Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:3.4.21.4 (
trypsin
)
42,187
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
ZGM was purified from both primary and metastatic colonic carcinomas demonstrably positive for ZGM by immunofluorescence microscopy. ZGM purification included preparative Pevikon electrophoresis, Sepharose 4B molecular exclusion chromatography and Con A-Sepharose affinity chromatography. ZGM had an alpha2 electrophoretic mobility, an estimated molecular weight by Sepharose 4B equal to or greater than 2 x 10(6), and did not bind to Con A-Sepharose, although having determinants with CEA-like activity. Its immunologic activity was resistant to
trypsin
or phospholipase A but not to neuraminidase. Antisera prepared to ZGM and absorbed with saliva, when tested by double immunodiffusion, formed a single precipitation line with saline extracts of colon tumors and did not cross-react with CEA, AFP, normal tissue extracts, ferritin, NCA, NCA-2, CSAp, blood groups A, B, H, Lewis antigen, or buffy coat, alpha-2 macroglobulin, saliva or ovarian cyst fluid. Immunofluorescence microscopy confirmed the presence of ZGM in 40 out of 45 adenocarcinomas of the GI tract staining primarily in tumors, the apical cytoplasm, and in grossly nonmalignant tissues, the deep crypts of the villi, while all of 22 non-GI tumors in the study were ZGM negative.
Cancer
1978 Sep
PMID:Present status of the zinc glycinate marker (ZGM). 70 28
An ovarian cystadenocarcinoma-associated antigen (OCAA) was found to be common to all serous and mucinous cystadenocarcinomas of the ovary. It was apparently absent in tissues of normal reproductive organs. Furthermore, OCAA was not detected in benign ovarian serous and mucinous cyst-adenomas or in any other gynecologic or nongynecologic cancers thus far tested. The antigenic determinant of OCAA was immunologically unrelated to the carcinoembryonic antigen, other known tumor antigens, or the histocompatibility antigens. We purified and partially characterized OCAA. The antigen was a high-molecular-weight glycoprotein soluble in 0.6 M perchloric acid. It consisted of about 50-60% protein (based on dry wt). Amino acid composition in OCAA was characterized by a high percentage of threonine, serine, proline, and valine. Galactose and N-acetylglucosamine were the principal carbohydrate constituents. The antigenic activity was resistant to treatment with
trypsin
and protease and also to treatment with DNase, RNase, and N-acetylneuraminidase. The antigenicity was considerably reduced by mild periodate oxidation.
Natl
Cancer
Inst Monogr 1975 Oct
PMID:Tumor-associated antigen for cystadenocarcinomas of the ovary. 82 81
A chimpanzee anti-human melanoma antiserum was used to study the enzymatic susceptibility and spontaneous release into tissue culture medium of human melanoma tumor-associated antigens (TAA). Limited proteolytic digestion of melanoma cells with
trypsin
or with pronase rendered these cells refractory to lysis by the chimpanzee antiserum and complement. Longer periods of incubation of higher concentrations of enzyme caused an increased sensitivity to lysis. Digestion of melanoma cells with neuraminidase apparently exposed antigens reactive with natural antibodies in rabbit complement because cells so treated had a marked increase in sensitivity to cytolysis. Absorption of the complement with either neuraminidase-treated human melanoma cells or washed human spleen cells prior to its use in the cytotoxicity assay removed this activity. When absorbed complement was used, neuraminidase had no noticeable effect on the expression of malanoma TAA. These results suggest that proteolytic digestion of melanoma cells may prove to be a useful means of solubilizing TAA. The spontaneous release of melanoma cell membrane TAA was studied. Protein precipitated by (NH4)2SO4 from four of six samples of tissue culture medium used to feed malanoma cell lines contained significant antigenic activity compared to a control "antigen" preparation, whereas one preparation contained only limited TAA activity. One melanoma cell line that apparently failed to release TAA into the culture medium had previously become nonreactive with the chimpanzee antiserum. From these data, we conclude that melanoma cells growing in tissue culture rapidly release large amounts of TAA into the culture media and, as a result, the spent culture medium may be a good source for obtaining TAA for further study. The significance of these results is discussed.
J Natl
Cancer
Inst 1977 Feb
PMID:Enzymatic susceptibility and spontaneous release of human melanoma tumor-associated antigens. 83 72
Three assays of cell-mediated cytotoxicity in mice, involving release of either 51Cr (CRA), 125iododeoxyuridine (IRA), or [3H]proline (PRA), were compared under identical test conditions. Experiments were performed with effector cells from mice immunized with FBL-3 tumor cells, a syngeneic Friend virus-induced leukemia, or with allogeneic normal spleen cells. With established tissue culture cells as targets, similar results were obtained in all three assays. The cytotoxicity produced by cells from in vivo-immunized mice and the induction of cytotoxicity in vitro were T-cell-dependent. When short-term culture target cells were used, the IRA gave a more selective pattern of cytotoxicity than did the other two assays. However, when remaining target cells at the end of the assay were treated with
trypsin
, higher levels of 125iododeoxyuridine (125IUDR) release were seen, and the results were then comparable to those in the CRA and PRA. These results indicated that 125IUDR, a nuclear label, could only be released after lysis of cells. In contrast, 51Cr or [3H]proline, which are cytoplasmic labels, could also be released from damaged but unlysed cells. These fundamental differences could give different results in these assays, which could determine their correlation with in vivo transplantation immunity.
J Natl
Cancer
Inst 1977 Feb
PMID:Comparison of three isotopic assays of cell-mediated cytotoxicity against mouse tumor cells. II. Sensitivity and specificity of the assays and characteristics of effector and sensitizing cells. 83 81
Regression of MTW9 mammary carcinoma, which consistently follows withdrawal of mammotropic hormones, was characterized by a rapid decrease of thymidine incorporation into DNA but only a slight reduction or uridine incorporation into RNA and amino acid incorporation into proteins. Within 24 hr of hormone withdrawal, cytosol proteins of MTW9 became more easily degraded by
trypsin
, alpha-chymotrypsin, or subtilisin BPN'. Labilization of cytosol proteins occurred much earlier than any change in the level of protein synthesis or lysosomal enzyme activity. The data showing increased susceptibility to proteolysis could not be explained either by the presence of endogenous proteases, by the destruction of the exogenous proteases used in the assay, or by the existence of protease inhibitors. Nor were any differences detected either in the distribution of radioactive precursor among the cytosol proteins from growing or regressing tumors or in the electrophoretic pattern of the same proteins. Preincubation of the cytosol proteins with dithiothreitol or with prolactin, 17 beta-estradiol, progesterone, and hydrocortisone did not modify the susceptibility to proteolysis. However, after heat denaturation, cytosol proteins of regressing and growing tumors became equally susceptible to proteolysis. It is suggested that regression of MTW9 mammary carcinoma occurs not only because cell reproduction is arrested, but also because susceptibility of cytosol proteins to proteolysis is increased.
Cancer
Res 1977 Mar
PMID:Increased susceptibility of cytosol proteins to proteolytic digestion during regression of a hormone-dependent mammary tumor. 83 67
We investigated whether the
malignancy
of hybrids between normal and malignant cells could be correlated with the loss of specific genes borne by specific chromosomes from the normal parent cells. Tumors produced in mice by the inoculation of Cl.1D cells (an L cell derivative) contained tumor x host cell hybrids. Hybrid cell populations isolated from 14 tumors were injected into 123 mice, of which 108 (87%) developed tumors. Metaphases of growing hybrid cell tumors were analyzed by use of a
trypsin
-Giemsa banding technique. The chromosomes contributed by the host (normal) parent cell could be distinguished from Cl.1D chromosomes, since the latter exhibited morphologic differences due to rearrangements. In the 14 hybrid tumors analyzed, we found that any one of the chromosomes of the host cell might be present, which indicated that none of the chromosomes from the normal cell bore genetic information capable of suppressing the
malignancy
of Cl.1D cells. Absence of complimentation in the hybrids suggested that, even if the accumulation of several mutations were necessary for
malignant tumor
growth of Cl.D1 cells, none of these mutations is recessive.
J Natl
Cancer
Inst 1977 May
PMID:Tumor x host cell hybrids in the mouse: chromosomes from the normal cell parent maintained in malignant hybrid tumors. 85 28
We have purified epithelial cells from human colonic tumours by velocity sedimentation in an isokinetic density gradient of Ficoll in tissue culture medium. In frozen sections of colonic carcinoma, histochemically demonstrable N-acetyl-beta-D-glucosaminidase (HDAG) was observed primarily in epithelial cells. We used this enzyme as a histochemical marker of epithelial cells. Initial suspensions of cells from colonic tumours suspended with 0-25%
trypsin
contained an average of 24% of the nucleated cells with HDAG. In the purest fraction obtained from gradient centrifugations, an average of 74% of the nucleated cells contained HDAG. After centrifugation, the quarter of the density gradient which contained the most rapidly sedimenting cells was purified 2-4-fold over that in the initial suspension. Cells in this zone of the gradient also gave rise to colonies in soft agar. Cells from initial suspension resulted in 15-25% as many colonies of 7 or more cells in cultures inoculated with the same number of nucleated cells. For the most part, cells obtained from the other zones of the gradient did not give rise to colonies in soft agar.
Br J
Cancer
1977 Jun
PMID:Partial purification of human colonic carcinoma cells by sedimentation. 87 70
Our investigation of normal, hyperplastic, and neoplastic prostatic tissue during the past 2 1/2 years has produced several findings which have been published or accepted for publication. (a) Cells from hamster prostates with intense histochemically demonstrable acid phosphatase activity (HDAP) after fixation with formaldehyde which we believe to be epithelial cells can be obtained in 97.2% +/- 0.8% purity by velocity sedimentation in a previously described isokinetic density gradient; (b) similarly, cells with HDAP, many of which contain lipofuscin granules, can be obtained as 81.0% +/- 12.2% of nucleated cells from hyperplastic human prostates and as 86.4% +/- 9.4% of nucleated cells from human prostatic carcinomas; (c) more cells were obtained from human hyperplastic prostates and prostates with prostatic carcinoma per gram of tissue with the aid of Pronase than were obtained with
trypsin
, collagenase, or mechanical methods; (d) more cells per gram of tissue were obtained from surgically removed prostates than from prostates obtained at even very rapid autopsies, and a much larger proportion of the cells from surgically removed prostates were viable as assessed both by dye exclusion and by plating efficiency; (e) none of several substrates and inhibitors which we tested were highly specific for acid phosphatase from purified prostatic epithelial cells compared with several other kinds of purified human cells; and (f) purified hamster prostatic epithelial cells incorporate large amounts of tritiated thymidine in 72-hour cultures.
Cancer
Treat Rep
PMID:Separation and characterization of epithelial cells from prostates and prostatic carcinomas: a review. 87 27
Pancreatic secretory abnormalities develop in most persons with pancreatic cancer and have been attributed to ductal obstruction. These experiments investigated whether abnormal secretion results instead from carcinogen-induced changes in the secreting cells. Fifty male Syrian Golden hamsters (40 to 100 grams) received weekly injections of di-isopropyl-nitrosamine (250 mg/kg, subcutaneously), and survivors and age-matched controls were studied after 3.5 to 6.5 months of treatment. Pancreatic secretion was stimulated by secretin or cholecystokinin (2 units/kg, intravenously, as a bolus). After each stimulus four 15-minute collections of pancreatic juice were analyzed for HCO3- and Cl- or total protein, amylase,
trypsin
, and chymotrypsin. The organs were examined histologically. Pancreatic ductal adenocarcinoma developed in 30% of the animals at 5 months, 56% at 5.5 months, and 100% at 6.5 months. The animals without
cancer
either had hyperplasia of the duct epithelium or were histologically normal. The histologic appearance of acinar tissue and protein secretion were normal in all groups. The tumors did not obstruct the major ducts. In all treated animals the pancreatic secretory response to secretin was of low volume, low maximal [HCO3-] and HCO3- output, and low [Cl- + HCO3-]; these changes progressed with time. The secretory abnormalities antedated the appearance of the neoplasms and were not caused by obstruction.
...
PMID:Pancreatic secretion in hamsters with pancreatic cancer. 87 54
We undertook to test the recent suggestion that measurement of immunoreactive carcinoembryonic antigen (CEA) in pancreatic secretion may be useful in diagnosis of pancreatic cancer. Using duodenal intubation and a perfusion method in 57 cases, we measured the rate of pancreatic CEA secretion into the duodenum under basal saline perfusion, alone and with continuous intravenous infusion of secretin (2 clinical units per kg per hr) and of cholecystokinin-pancreozymin (CCK, 15 Crick-Harper-Raper units per kg per hr); and we compared the CEA output with secretion of
trypsin
, lipase, and bicarbonate under the same conditions. Subsequent laparotomy revealed pancreatic carcinoma in 25 patients, pancreatitis in 7, other intraabdominal
malignancies
in 6, and benign nonpancreatic disorders in 19. CEA output rates did not differentiate all pancreatic-
cancer
patients from other patients in any test condition. However, pancreatic enzyme outputs were abnormal with almost 90% of cancers of the pancreatic head and with 75% of cancers of the pancreatic body and tail. For detection of pancreatic cancer, enzyme and bicarbonate outputs in response to CCK are more accurate than pancreatic CEA or bicarbonate outputs in response to secretin. Since CCK-stimulated enzyme outputs can be related accurately to malabsorption (not reported here), we prefer them to bicarbonate output for assessment of pancreatic function.
...
PMID:Prospective evaluation of the pancreatic secretion of immunoreactive carcinoembryonic antigen, enzyme, and bicarbonate in patients suspected of having pancreatic cancer. 89 42
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