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)

The cell surface antigen, epithelial glycoprotein, defined by the monoclonal antibody HEA 125, is expressed on virtually all epithelial cell membranes but not on mesodermal or neural cell membranes. The cDNA encoding epithelial glycoprotein was isolated by HEA 125 antibody enrichment of colon tumor cDNA expressed transiently in COS cells. The sequence of the epithelial glycoprotein antigen is identical to the cell membrane protein recognized by the monoclonal antibody KS 1/4 and is homologous to the tumor-associated antigen GA733. These proteins share sequence homology to nidogen, an extracellular matrix component that appears to participate in cell-matrix adhesion. These proteins also share a homologous domain found in the B1 chain of laminin, a matrix adhesion protein, and placental protein 12, an insulin-like growth factor I binding protein secreted during pregnancy that has been implicated in regulation of fetal growth. This common domain is also repeated multiple times within the thyroglobulin precursor. These findings suggest epithelial glycoprotein is a cell surface molecule involved in cell-cell or cell-matrix interaction.
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PMID:Epithelial glycoprotein is a member of a family of epithelial cell surface antigens homologous to nidogen, a matrix adhesion protein. 210 41

A monoclonal antibody, H23, that specifically recognizes a breast-tumor-associated antigen, was used to isolate a cDNA insert that codes for the antigenic epitope. Nucleotide sequencing of this cDNA, as well as a longer 850-bp cDNA insert, shows that they are composed of 60-bp (G + C)-rich tandem repeating units. The coding strand was determined and codes for a proline-rich 20-amino-acid repeat motif. A comparison of the highly conserved repeat unit with the deduced flanking amino acid sequences demonstrates conservation of specific subregions of the repeat consensus within the flanking amino acids. Hybridization of the 60-bp cDNA probe with RNAs extracted from a variety of primary and metastatic human tumors yields relatively high levels of hybrid with the breast carcinomas, as compared to lower hybrid levels with RNAs from other epithelial tumors. RNA extracted from breast tissue adjacent to the tumor or from benign breast tumors, demonstrates low or undetectable levels of hybridization. Probing Southern blots with the 60-bp repeat shows that the tumor antigen is highly polymorphic and contains a variable number of tandem repeats (VNTRs). The VNTR nature of the gene was confirmed by probing Southern blots with unique genomic sequences that are physically linked to an isolated gene fragment that also contains the tandem repeat array. Mouse cells transfected with this gene fragment produce tumor antigen that is readily detected by H23 monoclonal antibodies. The allelic forms seen in 10 different primary human tumors demonstrate 100% concordance with the various mRNA species expressed. These studies are extended to the protein forms detected by immunoblot analyses that show both a correlation of the expressed tumor antigen species with the allelic forms as well as significantly increased expression in breast cancer tissue. The above studies unequivocally establish the over-expression of a VNTR gene coding for an epithelial tumor antigen in human breast cancer tissue.
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PMID:A transcribed gene, containing a variable number of tandem repeats, codes for a human epithelial tumor antigen. cDNA cloning, expression of the transfected gene and over-expression in breast cancer tissue. 211 60

A mouse monoclonal antibody ACFH18, produced by immunizing with human gastric cell line MKN-74, recognizes a novel glycolipid antigen, fucosyl-lactoneodecaosylceramide. In the present study, we investigated the immunohistological localization of this antigen and its biochemical detection in glycolipid fraction in normal and malignant human gastric tissue, compared with other tumor-associated type-2 chain glycolipid antigens such as sialyl Lex, sialyl Lex-i and Ley. Reactivity with ACFH18 was detected immunohistologically in the proliferation zone of normal fundic gland region as well as in 38 of 54 cases of gastric cancer, with preferential binding to undifferentiated type cancer. Glycolipids reacting with ACFH18, especially slow-migrating glycolipids on thin-layer chromatography, were accumulated in all of four cancer specimens compared with normal mucosa obtained from the same patients. Many glycolipids with sialyl Lex or sialyl Lex-i epitope were detected in normal mucosa and almost all of these glycolipids were accumulated in cancer specimens. Sialyl LeX-i antigen was increased more specifically in cancer than sialyl LeX was. A Ley antigenic glycolipid was considerably decreased in three of four cancer cases and increased in one case. From these results, glycolipid detected by ACFH18 appeared to be a tumor-associated antigen comparable to sialyl LeX and sialyl Lex-i antigens, but with a unique character as an undifferentiated-type tumor-associated antigen.
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PMID:Immunohistological and biochemical detection of fucosylated polylactosamine antigen with monoclonal antibody ACFH18 in gastric cancer and normal gastric mucosa. 211 68

The presence of two ovarian tumor-associated antigens (TAAs) defined by monoclonal antibodies BC3 and CC4 in primary and metastatic breast, gastric, and colonic malignant tumors was determined by immunohistochemistry. The BC3 TAA was present in all gastric, colonic, and breast tumors, typically with a large proportion of tumor cells expressing antigen. The CC4 TAA was present in most of these tumors, generally with a lower proportion of tumor cells expressing antigen compared with that of BC3. Both of these TAAs were found in some epithelial cells in normal breast, stomach, and colon, however, the location of the two TAAs in normal tissue was different. With the use of both antibodies, an increase in the number of tumor cell-positive lymph nodes was found in patients with breast, gastric, colonic, and ovarian tumors, including detection of micrometastases in nodes from patients considered node negative on purely morphologic grounds. Immunohistochemical detection of micrometastases derived from adenocarcinomas appears to be superior to purely morphologic detection.
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PMID:Demonstration of two ovarian tumor-associated antigens in primary and metastatic breast, gastric, and colonic tumors. 216 66

The focus of this review has been the application of MAbs as adjuncts in the interpretation of cytology specimens. It is evident that most if not all of the MAbs studied thus far are neither completely tumor-specific nor -sensitive; however, when used to address a directed clinical question, they may be "operationally specific." More important, there continues to be no current substitute for the understanding and practice of sound diagnostic cytopathologic principles. Ultimately, the application of MAbs resides in the importance of tumor-associated antigen expression and phenotyping of tumors with therapeutic and prognostic implications.
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PMID:The application of monoclonal antibodies in the cytologic evaluation of tumors. 218 81

Recombinant techniques allow one to engineer an antibody molecule and, in this way, manipulate its properties and functions. We engineered a chimeric human/mouse antibody to the tumor-associated antigen ganglioside GD2, with the aim of decreasing its serum half-life, maintaining its full antigen-binding capacity, and deleting its effector functions, thus making it a potentially useful reagent for the radioimaging of tumors. To this end, the constant region of the human gamma 1 chain was mutated by deleting the second domain (CH2). Here we show that the CH2-deleted antibody (ch14.18-delta CH2) was cleared from the blood of athymic (nu/nu) mice bearing human melanoma tumors with the same kinetics as human IgG F(ab')2. At a beta t1/2 of 12 hr, 0.9% of the injected dose of 125I-labeled ch14.18-delta CH2 was found per milliliter of blood 24 hr after i.v. injection. In biodistribution experiments, 125I-labeled ch14.18-delta CH2 targeted specifically to melanoma xenografts, achieving optimal tumor-to-tissue ratios 12-16 hr after i.v. injection. ch14.18-delta CH2 was localized to the melanoma tumors more rapidly and with better localization ratios than the intact chimeric antibody ch14.18. Sixteen hours after i.v. injection, the tumor-to-blood and tumor-to-liver ratios of ch14.18-delta CH2 were 5 and 12, respectively, while optimal localization ratios obtained for ch14.18 were 1 and 5, respectively, but 96 hr after injection. A reagent such as ch14.18-delta CH2 should be useful for radioimmunodetection of human tumors because of reduced immunogenicity, increased targeting specificity, and rapid clearance from circulation.
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PMID:Serum half-life and tumor localization of a chimeric antibody deleted of the CH2 domain and directed against the disialoganglioside GD2. 219 70

A panel of six monoclonal antibodies (MAbs) was employed to evaluate antigen expression in pulmonary adenocarcinomas and mesotheliomas. Monoclonal anti-human milk fat globulin (HMFG-2), anti-carcinoembryonic antigen (NP-2), anti-epithelial membrane antigen (EMA), anti-cytokeratin (PKK-1), anti-tumor-associated antigen 72 (B72.3), and anti-human myelomonocytic antigen (Leu M-1) antibodies were used to localize their respective antigens in formalin-fixed, paraffin-embedded tumors by using the avidin-biotin-complex immunoperoxidase technique. In all, 28 mesotheliomas obtained from Ohio State University Anatomic Pathology files and from a Southwest Oncology Group (SWOG) protocol were compared to 22 pulmonary adenocarcinomas by using this MAb panel. None of the mesotheliomas demonstrated positive staining with MAbs NP-2 (anti-CEA) or Leu M-1. However, 95% (21/22) of adenocarcinomas stained with one of these two antibodies. Although neither of these two MAbs stained all adenocarcinomas, each antibody demonstrated positive immunostaining in more than 90% of the adenocarcinomas studied. Therefore, MABs NP-2 and Leu M-1 are, individually, quite useful for distinguishing mesothelioma from adenocarcinoma. However, in our study, no single MAb could be used to distinguish these two tumor types in every case. MAb B72.3 stained 91% (20/21) adenocarcinomas but also stained 7% (2/28) of mesotheliomas. MAb HMFG-2 reacted positively with 95% of adenocarcinomas, but also stained 39% of the mesotheliomas, usually in a membranous pattern. MAbs EMA and PKK-1 were not found useful in distinguishing mesothelioma from adenocarcinoma. We conclude that MAbs Leu M-1 and NP-2 were both useful in distinguishing mesothelioma from pulmonary adenocarcinoma in that positive staining was demonstrated in adenocarcinomas and not mesotheliomas.
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PMID:Distinguishing malignant mesothelioma from pulmonary adenocarcinoma: an immuno-histochemical approach using a panel of monoclonal antibodies. 221 94

Cyst and ascites fluids from patients with ovarian epithelial neoplasms contain immunoglobulins with antitumor activity. Autologous antibodies bound to the cellular membrane fragments obtained from human ovarian neoplastic effusions react with cell-surface antigens on different human ovarian cell lines, surgical specimens of human ovarian adenocarcinoma, and human ovarian tumors grown in athymic Balb/c mice. The antibodies do not react with tissue preparations from normal human ovaries, other nonovarian normal or neoplastic tissues, and nonovarian human cell lines. These studies indicate that these antibodies are capable of complement-mediated lysis of human ovarian tumor cell lines in vitro. Preliminary characterization of the autologous ovarian tumor-associated antigen(s) indicates that it may be composed of three large-molecular-weight proteins of 182,000, 164,000, and 122,000 d.
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PMID:Autologous antibodies eluted from membrane fragments in human ovarian epithelial neoplastic effusions. III. Cytotoxic potential in vitro and characterization of antigen(s). 222 Sep 42

A rat tumor-associated antigen with properties similar to those of human carcinoembryonic antigen (CEA) has been detected with rabbit immune sera in extracts of transplantable rat colonic adenocarcinoma, RCA-1. This antigen, termed rat CEA, was also detectable by a monkey antihuman CEA serum and a rat monoclonal antibody to rat CEA. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of perchloric acid extracts of RCA-1 tumor, followed by immunoblotting with the above-mentioned anti-CEA reagents, revealed that rat CEA activity resided in components with a molecular weight of approximately 350 kD. The glycoprotein nature of these components was indicated by positive staining with periodic acid-Schiff. Sephadex G-200 chromatography, as well as Sepharose 4B chromatography with and without sodium dodecyl sulfate indicated that the 350-kD components existed in the extracts as molecular aggregates. The 350-kD material, which had been purified by an affinity column containing rat monoclonal antibodies to rat CEA, reacted with the rabbit and monkey anti-CEA sera. This provided strong evidence that serological activity of rat CEA was confined to the 350-kD components.
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PMID:Isolation and characterization of rat carcinoembryonic antigen. 224 75

Recurrence of the underlying malignancy remains a major cause of treatment failure after autologous bone marrow transplantation (BMT) for patients with lymphoma. In this regard, we have developed an immunotherapeutic approach designed to induce resistance against residual tumor cells persisting after BMT. Previous studies in the model system of 38C13, a lethal B-cell lymphoma of C3H origin, have shown that active immunization with purified tumor-derived surface immunoglobulin (Id), as a tumor-associated antigen, produces resistance to tumor growth. Id immunization of lethally irradiated mice at 3 or 5 weeks after reconstitution with syngeneic bone marrow resulted in significantly prolonged survival after tumor challenge compared with nonspecifically immunized controls. Low levels of idiotype-specific antibody were also demonstrated in the sera of specifically immunized mice at this early time, when other functional studies in the literature of immunocompetence after syngeneic reconstitution might have predicted incomplete recovery. Immunization of mice before lethal irradiation and syngeneic marrow reconstitution also induced significant resistance to tumor challenge, suggesting the persistence of established host antitumor immunity through total body irradiation. These studies demonstrate the feasibility of id immunization in conjunction with bone marrow transplantation.
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PMID:Combined syngeneic bone marrow transplantation and immunotherapy of a murine B-cell lymphoma: active immunization with tumor-derived idiotypic immunoglobulin. 225 10


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