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)

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.
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PMID:Inflammatory cells in solid murine neoplasms. I. Tumor disaggregation and identification of constituent inflammatory cells. 18 47

Primary functional bovine adrenal cortical cell cultures have been developed to study the factors controlling adrenal cell growth. Cells were prepared by the collagenase technique and maintained in F-12 medium containing fetal calf serum and horse serum. Cells contained abundant lipid as demonstrated by staining with Oil Red O and showed strongly positive staining for delta5,3beta-hydroxysteroid dehydrogenase. ACTH inhibited DNA synthesis and stimulated steriodogenesis in these cells. Fibroblast growth factor (FGF) was shown to be a potent stimulator of the growth of normal bovine adrenal cortical cells maintained in tissue culture. The minimal effective dose of FGF was 1 ng/ml with maximal effects being observed at 100 ng/ml. The effect of FGF was dependent on the serum concentration. Inclusion of FGF in F-12 medium containing serum permitted cloning of functional bovine adrenal cortical cells from cultures seeded at low density (4 cells/cm2). ACTH inhibited the mitogenic effects of FGF. In addition to its mitogenic action, FGF is a migratory factor for bovine adrenal cortical cells. Though ACTH inhibited the mitogenic effects of FGF, it did not block the migratory activity. Epidermal growth factor did not affect the growth of either normal bovine adrenal or functional mouse adrenal tumor cells (Y-1) in tissue culture. FGF is the first direct mitogen identified for adrenal cortical cells; ACTH opposes this mitogenic action and functions directly as a differentiate function signal.
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PMID:Control of bovine adrenal cortical cell proliferation by fibroblast growth factor. Lack of effect of epidermal growth factor. 18 90

Human osteosarcoma and mammary carcinoma cells were cultured separately in a medium supplemented with fetal calf serum, until they were confluent. The medium was then replaced by serum-free medium supplemented with heparin. Both cell cultures secreted collagenase, and this activity was inhibited by a cartilage-derived protein of low molecular weight. Since cartilage is rarely invaded by neoplasms, the presence of this inhibitor may play an important role in the regulation of tumor invasion.
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PMID:Tumor cell collagenase and its inhibition by a cartilage-derived protease inhibitor. 19 81

Gonadotropic hormones are required for the induction and maintenance of tumors arising in ovaries that have been transplanted to the spleens of gonadectomized mice. The characteristics of gonadotropin receptors for human chorionic gonadotropin (HCG)-luteinizing hormone on cells from these tumors of varying size, age, and morphology have been determined. The specific binding of 125I-labeled HCG to cells obtained by collagenase digestion, 15 to 65 weeks postimplantation from granulosa cell or luteinized cell, or mixed granulosa-luteal tumors was analyzed by Scatchard plot. Neither the size, weight, duration of implantation, nor histological morphology affected the receptor-binding affinity [equilibrium dissociation constant (Kd), 6 X 10(-10) M], and, presumably, the receptor is qualitatively similar. In contrast, the number of HCG receptors per cell increased 17-fold and was related to the degree of morphological luteinization of the tumor. HCG-sensitive adenyl cyclase was also demonstrated and compared to HCG binding in a highly luteinized tumor.
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PMID:Gonadotropin receptors in experimentally induced ovarian tumors in mice. 19 83

Serum-free media of minced tissue cultures of VX-2 rabbit carcinoma contained a specific collagenolytic activity capable of releasing soluble radioactive peptides from [14C]-labeled collagen fibrils. It was also capable of reducing the viscosity of acid-soluble collagen solutions by cleaving the tropocollagen (TC) molecules primarily at one site to TCA (75%) and TCB (25%) fragments. Three chromatographic fractions were separated by gel filtration: F1, (MW 85-110,000) present in larger amounts in early cultures of younger tumor tissue; F2, (MW-35-40,000) the major component with maximum production in the day 3 media of younger and advanced tumor tissues; F3, (MW 18-22,000) the minor component. Early cultures of younger tumor tissue contained a latent collagenase and were subject to trypsin activation suggesting the presence of inactive enzyme precursors or an enzyme-inhibitor complex.
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PMID:Changes in the collagenolytic activity released by primary VX-2 carcinoma cultures as a function of tumor growth. 19 82

Samples of 35 tumors from the head and neck region (25 squamous cell, 2 basal cell, 5 parotid, 3 melanoma, and 1 lymphosarcoma) were cultured after dispersement with either trypsin or collagenase treatment. Growth was established in 14 (40%). Cultured tumor cells were then used as target cells in in vitro assays of patients' cellular and humoral immunity to their own or similar tumors. Preliminary data suggest this may be a reliable method of monitoring responses in patients receiving immunotherapy for head and neck malignancies.
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PMID:Tissue-cultured head and neck tumors: their use in in vitro assays of immune response. 19 78

Human skin collagenase was quantitated by radioimmunoassay in 21 basal cell carcinomas. Immunoreactive collagenase protein was found to be approximately 2-fold greater in extracts of these tumors than in extracts of normal skin, suggesting that this enzyme may be important in the pathogenesis of soft tissue destruction in vivo. To further define the role of collagenase in such destruction, immunofluorescent staining with specific antiserum to human skin collagenase was used to localize collagenase in the basal cell carcinomas. The enzyme was found only in the stromal elements surrounding the tumor islands. No staining of the epithelial components of the basal cell carcinomas was found. These findings suggest that the normal connective tissue elements may have been stimulated to produce an increased amount of collagenase and emphasize the importance of epithelial-stromal interaction in soft tissue invasiveness.
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PMID:Quantitation and immunocytochemical localization of human skin collagenase in basal cell carcinoma. 19 78

Preneoplastic mammary nodule lines D1, D2, and C4 were enzymatically dissociated with collagenase, hyaluronidase, and pronase or with only collagenase and hyaluronidase to produce high yields of viable single cells; 10(5) cells were injected into the cleared mammary fat pads of syngeneic BALB/cCrgl mice. In 11 experiments involving three different preneoplastic nodule lines with different tumor potentials, all dissociated nodule cell lines showed a marked increase in tumorigenicity as compared to the same tissues transplanted as 1-mm3 pieces. The results could not be explained on the basis of differences between the amounts of cells transplanted in the two procedures. In a second series of experiments, normal mammary cells from virgin, pregnant, or lactating mice were mixed in different ratios with 10(5) nodule cells and injected into the mammary fat pads. The presence of normal cells reversed the marked increase in the tumorigenicity of enzymatically dissociated nodule cells to a level equal to or less than the tumorigenicity of control transplants (1-mm3 pieces). The growth of 10(5) mammary tumor cells was not inhibited when tumor cells were mixed with 3 x 10(5) normal cells and transplanted into the mammary fat pads. These results showed that enzymatic dissociation can lead to an increase in tumor potential of preneoplastic mammary nodule lines, and they supported the hypothesis that nodule cells, but not neoplastic cells, are sensitive to the growth-inhibitory effects of normal mammary cells.
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PMID:Enhancement of the tumorigenicity of preneoplastic mammary nodule lines by enzymatic dissociation. 20 61

Inapparent nodule-transformed cells were recovered from morphologically normal mammary tissue from virgin female BALB/cfC3H/Crgl (mouse mammary tumor-positive) mice before the appearance of hyperplastic alveolar nodules (HAN) or tumors, by means of the cell dissociation technique. Mammary tissues were dissociated by means of collagenase (0.1%), hyaluronidase (0.1%), and pronase (1.25%). Aliquots of 10(5) viable cells in 0.01 ml medium were injected into the gland-free mammary fat pads of 3-week-old female syngeneic mice. After 10 weeks the outgrowths were examined and classified as ductal, HAN, tumor, or combinations of these types. The presence of HAN outgrowths indicated the presence of nodule-transformed cells in the donor mammary tissues. Nodule-transformed cells were recovered from 2-month-old donors, and the number of HAN outgrowths increased with donor age. Overt HAN and tumors did not appear in virgin female BALB/cfC3H/Crgl mice younger than 8 to 9 months of age. The data suggest that inapparent nodule-transformed cells occurred long before the appearance of HAN of tumors and that the numbers of transformed cells increased with donor age.
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PMID:Detection of inapparent nodule-transformed cells in the mammary gland tissues of virgin female BALB/cfC3H mice. 20 23

By means of a biological assay for the enzyme collagenase the activity of this protease was examined in 12 invasive adenocarcinomas of the colon. In spite of considerable quantitative differences collagenolytic activity in the dimensions of 10(-3) units/mm theta tissue could be revealed in all cases. EDTA inhibited the reaction by 19%, normal human serum by 23% in the average, whereas 1,10-0-phenanthroline, D-penicillamine as well as the cytostatic 5-fluorouracil resulted in nearly total inhibition. It can be suggested that the activity of the colonic carcinoma is not derived from granulocytes, serum, or normal mucosa, but from the tumor itself. Contrasting to the limited inhibition by normal serum inhibitors, the enzyme is nearly fully inhibited by 5-fluorouracil.
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PMID:[5-fluorouracil inhibits the collagenolytic activity of invasive colonic adenocarcinomas in vitro]. 21 50


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