Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been proposed that a cysteine proteinase inhibitor (CPI) found in the ascitic fluid of Sarcoma 180 tumor-bearing mice is a kind of kininogen (Itoh, N., Yokota, S., Takagishi, U., Hatta, A., and Okamaoto, H. (1987) Cancer Res. 47, 5560-5565). The first 40 NH2-terminal residues and 54 residues of the COOH-terminal sequence, including the bradykinin moiety of highly purified ascites CPI, were determined and compared with those of mammalian low molecular weight kininogens (LMWK). The significant identity between these amino acid sequences with those of other mammalian LMWKs suggests that ascites CPI corresponds precisely to mouse LMWK. This kininogen has a light chain composed of 43 amino acid residues, which contains a unique Met-Ala-Arg-bradykinin sequence. Hydroxyproline, which was recently identified in the bradykinin sequence of kininogen from the ascitic fluid of a cancer patient, was not found in the kinin moiety of this mouse kininogen. Among purified glandular kallikreins from human, hog, rat, and mouse, only mouse submaxillary gland kallikrein was able to release bradykinin from this kininogen. Kinetic studies using a newly synthesized fluorogenic substrate, N-t-butoxycarbonyl-Met-Ala-Arg-MCA, revealed that mouse kallikrein hydrolyzes this substrate approximately 80-fold faster than does hog kallikrein, suggesting that the unique Met-Ala-Arg-bradykinin sequence is responsible for the varied susceptibility of mouse kininogen to different kallikreins.
 ...
PMID:Cysteine proteinase inhibitor in the ascitic fluid of sarcoma 180 tumor-bearing mice is a low molecular weight kininogen. Partial NH2- and COOH-terminal sequences and susceptibility to various glandular kallikreins. 235 46

Two new human cell lines, RCM-1 and CoCM-1, have been established from primary colorectal adenocarcinomas. Both cell lines were unique in that the cultures secreted trypsin inhibitors in vitro. The activities of these inhibitors were accumulated in serum-free media of both cell lines over a period of several days. Two inhibitors (PI-1 and PI-2) were isolated from serum-free conditioned medium in which RCM-1 was grown by anion-exchange and gel filtration high-performance liquid chromatography. PI-1 inhibited trypsin and chymotrypsin strongly, and pancreatic elastase weakly. Its molecular weight was about 57 kilodaltons (Kd) as determined by gel filtration chromatography. It cross-reacted with the antiserum elicited against human alpha 1-antitrypsin in double immunodiffusion. PI-1 corresponding to alpha 1-antitrypsin was also demonstrated immunohistochemically in both cell lines. PI-2 inhibited trypsin strongly, and chymotrypsin, kallikrein and plasmin weakly. It had higher molecular weight (200-300 Kd) than that of PI-1, and did not cross-react with antisera against human alpha 1-antitrypsin, alpha 2-macroglobulin, alpha 1-antichymotrypsin, alpha 2-plasmin inhibitor, inter-alpha-trypsin inhibitor and urinary trypsin inhibitor. RCM-1 and CoCM-1 are the first colorectal adenocarcinoma cell lines that secrete functionally active trypsin inhibitors, including alpha 1-antitrypsin in vitro, and are useful for the study of tumor-cell derived proteinase inhibitors.
 ...
PMID:New human colorectal carcinoma cell lines that secrete proteinase inhibitors in vitro. 257 Apr 82

Kallikrein was identified immunohistochemically and biochemically in a transplantable pancreatic acinar cell carcinoma of the rat. The concentration of immunoreactive kallikrein in tumor homogenates was the same as in the pancreas. Kallikrein in tumor cells exists as a proenzyme and is released into blood in high concentrations. The impact of the presence of a kallikrein-producing tumor on other kallikrein-containing organs and other possibly interrelated systems was investigated. The concentration of kallikrein in the submandibular gland and pancreas of host rats was not significantly different from that of control rats. Urinary kallikrein secretion was significantly increased, although this may be a result of the high plasma glandular kallikrein concentration combined with kidney damage. The plasma concentration of kininogen, kininase, and renin was not significantly different from control rats. Rats with tumor had significantly lower blood pressure than did control animals, and blood pressure was inversely related to the concentration of glandular kallikrein in plasma. However, it was not proven that the low blood pressure was due to the high concentration of kallikrein. Nephrectomized tumor rats gave a smaller hypotensive response to kininase inhibition than was expected from their high concentration of circulating kallikrein. This may be explained by the absence of the "free kallikrein" fraction in plasma of host rats.
 ...
PMID:Demonstration of kallikrein in a rat pancreatic acinar cell carcinoma. 257 95

Enhanced vascular permeability in tumor tissue has profound pathological consequences in tumor biology. However, details of the mechanism involved are not clear. The present work on tumor vascular permeability has led to the following three findings. (i) Ascitic tumor fluid contained kinin (about 1-40 ng/ml), which is known to enhance vascular permeability and induce pain in vivo. (ii) Kinin is generated via the kallikrein-dependent cascade in the ascitic tumor fluid. By blocking this kinin-generating cascade with Kunitz-type soybean trypsin inhibitor the formation of ascites was suppressed. (iii) Blocking of kinin-degrading enzymes (kininases I and II) by an appropriate kininase inhibitor (e.g., captopril) may result in increased permeability, leading to accumulation of the ascitic fluid. This phenomenon was verified by an about 1.2-1.5 fold increase in leakage of 51Cr-labeled bovine serum albumin into the ascites when kininase inhibitors had been administered orally 30 min before intravenous administration of the bovine serum albumin.
 ...
PMID:Involvement of the kinin-generating cascade in enhanced vascular permeability in tumor tissue. 314 3

The proteolytic activities of human tumor cell lines deriving from bronchial squamous cell carcinoma, a lung metastasis of an embryonal rhabdomyosarcoma and a pleural mesothelioma were measured by use of chromogenic substrates. N-acetyl-alanine aminopeptidase activity, plasminogen activator activity, H-D-Ile-Pro-Arg-p-NA splitting activity as well as plasmin-like activity, cathepsin G-like activity and plasma-kallikrein-like activity were found in cell lysates. The enzymatic activity of N-acetyl-alanine aminopeptidase, plasminogen activator and H-D-Ile-Pro-Arg-p-NA splitting activity changed during culturing. Plasminogen activator and H-D-Ile-Pro-Arg-p-NA splitting activity decreased to very low values, whereas N-acetyl-alanine aminopeptidase activity leveled at 1 x 10(-5) mU/cell. Unlike other proteolytic activities, plasminogen activator was released into the medium. Plasminogen activator activity could be measured in culture medium which contained no fetal calf serum.
 ...
PMID:Proteolytic activity of human tumor cell lines deriving from bronchial squamous cell carcinoma, pulmonary metastasis of rhabdomyosarcoma and pleural metastasis of mesothelioma. 332 2

A 24-yr-old woman with hypertension, hypokalemic alkalosis, low plasma renin and hypoaldosteronism was studied. Plasma aldosterone, renin and potassium returned to normal and blood pressure fell after sodium restriction or the administration of triamterene. Thiazide therapy also normalized her blood pressure while dexamethasone, spironolactone and furosemide did not improve her symptoms. Plasma aldosterone levels were low and responded poorly to a short term ACTH injection, but responded well to the maximal adrenal stimulation by ACTH-Z. Plasma levels of cortisol, corticosterone and deoxycorticosterone were within the normal range. Adrenal scintigram with 131I-adosterol and abdominal computed axial tomography did not reveal the presence of a sizeable adrenal tumor. In addition, the urinary kallikrein excretion was low after sodium restriction and showed no response to saline infusion. These findings suggest that the excessive secretion of unusual mineralocorticoids may not exist in this case. From these observations and the results of the therapeutic responses to the diuretic agents, we conclude that the primary cause of the disorder of this patient seems to be a renal defect in the distal tubule in handling sodium and potassium which is similar to that in Liddle's syndrome.
 ...
PMID:Hypertension, hypokalemia and hypoaldosteronism with suppressed renin: a clinical study of a patient with Liddle's syndrome. 627 44

The C3d-K fragment generated from human iC3b by plasma kallikrein is a potent suppressant of cellular proliferation. Originally characterized as inhibiting human and murine T lymphocyte function, C3d-K is shown in these studies to suppress mitogen-induced B cell growth, the spontaneous proliferation of several tumor cell lines, as well as all forms of T cell proliferation, including that induced by interleukin 2 (IL 2). In addition, synthesis of IL 2 in mixed lymphocyte cultures is blocked by C3d-K, but not IL 2 synthesis induced by Con A. The C3d-K fragment has no effect on resting cells; however, sensitivity to the inhibitory effect of C3d-K is acquired during the activation process. Because the proliferation of mitogen-activated spleen cells is not inhibited by exposure to C3d-K for the initial 24 hr of culture, only late steps in the cell activation process are C3d-K sensitive. When C3d-K is present throughout the course of the 72-hr culture, suppression was observed. Data obtained with the tumor cell lines suggest that once suppression is achieved, it is long-lasting even in the absence of C3d-K.
 ...
PMID:C3d-K, a kallikrein cleavage fragment of iC3b is a potent inhibitor of cellular proliferation. 633 57

We report the isolation of a specific protease zymogen from chicken plasma. The purification procedure involves barium citrate precipitation, ammonium sulfate fractionation, removal of plasminogen and plasmin on lysine-Sepharose, followed by anion and cation exchange, and gel permeation chromatography. Based on quantitative radioimmunoassay the zymogen is present in plasma at a concentration of 160 mg/liter, and it is obtained by our procedure in highly purified form with a yield of 1.4%. The single polypeptide chain contains an NH2-terminal alanine residue. The native molecule migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 84,000 under reducing conditions. It can be identified as an inactive proenzyme because it has very low amidolytic activity, does not react with the fluorescent active site titrant 4-methyl-lumbelliferyl p-guanidinobenzoate, and does not incorporate radioactive [3H]diisopropylfluorophosphate. It is very susceptible to limited proteolysis which converts it to an active enzyme with trypsin-like specificity. The active enzyme, likewise a single polypeptide chain, migrates as a doublet with apparent molecular weights of 39,000 and 40,000. Its amidolytic activity with synthetic peptide substrates is at least 40-fold higher than that of the proenzyme, it reacts efficiently with 4-methylumbelliferyl p-guanidinobenzoate, and incorporates [3H]diisopropylfluorophosphate while undergoing irreversible inactivation. The enzyme appears to be a reasonably efficient plasminogen activator in zymographic gels, but not in solution. With human high molecular weight kininogen as substrate the enzyme was about 25% as efficient as human plasma kallikrein. It lacks any plasminogen-independent proteolytic activity with other protein substrates, and it hydrolyzes small peptide substrates designed for both human kallikrein and urinary urokinase, respectively. Inhibition studies with peptide chloromethyl ketones indicate enzymatic properties closer to human plasma kallikrein than to the human plasminogen activator urokinase (EC 3.4.21.31). The chicken plasma enzyme and the plasminogen activator from the conditioned media of Rous sarcoma virus-transformed chick embryo fibroblasts treated with tumor promoter are different by criteria of tryptic peptide maps, and amino acid composition and enzymatic specificity. The designations chicken plasma prekallikrein plasminogen proactivator and chicken plasma kallikrein plasminogen activator are proposed for the zymogen and enzyme forms, respectively. Using rabbit antibodies against the proenzyme we developed a solid phase immunoadsorption procedure that allowed us to isolate the protein with an overall yield of 11.4%.
 ...
PMID:A proenzyme from chicken plasma similar to human plasma prekallikrein. 655 13

Monoclonal antibody (MAb) was obtained to rat plasma kallikrein after immunization of BALB/c mice with the purified enzyme. Spleen cells from immunized mice were fused to P-3 mouse myeloma cells. Four antibody secreting hybridomas were identified by enzyme-linked immunosorbant assay (ELISA) for production of antibody to rat plasma kallikrein. One hybrid was cloned by limiting dilution and expanded as ascites tumor by injection of 5 X 10(6) cells into the peritoneal cavity of male BALB/c mice primed with 2,6,10,14-tetramethylpentadecane. Antibodies at a dilution as great as 1:20,000 were detected in ascites fluid and sera of immunized animals. The lower limit of detection of kallikrein was 0.1 microgram/ml. Secreted antibodies bound specifically to rat and human plasma kallikrein, but did not show any immunological interaction with human urinary or porcine pancreatic kallikrein. The MAb provides the necessary component for an enzyme-linked plasma kallikrein immunoassay.
 ...
PMID:Monoclonal antibody to rat plasma kallikrein. 656 1

3-Methylcholanthrene-induced tumor was challenged with a low molecular synthetic protease inhibitor, [N,N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate. This drug at a dosage of 10 mg/kg or 20 mg/kg was administered by ip injection to 20 mice each harboring a solitary tumor twice daily for 10 weeks. This protease inhibitor significantly inhibited tumor growth and prolonged the survival time of the tumor-bearing mice (P less than 0.001). The results suggest the involvement of kinin-forming proteases, such as trypsin, plasmin and kallikrein, in the tumor growth.
 ...
PMID:Inhibition of growth of 3-methylcholanthrene-induced mouse skin tumor by protease inhibitor [N,N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate. 734 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>