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Biomedical subjects

G Cowley

Publications and source records attributed to G Cowley.

88 records · Page 5Linked to original sources

Evidence for increased epidermal growth factor receptors in human sarcomas.

The results of an immunocytochemical study of the epidermal growth factor receptor (EGFR) in 35 human soft-tissue sarcomas, using a murine monoclonal antibody (MAb) EGF-R1, are reported. In many of the tumours staining was stronger than in the adjacent stroma, suggesting increased levels of receptor. Particularly strong staining was seen in one epithelioid sarcoma and in the spindle-cell component of a synovial sarcoma. Binding studies carried out on an epithelioid sarcoma cell line established from one of the specimens, using radiolabelled EGF, showed that approximately 8% of the receptors were of high affinity with a dissociation constant (KD) of approximately 10(-10)M, while the remainder were of lower affinity with a KD of 10(-9)M. The cells expressed a total of 1.7 X 10(6) receptors/cell which is equivalent to that found in some epidermoid tumours where gene amplification has been demonstrated. These data suggest that, as with other tumours recently reported, increased levels of epidermal growth factor receptor may be related to transformation.

Antibodies, Monoclonal↗

Production of beta-human chorionic gonadotrophin by human squamous carcinoma cell lines.

Eight out of 9 human squamous carcinoma cell lines ectopically secrete the beta subunit of human chorionic gonadotrophin (beta-HCG) in amounts detectable by radioimmunoassay. In contrast, both normal and SV40-transformed keratinocytes show no such evidence of beta-HCG secretion. Ectopic beta-HCG is identical in its gel exclusion and high-performance liquid chromatographic properties to placental beta-HCG and, in radioimmunoassay, yields a dilution curve parallel to that of placental beta-HCG. Dibutyryl cyclic AMP, but not sodium butyrate, stimulates beta-HCG secretion by the one human cell line examined, LICR-LON-HN-5, suggesting that ectopic production by these cells is similar to trophoblastic beta-HCG secretion, and differs from most other non-trophoblastic cell lines previously examined.

Bucladesine↗

Cellular localisation of human epidermal growth factor receptor.

We show here, using immunohistological techniques and a monoclonal antibody to the receptor for epidermal growth factor (EGFR) (Waterfield et al. 1982) that EGFR is present on a wide range of normal epithelial tissues and tumours arising from those sites. The distribution of the receptor suggests that EGF may be involved in the control of proliferation and possibly differentiation of surface epithelia. The strong tumour cell staining suggests an increased expression of the receptor in certain carcinomas.

Cell Division↗

Differentiation of normal and malignant human squamous epithelium in vivo and in vitro: a morphologic study.

We report a light microscopic and ultrastructural analysis of the comparative degrees of differentiation seen in keratinocytes derived from the tongue and epidermis with those of a well-differentiated human squamous carcinoma cell line (LICR-LON-HN5). When growing on plastic substrates, all cultures had a similar morphology, with multilayering and the production of cornified envelopes. When cultured on collagen gels the structure was more organized, with keratohyalin granules and keratin whorl formation in both the normal and the malignant cultures. Normal keratinocytes injected into athymic mice produced epidermal cysts, while cells from the cell line produced well-differentiated squamous cell carcinomas, which were partially solid and partially cystic. the tumor was well organized, with identifiable basal cells, spinous cells, keratohyalin granules, and a prominent basal lamina at the stromal/epithelial interface. This model is to be developed for comparative studies between normal and malignant cells, with particular reference to basement membrane production and to investigations of the relative importance of extrinsic and intrinsic factors in the control of squamous differentiation.

Animals↗

Differentiation of a squamous carcinoma cell line in culture and tumourigenicity in immunologically incompetent mice.

The process of differentiation in keratinocytes is accompanied by specific membrane and cytoplasmic changes. Using simple tissue culture techniques a well differentiated squamous carcinoma cell line is shown to exhibit in vitro keratinization with the formation of a multilayered structure and shedding of cells with a cornified envelope. The cell line produces tumours when xenografted into mice which are well differentiated and indistinguishable at the light and electron microscope level from the original surgical biopsy. It is concluded that the tumour will provide a suitable model for detailed in vitro and in vivo studies to compare both biological and pathological features of normal keratinocytes and their malignant counterparts.

Animals↗

Growth in agar and tumor formation in immunologically incompetent mice as criteria for keratinocyte transformation.

Established cell lines from 8 human squamous cell carcinomas (SCC) together with normal human keratinocytes, have been investigated for their ability to grow in soft agar and as xenografts when injected as a single cell suspension into immunologically incompetent mice. One of 8 SCC lines formed colonies with efficiencies greater than 1% in soft agar, and only 2 formed progressively growing tumors when injected into animals. It is concluded that these 2 criteria are not reliable markers of malignant transformation in squamous epithelia unless cytological criteria are also applied.

Agar↗