Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A new type of immuno-cell therapy called BRM-activated killer (BAK) therapy using non-MHC-restricted lymphocytes, CD56-positive cells, was devised. Peripheral blood lymphocytes were selected by immobilization with anti-CD3 monoclonal antibody and cultured for 2 weeks in the presence of IL-2. Thereafter, they were reactivated by 1,000 U/ml of IFN-alpha for 15 min. Twenty-six outpatients with cancer whose performance status were over 80% on Karnofsky scale were selected for this study. About 6 x 10(9) BAK cells were returned by intravenous drip infusion, at one month intervals at an outpatient clinic to each of 20 advanced cancer patients in whom many metastatic lesions were found postoperatively, and to 6 patients with no postoperatively detectable metastases. The proportion of CD56-positive cells increased from 20% to 50% with culture. CD56-positive cells have strong cytotoxic activity and produced 20 ng/10(9) cells of beta-endorphin, an intracerebral hormone. During the course of BAK therapy, we adopted the Face scale as a QOL indicator. The QOL of all patients remained satisfactory or improved. Beta-endorphin is thought to make patients feel well and maintains good QOL because of its potent analgesic, sedative activity. From that facts that CD56 is a neural cell adhesion molecule and a member of the Ig superfamily, and that the CD56-positive cell produces beta-endorphin, we concluded that the CD56-positive cell is a multifunctional, integrated NIE (neuro-immune-endocrine) cell. Administration of BAK cells allowed all 20 advanced cancer patients with metastases to survive for over one year. All 6 patients receiving the same therapy for prevention of postoperative metastasis have been recurrence-free for one to five years.
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PMID:Effector mechanism and clinical response of BAK (BRM-activated killer) immuno-cell therapy for maintaining satisfactory QOL of advanced cancer patients utilizing CD56-positive NIE (neuro-immune-endocrine) cells. 1147 30

Four pituitary carcinoma metastases [two adrenocorticotropic hormone (ACTH) and prolactin cell tumors each] were studied by comparative genomic hybridization. Chromosomal gains were found in all four carcinoma metastases, but losses only in the two prolactin cell carcinoma metastases. Overall, pituitary carcinoma metastases showed an average of 8.3 chromosomal imbalances per tumor (7 gains vs 1.3 losses), 10 in prolactin cell carcinoma metastases (7.5 gains vs 2.5 losses) and 6.5 in ACTH cell carcinoma metastases (6.5 gains vs 0 loss). The most common changes were gains of chromosome 5, 7p, and 14q (in three tumors each). High-level gains were found on 13q22-qter and 14q (two cases each) and on 1q, 3p, 7, 8, 9p, and 21q (one case each). To date, gains of chromosome 14q have not been reported among pituitary tumors. It remains to be shown whether gain of 14q is associated with malignant progression and metastatic dissemination of pituitary carcinomas.
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PMID:Chromosomal aberrations in pituitary carcinoma metastases. 1156 25

Megestrol acetate (MA) has glucocorticoid activity and can induce significant secondary adrenal suppression. We designed this study to determine the extent of adrenal insufficiency in cancer patients receiving MA by utilising a sensitive low-dose adrenocorticotropin (ACTH) stimulation test. Adrenal function was assessed by a low-dose (0.625 microg) ACTH (1-24) stimulation test in 30 patients receiving MA for metastatic cancer. 10 of the patients who failed this test underwent a standard (250 microg) test on another day. Adrenal function was also evaluated in 15 of the patients by measuring the excretion of free cortisol in 24-h urine samples. Peak serum cortisol levels following stimulation with low-dose (0.625 microg) ACTH (1-24) were <18 microg/dl in 16 of 30 (53%) patients, of whom 9 had a basal serum cortisol level of <5 microg/dl. Five of 16 poor responders to the low-dose test showed normal stimulation with the standard (250 microg) ACTH (1-24) test. Thus, adrenal insufficiency would fail to be detected by the standard high dose test in these patients. Patients who failed the low-dose ACTH (1-24) test had lower 24-h urinary free cortisol excretion (8.7+/-10.3 microg/24 h) than normal responders (35+/-12.7 microg/24 h). Impaired adrenal function is common in cancer patients receiving MA. The low-dose ACTH (1-24) test is apparently capable of revealing adrenal insufficiency undetected by the standard high-dose ACTH test. Patients receiving MA might have inadequate adrenal function during episodes of infection or after withdrawal of MA therapy and this may require prompt corticosteroid treatment.
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PMID:A low-dose adrenocorticotropin test reveals impaired adrenal function in cancer patients receiving megestrol acetate therapy. 1455 38

We report five silent corticotroph carcinomas of the pituitary gland. They represent 0.05% of adenohypophyseal tumors surgically treated at Mayo Clinic during a 20-year period and about 5% of all reported pituitary carcinomas. The patients (three females and two males), ranging in age from 26 to 58 years (mean 39 years, median 35 years) presented with symptoms of mass effect; none had Cushing's disease. All tumors were initially invasive macroadenomas, recurred locally, and metastasized, three outside the central nervous system. The follow-up period ranged from 2 to 23 years (mean 10.6 years). All patients died, four of disseminated tumor and one of myocardial infarction. Histologically, three of the primary lesions were indistinguishable from an ordinary benign adenoma. Two were initially diagnosed as atypical adenomas as they featured nuclear pleomorphism, prominent nucleoli, mitotic activity, high MIB-1 labeling indices, and p53 overexpression. For the purpose of comparison, 17 silent corticotroph adenomas were also investigated. In addition, the clinicopathologic features of the silent carcinomas were compared with those of a meta-analysis of published Cushing's disease-associated pituitary carcinomas. The silent adrenocorticotropin carcinomas showed a propensity for extraneural dissemination and an outcome similar to those of the Cushing's disease-associated carcinomas. The two patients with initial atypical tumors died with metastases outside the central nervous system at 2 and 4 years, whereas the three patients with tumors lacking atypia died 16, 18, and 23 years after initial sellar surgery.
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PMID:Silent corticotroph carcinoma of the adenohypophysis: a report of five cases. 1265 32

Scintigraphic imaging of metastatic melanoma lesions requires highly tumor-specific radiopharmaceuticals. Because both melanotic and amelanotic melanomas overexpress melanocortin-1 receptors (MC1R), radiolabeled analogues of alpha-melanocyte-stimulating hormone (alpha-MSH) are potential candidates for melanoma diagnosis. Here, we report the in vivo performance of a newly designed octapeptide analogue, [betaAla(3), Nle(4), Asp(5), D-Phe(7), Lys(10)]-alpha-MSH(3-10) (MSH(OCT)), which was conjugated through its N-terminal amino group to the metal chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to enable incorporation of radiometals (e.g., indium-111) into the peptide. DOTA-MSH(OCT) displayed high in vitro MC1R affinity (IC(50) 9.21 nM). In vivo [(111)In]DOTA-MSH(OCT) exhibited a favorable biodistribution profile after injection in B16-F1 tumorbearing mice. The radiopeptide was rapidly cleared from blood through the kidneys and, most importantly, accumulated preferentially in the melanoma lesions. Lung and liver melanoma metastases could be clearly imaged on tissue section autoradiographs 4 h after injection of [(111)In]DOTA-MSH(OCT). A comparative study of [(111)In]DOTA-MSH(OCT) with [(111)In]DOTA-[Nle(4), D-Phe(7)]-alpha-MSH ([(111)In]-DOTA-NDP-MSH) demonstrated the superiority of the DOTA-MSH(OCT) peptide, particularly for the amount of radioactivity taken up by nonmalignant organs, including bone, the most radiosensitive tissue. These results demonstrate that [(111)In]DOTA-MSH(OCT) is a promising melanoma imaging agent.
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PMID:DOTA alpha-melanocyte-stimulating hormone analogues for imaging metastatic melanoma lesions. 1285 39

Most patients suffering from breast carcinoma do not die due to the primary tumor but from the development of metastases. Active migration of cancer cells is a prerequisite for development of these metastases. We used time-lapse videomicroscopy and computer-assisted cell tracking of MDA-MB-468 human breast carcinoma cells, which were incorporated into a three-dimensional collagen matrix, in order to analyze the migratory activity of these cells in response to different neurotransmitters. Our results show that met-enkephalin, substance P, bombesin, dopamine, and norepinephrine have a stimulatory effect on the migration of the breast cancer cells; moreover, these cells show positive chemotaxis towards norepinephrine as was analyzed by the directionality and persistence on a single-cell basis. Gamma-aminobutyric acid (GABA) however has an inhibitory effect. Endorphin and leu-enkephalin, as well as histamin and acetylcholine, had no influence on the migratory activity of the cells. In summary, we provide evidence for a strong regulatory involvement of neurotransmitters in the regulation of breast cancer cell migration, which might provide the basis for the use of the pharmacological agonists and antagonists for the chemopreventive inhibition of metastasis development.
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PMID:Effects of neurotransmitters on the chemokinesis and chemotaxis of MDA-MB-468 human breast carcinoma cells. 1288 99

Iris melanomas are less likely to metastasize than posterior compartment melanomas. The anterior chamber of the eye is an immunosuppressed microenvironment where a wide range of immunosuppressive factors in aqueous humor contribute to the immune privilege. One such factor is alpha-melanocyte-stimulating hormone, a potent anti-inflammatory neuropeptide that exhibits efficacy in many studies of acute and chronic inflammation. The aim of this study was to investigate whether the different metastatic behavior of iris melanomas versus posterior compartment melanomas might be explained by the differing immunosuppressive/anti-inflammatory environments of these tumors in vivo. To investigate this hypothesis, we studied the effect of human aqueous and vitreous fluids, of the proinflammatory cytokine tumor necrosis factor alpha, and of the anti-inflammatory peptides alpha-melanocyte-stimulating hormone and melanocyte-stimulating hormone 11-13 (KP-D-V) on the invasion of three human uveal melanoma cell lines through human fibronectin. Fresh aqueous humor samples significantly decreased the invasion in two out of three uveal melanoma cell lines. In contrast, vitreous humor did not reduce invasion. Tumor necrosis factor alpha significantly increased the invasiveness of uveal melanoma cell lines by approximately 50%-80% over 20 h. Full-length alpha-melanocyte-stimulating hormone, at concentrations present in the aqueous humor (10-9 M), as well as melanocyte-stimulating hormone 11-13 (KP-D-V) reduced the invasion of cells through human fibronectin by 45%-50% and also protected uveal melanoma cells from the pro-invasive actions of tumor necrosis factor alpha. These data are consistent with inflammation playing a major role in affecting the metastatic ability of uveal melanomas. Thus, ocular microenvironments that differ in their immunosuppressive/anti-inflammatory properties may influence the invasiveness of developing tumors.
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PMID:Tumor necrosis factor alpha increases and alpha-melanocyte-stimulating hormone reduces uveal melanoma invasion through fibronectin. 1292 15

Following the first synthesis of tritiated alpha-melanocyte-stimulating hormone (alpha-MSH, alpha-melanotropin) in 1974 by Medzihradszky et al., several alpha-MSH analogs were designed containing between 2 and 12 tritium atoms, the latter of which displayed a specific radioactivity of 12.21 GBq/micromol (330 Ci/mmol). Similarly, radioiodinated alpha-MSH analogs of high purity, full biological activity and a specific radioactivity of approximately 140 GBq/micromol were obtained. Although tritiated and radioiodinated alpha-MSH became indispensable tools as tracer molecules for numerous in vitro and in vivo studies, above all for receptor identification and characterization as well as for structure-activity studies, they did not fulfill the criteria required for therapeutic in vivo targeting of metastatic melanoma. Therefore, we recently developed alpha-MSH analogs containing the universal metal chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) in different positions of the molecule. As DOTA can equally well incorporate diagnostic (e.g. (111)In, (67,68)Ga) and therapeutic (e.g. (90)Y, (67)Cu) radionuclides, DOTA-MSH compounds may serve for both melanoma scintigraphy and therapy. The analog DOTA-[betaAla(3), Nle(4), Asp(5), D-Phe(7), Lys(10)]-alpha-MSH(3-10) (DOTA-MSH(OCT)), which contains the metal chelator at its N-terminal end, displayed good in vitro MC1R affinity (IC(50) 9.21 nm). In vivo, [(111)In]DOTA-MSH(OCT) exhibited a favorable biodistribution profile after injection in B16-F1 tumor-bearing mice. The radiopeptide was rapidly cleared from blood through the kidneys and, most importantly, accumulated preferentially in the melanoma lesions. Lung and liver melanoma metastases could be clearly imaged on tissue section autoradiographs 4 h after injection of [(111)In]DOTA-MSH(OCT). A comparative study of [(111)In]DOTA-MSH(OCT) with [(111)In]DOTA-[Nle(4), D-Phe(7)]-alpha-MSH ([(111)In]DOTA-NDP-MSH) demonstrated the superiority of the DOTA-MSH(OCT) peptide, particularly with respect to the amount of radioactivity taken up by non-malignant organs, including bone, the most radiosensitive tissue. These results demonstrate that [(111)In]DOTA-MSH(OCT) specifically targets melanoma metastases and represents a lead compound for the development of therapeutic DOTA-MSH analogs.
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PMID:Radiolabeled alpha-melanocyte-stimulating hormone analogs for receptor-mediated targeting of melanoma: from tritium to indium. 1452 36

Adrenocorticotropic hormone (ACTH)-independent hypercortisolism accounts for 15%-20% of cases of Cushing syndrome and always arises from primary adrenal disease. Computed tomographic (CT) and magnetic resonance (MR) imaging findings in 37 patients with primary adrenal Cushing syndrome were analyzed and correlated with pathologic findings. Hyperfunctioning adenomas (n = 24), together with functioning carcinomas (n = 10), accounted for 92% of cases. Adenomas had a significantly smaller mean size (3.5 vs 14.5 cm) and lower mean unenhanced CT attenuation value (11 vs 28 HU) than did carcinomas. The presence of necrosis, hemorrhage, and calcification favored a diagnosis of carcinoma. Six of 10 carcinoma patients had metastases at presentation. Two adenomas were seen within a myelolipoma, which was recognized at both CT and MR imaging due to its fat content, and two adenomas were of uncertain malignant potential. Bilateral disease--primary pigmented nodular adrenal dysplasia (PPNAD) (n = 2) and ACTH-independent macronodular adrenal hyperplasia (AIMAH) (n = 1)--had characteristic imaging features. In PPNAD, multiple tiny (2-5-mm) nodules were visible bilaterally, with no overall glandular enlargement and normal intervening adrenal tissue. In AIMAH, both glands were grossly enlarged and contained nodules up to 3 cm in diameter. Familiarity with the range of imaging appearances of the adrenal glands in primary adrenal Cushing syndrome may help establish the underlying diagnosis.
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PMID:CT and MR imaging of the adrenal glands in ACTH-independent cushing syndrome. 1502 92

Pituitary carcinomas, defined as distant metastases of a pituitary neoplasm, are rare; fewer than 140 reports exist in the English literature. The initial presenting pituitary tumor is usually a secreting, invasive macroadenoma, with adrenocorticotropic hormone (ACTH)--and prolactin (PRL)--secreting tumors being the most common. The latency period between the diagnosis of a pituitary tumor and the diagnosis of a pituitary carcinoma is 9.5 years for ACTH-producing lesions and 4.7 years for PRL-secreting tumors. Survival after documentation of metastatic disease is poor; 66% of patients die within 1 year. Treatment options include additional surgery, radiotherapy, and chemotherapy, all of which are associated with poor results. Future studies will focus on identifying those invasive pituitary tumors most likely to metastasize and treating them aggressively before they progress to pituitary carcinomas.
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PMID:Pituitary carcinoma: a review of the literature. 1619 64


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