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Biomedical subjects

D M Goldenberg

Publications and source records attributed to D M Goldenberg.

At least 325 records · Page 18Linked to original sources
PubMed1978

Further characterization of CSAp, an antigen associated with gastrointestinal and ovarian tumors.

Colon-specific antigen-p, or CSAp, was originally extracted from GW-39 tumors, which are human colonic carcinomas serially transplanted in golden hamsters, and antibodies to CSAp have been produced in the same animal hosts. By means of immunodiffusion and a hemagglutination-inhibition assay, CSAp has been found to be restricted to adult and fetal small intestine, neoplastic gastric and colonic tissues, inflamed colon, and cystic mucinous tumors of the ovary. CSAp was shown to be distinct from blood group antigens, including Lea and Leb blood group substances, liver ferritin, AFP, CEA, CSA, CMA, ZGM, and BOFA, and to have the electrophoretic mobility of an alpha2-globulin. Gel filtration studies indicated that CSAp in GW-39 tumor, primary human colonic carcinoma, and ovarian cancer mucinous cyst fluid had a peak molecular size range of 70,000--110,000. Quantitation of CSAp in 214 tissue specimens by the hemagglutination-inhibition assay revealed a progressive increase in fetal, inflamed, and neoplastic intestine, such that CSAp in colonic tumors was increased over normal colon tissue. Thus, CSAp appears to be an organ-specific antigen showing increased levels in some gastrointestinal and ovarian neoplasms, as well as in specimens with colitis.

Alpha-Globulins↗
PubMed1978

Carcinoembryonic antigen in carcinoma of the uterine cervix. 1. The prognostic value of serial plasma determinations.

Plasma carcinoembryonic antigen (CEA) determinations were obtained prior to therapy in 300 patients with invasive carcinoma of the uterine cervix followed at the University of Kentucky Medical Center from 1971 to 1976. Carcinoembryonic antigen levels were elevated (greater than 2.5 ng/ml) in 48% of cervical cancer patients, and varied directly with stage of disease and histologic differentiation of the tumor. Plasma CEA levels were more commonly elevated in patients with endocervical adenocarcinoma than in those with squamous cell carcinoma, but were not related to vascular invasion in the specimen or regional lymph nodal morphology. Two hundred and four patients had 2 to 15 (mean = 5) follow-up plasma CEA determinations after treatment. Thirty patients had progressively increasing plasma CEA levels following therapy, of which 29 developed recurrent cervical cancer. A progressive rise of plasma CEA preceded the clinical diagnosis of recurrence by 1 to 23 months (mean = 6 months) in 13 of these patients, and occurred at the same time or after the clinical diagnosis of recurrence in 16 cases. Patients with progressively rising plasma CEA levels following therapy for cervical cancer should be extensively evaluated to rule out the presence of occult recurrence.

Adenocarcinoma↗
PubMed1978

Immunoperoxidase staining of carcinoembryonic antigen in urinary bladder cancer.

An immunoperoxidase study of the presence of carcinoembryonic antigen (CEA) in primary cancers of the urinary bladder, metastases to the bladder, non-malignant diseased bladder, and normal bladder tissues revealed that approximately 10 percent of the urothelial carcinomas (transitional cell and squamous cell types) contained detectable quantities of this antigen. The other tissues were devoid of stainable CEA. It thus appears that the incidence of positive CEA by immunoperoxidase staining of formalin-fixed, paraffin-embedded tumour tissue sections is much less than the frequency of blood or urinary CEA elevations in patients with urothelial cancer.

Carcinoembryonic Antigen↗
PubMed1978

Identification of beta-oncofetal antigen in cervical squamous cancer and its demonstration in neoplastic and normal tissues.

An extract of a human cervical squamous carcinoma was used to produce rabbit antiserum with immunoreactivity against an antigen in several types of normal and neoplastic tissues. This antigen was abundant in cervical cancer as well as in normal adult and fetal kidney and liver. The antigen had a beta mobility in immunoelectrophoresis and a molecular weight range of 74, 000 to 90,000 as determined by gel chromatography. Since some of its properties were similar to those of the beta-oncofetal antigen described by Fritsche and Mach, a comparison was undertaken that indeed revealed identical immunoreactivity of the anti-beta-oncofetal antigen and anti-cervical cancer antisera when reacted in immunodiffusion against a cervical cancer extract. These results do not support the designation of this antigen as an oncofetal antigen.

Animals↗
PubMed1977

An analysis of the G-banded chromosomes of the golden hamster.

Chromosomes from 20 G-banded karyotypes of golden hamster cheek pouch cells were precisely measured to determine total lengths and arm ratios. Mean values were used to establish an idiogram which may serve as the basis for a standard hamster karyotype.

Animals↗
PubMed1977

The prognostic significance of carcinoembryonic antigen in the plasma and tumors of patients with endometrial adenocarcinoma.

Carcinoembryonic antigen (CEA) levels in plasma and the immunocytochemical detection of tumor CEA were studied in patients with endometrial adenocarcinoma treated at the University of Kentucky Medical Center from 1973 to 1976. The incidence of CEA elevation in a group of 60 patients varied directly with uterine size, histologic differentiation, and stage of disease. Immunoperoxidase staining for CEA was performed on 42 specimens, and four were positive, indicating a tissue concentration of CEA of at least 5 microng per gram. Following operation, CEA levels returned to normal within eight weeks in all but two patients, both of whom were later shown to have persistent or recurrent cancer. These data suggest that serial plasma CEA determinations may be useful in predicting occult recurrence of endometrial cancer in patients in whom the plasma or tumor initially contains elevated concentrations of this antigen.

Adenocarcinoma↗
PubMed1977

Karyology of a human colonic carcinoma (GW-39) serially xenografted in hamsters and in nude mice.

A karyological analysis of the G-banded chromosomes of the serially transplantable GW-39 human colonic carcinoma was undertaken. GW-39 cells harvested from hamsters, nude (athymic) mice and cell cultures from 1972 to 1976 revealed a hypodiploid stemline of 45 human chromosomes, with a consistent loss of a 21-chromosome. No apparent alterations of the near-diploid stemline resulted during long-term xenogeneic propagation of this human cancer line.

Animals↗
PubMed1977

Localization by immunoperoxidase and estimation by radioimmunoassay of carcinoembryonic antigen in colonic polyps.

A 3-layer immunoperoxidase technique was used to demonstrate carcinoembryonic antigen (CEA) in colonic polyps from patients with or without previous or concurrent malignancy. CEA was demonstrated in a higher percentage of the polyps received as fresh specimens that were rapidly frozen and fixed in ethanol, than in formalin-fixed, paraffin-embedded sections. Tissue CEA content of both colonic carcinomas and polyps was determined by radioimmunoassay, and it was found that benign colonic tumours had levels of tissue CEA comparable to colonic cancer, indicating that CEA concentration in a tumour does not reflect its grade of malignancy. In fact, in one case in which both colonic cancer and polyps were removed, the polyps had the higher quantities of tissue CEA. Further, tissue CEA concentration of a polyp was not dependent on its size or location. Studying the titres of circulating CEA in these patients revealed an elevation of plasma CEA in one-third of the patients with only colonic polyps, whilst the patients with cancer all had increased titres.

Carcinoembryonic Antigen↗
PubMed1977

Human colon adenocarcinoma cells. II. Tumorigenic and organoid expression in vivo and in vitro.

A human colon epithelial tumor cell line (LS174T) recultured in vitro following passage through hamsters displayed differences in its cell doubling time and synthesis of carcinoembryonic antigen when compared with the cells grown solely in vitro. These animal-passaged cells more closely resembled the parent tumor cell line (LS180) derived from the primary tumor than LS174T, the trypsinized variant of LS180. Analysis of lactate dehydrogenase isoenzymes indicated that the tumor cells recovered from the hamsters were free of xenogeneic host tissue. Furthermore, LS174T grafted to athymic (nude) mice grew as a mucinous adenocarcinoma microscopically resembling the original tumor. The altered growth potential of LS174T was also demonstrated on confluent feeder monolayers of normal cells and by uninhibited multiplication in vitro. These results suggest that, at least in this one case, short-term passage of long-term cultured cells into xenogeneic hosts may effect a phenotypic reversion such that the cells regain properties observed in the primary tumor and the initial in vitro explant.

Adenocarcinoma↗
PubMed1977

A putatively new antigen (CSAp) associated with gastrointestinal and ovarian neoplasia.

CSAp is an antigen originally identified in the GW-39 human colonic carcinoma xenograft, and also found in gastric and colonic cancers, fetal colon, normal and inflammatory adult colon, and in some ovarian tumors. However, it appears to be increased primarily in inflammatory, benign , malignant, and fetal human intestine, gastric cancer, and ovarian tumors, as determined by an hemagglutination-inhibition assay. Gel immunodiffusion patterns show that CSAp is immunologically distinct from CEA, NCA, AFP, BOFA, and human liver ferritin. CSAp thus appears to be a putatively new fetal substance with a high degree of specificity for gastric, colonic, and ovarian tissues.

Animals↗
PubMed1977

Localization of GW-39 human tumors in hamsters by affinity-purified antibody to carcinoembryonic antigen.

With the paired-labeled antibody technique, the in vivo localization of radioiodinate, affinity-purified antibody to carcinoembryonic antigen (CEA) was studied in GW-39, a xenografted, CEA-producing tumor model. When compared to the whole immunoglobulin G fraction, a 4-fold greater tumor accumulation of radioantibody was obtained with affinity-purified specific CEA antibody. The degree of increased tumor localization of affinity-purified antibody was similar to its improved immunoreactivity as observed in radioimmunoassay and binding to CEA immunoadsorbent. Affinity-purified antibody cross-reactive with CEA and colon carcinoma antigen III was as equally effective in tumor localization as was specific CEA antibody prepared similarly. It thus appears that affinity-purified CEA radioantibody will provide a superior tumor-imaging agent for clinical use.

Animals↗
PubMed1976

Carcinoembryonic antigen and glucose phosphate isomerase in a human colonic cancer model (GW-39).

Levels of carcinoembryonic antigen (CEA) and glucose phosphate isomerase (GPI) have been compared in the circulating blood of hamsters bearing intra-muscular grafts of GW-39 human colonic tumour. CEA in the sera of GW-39 tumour-bearing hamsters ranged from 2-6 to 8-4 ng/ml (mean = 4-5 +/- 1-7 ng/ml). GPI in the sera of normal hamsters ranged from 332 to 749 iu/1 (mean = 602 +/- 110 iu/1) while those with 14-week-old intra-muscular grafts of a hamster amelanotic melanoma, (A.Mel.3), or GW-39 human colonic carcinoma had a range of 664 to 1267 iu/1 (mean = 1024 +/- 220 iu/1) and 1430 to 4719 iu/1 (mean = 2065 +/- 601 iu/1) respectively. Thus, the ratio of enzyme activity in GW-39, A.Mel.3, and normal hamsters was 3-4:1-7:1, indicating a significant elevation (P less than 0-01) in animals bearing a human colon carcinoma or a hamster melanoma, with particularly high values obtained in hamsters with GW-39. Sequential determinations of CEA and GPI in a group of hamsters transplanted intra-muscularly with GW-39 tumours revealed that both markers increased proportionately with duration of tumour growth, suggesting that both serum CEA and GPI may be used as measures of tumour growth. The concentration of GPI in GW-39 human colonic carcinoma xenografts was also significantly higher than that measured in normal human colon, primary human colonic cancer, or normal hamster tissues. These results support the view that GPI, in addition to CEA, is a quantitatively increased marker in this tumour model, and is liberated into the circulation in proportion to the increase in tumour mass.

Animals↗
PubMed1976

Carcinoembryonic antigen in histopathology: immunoperoxidase staining of conventional tissue sections.

A triple-bridge, indirect peroxidase-antiperoxidase method for demonstrating carcinoembryonic antigen (CEA) in frozen, ethanol-fixed or formalin-fixed, paraffin-embedded specimens was evaluated. Examination of 359 tissue specimens--234 malignant tumors, 37 benign neoplasms, 41 nonneoplastic diseased tissues, and 47 normal specimens--showed that CEA could usually be demonstrated in a group of cancers. We could detect CEA in carcinomas of the stomach, colon, rectum, pancreas, lung, and cervix. However, malignant tumors of the breast, prostate, kidney, larynx, brain, lymphoreticular system, soft tissues, and skin proved negative for CEA by the immunoperoxidase test. CEA could be detected in ethanol- or formalin-fixed sections. The only nonmalignant specimens showing CEA staining were a few benign tumors, the mucosae of some cases of colitis, and the resection margins of 2 cases of colon cancer; however, these were commonly very weak reactions. Measurement of tumor CEA content by radioimmunoassay revealed two causes for this relative specificity of the immunoperoxidase test for CEA:1) a quantitative difference existed in tissue CEA among the various specimens, and 2) the threshold for CEA staining in malignant specimens was usually above that in nonmalignant specimens. An analysis of the formalin-paraffin-treated sections showed that immunoperoxidase-tested CEA positivity reflected CEA levels in tissue of at least 3.0-5.0 mug/g; this permitted retrospective estimates of minimal tissue CEA concentrations in older histopathologic specimens by the immunoperoxidase reaction method. Formalin-paraffin-treated sections as old as 10 years still had demonstrable CEA. Although tumor CEA concentration correlated well with immunoperoxidase staining for CEA, plasma CEA titer did not necessarily reflect tumor CEA content. CEA positivity in primary and secondary tumors was strongly correlated; it was less strongly correlated with level of tumor differentiation.

Carcinoembryonic Antigen↗
PubMed1976

Carcinoembryonic antigen in patients treated with radiation therapy for invasive squamous cell carcinoma of the uterine cervix.

Plasma carcinoembryonic antigen (CEA) levels in 75 patients with invasive cervical cancer were measured during and after radiation therapy. Initial CEA levels were elevated in 65% of the patients, the incidence varying with stage of disease. Of the 32 patients followed during therapy, CEA levels rose in 26 (81%). CEA values after therapy in the same 32 patients showed three patterns: (1) decline to normal, associated with a disease-free state; (2) decline but not to normal, associated with heavy cigarette smoking or persistent disease; and (3) decline to normal, followed by a rise to abnormal, associated with tumor recurrence. Elevation of CEA levels preceded recognition of recurrent cervical cancer by as much as 4 months in five of seven patients.

Carcinoembryonic Antigen↗