Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific cell-mediated immunity to SV40 tumor-specific transplantation antigen (TSTA) in BALB/c mice undergoing progressive tumorigenesis by syngeneic SV40-transformed cells (VLM) was investigated in vivo using a tumor-cell neutralization test. Specific cellular reactivity to SV40 TSTA was not detected in BALB/c mice bearing large tumors (10-15 mm mean diameter) but was demonstrable after tumor excision. Specific cytotoxic reactivity against syngeneic SV40-transformed cells in vivo could be restored to lymphoid cells from VLM tumor-bearing mice either by culturing the lymphoid cells in vitro or by treating them with papain or trypsin. Enzyme-treated lymphoid cells from MCA tumor-bearing BALB/c mice had no cytotoxic reactivity against VLM cells. These studies suggest that tumor-bearing hosts possess lymphocytes which are sensitized to the TSTA of the tumor but that the reactivity of these lymphocytes is blocked.
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PMID:Restoration of specific immunity against SV40 tumor-specific transplantation antigen to lymphoid cells from tumor-bearing mice. 5 Oct 12

Histophysiology, ultrastructure, chemical analyses of transplants and implants of Dunn and Ridgway mouse osteosarcomas demonstrate that tumorigenesis is a manifestation of deranged morphogenesis in developing mesenchymal cell populations. The end product of development is defective, incompletely calcified, disorganized bone without any inclusions of bone marrow tissue. When Dunn osteosarcoma is freeze-dried and then implanted, the tumor is resorbed and replaced by deposits of normal cartilage, bone, and bone marrow. Freeze-dried Ridgway osteosarcoma is replaced only by a fibrous connective tissue scar. Disaggregated Dunn tumor osteoblasts synthesize a trypsin-labile collagenase-resistant cell surface localized bone morphogen. Tumor matrix stroma, prepared by sequential chemical extraction of soluble non-collagenous proteins also contains significant quantities of the same bone morphogen. Tumor tissue pulverized to particle size as small as 44 micrometer3 transmitted bone morphogen more rapidly than intact tumor tissue. The total tumor cell and stroma mediated bone morphogen produces three times more normal bone than normal cortical bone matrix. Our working hypothesis is that a normal bone morphogenetic polypeptide (BMP) is synthesized by Dunn osteosarcoma cells and retained by the tumor matrix stroma. Neither the mechanism of transmission nor the mesenchymal cell receptor sites of BMP are known.
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PMID:An osteosarcoma cell and matrix retained morphogen for normal bone formation. 27 29

In order to study the effect of synthetic trypsin inhibitor on the oncogenesis of pancreatic cancer, the histology, the kinetics of the B, A and D cells in the islets of Langerhans and activities of free radical scavengers, superoxide dismutase (SOD), glutathion peroxide (GSH-Px) and malon dialdehyde (MDA) in the tumor bearing tissues were measured in hamsters with pancreatic cancer induced by di-iso-propanol nitrosamine (DIPN) with or without camostat (FOY-305). In DIPN group (DIPN alone), the tubular adenocarcinoma was found in 80%, however, in FOY group (DIPN+FOY-305), papillary adenocarcinoma was found in 91%. In both DIPN and FOY groups, the number of B cells was decreased at 8 weeks and the number of A and D cells was decreased at 16 weeks. Activities of SOD in the tumor and borderzone in DIPN group were significantly lower than those in non-tumor region and normal tissue. However, activities of SOD in the tumor and borderzone in FOY group were higher than those in DIPN group. GSH-Px and MDH levels were significantly higher in FOY group suggesting the involvement in the reaction of free radicals. These results suggest that trypsin inhibitors have a prophylactic effect on the development of pancreatic cancer.
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PMID:[Effect of synthetic protease inhibitor on the oncogenesis of pancreatic cancer in hamsters: study on pancreatic endocrine cells and free radicals]. 182 14

The Bowman-Birk protease inhibitor (BBI) is a legume-derived inhibitor of chymotrypsin and trypsin that has been shown to suppress cellular transformation and tumorigenesis. In the present investigation the effects of various BBI administration schedules were evaluated for suppression of 3-methylcholanthrene (3-MCA)-induced transformation of C3H/10T1/2 cells. At a concentration of 30 micrograms/ml, BBI demonstrated no toxicity to C3H/10T1/2 cells treated with 3-MCA. However, transformation of C3H/10T1/2 cells was significantly reduced when BBI was added to the cultures for a period of 14 or 42 days, starting immediately after exposure to the carcinogen. When BBI was administered only during the time of carcinogen exposure or alternatively beginning on day 15 and then continuously throughout the remainder of the 6-week transformation assay, it was ineffective for suppressing 3-MCA-induced cellular transformation. These findings indicate that BBI exerts its chemopreventive effect during the early stage of chemical carcinogen-induced cellular transformation.
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PMID:Suppression of 3-methylcholanthrene-induced cellular transformation by timed administration of the Bowman-Birk protease inhibitor. 202 60

LNCaP cells represent a useful tool to explore the mechanism of sex hormone action on cell proliferation in an "in culture-in animal" model. Results indicated that: (a) these cells were inhibited from proliferating for extended periods (up to 30 days) when placed in charcoal-dextran-stripped sera; they remained, however, viable because they proliferated when sex hormones were added to this medium; (b) the inhibitory effect of sera was reversed by the addition of 5 alpha-dihydrotestosterone at 3 x 10(-10) M, 17 beta-estradiol at 3 x 10(-8) M and higher concentrations, and progesterone at 3 x 10(-10) M and higher concentrations; (c) while the dose response to androgens was biphasic (i.e., 5 alpha-dihydrotestosterone at concentrations higher than 3 x 10(-10) M resulted in progressively lower cell yields), estrogens and progestagens exhibited a monophasic pattern; (d) these cells were exceedingly sensitive to the nutritional environment in which they grew; (e) while these cells have androgen receptors (68 fmol/mg protein; Kd = 2 x 10(-9) M), estrogen and progestagen receptors could not be detected by biochemical and immunocytochemical techniques; (f) tumors grew at the site of inoculation in castrated nude mice carrying 17 beta-estradiol and progesterone pellets and in intact male nude mice implanted with placebo pellets, while tumors did not grow in castrated nude mice implanted with a 5 alpha-dihydrotestosterone pellet. Taken together the data collected are compatible with the following conclusions: (a) the proliferative response in LNCaP cells seems not to be directly mediated by their intracellular androgen receptors; (b) plasma-borne trypsin-sensitive inhibitors of the proliferation of these cells (androcolyone I) appear to play a significant role in the proliferative event; (c) natural and synthetic androgens, estrogens, and progestagens cancelled the inhibition by charcoal-dextran-stripped human sera; (d) only androgens were able to trigger an inhibition of cell proliferation (shutoff effect) at concentrations higher than those that affected maximal cell yields (direct negative hypothesis); and (e) a faulty shutoff response is probably a crucial event for the tumorigenesis of these human prostate cells.
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PMID:Negative controls of cell proliferation: human prostate cancer cells and androgens. 273 Nov 69

The chvB operon of Agrobacterium tumefaciens is required for bacterial attachment to plant cells and for efficient crown gall tumor formation. As defined by the virulence phenotypes of mutants with transposon insertions mapping in the region, the operon was previously mapped to a 5-kilobase (kb) stretch of chromosomal DNA. We report here that the operon is actually about 8.5 kb long and that it contains a 7-kb gene coding for a large membrane protein involved in the synthesis of cyclic beta-1,2-glucan. Mutants with transposon insertions within the 5-kb phenotypically defined operon do not synthesize this functional protein, do not synthesize beta-1,2-glucan, and do not form tumors. However, mutants with insertions that map up to 3.5 kb downstream of the phenotypically defined operon synthesize truncated proteins that are active in beta-1,2-glucan synthesis. These mutants form tumors. The truncated proteins correspond closely in size with the map positions of the insertions, suggesting that the insertions truncate the proteins by translational termination. A plasmid that contains only the phenotypically defined chvB operon also codes for a truncated protein. A fusion product between the protein and beta-galactosidase carried on a Tn3-HoHo1 insertion was observed in one mutant. Partial trypsin digestion of wild-type inner membranes generated truncated proteins that were active in beta-1,2-glucan synthesis, demonstrating that a large portion of the protein is not required for beta-1,2-glucan synthesis. The correlation between beta-1,2-glucan synthesis by the truncated proteins and tumorigenesis strongly implicates the polysaccharide product of this protein in tumor formation.
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PMID:Identification of the product of an Agrobacterium tumefaciens chromosomal virulence gene. 285 22

We have purified and determined the complete primary structure of human stromelysin, a secreted metalloprotease with a wide range of substrate specificities. Human stromelysin is synthesized in a preproenzyme form with a calculated size of 53,977 Da and a 17-amino acid long signal peptide. Prostromelysin is secreted in two forms, with apparent molecular masses on NaDodSO4/PAGE of 60 and 57 kDa. The minor 60-kDa polypeptide is a glycosylated form of the major 57-kDa protein containing N-linked complex oligosaccharides. Zymogen activation by trypsin results in the removal of 84 amino acids from the amino terminus of the enzyme generating a 45-kDa active enzyme species. Human stromelysin is capable of degrading proteoglycan, fibronectin, laminin, and type IV collagen but not interstitial type I collagen. The enzyme is not capable of activating purified human fibroblast procollagenase. Analysis of its primary structure shows that stromelysin is in all likelihood the human analog of rat transin, which is an oncogene transformation-induced protease. The pattern of enzyme expression in normal and tumorigenic cells revealed that human skin fibroblasts in vitro secrete stromelysin constitutively (1-2 micrograms per 10(6) cells per 24 hr). Human fetal lung fibroblasts transformed with simian virus 40, human bronchial epithelial cells transformed with the ras oncogene, fibrosarcoma cells (HT-1080), and a melanoma cell strain (A 2058), do not express this protease nor can the enzyme be induced in these cells by treatment with phorbol 12-myristate 13-acetate. Our data indicate that the expression and the possible involvement of secreted metalloproteases in tumorigenesis result from a specific interaction between the transforming factor and the target cell, which may vary in different species.
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PMID:Human skin fibroblast stromelysin: structure, glycosylation, substrate specificity, and differential expression in normal and tumorigenic cells. 347 4

Glycopeptides from the surface of clones of hamster embryo cells were examined at various intervals after infection with polyoma virus. Two types of transformed cells were examined: (i) clones that showed delayed transformation or an initially low tumorigenicity, and (ii) clones that were rapidly transformed showing an initially high tumorigenicity. The glycopeptides were removed from the cell surface by trypsin and, after Pronase digestion, were examined by filtration through Sephadex G-50. With delayed transformation, a specific group of glycopeptides was increasingly evident over an 85-day period as the cells showed phenotypic properties of transformation and the ability to form tumors. In the other series, all but one clone of hamster embryo cells showed rapid transformation after infection with polyoma virus. This clone was less tumorigenic and showed little of the specific glycopeptides. In all cases of delayed or rapid transformation examined, the specific group of glycopeptides increased proportionately to the ability of the cells to form tumors. All of the cells derived from progressively growing tumors formed by injection of these transformed hamster cells into adult animals showed an abundance of this group of glycopeptides. These results suggest that specific surface membrane glycopeptides accompany viral transformation and tumorigenesis.
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PMID:Surface membrane glycopeptides which coincide with virus transformation and tumorigenesis. 436 56

A primary subcutaneous tumour of low spontaneous metastatic capacity, produced after inoculation of Herpes-virus hominis type-2-transformed hamster fibroblasts (parent line) and two in vivo derived highly metastatic lung deposits (Met A and Met B) were karyotyped and compared after trypsin G-banding. The parent line was cytogenetically heterogeneous with a modal chromosome number of 74. However, a number of cells were of a higher ploidy level. A large variation in both numerical and structural abnormalities was observed, the chromosome rearrangements were often complex and unstable, but all the cells contained a theme of common marker chromosomes. Met A and Met B were near diploid (mean chromosome numbers 42 and 44 respectively) with a low level of tetraploid cells. They shared many chromosome rearrangements but could be readily distinguished by an additional translocation unique to Met A. Cytogenetic homogeneity within and between metastases suggested that they were of monoclonal origin and had been derived from a karyotypically similar subpopulation within the parent tumour. We were unable to detect such cells in the parent line; thus, their numbers within the parent tumour were likely to be low. Metastasis, therefore, has been highly selective, depending on the particular phenotypic properties of Met A and Met B. All cells of the parent and metastatic lines have homogeneously staining regions (HSR) and abnormalities of chromosomes 15 (C15) which may be important in tumorigenesis. In addition, Met A and Met B cells have a number of chromosome rearrangements [translocations, deletions and a double minute chromosome (DM)] not present in the parent cells. They are retained at a high frequency in the cells of Met A and Met B and thus it seems likely that the metastatic phenotype is associated with one or more of these chromosome aberrations.
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PMID:Non-random chromosome changes in a herpes-virus-transformed Syrian hamster cell line and its metastatic derivatives. 609 77

In an effort to isolate genes with down-regulated expression at the mRNA level during oncogenic transformation of human mammary epithelial cells (MECs), we performed subtractive hybridization between normal MEC strain 76N and its radiation-transformed tumorigenic derivative 76R-30. Here, we report the isolation of cDNA clones corresponding to a 1.4-kb mRNA species that is abundantly expressed in 76N cells but is drastically reduced in 76R-30 cells. Based on its selective expression in MECs compared with fibroblasts, the corresponding gene is designated NES1 (normal epithelial cell-specific 1). Sequence analysis of the full-length NES1 cDNA clones revealed it to be a novel gene with a predicted polypeptide of 30.14 kilodaltons; in vitro transcription and translation confirmed this prediction. Database searches revealed a 50-63% similarity and 34-42% identity with several families of serine proteases, in particular the trypsin-like proteases, members of the glandular kallikrein family (including prostate-specific antigen, nerve growth factor gamma, and epidermal growth factor-binding protein) and the activators for the kringle family proteins (including the human tissue plasminogen activator and human hepatocyte growth factor activator). Importantly, all of the residues known to be crucial for substrate binding, specificity, and catalysis by the serine proteases are conserved in the predicted NES1 protein, suggesting that it may be a protease. An antipeptide antibody directed against a unique region of the NES1 protein (amino acids 120-137) detected a specific 30-kilodalton polypeptide almost exclusively in the supernatant of the mRNA-positive MECs, suggesting that NES1 is a secreted protein. The 1.4-kb NES1 mRNA was expressed in several organs (thymus, prostate, testis, ovary, small intestine, colon, heart, lung, and pancreas) with highest levels in the ovary; a 1.1-kb transcript was found in the pancreas. Although expression of the NES1 mRNA was observed in all normal and immortalized nontumorigenic MECs, the majority of human breast cancer cell lines showed a drastic reduction or a complete lack of its expression. The structural similarity of NES1 to polypeptides known to regulate growth factor activity and a negative correlation of NES1 expression with breast oncogenesis suggest a direct or indirect role for this novel protease-like gene product in the suppression of tumorigenesis.
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PMID:Identification of a novel serine protease-like gene, the expression of which is down-regulated during breast cancer progression. 876 36


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