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

Six patients with liver metastases from carcinoid or colon carcinoma underwent hepatic derterialization. This operation, known to cause both tumor necrosis and liver cell damage, caused considerable increases of several lysosomal acid hydrolases in the circulation. Thus, beta-glucosidase showed a small temporary increase during the operation, followed by a slower but higher reaction reaching a maximum 12 to 36 hours postoperatively. Similar reactions were noted for beta-glucuronidase, acid phosphatase, beta-galactosidase, arylsuphatase A, and N-acetyl-beta-glucosaminidase while no reactions were found for cathepsin D. Very high enzyme levels occurred in a patient dying from bleeding complications in the postoperative period.
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PMID:Plasma activities of lysosomal enzymes after hepatic dearterialization in man. 0 1

Ascites fluid accumulation accompanying a mastocytoma or L1210 murine tumor is significantly retarded following the i.p. or s.c. injection of moderate quantities of pepstatin, a known acid protease inhibitor. No effect on cell count was noted by pepstatin treatment. The probable mechanism by which pepstatin acts is by inhigiting the enzymatic formation of chemical mediators known as leukokinins. These are pharmoacologically active peptiedes having potent permeability characteristics previously described by this laboratory. Leukokinins are formed by cathepsin D-like enzymes present in the invading cells and in the ascites fluid acting on a protein substrate, leukokininogen. present in the ascites fluid. Pestatin inhibits the action of these leukokinin-forming enzymes invitro but has no effect on kallikreins (bradykinin-forming enzymes) in vitro. Human ascites fluid from a patient with ovarian carcioma was found to have a paepstatin-inhibited, leukokinin-generating system, as does the mouse. A 'chemical mediator' theory is proposed for ascites fromation which broadens the previously held theory of lymphatic blockage (Holm-Nielsen) and may explain the recent findings of Hirabayashi and Graham of increased plasma-ascites exchange in peritoneal carcionmatosis. Pepstatin inhibition of chemical mediator formation may represent a new therapeutic approach to ascites fluid accumulation in neoplastic disease.
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PMID:Pepstatin, an inhibitor of leukokinin formation and ascitic fluid accumulation. 4 79

Evidence is reviewed that pepstatin, an inhibitor of acid kininogenases such as cathepsin D, may be an effective therapeutic agent in retarding ascites accumulation in certain cancers. The evidence for this conclusion is based on the actions of pepstatin in retarding ascites in six different tumor strains inoculated into various species of mice, as well as the demonstration that cathepsin D activity is reduced in vivo in several organs following pepstatin administration. The latter is significant since we have postulated that ascites formation, in good part, is due to leukokinin formation, which is catalyzed by cellular-released cathepsin D.
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PMID:Pepstatin, an inhibitor of acid kininogenases and ascites retardant in neoplastic disease. 9 21

The measurement of the activity of acid hydrolases and of alkaline phosphatase in bronchial aspirates obtained through bronchoscopic procedures from a series of 300 patients forms the basis for a screening program to diagnose bronchial malignant neoplasms more effectively. We define such a screening test as one permitting rapid measurements indicative of pathologic abnormalities and producing a preliminary diagnosis which, if in error, yields preferably a false-positive result. Using this approach, we demonstrated that an elevation of the activity of alkaline phosphatase or cathepsin D predicts a 50 percent likelihood of cancer, but elevation of both the concentrations of alkaline phosphatase and cathepsin D has an additive prediction of 71 percent. Data obtained in this study showed that the presence of a pulmonary tumor can cause increased levels of alkaline phosphatase or cathepsin D (or both) in bronchial aspirates before the presently accepted methods yield a diagnostic result. Furthermore, those patients with an elevated activity of alkaline phosphatase or cathepsin D (or both) but with no histologically demonstrable pulmonary carcinoma can be reexamined intermittently.
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PMID:The diagnostic value of lysosomal enzyme patterns in bronchial aspirates of patients with suspected bronchial carcinoma. 20 50

A possible mechanism for tumor cell invasion of normal tissue might be secretion of proteolytic enzymes. This study compares and contrasts production and secretion of proteinases by cell cultures of normal and chemically transformed mouse epithelial cells. Lysates of normal and neoplastic cells contain similar amounts of neutral proteinase, cathepsin D and plasminogen activator. Neither collagenase nor elastase could be identified in lysates of, or serum-free culture medium bathing, normal or neoplastic cells. Neoplastic cells secrete ten times more plasminogen activator than normal cells. Our data support the hypothesis that plasminogen activator produced by neoplastic cells could fuction to activate latent proteolytic enzymes secreted by connective tissue cells which might result in spread of neoplastic cells into normal tissue.
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PMID:Production and secretion of proteolytic enzymes by normal and neoplastic cells. 45 22

Cathepsin D expression was assessed by immunohistochemistry in 59 node-negative and 77 node-positive infiltrative ductal not otherwise specified (NOS) breast carcinomas and compared with overall survival at 90 months. Cancer cells in 60% (81/136) of the tumors expressed cathepsin D. In the stroma of 33% (18 of 55) cathepsin D negative tumors, numerous strongly cathepsin D positive, benign macrophage-like cells were found. Multivariate analysis showed no significant correlation of cathepsin D expression and overall survival for all patients for node-negative and node-positive patients and for patients with vimentin-positive and -negative tumors. However, in node-negative but not in node-positive patients, a trend for better survival for patients with cathepsin-positive vimentin-negative tumors and worse survival for those with cathepsin-positive vimentin-positive tumors was noted. Due to the low number of patients in these subgroups, neither trend reached significance. Cathepsin D expression was independent of patient age, size, and histologic grade of tumor, and vimentin expression. However, in the node-positive group, negative correlation of cathepsin D and vimentin expression was found. We suggest that prognostic significance of cathepsin D in infiltrative ductal NOS breast carcinomas may be associated with the pathway of its synthesis rather than with its mere presence in tumor cells.
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PMID:Cathepsin D in invasive ductal NOS breast carcinoma as defined by immunohistochemistry. No correlation with survival at 5 years. 133 83

We conducted a trial in 42 benign and malignant meningiomas to assess a possible influence of preoperative dexamethasone therapy on mitotic index, labelling indices of proliferating cell nuclear antigen (PCNA), progesterone receptor, epidermal growth factor receptor (EGF-R), c-erbB-2 oncoprotein, cathepsin D, gamma-gamma enolase as well as the mean number of silver-stained nucleolar organizer region-associated proteins (AgNORs). Tumors with preceding dexamethasone therapy for more than 1 day display significantly less immunohistochemical staining for PCNA. A correlation between the labelling index of PCNA and the degree of malignancy could not be identified. There was no significant effect of preoperative dexamethasone therapy on the other parameters. Our data suggest that dexamethasone may selectively inhibit the expression of PCNA in the G1/S-phase of the cell cycle. Thus, we emphasize the necessity to heed factors, e.g. dexamethasone, which may affect the expression of proliferating markers.
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PMID:Influence of preoperative dexamethasone therapy on proliferating cell nuclear antigen (PCNA) expression in comparison to other parameters in meningiomas. 136 Aug 48

This is a retrospective study on 162 node-negative patients, with both biochemical and clinical factors being measured for determination of prognostic markers. Steroid receptors were measured on all tumors, while tumor size, histological grade, ploidy status, and cell cycle kinetics indicators could not be found or measured on 25 or less of the patient group. The primary focus of this study was the measurement of cathepsin D, analyzed by two different procedures, and 161 of the 162 patients had at least one value. The antigenic assay was performed using the US-CIS kit, and it was sensitive and reproducible. A biochemical assay using the enzymatic activity of cathepsin D was developed, and it gave proportional values, compared to the antigenic assay values (r2 = 0.79). Our results indicated that the mean antigenic levels were 20% higher than the biochemical assay levels (P = 0.001). High levels of cathepsin D by the antigenic assay predicted poor relapse-free (P = 0.0001) and overall (P = 0.0004) survival. High levels of cathepsin D by the biochemical assay also predicted poor relapse-free (P = 0.031) and overall (P = 0.0013) survival. The cathepsin D values were still useful as predictors of outcome after multivariate analysis. Several other factors, such as grade and S phase, were useful as additional prognostic indicators. In conclusion, cathepsin D is the most useful marker in node-negative patients, and the analysis can be performed by both a biochemical and an antigenic assay.
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PMID:Cathepsin D as a prognostic indicator for node-negative breast cancer patients using both immunoassays and enzymatic assays. 139 23

Ovarian cancers are highly invasive. In a first attempt to define the hormones and factors involved in the control of tumor invasion and metastasis, we have used the human ovarian cancer cell line BG-1 which contains both estrogen and progesterone receptors. Protein synthesis and secretion was assayed by [35S]methionine incorporation and polyacrylamide gel electrophoresis followed by fluorography. Three responses to estradiol were found: 1) procathepsin D secretion was increased, whereas the corresponding intracellular proteins were not significantly affected; 2) an abundant but nonidentified 120-kilodalton (kDa) estrogen-induced secreted glycoprotein, different from CA125, was detected for the first time; and 3) the number of cells as determined by DNA assay was markedly stimulated, reaching a higher level of confluency. The antiestrogen OH-tamoxifen was weakly agonist at low concentrations to stimulate cell growth but was a pure antagonist on the 120-kDa protein. The steroid specificity of these responses strongly suggests that they are mediated by the estrogen receptor. We conclude that cathepsin D secretion is specifically stimulated by estrogen in this ovarian cancer cell line as it is in estrogen receptor-positive breast cancer cells. Both cathepsin D and a newly described 120-kDa secreted glycoprotein are potential markers of hormone responsiveness and/or aggressiveness which deserve to be further studied in clinical ovarian cancers.
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PMID:Estradiol stimulates cell growth and secretion of procathepsin D and a 120-kilodalton protein in the human ovarian cancer cell line BG-1. 146 54

Forty patients with intermediate stage (T2 > 3 cm-T3, N0-N1) operable breast cancer received neoadjuvant chemotherapy by MCF (mitoxantrone, cyclophosphamide, 5-fluorouracil). Four cycles were administered at 3-week intervals. The obvious hematological toxicity (64% of grade III for the leucocytes and up to 34% of grade IV for the granulocytes) was rapidly reversible and did not hinder completion of the treatment. Ten patients showed a complete remission and a tumor volume regression of more than 50% was observed in 12 other patients. Tumor shrinkage allowed breast-saving surgery in 50% of the cases. A complete sterilisation of the surgical specimen was found in only two of the 40 patients and a few persisting neoplastic cells were found in ten other cases. A positive response at the level of the axillary lymph nodes was also obtained in more than 50% of the cases. In 25 of the 36 cases examined, the primary chemotherapy induced cellular lesions (fibrosis, necrosis) at the tumor level. A feasibility study was undertaken in order to determine quantitatively several biochemical parameters (steroid hormone receptors, cathepsin D, c-erbB-2 oncoprotein) in very small tumor samples obtained by Tru-Cut before any treatment and in surgical specimens. In the future, these micromethods will be used systematically with the aim of estimating the value of these potential prognostic factors for therapeutic follow-up of the patients.
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PMID:[Neoadjuvant chemotherapy, with mitoxantrone, cyclophosphamide and fluorouracil, in operable breast cancer of intermediate stage: first results of a phase II study in 40 patients]. 148 24


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