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Biomedical subjects

C L Eaton

Publications and source records attributed to C L Eaton.

15 recordsLinked to original sources
PubMed1994

Transforming growth factor beta 1 expression in benign and malignant prostatic tumors.

The expression of transforming growth factor beta 1 (TGF-beta 1) in prostate specimens obtained from patients with benign prostatic hyperplasia (BPH, n = 32) and prostate carcinoma (n = 66) was investigated using Northern blot analysis and immunohistochemistry. Northern blot analysis revealed TGF-beta 1 message (2.5 kb) in virtually all of the samples examined, reflecting the ubiquitous nature of this growth factor. No statistical difference was found between the levels of mRNA detected in benign and malignant tissues due, in part, to the inherent heterogeneity of prostate tissue. Immunohistochemical methods using an antibody to native TGF-beta 1 revealed a novel pattern of immunoreactivity. Staining observed only in certain epithelial cells of benign glands was associated with areas of infection rather than tumorigenesis. Interestingly, intense staining was also seen in polymorphonuclear leukocytes. No correlation was found with the mRNA results, suggesting that this antibody is binding to TGF-beta 1 activated in response to infection rather than detecting sites of synthesis of latent TGF-beta 1.

Blotting, Northern↗
PubMed1991

Steroids and the prostate.

Interelationships between steroid and growth factor regulation of cell proliferation has been examined in two androgen sensitive prostatic cell lines, grown in defined medium. The cell lines used were derived from normal (CAPE) and neoplastic (LNCaP) tissues. The growth of both cell lines was elevated by challenge with serum, androgens and epidermal growth factor (EGF) used as single agents. The effects of androgen in CAPE were small, but significant while the profound effects of these agents on the growth of LNCaP were confirmatory of other studies. Androgens upregulated EGF receptor expression in LNCaP measured by both ligand binding capacity and mRNA analysis. This was not observed in the CAPE cells. Addition of serum (whole or charcoal stripped) suppressed the observed androgenic stimulation of EGF receptor expression in LNCaP. This apparent anomaly is discussed in relation to the growth enhancing properties of serum in these cell lines and in the wider context of normal and neoplastic growth control in the prostate.

Androgens↗
PubMed1991

Steroid hormones and the pathogenesis of benign prostatic hyperplasia.

The pathogenesis of benign prostatic hyperplasia (BPH) is still poorly understood: there is, however, general acceptance that the condition is not premalignant and that it has an etiology distinct from that of cancer. Interest now focuses on the biochemistry of the target prostate cells and the propensity of the gland for uncontrolled growth. Dihydrotestosterone (DHT) is the active intracellular androgen formed from testosterone by 5 alpha-reductase. DHT concentrations appear a little higher in BPH tissue than in normal tissue, and there is no doubt that DHT-receptor complex modulates gene expression. Current studies suggest that DHT is essential but not sufficient for proliferation, and that other regulatory factors, including peptide growth factors, are prerequisite. The growth responsiveness of prostate tissue to androgens may be dependent on the balance between epithelial and stromal tissues, with biologic processes in the epithelium indirectly controlled by androgen-dependent mediators of stromal origin.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1990

The role of endocrine therapy in prostatic cancer.

When judged by randomized clinical trial, current endocrine therapies offer symptomatic relief to prostatic cancer patients for an average period of 1-2 years following initiation of therapy. Medical castration with LHRH analogues is a safe and effective way of achieving 'castrate' levels of circulating androgens without the undesirable aspects of surgery. While there is some evidence for the value of combined therapies using these agents in combination with anti-androgens for 'total androgen blockade' in some patients, overall this approach has not been shown to offer advantages over castration, either surgical or medical, alone in controlled trials. Secondary endocrine therapy does not offer convincing objective response rates, suggesting that disease progression is independent of androgens.

Androgen Antagonists↗
PubMed1989

Binding of epidermal growth factor by human normal, hypertrophic, and carcinomatous prostate.

Saturable binding sites for radioiodinated epidermal growth factor (EGF) have been quantified in surgical specimens of benign prostate hypertrophy (BPH), histologically normal (HN) prostate, and prostate cancer. Values for EGF binding did not differ significantly between HN prostate and prostate cancer, although dedifferentiated samples tended to higher levels. These were coincident with lower comparative levels of androgen receptors. Unfractionated BPH tissue contained lower levels of EGF binding than either HN or carcinomatous prostate, but in separated epithelial cells EGF binding fell into the same range. Saturation analyses showed two affinity classes of binding in all except dedifferentiated tissues.

Binding Sites↗
PubMed1989

Prostatic cancer: aetiology and endocrinology.

Prostate cancer is common in the male population, worldwide. Several therapies are currently available, but only greater understanding of the complex processes that govern the growth of the cancer will produce real progress in treatment.

Humans↗
PubMed1988

Growth of a spontaneous canine prostatic adenocarcinoma in vivo and in vitro: isolation and characterization of a neoplastic prostatic epithelial cell line, CPA 1.

Neoplastic epithelium derived from a spontaneous canine prostatic adenocarcinoma has been maintained and grown in cell culture and as xenografts in athymic mice. An epithelial cell line (CPA 1) has been isolated from primary cultures and has been partially characterized in vitro. The growth of this cell line was not modified by either androgens or estrogens, and high-affinity receptors for these steroids could not be demonstrated in these cells. Xenografts were serially transplantable, with growth being similar in both sexes. Receptors for androgens and estrogens could not be detected in homogenates of xenografts or primary tumor. The histological appearances of serially transplanted tumors, and of xenografts generated by inoculation of the cell line (CPA 1) and several cloned substrains, were very similar to that of the primary tumor and were judged to be well differentiated. The characteristics of this neoplastic cell type have been compared with those of normal prostatic epithelium.

Adenocarcinoma↗
PubMed1988

Growth factor involvement and oncogene expression in prostatic tumours.

The effects of EGF, TGF alpha and 5 alpha-dihydrotestosterone on the growth of a prostatic epithelial cell line have been evaluated in clonal growth assays. Similar bioassay systems have been used to identify tumour-associated growth promoters derived from a human prostatic carcinoma cell line (PC3). Growth factor activity was associated with proteins of Mr 20-30 kDa. In a separate study, EGF receptor concentration and cellular proto-oncogene expression was assessed in prostatic tumour samples. In prostatic carcinoma samples, strong correlation was observed between EGF receptor concentration and c-myc expression. There were no significant correlations between EGF receptor concentration and tumour grade or androgen receptor content in carcinoma samples. EGF receptor concentration was significantly higher in prostatic carcinoma specimens than in BPH.

Animals↗
PubMed1988

Growth factor receptors and oncogene expression in prostate cells.

Specimens of benign prostatic hypertrophy (BPH) and prostate carcinoma and prostate cells in culture were assessed for their capacity to bind androgens, radioiodinated EGF, and IGF-I, and to express certain cellular protooncogenes. Prostate cell lines contained receptors for both EGF and IGF-I. Similarly, clinical samples of human diseased prostate contained receptors for both of these factors. Prostate carcinoma contained higher concentrations of EGF receptors based on DNA than did BPH, although it is accepted that BPH may not be the appropriate comparison for carcinoma. Increased EGF receptors were associated circumstantially with a decline in androgen receptors with deteriorating differentiation status and with an increase in expression of c-myc. Androgen receptor concentration correlated with increased expression of c-fos. Deteriorating differentiation status was associated with the appearance or increase in secondary sites with lower affinity for IGF-I. Whereas c-myc expression was increased in all grades of carcinoma compared to BPH, expression of c-H-ras accompanied loss of differentiation. Although those alterations are hindered by tissue heterogeneity and correlations are essentially circumstantial, they may provide clues to the progression of prostate cancer that can be validated in prostate cell lines with similar growth response capabilities.

Animals↗
PubMed1982

Epithelial and fibroblastoid cell lines derived from the normal canine prostate. I. Separation and characterization of epithelial and stromal components.

Cell cultures displaying exclusively epithelial or fibroblastoid morphology have been isolated by spillage and collagenase digest techniques, respectively. Primary cultures of both cell types have been readily subcultured. The use of a type I collagen substrate has been shown to be essential to the growth of normal prostatic epithelium in monolayer cultures. The ability to generate replicate subcultures of both cell types has allowed the quantitative characterization of the mitogenicity of fetal bovine serum and insulin in early subcultures. The control of culture conditions has permitted uniform cell population growth in early subculture with regular population doubling times in log phase of growth. Epithelial cultures have been shown to display many ultrastructural characteristics common to the normal epithelium of the canine prostate.

Animals↗