Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty patients with malignant carcinoid tumors were treated for 6 months with recombinant interferon alfa-2b (IFN alpha-2b; Intron-A; Schering Corp., Bloomfield, NJ) at a mean dose of 5.9 megaunits three times per week. Eleven of the 20 patients (55%) had a greater than 50% reduction of tumor markers (urinary 5-hydroxyindoleacetic acid or plasma neuropeptide K), showing objective tumor response. Six patients (30%) had stable disease with no significant change in tumor markers or tumor size, and three (15%) had progressive disease with an increase in tumor markers and size. These results are similar to those reported earlier for treatment with natural leukocyte IFN in patients with carcinoid tumors. Only two patients (35%) had a slight reduction of tumor size after 6 months of treatment. Three patients developed neutralizing antibodies to IFN alpha-2b. Two of these patients initially showed an objective response, which lasted until IFN antibodies developed. In one of these patients, a change to human leukocyte IFN resulted in normalization of antibody titers within 3 months, and the patient had a second objective clinical response. There was no correlation between development of IFN antibodies and development of autoimmune phenomena such as increased titers of antinuclear antibodies or thyroid autoantibodies. IFN alpha-2b seems to be as potent as human leukocyte IFN in the treatment of patients with malignant carcinoid tumors, but it is important to recognize that antibodies neutralizing IFN may develop in some patients, with concomitant loss of antitumor effects. A change to natural leukocyte IFN might be beneficial in these patients.
J Natl Cancer Inst 1989 Apr 05
PMID:Treatment of malignant carcinoid tumors with recombinant interferon alfa-2b: development of neutralizing interferon antibodies and possible loss of antitumor activity. 246 28

This report presents concomitant occurrence of an adrenal ganglioneuroma and a contralateral pheochromocytoma in a patient with von Recklinghausen's disease. The patient's daughter also has cutaneous neurofibromatosis and an adrenal medullary tumor indicating that the observed "three component disease" may represent an inherited neurocristopathy. Immunocytochemically the ganglioneuroma showed a positive reaction with a tyrosinhydroxylase antiserum, but a negative reaction with a dopamine-beta-hydroxylase antiserum, suggesting the capacity of dopamine synthesis. Frequent ganglion cells were immunopositive against neuropeptide Y, but occasional ganglion cells were also positive against enkephalin and substance P. Adrenergic nerve fibers were abundant in the Schwann cell portion of the tumor, but peptide containing nerve cell processes were also demonstrated.
Cancer 1989 Jan 15
PMID:Concomitant occurrence of an adrenal ganglioneuroma and a contralateral pheochromocytoma in a patient with von Recklinghausen's neurofibromatosis. An immunocytochemical study. 249 53

The common acute lymphoblastic leukemia antigen (CALLA) is a 749-amino acid type II integral membrane protein expressed by most acute lymphoblastic leukemias, certain other lymphoid malignancies with an immature phenotype, and normal lymphoid progenitors. A computer search against the most recent GenBank release (no. 56) indicates that human CALLA cDNA encodes a protein nearly identical to the rat and rabbit neutral endopeptidase 24.11 ("enkephalinase;" EC 3.4.24.11). This zinc metalloendopeptidase, which has been shown to inactivate a variety of peptide hormones including enkephalin, chemotactic peptide, substance P, neurotensin, oxytocin, bradykinin, and angiotensins I and II, had not been identified in lymphoid cells. To determine whether CALLA cDNA derived from human acute lymphoblastic leukemia cells (Nalm-6 cell line) encodes functional neutral endopeptidase activity, we generated CALLA+ stable transfectants in the CALLA- murine myeloma cell line J558 and analyzed them for enzymatic activity in a fluorometric assay based upon cleavage of the substrate glutaryl-Ala-Ala-Phe 4-methoxy-2-naphthylamide at the Ala-Phe bond. Total lysates as well as whole-cell suspensions of the Nalm-6 line and of the CALLA+ transfectants, but not of the CALLA- J558 cells, possessed neutral endopeptidase activity. This enzymatic activity was associated with the cellular membrane fraction and was abrogated by the specific neutral endopeptidase inhibitor phosphoramidon. The unequivocal identification of CALLA as a functional neutral endopeptidase provides insight into its potential role in both normal and malignant lymphoid function.
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PMID:Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 ("enkephalinase"): direct evidence by cDNA transfection analysis. 252 88

Mid-gut carcinoid tumors have been shown to produce substance P, a tachykinin. A recent addition to this family of peptides is neurokinin A which is cleaved from the same precursor as substance P; beta-pre-pro-tachykinin. The authors have examined mid-gut and pulmonary carcinoid tumors for the presence of the two tachykinins, using immunocytochemical study and radioimmunoassay, and have applied the techniques of in situ hybridization and Northern blot analysis to investigate the expression of mRNA for beta-pre-pro-tachykinin. All gut tumors (n = 8) and three of the six lung tumors examined were found by immunocytochemical study to contain both tachykinins or neurokinin A alone. Chromatographic analysis of tumor extracts suggests that this peptide is being detected as a separate molecule and/or as the C-terminal portion of a larger, uncleaved form. Three of the cases positive for tachykinins showed no detectable serotonin immunoreactivity. Strong hybridization signals for beta-pre-pro-tachykinin mRNA were seen in all but one of the cases studied which contained tachykinin immunoreactivity. Intact mRNA and positive hybridization was found by Northern blot analysis in two mid-gut tumors. Concentrations of tachykinins were found by radioimmunoassay to be higher in mid-gut tumors (substance P 27.2 +/- 19.7 pmol/g; neurokinin A 31.8 +/- 24.2 pmol/g; mean +/- SEM, n = 5) than in lung cases (substance P mean 0.8, range 0.5-1.0 pmol/g; neurokinin A mean 11.0, range 10.0-12.0 pmol/g; n = 3). These results show that mid-gut and pulmonary carcinoid tumors produce tachykinins, which are detected, in some cases, where no serotonin immunoreactivity can be found, possibly because of a high rate of amine secretion. Screening for tachykinins may prove to be a useful diagnostic adjunct for these tumors.
Cancer 1989 Mar 15
PMID:Expression of tachykinins by ileal and lung carcinoid tumors assessed by combined in situ hybridization, immunocytochemistry, and radioimmunoassay. 264 37

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.
J Cancer Res Clin Oncol 1988
PMID:Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects. 283 87

Bombesins are potent growth factors for murine Swiss 3T3 cells. Using these cells in chemically defined conditions we have been able to characterise the bombesin receptor and the early signals preceding DNA synthesis. We describe two substance P analogues [DArg1, DPro2, DTrp7,9, Leu11] substance P and [DArg1, DPhe5, DTrp7,9, Leu11] substance P which competitively block the binding of bombesins to their receptor and all the events leading to mitogenesis. Bombesins are secreted by human small cell lung cancers (SCLC) and may act as autocrine growth factors for these tumours, so the development of peptide bombesin antagonists could have therapeutic implications. We demonstrate that the antagonists can reversibly inhibit the growth of SCLC in vitro, with relatively little effect on other lung tumours.
Br J Cancer 1988 Jun
PMID:Bombesin and bombesin antagonists: studies in Swiss 3T3 cells and human small cell lung cancer. 284 62

Using the "Bi-Digital O-Ring Test Molecular Identification and Localization Method," one can identify and localize minute amounts of bioactive substances (including neurotransmitters), micro-organisms, toxic substances, or drugs, and, in addition, one can non-invasively image normal organs as well as screen for and image the distribution of specific types of cancer of specific internal organs without using any expensive instrumentation. One can also use this method to perform a qualitative analysis of neurotransmitters, neuromodulators, and hormones on different parts of the imaged organs. The molecule or substance being investigated is compared with a minute amount of a pure control reference substance, and if the substance identical to the control reference substance exists, then the electro-magnetic waves emitted by the identical substance will produce an electro-magnetic resonance phenomenon with the electro-magnetic waves of identical resonance frequency emitted by the control reference substance, and this resonance phenomenon is hypothesized to be the basis of the "Bi-Digital O-Ring Test Molecular Identification and Localization Method." The following substances have been used as control reference substances to identify and localize identical substances in vitro and in vivo: pure neurotransmitters (e.g. serotonin, beta-endorphin, methionine-enkephalin, norepinephrine, dopamine, L-dopa, substance P, etc.), as well as L-tryptophan and L-tyrosine; cholesterol; steroid hormones (including aldosterone, corticosterone, cortisol, progesterone, testosterone, etc.); peptide hormones; microscopic slides of normal organs; microscopic slides of specific cancer cells of specific organs (e.g. adenocarcinoma of the head of the pancreas, adenocarcinoma of the descending colon, etc.); microscopic slides of pure micro-organisms; toxic substances (e.g. lead, mercury, KCN); drugs (including non-steroidal anti-inflammatory drugs, antibiotics, beta-blockers, calcium channel blockers, etc.); and antibodies against specific substances or micro-organisms. An intensive network of serotonin and L-tryptophan was discovered, by using the "Bi-Digital O-Ring Test Molecular Identification and Localization Method," in different parts of the body. In general, in painful areas, frequently serotonin is markedly reduced, L-tryptophan is markedly increased, and substance P is markedly increased, while in non-painful areas, serotonin is markedly increased, L-tryptophan is markedly decreased, and substance P is markedly decreased.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:"Bi-digital o-ring test molecular identification and localization method" and its application in imaging of internal organs and malignant tumors as well as identification and localization of neurotransmitters and micro-organisms--Part 1. 287 19

This study was undertaken to assess the prevalence and characteristic hormonal profile of endocrine cells in Barrett's mucosa and to determine to what extent this profile was shared by endocrine cells of adenocarcinomas arising therefrom. In addition, lower oesophageal carcinomas, not associated with columnar metaplasia, were examined to see if they exhibited a different hormonal profile. The patients studied comprised 43 who had had multiple oesophageal biopsies. 35 who had had oesophagogastric resection for adenocarcinoma arising in Barrett's mucosa and 26 in whom the resection showed no metaplastic epithelium adjacent to tumour. Argyrophil cells were present in 90% of biopsies and resections of Barrett's mucosa combined, irrespective of the histological type of metaplastic epithelium. By immunocytochemistry the most frequently identified substance in mucosal endocrine cells was serotonin (82%) followed by somatostatin (54%), secretin (22%) and pancreatic polypeptide (17%). Gastrin, bombesin, cholecystokinin, ACTH and substance P were not identified in metaplastic mucosa in any case. The difference in expression of serotonin by endocrine cells of tumours arising in Barrett's mucosa (31%) and those not (3.8%) was statistically significant (P less than 0.0186). Carcinoembryonic antigen (CEA) was demonstrated in 60% of oesophageal carcinomas, both endocrine positive and endocrine negative. Focal CEA expression was seen in 4.6% of biopsies and 14% of Barrett's mucosa adjacent to tumour. These results indicate a higher prevalence of endocrine cells in Barrett's mucosa than hitherto documented and suggest that serotonin may be a useful marker in distinguishing between primary oesophageal and putative gastric cancers at the gastro-oesophageal junction. The identification of CEA in oesophageal columnar epithelium is of little value in predicting the development of malignancy.
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PMID:The relationship of endocrine cells, dysplasia and carcinoembryonic antigen in Barrett's mucosa to adenocarcinoma of the oesophagus. 288 73

Tumour cells from a lymph-node metastasis of a midgut carcinoid tumour, immunoreactive for serotonin and substance P, were isolated and kept in culture for 2 months. The formation of large clusters or islets of tumour cells was paralleled by an increase in immunoreactive tachykinins (neuropeptide K and substance P) in the culture medium. The concentration of tachykinins declined subsequently despite good viability of the cells. Spontaneous release of serotonin into the culture medium was much greater than that of tachykinins, and remained stable throughout the study. These findings indicate different turnover rates and/or different storage sites for the peptides and the amine. In stimulation experiments, a dose-dependent release of serotonin, but not of tachykinins, was induced by a beta-adrenoceptor agonist (isoprenaline), while stimulation of alpha-adrenoceptors (noradrenaline) was not effective in releasing any of the substances. Pretreatment of the cultures with a beta-adrenoceptor antagonist (propranolol) or stimulations after calcium deprivation did not influence the isoprenaline-induced release of serotonin. These findings may indicate a modification of genuine beta-adrenoceptors during culture.
Int J Cancer 1988 Oct 15
PMID:Carcinoid tumour cells in long-term culture: release of serotonin but not of tachykinins on stimulation with adrenoceptor agonists. 290 16

The assumption that life changes and stressful events can alter host defense is based mainly on studies of changes in a variety of immune and inflammatory reactions. Whether those changes also confer an increased susceptibility to infectious agents and neoplasms, or modify the course of such diseases, is still less well substantiated. Nonetheless, psychological and neural modulation of immunity has recently been possible to approach from a mechanistic viewpoint. For instance, generation of a variety of lipid mediators from arachidonic acid may be under control of dietary and endocrine factors that can be affected by stress. Since these lipids, eg, lipoxygenase products, are potent regulators of leukocyte functional responses, their significance as one of several mechanisms is discussed. The role of various neuropeptides in leukocyte function has only recently been discovered. Since the release of, eg, substance P, enkephalins, and endorphins, which all have modulating effects on leukocyte functional responses, is under neural control and can occur in the vicinity of immunocompetent cells, they might constitute one of several links between the mind and the immune system.
Cancer Detect Prev Suppl 1987
PMID:Stress-related modulation of immunity: a review of human studies. 331 52


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