Telomerase expression in gliomas including the nonastrocytic tumors

Chong, Edith Y.Y.; Lam, Paula Yeng Po; Poon, Wai-sang; Ng, Ho Keung

doi:10.1016/s0046-8177(98)80009-9

Cited by 28 publications

(22 citation statements)

References 15 publications

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“…Within the glial neoplasms, low-grade gliomas lack telomerase activity and ALT, and thus fail to maintain their telomeres (Chong et al, 1998;Tabori et al, 2006b). This results in progressive telomere attrition and may be associated with the unique tendency of paediatric low-grade gliomas to undergo growth arrest (Tabori et al, 2006b) and their associated excellent survival.…”

Section: Discussionmentioning

confidence: 99%

Telomere maintenance and dysfunction predict recurrence in paediatric ependymoma

Tabori

Wong

et al. 2008

Br J Cancer

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We have recently described the enzymatic subunit of telomerase (hTERT) as an important prognostic marker for paediatric ependymoma. Because of the lack of good, representative pre-clinical models for ependymoma, we took advantage of our large cohort of ependymoma patients, some with multiple recurrences, to investigate telomere biology in these tumours. Our cohort consisted of 133 ependymomas from 83 paediatric patients and included 31 patients with recurrences. Clinical outcome was measured as overall survival, progression-free survival and response to therapy. In all 133 tumours, hTERT expression correlated with proliferative markers, including MIB-1 index (Po0.0001) and mitotic index (P ¼ 0.005), as well as overall tumour grade (P ¼ 0.001), but not with other markers of anaplasia. There was no correlation between telomere length and hTERT expression or survival. Surprisingly, prior radiation or chemotherapy neither induced sustained DNA damage nor affected telomere maintenance in recurrent tumours. There was an inverse correlation between hTERT expression and telomere dysfunction as measured by gH2AX expression (P ¼ 0.016). Combining gH2AX and hTERT expressions could segregate tumours into three different survival groups (log rank, Po0.0001) such that those patients whose tumours expressed hTERT and showed no evidence of DNA damage had the worst outcome. This study emphasises the importance of telomere biology as a prognostic tool and telomerase inhibition as a therapeutic target for paediatric ependymoma. Furthermore, we have demonstrated that analysing tumours as they progress in vivo is a viable approach to studying tumour biology in humans.

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Section: Discussionmentioning

confidence: 99%

Telomere maintenance and dysfunction predict recurrence in paediatric ependymoma

Tabori

Wong

et al. 2008

Br J Cancer

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“…9,10 The percentage of GBM tumors that have been shown to express telomerase enzyme activity varies between 26% and 67%. [11][12][13][14][15] This variability probably reflects the highly heterogeneous nature of GBM. In fact, where sampling of multiple regions from the same tumor or microdissection for selective analysis of tumor cells were used, 100% of GBM were found to show telomerase activity.…”

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confidence: 99%

Telomerase inhibition by stable RNA interference impairs tumor growth and angiogenesis in glioblastoma xenografts

Pallini

Sorrentino

Pierconti

et al. 2005

Intl Journal of Cancer

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Telomerase is highly expressed in advanced stages of most cancers where it allows the clonal expansion of transformed cells by counteracting telomere erosion. Telomerase may also contribute to tumor progression through still undefined cell growth-promoting functions. Here, we inhibited telomerase activity in 2 human glioblastoma (GBM) cell lines, TB10 and U87MG, by targeting the catalytic subunit, hTERT, via stable RNA interference (RNAi). Although the reduction in telomerase activity had no effect on GBM cell growth in vitro, the development of tumors in subcutaneously and intracranially grafted nude mice was significantly inhibited by antitelomerase RNAi. The in vivo effect was observed within a relatively small number of population doublings, suggesting that telomerase inhibition may hinder cancer cell growth in vivo prior to a substantial shortening of telomere length. Tumor xenografts that arose from telomerase-inhibited GBM cells also showed a less-malignant phenotype due both to the absence of massive necrosis and to reduced angiogenesis. ' 2005 Wiley-Liss, Inc.

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“…Telomerase activity, which is generally undetectable in normal somatic cells, is expressed in approximately 90% of tumors (Kim et al, 1994;Broccoli et al, 1995;Hiyama et al, 1995). In malignant gliomas, telomerase activity is very often detected (Table 1) (Langford et al, 1995;DeMasters et al, 1997;Sallinen et al, 1997;Sano et al, 1998;Kleinschmidt-DeMasters et al, 1998;Chong et al, 1998;Hiraga et al, 1998;Le et al, 1998;Weil et al, 1999;Carroll et al, 1999;Falchetti et al, 1999;Huang et al, 1999;Kleinschmidt-DeMasters et al, 2000;Harada et al, 2000). In Grade I or II of gliomas, telomerase activity is detected in 0% or 0 to 33%, respectively.…”

Section: Telomerase In Malignant Gliomasmentioning

confidence: 99%

Telomerase as a therapeutic target for malignant gliomas

et al. 2002

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Telomerase, a ribonucleoprotein enzyme, is considered as a potential target of cancer therapy because of its preferential expression in tumors. In particular, malignant gliomas are one of the best candidates for telomerasetargeted therapy. It is because malignant gliomas are predominantly telomerase-positive, while normal brain tissues do not express telomerase. In theory, there are two telomerase-associated therapeutic approaches for telomerase-positive tumors. One approach is the antitelomerase cancer therapy to directly inhibit telomerase activity, resulting in apoptotic cell death or growth arrest. Two major components of the telomerase holoenzyme complex, the RNA template (hTER) and catalytic subunit (reverse transcriptase, hTERT) are well considered as therapeutic targets. The other approach is the telomerasespeci®c cancer therapy by targeting telomerase-expressing tumor cells as a means to directly kill the cells. Strategies using the transfer of therapeutic gene under the hTERT promoter system as well as immunotherapy directed against telomerase-positive cells are generally included. These telomerase-associated therapies are very promising for the treatment of malignant gliomas.

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Telomerase expression in gliomas including the nonastrocytic tumors

Cited by 28 publications

References 15 publications

Telomere maintenance and dysfunction predict recurrence in paediatric ependymoma

Telomere maintenance and dysfunction predict recurrence in paediatric ependymoma

Telomerase inhibition by stable RNA interference impairs tumor growth and angiogenesis in glioblastoma xenografts

Telomerase as a therapeutic target for malignant gliomas

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