenocarcinomatous tissue (11.94 +/- 1.77 pmol/g wet wt) and colon polyps without focus of carcinoma (10.71 +/- 1.50 pmol/g wet wt) were found to be significantly higher than those in the mucosal layer (6.86 +/- 0.64 pmol/g wet wt) and muscle layer (8.30 +/- 0.68 pmol/g wet wt) of normal colon. These data suggest that the production of beta-endorphin-like immunoreactivity is specifically increased in some adenocarcinomas and adenomatous polyps and may be related to the alteration of bowel habits. Gel exclusion chromatography of beta-endorphin-like immunoreactivity revealed three peaks corresponding to beta-endorphin, beta-lipotropin, and an immunoreactive form between the two. In the mucosal layer and muscle layer of the colon, a broad major peak was eluted at the position of beta-endorphin, and minor peaks were eluted at the position of beta-lipotropin and between beta-endorphin and beta-lipotropin. In adenocarcinoma and polyp, the peak size corresponding to authentic beta-lipotropin was greater than that of beta-endorphin. This study demonstrated that beta-endorphin-like immunoreactivity existed at a high concentration in some colon adenocarcinomas and polyps whose elution patterns were different from those of normal colon tissue.

Topics: Adenocarcinoma; Adult; Aged; beta-Endorphin; beta-Lipotropin; Chromatography, Gel; Colon; Colonic Neoplasms; Colonic Polyps; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Muscle, Smooth; Radioimmunoassay; Reference Values

beta-Endorphinlike immunoreactivity and somatostatinlike immunoreactivity were detected in the mucosa and muscle layer of normal gastric antrum and corpus and in moderately differentiated adenocarcinoma derived from the antral mucosa. The concentration of beta-endorphinlike immunoreactivity in the normal gastric tissues was 4-15 pmol/g wet wt tissue; this value varied from 9.64 to 241.39 pmol/g wet wt tissue (81.38 +/- 37.82 pmol/g wet wt tissue) in adenocarcinomas. The concentration of somatostatinlike immunoreactivity was 18-25 pmol/g wet wt tissue in normal gastric mucosa, whereas it was 1-2 pmol/g wet wt tissue in adenocarcinomas. Gel exclusion chromatography of beta-endorphinlike immunoreactivity revealed two peaks corresponding to beta-endorphin and beta-lipotropin. In normal mucosa and in the whole layer of antrum, the major peak was eluted near the position of beta-lipotropin, and the minor broad peak was eluted near the position of beta-endorphin. In contrast, in adenocarcinoma, beta-endorphinlike immunoreactivity was eluted broadly at the position of beta-endorphin and the other smaller peak was at the position of beta-lipotropin. Gel exculsion chromatography of somatostatinlike immunoreactivity also showed different patterns between antral mucosa and adenocarcinoma. This study revealed the presence of the opioid peptide, beta-endorphinlike immunoreactivity, not only in normal gastric tissue but also in adenocarcinomas with highly increased concentration and different elution patterns in combination with decreased concentration of somatostatinlike immunoreactivity.

Topics: Adenocarcinoma; beta-Endorphin; Chromatography, Gel; Endorphins; Gastric Mucosa; Humans; Lipoproteins, LDL; Muscles; Peptides; Pyloric Antrum; Radioimmunoassay; Stomach Neoplasms

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