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D M Goldenberg

Publications and source records attributed to D M Goldenberg.

At least 343 records · Page 19Linked to original sources

Antibody to carcinoembryonic antigen in hamsters bearing GW-39 human tumors.

The appearance of anti-carcinoembryonic antigen (CEA) activity in the sera of hamsters bearing i.m. heterografts of GW-39, a CEA-producing colonic tumor of human origin, was demonstrated in radioimmunoassay using radioiodinated CEA purified from GW-39. Column chromatography, sucrose gradient ultracentrifugation, and radioimmunoelectrophoresis of pooled sera from tumor-bearing hamsters showed that the CEA antibody was of the immunoglobulin M type. The CEA antibody in tumor sera contained two specificities that reacted with different determinants on the CEA. On specificity reacted with a blood group-related determinant, whereas the remaining specificity was against a unique site on the CEA. Sequential analysis of individual tumor-bearing animals revealed that an increase in tumor growth paralleled the concomitant appearance of circulating CEA and highest antibody titer, suggesting that immunoglobulin M antibody, antigen, or complexes thereof influence tumor growth in this model.

Animals↗

Antigens associated with normal and malignant gastrointestinal tissues.

Immunization of hamsters with phenol-alcohol extracts of GW-39 human colonic tumor tissues has resulted in the identification of three gastrointestinal tissue-associated antigens, on the basis of precipitin immunoreactivity. Sephadex G-200 and Bio-Gel A-15m chromatography of normal colonic tissue and GW-39 tumor extracts revealed antigen immunoreactivity in the 46,000 (low-molecular-weight), 170,000 to 900,000 (high-molecular-weight), and 5 to 10 million (very high-molecular-weight) ranges or low-molecular-weight colon-specific antigen (LMW/CSA), high-molecular-weight colon-specific antigen (HMW/CSA), and very-high-molecular-weight colon-specific antigen (VHMW/CSA), respectively. Immunodifussion reactions indicated that the HMW/CSA was human gastrointestinal tissue-specific, increasing in concentration from the esophagus to the colon [for which reason the term colon-specific antigen (CSA) has been retained], whereas the LMW/CSA was found in human gastrointestinal tissues, hamster and rat colon, human saliva, and normal human cervix. Colon-specific antigen (CSA) could be demonstrated in human gastrointestinal tumors, including the LS-174T colonic cancer cell line, but not in cancers of other sites tested. Likewise, CSA's were found in fetal human gut tissue. Whereas HMW/CSA and VHMW/CSA showed partial identity in immunodiffusion, HMW/CSA and VHMW/CSA, as well as LMW/CSA and VHMW/CSA, showed distinct immunoprecipitin bands, respectively. The immunoelectrophoretic mobility of VHMW/CSA was similar to an alpha-globulin, whereas HMW/CSA and LMW/CSA migrated to the prealbumin region. CSA appeared in immunofluorescence of GW-39 tumor cells and in the goblet cells of human colon predominantly as a cell-surface component. Staining with periodic acid-Schiff and solubility characteristics of the CSA's suggest that they are glycoprotein in nature. These studies thus support the view that organ-specific and organ-associated antigens of the colon can be maintained and expressed in human colonic carcinomas, including the xenografted GW-39 human colonic tumor system.

Adenocarcinoma↗

Oncogenesis by interspecific interaction of malignant murine and non-malignant hamster cells in vitro.

A clone of Cloudman S91 murine melanoma was fused in vitro with non-malignant hamster cheek pouch cells by means of lysolecithin, and the putative hybrid progeny cells, HCP-MM, were found to be highly malignant in hamster, but not in appropriate mice. A malignant clone of HCP-MM cells was shown to have hamster species-specific surface antigens (as demonstrated by immunofluorescence and the cytotoxic antibody) and hamster-like lactate dehydrogenase and NAD-dependent malate dehydrogenase isoenzyme profiles. Nevertheless, chromosomes similar to those of both murine and hamster parental cells could be distinguished in cells of this malignant clone and in hamster tumor grafts by the method of trypsin-Giemsa banding. A majority of the murine chromosomes, however, appeared to be lost. This study indicates that a murine melanoma previously found untransplantable in hamsters could produce a highly malignant and lethal tumor for hamsters after being mixed in vitro with non-malignant hamster cells, in the presence of a fusing chemical. It is not as yet certain whether the production of transformed cells in vitro and of highly malignant tumors in the hamster (both with predominantly hamster properties) required heterosynkarion formation between the murine melanoma and hamster cheek pouch cells. Nevertheless, our results suggest that the presence of the murine melanoma, and possibly the interaction of its genome with non-malignant hamster cells, was implicated in this process.

Animals↗

Detection of carcinoembryonic antigen in tissue sections by immunoperoxidase.

A triple-bridge, indirect, immunoperoxidase method for detecting and localizing carcinoembryonic antigen (CEA) in tissue sections is described. By this technique, a cell-surface localization of CEA in colonic carcinoma and ovarian mucinous cystadenocarcinoma cells could be visualized. In the case of the colonic cancer, both the tumor from the descending colon and a metastasis to the skin gave positive peroxidase reactions for CEA. This immunocytochemical method for demonstrating the presence of CEA functioned in both frozen, ethanol-fixed and formalin-fixed, paraffin-embedded tissues, thus making it applicable for use with tissue sections conventionally prepared for light microscopy.

Adenocarcinoma↗

Ultrastructure and virus particles of L1210/Mes. A hamster-adapted murine leukemia.

The ultrastructural features and virus particle content of L1210/Mes., the hamster-adapted strain of murine leukemia L1210, has been studied in cheek pouch tumors and cell cultures. In comparison with the parental murine tumor in culture, L1210/Mes. has experienced certain morphologic alterations, such as a striking increase in cell size, enlarged and more bizarre nuclei, and an increase in the number of lysosome-related structures. Type A (intracytoplasmic and intracisternal) and type C virus particles could be demonstrated in cell cultures of murine leukemia L1210, and in cheek pouch grafts and cell cultures of L1210/Mes. No. "H" (or "R") hamster-associated virus particles, however, could be distinguished in L1210/Mes. tumors or in vitro cultivated cells. It appears that a murine lymphoma capable of serial propagation in a xenogeneic host permits the replication of virus particles structurally indistinguishable from those indigenous to it.

Animals↗

Identification of a colon-specific antigen (CSA) in normal and neoplastic tissues.

An antigen has been isolated from a human signet-ring cell carcinoma serially growing in hamsters, GW-39, by saline, PCA, or phenol extraction, and has been found immunologically identical to a similarly extracted substance in normal human or hamster colon. No other hamster or human tissues or cells were found to contain this antigen, for which reason we have termed it colon-specific antigen, or CSA. CSA has been found to be distinct from the major blood group-specific antigens and from othercolon tumor-associated antigens, such as CEA, CCA-II, and CCA-III. It thus seems that a colon organ-specific antigen can be synthesized by this particular human tumor system. Hamsters immunized with CSA could reject cheek pouch grafts of GW-39 tumors, and tumor rejection by these animals correlated with their anti-CSA antibody titers. Preliminary characterization of CSA suggested that it is a glycoprotein on the cell surface having a molecular size of 30,000 to 50,000 daltons. It is proposed that CSA may play a role in the diagnosis of mucin-producing adenocarcinoma of the colon and in ulcerative colitis.

Animals↗

A study of cyst fluid and plasma carcinoembryonic antigen in patients with cystic ovarian neoplasms.

Cyst fluid and plasma carcinoembryonic antigen (CEA) levels were measured in 11 patients with ovarian cyst-adenocarcinoma and in 16 patients with benign ovarian neoplasms. In patients with ovarian cancer, plasma CEA levels were not elevated above 2.5 ng/ml unless cyst fluid CEA levels were 4 to 16 mu-g/ml. In this series, cystic and plasma CEA levels were elevated most consistently in patients with mucinous ovarian tumors. Furthermore, on the basis of molecular size and immunoreactivity by immunodiffusion, ovarian cancer cyst fluid CEA and colonic cancer CEA had similar immunochemical properties. Consistent with the findings in other neoplasms, follow-up studies showed that plasma CEA levels returned to the normal range between 2 and 12 weeks after surgical excision of the ovarian tumor. It is concluded that plasma CEA is of value in the management of patients with ovarian mucinous cystadenocarcinoma.

Carcinoembryonic Antigen↗

Electric enhancement of bone healing.

A human congenital pseudarthrosis of the tibia, unresponsive to conventional treatment, was stimulated to healing by direct electric current. The method was modeled after prior experimental work in vivo in rabbits. X-ray photographs, histological techniques, and electron microscopy confirmed the presence of newly formed bone in the defect region.

Adolescent↗