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 monoclonal antibody NCC-CO-450 (IgM kappa) was selected by screening of reactivity with high-molecular-weight antigens (Mr greater than 10(6] isolated from ascitic fluid of a colon cancer patient. This antibody detected heterogeneous but predominantly high-molecular-weight antigens in 4 of 6 ascitic fluid samples from gastrointestinal cancer patients by immunoblotting analysis. A sandwich radioimmunoassay was developed in order to examine the serum level of this antigen, and the cutoff value was defined as the mean plus 2 SD of values obtained with sera from normal donors. While 97% (93 of 96) of sera had a negative antigen value in normal donors, 56% (14 of 25) of patients with colorectal carcinoma and 40% (8 of 20) of patients with gastric carcinoma showed a positive antigen value. The distribution of the antigen in sera of patients with various cancers did not show any correlation with the distribution of carcinoembryonic antigen or CA 19-9. From immunohistochemical and biochemical analyses, NCC-CO-450 antigen was characterized as a mucin-like glycoprotein abundant in normal colonic epithelium as well as in carcinomas of the colon, stomach, and pancreas. The immunohistochemical reactivity of NCC-CO-450 was distinct from that of other monoclonal antibodies reported to be useful for serological diagnosis. The epitope recognized by NCC-CO-450 is considered to be an O-linked carbohydrate chain without terminal sialic acid but is different from the known carbohydrate chains, i.e., Lea, Lex, LeY, Tn, sialyl-Lea, and sialyl sugar chain defined by NCC-ST-439 in a competitive binding inhibition assay of monoclonal antibodies. This newly defined antigen is a good example of a normal antigen shed from cancer cells that can be used successfully as a serum tumor marker.
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PMID:Selection of a monoclonal antibody reactive with a high-molecular-weight glycoprotein circulating in the body fluid of gastrointestinal cancer patients. 245 34

Murine hybridomas were generated against purified carcinoembryonic antigen (CEA), and their monoclonal antibodies (MAb) were assayed for their ability to recognize specific CEA epitopes. One of the MAb, designated 7F, was found to recognize an epitope of CEA that was expressed in human colonic carcinoma tissues but not in normal colonic tissues. When extracts of 13 colonic carcinoma tissues and 9 normal colonic tissues were examined with the Western blot technique using MAb 7F, 11 colonic carcinoma tissues (85%) reacted with 7F, but none of the 9 normal colonic tissues (including many obtained from the areas adjacent to the colonic carcinomas) did. Western blot analysis indicated a Mr 180,000 band in 11 of 13 (85%) colonic carcinoma extracts. The limit of detectability of CEA was 0.5 micrograms/lane. According to immunohistochemical techniques, 16 of 18 (89%) formalin-fixed paraffin-embedded sections of colonic carcinomas reacted with MAb 7F, whereas 9 of 9 (100%) frozen sections of colonic carcinomas reacted with the antibody. Of the 32 paraffin-embedded and frozen sections of normal colonic tissues examined, none showed any reactivity with MAb 7F. MAb 7F did not react with nonspecific cross-reacting antigen either. This antibody has been examined for its usefulness in detecting CEA in suspension and has been found to work both in sandwich enzyme-linked immunosorbent assays and in sandwich radioimmune assays. The detection of CEA in colon tumors but not in normal colonic tissues may be attributed to two possible explanations. It is possible that the level of CEA expression in normal colonic tissue is below the sensitivity of the assays employed. Alternatively, MAb 7F may recognize a "specific" epitope of CEA which was found in colon tumors but not in CEA of normal colonic tissues. At the present time, it is not possible to discern between these two possibilities. Nevertheless, MAb 7F was capable of detecting the differential expression of CEA in colonic carcinomas and, therefore, may be useful for the immunodiagnosis, radioimaging, and immunotherapy of colon cancer.
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PMID:Monoclonal antibody recognizing a carcinoembryonic antigen epitope differentially expressed in human colonic carcinoma versus normal adult colon tissues. 247 48

Recombinant human interferons have recently been shown to enhance tumor antigen expression, including carcinoembryonic antigen (CEA), on the surface of human carcinoma cells, which results in an increase in the targeting of antitumor monoclonal antibodies (MAb) in vivo. We report here the effect of recombinant human gamma-interferon (HuIFN-gamma) on the expression of human CEA and its related transcripts in several human colon carcinoma and normal human fibroblast cell lines. The colon tumor cell lines HT-29, WiDr, and LS-174T were each shown to express different constitutive levels of CEA glycopeptide, as measured by the binding of the CEA-specific MAb COL-4. Treatment with HuIFN-gamma enhanced the level of binding of COL-4 in total cell extracts of HT-29 and WiDr cells 2.5- and 6.5-fold, respectively. Using a CEA complementary DNA probe, this increase in MAb binding was shown to be accompanied by a 6- to 11-fold increase in the steady state levels of three CEA transcripts with sizes of 4.2, 3.5, and 2.8 kilobases. On the other hand, HuIFN-gamma treatment had no effect on the level of COL-4 binding or expression of CEA transcripts in LS-174T colon carcinoma cells, which are high constitutive expressors of CEA glycoprotein. Normal human fibroblast cell lines MRC-5 and WI38 had no detectable cytoplasmic CEA glycopeptide levels nor did they contain detectable levels of CEA mRNA, either before or after treatment with HuIFN-gamma. In contrast, HuIFN-gamma induced the de novo expression of the normal major histocompatibility complex class II antigen, HLA-DR, on HT-29 and WiDr colon cancer cells as well as the two fibroblast cell lines. Treatment of the LS-174T cell line with HuIFN-gamma did not result in the induction of class II HLA-DR antigen. These observations suggest that some common factors may be involved in the regulation of the CEA and class II histocompatibility genes. In addition, the demonstration that HuIFN-gamma enhances CEA expression in some carcinoma cell lines but fails to induce de novo expression of CEA transcripts in fibroblasts supports the potential application of HuIFN-gamma in enhancement of tumor targeting of antitumor MAbs and adds to our understanding of the mechanism of gamma-interferon-mediated up-regulation of some tumor antigens.
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PMID:Modulation of carcinoembryonic antigen messenger RNA levels in human colon carcinoma cells by recombinant human gamma-interferon. 249 18

We reported 2 patients treated with Methotrexate (MTX)-Fluorouracil (5-FU) sequential therapy combined with Doxifluridine (5'-DFUR). The method of administration was as follows: MTX 60 mg was given intravenously (iv) followed by 5-FU 600 mg iv 2 hours later in colon cancer and 5 hours later in gastric cancer. Leucovorin 20 mg was administered 3 times every 6 hours beginning 6 hours after 5-FU infusion. This cycle was repeated once a week for 5 weeks. 5'-DFUR 1,200 mg was given orally daily and continued after MTX.5-FU therapy. Patient 1 was a 60-yr-old female with recurrent colon cancer developed four years after sigmoidectomy. She was referred to our hospital for further examinations of elevated serum carcinoembryonic antigen (CEA). The enlarged intraabdominal lymph nodes due to recurrence were demonstrated on computer tomography and the chemotherapy was performed as described above. The swelling of lymph nodes showed marked reduction in size and CEA value was normalized. Patient 2 was a 59-yr-old man with advanced gastric cancer accompanied by giant liver metastasis. Both primary and metastatic lesion responded favorably to this regimen. There was no remarkable side effect in either patient. These results suggest that this method is worth performing in further clinical trials for cancer patients.
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PMID:[Two cases of gastrointestinal cancers with major responses to sequential methotrexate 5-FU plus 5'-DFUR]. 252 5

We have recently characterized the growth-inhibitory and cellular responses [carcinoembryonic antigen (CEA) secretion, protein secretion, protein expression, fibronectin and laminin synthesis] of the human colon carcinoma MOSER cell line to transforming growth factor-beta (TGF-beta) (Cancer Res., 47: 2950, 1987; 48: 4059, 1988). We have also recently isolated a subline (MOSER R2) from the parental MOSER cells which, unlike the parental line, is relatively resistant to the growth-inhibitory effect of TGF-beta (Biochem. Biophys. Res. Commun., 150: 711, 1988). We now report on the characterization of the cellular responses of this resistant MOSER R2 subline to TGF-beta and compare its responses to that of the highly growth-inhibition-sensitive MOSER cell line. In view of the reported relationship between CEA expression and differentiation in colon cancer and the ability of colon-derived substrata material to modulate the phenotypic properties of colon cancer cells, additional characterization and direct comparison of the effects of TGF-beta on the two cell lines were also performed with respect to (a) cellular expression of CEA and CEA cross-reactive glycoproteins; and (b) colon-derived substrata material. Unlike the growth-inhibition-sensitive MOSER cells, TGF-beta had no effects on fibronectin/laminin synthesis nor on the cellular morphology of the resistant MOSER R2 cells. TGF-beta was also unable to modulate protein secretion and deposition of substrata material by these cells. However, several other responses of the resistant cells to TGF-beta were found to be similar to that of the sensitive MOSER cells. These responses include: (a) a prolonged and stable secretion of CEA; (b) a prolonged and stable induction of elevated cellular expression of CEA and CEA cross-reactive glycoproteins; and (c) enhancement of the expression of three cellular proteins with molecular weights corresponding to 52,000, 48,000, and 42,000. We further report that the differences observed in the responses to TGF-beta in the two cell lines were not due to differences in TGF-beta binding or other receptor parameters such as the expression of distinct TGF-beta receptor subspecies.
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PMID:Diverse cellular responses elicited from human colon carcinoma cells by transforming growth factor-beta. 253 53

The effects of vasoactive intestinal polypeptide (VIP) and dibutyryl cyclic adenosine 3':5'monophosphate (dbcAMP) on two human colon carcinoma cell lines, HCT 116 and GEO, were investigated. VIP and dbcAMP inhibited the growth of both cell lines in monolayer culture in a dose-dependent manner. Within 6 h of treatment with 1 mM dbcAMP or 0.3 microM VIP, numerous mucin-like droplets were secreted by GEO cells. VIP and dbcAMP also increased carcinoembryonic antigen (CEA) secretion. In both cell lines, a 9-fold increase in conditioned medium CEA levels was observed at 1 mM dbcAMP and a 2.6-fold increase at 1.5 microM VIP. Time- and concentration-dependent evaluation in cAMP levels were elicited by VIP in the two cell lines. Immunocytochemical studies for cell-surface glycoprotein detection in GEO cells showed that VIP induced a morphological and functional organization of mucin-secreting cells. These results indicate that VIP and dbcAMP have antiproliferative and strong differentiation-promoting effects in colon cancer cells. This is the first report of VIP-induced mucin secretion in colon tumor cells.
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PMID:Promotion of differentiation in human colon carcinoma cells by vasoactive intestinal polypeptide. 254 28

The aim of a primary screening system is to detect premalignant lesions and carcinomas when amenable to "curative" surgery. Although a number of "classical" tumor markers have acquired potential for clinical management, none is presently adequate for presymptomatic diagnosis or screening. In colorectal carcinoma, the screening potential of carcinoembryonic antigen (CEA), the gastrointestinal-related antigen, CA19-9, and other more recently characterized "biochemical markers" is virtually nonexistent, even in patients at high risk to develop the disease. Promising new leads are beginning to emerge from somatic cell genetic and molecular biological approaches. In common with other epithelial neoplasms, perturbations in oncogene expression have been demonstrated in colorectal cancers, and probably reflect important events in malignant transformation and progression. Studies of oncogene expression have, however, not yet yielded clinically useful information. Recently, an intensive search for specific chromosomal and gene abnormalities in the hereditary colon cancer syndromes led to the location of the familial adenomatous polyposis (FAP) gene at chromosome 5q21-q22. Significant is that the loss of alleles on chromosome 5 has also been observed in the tumor cells of at least 20% of sporadic colon cancer patients. This type of association between constitutional genetic change and genetic aberration in the cells of sporadic tumors is reminiscent of other malignant diseases with a genetic component (e.g., retinoblastoma and Wilms' tumor).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Current status of tumor markers in large bowel cancer. 265 54

In 1978, a prospective program was initiated to evaluate postoperative monitoring of patients after resection of carcinoma of the colon and rectum. The program included clinical examination, interval endoscopy, measurement of carcinoembryonic antigen (CEA), selected liver function tests (alkaline phosphatase and gamma glutamyl transferase) and roentgenologic testing: roentgenograms of the chest, barium enema, intravenous pyelogram (IVP) and computerized axial tomographic (CAT) scan. Of the initial 226 patients enrolled, 179 had at least one abnormal elevation of the CEA level, and in 70 (39 per cent), recurrence developed. Of the 70 with recurrence, 62 (89 per cent) had elevated CEA levels (greater than 3.0 nanograms per milliliter) prior to detection of recurrence by other means. Eight patients had normal levels (two were false-negative and the other six were tested at inappropriate times). Although other test results often complemented CEA, they were generally less sensitive for early detection. Selective use of these tests frequently documented site and extent of recurrence. The detection sensitivity of these other tests was highest with CAT scan (83 per cent), followed by barium enema and endoscopy (56 and 46 per cent). Forty-five patients underwent re-exploration. Recurrence was found in 42, of whom 23 had resectable disease (five of 11, liver; 17 of 24, local or pelvis, and one of one, lung). In three patients, nothing abnormal was found at exploration; two of these patients ultimately had metastases develop. The median survival time was 43 months and the estimated five year survival rate was 38 per cent. CEA is the best over-all indicator of early recurrence and frequent testing at short intervals is most important. Periodic clinical examination and selected other studies are also essential for early documentation of recurrence. Second-look surgical procedures appear beneficial for survival time in selected patients.
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PMID:Prospective monitoring trial for carcinoma of colon and rectum after surgical resection. 268 53

Sodium butyrate induces morphological and biochemical changes consistent with a more differentiated phenotype in some colon cancer cell lines. These changes include increased expression of carcinoembryonic antigen (CEA) and other oncodevelopmental markers. We utilized domain-specific probes and polyclonal antibodies against CEA-related antigens to study sodium butyrate-induced expression of the CEA gene family in a villous adenoma-derived cell line, which is nontumorigenic in nude mice (VACO 235), and two colonic carcinoma cell lines known to respond to sodium butyrate exposure by phenotypic differentiation (HT-29 and LS 174T). The induction begins as quickly as 24 h after exposure and occurs primarily at a transcriptional level, although some translational control is also evident. No evidence was found for gene amplification, rearrangement, or methylation to account for the mechanism of this transcriptional control. [35S]Cysteine pulse-labeled cell lysate immunoblots and polyadenylated RNA blot hybridization suggest that increases in mRNA transcript and CEA-related glycoprotein levels are primarily due to increased synthesis rather than decreased degradation. A considerable amount of heterogeneity is seen in the biosynthesis of the CEA-related glycoproteins, with each cell line showing a distinct pattern of CEA-related antigen expression from a limited number of mRNA transcripts.
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PMID:Heterogeneity in the induction and expression of carcinoembryonic antigen-related antigens in human colon cancer cell lines. 272 Jun 85

The follow-up of colon cancer patients by monitoring serum carcinoembryonic antigen has advantages (better survival after early detection of recurrence by CEA rise) as well as disadvantages (false-positive rise of CEA, and early detection of incurable recurrences in asymptomatic patients). The effects of CEA follow-up on quality-adjusted life expectancy (QUALE) of patients with curatively resected colon carcinoma have been simulated by a Markov analysis using literature data. The value of CEA seems insignificant and varies, depending on the literature data used, from a mean increase of QUALE by 6 days (+0.4%) to a mean decrease by 2 days (-0.07%). This value depends on patient-related variables; the negative effects of CEA especially predominate in older patients with favourable Dukes' stages of primary tumour.
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PMID:[Carcinoembryonal antigen and the follow up of patients after resection of colon carcinoma with curative intent: a Markov process in decision analysis]. 281 76


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