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- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 4. |
- Kikuta, H, et al.
(författare)
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Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates
- 2007
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 17:5, s. 545-555
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Tidskriftsartikel (refereegranskat)abstract
- We report evidence for a mechanism for the maintenance of long-range conserved synteny across vertebrate genomes. We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated “bystander” genes. Bystander genes are not specifically under the control of the regulatory elements that drive the target genes and are expressed in patterns that are different from those of the target genes. Reporter insertions distal to zebrafish developmental regulatory genes pax6.1/2, rx3, id1, and fgf8 and miRNA genes mirn9-1 and mirn9-5 recapitulate the expression patterns of these genes even if located inside or beyond bystander genes, suggesting that the regulatory domain of a developmental regulatory gene can extend into and beyond adjacent transcriptional units. We termed these chromosomal segments genomic regulatory blocks (GRBs). After whole genome duplication in teleosts, GRBs, including HCNEs and target genes, were often maintained in both copies, while bystander genes were typically lost from one GRB, strongly suggesting that evolutionary pressure acts to keep the single-copy GRBs of higher vertebrates intact. We show that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment. These findings explain the absence of evolutionary breakpoints from large vertebrate chromosomal segments and will aid in the recognition of position effect mutations within human GRBs.
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- Oates, Thomas, et al.
(författare)
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Two-dimensional combinatorial investigation of raman and fluorescence enhancement in silver and gold sandwich substrates
- 2009
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 113:22, s. 9588-9594
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Tidskriftsartikel (refereegranskat)abstract
- We present a two-dimensional combinatorial investigation of resonant Raman and fluorescence enhancement in silver and gold sandwich structures. Gold and silver, separated by a thin alumina spacer layer, were deposited in two orthogonal gradients, with a thickness from a few hundred to a few nanometers, covering the range from island films through percolation to continuous films. Resonant Raman spectra of Rhodamine 6G adsorbed on the substrate surface were recorded in a 13 × 13 matrix using an automated scanning stage. The most Raman-active substrates were composed of silver (8 nm)-on-alumina (7 nm)-on-gold (5 nm). They consist of both gold and silver discontinuous nanoparticle films separated by alumina, forming a labyrinthine network structure. Gold-on-alumina-on-silver substrates also displayed increased activity compared with that of goldon-alumina substrates. Maximum fluorescence intensity was observed on silver films nominally 35 nm thick covered by 8 nm of alumina. The efficacy of the combinatorial method to correlate multiple aspects of the measurements and reduce uncertainties is demonstrated.
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| 6. |
- Oates, Thomas W.H., et al.
(författare)
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Combinatorial surface-enhanced raman spectroscopy and spectroscopic ellipsometry of silver Island films
- 2009
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 113:12, s. 4820-4828
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Tidskriftsartikel (refereegranskat)abstract
- Utilizing a combinatorial method, we used spectroscopic ellipsometry to determine the dielectric functions of silver island films over a large range of sizes and morphologies from the percolation threshold down to average particle size smaller than 5 nm. We measured films on silicon substrates with 2 and 20 nm oxide layers and compared the surface-enhanced Raman scattering properties of the films. As expected, the films on 20-nm-thick oxide substrates showed increased Raman counts due to reduced damping of the plasmon resonance; however, the optical absorption was greater in the films on 2 nm oxide. The maximum Raman scattering was observed for average particle diameters of 13.6 and 25 nm and interparticle spacings of 3.3 and 4.1 nm for the 2 and 20 nm oxide substrates, respectively. The use of a combinatorial method resulted in significantly reduced uncertainties by avoiding multiple sample preparations and allowed unambiguous identification of optimal film parameters for the different substrates.
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