Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cysteine had been reported to increase survival time in thymoma-bearing mice and the interpretation suggested was that this was due to inhibition of a collagenase activity associated with some tumor cells by a chelating action of cysteine. In the present work it was shown that cysteine was a particularly potent inhibitor of amino acid transport into S37 ascites tumor cells, raising another possible interpretation of the earlier data. Sarcomas have previously been reported to lack collagenase activity; a survival study using S37 cells was therefore undertaken in an attempt to distinguish between possible interpretations of the earlier data involving thymomas. A null result was obtained with either cysteine or EDTA, reinforcing the earlier interpretation that survival enhancement with thymoma-bearing mice was due to an effect on collagenase. Other sulfhydryl analogs were found to inhibit transport also, and the effect was more pronounced with system L than system A. The reason for cysteine's particularly potent action on amino acid transport may be associated either with chelation of a metal ion involved in transport, or the involvement of the gamma-glutamyl cycle in the support of amino acid transport.
Cancer Biochem Biophys 1977
PMID:Effects of cysteine upon tumor cells. 2 29

A specific collagenase (EC 3.4.24.3) has been found and purified from serum-free culture medium of 11095 epidermoid carcinoma of rat prostate. The molecular weight of this collagenase was estimated at 71 000 and the pH optimum was approx. 7. At 26 degrees C, the collagenase cleaved collagen at a site 3/4 the length from the N-terminus. At 37 degrees C, this collagenase degraded collagen to smaller peptides. The enzyme activity was inhibited by serum, cysteine and EDTA, but not by protease inhibitors. The presence of collagenase in rat tumor tissue suggests that this enzyme might play a significant role in tissue invasion by cancer cells.
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PMID:Collagenase activity in cultures of rat prostate carcinoma. 3 9

In untreated patients with inoperable lung cancer, serum levels of alpha1-antitrypsin were found significantly increased in comparison to patients with non malignant diseases of the lung, alpha2-macroglobulin levels were unchanged in both groups of patients. There was also no difference in alpha2-macroglobulins in cancer patients reacting with DNCB and in non-reactors. Thus alpha2-macroglobulin levels do not seem to correlate with the immunestatus of cancer patients. Proteinase inhibitors are involved in a variety of biological processes including blood, clotting, digestion, and sperm capacitation. alpha1-antitrypsin, a alpha-globulin with a molecular weight of about 60,000 has been found to be decreased in patients' serum under several pathological conditions. A clear correlation exists between alpha1-antitrypsin deficiency and hereditary pulmonary emphysema (1, 2), respiratory distress syndrome (3), and juvenile cirrhoses of the liver (4). Elevated serum levels of alpha1-antitrypsin have also been found in some cancer cases. Thirty years ago a cancer test was developed on the basis of differences in the antiproteolytic activity in cancer patients' sera and in patients with other non-neoplastic diseases (5, 6). Several authors have tried to confirm these early data regarding specifity and sensitivity with respect to a screening test for cancer (7, 8). Methods of these authors were based mainly on enzyme substrate inhibition assays by addition of the patients' sera. Recently a commercially available test, based on immune-precipitation according to Mancini (9), has been developed (Behring-Werke, Partigen). By using this standardized method for determinating alpha1-antitrypsin, Harris et al. have recently demonstrated that patients with inoperable lung cancer have significantly elevated levels of this antiprotease in their sera (10), in comparison to patients with non malignant diseases of the lung. alpha2-macroglobulin is a serum protein with a molecular weight of 800,000 and with known antiprotease activity and can therefore bind trypsin, plasmin, elastase, and collagenase and it is known that alpha2-macroglobulin decreases with increasing of age. Changes of alpha-macroglobulin have also been observed in several pathological conditions (11). James et al. 4ave found decreases in serum of myeloma patients (12). An association between the development and function of lymphocytes and alpha2-macroglobulin has been suggested by several authors (13, 14). This alpha2-globulin has also been demonstrated on the surface of peripheral blood lymphocytes (15) and there is evidence that it is synthesized by lymphocytes (16). The purpose of the present study was to determine serum alpha1-antitrypsin levels in patients with inoperable lung cancer and to determine whether there is also an inverse correlation to alpha2-macroglobulin. It was further attempted to correlate alpha2-macroglobulin with general immunological parameters, as it is known that patients with lung cancer show a decreased general immune-reactivity (17).
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PMID:Serum levels of alpha1-antitrypsin and alpha2-macroglobulin in lung cancer. 6 86

Benign and malignant prostatic tissue was removed in surgery and partitioned for (a) ultrastructural study, (b) tissue culture, and (c) (c) immunochemical study. Fourteen malignant and 18 benign prostatic cancer specimens were examined by transmission electron microscopy (TEM) for the presence of viruses or virus-like particles. Viruses could not be identified with assurity in thin sections. Acinar cells of normal, benign prostatic hypertrophy (BPH), and neoplastic prostate tissue were examined in the scanning electron microscope and TEM and found to be extremely heterogenous in their surface morphologies. Three major types of surface morphologies were present: microvillous, ruffled, and bare. All three types of cells were present in normal, BPH, and neoplastic acini. A collagenase procedure was utilized to remove the stromal cells from glandular structures prior to in vitro cultivation. Partially purified extracts from 71 human urothelial tumors and 75 human urothelial nontumor tissues were used as competing antigens in competition radioimmunoassay in an effort to detect the presence of one of the structural components of type-C ribonucleic acid viruses, the p30 core protein. The urothelial tumors tested included 42 BPH specimens and 18 prostatic carcinoma specimens. Thirty-eight percent of the prostatic carcinoma tissues and 48% of the BPH tissues demonstrated the presence of a protein antigenically similar to the p30 core protein of an oncogenic RNA virus.
Cancer Treat Rep
PMID:Morphologic and immunologic studies of human prostatic carcinoma. 6 19

Urogenital tissue specimens were maintained in culture for 2 years. Epithelioid growth was enhanced with use of collagenase digestion rather than trypsinization. Twenty of 34 prostate cancer cell cultures survived more than ten in vitro passages, during which time four of 20 demonstrated epithelioid morphology. One epithelioid line (T-157) survived 32 in vitro passages. The cells demonstrated lack of contact inhibition in culture, were slightly positive in acid phosphatase tests, and reacted positively with cytomegalovirus (CMV)-immune sera in indirect immunofluorescence (IF) tests. These cells, which were proven to be of human male origin, failed to yield infectious virus and could be re-isolated from a nodule induced by the cells when injected sc into weanling athymic nude mice. The serum of the patient from which the tumor cells were derived demonstrated high CMV antibody titers and reacted with the virus-specific membrane and intracellular antigens of CMV-transformed human cells in IF tests. A CMV strain isolated from one of the normal prostate cell cultures established an in vitro long-term persistent infection of human embryo lung cells which resulted in the development of two transformed cell lines. The transformed cells possessed CMV antigenic markers and induced non-differentiated tumors when transplanted into athymic nude mice. The results constitute further evidence of the transforming capacity of CMV, and suggest that the virus may be oncogenic in its natural (human) host.
Cancer Treat Rep
PMID:Cytomegalovirus and cancer of the prostate: in vitro transformation of human cells. 6 20

Summary--Tumor invasion requires the breadkdown of the main structural protein, collagen. A series of fourteen epidermoid carcinomas of the larynx and oral cavity produced a collagen dissolving enzyme in vitro as demonstrated by the breakdown of 14C-labeled collagen. Oral cavity tumors showed greater activity than laryngeal carcinomas while both sites were more active than uninvolved mucosa from the same patients. Tumor associated collagenase activity, in common with previously described collagenases, can only be demonstrated in vitro and requires protein synthesis. Maximum tumor collagenase occurred at 24 hours in vitro and then declined as compared with the maximum collagenase at 72 hours in vitro produced by oral cavity mucosa. The 14 patients in our series were ranked in order of the collagenase activity of their tumors. At 18 months after the diagnosis, four of the six patients with the most active tumors were dead of cancer and one patient was alive with persistent cancer. High collagenase activity may be a factor in the clinical aggressiveness of epidermoid carcinomas of the head and neck.
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PMID:Collagenase activity in epidermoid carcinoma of the oral cavity and larynx. 16 14

An organ culture method suitable for the maintenance of viable human breast cancer for at least 14 days has been described. This method was applied to a total of 94 breast cancer specimens. It allowed good survival of "soft" tumors of various histological types, with loose connective stroma even in hormone-free medium. In contrast, "scirrhous" cancers showed poor survival in hormone-free medium; viable cells were maintained only at the very periphery of the explants. Supplementation of the medium with insulin (10 mug/ml), ovine prolactin (5 mug/ml), and hydrocortisone (1 mug/ml) in various combinations seemed to induce enlargement of viable cancer cells and moderate loosening of the stroma in some cases. However, it did not improve the survival of central tumor cords in scirrhous explants. Further supplementation of the medium with 17 beta-estradiol (minimum effective dose, 0.1 to 10 ng/ml), although it did not affect soft tumors, markedly improved survival of the cancer cells of scirrhous tumors throughout the whole explants, with evidence of collagen digestion around the neoplastic cells. This was observed in 18 of 20 scirrhous cancers subjected to this treatment. Estradiol need not be present during the whole culture period; the results at 14 days were identical in explants treated with estradiol for the first 7 days only or for the entire period. Addition of purified collagenase during the first 24 or 48 hr of culture resulted in complete dissolution of the collage. After such treatment, culture under the usual conditions resulted in excellent survival of the explants without improvement from hormone supplementation; thus, while estradiol was necessary when collagen was present, it was not longer required after collagen digestion. It can be concluded that breast cancer cells in organ culture are only slightly, or not at all, hormone dependent for survival, provided that they are not restrained by a dense collagen barrier. The estrogen-induced changes allowing survival inside the scirrhous explants strongly suggest the presence of an estrogen-dependent collagenolytic enzyme system in the collagen-rich breast cancers. This system could represent an important component of the hormone dependency of human breast cancer growth.
Cancer Res 1975 Aug
PMID:Estradiol-dependent collagenolytic enzyme activity in long-term organ culture of human breast cancer. 16 44

Thirty epithelial cell strains were isolated from human carcinomas and normal epithelial tissues by collagenase digestion and selective removal of fibroblasts with trypsin-Versene. Most strains were obtained from metastatic carcinomas or epithelia of the urinary and intestinal tracts. The success rate for growth of both neoplastic and normal tissues (excluding skin) was 38%. Six of these strains showed gross morphologic and chromosome changes typical of malignant cells. Nine resembled normal epithelium. The other 15 exhibited some degree of morphologic change from normal.
J Natl Cancer Inst 1976 Apr
PMID:Epithelial cell cultures from normal and cancerous human tissues. 17 12

A new technique for infection of mature lymphocytes with murine leukemia virus (Friend) MuLV-F) is described. Spleen cells for normal, non-infected donors were placed into diffusion chambers (constructed with 0.22 mum por size Millipore filters) which were then implanted into the peritoneal cavities of normal syngeneic recipient mice. The cells were infected with an injection of MuLV-F into the peritoneal cavity and, in some instances, also by placing virus into the chambers. Cells were recovered by treating the chamber content with elastase and collagenase. The infection was determined in two ways: (1) cells with replicating MuLV were enumerated as infection centers (IC) on S+L- indicator cells; and (2) virus-related cell membrane antigen (MA) was detected by immunofluorescence. Cells recovered from chambers after 2-3 weeks of culture represented about 10% of the original inoculum; viability was approximately 90%. The number of IC in MuLV-F-infected chambers was about 10 times higher than obtained by infection and cultivation of spleen cells in vitro. The kinetics of IC and MA in chamber-cultured. MuLV-F-infected spleen cells was similar to that in the spleen of infected mice during the first 10 days after infection. Later on, the process of infection within the chambers slowed down, reaching about 50% MA-positive and about 10% IC-positive cells, whereas the number of both IC- and MA-positive cells in the spleen reached 80% or more. The infection of splenic lymphocytes in diffusion chambers occurred equally well when chambers were implanted into: (1) syngeneic, virus susceptible hosts; (2) syngeneic, lethally irradiated hosts; and (3) allogeneic, virus-resistant hosts, suggesting that the process within the chamber is independent of MuLV replication in the tissues of the chamber-bearing mouse. The diffusion chamber technique seems to provide an environment in which various types of isolated lymphocytes of different mouse strains can interact with MuLV almost as efficiently as in vivo.
Int J Cancer 1976 Aug 15
PMID:Interactions of murine leukemia virus (MuLV) with isolated lymphocytes. I. Virus replication in lymphocytes infected with Friend virus and cultures in diffusion chambers in vivo. 18 44

Mechanical and enzymatic methods of disaggregating tumors were studied with the goals of (1) minimizing cell losses while (2) maintaining functional and surface membrane markers needed to objectively identify inflammatory cells (IC)1 in resultant suspensions. Application of the principles and methods described makes accurate estimation of the percentage of each IC type present in neoplasms possible for the first time. Compared to purely mechanical means of disaggregating tumors, all enzyme mixtures tested markedly increased yields of viable cells/g neoplasm. Best results were obtained with a combination of collagenase and a protease of broader substrate range (alpha chymotrypsin, papain, pronase or trypsin). The combination of enzymes that gave the highest yields with the least effect on inflammatory cell markers was trypsin, collagenase and DNAse (TCD). Because mechanical injury appeared to be the greatest single cause of cell loss (the enzymes themselves had little direct effect), potential sources were identified and either eliminated or minimized. With TCD, depending on the tumor system, cell recovery (measured as DNA recovered in cell suspensions) was as high as 50% and yields were as much as 6.9 X 10(8) viable cells/g tumor. Complete disaggregation was not required to obtain representative IC populations from tumor fragments. Neutrophils, eosinophils and mast cells from disaggregated neoplasms were counted in Giemsa stained cytocentrifuge preparations based on their unique morphologic appearances. Macrophages were identified by their capacity to phagocytose zymosan, a function which proved highly resistant to the effect of enzymes. Flourescent microscopic identification of brain associated thymus antigen (BATA) allowed quantification of T lymphocytes, since this marker was virtually unchanged by enzyme exposure. Surface immunoglobulin (Ig) was stripped from B lymphocytes most rapidly by pronase and chymotrypsin, slowly by trypsin and papain, and not at all by collagenase. Ig positive cells therefore could be quantified in suspensions generated by collagenase or very short (20 min) exposure of fragments to trypsin.
Int J Cancer 1976 Sep 15
PMID:Inflammatory cells in solid murine neoplasms. I. Tumor disaggregation and identification of constituent inflammatory cells. 18 47


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