Glioma stem cells promote radioresistance by preferential activation of the DNA damage response

@article{Bao2006GliomaSC,
  title={Glioma stem cells promote radioresistance by preferential activation of the DNA damage response},
  author={Shideng Bao and Qiulian Wu and Roger E. McLendon and Yueling Hao and Qing Shi and Anita B. Hjelmeland and Mark W. Dewhirst and Darell D. Bigner and Jeremy N. Rich},
  journal={Nature},
  year={2006},
  volume={444},
  pages={756-760}
}
Ionizing radiation represents the most effective therapy for glioblastoma (World Health Organization grade IV glioma), one of the most lethal human malignancies, but radiotherapy remains only palliative because of radioresistance. The mechanisms underlying tumour radioresistance have remained elusive. Here we show that cancer stem cells contribute to glioma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity. The fraction… 

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References

SHOWING 1-10 OF 33 REFERENCES

Identification of human brain tumour initiating cells

The development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo gives strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.

Identification of a cancer stem cell in human brain tumors.

The identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation is reported.

DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis

It is shown that in clinical specimens from different stages of human tumours of the urinary bladder, breast, lung and colon, the early precursor lesions commonly express markers of an activated DNA damage response.

Cancerous stem cells can arise from pediatric brain tumors

It is found that tumor-derived progenitors form neurospheres that can be passaged at clonal density and are able to self-renew, which may have important implications for treatment by means of specific targeting of stem-like cells within brain tumors.

Isolation and Characterization of Tumorigenic, Stem-like Neural Precursors from Human Glioblastoma

It is reported that, unlike other brain cancers, the lethal glioblastoma multiforme contains neural precursors endowed with all of the critical features expected from neural stem cells.

Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions

It is proposed that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations.

Human cortical glial tumors contain neural stem‐like cells expressing astroglial and neuronal markers in vitro

The data suggest that the latent critical stem cell characteristics can be epigenetically induced by growth conditions not only in cells from neurogenic regions of normal CNS but also in cells in cortical glial tumors.

Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints.

The molecular mechanisms of DNA repair and the DNA damage checkpoints in mammalian cells are analyzed and apoptosis, which eliminates heavily damaged or seriously deregulated cells, is analyzed.

Direct isolation of human central nervous system stem cells.

  • N. UchidaD. Buck I. Weissman
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2000
Upon transplantation into brains of immunodeficient neonatal mice, the sorted/expanded hCNS-SC showed potent engraftment, proliferation, migration, and neural differentiation.

Cell cycle checkpoint signaling through the ATM and ATR kinases.

These checkpoints contain, as their most proximal signaling elements, sensor proteins that scan chromatin for partially replicated DNA, DNA strand breaks, or other abnormalities, and translate these DNA-derived stimuli into biochemical signals that modulate the functions of specific downstream target proteins.