beta-endorphin and Liver-Neoplasms

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

To investigate the mechanism of cinobufagin-reduced cancer pain in mouse cancer pain model and in vitro cell co-culture system.. Female Kunming mice were randomly divided into 4 groups. One group of animals was set as normal control without any treatment. Other three groups of animals received H22 hepatoma cell inoculation in right hind paw. At day 9 after inoculation, mice in other three groups were injected intraperitoneally once a day for 8 days with the solvent, morphine or cinobufagin, respectively. The pain behavior was recorded daily. On the last day, all mice were sacrificed and xenograft tissues homogenate and plasma levels of β-endorphin (β-END), corticotropin-releasing factor (CRF) and interleukin-1β (IL-1β) were assessed by ELISA assay. Immunohistochemistry was performed to determine the expression of β-END, pro-opiomelanocortin (POMC) and the μ-opioid receptor (μ-OR) in the xenograft tissues. Immunofluorescence was used to localize lymphocytes with expression of CD3+, CD4+ and CD8+ in xenograft tumors and adjacent tissues. Mice splenic lymphocytes and H22 hepatoma carcinoma ascites cells were prepared for co-culture. β-END and CRF were detected in co-culture supernatants. The MTT assay and cytometry were used to assess cell proliferation. RT-PCR was conducted to determine the gene expression of POMC and Cathepsin L (CTSL). Chemotaxis was examined using a transwell-based migration assay.. Compared to the model group, the thermal and mechanical pain thresholds were increased in mice after cinobufagin treatment. The expression of β-END and CRF in the plasma and tumor tissues of cinobufagin group were much higher than that of the model group mice, but the expression of IL-1β in the plasma and tumor tissues was much lower than that in the model group mice. Meanwhile, the expression of β-END, POMC and μ-OR proteins was significantly increased in the xenograft tissues from cinobufagin group. Lymphocyte population of CD3+, CD4+, CD8+ were also elevated in xenograft tumors and adjacent tissues. In the cell co-culture assays, the content of β-END in the supernatant was significantly increased by cinobufagin in a dose-dependent manner. Cinobufagin also largely increased the proliferation of immune cells and inhibited H22 hepatoma carcinoma cell proliferation in single or co-culture cell assays. Gene expression of POMC and CTSL in cinobufagin group was significantly up-regulated comparing to the control group. Finally, cinobufagin addition enhanced the migration of immune cells in transwell assay.. Cinobufagin-induced local analgesic effect might be associated with increased activity of POMC/β-END/μ-OR pathway released from invaded CD3/4/8 lymphocytes in cancer tissues.

Topics: Analgesics; Animals; beta-Endorphin; Bufanolides; Carcinoma, Hepatocellular; Cell Line, Tumor; Coculture Techniques; Corticotropin-Releasing Hormone; Disease Models, Animal; Drugs, Chinese Herbal; Enzyme-Linked Immunosorbent Assay; Female; Immunohistochemistry; Interleukin-1beta; Liver Neoplasms; Lymphocytes, Tumor-Infiltrating; Mice; Neoplasms, Experimental; Pain; Pain Threshold; Polymerase Chain Reaction; Random Allocation

Topics: Animals; beta-Endorphin; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Ethanol; Female; Hypothalamus; Liver Neoplasms; Male; Neurons; Pregnancy

Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer.. Male rats received either BEP neuron transplants or control transplants in the hypothalamus and were randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer.. Alcohol feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased the levels of triglyceride, hepatic stellate cell (HSC) activation factors, and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocellular carcinoma (HCC), collagen deposition, numbers of preneoplastic foci, levels of HSC activation factors and catecholamines, as well as inflammatory milieu and increased the levels of natural killer cell cytotoxic factors in the liver.. These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and HCC formation possibly via influencing the immune function.

Topics: Animals; beta-Endorphin; Cells, Cultured; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Ethanol; Female; Hypothalamus; Liver Neoplasms; Male; Neurons; Pregnancy; Random Allocation; Rats; Rats, Inbred F344; Rats, Sprague-Dawley

The case of a 60-year-old female with severe and rapidly progressing Cushing's syndrome with fatal consequences is described. Both the clinical and the biochemical findings were consistent with ectopic ACTH production. A computed tomographic (CT) scan revealed intact pituitary and enlarged adrenal glands. Liver metastases were seen but the primary neoplasm was not found. Treatment with aminoglutethimide and other therapeutic measures were unsuccessful. A carcinoma of the right ovary was discovered on autopsy. The tumour cells showed immunoreactivity for neuron-specific enolase (NSE), ACTH and beta-endorphin with differing degree of intensity.

Topics: ACTH Syndrome, Ectopic; Adrenocorticotropic Hormone; beta-Endorphin; Cushing Syndrome; Fatal Outcome; Female; Humans; Liver Neoplasms; Lymphatic Metastasis; Middle Aged; Ovarian Neoplasms; Phosphopyruvate Hydratase

We have investigated whether parotin subunit (PS) and its partial synthetic peptide (P-10.2: TDDTAIVLLK), possess interleukin 1 (IL-1)-like activities, and act on cell lines other than lymphocytes. When Chang liver cells were cultured with P-10.2, PS or IL-1, P-10.2 and PS augmented the growth of Chang liver cells. On the other hand, IL-1 enhanced the growth of Change liver cells at 1 day of the initial culture and subsequently failed to enhance during at least 4-day incubation. Next, effects of P-10.2 and PS on the growth of Alexander cells and MH134 were investigated. The proliferation of Alexander cells was inhibited with P-10.2 or PS but not with IL-1. P-10.2 inhibited the growth of MH134 at day 1 and 3, while the growth of MH134 was shown not to be inhibited with PS and IL-1 at day 1, but rather suppressed them at day 3. These results suggest that P-10.2 augments the growth of non-malignant liver cells (Chang liver cells) but inhibits that of hepatoma cells (Alexander cells and MH134). P-10.2 enhanced fibrinogen and hepatoglobin secretion from Chang liver cells. In addition to their liver cell activation, P-10.2 and PS stimulated ACTH and beta-endorphin secretion from AtT-20 cells.

Topics: Adrenocorticotropic Hormone; Amino Acid Sequence; Animals; beta-Endorphin; Brain; Carcinoma, Hepatocellular; Cell Division; Cell Line; Fibrinogen; Globins; Humans; Interleukin-1; Liver; Liver Neoplasms; Liver Neoplasms, Experimental; Macromolecular Substances; Mice; Molecular Sequence Data; Peptide Fragments; Pituitary Neoplasms; Salivary Proteins and Peptides; Tumor Cells, Cultured

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

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