Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A tumor-associated antigen that shares antigenicity with a pregnancy-associated protein has been detected in ascitic fluid of patients with advanced ovarian cancer. The protein, prepared from malignant ascitic fluid by the combination of poly(ethylene glycol) 4000 fractionation, DEAE-Sepharose column chromatography and preparative polyacrylamide gel electrophoresis (PAGE), was subsequently separated on sodium dodecyl sulfate-PAGE, as a single band corresponding to an approximate molecular mass of 91 kDa. Immunological analysis showed that this protein was a circulating species of an ectopic developmental antigen that markedly increases in biological fluids in tumor-bearing statuses.
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PMID:Identification of an ectopic developmental antigen that appears in malignant ascitic fluid. 166 74

Sialylated carbohydrate antigens, such as CA19-9 (sialyl Lea), CA-50 (sialyl Le4), CSLEX1 (sialyl Lex) and SLX (sialyl Lex-i), were assayed in the same preoperative serum samples of 63 patients with colorectal cancer, and compared with CEA. In addition immunohistochemical expressions of sialyl Lea, sialyl lex and sialyl Lex-i antigens were studied in 62 colorectal carcinomas and 42 normal mucosal sites remote from the malignant lesion using monoclonal antibodies CSLEA1, CSLEX1 and FH-6, respectively, in order to elucidate their tumor-specificity and clinical usefulness as a tumor-associated antigen. Serologically, the percent positive rates of CA19-9, CA-50, CSLEX1, SLX and CEA were 30.2%, 17.7%, 23.8%, 16.1% and 44.4%, respectively. In dukes' A and B, these sialylated carbohydrate antigens, especially CSLEX1 and SLX, showed low positive rates, but the percent positive rates of CSLEX1 and SLX correlated with operative radicality. The positive spectrum of CSLEX1 differed from that of CA19-9 in sera, and CEA had no correlation with these two antigens. The immunohistochemical expression rates of sialyl Lea, sialyl Lex and sialyl Lex-i were 88.1%, 17.0% and 9.5% in normal mucosa, but were 77.8%, 90.5% and 71.4% in carcinoma, respectively. These data suggested that the type 2 chain antigens CSLEX1 and SLX, which have high tumor-specificity compared with CA19-9, may be useful in preoperative diagnosis for extension of carcinoma and operative radicality, although early diagnosis using these sialylated carbohydrate antigens may be difficult, while the combined use of CA19-9, CSLEX1 and CEA should make it possible to detect a wide range of colorectal cancer patients.
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PMID:Serological and immunohistochemical studies on sialylated carbohydrate antigens in colorectal carcinoma. 171 32

We analyzed the immunohistochemical expression of three epitopes of the tumor-associated glycoprotein 72 (TAG-72) in whole cross-sections of primary colorectal carcinomas and in regional lymph node metastases using monoclonal antibodies (MAbs) B72.3, CC-49, and CC-83, which recognize distinct carbohydrate antigenic determinants. B72.3, CC-49, and CC-83 reacted with 13 of 27 (48%), 25 of 27 (92%), and 21 of 27 (77%) carcinomas, respectively. The immunoreactivity with lymph node metastases followed a similar pattern; MAb CC-49 was again the most reactive of the three antibodies, since it labeled 13 of 15 metastatic lesions. Positive reactions of the MAbs with the primary tumors were not always predictive of the immunorecognition of their metastases. Distinct areas within whole cross-sections of TAG-72-positive primary carcinomas demonstrated marked differences in the expression of the three epitopes. CC-49 tended to react with the highest number of areas and with the highest percentages of carcinoma cells within each area. In no instances did B72.3 demonstrate reactivity superior to that of either CC-49 or CC-83. Tumors negative for the CC-49 epitope in any area also did not express the other two TAG-72 epitopes. However, the comparison of the immunostaining obtained with each MAb in TAG-72-positive primary lesions revealed areas where CC-83 was clearly more reactive than CC-49. Moreover, one lymph node metastasis, negative for CC-49, was recognized by CC-83. Thus, the combined use of MAbs CC-49 and CC-83 resulted in additive immunostaining of primary and metastatic colorectal carcinoma cells. The study provides evidence of intratumoral heterogeneity in the glycosylation pattern of the TAG-72 antigen in colorectal cancer and emphasizes the advantages of cocktails of anti-tumor-associated antigen MAbs in the immunodetection of colorectal tumor cells.
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PMID:Regional heterogeneity and complementation in the expression of the tumor-associated glycoprotein 72 epitopes in colorectal cancer. 171 50

In clinical studies we have evaluated a unique monoclonal antibody-based drug delivery system, a bifunctional antibody designed to deliver imaging or therapeutic agents, such as radioisotopes, drugs, or biologics, to tumor cells, while minimizing the dose to normal tissue. The bifunctional antibody, with one specificity to a tumor-associated antigen (carcinoembryonic antigen) and another specificity to a hapten, is injected and allowed to localize at a tumor site for 4 days. A hapten, tagged with a radioisotope, is subsequently injected for delivery to and capture by the prelocalized antibody at the tumor site. In studies reported here, the sulfhydryl groups of Fab' fragments of ZCE-025 and CHA-255 were linked with bis-maleimidomethyl ether to form an F(ab')2 bifunctional antibody coupled by a stable thioether linkage. EOTUBE, a hydroxyethylthiourido derivative of benzyl EDTA, was used as the hapten carrier of 111In. Fourteen patients 62-82 years old with recurrent or metastatic adenocarcinoma of the colon were studied. Twenty of 21 known lesions were imaged, and eight of nine new lesions were confirmed. With this fundamentally new approach to drug delivery, clearance from normal tissue is rapid, and high tumor:normal tissue ratios are expeditiously achieved.
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PMID:Bifunctional antibody: a binary radiopharmaceutical delivery system for imaging colorectal carcinoma. 174 39

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

More than 50% of the patients with large bowel cancer develop disseminated disease and invariably succumb. Adjuvant chemotherapy with 5-FU and levamisole have been shown to be more efficient than 5-FU alone or in combination with cytostatics. The combination of 5-FU, leukovorin and methotrexate induces prolonged survival with a good quality of life in metastatic colorectal cancer (CRC). During the last decade tumor immunotherapy has been an alternative facilitated by isolation and large scale production of cytokines and monoclonal antibodies. The mouse monoclonal antibody (MAb) 17-1A recognizes a tumor-associated antigen (TAA), present in high concentrations on the surface of gastrointestinal tumor cells. Injections of MAb 17-1A in patients with metastatic CRC induced generation of anti-idiotypic (ab2) in 90% and anti-anti-idiotypic (ab3) antibodies in 47% of the treated patients. The development of ab3 correlated significantly with survival (mean 80 weeks) while ab3- patients survive only 38 weeks. One of 52 patients treated with MAb 17-1A is a complete remission after 66 months, 3 had minor regression and 6 had a stable disease (19% RR). Based on in vitro findings showing increased antibody-dependent cellular cytotoxicity (ADCC) by the combination of granulocyte-macrophage colony stimulating factor (GM-CSF) and MAb 17-1A, 16 CRC patients have been treated with subcutaneously injections of GM-CSF for 10 days and intravenous infusions of MAb 17-1A at day 3. Two of 16 are in CR, 1 in MR and 3 in SD (37.5% RR). Minor side-effects were registered. A further development of immunotherapy of CRC might imply vaccination by injection of specific human anti-idiotypic antibodies (ab2) which mimics the nominal antigen, in order to induce a specific immunity.
Med Oncol Tumor Pharmacother 1991
PMID:Chemotherapy and immunotherapy of colorectal cancer. 180 82

Placental protein 4 (PP-4), a recently characterized glycoprotein from human placenta, was studied using a specific double-antibody radioimmunoassay in sera of 130 volunteers, 76 ovarian tumor patients and in ovarian tumor cyst fluid and ascites of 21 patients. Elevated levels (greater than 3 micrograms/l) were found in 45 of 52 ovarian cancer patients (86.5%). PP-4 levels correlated significantly with staging. 31 patients with malignant ovarian tumor were monitored on 2-9 occasions during 5-82 weeks. Rising or falling levels of PP-4 correlated with progression or regression of disease in 25 of 31 instances (80.6%). Elevated levels were found in 10 of 24 benign and borderline ovarian tumors. Elevated PP-4 level does not indicate malignancy in each case. PP-4 can be regarded as tumor-associated antigen and an tumor marker in oncological practice.
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PMID:Placental protein 4 as a possible tumor marker in ovarian tumors. 183 96

177Lutetium (177Lu) is a member of the family of elements known as lanthanides or rare earths. Monoclonal antibody (MAb) CC49, a murine IgG1, which is reactive with the tumor-associated antigen, TAG-72, has been shown previously to react with a wide range of human carcinomas; CC49 reacts to a different epitope on the TAG-72 molecule than MAb B72.3 and has a higher binding affinity. We report here the first use of a 177Lu-labeled immunoconjugate, 177Lu-CC49, in an experimental therapy model for human carcinoma. 177Lu-CC49 was shown to delay the growth of established LS-174T human colon carcinomas in athymic mice at a single dose of 50 microCi. Overt toxicity was observed with the administration of approximately 500 microCi of 177Lu-CC49 in which 5 of 9 mice died of apparent marrow toxicity. A single administration of 200 or 350 microCi of 177Lu-CC49, however, was shown to eliminate established tumors through the 77-day observation period after MAb administration. Dose fractionation experiments revealed that at least 750 microCi of 177Lu-CC49 (250 microCi/week for 3 consecutive weeks) was well tolerated in that 9 of 10 mice survived. Moreover, this dose schedule was able to eliminate the growth of relatively large (300 mm3) human colon tumor xenografts in 90% of the animals treated. Single-dose and dose fractionation studies were also carried out with an isotype-matched control MAb, 177Lu-MOPC-21. In all dose schedules, a large differential was seen between the therapeutic effects of the 177Lu-CC49 versus that of the 177Lu-control MAb. The merits and limitations of the use of 177Lu-labeled immunoconjugates (in particular, 177Lu-CC49) are discussed in terms of potential novel therapeutics for human carcinoma.
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PMID:Monoclonal antibody-based therapy of a human tumor xenograft with a 177lutetium-labeled immunoconjugate. 185 65

Monoclonal antibodies against a tumor-associated antigen (TAG-72) with mucin-like properties have been generated. MAb B72.3 was used to identify and help characterize this antigen. B72.3 has been successfully used for the localization of tumor metastases in situ after i.v. administration. MAb B72.3 has also been used in conjunction with CC49, another anti-TAG-72 MAb, to measure TAG-72 levels in sera and effusions. TAG-72 can be found in the fluids of patients with adenocarcinomas from many different sites. This CA 72-4 double determinant radioimmunoassay in conjunction with assays for carcinoembryonic antigen can identify patients with malignancies with greater sensitivity than either assay alone.
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PMID:In vivo and in vitro clinical applications of monoclonal antibodies against TAG-72. 186 28

Fusion of tumorigenic HeLa cells with human skin fibroblasts results in genetically stable hybrids which are nontumorigenic and no longer express the HeLa tumor-associated antigen, intestinal alkaline phosphatase (IAP). Previous analysis of spontaneous segregants of the nontumorigenic hybrid have implicated the loss of one copy of human fibroblast chromosome 11 with reexpression of IAP and tumorigenicity. This observation suggests that a putative HeLa tumor suppressor gene(s) is located on chromosome 11 and that this gene may be a negative regulator of the IAP gene. We have isolated several gamma-ray-induced mutants (GIMs) of the nontumorigenic HeLa x skin fibroblast hybrid CGL1 that were specifically selected for reexpression of IAP to further investigate the potential linkage between IAP regulation and the putative tumor suppressor locus. The GIMs have a wide range of cell morphology and level of IAP expression (nearly a factor of 40). The tumorigenicity of the GIMs was examined by s.c. injection into nude mice and all were found to be tumorigenic. The tumor volume-doubling time is in the range of 4 to 8 days for all the cell lines; however, the lag time to reach 500 mm3 tumor volume was significantly longer when the GIM IAP activity was low (less than 20% relative activity), suggesting perhaps that there is a threshold level of IAP expression required for tumor formation and selection for high IAP expression in vivo. However, studies with tumor reconstitutes of the GIMs and transfection studies with an IAP complementary DNA expression vector indicate that high IAP expression alone is not sufficient to confer rapid tumor growth. Therefore, while the data lend strong support to the continued tight correlation between IAP reexpression and tumorigenicity and to our proposal that the tumor suppressor may negatively regulate the IAP gene, it suggests that selection for other gene activities may be responsible for aggressive tumor growth in this cell hybrid system.
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PMID:Characterization of intestinal alkaline phosphatase expression and the tumorigenic potential of gamma-irradiated HeLa x fibroblast cell hybrids. 186 67


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