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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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- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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- Kokaia, Zaal, et al.
(författare)
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Regional brain-derived neurotrophic factor mRNA and protein levels following transient forebrain ischemia in the rat
- 1996
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Ingår i: Brain Research. Molecular Brain Research. - 0169-328X. ; 38:1, s. 139-144
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Tidskriftsartikel (refereegranskat)abstract
- Levels of BDNF mRNA and protein were measured in the rat brain using in situ hybridization and a two-site enzyme immunoassay. Under basal conditions, the highest BDNF concentration was found in the dentate gyrus (88 ng/g), while the levels in CA3 (50 ng/g), CA1 (18 ng/g) and parietal cortex (8 ng/g) were markedly lower. Following 10 min of forebrain ischemia, BDNF protein increased transiently in the dentate gyrus (to 124% of control at 6 h after the insult) and CA3 region (to 131% of control, at 1 week after the insult). In CA1 and parietal cortex, BDNF protein decreased to 73-75% of control at 24 h. In contrast, BDNF mRNA expression in dentate granule cells and CA3 pyramidal layer was transiently elevated to 287 and 293% of control, respectively, at 2 h, whereas no change was detected in CA1 or neocortex. The regional BDNF protein levels shown here correlate at least partly with regional differences in cellular resistance to ischemic damage, which is consistent with the hypothesis of a neuroprotective role of BDNF.
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- Sha, Mahesh Kumar, et al.
(författare)
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Validation of methane and carbon monoxide from Sentinel-5 Precursor using TCCON and NDACC-IRWG stations
- 2021
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 14:9, s. 6249-6304
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Tidskriftsartikel (refereegranskat)abstract
- The Sentinel-5 Precursor (S5P) mission with the TROPOspheric Monitoring Instrument (TROPOMI) on board has been measuring solar radiation backscattered by the Earth's atmosphere and surface since its launch on 13 October 2017. In this paper, we present for the first time the S5P operational methane (CH4) and carbon monoxide (CO) products' validation results covering a period of about 3 years using global Total Carbon Column Observing Network (TCCON) and Infrared Working Group of the Network for the Detection of Atmospheric Composition Change (NDACC-IRWG) network data, accounting for a priori alignment and smoothing uncertainties in the validation, and testing the sensitivity of validation results towards the application of advanced co-location criteria. We found that the S5P standard and bias-corrected CH4 data over land surface for the recommended quality filtering fulfil the mission requirements. The systematic difference of the bias-corrected total column-averaged dry air mole fraction of methane (XCH4) data with respect to TCCON data is -0.26 +/- 0.56 % in comparison to -0.68 +/- 0.74 % for the standard XCH4 data, with a correlation of 0.6 for most stations. The bias shows a seasonal dependence. We found that the S5P CO data over all surfaces for the recommended quality filtering generally fulfil the missions requirements, with a few exceptions, which are mostly due to co-location mismatches and limited availability of data. The systematic difference between the S5P total column-averaged dry air mole fraction of carbon monoxide (XCO) and the TCCON data is on average 9.22 +/- 3.45 % (standard TCCON XCO) and 2.45 +/- 3.38 % (unscaled TCCON XCO). We found that the systematic difference between the S5P CO column and NDACC CO column (excluding two outlier stations) is on average 6.5 +/- 3.54 %. We found a correlation of above 0.9 for most TCCON and NDACC stations. The study shows the high quality of S5P CH4 and CO data by validating the products against reference global TCCON and NDACC stations covering a wide range of latitudinal bands, atmospheric conditions and surface conditions.
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- Romanenko, LA, et al.
(författare)
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Pseudomonas pachastrellae sp nov., isolated from a marine sponge
- 2005
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Ingår i: INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY. - : Microbiology Society. - 1466-5026 .- 1466-5034. ; 55, s. 919-924
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Tidskriftsartikel (refereegranskat)abstract
- Two Gram-negative, non-fermentative, non-denitrifying, non-pigmented, rod-shaped bacteria that were motile by means of polar flagella, designated strains KMM 330T and KMM 331, were isolated from a deep-sea sponge specimen and subjected to a polyphasic taxonomic study. The new isolates exhibited 16S rRNA gene sequence similarity of 99·9 %, and their mean level of DNA–DNA relatedness was 82 %. Phylogenetic analysis based on their 16S rRNA gene sequences placed the strains within the genus Pseudomonas as an independent deep clade. Strain KMM 330T shared highest sequence similarity (96·3 %) with each of Pseudomonas fulva NRIC 0180T, Pseudomonas parafulva AJ 2129T and Pseudomonas luteola IAM 13000T; sequence similarity to other recognized species of the genus Pseudomonas was below 95·7 %. The marine sponge isolates KMM 330T and KMM 331 could be distinguished from the other recognized Pseudomonas species based on a unique combination of their phenotypic characteristics, including growth in 8 or 10 % NaCl, the absence of pigments, the inability to denitrify and lack of carbohydrate utilization. On the basis of phylogenetic analysis, physiological and biochemical characterization, strains KMM 330T and KMM 331 should be classified as a novel species of the genus Pseudomonas, for which the name Pseudomonas pachastrellae sp. nov. is proposed. The type strain is KMM 330T (=JCM 12285T=NRIC 0583T=CCUG 46540T).
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- Uchino, Yuichi, et al.
(författare)
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Galectin-3 is an amplifier of the interleukin-1β-mediated inflammatory response in corneal keratinocytes
- 2018
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Ingår i: Immunology. - : Wiley. - 0019-2805. ; 154:3, s. 490-499
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-1β (IL-1β) is a potent mediator of innate immunity commonly up-regulated in a broad spectrum of inflammatory diseases. When bound to its cell surface receptor, IL-1β initiates a signalling cascade that cooperatively induces the expression of canonical IL-1 target genes such as IL-8 and IL-6. Here, we present galectin-3 as a novel regulator of IL-1β responses in corneal keratinocytes. Using the SNAP-tag system and digitonin semi-permeabilization, we show that recombinant exogenous galectin-3 binds to the plasma membrane of keratinocytes and is internalized into cytoplasmic compartments. We find that exogenous galectin-3, but not a dominant negative inhibitor of galectin-3 polymerization lacking the N-terminal domain, exacerbates the response to IL-1β by stimulating the secretion of inflammatory cytokines. The activity of galectin-3 could be reduced by a novel d-galactopyranoside derivative targeting the conserved galactoside-binding site of galectins and did not involve interaction with IL-1 receptor 1 or the induction of endogenous IL-1β. Consistent with these observations, we demonstrate that small interfering RNA-mediated suppression of endogenous galectin-3 expression is sufficient to impair the IL-1β-induced secretion of IL-8 and IL-6 in a p38 mitogen-activated protein kinase-independent manner. Collectively, our findings provide a novel role for galectin-3 as an amplifier of IL-1β responses during epithelial inflammation through an as yet unidentified mechanism.
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