The long term survivors

Abstract

Recent research indicates that approximately 60% of children diagnosed with cancer in Britain are cured and as a result, about 1 in a 1000 of the general population will soon be survivors of childhood cancer. Unfortunately some elements of the therapies which are responsible for this remarkable success are associated with serious complications, sometimes decades after their administration. Therefore, a comprehensive knowledge of the risks and benefits of different therapies will only be obtained by monitoring the health of survivors indefinitely. With such therapeutic success, increasingly the composition of future treatment protocols will be influenced by knowledge of the risks of long term morbidity and mortality associated with past therapies. An awareness of the long term risks of complications of treatment is also important for estimating the future demand on the health services of this increasing proportion of the general population who together represent many life years of care. This chapter reviews what is known concerning the long term risks of complications of different treatments. Appropriate strategies for future clinical and epidemiological follow-up of the survivor population are discussed and the need for indefinite follow-up of the survivor population is emphasised.

The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis

“…There are also multiple reports that E6 has p53 independent transformation properties, implying that HPV E6 genes may uncouple cellular growth and apoptotic responses. However, both proand anti-apoptotic activities of E6 have been reported, and in some experimental systems, the apoptosis modulatory e ects were thought to represent a p53-independent function of E6 (Fan et al, 1995;Hawkins et al, 1996;Griep 1994, 1995;Puthenveetil et al, 1996;Steller et al, 1996;Thomas et al, 1996;Tsang et al, 1995;Wahl et al, 1996;Xu et al, 1995;Yu et al, 1997). Since BPV-1 E6 does not bind p53 in vitro or promote its degradation in vivo, it provides an excellent model to explore the p53-independent functions of E6.…”

“…Since E6 proteins from high-risk HPVs bind and promote the degradation of p53, it is intuitive to propose that they would suppress apoptosis. Multiple diverse studies have addressed the role of high-risk HPV E6 in apoptosis, and both proand anti-apoptosis activities of E6 have been reported (Fan et al, 1995;Hawkins et al, 1996;Griep, 1994, 1995;Puthenveetil et al, 1996;Steller et al, 1996;Thomas et al, 1996;Tsang et al, 1995;Wahl et al, 1996;Xu et al, 1995;Yu et al, 1997). The apparent inconsistency in determining the e ect of E6 on apoptosis could be due to experimental conditions.…”

p53 mediated sensitization of squamous cell carcinoma of the head and neck to radiotherapy

“…In addition, chemosensitivity, along with apoptosis, was restored by expression of wtp53 in non-small cell lung carcinoma mouse xenografts carrying mtp53 (Fujiwara et al, 1994). However, the presence of some A p53 sensitizes head and neck cancer to radiotherapy KF Pirollo et al con¯icting reports, (Wahl et al, 1996;Hawkins et al, 1996) indicate that the relationship between p53 and chemoresistance may have a tissue or cell type-speci®c component.…”

Human lymphoblastoid cell lines expressing mutant p53 exhibit decreased sensitivity to cisplatin-induced cytotoxicity

“…Previously cisplatin has been reported to induce p21/Waf1 protein within 6 h in human foreskin ®broblasts (Hawkins et al, 1996). MDM2 was also induced with both treatments although the kinetics of that induction varied with the type of genotoxic stress.…”