Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In metastases and malignant tumors arising from gastric mucous membrane irrespective of their localization the method of electrophoresis and enzyme-electroporesis in agar gel demonstrates the presence of rapidly moving anode fractions I, II, and III corresponding to pepsinogen-pepsin isoforms of normal gastric mucosa but lacking proteolytic activity.
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PMID:[Biochemical test for the presence of pepsinogen-pepsin for the diagnosis of stomach cancer metastases]. 33 43

Prostaglandins and serotonin are vasoactive compounds with profound effects on the gastrointestinal tract. Both cause inhibition of gastric acid secretion (although serotonin stimulates gastric pepsin secretion), stimulation of intestinal motility, and conversion of small intestinal mucosa from absorption to secretion of water and electrolytes. Their effects on pancreatic and biliary function are still not clear. Although prostaglandins appear to elicit their effects primarily by a paracrine mode of action, and serotonin is primarily a neurotransmitter (neurocrine), it is clear that even under normal conditions both can function as humoral agents. For example, we have shown that serotonin plays a physiologic role as a humoral inhibitor of gastric acid secretion. However, the effects of these agents become more pronounced in patients with humorally mediated diarrheogenic syndromes. Serotonin (and related indoles, particularly 5-hydroxytryptophan) has been firmly implicated as a cause of diarrhea in patients with carcinoid syndrome; our recent studies suggest that the diagnosis can be more effectively made by measuring circulating immunoreactive serotonin concentrations than urinary excretion of 5-HIAA; that some circulating serotonin escapes hepatic inactivation and, thus, large intestinal tumors can cause carcinoid syndrome in the absence of hepatic metastases; and that large amounts of serotonin are produced by some noncarcinoid diarrheogenic tumors, including medullary carcinomas of the thyroid and tumors associated with the WDHA syndrome. A large number of tumors of probable neural crest origin, including medullary thyroid carcinoma, carcinoids, and tumors associated with the WDHA syndrome, secrete large amounts of prostaglandins, particularly PGE2. The clinical response of at least some of the patients harboring these tumors to inhibitors of prostaglandin synthesis (particularly indomethacin) suggests that prostaglandins play a role in the etiology of these diarrheogenic syndromes.
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PMID:Prostaglandins and serotonin: nonpeptide diarrheogenic hormones. 39 Aug 99

Immunohistological tests for pepsin and gastricsin were carried out in bioptic samples of 51 patients with carcinoma of the stomach. Pepsin was detected in only 2 cases (4%), gastricsin in 26 patients (55%). Compared to the histological picture, the rate of incidence of gastricsin showed no difference between the intestinal and diffuse types of this tumour. In all examined cases, only gelatinous carcinomas were negative. Nor were any differences found in the cardia, the body or antrum. Surprisingly, these enzymes were found in the cytoplasma of neutrophylic granulocytes in the inflammatory infiltrate of the mucosal and tumorous stroma. Intestinal metaplasia of the epithelium was always negative even in the neighbourhood of positive tumours. The detected changes are evidence against the possibility of different histogenesis of the diffuse and intestinal forms of carcinoma of the stomach as well as against the possibility that intestinal metaplasia in a chronic inlammation of the stomach could be regarded as a direct first stage of the intestinal form of carcinoma of the stomach. In cases of metastases of unknown origin, pepsin and gastricsin cannot serve as markers due to their insufficient organ and cell specificities.
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PMID:[Immunohistologic detection of pepsin and gastricsin in carcinoma of the stomach]. 250 Feb 49

A new technique was developed to coat Nuclepore filters with basement membrane matrix components. Using the EHS tumour as a source, a proteoglycan and laminin-containing fraction was extracted with guanidine and collagen type IV was solubilized in a second fraction by limited digestion with pepsin. When the two fractions are combined and guanidine removed by dialysis, a gel is rapidly formed. A flat-bed dialysis apparatus was devised, allowing gels to form on filters that are soaked in the mixture, thus coating them with components of the basement membrane. Such filters were used for selection of B16 melanoma cells penetrating the gels. 10 clones were isolated after three selection passages, and assayed for spontaneous metastasis in C57Bl/6 mice after intracutaneous injection. The metastasis rates were strongly increased to the lungs and to inguinal and axillary lymph nodes. Less accessible sites such as mediastinal and maxillary lymph nodes were reached only by selected cells. There was no particular preference for the haematogenous or lymphatic routes, indicating that the ability to traverse the basement membrane leads to a general increase of metastasis. The described method provides a valuable tool for isolating those subpopulations able to traverse basement membranes and to assess this capacity in new tumour samples.
Invasion Metastasis 1989
PMID:Selection of highly malignant tumour cells using reconstituted basement membrane matrix. 270 99

Pepsinogens were studied in histological specimens of gastric carcinoma by indirect immunoperoxidase method. They were identified in 14 out of 24 intestinal tumors and in 2 out of 6 mixed carcinomas, but none was found in any of 10 diffuse carcinomas. Pepsinogen C was found in all pepsinogen-positive tumors, pepsinogen A--in 11 of them, and an antigen common with swine pepsin--in 2 tumors only. The pepsinogens were also observed in metastases of pepsinogen-positive primary tumors.
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PMID:[Immunomorphologic study of pepsinogens in stomach cancer]. 328 63

Activity of neutral protease was increased in sera of rats bearing ascites hepatoma AH109A compared to those of normal rats. The protease was isolated from serum protein and partially purified approximately 1,150 times in specific activity after sequential column chromatography of hemoglobin affinity, lysine-Sepharose, Ultrogel AcA34 and TSK-gel G2000SW in that order. The protease fraction still seemed to contain at least two kinds of proteases, serine and cysteine protease. It had a molecular weight of 18-21 kilodaltons with broad optimal pH range of 7.0-9.0, maximum at 8.0. Intradermal injection of the crude preparation of the neutral protease fraction induced extravascular emigration of circulating tumor cells in vivo. Moreover, partially purified protease degraded pepsin-treated chains of bovine glomerular type IV collagen in vitro, but such an in vitro action of the protease was inhibited by an addition of soybean trypsin inhibitor or mercuric chloride. It failed to cleave salt-extracted rat skin type I collagen under the same digestive conditions for bovine type IV collagen. The serum neutral proteases of tumor-bearing host may play some cooperative roles during extravascular emigration of tumor cells by destruction of vascular basement membrane.
Invasion Metastasis 1986
PMID:Partial purification and characterization of serum protease from tumor-bearing rats which cleaves type IV collagen. 353 Oct 79

The expression of three lysosomal cysteine proteases was examined in a lowly metastatic, MCF-7 human breast cancer cell line and its highly metastatic, Adriamycin-resistant variant, MCF-7/AdrR. While levels of cathepsin H activity were similar in all cell lines at each stage of growth, intracellular cathepsin B and L activities were highest in MCF-7/AdrR. These high levels were accompanied by growth-related increases in acid/pepsin-activatable cathepsin activity in the culture medium. Analyses of endogenous cathepsin B inhibitor activity in control and heat-treated cell homogenates after fractionation by fast protein liquid chromatography suggested that alterations in cystatin-like, cysteine protease inhibitor activities contribute to increased levels of cathepsin activities in metastatic MCF-7/AdrR cells.
Invasion Metastasis 1993
PMID:Characterization of cysteine proteases and their endogenous inhibitors in MCF-7 and adriamycin-resistant MCF-7 human breast cancer cells. 786 Feb 23

Normal and neoplastic cells interact with laminin via a variety of cell surface proteins. The specific binding sites on laminin for each particular cell surface laminin-binding protein have not yet been identified. In this study, the interaction between laminin and the high affinity metastasis-associated 67 kD laminin receptor (67 LR) was investigated by electron microscopy using the rotary shadowing technique. Laminin receptor that was purified from human colon carcinoma metastases appeared as a globular structure with a diameter of 5.2 +/- 0.8 nm. The 67 LR specifically bound to laminin on its long arm close to the intersection of the long and the short arms. There was no specific interaction of bovine serum albumin with laminin. Biochemical confirmation of the rotary shadowing experiments included slot blot solid phase assays in which [I125]-labeled 67 LR bound in a dose dependent manner to laminin as well as to the chymotrypsin resistant (C1) fragment of laminin that contains a short piece of the long arm. [I125]-labeled 67 LR did not bind to the pepsin resistant (P1) fragment of laminin that did not contain that segment on the long arm. This study therefore identifies the binding site on laminin for the 67 kD metastasis-associated laminin receptor as a region on the long arm of laminin close to the intersection of the four arms.
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PMID:Interaction between the 67 kilodalton metastasis-associated laminin receptor and laminin. 843 67

Plasma and ascitic fluid of rats bearing the Yoshida ascites hepatoma AH-130 were shown to contain high levels of proteolytic enzymes belonging to different classes active at neutral and acidic pH. Relative to those measured in control rat plasma, in tumor-bearing animals, the activity levels of lysosomal cathepsins B and L, in their latent, acidic-activatable form, were approximately 5-fold higher in plasma and 9-fold higher in ascitic fluid, and cathepsin D activity was about 5-fold higher in both plasma and ascitic fluid. Plasma and ascitic fluid of tumor-bearing rats also contained novel neutral and acidic gelatinolytic activities. The latter, as revealed by zymographic analysis conducted at pH 6.0, in the presence of dithiothreitol and in the absence of divalent metal ions, was sensitive to iodoacetamide inhibition but not to EDTA, showed a molecular mass of approximately 90 kD on SDS-PAGE, and was lost upon limited proteolysis with pepsin. Therefore, this enzyme is not identifiable as cathepsin B or L or their related latent forms and may represent a novel, so far undescribed, gelatinase. Its presence exclusively in the body fluids of AH-130-bearing rats suggests its possible use as a tumor marker.
Invasion Metastasis 1995
PMID:High levels of proteolytic enzymes in the ascitic fluid and plasma of rats bearing the Yoshida AH-130 hepatoma. 862 Dec 67

In order to determine the effects of the multifunctional iron-binding glycoprotein, lactoferrin (LF), and related compounds on tumor growth and metastasis, bovine LF (bLF), and bLF hydrolysate and lactoferricin (bLFcin), active products generated by acid-pepsin hydrolysis were administered orally to BALB/c mice bearing subcutaneous (s.c.) implants of the highly metastatic colon carcinoma 26 (Co 26Lu). bLF and the bLF hydrolysate demonstrated significant inhibition of lung metastatic colony formation from s.c. implanted tumors without appreciable effects on tumor growth. bLFcin displayed a tendency for inhibition of lung metastasis. On the other hand, bLF did not exert marked anti-metastatic activity in athymic nude mice bearing Co 26Lu, though bLF had a tendency to inhibit the lung metastatic colony formation associated with anti-asialoGM1 antibody (Ab) treatment. AsialoGM1+ and CD8+ cells in white blood cells were increased after treatment with bLF. In vitro, the viability of Co 26Lu-F55 cells was markedly decreased when co-cultured with white blood cells from mice administrated bLF p.o., but recovered on treatment with anti-asialoGM1 Ab or anti-CD8 mAb and complement. The results suggest bLF and related compounds might find application as tools in the control of metastasis and that asialoGM1+ and CD8+ cells in the blood are important for their inhibitory effects.
Clin Exp Metastasis 1999 Feb
PMID:Inhibitory effects of bovine lactoferrin on colon carcinoma 26 lung metastasis in mice. 1039 Jan 45


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