Defective v-erbB genes can be complemented by v-erbA in erythroblast and fibroblast transformation

We have introduced 3'-terminal deletions of increasing size in the v-erbB oncogene and analysed the effects of these mutations on the transformation of fibroblasts and erythroblasts. The results show that the transforming activity of the mutants is gradually diminished, and completely abolished in those mutants that do not produce stable v-erbB proteins. The capacity to transform erythroblasts is lost before fibroblast transformation is severely affected, suggesting that a larger part of the C-terminal domain is required for mitogenic signalling in erythroid cells than in fibroblasts. In addition, the v-erbA oncogene was found to cooperate with v-erbB not only in erythroblast but also in fibroblast transformation, inducing a fully transformed phenotype in fibroblasts partially transformed by a mutant erbB oncogene.     

Redistribution of blood flow in experimental hepatic tumours with noradrenaline and propranolol

Noradrenaline induced changes in the distribution of blood flow in implanted tumour and normal liver tissue was measured using blood flow tracer microspheres. The ratio of embolised microspheres in tumour compared to normal tissue was determined before and after the intravenous infusion of noradrenaline, propranolol and a combination of the two drugs. The ratio was significantly decreased by noradrenaline alone but significantly increased when propranolol was added to the infusate. Propranolol had no effect on the ratio. The drug combination increased the tumour to normal ratio by approximately 69% and also doubled the proportion of microspheres entering the internal tumour circulation. This represents an enhanced relative blood supply to tumour and would provide a means of preferential carriage of blood borne cytotoxic agents to tumour tissue rather than normal tissue.     

Regulation of differentiation of the tracheobronchial epithelium.

The study of differentiation has been the domain of embryologists and developmental biologists and, in the pulmonary field, the concern of neonatologists. Why should those of us who are neither be interested in differentiation of the epithelium lining the conducting airways? The reason is that injury to the airway epithelium and disruption of its steady state and its normal differentiation are common occurrences in both acute episodes of infection and during chronic diseases such as chronic obstructive pulmonary disease and asthma. Thus, it is important to know how injury is repaired and which are the critical mechanisms that control and regulate differentiation.     

A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial

Data on 1711 patients, aged up to 55 years, in the MRC AML 10 trial were used to create a prognostic index for use in risk-directed therapy decision making for younger patients with acute myeloid leukaemia (AML). Two parameters, response after course 1 and cytogenetics, were strongly predictive of outcome. For patients with complete remission, partial remission and resistant disease, 5-year survival from the start of course 2 was 53%, 44% and 22% and relapse rates were 46%, 48% and 69% respectively, and for patients with favourable, intermediate and adverse karyotypic abnormalities, survival was 72%, 43% and 17% and relapse rates were 34%, 51% and 75% respectively (all P < 0.0001). Patients with FAB type M3 but no cytogenetic t(15;17) also had a low relapse rate (29%). These three factors were combined to give three risk groups: good (favourable karyotype or M3, irrespective of response status or presence of additional abnormalities), standard (neither good nor poor), poor (adverse karyotype or resistant disease, and no good-risk features). Survival for these three groups was 70%, 48% and 15% respectively and relapse rates were 33%. 50% and 78% (both P < 0.0001). The index is simple (based on just three parameters), robust (derived from 1711 patients), highly discriminatory (55% survival difference between good and poor risk) and validated, so can be applied in the clinical setting to assist with therapeutic decisions as in the current AML 12 trial.