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Biomedical subjects

D M Goldenberg

Publications and source records attributed to D M Goldenberg.

At least 271 records · Page 15Linked to original sources
PubMed1984

Second antibody clearance of radiolabeled antibody in cancer radioimmunodetection.

The imaging of tumors using radiolabeled antibodies previously has required the implementation of computer-assisted subtraction techniques to reduce background radioactivity. A decrease in radioactivity in the blood of hamsters bearing human colonic tumor xenografts has been achieved by administering a second antibody directed against a radiolabeled primary antibody to carcinoembryonic antigen (CEA). This method was found to reduce the level of blood radioactivity by a factor of 4 within 2 hr after injection of the second antibody and to enhance tumor/nontumor ratios within 24 hr. Unlike liposomally entrapped second antibody, the primary anti-CEA antibody did not show increased accretion of radioactivity in the liver, spleen, or other major organs. These results suggest that administration of a second antibody alone may improve tumor imaging with a radiolabeled antitumor antibody.

Animals↗
PubMed1984

Clinical studies of prostatic cancer imaging with radiolabeled antibodies against prostatic acid phosphatase.

Conventional antibodies against prostatic acid phosphatase, labeled with iodine-131, have been administered to patients with prostatic carcinoma for the external scintigraphic imaging of tumors containing prostatic acid phosphatase (radioimmunodetection). The method has been found to be safe and reliable for imaging of primary tumors and non-bone metastases, even differentiating between lung tumors of prostatic and pulmonary origin.

Acid Phosphatase↗
PubMed1983

Radioimmunodetection of prostatic cancer. In vivo use of radioactive antibodies against prostatic acid phosphatase for diagnosis and detection of prostatic cancer by nuclear imaging.

Radioimmunodetection (RAID) of prostatic cancer is done by injecting 131I-labeled rabbit antibody IgG against prostatic acid phosphatase (PAP) and performing total-body photoscans with a gamma scintillation camera. Of two patients tested, the PAP RAID scintiscans located the primary or recurrent prostatic cancers in both and showed no disease in the lungs of the patient shown subsequently to have lung cancer. The lung tumor nodules showing anti-PAP IgG accretion were assumed to be of prostatic cancer origin, since one of the original tumors removed from this patient's other lung a year earlier stained for PAP by immunohistochemistry. This study showed that PAP RAID can locate primary and metastatic tumors of prostatic origin.

Acid Phosphatase↗
PubMed1983

Immunological heterogeneity of carcinoembryonic antigen: antigenic determinants on carcinoembryonic antigen distinguished by monoclonal antibodies.

Murine monoclonal antibodies against carcinoembryonic antigen (CEA) derived from a colonic tumor were analyzed by radioimmunoassay for reactivity with CEA and the CEA-related antigens, meconium antigen (MA) and nonspecific cross-reacting antigen. Antibody-antigen binding profiles revealed three classes of hybridomas. The Class I antibody, NP-1, recognized an epitope shared among all three antigens, and its affinity for CEA and MA was high but low for nonspecific cross-reacting antigen. The Class II antibodies reacted with sites shared between CEA and MA, while those of the Class III type only bound CEA. The Class III antibody, NP-4, bound less than 50% of the CEA molecules recognized by goat specific anti-CEA antibody and the other classes of monoclonal antibodies. Two Class II antibodies, NP-2 and NP-3, bound similar amounts of CEA and MA with moderate but different affinities for CEA. Studies using labeled monoclonal antibodies for CEA epitope blocking revealed that NP-2 and NP-3 recognize two separate epitopes on CEA within the Class II category. Thus, monoclonal antibodies to CEA can differentiate at least four antigenic sites on colonic cancer CEA. One is shared by CEA, MA, and nonspecific cross-reacting antigen; two others are shared by CEA with MA; and a fourth appears specific for a subpopulation of CEA molecules.

Adenocarcinoma↗
PubMed1983

Immunological heterogeneity of carcinoembryonic antigen: immunohistochemical detection of carcinoembryonic antigen determinants in colonic tumors with monoclonal antibodies.

The immunoperoxidase localization of carcinoembryonic antigen (CEA) determinants was studied in colonic adenocarcinomas using four murine monoclonal antibodies to CEA in a bridged avidin:biotin technique. One of the monoclonal antibodies, NP-1, recognizes a CEA epitope shared with the nonspecific cross-reacting antigen and meconium antigen. Two others, NP-2 and NP-3, discriminate two separate CEA epitopes shared with meconium antigen only, whereas NP-4 reacts with a unique determinant expressed on a subpopulation of CEA molecules. The monoclonal antibodies and polyclonal goat antisera against CEA and nonspecific cross-reacting antigen stained columnar epithelial cells in morphologically normal mucosa. Neutrophils were stained by only the NP-1 monoclonal antibody and goat anti-nonspecific cross-reacting antigen antiserum. All moderately differentiated colorectal adenocarcinomas and most of their nodal and liver metastases reacted with the goat antisera and cross-reactive monoclonal antibodies. Thirty % of these primary tumors and most of the nodal and/or liver metastases from six patients with NP-4-positive primary tumors failed to stain with NP-4. These results suggest heterogeneity in the expression of a CEA variant and/or determinant recognized by the NP-4 monoclonal antibody that perhaps identifies a subgroup of colonic cancers which differ in their functional differentiation.

Adenocarcinoma↗
PubMed1983

Carcinoembryonic antigen radioimmunodetection in the evaluation of colorectal cancer and in the detection of occult neoplasms.

Radioimmunodetection of colorectal cancer was evaluated in 51 patients by injecting 131I-labeled goat antibody immunoglobulin G against carcinoembryonic antigen and performing total-body photoscans with a gamma scintillation camera 24 and 48 h later. The scintigrams were then processed by computer to subtract the images of the 99mTc-serum albumin and pertechnetate administered, which reflect background and nontarget radioactivity, from the 131I-antibody scans. The results indicate that radioimmunodetection is a safe and a potentially clinically useful cancer detection method, which in this study demonstrated primary colorectal carcinomas in 10 of 12 (83%) of the patients evaluated preoperatively and between 87% (46 of 53) and 92% (49 of 53) of known metastatic tumor sites. Thus, the method's overall sensitivity (true-positive rate) was 86%-91% on a tumor-site basis. A false-negative rate of between 9% and 14% and a false-positive rate of less than 4% were found. In 11 of the 51 patients evaluated, tumor sites were detected that were not found by other clinical methods of cancer detection. These sites of tumor were then confirmed later, as much as 40 wk after radioimmunodetection was performed. It is concluded that in colorectal cancer patients, the current method of carcinoembryonic antigen radioimmunodetection can (a) contribute to the preoperative clinical staging of the patients, (b) assist in the postoperative evaluation of tumor recurrence or spread, (c) complement other methods used to assess tumor response to therapy, (d) support the indication of a rising carcinoembryonic antigen titer (when other methods cannot detect tumor) for second-look surgery, and (e) confirm the findings of other detection measures that are less tumor-specific.

Aged↗
PubMed1983

Immunological heterogeneity of carcinoembryonic antigen: purification from meconium of an antigen related to carcinoembryonic antigen.

Two antigens cross-reactive with carcinoembryonic antigen (CEA) and distinct from the nonspecific cross-reacting antigen were identified in meconium by double immunodiffusion with a conventional goat anti-CEA antiserum. These two antigens together competitively inhibited cross-reacting antibodies against them in CEA radioimmunoassay and contributed to the measurement of meconium CEA levels which averaged 6 times higher than that determined with anti-CEA specific antibody. A purification method for one of these antigens, tentatively designated meconium antigen, is described and uses a combination of ethanol fractionation, ion-exchange and molecular sieve chromatography, and adsorption to an immunoadsorbent containing a cross-reactive murine monoclonal antibody to CEA. Preliminary characterization of the purified meconium antigen showed it to be a glycoprotein, migrating as an alpha-globulin and having a molecular size similar to that of CEA (Mr 185,000 versus 200,000). Antigenically, it lacks at least one determinant present on CEA and differs further from CEA by being weakly reactive with concanavalin A and resistant to proteolytic digestion with Pronase E. Although these properties of meconium antigen suggest that it may be nonspecific cross-reacting antigen 2, additional chemical and antigenic studies are required to establish its relationship to CEA and other CEA-related antigens in meconium.

Adenocarcinoma↗
PubMed1983

Differential expression of tumor-associated antigens in human colon carcinomas xenografted into nude mice.

The tumor-associated antigen profile of a number of different human colon carcinomas xenografted into inbred Swiss nude mice was examined to determine whether the tumors could serve as useful models for antigen purification, radioimmunodetection, and immunotherapy. Extreme heterogeneity was observed both by radioimmunoassay and immunohistochemical procedures for the expression of carcinoembryonic antigen (CEA), colon-specific antigens (CSAp), and colonic mucin antigen (CMA) within the tumors. Four of 10 tumors (DLD-2, DLD-3, DLD-5, and HCT-10) were high producers of CEA (greater than 75 micrograms/g wet tissue wt). Two of these (DLD-2 and HCT-10) correlated with a high production of CSAp and CMA, whereas the other 2 produced low quantities of these antigens. Another tumor, HCT-14-OM1, produced large amounts of CMA yet produced moderate amounts of CEA and low quantities of CSAp. Immunohistochemical analyses of CEA gave a mostly diffuse cellular and cell surface staining for all of the tumors. Staining for CSAp was very focal, as in DLD-5 where only a few of the tumor cells were stained. Staining of CMA was limited; however, DLD-2, HCT-10, and HCT-14-OM1 showed intense cystoplasmic and intraluminal staining. A determination of the tumor antigen profile may be useful in characterization and classification of the tumor as well as enabling the selection of the proper antibody or antibodies for immunodetection and immunotherapy.

Animals↗
PubMed1982

Colon-specific antigen-p (CSAp). I. Initial clinical evaluation as a marker for colorectal cancer.

A radiometric immunoassay for detecting colon-specific antigen-p (CSAp) in the blood of patients suspected of having colorectal cancer has been developed and evaluated in 272 subjects of various disease entities. Using 10 units/ml as the cutoff value for normalcy, the results indicate that the highest number of elevated CSAp titers occurred in patients with advanced colorectal cancer (61%). Only one of 12 colonic adenoma patients had an elevated CSAp titer, and this was slightly above the 10 units/ml cutoff. Other nonneoplastic gastrointestinal disorders showed an 18% abnormal CSAp titer frequency, of which more than half bordered the upper limit of normalcy. CSAp elevations were also found in gastric cancer (20%), pancreatic cancer (20%), breast cancer (5%), and normal individuals (3%). CSAp was compared to carcinoembryonic antigen (CEA) in 44 colorectal cancer patients, in 12 patients with colonic adenomas, and in 62 patients with diverse gastrointestinal disorders. Using a CEA cutoff of 5 ng/ml, CSAp could increase the diagnostic accuracy of the CEA plasma test in colorectal cancer patients by 14%. In patients with colonic adenomas, the CSAp titer was normal when the CEA value was elevated in 25% of the cases. However, both were simultaneously elevated in only 3% of the patients with benign gastrointestinal disorders. Since the CSAp test was less frequently elevated (0-7%) in patients with breast, ovarian, lung, or cervical cancer than was found for CEA (39-75% elevated), it seems that the CSAp blood assay detects colorectal cancer more specifically than the more generally distributed CEA. These results suggest that the combined use of blood CEA and CSAp could enhance the discrimination of colorectal cancers from other nonmalignant gastrointestinal diseases, and could also serve to enhance the colorectal cancer-specificity of the CEA assay. Furthermore, serial monitoring of both markers in four advanced colorectal cancer patients indicated that they reflect disease activity, falling after successful treatment and rising again with recurrence and disease progression.

Adenocarcinoma↗
PubMed1982

Colon-specific antigen-p (CSAp). II. Further characterization in colorectal and pancreatic cancer.

The physicochemical and immunological characteristics of colon-specific antigen-p (CSAp) in plasma and in colorectal and pancreatic tumors were investigated. CSAp in the plasma of a rectal cancer patient and in a colonic carcinoma xenografted in hamsters (GW-39 tumor) appeared to have similar chromatographic properties, being of a molecular size of 4 million or more. The activities of CSAp in both plasma and tumor were similarly destroyed by treatment with a thiol reagent. Finally, identical immunological reactions in radioimmunoassay and gel diffusion tests were obtained between the CSAp's in patient plasma and in GW-39 tumor tissue. Also CSAp in human pancreatic cancers xenografted in nude mice showed a precipitin line of complete identity with CSAp extracted from GW-39 human colonic carcinoma transplants. Thus, the CSAp's found in colorectal cancer patient plasma, in colonic carcinoma, and in pancreatic cancer tissues appear to be immunologically identical.

Animals↗
PubMed1982

Carcinoembryonic antigen in carcinoma of the uterine cervix: antigen distribution in primary and metastatic tumors.

Immunohistochemical staining for carcinoembryonic antigen (CEA) was performed on primary tumors and regional lymph nodes from 100 patients undergoing radical hysterectomies and pelvic lymphadenectomies for invasive carcinoma of the uterine cervix. Antigen staining was present in 82% of keratinizing squamous carcinomas as compared with 50% in nonkeratinizing tumors. Seventeen patients with CEA-producing cervical cancer had regional lymph nodes metastases, all of which stained positively for CEA. Conversely, antigen could not be detected in lymph nodal metastases from primary tumors devoid of CEA. The pattern and intensity of CEA staining in primary tumors and their metastases were similar in all cases. Antigen was present in highest concentrations in the cytoplasm and tumor cell membrane of all tissues examined and isolated nuclear staining was absent. The clinical implications of these findings are discussed.

Adenocarcinoma↗
PubMed1982

In vivo horizontal oncogenesis by a human tumor in nude mice.

A human mucinous cystadenocarcinoma of the ovary was propagated in nude mice. After cryopreservation of the 3rd-passage xenograft for 4 years, subsequent in vivo transplants showed the emergence of two distinct populations, one resembling the original human adenocarcinoma and the other resembling a spindle-cell sarcoma. These two tumor cell populations were confirmed to be human and murine, respectively, by cytogenetic study, and the epithelial tumor cells were further shown to be of human origin by immunoperoxidase staining of blood group A antigen. Separation of the two tumor cell populations in vitro permitted the independent propagation of the human and murine tumor cells in vitro and in vivo. The murine sarcoma was also capable of growth in ordinary BALB/c mice. These results indicate that human cancer cells can induce malignancy in adjacent, putatively normal, cells of nude mice in vivo.

Animals↗
PubMed1982

Neutron-capture therapy of human cancer: in vitro results on the preparation of boron-labeled antibodies to carcinoembryonic antigen.

Two samples of 2-phenyl-1,2-dicarba-closo-[1-3H]dodecaborane(12) were prepared by treating 1-lithio-2-phenyl-1,2-dicarba-closo-dodecaborane(12) with 3H2O (0.1 and 5.0 Ci/ml, respectively). These tritiated phenylcarborane samples were subsequently converted to corresponding samples of p-[1,2-dicarba-closo-[1-3H]dodecaboran(12)-2-yl]benzenediazonium ion ([3H]DBD) suitable for azo-coupling reactions. Reaction of the two tritiated diazonium ion samples with 2-napthol resulted in the formation of an azo dye (epsilon = 1.98 X 10(4) M-1 cm-1 at 485 nm). Experiments relating absorbance to 3H activity proved the two [3H]DBD sources to have 3.81 X 10(11) and 2.45 X 10(13) cpm of 3H per mol of tritiated carborane substituent. Purified antibodies to carcinoembryonic antigen were coupled to the [3H]DBD and, after extensive dialysis, the average number of carborane moieties per antibody molecule was determined by measuring the 3H activity associated with a known protein concentration. Further examination of these tritiated carborane-labeled antibodies by affinity chromatography proved that boron labeling did not destroy their immunoreactivity. Correlations of azo-coupling conditions (reactant ratios, pH) with immunoreactivity and antibody protein recovery are presented.

Antibodies, Neoplasm↗
PubMed1982

In vivo radioimmunological lymphoscintigraphy in cancer: the implications of positive findings.

Radionuclide-labeled antibodies to tumor-associated antigens were applied to the detection of the lymphatic spread of carcinoma by the technique of lymphoscintigraphy. In women with proven carcinoma of the breast, all of whom had clinical or surgically proven axillary metastases, 100% of metastases were detected by gamma imaging. In three cases of squamous cell carcinoma of vulva, one with bilateral inguinal metastases, one with ipsilateral metastases, and one with no metastases, imaging revealed that I-131 labeled antibodies were sequestered bilaterally in the inguinal lymph nodes of all three patients. Submucosal injections of the uterine cervix with labeled antibodies were performed in patients with carcinoma of the cervix, and again sequestration of radioactivity was detected in pelvic nodes. Subsequent hysterectomy with lymph node dissection revealed high levels of radioactivity in specific lymph nodes but no evidence of metastatic tumor. In view of previous work by Nossal and his group, we speculate that the sequestration of the antibody was based on trapping of the antigen by the lymph nodes, and an antibody-antigen reaction on the surface of cells within the nodes. To prove this hypothesis, appropriate animal experiments were performed. The detection of antigen trapping may have important implications in the diagnosis and therapy of cancer.

Antibodies, Neoplasm↗