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)

Squamous cell carcinoma (SCC) antigen was tested, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, for its ability to inhibit the activity of serine proteases, i.e., trypsin, chymotrypsin and elastase. We demonstrated that the serine protease inhibitor (serpin) of SCC antigen is specific for chymotrypsin. Preincubation of chymotrypsin with recombinant SCC antigen inhibited chymotryptic digestion of gelatin and ovalbumin through the formation of sodium dodecyl sulfate-stable complexes. These findings promote understanding of the biological functions of SCC antigen as serpin in the stratification of the normal squamous cells and in the malignant behavior of the tumor cells.
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PMID:Serine protease inhibitor activity of recombinant squamous cell carcinoma antigen towards chymotrypsin, as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 749 25

From a panel of 4 murine monoclonal antibodies directed against keratin 19 various antibody combinations were evaluated in solid-phase enzyme-linked sandwich immunoassays for detection of soluble keratin 19 fragments in patient sera. One of these antibody combinations, comprised of the monoclonal antibodies Ks 19.1 and BM 19.21, was selected for further development to a routine test (Enzymun-Test CYFRA 21-1) because of its high diagnostic sensitivity and specificity for non-small cell lung carcinoma (NSCLC). Both antibodies are specific for keratin 19, no reactivity could be observed with cytokeratin 8 or 18. The epitopes of the two antibodies were determined to be within helix 2B of the rod romain. The epitope sequences lie within the sequence 311-335 for the catcher antibody Ks 19.1 and 346-367 for the detector antibody BM 19.21. These sequences are unique, as could be confirmed from sequence databases. The standard material for the assay was prepared from a cytoskeleton fraction of cultivated MCF-7 cells. Subsequent digestion of this fraction with chymotrypsin yielded a soluble and stable standard material. Both the standard material and the serum analyte appeared as oligomers when analysed on gel chromatography: the serum analyte appeared exclusively at a M(r) of 100 +/- 10 kD, whereas the standard material eluted in fractions corresponding to 100 +/- 10 kD and 450 kD. Due to the precise definition of the antigen and the localisation of the antibody binding sequences, Enzymun-Test CYFRA 21-1 is one of the best characterised tumor markers so far.
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PMID:Lung cancer-associated keratin 19 fragments: development and biochemical characterisation of the new serum assay Enzymun-Test CYFRA 21-1. 752 45

PSA is a 34-kDa 240-amino-acid glycoprotein produced exclusively by prostatic epithelial cells. PSA is a serine protease, is a member of the kallikrein gene family, and has a high sequence homology with human glandular kallikrein. It has chymotrypsin-, trypsin-, and esterase-like activities. In the serum it is present mainly in a complex form with alpha 1-antichymotrypsin. It is secreted in the seminal plasma and is responsible for liquefaction of the seminal coagulum. The production of PSA proteins appears to be under the control of circulating androgens acting through the androgen receptors. The PSA gene is up-regulated predominantly by androgens at both the protein and mRNA levels. DRE causes minimal changes in the PSA level, while prostate massage, ultrasonography, systoscopic examination, and prostate biopsy can all cause clinically significant elevations. Other conditions, such as prostatitis, prostate intraepithelial neoplasia, acute urinary retention, and renal failure can also elevate the PSA level. The value of PSA as a screening tool is questionable because of the great deal of overlap in PSA levels between BPH and prostate cancer. However, if used in men over 50, in conjunction with DRE and/or ultrasonography, it may become a vital part of the early detection program. PSA's role in determining the clinical and pathological stage is also limited, in spite of the direct correlation between the pathological stage and the PSA level, because of great overlap in the PSA levels in various stages. The most important clinical utility of PSA is in monitoring patients after definitive therapy. PSA is most sensitive and reliable in the detection of a residual tumor, possibly recurrence, or disease progression following treatment, irrespective of the treatment modality. PSA can accurately predict the tumor status and can detect recurrence several months before its detection by any other method. PSA is also a very sensitive and specific immunohistochemical marker for tumors of prostatic origin. Compared to PAP, PSA is a more precise and meaningful marker in all clinical situations. With the development of ultrasensitive assays and the adoption of an international standard PSA calibrator, so that results from multicenter studies can be compared, PSA could become one of the most useful tumor marker in cancer biology.
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PMID:Prostatic specific antigen. 753 74

Serine proteinase inhibitors play major roles in physiological and pathophysiological processes such as angiogenesis, intravascular fibrinolysis, wound healing, and tumor invasion, and metastasis. Here, we report that human umbilical vein endothelial cells (HUVEC) synthesize three inhibitors (33,000, 31,000, and 27,000 Da) which inhibit degradation of gelatin or casein by trypsin, elastase, plasmin, and alpha-chymotrypsin. The 33- and 31-kDa inhibitors were constitutively found in the cell lysate and extracellular matrix, but not in the conditioned medium of HUVEC. Following treatment with phorbol 12-myristate-13-acetate (PMA), all the three inhibitors were expressed in the CM and increased activity was found in cell lysates and extracellular matrix. The inhibitors were not detected in PMA-treated cells in the presence of cycloheximide or actinomycin D. The inhibitors specifically bound to trypsin and were recovered from trypsin affinity column as smaller-sized inhibitors without loss of antitrypsin activity. Polyclonal antibodies to inter-alpha-trypsin inhibitor did not cross-react with the 33-, 31-, and 27-kDa inhibitors. These results suggest that HUVEC synthesize and secrete novel 33-, 31-, and 27-kDa serine proteinase inhibitors.
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PMID:Partial characterization of novel serine proteinase inhibitors from human umbilical vein endothelial cells. 753 5

Prostate-specific antigen (PSA) is a tissue-specific serine protease similar in structure to the trypsin-like glandular kallikreins but which is unique inasmuch as the enzyme activity is similar to that of chymotrypsin. The active enzyme is a single chain glycoprotein of 237 amino acids. The major form of PSA in serum is complexed to alpha 1-antichymotrypsin (ACT). A small amount is free, non-complexed despite a large excess of ACT. This suggests that the form in serum lacks enzyme activity. Although serum PSA concentrations are regularly abnormally high (above 4 micrograms/L) in prostate cancer (CAP), the utility of PSA measurements in the early detection of CAP is limited, as many tumors are undetected at a cut-off of 4 micrograms/L. Also, 25% of all men with benign prostate hyperplasia (BPH) have serum PSA levels above 4 micrograms/L. Using assays specially developed to measure free and complexed forms of PSA in serum, we found the proportion of PSA-ACT complexes to be higher in CAP than in BPH, but the ratio of free-to-total PSA in serum to be lower. Using an abnormally low ratio of free-to-total PSA to detect CAP increases diagnostic specificity by 15 to 20%, compared to using a high serum PSA concentration. This suggests that the ratios of free-to-total PSA significantly increase the ability to distinguish BPH from localized CAP. The molecular basis is unclear, but may be related to the high incidence of prostate tumor cells producing both PSA and ACT. This is in contrast to the lack of ACT production in BPH epithelium. Possibly owing to lack of ACT production in BPH areas, conditions are not optimal for complex formation, whereas tumors producing both ACT and PSA may promote the formation of PSA-ACT complexes in CAP.
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PMID:Regulation of the enzymatic activity of prostate-specific antigen and its reactions with extracellular protease inhibitors in prostate cancer. 754 78

Tumor cells avidly secrete various proteinases, and cascades of proteolytic activation occur around the cells. Therefore, cell surface receptors of tumor cells are under the constant influence of proteinases. In this study, the effects of serine proteinases on integrin-medicated cell-matrix interactions were studied in C32TG and Mewo human melanoma cells. These melanoma cells were pretreated with proteinases and their adhesive properties on various substrata were evaluated by cell adhesion assays. Paradoxically, appropriate cell surface proteolysis enhanced the RGD-sensitive cell adhesion on fibrinogen and vitronectin, but not the RGD-insensitive adhesion on type I collagen or laminin. Pretreatment of these cells with 0.1 to 1 microM of trypsin, chymotrypsin, or plasmin for 30 min at 37 degrees C increased the number of spread cells on fibrinogen and vitronectin by 200-300%. The enhancement of cell spreading was not accompanied by up-regulation of the relevant RGD-sensitive integrin expression. Analysis of the cell surface receptor by GRGDSPK-Sepharose affinity chromatography showed that trypsin treatment did not up-regulate alpha v beta 3 integrin, an RGD-sensitive receptor for fibrinogen and vitronectin in the melanoma cells, nor the induced appearance of novel receptors. Treatment of cells with 100 nM proteinases increased cell binding of both monoclonal and polyclonal antibodies against alpha v beta 3 integrin subunits by 70%, but not that of monoclonal antibody against alpha 2, alpha 3, or alpha 6 subunit, indicating that cell surface proteolysis exposed more alpha v beta 3 integrin on the cell surface. These results suggest that exposure of alpha v beta 3 integrin is a part of the mechanisms underlying the serine proteinase-induced enhancement of melanoma cell adhesion on fibrinogen and vitronectin.
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PMID:Cell surface proteolysis by serine proteinases enhances RGD-sensitive melanoma cell adhesion on fibrinogen and vitronectin. 754 29

Complex formation of prostate specific antigen (PSA) with its inhibitor alpha 1-anti-chymotrypsin (ACT) in vivo and in vitro was studied. Patients with benign prostatic hyperplasia (BPH) were treated with the computer assisted device "Prostatron." This instrument acts by means of thermal destruction of prostatic tissue. The effect of the treatment was followed by measurement of serum PSA concentrations using commercially available immunoassays from Roche (Cobas Core), Wallac (Delfia) and Abbot (IMx) and Hybritech Tandem. Serum samples were further analyzed by molecular sieving on S.300 (Pharmacia) and analyzed for PSA by immuno assay. The complex formation of PSA with ACT in serum was studied, demonstrating this process to be influenced by external stimulus. Patient sera revealing initially normal PSA levels (3 to 5 ng/ml) were stimulated to very high levels of PSA (> or = 140 ng/ml) by Prostatron treatment. The absolute PSA level depends on the assay system and not only on the staging of the prostate tumor. In addition, complex formation was studied in athymic nude mice and in vitro revealing the possible pathways of PSA release. PSA from LNCAP cells kept in vitro show predominantly uncomplexed (free) PSA, whereas PSA from LNCAP cells injected into nude mice appears in the serum of the animals in complexed form. This demonstrates how in the immunization process free and complexed PSA serve as antigens in the standard procedure for the production of antisera for PSA. This model system also can be used for studies of the release mechanism of PSA into blood circulation.
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PMID:In vivo and in vitro complex formation of prostate specific antigen with alpha 1-anti-chymotrypsin. 868 58

The clinical and immunohistochemical features of supratentorial (5 patients) and cerebellar (1 patient) glioblastomas, in which giant cells were conspicuous were examined. Three of the patients died within 26 months after the first treatment, and the follow-up period is presently 1 year or less in the remaining patients. The giant cells either showed large and bizarre nuclei or were multinucleated. Both giant and smaller cells excluding neuronal, endothelial and infiltrative cells were positive for GFAP, vimentin, and alpha-1 anti-chymotrypsin. The strong positivity for PCNA staining indicated that the capacity of the giant cells to synthesis DNA was preserved. DNA fragmentation, measured by the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine-5'-triphosphate (dUTP)-biotin nick end labeling method, was observed in only 1 patient, who had received radiotherapy just before biopsy, and none of the patients showed bcl-2 positivity. Mutant type of p53 tumor suppressor gene was observed in the giant cells of 3 patients. Giant cell in glioblastoma is of glial origin, synthesizes DNA, and its progression may be related to tumor suppressor gene.
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PMID:Immunohistochemical study of giant cell in glioblastoma. 760 97

Polymorphonuclear neutrophils (PMN) can be primed for enhanced release of reactive oxygen species (ROS) by exposure to cytokines and biological response modifiers. ROS are considered to possess tumoricidal activity. The polyenzyme preparation Wobenzym (WE) contains pancreatin, papain, bromelain trypsin and chymotrypsin and is used in adjuvant tumor therapy. We investigated killing of WE-exposed PMN against tumor cells and analyzed WE influence on ROS production in a chemiluminescence assay in PMN in vitro and in vivo. Depending on dose WE stimulates the cytotoxic capacity of PMN in vitro against tumor cells (50 micrograms/ml:p < 0.01). Exposure of PMN to Wobenzym caused a time-dependent significant (p < 0.02) increase in release of ROS. Similarly, oral administration of Wobenzym to healthy volunteers (n = 28) resulted in significant increases (p < 0.01) in ROS production, depending on dose (peak with 20 tablets) and time (peak 4 hours after Wobenzym administration). In contrast, ROS production was not elevated in the PMN of healthy volunteers receiving placebo (n = 8) or no treatment (n = 16). These findings point to an immunomodulatory capacity of WE in adjuvant tumor therapy.
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PMID:Stimulation of reactive oxygen species production and cytotoxicity in human neutrophils in vitro and after oral administration of a polyenzyme preparation. 766 74

Effects of alpha-chymotrypsin and deoxyribonuclease I (DNase I) on the early phase of blood-borne lung metastasis in rats were studied using confocal laser scanning microscopy and AH-109A cells labeled either with carboxyfluorescein diacetate succinimyl ester or with 51Cr. Intravenous administration of alpha-chymotrypsin or DNase I appeared to enhance or inhibit, respectively, the tumor cell arrest in lung microvasculature as a reflection of reduction or promotion of the tumor cell clearance in the microvasculature. These results suggest that the effects of alpha-chymotrypsin and DNase I are related to induction of tumor cell aggregation and disaggregation in the blood stream, respectively.
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PMID:Effects of serine protease and deoxyribonuclease on intravascular tumor cell arrest in rat blood-borne lung metastasis. 767 31


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