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)

Although there is extensive data available on Ca2+ effects in normal tissues, comparatively little is known about its effects or regulation in tumor cells. The present studies were undertaken to investigate whether various extracellular calcium concentrations could modulate the expression of the tumor-associated antigen (TAA) recognized by monoclonal antibody (MAb) 44-3A6. It is highly expressed by the human lung adenocarcinoma cell line A549 and has been shown to be a 40-kD integral plasma membrane protein. Treatment of the A549 cell line with various concentrations of exogenous calcium showed a dose-dependent rise in the internal free calcium levels up to 2.4-2.9 mM (external calcium treatment). At higher concentrations, the internal calcium level showed a decline, indicating a higher calcium efflux. The calmodulin-dependent Ca(2+)-ATPase enzyme involved in calcium homeostasis was assayed under these same conditions. The enzyme activity increased with increasing external calcium concentrations showing a 5-fold increase in cells treated with 4.05 mM calcium. These data suggest that as the internal calcium approaches toxic levels, the Ca(2+)-regulated ATPase activity increases to reduce the calcium overload within the cell. Employing Western blot analysis and immunoperoxidase staining studies, this report shows that the antigen recognized by MAb 44-3A5 on A549 cells increased with an increase in calcium concentration. Evidence that this antigen is phosphorylated is presented using Western blot analysis of a radiolabeled antigen-enriched plasma membrane fraction. The previously reported subcellular localization, and now the phosphorylation and responsiveness to calcium by this TAA, gives it the properties predicted to be seen in a calcium 'pump-like' molecule. Thus, these studies support the hypothesis that this TAA may be important in intracellular calcium concentration control or that it is regulated via some calcium-mediated process.
Tumour Biol 1992
PMID:Changes in the expression of the tumor-associated antigen recognized by monoclonal antibody 44-3A6 in A549 cells due to calcium. 138 56

TAG-72 is a tumor-associated antigen identified by the monoclonal antibody B72.3. Serum levels of TAG-72 were measured in patients with non-malignant and malignant disease. TAG-72 is not a specific marker of cancer and slightly elevated levels of this antigen can also be detected in the serum of healthy subjects. However, our results show that specificity (92%) and positive predictive value (86%) of this marker are very high. TAG-72 levels above the cut-off limit of 6 U/mL were found in patients with tumors of various organs, including gastrointestinal, ovarian, lung and breast cancer. TAG-72 assay sensitivity is related to tumor stage with values being highest with advanced disease, especially in patients with gastric cancer and lung adenocarcinoma.
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PMID:Tumor associated glycoprotein-72 (TAG-72) levels in patients with non-malignant and malignant disease. 139 66

This report describes the development and applicability of a tumor-associated-antigen-specific immune complex (IC) detection assay to denote the presence of tumor cells in a cancer host. This assay utilizes a murine monoclonal antibody, AD1-40F4, which was produced to a glycoprotein tumor-associated antigen (TAA). In Western blot, the murine monoclonal antibody recognized a 90-100 kD subunit of the antigen. This antigen is immunogenic in cancer patients and induces formation of endogenous antigen-antibody complexes. Analysis of 250 sera from normal individuals and 419 sera from cancer patients revealed that a significantly (P less than .0005) greater proportion (234/419; 55.9%) of cancer sera was positive for the marker than the normal sera (8/250; 3.2%). The incidence of the 90 kD-TAA-specific-IC was consistently and significantly higher in melanoma (58.5%; 38/65), sarcoma (52.9%; 83/157), and carcinoma of breast (50.9%; 58/114), lung (68.2%; 30/44), and colon (64.1%, 25/39) than in the normal group. The age of serum donors did not affect the incidence of the reactivity. Also, at least in the cancer group the gender of the serum donor did not affect the incidence of the 90 kD-TAA-specific-IC positivity. In a retrospective study where sequential serum samples obtained postoperatively from 105 patients with melanoma were analyzed, the 90 kD-TAA-specific-IC could be detected in 72 (69%) of patients several years before the appearance of clinically detectable disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monoclonal antibody-based ELISA to detect glycoprotein tumor-associated-antigen-specific immune complexes in cancer patients. 140 55

Murine IgG3 monoclonal antibody (Mab) 1H10, which recognizes a tumor-associated antigen expressed on the surface of more than 40% of human cervical carcinoma tissues, was used for in vivo localization and therapy of cervical tumor xenografts. A human cervical carcinoma cell line, CaSki, was used as our experimental tumor system. Mab 1H10 antigen expression on the surface of CaSki cells was found to be cell-cycle independent. The ability of Mab 1H10 F(ab')2 to bind to CaSki tumor xenografts was verified by direct immunohistochemical staining of thin tumor sections with a Mab 1H10-peroxidase conjugate. Radioimmunoscintigraphy of nude mice bearing CaSki tumors after iv administration of [131I]1H10 F(ab')2 showed clear tumor images 48 hr after Mab injection. Radiolabeled Mab 1H10 F(ab')2 was found to specifically localize in solid CaSki tumors 96 hr after antibody injection. Radioactivity in tumor tissue was 4 times higher than that in kidney tissue and over 6 times higher than that in liver tissue. Mab 1H10 F(ab')2 binding to xenografted CaSki tumors was 17 times greater than a control IgG3 F(ab')2 after 96 hr. Therapy of athymic mice bearing established CaSki tumors with three iv injections of 100 microCi [131I]1H10 F(ab')2 resulted in extensive tumor necrosis and significant suppression (p < 0.05) of tumor growth compared to that in control mice. These results indicate that Mab 1H10 F(ab')2 may be clinically useful for detection or treatment of cervical cancer.
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PMID:Localization and therapy of human cervical tumor xenografts with radiolabeled monoclonal antibody 1H10. 142 9

Bispecific antibody (bsAb) which binds to CD3 and a tumor-associated antigen can induce lysis of tumor cells by T cells. Lymphocytes targeted by bsAbs are also capable of inhibiting the growth of human xenografts in athymic mice. However, little is known about the impact of this form of therapy in immunologically intact animals. The 38C13 murine B-cell lymphoma model is well suited for the study of bsAb therapy. BsAb, consisting of an IgG that is monospecific for both CD3 and the idiotype expressed by V 38C13 cells, was obtained from hybrid-hybridoma supernatant. Immunocompetent C3H mice were inoculated with V 38C13 cells and treated 2 days later with antibody. Over 90% of mice treated with monospecific antibody died of lymphoma, while only 27% of mice treated with bsAb developed tumor and died. In studies of bsAb/IL-2 synergy, treatment was delayed until 5 days after inoculation to allow for a larger tumor burden at the time of treatment. IL-2 was administered on days 3 to 6. All mice treated with IL-2 alone died of lymphoma, as did 75% of mice treated with bsAb alone. Only 18% of mice treated with both bsAb and IL-2 developed lymphoma. Thus, therapy with bsAb and IL-2 eliminated a tumor load 100- to 1000-fold greater than can be eliminated by therapy with anti-tumor antibody alone. These studies demonstrate the value of using immunocompetent animal models, and support the further exploration of bsAbs as an immunotherapy for human malignancy.
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PMID:Bispecific IgG and IL-2 therapy of a syngeneic B-cell lymphoma in immunocompetent mice. 142 8

This review summarizes several strategies under investigation for targeted delivery of antineoplastic agents to tumor cells, which avoids normal tissue damage. Monoclonal antibodies remain the molecules of choice for targeted therapy, and several improvements to immunotargeting are discussed. These improvements include the use of novel radioisotopes, cytokines, new linkers for chemotherapeutic drugs, more potent drugs, and improved immunotoxins. Bifunctional antibodies, in which one antigen-binding site recognizes a tumor-associated antigen and the other an antineoplastic agent, have been investigated for radioimmunotherapy and for the activation of cytotoxic cells for targeted immunotherapy. The activation of relatively nontoxic prodrugs by antibody-enzyme conjugates is increasingly being investigated in an effort to reduce the systemic toxicity associated with conventional chemotherapy. Finally, the use of liposomes as carriers of drugs or as activators of macrophages is described.
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PMID:Targeted delivery of biologic and other antineoplastic agents. 145 28

Tumor-associated antigens that are expressed in lymphosarcoma B cells of cattle with enzootic bovine leukosis had been analyzed in terms of their reactivity with 13 monoclonal antibodies (MAB). By use of flow cytometry and radioimmunoprecipitation, 1 of the MAB (c143) that recognized a tumor-associated antigen cross-reacted with blood lymphocytes (BL) from various mammalian species. By use of flow cytometry, the c143 MAB reacted with 10 to 49% of BL derived from human beings, mice, dogs, horses, pigs, llamas, sheep, goats, and cattle. Titer of the c143 MAB with BL from horses, pigs, human beings, and llamas ranged between 1:6.0 x 10(4) and 1:5.3 x 10(5); titer associated with BL of goats and sheep was 1:1.6 x 10(6); and that associated with BL of cattle was 1:4.3 x 10(7). The c143 MAB specifically immunoprecipitated 3 homologous proteins from cell extracts of caprine, ovine, and bovine BL (32-, 34-, and 36- to 37-kDa bovine proteins; 31-, 32-, and 36- to 37-kDa caprine proteins; and 31.5-, 33-, and 36- to 37-kDa ovine proteins), but none was immunoprecipitated from human, murine, canine, porcine, and llama BL. These results indicate that the avidity of the c143 MAB in binding to BL from ruminants (eg, goats, sheep, and cattle) is higher than that to BL from human beings, mice, dogs, horses, pigs, and llamas. In sheep, the c143 MAB could immunoprecipitate the aforementioned proteins from BL of the Suffolk breed, but not BL from the Corriedale breed, whereas the c143 MAB immunoprecipitated apparently identical proteins from BL of 4 breeds of cattle.
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PMID:Cross-reactivity between a monoclonal antibody that recognizes a tumor-associated antigen on bovine lymphosarcoma cells and blood lymphocytes from various mammalian species. 146 90

B700 is a murine melanoma antigen that is closely related to, but distinct from, serum albumin. The present study examined the metabolic fate and anatomic distribution of radioiodinated B700 and mouse serum albumin (MSA) administered s.c. to mice. In blood, both proteins were associated with the plasma fraction where the halflife of B700, a glycoprotein, was 0.5 days, compared to 2.7 days for MSA. Of particular interest was the observation that B700, a 67 kD anionic protein, was excreted primarily in urine. The selective B700-proteinuria did not alter urinary volumes or produce hematuria or edema. SDS-polyacrylamide gel electrophoresis and western blot analysis using the H-2-3-3 B700-specific monoclonal antibody revealed that B700 proteinuria occurred in B-16 murine melanoma bearing animals but not in control mice. These studies demonstrate that the tumor-bearing host readily distinguishes between very similar normal protein (MSA) and tumor-associated antigen (B700) molecules and processes them differently.
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PMID:Proteinuria of B700, a 67 kD albumin-like melanoma-specific antigen. 149 72

Six permanent human tumor cell lines (OV-MZ-1 to 6) were established from 6 patients with serous adenocarcinomas of the ovary. These cell lines were derived from both solid tumors and ascites, from pre-treated and untreated patients, and are available over a range of in vitro passage numbers. The tumor cells grow as monolayers and develop foci of "piled-up' cells in confluent cultures. Flow cytophotometry showed that all the lines exhibited DNA hyperdiploidy with DNA tetraploidy in one cell line and DNA aneuploidy in the other cell lines. The mean population doubling time ranged from 24 to 52 hr. Transmission electron microscopy demonstrated that the tumor cells of all cell lines exhibited features of epithelial differentiation such as desmosomes and intracellular gland-like lumina. Immunocytochemical analysis showed that the co-expression of cytokeratins and vimentin, which is a feature of ovarian serous cystadenocarcinomas in situ, was fully preserved in the majority of cell lines. The main cytokeratin polypeptides expressed were numbers 7, 8, 17, 18 and 19. The tumor-associated antigen CA-125, but not CEA, was shed in the culture supernatant. This was in accordance with FACScan analysis of the cell lines and the level of CA-125 and CEA in the patients' serum. The estrogen and progesterone receptors were negative both in the cell lines and in the original tumors. These new ovarian carcinoma cell lines will be valuable models for further investigations into a variety of biological properties.
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PMID:Morphological, immunohistochemical and biochemical characterization of 6 newly established human ovarian carcinoma cell lines. 150 Feb 30

I-A+ epidermal antigen-presenting cells (APCs, Langerhans cells) have been shown to present tumor-associated antigens (TAAs) and to induce tumor immunity in vivo. This study examined the effects of ultraviolet radiation (UVR) and the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha) on the ability of epidermal cells (ECs) to induce or to elicit immunity against the murine spindle cell tumor S1509a. Naive syngeneic mice were immunized three times at weekly intervals with ECs that had been cultured in GM-CSF for 18 h and then pulsed with TAA derived from S1509a. This resulted in protective immunity against subsequent tumor challenge, providing a model to study the conditions required for sensitization against TAAs by epidermal APCs. Culture of ECs in GM-CSF was required for induction of significant protective tumor immunity, and UV irradiation or incubation in TNF-alpha for 2 h after GM-CSF incubation abrogated the immunostimulatory effect of GM-CSF. However, unlike UVR, TNF-alpha did not significantly inhibit the induction of immunity when ECs were exposed to TNF-alpha before overnight incubation in GM-CSF, together with GM-CSF, or after pulsing with TAA, and anti-TNF-alpha antibody treatment did not abrogate the effects of UVR on this system. Furthermore, TNF-alpha incubation of ECs augmented their ability to elicit delayed-type hypersensitivity (DTH) and also enhanced elicitation of DTH by GM-CSF-cultured ECs, whereas UV-irradiation reduced it in a dose-dependent fashion. Taken together, these results demonstrate that GM-CSF, TNF-alpha, and UVR are significant regulators of tumor antigen presentation by epidermal APCs and that the effects of the cytokines examined differ with regard to induction or elicitation of immunity.
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PMID:Tumor antigen presentation by epidermal antigen-presenting cells in the mouse: modulation by granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and ultraviolet radiation. 150 78


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