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Sökning: WFRF:(Poon Leonard W.)

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1.
  • Poon, Leonard W., et al. (författare)
  • Understanding Very Old Age : Looking Back and Thinking Forward
  • 2016
  • Ingår i: Journal of Aging and Social Policy. - : Informa UK Limited. - 0895-9420 .- 1545-0821. ; 28:3, s. 208-217
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding human development among the oldest old is a sequential building process taking into account building-block data, theories, and models from childhood, adulthood, and old age toward a new territory of oldest-old survivors who have lived way beyond the average life-span. A central question is whether the oldest-old survivors have developed specific survival techniques and/or protective environments that nurture survival. Or are the oldest old statistical outliers who by happenstance continue to survive further into old age? This commentary provides a historical framework on the papers in this series that describe challenges confronted by the oldest-old survivors in order to advance our understanding of survival of the oldest old. A clear understanding of the contributors to longevity could guide public policies toward well-being and life satisfaction among our oldest-old citizens.
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2.
  • Zhukova, Nataliya, et al. (författare)
  • WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
  • 2014
  • Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
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