Telomeres and telomerase: new targets for the treatment of liver cirrhosis and hepatocellular carcinoma  André Lechel, Michael P. Manns, K.Lenhard Rudolph  Journal of Hepatology  Volume 41, Issue 3, Pages 491-497 (September 2004) DOI: 10.1016/j.jhep.2004.06.010

Fig. 1 There are two possibilities for telomerase therapy in liver disease: critical telomere leads to induction of replicative senescence and chromosomal instability. Replicative senescence impairs regeneration during ageing and chronic disease. Chromosomal instability elevates the rate of cancer initiation. In contrast, telomere dysfunction and chromosomal instability inhibit tumor progression and telomere stabilisation (e.g. by telomerase activation) is required for cancer progression. [This figure appears in colour on the web.] Journal of Hepatology 2004 41, 491-497DOI: (10.1016/j.jhep.2004.06.010)

Fig. 2 The effects of telomere shortening on regeneration and carcinogenesis. 1. Telomerase inhibitors will destabilise telomeres in telomerase-positive HCC thereby inducting tumour cell apoptosis and cell cycle arrest. Telomerase-negative, non-cancerous liver tissue will not be affected by telomerase inhibitors. 2. Telomerase activators will stabilise the telomeres in telomerase-negative cirrhotic liver. Telomere stabilisation will rescue hepatocyte senescence and will improve the regenerative capacity of the cirrhotic liver. This therapy will not affect the growth of telomerase-positive HCC. Senescent hepatocytes are shown as blue circles. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) Journal of Hepatology 2004 41, 491-497DOI: (10.1016/j.jhep.2004.06.010)