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D L Dexter

Publications and source records attributed to D L Dexter.

At least 73 records · Page 4Linked to original sources
PubMed1980

Maturation-induction of tumor cells using a human colon carcinoma model.

The establishment of a maturation-induction model using human colon cancer cells as targets is reported. Two colon carcinoma cell lines were established from human tumors; one line was heterogeneous and was cloned into two distant subpopulations. Cells from these lines and clones and cells from an established human colon carcinoma cell line were treated in vitro with N,N-dimethylformamide (DMF) and were compared to untreated cells according to two general sets of criteria. One set contains characteristics that define a cell as transformed (i.e., anchorage independence and tumorigenicity for nude mice), and the second set contains three antigenic marker systems that would provide evidence that maturation is occurring in treated human colon cancer cells. These colon tissue-or tumor-related markers include carcinoembryonic antigen (CEA), colonic mucoprotein antigen (CMA), and the human blood group determinants. DMF-treated cells are less malignant than untreated cells; the treated cells show a marked reduction in tumorigenicity and in clonogenicity in soft agar. Each of the markers indicates that the treated cells are better differentiated than their untreated counterparts. For example, treated cells show increased expression of normal-CMA and decreased expression of tumor-CMA compared to untreated cells. Cells removed from DMF reverted to express the tumorigenicity, growth properties, and antigens characteristic of their untreated counterparts. Therefore, DMF reversibly induces in cultured colon cancer cells a less malignant phenotype with concomitant maturational effects. These results indicate that this model is appropriate for study of maturation-induction in human colon tumor cells, and has potential application to other types of human carcinomas.

Adenocarcinoma↗
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

N,N-dimethylformamide-induced alteration of cell culture characteristics and loss of tumorigenicity in cultured human colon carcinoma cells.

Human colon carcinoma cell lines established in this laboratory were treated in vitro with N,N-dimethylformamide. This polar solvent caused morphological changes in the cells as well as alterations in their growth properties. Untreated cells had cloning efficiencies of up to 77% in soft agar; treatment with N,N-dimethylformamide resulted in a complete loss of clonogenicity in semisolid medium. Growth in the presence of the polar solvent also effected a marked reduction in the tumorigenicity of the cells. Ten of ten nude mice that received a s.c. inoculum of 1 X 10(6) untreated cells developed tumors histologically similar to colonic adenocarcinomas in 10 to 14 days, whereas nine of ten nude mice inoculated with 1 X 10(6) treated cells have shown no sign of tumor 3 to 6 months postinjection. Removal of the polar solvent from the culture medium was accompanied by the reappearance of tumorigenicity and the original cell culture characteristics. Therefore, it appears that N,N-dimethylformamide can reversibly effect the reversion of cultured human colon carcinoma cells to less malignant cell types.

Animals↗
PubMed1979

Adaptation of Sinclair swine melanoma cells to long-term growth in vitro.

Sinclair swine melanoma usually regresses in vivo. In the present study, swine melanoma cells were adapted to long-term growth in culture. The morphology of cultured melanoma cells ranged from dendritic to cuboidal, similar to that described for human melanoma cells. Doubling times of the swine melanoma cells were also similar to those of human melanoma cells in vitro. 3,4-Dihydroxy-L-phenylalanine oxidase-positive cells were detected by light microscopy, and melanin and premelanosomes were detected by electron microscopy. Cell cultures could be propagated from progressing, partially regressed, and primary cutaneous lesions, as well as from visceral metastases. Thus, it appears that, under these cell culture conditions, Sinclair swine melanoma cells can be adapted to prolonged growth in vitro.

Animals↗
PubMed1978

Heterogeneity of tumor cells from a single mouse mammary tumor.

By the use of a variety of cell culture and separation methods, four cell lines were isolated from a single autochthonous BALB/cfC3H mammary tumor. These lines differ markedly from each other in culture morphology, various in vitro growth properties, expression of murine mammary tumor virus antigen, and karyotype, yet all four lines are tumorigenic in normal, syngeneic hosts, yielding tumors of generally similar histology, although distinct from the original neoplasm. Three of the four lines have been cloned from soft agar. The clones exhibit the same growth properties as the lines from which they were derived. Karyotypic analysis of the parent tumor revealed the presence of cells with heterogeneous numbers of chromosomes similar to those seen in the isolated lines, suggesting both the presence of these distinct cell types in the original neoplasm and a genetic origin of the diversity.

Adenocarcinoma↗
PubMed1978

Heterogeneity in drug sensitivity among tumor cell subpopulations of a single mammary tumor.

Three distinct subpopulations of tumor cells derived from a single parent strain BALB/cfC3H mammary adenocarcinoma were tested in vivo for sensitivity to cyclophosphamide, methotrexate, and 5-fluorouracil. Treatment was begun either 2 days after s.c. tumor cell injection or at the time when the tumors became palpable. It was given on a weekly basis for 4 weeks. The mice were observed for growth of the primary implant and for development of spontaneous metastases. The three subpopulations differed markedly in their sensitivity to the drugs. The effects of the drugs ranged from induction of regression of the "primary" to enhancement of metastases. The effect on primary growth was independent of that on metastasis. The effect of the time of administration of the drugs also varied among the subpopulations. The sublines were also tested in vitro with methotrexate and 5-fluorouracil. Again there were marked differences in sensitivity to inhibition of cell division by the drugs. The relative sensitivities in vitro did not correlate with observations in vivo. The existence of subpopulations of tumor cells, differing in sensitivity to therapeutic agents, within a single neoplasm, presents a challenge to development of assays capable of predicting drug response and to the selection of combination therapies.

Adenocarcinoma↗
PubMed1977

Chemotherapy of cell-line-derived human colon carcinomas in mice immunosuppressed with antithymocyte serum.

An in vivo model is described for assessing the antitumor activity of chemotherapeutic agents. Tumors derived from human colon carcinoma cell lines injected into antithymocyte serum (ATS) immunosuppressed mice were used. In this system, both antitumor effects and host toxicity can be quantitated, permitting calculation of a Therapeutic Index. Compared with other xenograft models, the present system is simple, experiments are completed in less than 2 weeks, and the use of cultured cell lines allows in vitro studies to be performed. The in vitro sensitivities of one colon cell line to 22 chemotherapeutic agents and of four cell lines to three agents is reported. Four drugs used in treating colon cancer (Mitomycin C, 5-FU, BCNU, and methyl-CCNU) show antitumor activity in vivo in this system. Each has a low therapeutic index. Further work with this model is indicated, with the goal of finding new drugs with high Therapeutic Indices.

Animals↗
PubMed1977

N,N-Dimethylformamide-induced morphological differentiation and reduction of tumorigenicity in cultured mouse rhabdomyosarcoma cells.

N,N-Dimethylformamide treatment of cell cultures established from a transplantable murine rhabdomyosarcoma-induced morphological differentiation and a marked reduction in the tumorigenicity of the sarcoma cells. Fourteen of 17 CE/J mice receiving injections of inducer-treated cells did not develop tumors after 6 months, whereas all 21 mice receiving inocula of untreated sarcoma cells died of disease between 11 and 31 days. The drug-treated cells did not grow in soft agar; untreated tumor cells grew in the semisolid medium. The untreated tumor cells showed a reduced serum requirement and had a higher saturation density compared to drug-treated cells. Thus the reduction in tumorigenicity of N,N-dimethylformamide-treated cells correlated with certain in vitro growth properties that are more characteristic of normal, mesenchymally derived cells than of sarcoma cells.

Animals↗
PubMedDate not supplied

Chemotherapy of mammary carcinomas arising in ras transgenic mice.

Transgenic female mice carrying the V-Ha-ras transgene linked to the MMTV promoter, which developed mammary carcinomas, were treated with selected cancer chemotherapy drugs. Agents were administered i.p. on a daily x 9 schedule when mice developed tumors that were 50-100 mg in size. Drugs which are clinically effective against breast cancer were quite efficacious in the transgenic model at their maximum tolerated dose. Doxorubicin produced excellent responses in tumor-bearing transgenic mice, with several mammary carcinomas undergoing tumor shrinkage. Two anthrapyrazoles, DuP 937 and DuP 941, novel anticancer drugs with phase 2 activity against breast cancer, were as effective as doxorubicin in the oncomice. Mitoxantrone, a synthetic agent with some properties similar to the anthracyclines, also had antitumor activity, but not as pronounced as obtained with doxorubicin or the anthrapyrazoles. Cisplatin, a drug with limited use in human breast cancer, only caused modest antitumor responses. A computerized data analysis method based on the area under the tumor growth curve was developed to better quantitate the data and provide statistical information. This quantitative analysis confirmed the high statistical significance of the activity of doxorubicin or the anthrapyrazoles in the ras transgenic model, and defined an excellent dose response relationship for each drug tested. Our results suggest that the ras transgenic model may be useful for identifying drugs that have efficacy for breast cancer in women.

Animals↗
PubMedDate not supplied

A therapeutic monitoring assay for N-methylformamide in human serum and urine.

This report describes a gas chromatographic procedure using a packed column and a flame ionization detector, which is suitable for the therapeutic monitoring of N-methylformamide (N-MF). N-MF is a polar compound that induces cancer cell maturation in vitro and exhibits antitumor activity with human tumors xenografted in nude mice. Toxicology studies with mice have shown this compound to be hepatotoxic. N-MF is currently undergoing Phase I clinical trial as an anticancer drug at this institution. In concert with its clinical trial, a method for the analysis of N-MF in biological fluids has been developed to study its pharmacokinetics. This method involves direct injection of urine or acetone-deproteinized serum onto a Chromosorb 103 column, using N,N-diethylformamide as an internal standard.

Chromatography, Gas↗