Horizontal transmission of malignant conditions rediscovered.
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Animals↗
Biomedical subjects
D M Goldenberg
Publications and source records attributed to D M Goldenberg.
The role of radioimmunodetection in the management of testicular cancer.
Five patients with testicular cancer received an intravenous injection of between 1 and 2.5 mCi of iodine 131-labeled antibody to human chorionic gonadotropin (HCG) or alpha-fetoprotein (AFP), followed by total-body photoscanning to visualize areas of abnormal radioactivity. Blood-pool and nontarget sites of radioactivity were reduced by subtracting the images derived by injection of technetium Tc 99m-labeled components from the iodine 131 scans. The HCG-immune scintiscans proved helpful in tumor localization and in the selection of appropriate therapy, while the AFP scan presented corroborative evidence of widespread tumor. Elevated serum levels of these two markers did not hinder successful tumor detection and localization by this method of radioimmunodetection. Cancer radioimmunodetection with antibodies to HCG and to AFP appears to be a useful procedure for the pretreatment and posttreatment evaluation of patients with testicular cancer and can reveal sites of tumor not detected by other methods.
Adult↗
Malignant potential of murine stromal cells after transplantation of human tumors into nude mice.
Human malignant cancer tumors grafted into nude mice produce tumors containing both human cancer cells and the host's stromal cells. After short-term propagation of these tumors in vitro, the murine mesenchymal cells appear transformed and are tumorigenic in nude mice. However, established human cancer cell lines fail to similarly after adjacent murine stromal cells when used to produce tumors in nude mice. These experiments suggest that cancer cells may recruit normal cells to become malignant, qualifying the view of the clonal (unicellular) origin of cancer.
Adenocarcinoma↗
Experimental studies of tumor radioimmunodetection using antibody mixtures against carcinoembryonic antigen (CEA) and colon-specific antigen-p (CSAp).
Experiments with the GW-39 human colonic carcinoma growing in hamsters showed that injection of radioactive antibody to a colorectal-specific, tumor-associated antigen, CSAp, results in better tumor radiolocalization than was seen previously with radioantibodies to carcinoembryonic antigen (CEA). However, a mixture of both radioactive antibodies resulted in potentiation of CEA-tumor radioimmunodetection without affecting CSAp-tumor radiolocalization. Hence, multi-marker antibody mixtures may be the method of choice in cancer radioimmunodetection.
Animals↗
CEA (carcinoembryonic antigen): its role as a marker in the management of cancer.
A consensus Development Conference was held at the National Institutes of Health from September 29-October 1, 1980, to address issues concerning the role of carcinoembryonic antigen (CEA) as a marker in the management of cancer. The panel met following formal presentations and discussions to assess the issues based on the evidence presented. These issues included: Should CEA be used in cancer screening? Is CEA helpful in cancer diagnosis? What does CEA tell about the extent and outcome of cancer? Is CEA helpful in monitoring cancer treatment? This paper constitutes the panel's findings.
Carcinoembryonic Antigen↗
Human chorionic gonadotropin radioantibodies in the radioimmunodetection of cancer and for disclosure of occult metastases.
Radioimmunodetection (RaID) of tumors containing human chorionic gonadotropin (hCG; choriogonadotropin) was evaluated in 25 patients by injecting 131I-labeled goat antibody IgG against hCG and performing total-body photoscans with a gamma scintillation camera 24 and 48 hr later. All 10 testicular cancer patients with proven tumor sites had positive RaID results, whereas three cases without known tumor were negative. Four patients with hydatidiform mole and one with degenerative products of conception showed positive RaID results consistent with elevated serum hCG titers. Two putatively false-positive results were obtained in patients with lung or ovarian cancer, whereas a false-negative metastasis to the liver of a patient with lung cancer and an elevated serum hCG titer was observed. Of 14 tumor sites found by RaID in 10 testicular cancer patients, 4 were revealed by RaID prior to any other detection method used and provided a lead time to definitive diagnosis by other measures of a few days to greater than 1 yr. Although a number of patients had high serum hCG levels, even exceeding 3 microgram/ml, the xenogeneic antibody was capable of localizing in tumor. No adverse effects were noted in any of the patients studied. Thus, hCG RaID appears to be a safe and effective method of detecting and locating hCG-producing tumors and has been found to disclose occult testicular cancers.
Adenocarcinoma↗
Characterization of colon-specific antigen-p and isolation of immunologically active tryptic peptides.
CSAp was originally detected with antisera to an unfractionated extract of GW-39 human colonic carcinoma xenografts, and was determined to be restricted to normal and neoplastic gastrointestinal tissues and certain ovarian tumors. Gel filtration chromatography of GW-39 extract on Sepharose 4B columns reveals that more than 90% of the CSAp is associated with the void volume fraction. The smaller m.w. CSAp fraction is a population of fragments heterogeneous in respect to size but immunologically identical to the void CSAp. Efforts to dissociate intact CSAp from the void fraction by treatment with solutions of high ionic strength, SDS, non-ionic detergents, and 1 M lithium bromide have not been successful. CSAp is a glycoprotein that binds to Sepharose-concanavalin A and is distinct from other known tumor-associated antigens in immunologic and physicochemical properties. The antigen shows sensitivity to high concentrations of chaotropic reagents and especially to sulfhydryl reagents, even in low concentrations, which supports earlier results indicating that the CSAp antigenic determinant is associated with the polypeptide chain rather than with a carbohydrate moiety. CSAp has been reduced in size by either sonication or partial tryptic digestion. The former produces immunologically active fragments, heterogeneous in respect to size, that resemble the smaller size CSAp, whereas the tryptic digest generates 2 distinct peptides. The major tryptic peptide is found to have an approximate molecular size of 120,000, as determined by gel filtration.
Animals↗
Experimental radioimmunotherapy of a xenografted human colonic tumor (GW-39) producing carcinoembryonic antigen.
Experiments were undertaken to evaluate the antitumor effects of 131I-labeled goat antibody immunoglobulin G prepared against carcinoembryonic antigen in hamsters bearing the carcinoembryonic antigen-producing GW-39 human colonic carcinoma. At a single injection of 1 mCi 131I and higher, a marked growth inhibition of GW-39 tumors, as well as a considerable increase in the survival time of the tumor-bearing hamsters, could be achieved. At a dose of 1 mCi, the radioactive affinity-purified antibody appeared to be superior to radioactive normal goat immunoglobulin G in influencing tumor growth and survival time, but no significant difference could be seen at the higher dose of 2 mCi given. Radiobiological calculations indicated that the tumors received, at up to 20 days after therapy, 1325 rads for the specific antibody and only 411 rads for the normal immunoglobulin G preparation. These findings encourage the further evaluation of antibodies to tumor markers for isotopic cancer therapy.
Animals↗
Clinical radioimmunodetection of cancer with radioactive antibodies to human chorionic gonadotropin.
Injection of iodine-131-labeled goat immunoglobulin G antibody to human chorionic gonadotropin (hCG) into patients with hCG-secreting trophoblastic and germinal tumors permitted tumor detection and location by external gamma-ray scintigraphy. Excision of one of the metastatic tumors located by this method indicated a tumor/nontumor ration of 39.29. The method appears to offer a new clinical tool for precisely locating hCG-producing tumors in the body, even when tumor identification by other clinical methods has failed.
Antibodies↗
Clinical studies on the radioimmunodetection of tumors containing alpha-fetoprotein.
This study reports the use of radiolabeled antibodies to alpha-fetoprotein for the detection and localization of hepatocellular and germ cell carcinomas. Twelve patients with histories of histologically-confirmed neoplasia received a total dose between 1.0 and 4.4 mCi of 131I-labeled goat IgG prepared against human alpha-fetoprotein. Total-body photoscans were taken with a gamma scintillation camera at various intervals after injection of the radioactive antibody. Computer subtraction of radioactive technetium background images from the antibody 131I scans permitted the visualization of all tumor sites known to be present in 4 patients with either primary hepatocellular cancer or metastatic germ cell carcinoma of the testis. In contrast to the results with the specific antibody, radioactive normal goat IgG given to one of these patients with metastatic embryonal carcinoma of the testis failed to show equivalent localization. Among 8 patients with diverse neoplasms not believed to contain alpha-fetoprotein, 5 of 19 tumor sites showed radioactive antibody accretion, although significantly less than in the patients with liver or testicular cancer. Circulating antigen levels of up to 15,000 ng per milliliter did not prevent successful tumor imaging after intravenous injection of the radioantibody. This investigation indicates that alpha-fetoprotein-containing tumors can be detected and localized in vivo by the method of radioimmunodetection.
Adult↗
Radioimmunodetection of colorectal cancer.
This study examines the accuracy of colorectal cancer radioimmunodetection. Twenty-seven patients with a history of histologically-confirmed colonic or rectal carcinoma received a high-titer, purified goat anti-CEA IgG labelled with 131-I at a total dose of at least 1.0 muCi. Various body views were scanned at 24 and 48 hours after administration of the radioantibody. Three additional cases were evaluated; one had a villous adenoma in the rectum and received the 131-I-labelled anti-CEA IgG, while two colonic carcinoma patients received normal goat IgG labelled with 131-I. All of the 7 cases with primary colorectal cancer showed true-positive tumor localization, while 20 of 25 sites of metastatic colorectal cancer detected by immune scintigraphy were corroborated by other detection measures. The sensitivity of the radioimmunodetection of colorectal cancers (primary and metastatic) was found to be 90% (true-positive rate), the putative specificity (true-negative rate) was 94%, and the appraent overall accuracy of the technique was 93%. Neither the case of a villous adenoma receiving the anti-CEA IgG nor the two cases of colonic cancer receiving normal goat IgG showed tumor radiolocalization. Very high circulating CEA titers did not appear to hinder successful tumor radiolocalization. These findings suggest that in colorectal cancers the method of CEA radioimmunodetection may be of value in preoperatively determining the location and extent of disease, in assessing possible recurrence or spread postoperatively, and in localizing the source of CEA production in patients with rising or elevated CEA titers. An ancilliary benefit could be a more tumor-specific detection test for confirming the findings of other, more conventional diagnostic measures.
Antibodies, Neoplasm↗
Comparison of the sensitivity of the indirect, antibody-conjugated and the triple-bridge immunoperoxidase methods for immunohistochemical detection of carcinoembryonic antigen.
A comparison between two immunoperoxidase staining procedures, a triple-bridge and an indirect, antibody-conjugated method, was made to determine the relative sensitivity of each technique in the detection of carcinoembryonic antigen (CEA) in routine tissue sections. The enzyme-antibody conjugates for the indirect procedure were prepared according to the method of Nakane and Kawaoi (1974). The indirect, antibody-conjugated method, proved to be slightly more sensitive than the triple-bridge by two criteria. First, CEA could be localized using higher dilutions of the primary antiserum by the indirect technique, and secondly, tissues were shown to stain for CEA in specimens with lower tissue CEA levels by the indirect procedure than by the triple-bridge method. The preparation of enzyme-antibody conjugates is a relatively simple procedure and, in addition, the conjugates will remain stable when kept frozen or at 4 degrees C. Background staining due to non-specific interaction of the conjugate with the tissue can be eliminated easily by incubation with normal serum. These results indicate that the indirect, antibody-conjugated method can be used to enhance the staining of CEA in routine tissue sections.
Antibodies, Anti-Idiotypic↗
Colonic tumorigenesis in rats with 1,2-dimethylhydrazine.
Subcutaneous injections of the carcinogen dimethylhydrazine in inbred Fischer 344 male rats induced squamous-cell carcinomas in the ear canal, adenocarcinomas in the small bowel and duodenum, and adenomas and adenocarcinomas in the large bowel. The incidences of the tumors induced in the large bowel and ear canal were dose-related. As for tumors of the large bowel, the average size of adenomas was less than that of adenocarcinomas with massive infiltration beyond the muscularis mucosa. The average size of early adenocarcinomas was greater than that of adenomas but less than that of adenocarcinomas with massive infiltration beyond the muscularis mucosa.
Adenocarcinoma↗
Xenogeneic antitumor antibodies in cancer radioimmunodetection.
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Animals↗
Radioimmunodetection of cancer with radiolabeled antibodies to alpha-fetoprotein.
Sixteen patients with histologically proven malignant neoplasia were investigated by radioimmunodetection, using goat anti-alpha-fetoprotein (AFP) antibody radiolabeled with 131I. Images of the chest and abdomen were made with a scintillation camera, usually at 24 and 48 hr following injection of 1 to 2.5 mCi of radioiodinated antibody. Computer-assisted processing for the subtraction of 99mTc background radioactivity was used to enhance the detection and localization of tumors visualized by immune scintigraphy. All 12 sites involved by five AFP-producing tumors could be demonstrated by radioimmunodetection, while normal goat immunoglobulin G labeled with 131I failed to show similar results in one of the patients in whom the radioactive AFP antibody achieved tumor radiolocalization. Five patients in whom the tumors were not expected to produce AFP also had their large tumors demonstrated by immune scintigraphy in 6 of 16 tumor sites. The average tumor to non-tumor 131I image count density ratios were 3.20 and 1.96 for the AFP-containing and putatively AFP-deficient tumors, respectively. The image contrast was significantly greater for the AFP-containing tumors, and the subtraction technique enhanced the image contrast more than 2-fold. Based upon these initial results, the sensitivity of the method (true-positive rate) was 100%, its specificity (true-negative rate) was 80%, and the accuracy of the technique was 85%. This study thus indicates that radioimmunodetection of cancer with radioactive AFP antibodies can be useful in the evaluation of patients with AFP-containing neoplasms.
Adult↗
Immunological considerations in the use of goat antibodies to carcinoembryonic antigen for the radioimmunodetection of cancer.
Preparation of radioantibodies from carcinoembryonic antigen (CEA) antisera raised in goats by conventional procedures necessitates extensive absorption procedures to remove antibody activity against CEA-related substances. Further purification by affinity chromatography increases the antibody content of the radiolabeled preparation and enhances antibody uptake by a xenogeneic tumor. In patients given injections of CEA radioantibody, immune complexes form with CEA or a human antibody reactive with goat gamma-globulin, but these complexes do not appear to prevent tumor radioimmunodetection. Monoclonal antitumor antibodies from appropriate animal species would be a more suitable source, eliminating many of the problems encountered with conventional antisera.
Animals↗
Circulating immune complexes in cancer patients receiving goat radiolocalizing antibodies to carcinoembryonic antigen.
The circulating radioactivity and antibody immunoreactivity in patients with diverse cancers who had received 131I-labeled goat antibodies to carcinoembryonic antigen (CEA) were studied by Sephadex G-200 column chromatography and with solid-phase (SP) immunoadsorbents containing anti-goat immunoglobulin G(IgG), anti-human IgG, anti-CEA, or CEA. Upon gel filtration, more than 80% of the plasma radioactivity was distributed between native IgG and an excluded macromolecular radioactive fraction (Pool I). The native IgG and Pool I radioactive peaks were immunoreactive with the SP anti-goat IgG and SP CEA to the same extent as was the radioantibody prior to injection. The circulating CEA in patients with elevated titers only partially bound the injected radioantibody since less than 50% of the latter chromatographed as Pool I. Up to 50% of the Pool I radioantibody from this group of patients was bound to the SP anti-CEA, whereas it was minimally reactive with the SP anti-human IgG. The clearance of radioantibody was similar between groups having different amounts of Pool I radioantibody, and injection of CEA radioantibody was not accompanied by a decrease in circulating antigen. Patients with lower CEA titers had the majority of the plasma radioactivity chromatographing as Pool I radioantibody which showed elevated binding to the SP anti-human IgG but not the SP anti-CEA. Tumor localization by photoscanning was observed in seven of eight and nine of nine patients who had circulating CEA-radioantibody and anti-immunoglobulin-radioantibody complexes, respectively. Thus, these studies demonstrate that CEA, as well as human antibody reactive with goat IgG, can form immune complexes in patients given injections of CEA radiolocalizing antibody. However, these complexes do not appear to prevent tumor radioimmunodetection.
Animals↗
Improved protein labeling by stannous tartrate reduction of pertechnetate.
A procedure has been developed whereby small amounts of protein--specifically human serum albumin and immunoglobulin G--can be labeled with Tc-99m. Artifactual problems associated with electrolytic and stannous chloride labeling procedures are virtually eliminated. The procedure is satisfactory for labeling human serum albumin, normal goat immunoglobulin G, and goat anti-carcinoembryonic antigen immunoglobulin G.
Carcinoembryonic Antigen↗