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

There is considerable interest in the development of anti-idiotypic antibodies as vaccines in a number of diseases, including cancer. We have developed a human anti-idiotypic monoclonal antibody (105AD7) which binds at or very near to the binding site of mouse antitumor monoclonal antibody 791T/36. The 791T/36 antibody binds to a tumor-associated antigen (gp72) expressed on a number of human tumors, including colorectal and ovarian carcinomas and osteogenic sarcoma. This study shows that, in rats and mice, 105AD7 induces delayed-type hypersensitivity to human tumor cells bearing the gp72 antigen. Local transfer of delayed hypersensitivity was also demonstrated using lymphocytes from mice primed with 105AD7. These findings show that the human monoclonal anti-idiotypic antibody 105AD7 is likely to induce cellular immune responses to tumors in cancer patients.
 ...
PMID:Induction of delayed hypersensitivity to human tumor cells with a human monoclonal anti-idiotypic antibody. 187 Jan 51

In previous reports, we demonstrated that adoptively transferred T cells homed to the tumor site (among other sites) and that amplification of immune responses occurred in situ leading to the generation of cytotoxic CD8+ tumor-infiltrating lymphocytes (TIL) and macrophages. The present report extends these findings and shows that following adoptive immunotherapy (AIT) of mice bearing the immunogenic transplanted methylcholanthrene-induced rhabdomyosarcoma (MCA/76-9) there was a differential expansion of CD4+ and CD8+ TIL, the numbers peaking on days 6 and 8, respectively. At this time, CD8+ TIL accounted for the majority of Thy-1+ cells. Northern analyses of RNA extracted from positively selected (by panning) Thy-1+, CD8+ and CD4+ TIL isolated 8 days after AIT indicated the following: in five separate experiments, CD4+ cells expressed three- to sixfold more interleukin (IL)2 mRNA and six- to eightfold more IL6 mRNA than CD8+ cells, while CD8+ TIL expressed three- to sixfold more IL2 receptor (IL2R) mRNA and four- to sixfold more interferon-gamma mRNA than CD4+ cells. TIL cultured in 10% fetal bovine serum failed to release IL2 over a 24-h period, whereas both IL6 and interferon-gamma activities were demonstrable. The level of IL2R mRNA expression was reflected by a vigorous proliferative response of CD8+ TIL to exogenous recombinant IL2 and only a low response by CD4+ cells suggesting that most of the CD4+ TIL were in the resting stage. This was confirmed when it was shown that the incubation of panned CD4+ TIL with IL2 supplemented with irradiated spleen cells and "spent" 76-9 tumor culture supernatant (as a source of antigen) induced expansion of TIL resulting in a population consisting of greater than 90% CD4+ TIL. The overall data suggest that the relatively deactivated state of the CD4+ TIL at this particular time reflects the status of the rejection process in terms of the absence or low concentration of stimulating tumor-associated antigen.
 ...
PMID:Differential in situ expansion and gene expression of CD4+ and CD8+ tumor-infiltrating lymphocytes following adoptive immunotherapy in a murine tumor model system. 190 16

CA-125 is a high-molecular-mass glycoprotein expressed on the cell surface of some derivatives of embryonic coelomic epithelium. This tumor-associated antigen widely used to monitor ovarian carcinomas has been suggested as a promising noninvasive test that could differentiate benign from malignant conditions. Based on results of various studies, CA-125 measurement appears to be very useful in monitoring the response to therapy of ovarian carcinoma and for detecting tumor recurrence as exemplified in Case 1. However, because of the high frequency of false-positive results associated with many benign conditions, CA-125 is of little value as a screening test for ovarian carcinoma. A brief list of the most common benign conditions associated with CA-125 increase includes menstruation, pregnancy, benign pelvic tumors, pelvic inflammatory diseases, ovarian hyperstimulation syndrome, peritonitis, and many diseases leading to pleural effusion or ascites. According to several studies, a marked increase in CA-125 of greater than 1000 units/mL, as seen in Case 2, and even up to 5000 units/mL, could be seen in some benign conditions. This finding further limits the value of CA-125 as a potential noninvasive procedure to differentiate benign from malignant diseases. Although values up to 10,000 units/mL are occasionally seen in patients with ovarian carcinoma, we are reluctant to state that any concentration of CA-125 can be clearly diagnostic of malignancy.
 ...
PMID:CA-125 concentrations in malignant and nonmalignant disease. 193 71

The immunohistochemical analysis using the monoclonal antibodies to the carbohydrate antigens were performed and suggested that CA19-9 is a tumor-associated antigen in gastric cancer, Leb, Ley, CA19-9, CSLEX1, SLX in colorectal cancer and pancreatic cancer, and Lex, Ley, and CSLEX1 in breast and esophageal cancers, respectively. Expression of the type 2 carbohydrate antigens had relation to the prognosis of patients with breast cancer. In colorectal cancer, the patients with high degree of expression of CA19-9 had a poor prognosis, and high risk of distant metastasis. Higher intensity of staining was observed in hepatic in comparison with primary lesion. Thus carbohydrate antigens showed important role as tumor-associated antigens and good indicator for evaluation of prognosis.
 ...
PMID:[Carbohydrate antigens as a tumor-associated antigen and prognostic indicators in carcinomas of the breast, esophagus, stomach, colorectum, and pancreas]. 194 63

After immunization of mice with the human breast carcinoma cell line MCF-7, we produced monoclonal antibody (mAb) BCA 227, which allowed us to characterize a new tumor-associated antigen. This molecule is strongly expressed by well differentiated mammary carcinoma cell lines and by some other tumor cell lines of epithelial origin. Immunohistological study of frozen sections of different tissues and tumors confirmed its expression by tumor cells of epithelial origin, particularly infiltrating duct carcinomas of the breast. The antigen is also expressed, to a lesser extent, by some normal epithelial cells. Its biochemical characterization revealed a Mr 71,000 protein without an N-linked sugar moiety. Six to 40 x 10(3) binding sites are present on breast tumor cell surfaces. Although mAb BCA 227, which was found to be of the IgG2a isotype, did not mediate antibody-dependent cell-mediated cytotoxicity with either human or mouse effector cells, a 50% inhibition of SK-BR5 tumor growth was obtained in nude mice, suggesting that another mechanism is responsible for this inhibition. Biodistribution studies of radiolabeled F(ab')2 fragments of mAb BCA 227 in tumor-bearing nude mice showed a preferential localization in the tumor. All these data are in favor of the use of mAb BCA 227 as an immunodiagnostic tool for breast cancer.
 ...
PMID:A new tumor-associated antigen expressed on breast carcinomas, defined by monoclonal antibody BCA 227. 199 95

Intrapancreatic and subcutaneous (SC) inoculation of cultured pancreatic cancer cells, derived from an induced primary pancreatic cancer in a Syrian hamster, resulted in tumor take in all recipient hamsters. The intrapancreatic allografts grew rapidly, were invasive, and metastasized into the lymph nodes and liver in 2 of 9 cases. In comparison, SC tumors grew relatively slower and formed a large encapsulated mass without invasion and metastases. Histologically, tumors of both sites showed fairly well-differentiated adenocarcinomas of ductal/ductular type resembling the induced primary cancer. Similar to the primary induced pancreatic cancers, tumor cells of both allografts expressed blood-group-related antigens, including A, B, H, Le(b), Le(y), Le(x), and tumor-associated antigen TAG-72. The tumor cells did not express Le(a), CA 19-9, 17-1A, or DU-PAN-2. The expression of these antigens was retained in the metastases and presented the same patterns of reactivity as the allografts. Thus intrapancreatic transplantation provides a rapid model for production of pancreatic cancer with morphologic similarities to human pancreatic cancer.
 ...
PMID:Development of intrapancreatic transplantable model of pancreatic duct adenocarcinoma in Syrian golden hamsters. 200 Sep 35

A single chain glycoprotein with an estimated molecular mass of 160 kD (gp160) was previously identified as a human lung tumor-associated antigen. This tumor marker is shown here to be associated noncovalently with a second 130-kD protein. Sequential immunoprecipitation studies of surface iodinated lung tumor cell lysates reveal that this heterodimeric complex is indistinguishable serologically and structurally from the integrin VLA-2, found originally on activated T lymphocytes and platelets. The VLA-2-like complex expressed on the lung tumors possesses similar characteristic Mg2+ dependent binding of collagen and laminin as observed with VLA-2 on normal cells. RNA analysis indicates that human lung tumors express at least 20 times more VLA-2 alpha chain message than normal adult human lung tissue. The results presented here raise the possibility that the overproduction of VLA-2 may be involved in the pathogenesis of human lung tumors by modulating the invasive and metastatic potential of the tumor.
 ...
PMID:Human lung tumor-associated antigen identified as an extracellular matrix adhesion molecule. 202 22

It is widely believed that antigen heterogeneity and noninternalization of antigen-antibody complexes will severely limit the antitumor activity of monoclonal antibody-drug conjugates. The B72.3 monoclonal antibody binds to a tumor-associated antigen which is heterogeneously expressed in human carcinomas (J. Schlom, Cancer Res., 46: 3225-3238, 1986). We therefore performed studies to assess the degree of internalization of B72.3 antibody-antigen complexes and the level of in vivo antitumor activity that could be achieved with B72.3 conjugated to 4-desacetyl vinblastine-3-carboxhydrazide. Internalization studies were performed on LS174T colorectal carcinoma and OVCAR-3 ovarian carcinoma cells using iodinated B72.3 as well as an iodinated antibody that binds to the human transferrin receptor, IIB21. These data indicated that, in contrast to HB-21, the B72.3 antigen-antibody complex was not internalized. The B72.3-Vinca alkaloid immunoconjugate demonstrated significant antitumor activity against LS174T xenografts, although complete regressions of established tumors were not achieved. Immunohistochemical analyses indicated that the B72.3 antigen was heterogeneously expressed in the LS174T xenografts and that tumor cells which were not killed by high doses of B72.3-Vinca also expressed the B72.3 antigen. These studies indicated that significant antitumor activity may be achieved by monoclonal antibody-drug conjugates even when antigen heterogeneity and noninternalization of antigen-antibody complexes are encountered. The data also suggested that the formulation of antibody-drug conjugate cocktails to counteract antigen heterogeneity may not be sufficient to eradicate all malignant cells within a solid tumor mass.
 ...
PMID:In vivo antitumor activity of a monoclonal antibody-Vinca alkaloid immunoconjugate directed against a solid tumor membrane antigen characterized by heterogeneous expression and noninternalization of antibody-antigen complexes. 203 33

The anti-tumor effector functions of unconjugated MAb in cancer therapy are not fully understood. Direct cytotoxic mechanisms have been demonstrated as well as induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies. If such a humoral response is induced, then an idiotypic cellular response would also be anticipated. Human monoclonal ab2s which mimic a tumor-associated antigen (TAA) (CO17-1A) of colorectal carcinoma (CRC) cells ("the internal image of the antigen") were produced. These ab2s were injected intradermally to patients with metastatic CRC who had been treated with the anti-colon carcinoma MAb 17-1A (ab1). Five out of 12 patients had a specific DTH (delayed-type hypersensitivity) reaction of the tuberculin type, which was proven by immunohistochemical analysis of skin biopsies. Serum ab3 was demonstrated in 4/4 tested DTH+ patients and also in 4 DTH patients. Control patients did not show any skin reactivity. Generation of an idiotypic response induced by the infused antibody (ab1) might be regarded as an active anti-tumor "vaccination". Induction of an idiotypic cellular and humoral cascade might be an important anti-tumor effector function of MAb and should be considered in future strategies for such therapy in cancer patients.
 ...
PMID:Patients treated with a monoclonal antibody (ab1) to the colorectal carcinoma antigen 17-1A develop a cellular response (DTH) to the "internal image of the antigen" (ab2). 204 May 27

To estimate the utility of the tumor-associated antigen CA 15-3 in the diagnosis of patients with breast cancer, this tumor marker was measured preoperatively in 1342 patients. This group included 509 patients with malignant disease (134 breast cancer patients and 375 patients with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast and 738 patients with other benign diseases). The results were compared with those obtained for carcinoembryonic antigen (CEA) in the diagnosis of breast cancer. The CA 15-3 level was above normal (25 U/ml) in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. The CEA level was elevated in 26% of patients with breast cancer (more than 3 ng/ml). There was a good correlation of CA 15-3 levels with the tumor stage of breast cancer. Both CA 15-3 and CEA also were determined in 671 patients who had received initial curative surgery of breast cancer and who regularly attended our follow-up clinic. The CA 15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the postcare period, carcinoma recurred in 205 patients. Of these, 73% had CA 15-3 concentrations above 25 U/ml; only 50% had CEA values above 3 ng/ml (P less than 0.0001). Although neither CA 15-3 nor CEA were sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 was significantly better than CEA in the detection of breast cancer metastases.
 ...
PMID:The value of the tumor marker CA 15-3 in diagnosing and monitoring breast cancer. A comparative study with carcinoembryonic antigen. 206 78


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