Telomerase Activity in Small-Cell and Non-Small-Cell Lung Cancers

Abstract

Telomerase activity may be useful both as a diagnostic marker to detect the existence of immortal lung cancer cells in clinical materials and as a target for therapeutic intervention.

Telomerase activity in 144 brain tumours

“…Therefore, some of the tumours we studied may have been removed before any of their cells acquired immortality. In contrast, the telomerase positivity rate of metastatic brain tumours was as high as that of primary cancers (Chadeneau et al, 1995;Hiyama E et al, 1995b;Hiyama K et al, 1995;Tahara et al, 1995;Sommerfeld et al, 1996). This is because metastatic brain tumour cells have already become immortal at their primary lesion stage.…”

“…Therefore, and as originally recommended (Kim et al, 1994;Piatyszek et al, 1995), the TRAP assay was performed with 27 PCR cycles. Although relative telomerase activity of some systemic cancers has been evaluated by dilution analysis (Hiyama E et al, 1995a and b;Hiyama K et al, 1995); Tahara et al, 1995) and has even been semiquantified by several investigators (Taylor et al, 1996), the telomerase activity of tumour tissues has mostly been assessed visually as being either positive or negative (Kim et al, 1994;Chadeneau et al, 1995;Langford et al, 1995;Piatyszek et al, 1995;Sommerfeld et al, 1996). To justify the visual, 'all-or-nothing' evaluation of telomerase activity, we quantified the TRAP assays of brain tumours and compared the results with visually determined positivity.…”

Targeted therapy of human malignant glioma in a mouse model by 2-5A antisense directed against telomerase RNA

“…Therefore, in order to improve the prognosis in this invariably fatal disease, it will be essential to explore novel forms of treatment. Recently it was shown that 70 ± 80% of tumors, including malignant gliomas, show very high levels of expression of telomerase, whereas, with a few exceptions, normal cells do not (Counter et al, 1992;Kim et al, 1994;Broccoli et al, 1995;Hiyama et al, 1995;Langford et al, 1995). Telomerase is the ribonucleoprotein enzyme complex that elongates telomeric DNA (TTAGGG) n (Blackburn, 1991) and is now thought to be an important step in the development of cellular immortality and oncogenesis (de Lange et al, 1994).…”

Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis

“…Telomerase, a ribonucleic acid-protein complex, adds telomeric repeats to the ends of chromosomes (Greider and Blackburn, 1985). Overall, 70 ± 95% of malignant tumor cells express relatively high level of telomerase (Kim et al, 1994;Broccoli et al, 1995;Counter et al, 1995;Hiyama et al, 1995aHiyama et al, ,b, 1997Langford et al, 1995;De Masters et al, 1997). As telomeres play a role in protecting DNA, there is the possibility that, if telomerase activity is inhibited in tumor cells, they might be more vulnerable to DNA-damaging agents.…”