Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoclonal antibodies (Mabs) to human tumor antigens have potential for tumor detection and treatment. For bladder carcinoma, the detection of exfoliated tumor cells in urinary specimens may be accomplished with Mabs reacting to tumor cell-surface components. This method may be useful for screening and monitoring carcinogen-exposed workers. A Mab generated by our laboratory, 3G2-C6, reacts with high affinity to a cell-surface component expressed by bladder tumor cells. The potential utility of this Mab in detecting exfoliated tumor cells was evaluated in bladder wash specimens. The Mab method detected positive cells in 87% (56/64) of specimens from patients with bladder cancer, including a great majority with grade 1 tumor and carcinoma in situ, superior to the routine cytology done on the same specimens. Cells in specimens from patients with urinary calculi, chronic cystitis, and history of bladder cancer also reacted with the Mab, suggesting that other stimuli can induce antigen expression. The Mab method can also be performed on urine samples, thus allowing evaluation of the ability of the Mab to identify premalignant, malignant, and other abnormal exfoliated cells in urine. The Mab method represents a unique opportunity to develop noninvasive detection of bladder cancer and to monitor and screen bladder cancer high-risk groups.
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PMID:Detection of exfoliated bladder cancer cells by monoclonal antibodies to tumor-associated cell surface antigens. 207 18

Two murine monoclonal antibodies (Mabs), 3G2-C6 and C3, which react to surface components on human bladder carcinoma cells, were produced using cultured human bladder tumor cells as immunogens. The expression of these antigens is highly restricted to malignant cells, and as such these Mabs are potentially useful for cancer diagnosis and treatment. We report here the immunochemical characterizations and molecular size determinations of these two Mab-reacting bladder tumor-associated antigens. The 3G2-C6 antigen has a molecular weight of 92,000, while the C3 antigen is a macromolecule with a molecular weight of about 600,000, consisting of 4 subunits of identical size, as determined by high pressure liquid chromatography gel filtration and sodium dodecyl sulfate and gradient-gel electrophoresis. The apparent affinity constants for the binding of these two Mabs and the number of antigenic determinants per cell were determined in 4 human bladder tumor cell lines (MGH-U1 through MGH-U4) with different degrees of malignancy. The apparent affinity constants for 3G2-C6 ranged from 1.8 x 10(-10) to 1.7 x 10(-8) M, while those for C3 ranged from 1.9 x 10(-9) to 4.4 x 10(-8) M. The number of antigenic determinants per cell ranged from 3 x 10(5) to 2.9 x 10(3) for 3G2-C6 and from 2 x 10(6) to 1.2 x 10(5) for C3. This coincides with our earlier observation that bladder tumor cells of higher malignancy tend to express higher numbers of determinants of these antigens, particularly of 3G2-C6. Very low levels of both of the antigens were released from the cells; less than 10% of the antigens could be detected in 3-day spent culture medium. Radioactively labeled Mabs were used to assess the stability of the antibody bound to MGH-U1 cells. More than 70% of 3G2-C6 remained bound to the cell after 24 h, whereas more than 60% of C3 was lost from the cell and recovered in the culture medium as small fragments. This information may be useful for the clinical applications of these Mabs, including the improvement of in vitro detection of bladder cancer through identification of exfoliated tumor cells and determining the potential utilities of these Mabs in in vivo localization of in situ and metastatic bladder tumors.
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PMID:Immunochemical and biochemical characterizations of two monoclonal antibody-reacting antigens associated with human bladder carcinoma. 281 13

We have conducted two studies to evaluate the efficacy of using a specific monoclonal antibody (McAb) to detect exfoliated tumor cells in bladder washings. This is a preliminary step toward the development of immunological methods to improve the cytologic detection of bladder carcinoma. In this study, McAb 3G2-C6 was used. The McAb reacts to a bladder tumor-associated cell-surface antigen expressed in bladder tumors of various grades. Bladder washings from patients with and without carcinoma were stained with the McAb using two different indirect immunofluorescence methods (Methods A and B). The results of the immunological studies were compared with those obtained from the cytology laboratory and these in turn, were evaluated against the histopathological diagnosis of respective patients at the time the samples were taken. Immunofluorescence method A detected positive cells in 87% (56/64) of specimens from bladder cancer patients, including 18 of 19 from patients with grade 1 tumor. This method also had a low false-positive rate; only one of 17 specimens from patients with other urinary disorders had positively reacting cells. Immunofluorescence method B, evaluating a second group of specimens, detected positive cells in 68% (15/22) of specimens from patients with carcinoma, and in only one of 17 controls. However, it also identified positive cells in specimens from patients with chronic cystitis and urinary calculi. Overall the results of these studies indicate that the McAb method is superior to the routine cytology in detecting tumor cells in bladder washing specimens. More work must be done, however, to improve the specificity of the method before it can be used as an aid for routine tumor detection.
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PMID:Detection of tumor cells in bladder washings by a monoclonal antibody to human bladder tumor-associated antigen. 304 45

Monoclonal antibodies (McAbs) to human bladder carcinoma were generated by fusion of NS-1 mouse myeloma cells with spleen cells from BALB/c mice immunized with either cultured human bladder cancer cells or cells obtained from a fresh surgically removed bladder tumor. Four hybridomas which reacted strongly with bladder tumor cells and not to normal skin fibroblasts or urothelial cells were identified and cloned by limiting dilution to obtain monoclonality. One McAb, 3G2-C6, raised with cultured tumor bladder cells MGH-U1 (EJ) as the immunogen reacted more strongly to the bladder tumor lines tested than any of the other McAbs resulting from various fusion experiments. Hybridoma 3G2-C6 was found to secrete murine immunoglobulin G1 and to produce high titer ascites fluid when grown in BALB/c mice. Results from quantitative enzyme-linked immunosorbent assays on a panel of more than 35 cell lines demonstrated that McAb 3G2-C6 reacted with several bladder tumor cell lines 50 to 90 times more than with normal transitional urothelium. Two kidney and two testicular tumor lines also bound 10 times more 3G2-C6 than with normal cells. The 3G2-C6 antigen was only marginally detected on a number of other cancer and noncancerous cells tested such as breast and lung tumor cells, melanoma, fetal cells, and peripheral blood lymphocytes. To identify the antigen 125I-labeled membrane components from MGH-U1 cells were extracted with detergent, immunoprecipitated with Protein-A bound 3G2-C6, and analyzed by sodium dodecyl sulfate-gel electrophoresis. This revealed that McAb 3G2-C6 binds to a Mr 90,000 cell surface component. Indirect immunofluorescence microscopy with fluorescein isothiocyanate-anti-mouse immunoglobulin G also identified the antigen on the surface of cultured and fresh tumor cells and detected the antigen on 16 of 17 Grade 3 bladder tumor specimens as well as on some kidney and testicular tumor cells. This study confirms the potential of the hybridoma technique for producing McAbs capable of identifying tumor associated antigens which may be useful in the diagnosis and treatment of bladder cancer.
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PMID:Production and characterization of mouse monoclonal antibodies to human bladder tumor-associated antigens. 389 80