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)

The antigenic surface pattern of a continuous cell line (HT29) derived from a human primary carcinoma of the colon was studied by the immunofluorescence technique. Monovalent and polyvalent immune sera were used. The cells of this long-term culture kept the ability to synthesize the three principal colon tumor antigens: carcinoembryonic and nonspecific cross-reacting antigens, and the membrane-associated tissular autoantigen. On the HT29 cells, which still carry the original blood group of the tumor donor, no receptors for human Ig's were detected.
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PMID:Immunohistology of the antigenic pattern of a continuous cell line from a human colon tumor. 115 34

We recently reported the presence of an organ-specific 40 kD colonic protein which acts as an autoantigen(s) in patients with ulcerative colitis. Using a specific monoclonal antibody directed against 40 kD protein (7E12H12, IgM isotype), in conjunction with immunocytochemistry and flow cytometry, we examined the presence of the 40 kD protein on human colon cancer cells, DLD-1, and also characterized the ability of cytokines, IFN-gamma and tumour necrosis factor, to modulate the expression of this protein on these tumour cells. The presence of the 40 kD protein was localized to the plasma membrane; less was present within the cytoplasm. Following exposure to IFN-gamma (10-1000 U/ml), DLD-1 colon tumour cells showed a dose- and time-dependent increase in 7E12H12 antibody associated immunofluorescence, with the maximum 7E12H12 antibody binding observed with 100 U/ml IFN-gamma at 48 h. In contrast, tumour necrosis factor did not alter the levels of anti-40 kD antibody binding over that of control cells. Since IFN-gamma is also known to induce class II major histocompatibility antigens, we examined the possibility of cross-reactivity of HLA class II antigens and Mr 40 kD epitope. Neither pre-incubation of DLD-1 colon tumour cells with anti-HLA class II antibodies followed by 7E12H12 nor co-incubation of both antibodies altered the amount of 7E12H12 antibody binding. Using a direct ELISA, a highly enriched preparation of Mr 40 kD protein reactive to anti-40 kD antibody did not react with HLA class II antibodies. The present results suggest that 40 kD protein is present on DLD-1 human colon tumour cells and that although the 40 kD protein epitope expression is increased by the lymphocyte-derived cytokine, IFN-gamma, the epitope is separate and distinct from the class II HLA antigens. Further studies on the 40 KD protein may elucidate its autoantigenic role in the pathogenesis of inflammatory bowel disease.
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PMID:Expression of the 40 kD protein in DLD-1 colon cancer cells and the effect of cytokines. 137 49

An antigen, protein X (Px), was purified from immune complexes isolated from malignant pleural effusions from patients with adenocarcinoma of the lung by EDTA treatment, PEG 8000 precipitation, protein A affinity chromatography, and Sephadex G-200 separation in the presence of 3 M NaCl. The purified antigen had a M(r) 17,000 by SDS-PAGE, and consisted of isoelectric species of pI 6.3 and 6.6. Purified Px recombined with Ig isolated from pleural fluids from patients with lung adenocarcinoma, but not with Ig from patients with breast carcinoma. Using an autologous human and heterologous chicken antibody, Px was found, by immunohistology, in the cytoplasm of some of the well-differentiated lung adenocarcinoma cells, but was not seen in normal lung or a variety of other malignant tissues. A liquid-phase competitive-inhibition RIA was developed. Over 30 ng/ml of Px were found in 9 of 15 pleural fluids from patients with lung carcinoma, none of 20 from patients with breast, ovary, stomach or colon cancer, and in 3 of 15 patients with unknown primary tumor. Our data suggest that Px may be a lung-cancer-associated autoantigen which can elicit a host humoral response in vivo.
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PMID:Characterization of a lung-cancer-associated auto-antigen. 139 30

Saguinus oedipus, Callithrix jacchus, and Saguinus fuscicollis are three species of New World monkeys which develop a form of colitis that is similar to human ulcerative colitis. Only S oedipus, however, develop colon cancer. We examined intestinal tissues from these animals for the presence of an antigen cross reacting to the Mr 40,000 human colonic epithelial protein that acts as an autoantigen in ulcerative colitis. Using an anti-Mr 40,000 monoclonal antibody (7E12H12, IgM isotype), by an immunoperoxidase assay we showed that all colon specimens from S oedipus reacted with 7E12H12; however, the colonic tissue from C jacchus and S fuscicollis did not. In immunotransblot analysis eluted IgG antibody bound to human ulcerative colitis colon (CCA-IgG) reacted with Mr 40,000 protein(s) present in the extracts of colon from S oedipus animals and humans. Small intestinal tissue reacted neither with 7E12H12 nor with CCA-IgG. In S oedipus, the Mr 40,000 protein was localised exclusively to colonic epithelial cells. Preincubation of seven S oedipus colon specimens with eight of 10 sera from animals with acute or chronic colitis and 0 of four sera from animals without colitis almost completely inhibited the binding of 7E12H12 to the colonic epithelium. Four of these 10 sera inhibited the binding of 7E12H12 to the autologous colon. These results show the presence of circulating autoantibodies in S oedipus with colitis against an epitope(s) on Mr 40,000 protein shared by human and S oedipus colon.
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PMID:Mr 40,000 human colonic epithelial protein expression in colonic mucosa and presence of circulating anti-Mr 40,000 antibodies in cotton top tamarins with spontaneous colitis. 174 Feb 77

Inflammatory bowel disease, in particular ulcerative colitis, is characterized by localization of leukocytes in close proximity to the colonic epithelium, which may be mediated by the expression of intercellular adhesion molecules (ICAM-1; CD 54). We previously reported the presence of an organ-specific M(r) 40K colonic protein that acts as an autoantigen in ulcerative colitis and is present on the surface of colonic epithelial cells and also in DLD-1 colon cancer cells. Using the colon tumor cell line DLD-1 and flow cytometry, ICAM-1 antibody binding by untreated cultured DLD-1 cells was similar to background antibody binding (mean channel number, MCN = 9.77 +/- 2.13). Interferon-gamma (100 U) induced a 1-2 log increase in anti-ICAM-1 antibody binding from as early as 12 hr after exposure up to 72 hr and a moderate increase (up to about 100%) in the binding of anti-M(r) 40K antibody. Additional studies showed that anti-ICAM-1 and anti-M(r) 40K antibodies bound to DLD-1 cells regardless of the presence of the other antibody. Taken together, the present observations suggest that the epitopes of ICAM-1 and M(r) 40K molecules are coexpressed by colonic epithelial cells, regardless of the presence of the other molecule. Furthermore, lymphocytes in the colonic mucosa that are activated to produce interferon-gamma may upregulate the expression of both of these molecules.
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PMID:Amplified expression of intercellular adhesion molecule-1 (ICAM-1) and M(r) 40K protein by DLD-1 colon tumor cells by interferon-gamma. 809 38

Ulcerative colitis (UC) is associated with autoantibody response to a cytoskeletal protein, human tropomyosin (hTM) isoform-5 (hTM5). Because hTM5 is an intracellular protein, it may remain inaccessible to the autoantibodies. Therefore, we have investigated the possibility of externalization of hTM5 in colon epithelial cells. Freshly isolated colonic and small intestinal epithelial cells and LS-180 colon cancer cell line were examined for surface expression of hTM5 by flow cytometric analysis using hTM isoform-specific MoAbs. The extracellular release of hTM5 was determined by Western blot and radioimmunoprecipitation analyses. Physical association of hTM5 with a membrane-associated colon epithelial protein (CEP) was examined by co-immunoprecipitation of hTM5 with anti-CEP MoAb, and CEP with anti-hTM5 MoAb. Cell surface expression of hTM5 was observed in colonic epithelial and LS-180 cells but not in small intestinal epithelial cells. LS-180 cells spontaneously released hTM5 as well as CEP into the culture medium that was significantly stimulated by a calcium ionophore, A23187, but inhibited by phorbol-12-myristate-13-acetate, monensin and methylamine. Co-immunoprecipitation experiments revealed that hTM5 forms a complex with CEP. We conclude that hTM5 is externalized in colon but not in small intestinal epithelial cells. The physical association of hTM5 with CEP suggests a possible chaperone function of CEP in the transport of hTM5, a putative target autoantigen in UC.
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PMID:Externalization of tropomyosin isoform 5 in colon epithelial cells. 1054 Jan 82

AIE-75 is a protein identified as an autoantigen in patients with autoimmune enteropathy and as a colon cancer-related antigen. It has recently been assigned to be a causative gene for Usher type 1C congenital syndromic hearing loss. The novel protein has three PSD-95/Dlg/ZO-1 (PDZ) protein-protein interaction domains and is therefore implicated to function as a molecular anchor or sorter. We have identified a novel protein that binds to AIE-75 by yeast two-hybrid screening. The protein has a high homology to the tumor suppressor MCC (mutated in colon cancer; or MCC1 hereafter) and was named MCC2. MCC2 protein binds the first PDZ domain of AIE-75 with its C-terminal amino acids -DTFL. Since the MCC1 does not bind to AIE-75 and the MCC2 displays different expression patterns in various organs compared to MCC1, they appear to play distinct roles in cells. The MCC2 gene is located on chromosome 19p13 in the vicinity of APCL gene, while MCC1 maps near to APC tumor suppressor gene. Because of negative expression of MCC2 in a panel of cancer cell-lines compared to the corresponding normal tissues, we suggest that further study is necessary to investigate a possible role of MCC2 as a tumor suppressor.
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PMID:Interaction of MCC2, a novel homologue of MCC tumor suppressor, with PDZ-domain Protein AIE-75. 1131 60

We have cloned and characterized the cDNA, expression pattern, and subcellular localization of the human and murine orthologs of the centrosomal colon cancer autoantigen protein (CCCAP). We identified both the transcriptional start site of murine CCCAP (mCCCAP) and its TATA-less promoter within BAC genomic clones of the mCCCAP 5' region. The mCCCAP transcript is ubiquitously present in mouse tissues, but at very low copy number. The 2151 bp open reading frame of mCCCAP encodes an 83 kDa protein that possesses a large C-terminal coiled-coil domain, which is able to homo-oligomerize in the yeast 2-hybrid system. Endogenous mCCCAP localizes to the centrosomes of murine BALB/c 3T3 fibroblasts during both interphase and mitosis. This centrosomal localization was not disrupted by nocodazole-induced depolymerization of the microtubule cytoskeleton, suggesting that mCCCAP is an integral component of the centrosome rather than simply a microtubule-associated protein. We also cloned human CCCAP (hCCCAP). The 2139 bp open reading frame of hCCCAP encodes an 82.5 kDa protein that is 71% identical to mCCCAP at the amino acid level and has the same predicted secondary structure. Ectopically expressed full-length hCCCAP in human U2-osteosarcoma cells also displayed centrosomal localization during interphase and mitosis. This pattern of localization was abolished by truncations of the N- and C-terminus of the protein. We further discovered that the C-terminal portion of hCCCAP is identical to the human colon cancer autoantigen NY-CO-8 (Human Gene Nomenclature symbol SDCCAG8).
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PMID:Identification and characterization of the novel centrosome-associated protein CCCAP. 1255 64

We have identified CRASH, a human asparaginase-like protein which is composed of 308 amino acids and exhibits 32% homology to human aspartylglucosaminadase at the amino acid level. Database analysis revealed that the gene corresponding to CRASH is composed of 7 exons and 6 introns. Steady-state level of CRASH mRNA was found to be increased in 5 cell lines derived from metastatic lesions compared with 2 cell lines derived from primary mammary carcinoma and HMEC (human mammary epithelial cells). We found that the mRNA level of CRASH correlates with the metastatic propensity of several isogenic human colon cancer and pancreatic carcinoma cell lines. CRASH corresponds to a recently identified sperm autoantigen and furthermore we have demonstrated inducibility of CRASH mRNA by androgen and progesterone. Investigation of several types of human cancers and their corresponding normal tissues revealed high levels of CRASH mRNA in uterine, mammary and ovarian tumors compared with the corresponding normal tissues. CRASH mRNA expression was analysed in breast cancer samples with disclosed clinico-pathological features and corresponding normal tissues. The levels of CRASH mRNA were significantly up-regulated in tumors compared with normal breast tissues and correlate with lack of estrogen receptor expression of the tumors.
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PMID:Identification of CRASH, a gene deregulated in gynecological tumors. 1465 38

The carcinoembryonic antigen (CEA) is an attractive target for immunotherapeutic purposes because of its expression profile, its role in tumor progression, and its immunogenicity. However, CEA belongs to the CD66 immunoglobulin super-gene family that comprises highly homologous molecules expressed on leukocytes, making CEA a potential autoantigen expressed on hematopoietic cells. We used a MHC class II epitope prediction algorithm (TEPITOPE) to select 11 sequence segments of CEA that could form promiscuous CD4(+) T-cell epitopes and used synthetic peptides corresponding to the predicted sequences to propagate in vitro CD4(+) T cells from healthy donors and colon cancer patients. CD4(+) T cells from all subjects strongly recognized the sequence segment (LWWVNNQSLPVSP), repeated at residues 177-189 and 355-367. Importantly, we demonstrated that this highly immunodominant region contains a naturally processed epitope(s). Cross-recognition experiments with peptide analogues present on the CD66 homologous proteins showed that CEA(177-189/355-367)-specific CD4(+) T cells did not recognize the analogues, demonstrating that recognition of the immunodominant epitope is CEA specific. These data suggest that the repertoire of CEA(177-189/355-367)-specific CD4(+) T cells might have been shaped by a selective process to exclude CD4(+) T cells specific for CD66 homologues expressed on leukocyte, while preserving the CEA-specific repertoire. The features of strong immunogenicity and immunodominance in the absence of potential induction of autoimmunity make the identified CEA epitope of particular interest for the development of antitumor vaccines.
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PMID:CD4(+) T cells from healthy subjects and colon cancer patients recognize a carcinoembryonic antigen-specific immunodominant epitope. 1467 13


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