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| 2. |
- 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. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 5. |
- Al-Minawi, Ali Z., et al.
(författare)
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The ERCC1/XPF endonuclease is required for completion of homologous recombination at DNA replication forks stalled by inter-strand cross-links
- 2009
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 37:19, s. 6400-6413
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Tidskriftsartikel (refereegranskat)abstract
- Both the ERCC1-XPF complex and the proteins involved in homoIogous recombination (HR) have critical roles in inter-strand cross-link (ICL) repair. Here, we report that mitomycin C-induced lesions inhibit replication fork elongation. Furthermore, mitomycin C-induced DNA double-strand breaks (DSBs) are the result of the collapse of ICL-stalled replication forks. These are not formed through replication run off, as we show that mitomycin C or cisplatin-induced DNA lesions are not incised by global genome nucleotide excision repair (GGR). We also suggest that ICL-lesion repair is initiated either by replication or transcription, as the GGR does not incise ICL-lesions. Furthermore, we report that RAD51 foci are induced by cisplatin or mitomycin C independently of ERCC1, but that mitomycin C-induced HR measured in a reporter construct is impaired in ERCC1-defective cells. These data suggest that ERCC1-XPF plays a role in completion of HR in ICL repair. We also find no additional sensitivity to cisplatin by siRNA co-depletion of XRCC3 and ERCC1, showing that the two proteins act on the same pathway to promote survival.
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| 8. |
- Bryant, M.D., et al.
(författare)
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Headwater Streams in Southeast Alaska: Why Do We Care?
- 2005
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Headwater streams may comprise more than 70% of the area of a watershed and until recently, they have been largely over-looked by managers and ecologists in Southeast Alaska and elsewhere. However, their importance in shaping downstream processes isbecoming more widely recognized. Recently, a series of studies were completed in Southeast Alaska that examined the physical and biological features of headwater streams. We review and synthesize these studies to define headwater stream characteristics in Southeast Alaska, describe some processes that occur in these streams, and discuss their importance to watersheds. Alterations in large wood abundance anddistribution have predictable effects on sediment storage and transport in headwater streams. Legacy wood remaining in streams more than 25 yrs after logging was an important structural component. Invertebrate populations captured in drift samples arediverse, and more than 60 % of the taxa were aquatic. Downstream transport of invertebrate drift from reaches without fish may be an important to juvenile fish residing in the lower reaches. Drift density is inversely related to stream discharge, so smallstreams may provide better foraging and growth potential. Resident and anadromous fish live and spawn in headwater reaches with gradients > 10 % and occupied small step pools formed by large woody debris. Dolly Varden were the dominant species in higher gradient reaches, but juvenile coho were also present. Steelhead were seasonal residents. Headwater streams link hill slope processes to watersheds and can have important consequences for salmonid populations throughout a watershed
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| 9. |
- Bryant, M.D., et al.
(författare)
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Structures Linking Physical and Biological Processes in Headwater Streams of the Maybeso Watershed, Southeast Alaska
- 2007
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Ingår i: Forest Science 53:371-383.
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Tidskriftsartikel (refereegranskat)abstract
- We focus on headwater streams originating in the mountainous terrain of northern temperate rain forests. These streams rapidly descend from gradients greater than 20% to less than 5% in U-shaped glacial valleys. We use a set of studies on headwater streams in southeast Alaska to define headwater stream catchments, link physical and biological processes, and describe their significance within watersheds. We separate headwater stream systems into four units that have distinct hydrologic and geomorphic processes that link terrestrial processes to aquatic systems. Headwater streams collect, process, and transport material downstream. Physical and biological processes in headwater streams are complex and closely tied to terrestrial processes. Steps and step pools formed by large wood are keystone structures that link physical processes to biological processes and increase channel complexity. Large and coarse wood debris dams form in-channel step structures and act as valves that regulate the downstream flow of material. A large amount of inorganic and organic sediment is stored in step structures, which may be biological hotspots in headwater streams. Step pools formed by large woody debris are critical habitat for Dolly Varden (Salvelinus malma), juvenile coho salmon (Oncorhynchus kisutch), steelhead (0. mykiss), and cutthroat trout (0. clarkii) in reaches with gradients from less than 4% to those greater than 10%. Landslides and debris flows are the dominant channel-altering processes in headwater streams and remove the step profile. Management activities that increase the number and frequency of channel disturbance events in headwater streams can have important and long-term consequences throughout a watershed
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| 10. |
- Fröberg, M, et al.
(författare)
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Concentration and Fluxes of Dissolved Organic Carbon (DOC) in Three Norway Spruce Stands along a Climatic Gradient in Sweden
- 2006
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 1573-515X .- 0168-2563. ; 77:1, s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- Leaching of dissolved organic carbon (DOC) from the forest floor and transport in soil solution into the mineral soil are important for carbon cycling in boreal forest ecosystems. We examined DOC concentrations in bulk deposition, throughfall and in soil solutions collected under the O and B horizons in three Norway spruce stands along a climatic gradient in Sweden. Mean annual temperature for the three sites was 5.5, 3.4 and 1.2 °C. At each site we also examined the effect of soil moisture on DOC dynamics along a moisture gradient (dry, mesic and moist plots). To obtain information about the fate of DOC leached from the O horizon into the mineral soil, 14C measurements were made on bulk organic matter and DOC. The concentration and fluxes of DOC in O horizon leachates were highest at the southern site and lowest at the northern. Average DOC concentrations at the southern, central and northern sites were 49, 39 and 30 mg l−1, respectively. We suggest that DOC leaching rates from O horizons were related to the net primary production of the ecosystem. Soil temperature probably governed the within-year variation in DOC concentration in O horizon leachates, but the peak in DOC was delayed relative to that of temperature, probably due to sorption processes. Neither soil moisture regime (dry, mesic or moist plots) nor seasonal variation in soil moisture seemed to be of any significance for the concentration of DOC leached from the O horizon. The 14C measurements showed that DOC in soil solution collected below the B horizon was derived mainly from the B horizon itself, rather than from the O horizon, indicating a substantial exchange (sorption–desorption reactions) between incoming DOC and soil organic carbon in the mineral soil.
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| 13. |
- Selpi, Selpi, 1977, et al.
(författare)
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A First Step towards Learning which uORFs Regulate Gene Expression
- 2006
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Ingår i: Journal of integrative bioinformatics. - 1613-4516. ; 3:2, s. 31-
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Tidskriftsartikel (refereegranskat)abstract
- We have taken a first step towards learning which upstream Open Reading Frames (uORFs) regulate gene expression (i.e., which uORFs are functional) in the yeast Saccharomyces cerevisiae. We do this by integrating data from several resources and combining a bioinformatics tool, ORF Finder, with a machine learning technique, inductive logic programming (ILP). Here, we report the challenge of using ILP as part of this integrative system, in order to automatically generate a model that identifies functional uORFs. Our method makes searching for novel functional uORFs more efficient than random sampling. An attempt has been made to predict novel functional uORFs using our method. Some preliminary evidence that our model may be biologically meaningful is presented.
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