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D V Gold

Publications and source records attributed to D V Gold.

34 records · Page 2Linked to original sources
PubMed1986

Growth inhibition of a rat colon tumor by L-canavanine.

The effects of L-canavanine, a higher plant nonprotein amino acid, on the growth of a rat colon carcinoma were assessed. The 1 and 10% lethal dose values following a single s.c. injection in Fischer rats were 4.75 and 5.57 g/kg, respectively. Rats received s.c. injections of a 10% (w/v) tumor cell suspension. When the tumors reached a size of 500 to 1000 mm3, the rats received canavanine, 2.0 g/kg or 3.0 g/kg s.c. daily for 5 or daily for 9 days. Control animals received a 0.9% NaCl solution. Administration of canavanine, 2.0 g/kg for 5 days produced a treated versus control of 23%; the treated versus control for 9 days was 14%. The 3.0-g/kg dosing regimen resulted in a treated versus control value of -13% after 5 days and -8% after 9 days. The negative values indicated regression of the tumor. The reduction in tumor volume, expressed as the percentage of regression, was 22% in animals receiving canavanine, 3.0 g/kg daily for 5 days and 60% in the 3.0-g/kg-daily-for-9-days treatment group. Cumulative toxicity caused death in 2 of 5 animals in the 3.0-g/kg-for-9-days treatment group; the average weight loss was 31%. The 3.0-g/kg-for-5-days treatment also produced undesirable cumulative toxicity as indicated by a weight loss of 19%. Cumulative toxicity was reduced greatly when canavanine was administered at a dose level of 2.0 g/kg for 5 days (weight loss of 13%). Analysis of the relationship of caloric deprivation to tumor growth reduction established that canavanine-mediated curtailment of tumor growth was not caused by reduced food intake and its associated loss in body weight. Histological examination of tissues from rats receiving canavanine, 2.0 or 3.0 g/kg daily for 5 or 9 days failed to reveal lesions in any of the examined tissues, except for varying degrees of pancreatic acinar atrophy. All other tissues appeared normal. The white and red blood cell values of canavanine-treated rats were also normal following 1, 3, or 6 injections of canavanine, 2.0 or 3.0 g/kg. The results indicated that canavanine induced marked growth inhibition of the rat colon carcinoma. Our experiments also disclosed that further studies must be conducted to optimize the dosing schedule to enhance drug efficacy and to reduce its cumulative toxicity.

Animals↗
PubMed1983

Identification of a human pancreatic duct tissue-specific antigen.

Antiserum raised against a pancreatic duct mucin was absorbed with type AB red blood cells and used in the indirect immuno-glucose oxidase procedure to examine tissue specificity. All mucin-producing organs were stained by this antiserum. Absorption of the antiserum with mucinous ovarian cystadenocarcinoma fluid eliminated generalized mucin staining, and only pancreatic ducts and colonic goblet cells were positive. Further absorption with purified colonic mucin revealed a pancreatic duct tissue-specific determinant(s). This tissue-specific determinant(s) was detected in the RIP-1 and RIP-2 human pancreatic adenocarcinomas carried as xenografts in athymic nude mice. Because the majority of pancreatic adenocarcinomas are believed to arise from ductal tissue, pancreatic duct mucin may have a useful role as a marker in detection and differential diagnosis.

Animals↗
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↗
PubMed1983

Characterization of two metastatic subpopulations originating from a single human colon carcinoma.

Two separate cell lines originating from distinct metastatic deposits in a patient with a primary colonic carcinoma have been established both in vivo and in vitro. One metastasis, OM-1, was found in the omentum, and the other, HOT-3, was located on the ovary. These two metastases differ in several significant characteristics, including growth kinetics and the production of carcinoembryonic antigen by the cultured cells. OM-1 xenograft tumors contain about 8-fold more colonic mucin antigen than do HOT-3 heterografts. Similarities also exist. Both cell lines contain extra chromosomes in the A group, and both are missing chromosomes in Pair 14 of the D group and in Pair 18 of the E group. Xenograft tumors from these two metastases contain equivalent amounts of carcinoembryonic antigen and nonspecific cross-reacting antigen. These metastases developed through a process of progression and natural selection that occurred during the course of the patient's disease. Thus, the cell lines established from them provide material which may be used to study functional intraneoplastic diversity.

Antigens, Neoplasm↗
PubMed1982

alpha 1-Proteinase inhibitor production by human adenocarcinomas xenotransplanted into nude mice.

Human colon adenocarcinomas xenotransplanted into BALB/c nude mice were examined for the ectopic synthesis of alpha 1-proteinase inhibitor(s) (alpha 1Pi). Tumor extracts were prepared by homogenization followed by molecular sieve chromatography on Sepharose 4B. Fractions with immunoreactive alpha 1Pi were concentrated and adsorbed onto a concanavalin A-Sepharose 4B affinity column, then eluted, concentrated, and analyzed. All 4 colon tumors examined produced alpha 1Pi with full antigenic identity to normal human plasma alpha 1Pi. Electrophoretic mobilities of 3 of the tumor-derived alpha 1Pi were different from the electrophoretic mobility of the normal human plasma alpha 1Pi. Activities of the inhibitors were determined by the reaction of each tumor extract with pancreatic elastase (PE) followed by immunoelectrophoresis of the reaction mixture against both anti-human alpha 1Pi and anti-PE antisera. Two of the tumor-derived alpha 1Pi examined were active in inhibiting PE.

Adenocarcinoma↗
PubMed1981

Protease digestion of colonic mucin. Evidence for the existence of two immunochemically distinct mucins.

Colonic mucin was prepared by phenol-water partition extraction of th colonic mucosa, followed by ethanol precipitation of the water-soluble material, molecular sieve chromatography, and reductive sodium dodecyl sulfate-disc gel electrophoresis in an agarose-polyacrylamide gradient gel. Although this material as observed to be relatively homogeneous by physical criteria, it was shown to contain at least two components by immunodiffusion. Molecular sieve, ion exchange, adsorption, lectin affinity, and electrophorectic techniques failed to separate the two components. However, by protease digestion employing either 1% w/w pronase or papain, followed by molecular sieve chromatography, we were able to separate at least the portions of the molecules containing the immunodeterminants. Physicochemical and immunologic properties of both components were characteristic of mucins. Mucin A (pronase digest fraction 1 from molecular sieve chromatography) was enriched in threonine, proline, and sialic acid, while mucin B (pronase digest fraction 3 from molecular sieve chromatography) was enriched in serine, alanine, and fucose. Mucin A and mucin b were shown to be immunologically distinct. The evidence suggests that the protease-digested mucin fractions originate from two different mucins, one a sialomucin, the other a fucomucin; however, the alternative explanation, that these two mucin fragments may originate from a single mucin molecule, cannot be ruled out at present.

Amino Acids↗
PubMed1981

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↗
PubMed1981

Immunoperoxidase localization of colonic mucoprotein antigen in neoplastic tissues.

The distribution of colonic mucoprotein antigen in various types of cancer was examined to determine whether the antigen might have a role as a tissue marker. An antiserum prepared against normal colon-derived colonic mucoprotein antigen and appropriately absorbed with mucinous ovarian cystadenocarcinoma fluid had reactivity limited to the colon and cecum when tested by immunoperoxidase against various normal adult tissue specimens. Among colon carcinomas, 60% of the tumors were stained, and a correlation with tumor differentiation was noted: seven of seven tumors were well differentiated; 21 of 35 tumors were moderately differentiated; and one of seven poorly differentiated tumors expressed the determinants. Of note was the absence of staining with gastric, pancreatic, lung, and endometrial mucin-producing carcinomas. Only one of five mucinous ovarian cystadenocarcinomas was positive for colonic mucoprotein antigen. The potential role of the mucin as a marker for colon carcinoma is discussed.

Antigens, Neoplasm↗
PubMed1980

N,N-dimethylformamide-induced modulation of organ- and tumor-associated markers in cultured human colon carcinoma cells.

Cultured human colon carcinoma cells were induced by the polar solvent N,N-dimethylformamide (DMF) to express a more differentiated phenotype as indicated by three types of antigen markers. Carcinoembryonic antigen expression in all DMF-induced cell lines was enhanced. Exposure of cells to DMF resulted in a reduction in ability to bind antibody to tumor-derived colon mucoprotein antigen (CMA) with a concomitant gain in binding of antibody to normal CMA. DMF-induced differentiation was further indicated by modulation of blood group antigen expression. DMF treatment decreased the amount of expression of the H-gene determinant. When DMF-treated cells were cultured in the absence of DMF for 14 days, the levels of expression of the antigen markers reverted to those characteristic of their untreated counterparts.

ABO Blood-Group System↗
PubMed1979

Organ and tumor specificity of colon mucoprotein antigen in a rat model.

We purified a high-molecular-weight colon mucoprotein antigen (CMA) from normal F344 rat colon and from a transplantable dimethylhydrazine-induced colon carcinoma. Chemical analysis of the mucins showed similar amino acid and carbohydrate compositions. This finding was in contrast to the major differences that occurred in the composition of human CMA as a consequence of neoplasia. Immunohistochemical techniques were used in an examination of organ and tumor specificities. A New Zealand White rabbit antiserum against purified normal rat CMA, appropriately absorbed, detected a normal colon-specific determinant(s). The organ-specific determinant was lost as a consequence of neoplasia. However, a new tumor-specific determinant was then detected. CMA may have a potential role as an organ-specific marker of the neoplastic process.

Amino Acids↗
PubMed1978

A mucoprotein with colon-specific determinants.

The tissue specificity of colonic mucoprotein antigen (CMA) was examined to determine whether the antigen might have a role as a tissue marker. The immunofluorescent technique, using a rabbit anti-CMA antiserum, was employed to examine a wide range of tissues. Gastrointestinal mucosae as well as non-gastrointestinal mucin producing tissues were positive; however, non-gastrointestinal reactivity could be eliminated by the appropriate absorptions. Mucoproteins were purified separately from each gastrointestinal anatomic region and used to absorb the antiserum. This analysis demonstrated the existence of a family of mucoproteins with a common gastrointestinal specific determinant(s). Mucoproteins from neighboring regions, as seen by this antiserum, showed a greater structural similarity than did mucoproteins from distant regions. Absorption of the antiserum with ileal or cecal mucoprotein allowed the detection of a colon specific determinant present on CMA.

Colon↗
PubMedDate not supplied

Localization of pancreatic cancer with radiolabeled monoclonal antibody PAM4.

Experimental animal studies were performed with (111)In-labeled PAM4 anti-MUC1 antibody along with (111)In-labeled control antibody. Tumor uptake of radiolabeled PAM4 was significantly higher than for the control antibody at all time points. When normalized to a blood dose of 1500 cGy as an estimate of myelotoxicity, (90)Y-labeled PAM4 would provide 5344 cGy to the tumor, whereas an equitoxic dose of (90)Y-labeled control antibody would provide only 862 cGy to the tumor. In addition to the animal studies, five patients with proven pancreatic cancer were administered either (131)I-PAM4 IgG (n=2) or 99mTc-PAM4 Fab' (n=3). Tumor targeting was observed in four out of five patients. By immunohistochemistry, PAM4 was non-reactive with tumor from the one patient not targeted. Dosimetry from the patients given (131)I-PAM4 predicted that tumors would receive 10-20 cGy/mCi with tumor/red marrow dose ratios ranging from 3 to 10. Based upon these results, we have established a phase-I (111)In-labeled PAM4 imaging and (90)Y-labeled PAM4 therapy trial.

Aged↗
PubMedDate not supplied

Colonic tumor CEA, CSAp and MUC-1 expression following radioimmunotherapy or chemotherapy.

Understanding the changes in tumor biology following cytotoxic therapy may lead to a better understanding of the properties of surviving tumor cell populations and to an improved ability to target and treat these cells. This report addressed the time-dependent dynamic alterations in the expression of three tumor-associated antigens: carcinoembryonic antigen (CEA), colon-specific antigen (CSAp) and mucin-1 (MUC-1) following chemotherapy with 5-fluorouracil (5-FU) or radioimmunotherapy (RAIT; (131)I-labeled anti-CEA IgG) in human colonic tumor xenografts. Immunoassay results show that CEA and MUC-1 expression all increase rapidly after either 5-FU or RAIT. GW-39 tumors show a 2.7-fold increase in CEA expression after a maximum tolerated dose of RAIT, being highest after 21 days, while LS174T and HT-29 tumors maximally increase expression 8.3- and 2.6-fold on day 7 after RAIT, respectively. The change in LS174T is short-term, whereas the change in HT-29 is maintained for at least 4 weeks. Serum CEA levels in these tumor- bearing mice also increase in parallel to the changes observed in tumor. MUC-1 increases 2.5-fold by day 5-7 following RAIT in LS174T tumors and 6-fold by day 14 following RAIT in GW-39 tumors, with a corresponding increase in serum MUC-1. Dramatic increases in CSAp after RAIT were also demonstrated in GW-39 tissue by immunohistochemistry. Thus, these data indicate that the response of tumor cells to low-dose-rate radiation from RAIT or to chemotherapy is associated with an increase of CEA, MUC-1 and CSAp.

Animals↗