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- Geyer, C. E., et al.
(författare)
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Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer
- 2022
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 33:12, s. 1250-1268
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Tidskriftsartikel (refereegranskat)abstract
- Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDES and DDFS with no new safety signals.
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- Bounioux, C., et al.
(författare)
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Thermoelectric composites of poly(3-hexylthiophene) and carbon nanotubes with a large power factor
- 2013
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Ingår i: Energy and Environmental Sciences. - 1754-5692 .- 1754-5706. ; 6:3, s. 918-925
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Tidskriftsartikel (refereegranskat)abstract
- Composite films of poly(3-hexylthiophene) and single- as well as multi-walled carbon nanotubes are demonstrated to offer a competitive thermoelectric performance. The power factor significantly exceeds values obtained with either constituent alone provided that the conjugated polymer is sufficiently p-doped. The use of single-walled carbon nanotubes consistently results in a higher electrical conductivity with a maximum value above 10(3) S cm(-1) and thus gives rise to a power factor of 25 +/- 6 mu W m(-1) K-2 for a filler content of only 8 wt% and a maximum 95 +/- 12 mu W m(-1) K-2 for 42-81 wt%. Moreover, a carbon nanotube content of 8-10 wt% does not compromise the low bulk thermal conductivity of the polymer matrix, which promises a high figure of merit of at least ZT > 10(-2) at room-temperature. All samples are cast on plastic substrates, emphasising their suitability for large-area, flexible thermoelectric applications.
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- Pathak, Sagar J., et al.
(författare)
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EPCAM mutation update : Variants associated with congenital tufting enteropathy and Lynch syndrome
- 2019
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 40:2, s. 142-161
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Tidskriftsartikel (refereegranskat)abstract
- The epithelial cell adhesion molecule gene (EPCAM, previously known as TACSTD1 or TROP1) encodes a membrane-bound protein that is localized to the basolateral membrane of epithelial cells and is overexpressed in some tumors. Biallelic mutations in EPCAM cause congenital tufting enteropathy (CTE), which is a rare chronic diarrheal disorder presenting in infancy. Monoallelic deletions of the 3′ end of EPCAM that silence the downstream gene, MSH2, cause a form of Lynch syndrome, which is a cancer predisposition syndrome associated with loss of DNA mismatch repair. Here, we report 13 novel EPCAM mutations from 17 CTE patients from two separate centers, review EPCAM mutations associated with CTE and Lynch syndrome, and structurally model pathogenic missense mutations. Statistical analyses indicate that the c.499dupC (previously reported as c.498insC) frameshift mutation was associated with more severe treatment regimens and greater mortality in CTE, whereas the c.556-14A>G and c.491+1G>A splice site mutations were not correlated with treatments or outcomes significantly different than random simulation. These findings suggest that genotype–phenotype correlations may be useful in contributing to management decisions of CTE patients. Depending on the type and nature of EPCAM mutation, one of two unrelated diseases may occur, CTE or Lynch syndrome.
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