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)

Tissue specimens from 5 patients with metastatic midgut carcinoid tumours were kept in organ culture for up to 6 months. The tumour cells were confined to the suspension in the form of condensed cell clusters and appeared to retain their endocrine characteristics. Radioimmunoassay for tachykinin immunoreactivity showed high concentrations in 4 out of 5 culture media. The concentrations were highest in the beginning of the experiment, but subsequently decreased. The 4 patients from which these tumours were taken had all elevated tachykinin concentrations in extracted plasma. The fifth culture medium had low tachykinin concentration, and the concentration in extracted plasma from this patient was within the normal range. Reversed-phase high-performance liquid chromatography of the culture media with elevated tachykinin concentrations revealed immunoreactive components with the characteristics of synthetic neuropeptide K, neurokinin A and eledoisin, components also found in plasma and tumour tissues of carcinoid patients. Our findings indicate that carcinoid tumour cells produce tachykinins. These peptides are biologically very active, resulting in flush and hypotension when infused intravenously into normals, and might contribute to the clinical symptoms of the carcinoid syndrome.
Eur J Cancer Clin Oncol 1987 Jun
PMID:Tachykinin production by carcinoid tumours in culture. 347 59

Five carcinoid tumors of the thymus were screened immunohistochemically for the occurrence of neuropeptides (ACTH, calcitonin, calcitonin gene-related peptide, cholecystokinin, gastrin, neurotensin, somatostatin, substance P), as well as of serotonin, chromogranin A, and neuron-specific enolase. Most of the patients exhibited local symptoms evoked by growing tumor masses in the upper mediastinum without any clinical evidence of endocrine activity. Light and electron microscopic examination showed characteristic uniform large epithelial cells in polar or palisade arrangement, containing variable amounts of electron-dense secretory granules. Only a few of the tested neuropeptide antisera reacted with the investigated tumors. Cholecystokinin-immunoreactive cell populations were seen in all tumors. Expression of neurotensin could be observed in three neoplasms, two of which also exhibited ACTH immunoreactivity. Chromogranin A-immunoreactive cells were found in two neoplasms. Neuron-specific enolase showed strong staining in three tumors, one of the tumors also being immunoreactive for calcitonin. The results were confirmed by control reactions. Apart from the demonstration that conventional marker proteins are not reliable in identifying all carcinoid tumors, the present study proves that the visualization of neuropeptide-immunoreactive cells in thymus carcinoids does not necessarily correspond to the manifestation of the clinical symptoms. Furthermore, each of the investigated neoplasms, as also known from other carcinoid tumors, appears to be able to produce more than one hormone.
Cancer 1987 Nov 15
PMID:Carcinoid tumors of the thymus. An immunohistochemical study. 366 30

Eighty-one primary ovarian carcinoids and intraovarian metastases from six mid-gut carcinoids were examined for the presence of tumor cells immunoreactive with antisera raised against various neurohormonal peptides, mostly of gastroenteropancreatic (GEP) origin. Twenty of the primary and two of the metastatic carcinoids contained such tumor cells. The incidence of tumors with any kind of neurohormonal peptide immunoreactive tumor cells was 53% in the trabecular carcinoids, and 42% in the strumal carcinoids, whereas the incidence was much lower (7%) in the insular type. Immunoreactive pancreatic polypeptide (PP), glucagon, enkephalin, and somatostatin were those neurohormonal peptides most commonly observed in the tumor cells of the primary carcinoids. Those less commonly found were substance P, calcitonin, VIP, neurotensin, beta-endorphin, and ACTH. Four metastatic carcinoids were nonreactive with all the antisera used. Cells storing immunoreactive insulin, glucagon, PP, VIP, gastrin, substance P, or enkephalin were found in one of the two remaining metastatic carcinoids; in the other only gastrin-immunoreactive tumor cells were observed. The occurrence and distribution of tumor cells storing the neurohormonal peptides in ovarian carcinoids are discussed in relation to their possible origin in the ovary and to carcinoids in the gut.
Cancer 1982 Jan 01
PMID:Neurohormonal peptides in ovarian carcinoids: an immunohistochemical study of 81 primary carcinoids and of intraovarian metastases from six mid-gut carcinoids. 611 50

Twenty-five endocrine tumors of the rectum (rectal carcinoids) were examined immunohistochemically for various pancreatic and gut neurohormonal polypeptides. Twenty-one of the tumors were found to contain cells displaying pancreatic polypeptide (PP), glucagon, somatostatin, insulin, substance P, enkephalin or beta-endorphin immunoreactivity. At least 11 of the tumors contained more than one peptide hormone. In some of the tumors PP cells made up the major cell population, in others the glucagon cells constituted the majority. Only four of the tumors contained 5-hydroxytryptamine. Rectal endocrine tumors seem unique among gut endocrine tumors in that they may store immunoreactive enkephalin, beta-endorphin and even insulin. None of the patients displayed the carcinoid syndrome; symptoms were usually vague and uncharacteristic. In many cases the tumor was found at routine examination.
Cancer 1981 Dec 01
PMID:Immunohistochemical evidence of peptide hormones in endocrine tumors of the rectum. 617 Apr 21

Ten patients with metastatic carcinoid tumors in the liver showed elevated 5-hydroxytryptamine and substance P levels in plasma samples taken from hepatic or peripheral veins. Chromatographic characterization of the substance P-immunoreactivity showed that by gel permeation and high pressure liquid chromatography the substance P-immunoreactivity was indistinguishable from synthetic undecapeptide substance P. The results suggest that substance P, in addition to the 5-hydroxyinoles, may serve as a circulatory marker for some forms of carcinoid tumors.
Cancer 1984 Aug 15
PMID:Elevated concentrations of substance P and 5-HT in plasma in patients with carcinoid tumors. 620 35

Two cases of gastrin releasing peptide (GRP)-producing medullary thyroid carcinoma are presented. Immunohistochemical examination revealed the presence of GRP-like immunoreactivity (IR-GRP) in the primary tumor tissues. High concentration of IR-GRP was also demonstrated in extracts of the primary tumors by radioimmunologic means with use of a GRP-specific antiserum. Chromatographic analysis showed that the immunoreactivity was composed of at least two molecular forms: one behaved as synthetic porcine GRP on Sephadex G-50 gel filtration and the other as porcine GRP (14-27), a C-terminal active fragment of GRP. The IR-GRP was shown not to be attributed to bombesin-like immunoreactivity. Substance P-like immunoreactivity was not detected in the tumor tissues by either immunohistochemical or radioimmunologic means. This is, as far as the authors are aware, the first finding of IR-GRP as an ectopic product in medullary carcinoma.
Cancer 1984 Jun 01
PMID:Gastrin-releasing peptide immunoreactivity in medullary thyroid carcinoma. 637 Apr 16

Nine cases of endocrine carcinoma, intermediate-cell type of the uterine cervix, were found in a study of 404 cases listed in the files of the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston as adenocarcinoma of the cervix. Based on light microscopic patterns, these cases were divided into pure endocrine carcinoma (six cases), and endocrine carcinoma mixed with adenocarcinoma (three cases). All tumors were 3 cm or larger in at least one dimension. On light microscopic examination, the predominant pattern was trabecular; however, insular, glandular, and spindle patterns were also identified. Argyrophilic granules were demonstrated in all cases by Grimelius stain, and Fontana-Masson (argentaffin) stain was negative. Electron microscopic examination of three cases showed membrane-bound, dense-core granules of the neurosecretory type. Although no endocrine symptoms were found, immunoperoxidase studies demonstrated 5-hydroxytryptamine in seven cases, substance P in three, vasointestinal polypeptide in two, pancreatic polypeptide in one, and somatostatin in one. Clinical behavior of these tumors was extremely aggressive. Although five cases were Stage IB at presentation, two Stage IIB, one Stage IIIB, and one Stage IV, 87.5% of these patients died of their neoplasms within 3 years. This study emphasizes the importance of correctly diagnosing endocrine carcinoma, intermediate-cell type in the uterine cervix, because of the poor prognosis of this tumor when compared with adenocarcinoma of the cervix.
Cancer 1984 Oct 15
PMID:Endocrine carcinoma intermediate cell type of the uterine cervix. 638 96

Goblet-cell carcinoids are particular mucus-producing tumors combining features of typical carcinoids and adenocarcinomas. The immunoreactivity of five goblet-cell carcinoids of the appendix and one tumor of the ileum for 5-hydroxytryptamine (5-HT, serotonin), glucagon, somatostatin, substance P (SP), neuron-specific enolase (NSE), lysozyme, secretory component (SC) and carcino-embryonic antigen (CEA) was compared with that of the mucosa of the appendix (n = 24) and ileum (n = 12), and of typical carcinoids (appendix: n = 10; ileum: n = 3). The goblet-cell carcinoids were consistently lysozyme-, SC- and CEA-reactive and contained weakly NSE reactive endocrine cells, while typical carcinoids were lysozyme-, SC- and CEA-negative, but strongly NSE- reactive. Two goblet-cell carcinoids were glucagon-reactive, one displayed SP-reactivity, one malignant tumor was reactive to the alpha-chain of glycoprotein hormones; six of ten typical appendix carcinoids were SP reactive, as were the three typical ileum carcinoids. Using the immunogold technique combined with the alcian-blue reaction, the presence of 5-hydroxytryptamine (5-HT) and mucus was demonstrated within the same cell. These findings suggest histogenetic differences between goblet-cell carcinoids and typical carcinoids; the former are possibly derived from undifferentiated stem cells, whereas the latter probably arise from endocrine cells in the mucosal stroma.
 ...
PMID:Combined production of mucus, amines and peptides by goblet-cell carcinoids of the appendix and ileum. 648 83

Small cell lung cancers (SCLC) and some non-small cell lung cancers (NSCLC) have neuroendocrine features which include production of a variety of neuropeptides, cell surface expression of the receptors for these peptides, and autocrine stimulation by the peptides. Previous studies showed that some peptide antagonists and anti-peptide antibodies inhibited the growth of SCLC cell lines which expressed receptors for the specific peptide. We and others showed that the heterogeneity of peptide receptor expression and responsiveness was a major potential obstacle for developing therapeutic uses of peptide antagonists. In this manuscript we evaluated the effects of 11 peptide antagonists (3 bombesin-specific, 2 cholecystokinin-specific, 1 arginine vasopressin (AVP)-specific, and 5 substance P derivatives with broad specificity) on peptide-induced calcium mobilization and growth of SCLC and NSCLC cell lines. For each antagonist, we determined the dose-response effects, specificity of peptide antagonism, and biological stability in serum using Indo-1AM-based flow cytometric assays. We found that the three bombesin antagonists, S30, SC196, and L336,175, varied in potency from 10 nM to 10 microM, varied in serum stability from 6 h to more than 24 h, and had no effect on the calcium response elicited by other peptides. None of these compounds effectively inhibited the growth of SCLC cell lines in [3H]dThd and cell growth assays in vitro. Similarly, the three cholecystokinin and AVP antagonists were highly specific for cholecystokinin and AVP, respectively, had widely varying potency, but had little inhibitory effect on SCLC growth in vitro. In contrast, the five substance P derivatives inhibited the calcium response to bombesin, AVP, bradykinin, and fetal bovine serum. None of these five antagonists were as potent as the six specific antagonists described above, but they were more effective in inhibiting the growth of SCLC cell lines in vitro. These substance P derivatives inhibited the growth of peptide-sensitive SCLC cell lines more efficiently than their inhibition of peptide-insensitive NSCLC or breast cancer cell lines. Relatively high concentrations of these substance P derivatives were required to inhibit in vitro growth, even in the absence of added peptide. It is likely that more potent broad spectrum antagonists, toxins, or radiolabeled stable antagonists will need to be developed for maximal clinical development of this type of anti-growth factor therapy.
Cancer Res 1994 Jul 01
PMID:Effects of neuropeptide analogues on calcium flux and proliferation in lung cancer cell lines. 751 22

The effects of prolonged administration of neuropeptide substance P (SP) on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the labeling index of gastric mucosa were investigated in Wistar rats. Rats received subcutaneous injections of 12 micrograms/kg body weight of SP every other day after 25 weeks of oral treatment with MNNG. Long-term administration of SP significantly increased the incidence of gastric cancers in week 52. However, it did not affect the histological type and depth of involvement of gastric cancers. SP also caused a significant increase in the labeling index of the antral and fundic epithelial cells in week 52. These findings indicate that SP promotes gastric carcinogenesis and suggest that this effect may be related to its stimulation of antral epithelial cell proliferation.
Cancer Lett 1995 Sep 04
PMID:Promotion by substance P of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. 755 15


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