Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparan sulphate proteoglycans are rapidly released from VACO 10MS colon cancer cells that are triggered with phorbol esters to undergo terminal differentiation. This lag-free temperature-sensitive process is correlated with a conversion of the lipophilic proteoglycans of the cell surface into non-lipophilic proteoglycans that accumulate in the culture medium. The released proteoglycans are very similar to their lipophilic precursors in size, buoyant density and glycosaminoglycan characteristics; however, they exhibit slightly smaller core proteins after chemical and enzymic deglycosylation. The lipophilicity of the larger-sized core proteins of the cell-associated proteoglycans is also correlated with the presence of an easily iodinatable domain; this domain is missing in the released proteoglycans. Exogenous proteases (i.e. chymotrypsin, V8, trypsin and proteinase K) readily cleave this segment from the larger protease-resistant region of the proteoglycan structure. It is also released intact by treatment of the isolated proteoglycans with methanolic HCl. This component appears to be peptide in character, in that proteases readily degrade it and release iodotyrosines when the precursor has been iodinated. No evidence for the presence of covalently attached fatty acids in the cell-associated proteoglycans was found. These results are consistent with the hypothesis that the altered proteoglycan metabolism that is associated with the phorbol-ester-induced terminal differentiation of certain human colon cancer cells ensues upon the activation of a membrane-localized protease that cleaves a lipophilic anchor segment from the cell surface proteoglycans.
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PMID:Release of cell surface proteoglycans from differentiating colon cells proceeds by cleavage of lipophilic anchor peptides. 141 65

Two colon cancer cell lines, HT-29 (human) and DHD/K12/TRb (rat), were grown as monolayer cultures to various confluence degrees. The cytotoxic efficacies of doxorubicin and 4'-deoxydoxorubicin, evaluated by a survival assay, and the nuclear drug concentrations, measured by microspectrofluorometry, were shown to progressively decrease with the augmentation of confluence. This confluence dependent resistance (CDR) to anthracyclines was demonstrated independent of the multidrug resistance drug efflux mechanism. The cellular uptake of three compounds (sodium [51Cr]chromate, D-[14C]alanine, L-[14C]glucose) known to passively diffuse across the cell membrane as anthracyclines do was also reduced in confluent cells. After trypsin cell detachment, the kinetics of reversion of the sodium [51Cr]chromate uptake decrease and that of CDR were similar. Therefore, CDR may be attributed to a reduction of anthracycline cell intake due to a general alteration of passive diffusion across the cell membrane. However, CDR is only partly explained by this phenomenon since a reduced sensitivity of confluent cells was observed compared with nonconfluent cells for a similar amount of drug in their nuclei. CDR could explain the high resistance to anthracyclines of some solid tumors, such as colon tumors, in which cancer cells are tightly aggregated.
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PMID:Mechanisms of resistance of confluent human and rat colon cancer cells to anthracyclines: alteration of drug passive diffusion. 220 25

A new enzyme which hydrolyzes anilide substrates of p-guanidino-L-phenylalanine in preference to those of arginine was found in the ascitic plasma from Ehrlich ascites tumor-bearing mice. The activity of this enzyme on N alpha-benzyloxycarbonyl-p-guanidino-L-phenylalanine p-nitroanilide was strongly inhibited by diisopropyl fluorophosphate and phenylmethanesulfonyl fluoride but not by sulfhydryl-reactive reagents and metal chelating agents. Peptide substrates containing p-guanidino-L-phenylalanine were hydrolyzed by this enzyme much faster than those containing arginine. These results suggest that this enzyme is a different type of serine protease from trypsin and thrombin. This enzyme was also found in the human gastric and colon cancer cells and their surrounding ascitic plasmas.
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PMID:A new serine protease which preferentially recognizes p-guanidino-L-phenylalanyl residue in ascitic plasma from Ehrlich ascites tumor-bearing mice. 389 Aug 49

A human colon cancer cell line, HCT-8, is shown to be an appropriate target cell for study of natural killer (NK) activity in man. In parallel experiments, effector cell characteristics for NK and antibody-dependent cellular cytotoxicity (ADCC) were found to be vested in a single lymphocyte subpopulation, which bore receptors for the Fc fragment of IgG, but lacked other surface receptors. The effector cell failed to adhere to glass and was inactivated by exposure to 3500 rad x-irradiation. Cells forming rosettes with SRBC and cells bearing receptors for complement were inactive in both systems. A wide distribution of NK activity was noted among individuals that correlated with the distribution of effector cell activity in ADCC (r = 0.8). Preincubation of NK effector cells with antibody-coated ADCC target cells markedly reduced NK activity. Neuraminidase treatment of effector cells led to increased NK and diminished ADCC, while trypsin treatment led to reduced NK activity and showed no effect on ADCC. Thus, NK and ADCC effector cells are highly overlapping if not identical populations, but different structures on the cell membrane may mediate the two activities.
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PMID:Natural killer activity of human lymphocytes against colon cancer cells. 735 60

Epithelial cell surfaces possess a trypsin-like protease, referred to as guanidinobenzoatase (GB). The cytoplasm of these cells contains an extractable protein (I) which recognises the cell surface GB by forming an enzyme-inhibitor complex (GB-I). Rhodamine-agmatine (Rh-Agm) was designed as a red fluorescent probe, directed to the active centre of GB, which can be used to locate cells with GB, employing fluorescence microscopy. Rh-Agm has a high affinity for GB and will displace I from GB-I on the surfaces of cells in frozen sections. Rh-Agm has been used to displace I from immobilised GB-I complexes on the surface of cultured colonic carcinoma cells in an affinity procedure aimed at purifying the inhibitors of GB obtained from cultured carcinoma cells. These inhibitors have been tested on protected frozen sections of normal colon and carcinoma of the colon, the formation of GB-I complexes being followed by a second yellow fluorescent probe which competes for the active centre of GB. The study of the protein-protein interactions to form GB-I has been facilitated by employing two synthetic fluorescent inhibitors of GB with differing affinities for GB and different fluorescent properties. The use of sections of tissue in this study has enabled a sequence of reactions to be carried out on the same cell surface GB, such that reversible inhibition reactions can be quickly demonstrated and recorded by fluorescence microscopy.
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PMID:Affinity preparation of a protein inhibitor recognising a cell surface protease. 751 Jul 96

Mucins, high-M(r) glycoproteins with a large amount of O-glycosidically linked carbohydrate, protect the colonic epithelial surface and are altered in ulcerative colitis and colon cancer. At least two mucin genes, MUC2 and MUC3, are expressed at high levels in the human intestine. As an experimental model for studying the biosynthesis of human intestinal mucins, we used HM3 colon cancer cells. When mature mucins labelled with [3H]glucosamine or [3H]threonine were analysed by gel filtration, it was found that secreted mucins (M(r) > 10(8) were larger than soluble cellular mucins (M(r) approx. 5 x 10(6)). Only secreted mucin was sensitive to reduction. Both MUC2 and MUC3 proteins, identified by labelling with [3H]threonine or [35S]cysteine and immunoprecipitation with antibodies to synthetic mucin peptides, were already of large size (M(r) > 180,000) by the earliest labelling time (5 min). The MUC3 precursor was completely degraded by trypsin, but the MUC2 precursor had a trypsin-resistant fragment of M(r) approx. 240,000 containing threonine and cysteine. The trypsin-resistant MUC2 fragment contained N-linked carbohydrate, as indicated by a decrease in size as a result of peptidyl N-glycosidase digestion or tunicamycin treatment of HM3 cells. These results show that HM3 colon cancer cells produce at least two distinct human intestinal mucins. They also indicate that the mechanisms of biosynthesis of intestinal mucins differ from those of other mucin-like glycoproteins that have been studied.
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PMID:Biosynthesis of two distinct types of mucin in HM3 human colon cancer cells. 811 Jan 87

A co-culture study of purified rat Kupffer cells and human colon cancer cells was performed, and the process of the tumor cell injury was observed under an inverted type fluorescence microscope loaded with propidium iodide, and also under an electron microscope. Ultrastructurally there was direct membrane-to-membrane interaction between Kupffer cells and colon cancer cells in time. The interaction occurred 1 h after start of the co-culture, and injured tumor cells were observed closely attached to pseudopodia of Kupffer cells at 6 h. The number of propidium iodide-positive tumor cells with damage increased in time. Pretreatment with NG-monomethyl-L-arginine reduced the number of injured tumor cells without preventing morphological interactions, but superoxide dismutase did not prevent the tumoricidal effect. Pretreatment with trypsin completely inhibited cell interaction and damage to tumor cells. In conclusion, the morphological interaction of Kupffer cells as a first step and the involvement of nitric oxide-derived free radicals as a second step seem to play a significant role in the host-defense mechanism.
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PMID:Evidence of direct interaction between Kupffer cells and colon cancer cells: an ultrastructural study of the co-culture. 817 28

Preparation with enzymes plays an important part in obtaining good results in cellular DNA content measurements from paraffin-embedded tissue using flow cytometry. Therefore, we have compared two groups of DNA histograms obtained with pepsin (Hedley method) and trypsin digestion (Schutte method). Samples of five tumor types were compared: eight lung, seven breast, five thyroid, seven stomach, and six colon cancer cases. All samples were stained with propidium iodide (PI). The incidence of DNA aneuploidy determined by the Schutte method indicated a higher ratio in four tumor types than that determined by the Hedley method. Concerning the coefficient of variation (CV) used to estimate the quality of the DNA histogram, the diploid G1 peak determined by the Schutte method produced a smaller CV in five tumor types than did the Hedley method. This Schutte method had especially good results in lung and thyroid cancer. Furthermore, the amount of debris (background) determined by the Schutte method indicated a decrease in four tumor types compared with the Hedley method. In cell-cycle analysis of ten DNA diploid cases, DNA histograms by the Hedley method showed an increased S-phase fraction due to an overlapping of debris and aggregated cells. These results indicate that preparation by trypsin digestion is a method superior to pepsin digestion when the sample from paraffin-embedded tissue is stained with PI for the purpose of DNA content measurement.
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PMID:Comparison of pepsin and trypsin digestion on paraffin-embedded tissue preparation for DNA flow cytometry. 835 27

Monoclonal antibody (mAb) A33, which recognizes a M(r) approximately 43,000 differentiation antigen (A33) expressed in normal human colonic and small bowel epithelium as well as in 95% of colon cancers, shows specific targeting of colon cancer in humans and is currently being evaluated for clinical use. Here, we describe strategies for the purification and structural analysis of the A33 antigen from the human colorectal carcinoma cell lines LIM1215 and SW1222. Edman degradation of the intact protein and nine peptides, derived by proteolytic digestion of the A33 antigen with Asp-N endoproteinase, thermolysin, trypsin and pepsin followed by micropreparative reversed-phase high-performance liquid chromatography, allowed the unambiguous sequence assignment of 153 amino acid residues; these data reveal one N-glycosylation sequeon in Asp-N endoproteinase peptide D4, and a disulfide linkage between peptides D1 and D4. This amino acid sequence information has facilitated the cloning and subsequent sequencing of a cDNA for the A33 antigen which demonstrates that it is a novel human cell surface molecule of the immunoglobulin superfamily.
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PMID:Micro-sequencing strategies for the human A33 antigen, a novel surface glycoprotein of human gastrointestinal epithelium. 954 30

Pancreatic trypsin has been found to induce tight junction or dome formation in some colon cancer cell lines (HT-29, Caco-2), and a tumor-associated trypsinogen, trypsinogen type II, has been isolated from another colon cancer cell line (COLO 205). We have tried to determine if trypsinogen is present and how its expression varies during cell culture in HT-29 Glc+/- and Caco-2 cells, which exhibit enterocytic differentiation, and in HT-29 Glc+ cells, which never differentiate. Trypsinogen mRNA presence and expression were demonstrated in these cells by mRNA hybridization, RT-PCR, cytoimmunofluorescence, Western immunoblot analysis, and gel filtration. Trypsinogen was found to be trypsinogen type I and was mainly in zymogen form in culture media. Differentiating cells exhibited variations in trypsinogen I expression, but cells that remained undifferentiated did not. In the differentiated cells, a high and transient peak in trypsinogen I expression was observed during the first steps of differentiation.
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PMID:Pancreatic trypsinogen I expression during cell growth and differentiation of two human colon carcinoma cells. 969 8


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