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)

Goblet cell carcinoids are uncommon but distinctive tumours of the appendix. We have reviewed 11 cases diagnosed within the period 1976-1990. The mean age at presentation was 58 years (range 24-76), with a female:male ratio of 8:3. At presentation, in seven patients tumour was confined to the appendix or mesoappendix (mean age 51) and in four there was extension beyond the appendix (mean age 69). Of the seven patients with localized tumour, six are alive and without clinical disease after a mean follow-up period of 32 months and one died with recurrent tumour after 10 years. Of the four with more extensive disease, two died during follow-up (at 23 months with probable liver metastases and at 16 months with intestinal obstruction) and two are alive, one with disease and one clinically disease-free. Immunohistochemistry showed that all of the tumours stained positively for either neuron-specific enolase, chromogranin A or protein gene product 9.5. No tumour stained with antiserum to substance P and none showed glucagon-like immunoreactivity, but four cases stained positively for pancreatic polypeptide, an unusual feature in midgut carcinoids.
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PMID:Appendiceal goblet cell carcinoids: a clinicopathological and immunohistochemical study. 167 61

Sixteen patients with endocrine ileal tumors and liver metastases were analyzed with regard to the size, multicentricity, and growth pattern of the primary tumor, the occurrence of carcinoid syndrome, as well as the concentrations of serotonin and substance P (SP) in blood, 5-hydroxy-indole-acetic acid (5-HIAA) in urine, and the course of the disease. Excised specimens from the tumors were immediately processed for immunocytochemical investigations of the presence of neurohormonal peptides, using a broad spectrum of antisera and optimal histoprocessing techniques. In all patients the serotonin levels in blood and/or the 5-HIAA in urine were high. The SP concentration in plasma was markedly elevated in all but two of the ten patients investigated in this respect. A mixed growth pattern prevailed in the tumors of 7 patients with fatal disease. Serotonin cells were found in all tumors and SP-immunoreactive tumor cells in all but one; one of the carcinoids also contained a few tumor cells displaying enkephalin immunoreactivity. In conventionally fixed and paraffin embedded specimens of the same tumors usually no immunoreactive tumor cells at all could be demonstrated, showing that SP is among the peptides vulnerable to poor histotechniques. Nevertheless, SP, together with serotonin, constitute reliable clinical tumor markers for ileal carcinoids.
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PMID:Endocrine tumors of the ileum. Cytochemical and clinical aspects. 241 56

A case of midgut carcinoid with breast metastasis is reported. Hepatic metastases stored large amounts of serotonin as demonstrated by the Falck-Hillarp technique. Immunocytochemically serotonin and substance P, which may co-exist in gut enterochromaffin cells, were demonstrated in separate populations of tumor cells both in the hepatic and mammary neoplasms.
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PMID:A case of midgut carcinoid with breast metastasis and cellular localization of serotonin and substance P. 242 88

In a prospective study of 103 patients with carcinoid tumors consecutively referred for medical treatment, the most common sites of the primary tumors were the ileum (73%), bronchi (7%), and jejunum (4%). All patients had local metastases, and 96 (93%) also had liver metastases. The most common initial symptoms were diarrhea (32%), ileus (25%), and flush (23%). The overall frequency of diarrhea was 84% and of flush was 75%. Heart insufficiency caused by cardiac valve disease was seen in 33% of the patients. The carcinoid syndrome, including flush, diarrhea, and elevated urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations, was manifested by 69 patients (67%), 64 of whom (93%) had carcinoid tumors of mid-gut origin. Elevated urinary 5-HIAA was found in 91 patients (88%), of which 89 displayed liver metastases. The plasma concentration of the tachykinin neuropeptide K (NPK) was elevated in 67 patients (66%), 63 of whom had tumors of the mid-gut region. Serum pancreatic polypeptide (PP) and human chorionic gonadotrophin alpha levels were elevated in 43% and 28% of the patients, respectively, and the highest levels were found in patients with metastatic bronchial carcinoid tumors. Thirty-nine of the 103 patients are now dead; 18 died of tumor progression, whereas 14 patients died of heart failure secondary to a carcinoid tricuspidal valve insufficiency. The estimated median survival from the time of histologic diagnosis was 14 years, and from the time of carcinoid syndrome was 8 years.
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PMID:Malignant carcinoid tumors. An analysis of 103 patients with regard to tumor localization, hormone production, and survival. 244 Mar 90

The carcinoid syndrome, a common feature of small intestinal carcinoid tumors with liver metastases, includes flushing, diarrhea, bronchoconstriction, and right heart failure. The etiology of the carcinoid syndrome is not well understood, but serotonin seems to be involved in the diarrhea, whereas tachykinins may play a role in the flush reaction. In a double blind placebo-controlled study, we studied the effect of octreotide in 20 patients with midgut carcinoid tumors and liver metastases. A sc injection of 50 micrograms octreotide caused a significant (P less than 0.001) decrease in median plasma tachykinins and serum pancreatic polypeptide, GH, and insulin for up to 4 h. Administration of octreotide (50 micrograms, twice daily, sc) caused a 26% decrease in urinary 5-hydroxyindoleacetia acid excretion, but the number of flushing attacks or bowel movements did not change significantly. A typical flush was provoked by pentagastrin, and plasma tachykinin and serotonin levels were measured. The flush reaction was graded on a 10-point visual analog scale. Octreotide (50 micrograms, sc) given 45 min before flush stimulation prevented tachykinin release completely and significantly reduced the median flushing score from 8.5 to 2. Placebo administered in the same way did not prevent tachykinin release after pentagastrin administration. Thus, octreotide prevents pentagastrin-induced flushing and the related hormonal changes in patients with the carcinoid syndrome.
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PMID:The effects of octreotide on basal and stimulated hormone levels in patients with carcinoid syndrome. 246 45

Selective catheterization of hepatic, intestinal and adrenal veins with blood sampling for serotonin and catecholamine determination was evaluated regarding its use in the diagnosis, location and characterization of carcinoids and pheochromocytomas. Catheterization of intestinal veins via the transhepatic route and of the adrenal veins via the femoral and caval veins was performed in 49 patients without major complications. High pressure liquid chromatography with electrochemical detection was used to quantitate norepinephrine and epinephrine in plasma and serotonin in plasma and whole blood. Serotonin in plasma was also determined by an enzymatic procedure. In 30 patients with suspected or verified carcinoid tumors concentration of serotonin in tumor-draining veins was clearly elevated in all patients but one. In this patient, who previously had been treated with temporary liver dearterialization, the serotonin concentration in the hepatic vein was within the normal range in spite of the existence of liver metastases. Hyperserotoninemia was registered in one patient without detectable carcinoid tumor cells. In three patients determination of norepinephrine and epinephrine in adrenal venous blood diagnosed a hyperplasia and tumors in the adrenal medulla. In these cases angiography and computed tomography were negative. Microscopic analyses revealed serotonin in all carcinoids and substance P-like immunoreactivity in a large percentage of these tumors. PP-like and glucagon-like immunoreactivity were observed in two endocrine pancreatic tumors. In normal adrenal medulla and in adrenal medullary tumor tissue catecholamine fluorescence and enkephalin-like immunoreactivity were demonstrated. In the two pheochromocytomas ACTH-like, somatostatin-like and calcitonin-like immunoreactivities were identified. The technique with determinations of plasma serotonin and catecholamines in combination with selective catheterization is a useful investigation for the diagnosis, location and follow-up of patients with carcinoids and pheochromocytomas.
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PMID:Localization of carcinoids and pheochromocytomas with vein catheterization and amine determination. 717 48

The peptidergic/aminergic innervation of normal liver and tumour blood vessels was investigated in order to determine vascular control with a view to improving the efficacy of hepatic arterial cytotoxic infusion in the treatment of colorectal liver metastases. Selected areas of liver metastases and macroscopically normal liver from resection specimens (n = 13) were studied using light microscope immunohistochemistry for the presence of protein gene product 9.5 (PGP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), substance P (SP) and tyrosine hydroxylase (TH). The ultrastructure of blood vessels supplying liver metastases and their perivascular innervation were also examined by transmission electron microscopy. In the normal liver, perivascular immunoreactive nerve fibres containing PGP, NPY and TH were observed around the interlobular blood vessels and along the sinusoids and the central vein of the hepatic lobule. The greatest density of immunoreactive nerve fibres was seen for PGP, followed (in decreasing order) by NPY and TH. VIP, SP and CGRP immunoreactivity was observed only in nerve bundles associated with the large interlobular blood vessels. In contrast, no perivascular immunoreactive nerves were observed in colorectal liver metastases. Electron microscopy confirmed the absence of perivascular nerves in liver metastases. In addition, it showed that the walls of these blood vessels were composed of a layer of endothelial cells surrounded by an incomplete or, very rarely in the periphery of the tumour, a complete, layer of synthetic phenotype of smooth muscle-like cells. These results imply that the blood vessels supplying liver metastases are bereft of normal neuronal regulation; whether there is a role for endothelial cell control of blood flow in these vessels is not yet known.
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PMID:The absence of autonomic perivascular nerves in human colorectal liver metastases. 856 41

Hepatic arterial infusion (HAI) chemotherapy as treatment for human colorectal liver metastases is promising, but not entirely satisfactory. Improved drug delivery during HAI may be achieved by manipulating the different control mechanisms of normal versus tumour blood vessels. The peptidergic/aminergic innervation of vessels in normal liver and in two animal models of liver metastasis (Lister Hooded rat with syngeneic MC28 sarcoma; athymic (nude) rat with human HT29 carcinoma) was investigated to assess the suitability of these models for future pharmacological studies. Normal liver and metastases were studied immunohistochemically for the presence of protein gene product 9.5 (PGP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and substance P (SP). Perivascular innervation was also examined by transmission electron microscopy. In Lister rat normal livers, perivascular immunoreactive nerve fibres containing PGP, NPY, TH, CGRP and SP were observed around the interlobular blood vessels near the hilum and in the portal tracts. The highest density was seen for PGP, followed in decreasing order, by NPY, TH, CGRP and SP. VIP-immunoreactive nerves were absent. No immunoreactive nerves were observed in the hepatic lobule. In athymic rat livers, the pattern of innervation was similar, except that SP immunoreactivity was more sparse. No perivascular immunoreactive nerves were observed in either MC28 or HT29 tumours. Electron microscopy confirmed the absence of perivascular nerves. Smooth muscle cells were not observed in tumour blood vessel walls. These results are comparable with previous observations on human liver metastases and suggest that the animal models may be suitable for pharmacological studies on vascular manipulation of HAI chemotherapy.
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PMID:Blood vessels in liver metastases from both sarcoma and carcinoma lack perivascular innervation and smooth muscle cells. 924 51

Neuroendocrine gut and pancreatic tumors are known to contain and secret different peptide hormones and amines. During the last two decades, many radioimmunoassays and Elizas have been developed to analyze these substances in blood and urine, which has enabled clinicians to improve the diagnosis and monitoring of patients with various neuroendocrine tumors. Due to cost constraints in medical care, it is important to try to define the most useful biochemical markers from the clinical point of view. The glycoprotein chromogranin A has been shown to be a useful marker for diagnosing various neuroendocrine tumors, both by histopathology and circulating tumor markers. In patients with demonstrable endocrine tumors, about 90 percent of the patients present high circulating levels of chromogranin A. A hundred-fold increase of plasma chromogranin is seen in patients with midgut carcinoid tumors and liver metastases. The plasma levels of chromogranin A reflect the tumor mass and can be used for monitoring the patient during treatment and follow-up, although the day-to-day variation might be 30-40 percent. High circulating levels of the chromogranin A might be an indicator of bad prognosis in patients with malignant carcinoid tumors. Besides analyzing plasma chromogranin A, specific analyses such as urinary 5-HIAA in midgut carcinoid patients, serum gastrin in patients with Zollinger-Ellison syndrome and insulin/proinsulin in patients with hypoglycemia should be performed. In patients with small tumor masses or intermittent symptoms, provocative tests such as a meal stimulation test, secretin test or pentagastrin stimulation of tachykinin release can supplement the basal measurements of peptides and amines. To fully evaluate the growth potential in neuroendocrine tumors, traditional biochemical markers should be supplemented with indicators of growth proliferation (Ki-67, PCNA) and immunohistochemical staining for the adhesion molecule CD44 and the PDGF-alpha receptor. Finally, analysis of somatostatin receptor subtypes and induction of the enzymes 2-5A syntethase and PKR are of clinical value.
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PMID:Biochemical diagnosis of neuroendocrine GEP tumor. 982 77

Human mast cells are categorized into mast cells positive only for tryptase (MC(T)) and mast cells positive for both tryptase and chymase (MC(TC)). The structural appearance of tryptase-, and chymase-positive mast cells in metastatic liver disease and the variations in MC(T) and MC(TC) numbers in accordance with the origin of the primary tumors have been described in the present study. Liver mast cells are analyzed immunocytochemically using tryptase and chymase and by quantitative morphometry in 30 patients with colorectal (n = 15), gastric (n = 8), and pancreatic (n = 7) cancers and in 5 control livers. The numbers of MC(T) and MC(TC) are increased in the extratumoral liver tissue (mainly portal tracts) as compared to controls. The numbers of MC(T) and MC(TC) in and around metastases with moderate or high grade of differentiation are statistically significantly higher, as compared to those with low grades of differentiation. The numbers of MC(TC) are greater than that of MC(T) in the extratumoral liver tissue and in metastases themselves. Ultrastructurally, mast cells immunostained with tryptase and chymase have three types of granules: electron dense granules with darkly precipitated reaction product, electron lucent granules without reaction product and electron lucent granules with sparse reaction product (altered granules). Both types of mast cells have small and large in size granules, resembling the MC(TC) phenotype described earlier. Tryptase-positive mast cells have granules with discrete scrolls and particulate and beaded pattern. Chymase-positive mast cells have granules with finely granular or particulate material. Substance P (SP)- and vasointestinal polypeptide (VIP)-positive mast cells are not observed in livers with metastases. The present study suggests that liver mast cells are mainly from the MC(TC) type, and are accumulated in peritumoral and metastatic areas. They may play a role in the formation of tumor stroma, or in tumor immunology in liver metastases from various primary gastrointestinal cancers.
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PMID:Structural examination of tryptase- and chymase-positive mast cells in livers, containing metastases from gastrointestinal cancers. 1466 92


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