Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Influence of spatial configuration of carcinoma cell populations on the expression of a tumor-associated glycoprotein. 388 Nov 73

Monoclonal antibody AB/3 was produced from a fusion of spleen cells of a human breast cancer cell-primed BALB/c mouse with the murine myeloma cell line P3-NS1-Ag4-1. The antibody reacted strongly with the plasma membrane of human breast cancer cells. Tissue sections of both malignant and benign human mammary carcinomas and tumors of non-breast origin as well as apparently normal tissues were tested with immunoperoxidase. Ninety-six of 124 (77%) primary human breast cancers, 12 of 14 (86%) metastatic breast lesions, and 12 of 44 (27%) benign breast lesions reacted positively. Little or no appreciable reactivity was observed with apparently normal human tissues and carcinomas of non-breast origin, with the exception of colon carcinoma. Antibody AB/3 did not immunoprecipitate any identifiable protein from radiolabeled extracts of the immunizing cell line.
 ...
PMID:A monoclonal antibody (AB/3) reactive with human breast cancer. 389 78

The human colon carcinoma cell line HT-29 was adapted to grow in chemically defined medium (CDM). The spent CDM (S-CDM) was concentrated by Amicon filtration and the crude HT-29 S-CDM purified by 40% saturated (NH4)2 SO4 precipitation. The purified antigen was tested by a microcomplement fixation (MCF) assay against the sera of cancer patients of various histologic types and against the sera of normal donors. Fifteen of 20 (75%) colon cancer, 16/20 (80%) breast cancer sera, 14/19 (74%) lung cancer sera, and 13/20 (65%) miscellaneous carcinoma sera were positive in the MCF. By contrast, 2/21 (10%) melanoma sera, 7/20 (35%) sarcoma sera, and 2/19 (11%) normal sera were positive. These data suggest the presence of a carcinoma-associated antigen in the spent CDM of the HT-29 colon carcinoma cell line adapted to grow in CDM.
 ...
PMID:Presence of a carcinoma-associated antigen(s) in the spent chemically defined medium of a human colon carcinoma cell line. 615 28

We have shown previously that methotrexate pretreatment of murine leukemia and human colon carcinoma cell cultures results in augmented intracellular accumulation of 5-fluorouracil metabolites. Both of these drugs are commonly used for the treatment of women with breast cancer; thus, sequencing of methotrexate before 5-fluorouracil was evaluated in vitro using a human mammary carcinoma cell line, 47-DN. Intracellular 5-fluorouracil accumulation was maximally increased 4-fold in cultures pretreated with 10 microM methotrexate for 24 hr. This enhancement of 5-fluorouracil metabolism was associated with increased intracellular levels of 5-phosphoribosyl 1-pyrophosphate, resulting from the antipurine effect of methotrexate. Brief exposure to exogenous hypoxanthine at physiological concentrations reversed the biochemical synergism between methotrexate and 5-fluorouracil. Other antimetabolites associated with elevations of 5-phosphoribosyl 1-pyrophosphate enhanced intracellular accumulation of 5-fluorouracil up to 2.5-fold. In cloning assays, 18 hr of methotrexate pretreatment followed by 5-fluorouracil resulted in optimal synergistic cytotoxicity, which could be prevented if high concentrations of leucovorin were given between methotrexate and 5-fluorouracil administration. Since these results indicated that optimal breast tumor toxicity in vitro was achieved by 18- to 24-hr sequencing of methotrexate and 5-fluorouracil, clinical toxicity study was carried out to assess whether this drug schedule could be tolerated. Seven patients with advanced cancer were treated with 21 courses of sequential therapy. No toxicity occurred with 38% of treatment courses; mild to moderate leukopenia and mucositis occurred with 29 and 38% of courses respectively. Toxicity was related to treatment interval and not cumulative drug dose or elevated serum methotrexate levels. These clinical results suggest that Phase II studies evaluating 24-hr-sequenced methotrexate and 5-fluorouracil in breast cancer are warranted.
 ...
PMID:Optimal schedule of methotrexate and 5-fluorouracil in human breast cancer. 617 6

Two monoclonal antibodies were produced in mice immunized with the human breast carcinoma cell line MCF-7. One antibody (24-17.1) reacted with MCF-7 and other breast tumor cell lines and detected an antigen of Mr 95,000. This antigen was not breast-specific because other tumor cell lines were also reactive. The second antibody (24-17.2) detected an antigen of Mr 100,000 (initially appearing to be specific for breast tissue and possibly for breast carcinomas) which was present on 10 of 10 malignant breast lines and absent from 41 of 43 other cell lines of differing origins. The antigen could not be detected by absorption or a direct test on normal tissues (liver, kidney, heart, spleen) or on lymphocytes. In addition, the 24-17.2 antibody reacted absorptively with 12 of 13 fresh breast carcinoma samples but not with fresh colon carcinoma samples. The 100,000-Mr antigen detected by the 24-17.2 antibody appeared to be distinct from the other components of normal breast, such as casein, lactalbumin, or milk fat globulin protein. This evidence indicated that the 24-17.2 antibody detected a human breast carcinoma-associated antigen (HBCAA). However, further histologic studies were used to determine the cellular distribution of the HBCAA, which was found on malignant breast epithelium, the epithelium of gynecomastia, and in lesser amounts and differently distributed on normal breast epithelium. The antigen was also found in several other tissues; nonetheless, the anti-HBCAA could be detected in increased amounts in the sera of patients with breast cancer.
 ...
PMID:A human breast tissue-associated antigen detected by a monoclonal antibody. 618 62

The cytotoxic activity of 5'-deoxy-5-fluorouridine (5'-ddFUrd) was established in six cultured human tumor lines: 47-DN and MCF-7 breast carcinomas, MG-63 osteosarcoma, HCT-8 colon carcinoma, Colo-357 pancreatic carcinoma, and HL-60 promyelocytic leukemia. Cells were exposed to a wide range of 5'-dFUrd concentrations (from 0.1 microM to 1.0 mM) for 3, 6, or 24 hrs, and then cloned using standard in vitro clonogenic assays. 5'-dFUrd exhibited its best activity in the 47-DN and MCF-7 breast cell lines and in the MG-63 osteosarcoma line (3-hr LD50 values of 32, 34, and 38 microM, respectively). Less activity was observed in the HCT-8 colon (LD50 = 195 microM) and Colo-357 pancreatic (LD50 = 155 microM) tumor lines, and ver poor activity was noted in the HL-60 leukemia cell line (LD50 = 465 microM). The metabolism of 5'-dFUrd to 5-FU (FUra) and FUra-nucleotides was determined and found to directly correlate with the potency of 5'-FUrd in these cell lines. These results suggest that: (a) there is a marked variation in sensitivity of human cancer cells of different tissue origin to 5'-dFUrd, (b) there is a direct relationship between the sensitivity of human cells to 5'-dFUrd and the ability of the cell to metabolize 5'-dFUrd to FUra, and (c) increasing exposure period of cells to 5'-dFUrd did not markedly alter 5'-dFUrd potency in all human cancer cells examined, with the exception of the 47-DN breast cancer cells.
 ...
PMID:Cytotoxic activity of 5'-deoxy-5-fluorouridine in cultured human tumors. 622 89

Thirty patients with anti-carcinoembryonic antigen (CEA)-producing cancers of the colon, breast, or thyroid were injected with 1 to 2 mCi of Iodine-131 (131I)-labeled, affinity-purified, goat or baboon anti-CEA antibodies. Images were obtained daily for four days. Computerized background subtraction using technetium 99m (99mTC)-labeled compounds was used. Images obtained with and without background subtraction were correlated with other evidence of disease. Activity levels in plasma, urine, and thyroid gland were monitored. Significant deiodination of antibody occurred within the first 24 hours. The mean plasma half-disappearance-time of baboon antibody was significantly longer than the mean half-disappearance-time of goat antibody. With exogenous blockade, total thyroid uptake was less than 0.1% of the injected dose. Without background subtraction, scintigraphic localization of known tumor was possible in one of two patients with colon carcinoma, in three of 20 patients with breast cancer, and in one of five patients with medullary carcinoma of the thyroid. With background subtraction, potential false-positive results could be generated for every patients, depending on the normalization site chosen and the degree of subtraction used. In contrast to results of previous reports, CEA-producing tumor was found to be infrequently localized using highly purified goat or primate radiolabeled anti-CEA. Furthermore, the subtraction technique described by previous investigators may lead to a high false-positive rate.
 ...
PMID:Localization of I-131-labeled goat and primate anti-carcinoembryonic antigen(CEA) antibodies in patients with cancer. 675 92

Of 1,014 human solid tumors of various histologic types, 690 (68%) showed evidence of colony formation within 2 to 4 weeks. Tumors which grew particularly well were colon carcinoma (104/175), melanoma (134/155), lung carcinoma (62/85), breast cancer (100/140), ovarian carcinoma (50/67), and sarcoma (72/122). Histologic examination indicated that the colony-forming cells retained functional and morphologic features similar to those of the original tumor. Plating efficiencies varied between 0.01% and 0.2%, and the numbers of colonies observed formed a direct linear correlation with the number of cells plated. Recovery of viable tumor cells was increased when enzymatic tumor dissociation was used rather than a mechanical method. A simplified, supplemented medium resulted in improved cloning efficiencies when compared to previously reported methods (Hamburger and Salmon, 1977 b).
 ...
PMID:Cloning of human solid tumors in soft agar. 716 Sep 42

CD44 is a transmembrane glycoprotein occurring in several isoforms with different extracellular regions. The various transcripts are encoded by one gene locus containing 20 exons, of which at least 10 can be alternatively spliced in nascent RNA. Isoforms encoded by the variant exons (termed CD44v) are highly restricted in their distribution in nonmalignant tissue as opposed to the standard form of CD44 (CD44s) abundant in many tissues. Specific variant isoforms containing exon 6v have been shown to render nonmetastatic rat tumor cells metastatic. Based on the prominent role in rat metastasis formation, CD44v isoforms were suggested to be involved in human tumor progression. Correlations between prognosis and expression of CD44v have been reported for gastric and colon carcinoma, for non-Hodgkin's lymphoma, and recently for breast carcinoma. We evaluated the expression of CD44 isoforms in node-positive (n = 119) and node-negative (n = 108) cases of breast carcinoma by immunohistochemistry using CD44v exon-specific mAbs. In a subset of 43 cases of high-risk patients, reverse transcription-PCR was used to determine the exon composition of the transcripts. Protein and RNA expression data were probed statistically for their correlation to survival of the patients and clinical risk factors. In contrast to recently published data (M. Kaufmann et al., Lancet, 345: 615-619, 1995), in our cohort disease-free and overall survival data did not indicate significant correlations with the expression of the analyzed isoforms in univariate and multivariate analyses. Comparison of CD44 protein expression with established clinical risk factors for survival such as tumor size (pT1+pT2) and histological grading revealed correlations with the presence of CD44s (P = 0.02 and P = 0.03, respectively) and CD44-9v (P = 0.05 for histological grading). Carcinoma tissues with elevated estrogen and progesterone receptor levels showed positive correlation with CD44-6v (P = 0.001), while a trend for significant coexpression of CD44s and CD44-9v isoforms was observed in estrogen receptor-positive tissues (P = 0.08 and 0.06, respectively). In breast cancer, CD44s, CD44-9v, and CD44-6v are apparently markers for cellular differentiation but not for tumor progression. Our data suggest that steroid hormone receptors may be associated with the in vivo expression of CD44-6v-containing isoforms in human mammary carcinoma.
 ...
PMID:CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer. 758 12

The microbial product wortmannin has previously been shown to be a potent inhibitor of phosphatidylinositol-3-kinase. In view of the potential role of this enzyme in transduction of mitogenic signals, we determined the cytotoxic activity of wortmannin against several human tumor cell lines in vitro. The most sensitive lines included GC3 colon carcinoma, IGROV1 ovarian carcinoma, and CCRF-CEM leukemia (IC-50s ranging from 0.7-2.1 microM). The cytotoxicity of wortmannin was decreased approximately 10-fold by serum-free conditions. Wortmannin was generally less active in low passage human breast cancer cell lines that overexpress either epidermal growth factor receptor or Her2/neu. Wortmannin was also tested for in vivo antitumor activity against seven murine tumor and ten human tumor xenograft models. Activity (> 60% inhibition of tumor growth) was observed in only the C3H mammary carcinoma and the human BxPC-3 pancreatic carcinoma xenograft. In vivo antitumor activity did not correlate with in vitro sensitivity to wortmannin cytotoxicity.
 ...
PMID:In vitro and in vivo antitumor activity of the phosphatidylinositol-3-kinase inhibitor, wortmannin. 765 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>