Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Inhibition of leukocyte migration in agarose-agar was used as a probe for tumor-associated antigen in 3-M KCl solubilized extracts of gastric, colon, and lung cancers from humans. Twelve of 40 (30%) leukocyte preparations from gastric cancer patients, 10 of 21 (48%) from colon cancer patients, and 7 of 14 (50%) from lung cancer patients were inhibited by their respective histologically homologus cancer extract. However, among 75 preparations from various cancer patients, leukocytes from only 2 gastric cancer patients were inhibited by paired normal gastric tissue extracts. Only 2 of 68 preparations from normal individuals and none of 67 preparations from patients with nonmalignant diseases, such as gastric peptic ulcer, gastritis, colon polyposis, colitis, pulmonary tuberculosis, chronic bronchitis, and sarcoidosis, were inhibited by cancer extracts. These findings suggest the presence in KCl extracts of gastric cancer of presumed tumor-associated antigen(s) that is antigenically distinct from that of either colon or lung cancer.
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PMID:Inhibition of human leukocyte migration in agar by 3-M potassium chloride extracts of stomach, colon, and lung cancers. 28 34

We have compared by SDS-PAGE Western blotting the molecules detected by two human monoclonal antibodies, C-OU1 and 16.88. The antibodies have previously been shown to detect a cytoplasmatic antigen with an Mr of 43 kD present in colon adenocarcinoma cell lines and in colon cancer tissues. We now demonstrate that these antibodies differ significantly in their fine specificity, resulting in a quite dissimilar tumor selectivity. The antibody 16.88, in addition to reactivity with the 43-kD molecule, also recognizes a 190-kD molecule present both in melanoma cells and in cells previously reported as 16.88 antigen positive. The 16.88 antibody does not detect a 43-kD molecule in extracts of melanoma cells. The 190-kD component was not detectable in hepatoma or mamma carcinoma cells, both of which showed presence of the 43-kD molecule. The C-OU1 antibody shows no reactivity with the 190-kD molecule in any of the cells tested or with other proteins in melanoma cells. Radiolabeled 16.88 antibody shows better localization to melanoma cancer than to colon cancer xenograft transplanted onto nude mice. These findings indicate the presence of a tumor-associated antigen not previously described and have obvious implications for potential clinical uses of the antibodies.
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PMID:Antigens recognized by two human monoclonal IgM anticolon cancer antibodies, 16.88 and C-OU1 (B9165). 175 84

The LeY determinant, a difucosylated type 2 blood group-related antigen, is a positional isomer of the Leb blood group antigen and a fucosylated derivative of the LeX antigen. The LeX antigen behaves like an oncodevelopmental tumor-associated antigen in human colon cancer, and extended polyfucosyl LeX antigens are more specific for colon cancer tissues than are simple, monofucosyl LeX antigens. The present investigation compared the expression of simple and extended LeY antigens in a variety of malignant and nonmalignant human colonic tissues to gain insight into the normal distribution and cancer-associated expression of these antigens. Monoclonal antibody AH-6, which recognizes the LeY epitope irrespective of its carrier carbohydrate chain, stained the majority of specimens regardless of malignant potential or location within the colon. In contrast, CC-1 and CC-2 monoclonal antibodies, which recognize extended LeY structures, and KH-1, which is specific to trifucosyl LeY, preferentially stained malignant colonic tissues and rarely stained normal colonic mucosae. Mucosa immediately adjacent to cancer usually stained with AH-6 but not with KH-1, CC-1, or CC-2. Extended or trifucosyl LeY antigen expression was limited exclusively to premalignant (adenomatous) polyps and was invariably absent from nonpremalignant (hyperplastic) polyps. Moreover, among adenomatous polyps, extended LeY antigen expression tended to correlate with three parameters of malignant potential: larger polyp size; villous histology, and severe dysplasia. AH-6 failed to distinguish between hyperplastic and adenomatous polyps. In second-trimester fetal colonic mucosa, AH-6 bound to both proximal and distal segments whereas KH-1, CC-1, and CC-2 bound only to proximal segments. We conclude that in human colon, the LeY hapten is an oncodevelopmental cancer-associated antigen and extended LeY antigens are highly specific markers for malignancy and premalignancy.
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PMID:Expression of LeY and extended LeY blood group-related antigens in human malignant, premalignant, and nonmalignant colonic tissues. 242 90

The CA 19-9 antigen is a monosialosyl Lea blood group antigen which has been shown to be a useful tumor-associated antigen for the diagnosis of gastrointestinal cancers. Recently, a sialylated derivative of this antigen, disialosyl Lea, was isolated from a colon cancer liver metastasis and a monoclonal antibody (FH7) recognizing this novel determinant was developed. The present study simultaneously compared the expression of Lea, monosialosyl Lea, and disialosyl Lea antigens in a variety of nonmalignant, premalignant, and malignant tissues of the colorectum and pancreas with an aim toward elucidating whether disialosyl Lea is expressed as a tumor-associated antigen. In normal colonic mucosa, disialosyl Lea expression closely resembled Lea expression in overall frequency, segmental distribution, and cellular localization whereas monosialosyl Lea (CA 19-9) was essentially absent. Along the crypt axis, Lea was more often expressed in goblet cells of the upper crypt whereas disialosyl Lea was found in goblet cells along the entire crypt. Fetal colonic mucosa expressed all three antigens, as did most colorectal cancers regardless of location within the colon or degree of differentiation. The majority of hyperplastic polyps and practically all adenomatous polyps also expressed these three antigens, and in adenomas, antigen expression was independent of polyp size, villous morphology, or degree of dysplasia. In the normal pancreas, the three antigens were expressed on ductal, ductular and centroacinar cells of all specimens. The majority of pancreatic cancers expressed all three antigens. Thus, in the normal colon, the absence of monosialosyl Lea (CA 19-9) in the presence of disialosyl Lea suggests that an alpha 2,6 sialyltransferase is active, which results in the masking of CA 19-9 antigen expression. These results further support the concept that specific sialyltransferases play a role in regulating the expression of tumor-associated antigens.
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PMID:Immunohistochemical comparison of Lea, monosialosyl Lea (CA 19-9), and disialosyl Lea antigens in human colorectal and pancreatic tissues. 328 36

The mouse monoclonal antibody 17-1A (gamma 2a, kappa) recognizes a tumor-associated antigen expressed on human gastrointestinal malignancies and has been used in Phase I and II clinical trials. Chimeric genetic constructs have been produced using 17-1A variable region genes (VL and VH) and the constant region genes for human kappa light chains and gamma 1 heavy chains (C kappa and gamma 1). The chimeric gene constructs were transfected into mouse myeloma cells for antibody production. The secreted mouse/human chimeric antibody contains the antigen-binding domain of 17-1A and the human (gamma 1, kappa) constant regions. Native mouse 17-1A and the chimeric antibody (chIgG1) were analyzed for binding to two human colon cancer cell lines and for the mediation of cancer cell line antibody-dependent cellular cytotoxicity by normal human peripheral blood lymphocytes and monocytes in 4 h 51Cr-release assays. The 17-1A and chIgG1 gave similar results in these in vitro biologic assays. This study demonstrates the feasibility of using mouse/human chimeric antibodies in human therapeutic applications.
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PMID:Human lymphocyte and monocyte lysis of tumor cells mediated by a mouse/human IgG1 chimeric monoclonal antibody. 336 51

Monoclonal antibody B72.3 was generated using a membrane-enriched fraction of cells from a mammary carcinoma metastasis and has been shown previously to have a high degree of selective reactivity for human breast and colon carcinoma versus normal adult tissues. The reactive antigen has been shown to be a high-molecular-weight glycoprotein complex of approximately 220,000 to 400,000 and is termed tumor-associated glycoprotein 72 (TAG-72). We report here a dichotomy in the expression of TAG-72 in carcinoma biopsy material versus carcinoma cell lines. While 44% (25 of 56) of human breast carcinoma and 80% (16 of 20) of colon carcinoma biopsies express TAG-72 as assayed by radioimmunoassay or immunohistochemistry, only one of 25 breast cancer cell lines [MCF-7 (one variant)] and one of 18 colon cancer cell lines (LS-174T) express this antigen. Furthermore, TAG-72 expression in these two cell lines was shown to be a property of a low percentage of cells within each culture. Attempts to enhance TAG-72 expression in LS-174T cells by propagation on extracellular matrix proteins, such as collagen, laminin, and fibronectin, or in serum-containing or serum-free, hormone-supplemented medium proved unsuccessful. A pronounced increase in TAG-72 expression was observed, however, when the LS-174T cells were grown under culture conditions which promote three-dimensional growth. LS-174T cells grown in spheroid or suspension cultures demonstrated a 2- to 7-fold increase in TAG-72 antigen expression, while those grown on agar plugs demonstrated a 10-fold increase. When the LS-174T cell line was injected into athymic mice to generate tumors, the level of TAG-72 antigen increased over 100-fold, to levels comparable to those seen in the metastatic tumor masses from patients. Thus, spatial configuration of carcinoma cell populations is shown to influence the expression of a tumor-associated antigen and the subsequent surface binding of monoclonal antibody B72.3. The implications of these findings in the potential utility of monoclonal antibodies for the in vivo detection and destruction of carcinoma masses are discussed.
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PMID:Influence of spatial configuration of carcinoma cell populations on the expression of a tumor-associated glycoprotein. 388 Nov 73

Monoclonal antibody B72.3 reacts with a tumor-associated antigen that is found on human breast and colon carcinomas in significantly higher concentration than in normal adult tissues. Intact B72.3 IgG was labeled with I-131 or I-125 and injected into athymic mice bearing xenografts of human colon cancer. Whole-body scintiphotos obtained with a pinhole collimator demonstrated tumor localization within 24 hr after intravenous administration, and the tumor-to-background ratio rose continuously for at least 14 days. Progressive antibody accumulation was observed in the tumor during the first 3 days, but no significant normal organ localization was observed at any time. No localization was seen in control tumors, a human melanoma xenograft that lacks the antigen recognized by B72.3. The pharmacokinetics of this antibody in tumor-bearing mice suggest that I-131 B72.3 may be useful for radioimmunotherapy as well as radioimmunoscintigraphy of colon cancer in man.
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PMID:Radioimmunoscintigraphy of human colon cancer xenografts in mice with radioiodinated monoclonal antibody B72.3. 633 94

With the use of whole tumor cell vaccines in a rat colon cancer minimal residual disease model, we have recently demonstrated that although tissue type-specific tumor immunogens protect against recurrence in the absence of histocompatibility differences, these immunogens offer no predictable tumor-specific protection in the presence of such differences. We have therefore begun to test whether syngeneic and allogeneic rat colon cancer tumor-associated antigens (TAAs), when incorporated into the bilayers of liposomes, could function as effective immunogens in immunotherapy and immunoprotection models. Male Wistar/Furth (W/Fu) rats were inoculated with 5 X 10(6) DMH-W163 colon cancer cells. All nonimmunized animals died of widespread metastases within 2 weeks of complete local tumor resection. In experimental groups, four methods of immunotherapy were used after resection: (1) irradiated whole tumor cells, (2) butanol-solubilized membrane extracts containing TAA only, (3) liposomes only, and (4) liposomes containing TAA. Only animals receiving TAA incorporated into liposomes had a significant increase in survival (p = 0.026). Thirty percent remain disease-free 6 months later. In additional experiments, Buffalo rats were challenged with 1 X 10(6) Buffalo rat colon adenocarcinoma cells after immunization by irradiated whole tumor cells or liposomes and butanol-extracted colon cancer TAAs. Only animals in the group immunized with TAA incorporated into liposomes were significantly protected from subsequent tumor isograft challenge. These data provide evidence of a way to present solubilized colon cancer-associated immunogens that may be applicable in a more clinically relevant, allogeneic setting.
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PMID:Specific active immunotherapy with butanol-extracted, tumor-associated antigens incorporated into liposomes. 646 64

Urine samples collected from patients with colon carcinoma and from normal donors were tested for antigenic activity by the microcomplement-fixation assay. When autologous serum was used as the antibody source, 65.4% (17/26) of the urine samples from patients with colon carcinoma were positive for antigen as opposed to only 10% (2/20) from normal volunteers. Absorption of a representative serum with cultured colon cancer cells completely removed reactivity against its autologous urine. Using this serum to screen urine from colon carcinoma patients, antigenic activity was found in 71.4% (30/46) of the samples; however, only 10% (2/20) of the urine samples from apparently healthy volunteers were positive. Analysis of urine samples collected from three patients before and after resection of their primary colon carcinoma and from nine patients undergoing hyperthermia for liver metastases revealed that two of the patients who had curative surgical procedures had marked decreases in urinary antigen levels by the second postoperative day, while the third patient whose disease was unresectable had no significant decrease. Seven of nine patients with metastatic disease had a greater than fourfold increase in antigen activity after hyperthermia and chemotherapy. These results suggest that tumor-associated antigens were excreted into urine, possibly the result of treatment-caused tumor necrosis. Therefore, assessment of tumor-associated antigen(s) in the urine of patients with colon carcinoma may serve as a marker for response to treatment of this disease.
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PMID:Excretion of tumor-associated antigen(s) in the urine of patients with colon carcinoma. 713 64

Supernatants obtained after incubation of tumor patient lymphocytes with the homologous tumor-associated antigen (TAA) elicit adherence inhibition in normal guinea pig peritoneal cells. From 37 tested patients with different carcinomas, the supernatants of 30 caused more than 10 per cent adherence inhibition (breast cancer 11/11, lung cancer 7/8, colon cancer 6/7, stomach cancer 6/11). Besides 40 healthy blood donors were tested to a panel of TAA. There was a reactivity more than 10 per cent only in 2 cases. The supernatants of 14 patients with nonmalignant disorders produced adherence inhibition more than 10 per cent in 2 cases. By incubation of tumor patient lymphocytes with the human encephalitogenic protein the supernatants of 19/27 patients elicited a positive reaction. The results suggest that anti-tumor immunity can be detected in an indirect heterologous adherence inhibition system.
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PMID:Detection of anti-tumor immunity in man by the indirect macrophage adherence inhibition assay using guinea pig peritoneal cells as indicator cells. 727 53


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