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R H Shoemaker

Publications and source records attributed to R H Shoemaker.

62 records · Page 4Linked to original sources
PubMed1984

Potentials and drawbacks of the human tumor stem cell assay.

The human tumor stem cell assay (HTSCA) provides a means of performing drug sensitivity measurements on human tumor cells in primary culture. Results from such assays offer potential for improving cancer chemotherapy by identifying drugs useful for treatment of individual patients' tumors and through application to screening new compounds for antitumor activity. While existing data supports the potential of the assay in both areas, the assay also poses significant drawbacks. Many of these drawbacks relate to technical aspects of the assay and can be eliminated or reduced by further assay development. In this paper, we describe some of the technical drawbacks in detail and some approaches which have been successful in minimizing them. Continued advances in this area should make it possible to more fully realize the potential of the human tumor stem cell assay.

Animals↗
PubMed1983

Evidence for multidrug-resistant cells in human tumor cell populations.

Data are presented from two cell culture systems which support the notion that a multi-drug-resistant phenotype occurs in human tumor cell populations. Human small cell lung cancer cell lines derived from patients in relapse following intensive combination chemotherapy demonstrate broad cross-resistance to nine standard drugs in vitro. However, analysis of [14C]glucosamine-labeled glycoproteins in the small cell lung cancer cell lines failed to identify any consistent association between a specific glycoprotein marker and the drug-resistant phenotype. Evaluation of drug sensitivity of human tumor cells in primary culture (colony-forming assay) has indicated that multidrug-resistant cells may be present in tumor cell populations even in the absence of prior drug therapy. Several features of the multidrug-resistant phenotype, as observed in these human tumor cell populations, differ from those observed in Chinese hamster cell systems. In particular, the variability in patterns of resistance to various agents and in expression of glycoprotein markers suggests that a substantial amount of genetic heterogeneity underlies this phenotype in human tumors.

Antineoplastic Agents↗
PubMed1980

Chemical carcinogen induction of DNA-repair synthesis in human peripheral blood monocytes.

Fresh ex vivo cultures of normal human peripheral blood monocytes, which are nonreplicative and known to possess cytochrome P-450 associated mixed-function oxidase activity, were used to assay DNA-excision repair manifested as augmented [3H]thymidine (dThd) incorporation following treatment in culture with diverse mutagenic carcinogens. Untreated monocyte cultures established from pools of 3-6 normal donors incorporated a low level of cytoplasmic [3H]dThd throughout a majority of the cells during an 18-h incubation. This background incorporation into whole cells was 80-90% inhibited by hydroxyurea (HU) at concentrations greater than 5 mM. Dose-related increases in the cumulative 18-h [3H]dThd incorporation in monocytes were observed following treatment with UV, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methyl methanesulfonate (MMS), mitomycin C (MMC), N-acetoxy-acetylaminofluorene (NA-AAF), aflatoxin B1 (AFB1), benzo[a]pyrene (BaP), and dimethylnitrosamine (DMN). The presence of HU during chemical treatment and throughout this 18 h of incubation with [3H]dThd did not influence the dose-response curves obtained with UV, MMS, NA-AAF and BaP but it increased the input dose of MNNG, MMC, DMN and AFB1 required to give peak repair incorporation. When HU was added to cultures following MNNG damage no interference with repair response was observed. HU apparently influences the extent of DNA damage by direct reactivity with these chemicals or their endogenously generated metabolites rather than inhibiting DNA-repair processes. These results provide evidence that monocytes are enzymatically proficient in base and nucleotide excision pathways and have endogenous capacity to metabolize BaP, AFB1 and DMN to DNA-damaging metabolites. As such, the monocyte is a potentially useful human cell type for detecting genotoxic chemicals and studying individuality in chemical-biological interactions.

2-Acetylaminofluorene↗
PubMed1975

Relationship of hyperplasia to cancer in 3-methylcholanthrene-induced mammary tumorogenesis.

Light microscopic study of the evolution of 3-methylcholanthrene-induced mammary tumors in Wistar-Furth rats revealed a seriation of changes proceeding from early hyperplasia (8 days) to advanced hyperplasia (57 days) and cancer (78 days). Ultrastructurally, cellular changes in advanced hyperplasia and cancer were indistinguishable, being characterized by nuclear chromatin clumping, prominent nucleoli, cytoplasmic polyribosomal aggregates and pseudopodal extensions, and prominent Golgi structures. These features, as well as the lack of limiting lamina basalia, allowed for their distinction from the cells of early hyperplasia. Further, only nodules of both advantanced hyperplasia and cancer were transplantable in syngeneic recipients. Chromosomal aberrations were qualitatively similar in cells obtained from all lesions but were progressively more frequent. Although these findings do not allow for the discrimination of advanced hyperplasia and cancer, they indicate their close pathogenetic relationship as well as the very early occurrence of chromosomal alterations in the development of mammary cancer in this model system.

Animals↗
PubMed1975

Identification of premalignant hyperplasia in methylcholanthrene-induced mammary tumorogenesis.

Mammary lobuloalveolar hyperplasia induced in rats by the administration of estradiol or progesterone did not evolve into advanced hyperplasia or cancer as was noted in animals that received these hormones and peroral instillations of methylcholanthrene. Although the early hyperplastic changes encountered in both groups were histologically indistinguishable, only cells from the lesions of the rats treated with methylcholanthrene and hormones exhibited significant numbers of aneuploid cells. This information indicates that, at least in the rat, not all instances of mammary hyperplasia possess the potential to develop into cancer. Chromosome analysis appears to represent a useful technique for the discrimination of these forms of hyperplasia. The significance of an appropriate inducer, i.e., methylcholanthrene, for the development of mammary carcinoma in this model system, as well as the well recognized proper hormonal milieu, is apparent.

Aneuploidy↗
PubMedDate not supplied

X chromatin and aging.

X chromatin analysis of 30 aged and 30 control women failed to confirm X chromosome loss as responsible for the increase in incidence of hypodiploid cells observed with increasing age in women. No evidence was found to support a previously suggested relationship between X chromosome loss and the loss of mental function (senility) as measured by psychological tests.

Adolescent↗