Biomedical subjects
Publications and source records attributed to G Needham.
Mesenchymal chondrosarcomas are rare tumours, the minority arising in an extraskeletal site. We describe a case of extraskeletal mesenchymal chondrosarcoma occurring in the parapharyngeal space. This was demonstrated by computed tomography (CT), magnetic resonance imaging (MRI) and angiography.
Proteins regulated by or related to the oestrogen receptor (ER) may prove to be more reliable indicators of prognosis and hormone sensitivity then expression of the receptor itself. It has been shown recently that expression of epidermal growth factor receptor (EGFR) is associated with a poor prognosis in breast cancer. In a series of 60 breast cancers, we have studied relationships between ER, ER-D5 oestrogen receptor related protein, P24 oestrogen regulated protein, and EGFR using an immunohistochemical technique employing monoclonal antibodies in each case. In addition, radioligand binding assays for ER and EGFR were carried out and tumour histological grade was determined. Seventy-one per cent and forty-three per cent of tumours stained for ER-D5 and P24, respectively, but there was no relationship between staining for these and ER or EGFR status. There was a significant correlation between staining for ER and EGFR, and the respective biochemical assays. Relating ER to EGFR, very few ER-positive cases expressed EGFR, but this relationship fell short of significance. The prognostic significance of expression of the epitopes recognized by the ERD5 and P24 antibodies must await assessment of clinical outcome.
The endocrine effects of aminoglutethimide 125 mg twice daily and hydrocortisone 20 mg twice daily were assessed in 45 postmenopausal women with advanced breast cancer. Oestrone and oestradiol levels were suppressed by 60% within 2 weeks and suppression was maintained for more than 6 months of chronic treatment. In contrast to conventional dose AG with hydrocortisone, or low dose AG without hydrocortisone, delta 4 androstenedione was suppressed by 65%. This effect may contribute to optimal oestrogen suppression.
Aminoglutethimide 125 mg twice daily and hydrocortisone 20 mg twice daily was used to treat 76 postmenopausal women with advanced breast cancer. There were 4 CR, 17 PR (objective response rate 28%). Highest response was in soft tissue. CNS toxicity was less than with conventional dose AG (drowsiness 7% v. 31%), although the incidence of rash was equivalent. Previous responders to tamoxifen had a higher response (33%) than previous non-responders (9%). The lower toxicity and maintained efficacy suggest that this should be the standard dosage regimen.
Cell membranes from ten non-small cell lung cancers and four specimens of adjacent lung tissue were assessed for the presence of urokinase type plasminogen activator (uPA) receptors. Displacement binding studies using 125I labelled urokinase showed specific binding on lung cancer and lung membrane preparations. Scatchard analysis showed that the dissociation constant of high affinity sites on tumour membranes was 2.9 x 10(-11) M/1 and on lung membranes was 2 x 10(-9) M/1. The concentration of high affinity binding sites on tumour membrane was 54 fmol/mg of membrane protein and on normal lung membrane was 170 fmol/mg protein. Two-point binding assays showed specific binding of urokinase on five of eight tumour membranes and one of three normal lung membranes. There was no correlation between the amount of urokinase bound and tumour subtype or extent of disease. Because of interactions between uPA and epidermal growth factor receptors (EGFr) in cell culture and because lung cancers express increased EGFr we studied the association of uPA receptors and EGFr. Seven tumours expressed EGFr at 6.8-67.6 fmol/mg of protein of EGFr and four normal lung membranes had EGFr at 5.2-15.6 fmol/mg protein EGFr. There was no correlation between uPA receptors and EGFr in this series. We conclude that non-small cell lung cancers carry receptors for urokinase and this provides a novel mechanism for control of local proteolysis.