97 research outputs found
Loss of ATRX and DAXX expression identifies poor prognosis for smooth muscle tumours of uncertain malignant potential and early stage uterine leiomyosarcoma
published_or_final_versio
Telomere maintenance and dysfunction predict recurrence in paediatric ependymoma
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 (P<0.0001) and mitotic index (P=0.005), as well as overall tumour grade (P=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 ÎłH2AX expression (P=0.016). Combining ÎłH2AX and hTERT expressions could segregate tumours into three different survival groups (log rank, P<0.0001) 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
Telomerase inhibition improves tumor response to radiotherapy in a murine orthotopic model of human glioblastoma
Using naturally occurring tumours in dogs and cats to study telomerase and cancer stem cell biology
AbstractThe recently described cancer stem cell theory opens up many new challenges and opportunities to identify targets for therapeutic intervention. However, the majority of cancer related therapeutic studies rely upon rodent models of human cancer that rarely translate into clinical success in human patients. Naturally occurring cancers in dogs, cats and humans share biological features, including molecular targets, telomerase biology and tumour genetics. Studying cancer stem cell biology and telomere/telomerase dynamics in the cancer bearing pet population may offer the opportunity to develop a greater understanding of cancer biology in the natural setting and evaluate the development of novel therapies targeted at these systems
P53 and telomere maintenance in primary brain tumours
SIGLEAvailable from British Library Document Supply Centre- DSC:DXN058681 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
Group additivity calculations of the thermodynamic properties of unfolded proteins in aqueous solution: a critical comparison of peptide-based and HKF models
Ionization constants of aqueous amino acids at temperatures up to 250°C using hydrothermal pH indicators and UV-visible spectroscopy: Glycine, α-alanine, and proline
Ionization constants for several simple amino acids have been measured for the first time under hydrothermal conditions, using visible spectroscopy with a high-temperature, high-pressure flow cell and thermally stable colorimetric pH indicators. This method minimizes amino acid decomposition at high temperatures because the data can be collected rapidly with short equilibration times. The first ionization constant for proline and α-alanine, Ka,COOH, and the first and second ionization constants for glycine, Ka,COOH and Ka,NH4+, have been determined at temperatures as high as 250°C. Values for the standard partial molar heat capacity of ionization, ÎrCpo,COOH and ÎrCpo,NH4+, have been determined from the temperature dependence of ln (Ka,COOH) and ln (Ka,NH4+). The methodology has been validated by measuring the ionization constant of acetic acid up to 250°C, with results that agree with literature values obtained by potentiometric measurements to within the combined experimental uncertainty.
We dedicate this paper to the memory of Dr. Donald Irish (1932â2002) of the University of Waterlooâfriend and former supervisor of two of the authors (R.J.B. and P.R.T.)
ALT-associated promyelocytic leukaemia body (APB) detection as a reproducible tool to assess alternative lengthening of telomere stability in liposarcomas
The partial molar heat capacities of glycine and glycylglycine in aqueous solution at elevated temperatures and atp= 10.0 MPa
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