Time trends in the outcome of lung cancer management: a study of 9,090 cases diagnosed in the Mersey Region, 1974-86

The purpose of this paper is to describe temporal trends in the treatment of lung cancer in the Merseyside Region of England over the years 1974-86. A detailed analysis of 9,090 cases of histologically confirmed tumours showed that age at diagnosis and histological type were important prognostic factors, with the 5 year survival of adenocarcinoma, squamous carcinoma, undifferentiated carcinoma and small cell carcinoma after treatment being 22.5%, 18.5%, 10% and 3.5% respectively. An analysis of 741 cases of small cell carcinoma given chemotherapy over the same period showed progressive improvement in 2 year survival from 2.5 to 7.5% (P less than 0.001) and this was shown to be closely associated with the increasing use of intravenous combination chemotherapy. The survival of patients who underwent surgical resection in the three periods 1974-77, 1978-81 and 1982-86 showed a continuous improvement in median survival from 13 to 30 months (P less than 0.001). Overall survival curves of all treated cases showed a significant improvement in median survival from 8 to 10 months and 5 year survival from 12.5 to 17.5% (P = 0.001). With improved staging assessment, the value of surgical resection of all histological types is emphasised, and in the case of the small cell subtype, the increasing use of combination chemotherapy would appear to have paralleled an increase in median and 2 year survival. These data support the argument that with appropriate case selection, there is a survival benefit associated with active treatment for lung cancer.     

Anti-IgM induces transforming growth factor-beta sensitivity in a human B-lymphoma cell line: inhibition of growth is associated with a downregulation of mutant p53

We wished to examine the role of transforming growth factor-beta (TGF- beta) in the regulation of human lymphoma cell growth. The RL cell line is an immunoglobulin M (IgM)+, IgD+ B lymphoma cell line, which does not constitutively express receptors for TGF-beta, and thus has lost the ability to respond to the inhibitory effects of TGF-beta. We demonstrate here that anti-Ig antibodies can efficiently upregulate the expression of TGF-beta receptors and promote sensitivity to growth inhibition by TGF-beta. Furthermore, because TGF-beta has been shown to function in late G1 of the cell cycle, we examined the ability of TGF- beta to modulate two tumor suppressor proteins known to be critical regulators of the G1/S transition, Rb and p53. Rb is a 105- to 110-kD phosphoprotein, which has been shown to maintain its growth suppressive function when it is found in the hypophosphorylated state. Wild-type p53 is a 53-kD phosphoprotein that appears to be important in preventing cell-cycle progression and promoting apoptosis in cells with DNA damage, whereas mutant p53 can overcome those functions. We show here that TGF-beta treatment of phorbol myristate acetate (PMA) or anti- Ig-activated RL cells results in growth inhibition through a dual effect on Rb and mutant p53. After TGF-beta treatment, we observe a predominance of Rb in the hypophosphorylated, growth suppressive form. In addition, we show a decrease in levels of mRNA and protein for mutant p53. We also show that, although these changes are sufficient to halt progression through the cell cycle, the cells do not appear to undergo extensive programmed cell death following 72 hours of TGF-beta treatment. Thus, although these lymphoma cells maintain the capacity to be negatively growth regulated by TGF-beta, the ability of TGF-beta to induce apoptosis must be independently controlled.