Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the potential antigenic heterogeneity which might exist between a primary colon carcinoma lesion and its metastases, we stained the formalin and Zenker's fixed paraffin-embedded tissues from the resection specimens of 12 patients with Duke's Stage C adenocarcinoma of the colon with monoclonal antibody (MAb) B72.3. This MAb previously has been shown to react with a high molecular weight tumor-associated glycoprotein (termed TAG-72), which is selectively expressed in adenocarcinomas versus normal adult tissue. Five to 90% of malignant cells from all primary lesions stained with MAb B72.3 in paraffin-embedded tissue. A significantly diminished percentage of cells stained from the metastases in lymph nodes and distant sites. Pearson correlation coefficients showed that the antigenic expression of the metastasis in the lymph node was a better indicator of the antigenic expression of the metastasis in the distal site than was the primary lesion in the colon. These findings suggest that the effective use of monoclonal antibodies for diagnostic imaging or therapeutic purposes may require the evaluation of the antigenic expression in regional node metastases rather than that of the primary lesion.
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PMID:Phenotypic heterogeneity of a tumor-associated antigen in adenocarcinomas of the colon and their metastases as demonstrated by monoclonal antibody B72.3. 243 5

Over the last few years, many tumor markers have been proposed to clinicians but only a limited number of them meet the necessary criteria to be useful for either screening, diagnosis, prognosis or follow-up of gastrointestinal (GI) tumors. Both CEA and Ca 19-9 have proven to be clinically useful for the detection of recurrent tumors. AFP remains the most useful marker for the follow-up of hepatocellular carcinoma (HCC). Its interest for the early detection of primary tumor is debated. Recent data suggest that assays based on monoclonal antibodies to AFP could be used for detection HCC in high risk populations. Decarboxy-prothrombin assay may be a complement to the AFP test in this localization. In addition to GI hormones, serotonin and urinary 5HIAA, Neuron Specific Enolase appears to be a valuable marker for the follow-up of neuroendocrine tumors of the GI tract. Only a few of the new tumor-associated antigens detected by monoclonal antibodies, appear to be promising clinical ly e.g. Ca50 TAG-72, PAO. Monoclonal antibodies to tumor-associated markers have also been used with other techniques: Immunohistochemistry: this technique is useful to the pathologist for the diagnosis of undifferentiated tumors by demonstrating the presence of specific antigens on tissue samples. Immunoscintigraphy: it can be useful for the detection of either metastases of recurrences of colorectal cancer by using anti-ACE antibodies labeled with Iodine 131 iodine 123 or indium 111. However immunoscintigraphy is less sensitive than both ultrasonography and CT scan for localizing hepatic metastases. At the present time the best indication of this method remains the diagnosis of pelvic recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The value of tumor markers in digestive oncology]. 269 5

Radioimmunoscintigraphy (RIS) using 131I-labelled B72.3, a monoclonal antibody (MoAb) reacting against a tumor associated antigen (TAA) called TAG-72, has been performed in 36 patients with epithelial ovarian cancer. The patients were divided in three groups as follows: 17 patients with primary cancer before any therapy (Group 1); 10 patients studied after a partial therapeutic approach, having either bulky or minimal disease (Group 2); 9 patients with microscopic disease or in clinical remission at the moment of the study (Group 3). All the most important epithelial histotypes, including mucinous, were present. Results were confirmed at surgery and/or by other diagnostic procedures. Immunocytochemical (ICC) and immunocytofluorimetric (ICF) studies on ascitic collections were performed in order to demonstrate specificity of B72.3 and TAG-72 distribution on neoplastic cells. Immunohistochemistry (IHC) on tissue sections was also obtained. No cross reactions between B72.3 and mesothelial cells in the presence of specific uptake by neoplastic cells was found. Moreover, a non-homogeneous distribution of TAG-72 in the neoplastic population was demonstrated by ICF. RIS proved the intraperitoneal presence of disease in 15 out of 17 and in 5 out of 10 patients in Groups 1 and 2, respectively. One out of four (Group 1) and two out of four (Group 2) extraperitoneal metastases were also seen. False negative results were explained by lack of expression of the antigen, size and location of the lesion, and patho-physiological conditions. One false positive due to an aspecific uptake by a post-surgical active scar was also observed in a disease-free patient.
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PMID:Diagnosis of ovarian cancer with radiolabelled monoclonal antibodies: our experience using 131I-B72.3. 271 6

Twenty patients with known ovarian cancer have been investigated in this pilot study to verify the clinical usefulness of radioimaging using the B72.3 monoclonal antibody labelled with iodine-131. No adverse reactions occurred after intravenous injection of B72.3 MoAb. The radioimaging results were compared with those obtained with other diagnostic methods, including computed X-ray tomography and ultrasound. A sensitivity of 85% in the detection of primary ovarian cancers and collections of ascites, and of 84% in the detection of abdominal and extraperitoneal metastases has been demonstrated using this radioiodinated antibody in vivo. No false localization occurred. Immunohistochemical studies showed no cross-reactions between B72.3 MoAb and mesothelial cells, confirming the high specificity of binding between B72.3 MoAb and neoplastic cells in ascites. Negligible uptake of radiolabelled B72.3 MoAb has been demonstrated in the unaffected ovary. The major advantage of using this monoclonal antibody is related to the expression of a recognized antigen (called TAG 72) in mucinous, serous and in differentiated adenocarcinomas of the ovary.
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PMID:A prospective imaging study of 131I-B72.3 monoclonal antibody in patients with epithelial ovarian cancer: preliminary report. 284 8

Variability of tumor-associated antigens among and within human tumor cell groups presents a potential problem in the development and optimization of immunodiagnostic and therapeutic procedures for cancer. We determined the degree of expression of a tumor-associated antigen in the primary and metastatic lesions of 23 patients with infiltrating ductal carcinoma; this was accomplished using monoclonal antibody B72.3, an IgG1 generated against membrane-enriched fractions of human metastatic breast carcinomas and reactive with a 220,000-400,000 d glycoprotein complex, termed TAG-72, and the avidin-biotin complex immunoperoxidase method on fixed tissue sections. Sixteen of the 23 breast carcinomas (70%) demonstrated MAb B72.3 reactivity (range 5% to 100% of tumor cells staining). Reactivity of lymph node metastases was present in 14 of 21 patients (67%). MAb reactivity in metastases to distant sites, including bone, adrenals, liver, skin and effusions, was present in 10 of 18 patients (56%). In one patient, neither the primary carcinoma nor the metastasis to the lymph node demonstrated reactivity. There was a statistically significant positive correlation between MAb B72.3 reactivity in both primary and lymph node metastases (Kendall's Correlation Coefficient = 0.60, p = 0.0006) and between lymph node and distant metastases (Kendall's Correlation Coefficient = 0.48, p = 0.02) of the same patient. No correlation existed between antibody reactivity seen in the primary and that found in the distant lesions of that patient. These studies thus demonstrate that monoclonal antibody B72.3 can detect expression of a tumor-associated antigen in both primary and metastatic infiltrating ductal carcinoma lesions, and may prove valuable in the understanding of tumor biology of metastases and as a means for diagnosing occult disease.
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PMID:Tumor-associated antigen TAG-72: correlation of expression in primary and metastatic breast carcinoma lesions. 299 65

Phorbol ester binding was examined in two lines of murine fibrosarcoma cells. The two cell lines were isolated from the same parent tumor but respond differentially to stimulation with phorbol esters. In one of the lines, these agents stimulate a rapid attachment and spreading response and induce directional migration. The other cell line does not migrate in response to stimulation with phorbol esters and the attachment and spreading response is slow. The cell line which responds actively to phorbol ester stimulation is highly malignant when injected into syngeneic animals while the other line is of low tumorigenicity and is virtually non-metastatic. In spite of these differences, both lines were found in the present study to bind [3H]4 beta-phorbol-12 beta, 13 alpha-dibutyrate in a receptor-mediated fashion. The characteristics of binding were virtually identical between the two cell lines. In additional studies, arachidonic acid metabolism was examined in the same two lines. In the highly responsive line, PMA stimulated a rapid release of [3H]arachidonic acid and its conversion into cyclooxygenase and lipoxygenase products. In the less-responsive line, PMA stimulated a slower release of [3H]arachidonic acid from prelabeled cells. The quantity of arachidonic acid metabolites produced was also much less. These studies suggest that the disparity between the two cell lines in their response to phorbol ester stimulation is not the result of differences in the initial interaction between the cells and ligand but may result from alterations in their signal transductance mechanism. This may be the result of inherent differences in capacity for arachidonic acid metabolism.
Clin Exp Metastasis
PMID:Phorbol ester binding and phorbol ester-induced arachidonic acid metabolism in a highly responsive murine fibrosarcoma cell line and in a less-responsive variant. 308 51

Murine monoclonal antibody (MAb) B72.3 was prepared using a membrane-enriched fraction of breast carcinoma as the immunogen. MAb B72.3 has been previously shown, by in vitro assay, to have a high degree of specificity for carcinomas of the colon, ovary, breast and stomach versus normal adult tissues. The reactive antigen (termed TAG-72) has been purified and characterized. B72.3 IgG was radiolabeled with 131I and utilized for the in situ detection of colorectal cancer metastases. The radiolocalization of MAb B72.3 administered intravenously (i.v.) into colorectal cancer patients was sufficient to allow detection of more than 50% of the lesions by gamma-scanning. Radiolocalization indices (RI) (i.e., cpm 131I-labeled MAb/g of tumor versus cpm/g of normal tissue) were obtained by direct analyses of biopsy materials. Using an RI of greater than 3 to indicate positive localization, tumor lesions at various sites from 17/20 patients were positive. Seventy percent (99/142) of the tumor lesions had RIs of greater than 3, while only 12 of 210 normal tissues had RIs of greater than 3. 131I-B72.3 IgG was also intraperitoneally (i.p.) administered to 10 patients with colorectal cancer. Specific tumor localization via gamma-scanning (confirmed at surgery) was observed in 7/10 patients. Three of the 7 patients were negative for tumor detection by both CAT scan and X-ray but were positive for tumor localization via gamma-scanning of i.p.-administered MAb B72.3. Direct analyses of biopsy specimens of carcinoma and normal tissues demonstrated ratios greater than 70:1 for tumor MAb localization versus normal tissues. No clinical toxicity or adverse reactions were observed with the MAb when administered i.v. and i.p. These results thus demonstrate the efficacy of i.v. and i.p.-administered MAb B72.3 for the radiolocalization as well as potential use of MAb B72.3 in protocols aimed at tumor targeting and in MAb-guided therapy for human epithelial malignancies.
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PMID:[In vivo application of monoclonal antibodies in the management of human carcinomas]. 329 70

The monoclonal antibody B72.3 is a murine IgG1 that is reactive with a wide range of carcinomas while demonstrating little or no reactivity to normal adult tissues. We have shown (27) quantitative analyses demonstrating selective targeting of [131I]B72.3 IgG to metastatic colorectal cancer. We have also shown (28) that (a) B72.3 localization in metastases correlated with the percentage of tumor cells in the biopsy specimen; (b) B72.3 could localize in carcinomas of various degrees of differentiation with best localization in well-differentiated tumors and (c) [131I]B72.3 could penetrate tumor masses, as determined by autoradiographic studies. We report here the various parameters effecting radioimmunoscintigraphy with [131I]B72.3 IgG. Sixteen of 35 patients with colorectal carcinoma had positive scans (without blood-pool subtraction). High circulating TAG-72 antigen levels correlated with positive scans. No dose dependent differences were seen in biodistribution or tumor imaging. The plasma clearance and urinary excretion of [131I]B72.3 and [125I]BL-3 (nonspecific control) were not significantly different. No toxicity was noted. Approximately one-half of patients developed human anti-mouse immune response.
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PMID:Radioimmunoscintigraphy of colon cancer with iodine-131-labeled B72.3 monoclonal antibody. 337 12

The in vitro chemosensitivity of 11 human colorectal cell lines to seven chemotherapeutic agents was determined using a semiautomated tetrazolium-based colorimetric assay (MTT assay). Four of the cell lines were from primary tumors and seven from metastases. Eight lines were from patients with no prior chemotherapy. From assay results, we predict 5-fluorouracil (5-FU) to be the sole active agent of the seven tested. This is based on two observations: the range of drug concentrations which produced 50% inhibition of cell growth was greatest with 5-FU (388-fold versus 5- to 30-fold with the other six agents); and the area under the curve (AUC) which produced 50% growth inhibition was within a clinically achievable range only for 5-FU. Since the assay AUC of 5-FU at 50% inhibition was in a clinically achievable range for only two of the 11 cell lines, we performed a multivariate analysis to explore parameters which predict 5-FU sensitivity. In the best fitting model, sensitivity was positively correlated with cloning efficiency in media and with cell surface TAG-72 (a tumor-associated glycoprotein found on epithelial tumors of ovary, lung, colon, and breast origin) expression. If validated with an in vivo test such as the nude mouse model, the MTT assay could be very useful in new drug screening for colorectal carcinoma, for examining combination chemotherapy for synergy, for exploring strategies for biochemical modulation, and perhaps in individualizing therapy when cell lines can be established from a patient.
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PMID:Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay. 366 87

In previous in vitro studies, we have shown that murine splenocytes or cancer patient lymphocytes incubated in IL-2 become lytic for fresh syngeneic or autologous tumors. We have now performed the adoptive transfer of such lymphokine-activated killer (LAK) cells in a murine B16 metastasis model to test their in vivo efficacy. 1 X 10(8) LAK cells, infused intravenously into C57BL/6 mice with established B16 pulmonary metastases, led to a marked decreased in the number of lung nodules and improved survival. LAK cells administered 3 d after amputation of a tumor-bearing limb also decreased the incidence of spontaneous pulmonary metastases. LAK cells generated from tumor-bearer splenocytes had effects equivalent to those from normal animals, and this antimetastatic effect of the LAK cells did not require the prior administration of cyclophosphamide or other immunosuppressants. Fresh or unstimulated splenocytes had no effect. The antitumor effectors and precursors in vivo and in vitro were Thy-1+. The lymphokine required for the activation appeared to be interleukin 2 (IL-2), since incubation in partially purified supernatants from PMA pulsed EL-4 or Con A-pulsed splenocytes or purified Jurkat IL-2 led to the generation of LAK cells equally active in vivo. The use of IL-2-activated cells may provide a valuable method for the adoptive therapy of human neoplasms as well.
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PMID:Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin 2. 614 Dec 11


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