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| 2. |
- Ray-Coquard, I., et al.
(författare)
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Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:2, s. 439-448
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Tidskriftsartikel (refereegranskat)abstract
- AGO-OVAR 12 investigated the effect of adding the oral triple angiokinase inhibitor nintedanib to standard front-line chemotherapy for advanced ovarian cancer. At the primary analysis, nintedanib demonstrated significantly improved progression-free survival (PFS; primary endpoint) compared with placebo. We report final results, including overall survival (OS). Patients with primary debulked International Federation of Gynaecology and Obstetrics (FIGO) stage IIB–IV newly diagnosed ovarian cancer were randomised 2:1 to receive carboplatin (area under the curve 5 or 6) plus paclitaxel (175 mg/m2) on day 1 every 3 weeks for six cycles combined with either nintedanib 200 mg or placebo twice daily on days 2–21 every 3 weeks for up to 120 weeks. Between December 2009 and July 2011, 1,366 patients were randomised (911 to nintedanib, 455 to placebo). Disease was considered as high risk (FIGO stage III with amp;gt;1 cm residuum, or any stage IV) in 39%. At the final analysis, 605 patients (44%) had died. There was no difference in OS (hazard ratio 0.99, 95% confidence interval [CI] 0.83–1.17, p = 0.86; median 62.0 months with nintedanib vs. 62.8 months with placebo). Subgroup analyses according to stratification factors, clinical characteristics and risk status showed no OS difference between treatments. The previously reported PFS improvement seen with nintedanib did not translate into an OS benefit in the nonhigh-risk subgroup. Updated PFS results were consistent with the primary analysis (hazard ratio 0.86, 95% CI 0.75–0.98; p = 0.029) favouring nintedanib. The safety profile was consistent with previous reports. © 2019 UICC
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- Heitz, F., et al.
(författare)
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Early tumor regrowth is a contributor to impaired survival in patients with completely resected advanced ovarian cancer. An exploratory analysis of the Intergroup trial AGO-OVAR 12
- 2019
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Ingår i: Gynecologic Oncology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 152:2, s. 235-242
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings. Methods. Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle. The findings from surgical and radiologic assessment for disease extend were compared. Additionally, an integrated approach was assessed. Results. Complete data from all 3 assessment methods were available for 1345 patients. Of 689 patients with complete resection, tumor was observed in 28% and 22% of patients undergoing radiologic and integrated assessment, respectively. Patients with surgical- radiological and surgical-integrated concordant findings showed a 5-year overall survival (5Y-OS) of 72% and 71%, whereas patients with surgical-radiological and surgical-integrated discordant results showed inferior 5Y-OS of 47% and 49%, respectively. Patients with surgically assessed residual disease had a 5-YOS of 37%. The interval between surgery and baseline assessment was independently associated with discordance between assessment methods, which might reflect early tumor regrowth. Conclusions. Baseline tumor assessment before chemotherapy provides information that stratifies patients with complete resection into different prognostic groups. Integrating the data from different assessment methods might lead to improved definitions of prognostic groups. Further investigation to determine if earlier initiation of chemotherapy after debulking surgery could increase survival of patients with early tumor regrowth is warranted. (C) 2018 Published by Elsevier Inc.
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| 4. |
- Canelas, A.B., et al.
(författare)
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Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains
- 2010
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 1:9
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Tidskriftsartikel (refereegranskat)abstract
- The field of systems biology is often held back by difficulties in obtaining comprehensive, high-quality, quantitative data sets. In this paper, we undertook an interlaboratory effort to generate such a data set for a very large number of cellular components in the yeast Saccharomyces cerevisiae, a widely used model organism that is also used in the production of fuels, chemicals, food ingredients and pharmaceuticals. With the current focus on biofuels and sustainability, there is much interest in harnessing this species as a general cell factory. In this study, we characterized two yeast strains, under two standard growth conditions. We ensured the high quality of the experimental data by evaluating a wide range of sampling and analytical techniques. Here we show significant differences in the maximum specific growth rate and biomass yield between the two strains. On the basis of the integrated analysis of the high-throughput data, we hypothesize that differences in phenotype are due to differences in protein metabolism.
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| 5. |
- Peterziel, H, et al.
(författare)
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Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
- 2022
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Ingår i: NPJ precision oncology. - : Springer Science and Business Media LLC. - 2397-768X. ; 6:1, s. 94-
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Tidskriftsartikel (refereegranskat)abstract
- The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.
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| 8. |
- Enfors, Sven-Olof, et al.
(författare)
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Physiological responses to mixing in large scale bioreactors
- 2001
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Ingår i: Journal of Biotechnology. - 0168-1656 .- 1873-4863. ; 85:2, s. 175-185
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Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli fed-batch cultivations at 22 m(3) scale were compared to corresponding laboratory scale processes and cultivations using a scale-down reactor furnished with a high-glucose concentration zone to mimic the conditions in a feed zone of the large bioreactor. Formate accumulated in the large reactor, indicating the existence of oxygen limitation zones. It is suggested that the reduced biomass yield at large scale partly is due to repeated production/reassimilation of acetate from overflow metabolism and mixed acid fermentation products due to local moving zones with oxygen limitation. The conditions that generated mixed-acid fermentation in the scale-down reactor also induced a number of stress responses, monitored by analysis of mRNA of selected stress induced genes. The stress responses were relaxed when the cells returned to the substrate limited and oxygen sufficient compartment of the reactor. Corresponding analysis in the large reactor showed that the concentration of mRNA of four stress induced genes was lowest at the sampling port most distant from the feed zone. It is assumed that repeated induction/relaxation of stress responses in a large bioreactor may contribute to altered physiological properties of the cells grown in large-scale bioreactor. Flow cytometric analysis revealed reduced damage with respect to cytoplasmic membrane potential and integrity in cells grown in the dynamic environments of the large scale reactor and the scale-down reactor.
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| 11. |
- Clarke, A. L., et al.
(författare)
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Long-Term Trends in Eutrophication and Nutrients in the Coastal Zone
- 2006
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Ingår i: Limnology and Oceanography. - 0024-3590 .- 1939-5590. ; 51:1, s. 385-397
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Tidskriftsartikel (refereegranskat)abstract
- We used high-resolution paleoecological records of environmental change to study the rate and magnitude of eutrophication over the last century in two contrasting coastal ecosystems. A multiproxy approach using geochemical and biological indicators and diatom-based transfer functions provides a long-term perspective on changes in nutrient concentrations and the corresponding biological and sedimentary responses. In Roskilde Fjord, Denmark, total nitrogen (TN) increased 85% during the last century, with the most rapid increase occurring after the 1950s, corresponding to the postwar increase in N fertilizer use. In Laajalahti Bay, an urban embayment near Helsinki, Finland, total dissolved nitrogen (TDN) increased with growing wastewater inputs and decreased with the remedial actions taken to reduce these discharges. These changes are small relative to the order of magnitude increases in nutrient loading that have occurred in northwestern Europe, where the dissolved inorganic nitrogen (DIN) load has increased more than threefold in certain areas.
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| 13. |
- Tröger, Armin, et al.
(författare)
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Tetranorsesquiterpenoids as attractants of yucca moths to yucca flowers
- 2021
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Ingår i: Journal of Chemical Ecology. - : Springer Science and Business Media LLC. - 0098-0331 .- 1573-1561. ; 47:12, s. 1025-1041
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Tidskriftsartikel (refereegranskat)abstract
- The obligate pollination mutualism between Yucca and yucca moths is a classical example of coevolution. Oviposition and active pollination by female yucca moths occur at night when Yucca flowers are open and strongly scented. Thus, floral volatiles have been suggested as key sensory signals attracting yucca moths to their host plants, but no bioactive compounds have yet been identified. In this study, we showed that both sexes of the pollinator moth Tegeticula yuccasella are attracted to the floral scent of the host Yucca filamentosa. Chemical analysis of the floral headspace from six Yucca species in sections Chaenocarpa and Sarcocarpa revealed a set of novel tetranorsesquiterpenoids putatively derived from (E)-4,8-dimethyl-1,3,7-nonatriene. Their structure elucidation was accomplished by NMR analysis of the crude floral scent sample of Yucca treculeana along with GC/MS analysis and confirmed by total synthesis. Since all these volatiles are included in the floral scent of Y. filamentosa, which has been an important model species for understanding the pollination mutualism, we name these compounds filamentolide, filamentol, filamental, and filamentone. Several of these compounds elicited antennal responses in pollinating (Tegeticula) and non-pollinating (Prodoxus) moth species upon stimulation in electrophysiological recordings. In addition, synthetic (Z)-filamentolide attracted significant numbers of both sexes of two associated Prodoxus species in a field trapping experiment. Highly specialized insect-plant interactions, such as obligate pollination mutualisms, are predicted to be maintained through “private channels” dictated by specific compounds. The identification of novel bioactive tetranorsesquiterpenoids is a first step in testing such a hypothesis in the Yucca-yucca moth interaction.
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| 16. |
- Wysocki, Laura A., et al.
(författare)
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Spatial variability in the coupling of organic carbon, nutrients, and phytoplankton pigments in surface waters and sediments of the Mississippi River plume
- 2006
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Ingår i: Estuarine, Coastal and Shelf Science. - : Elsevier BV. - 1096-0015 .- 0272-7714. ; 69:1-2, s. 47-63
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Tidskriftsartikel (refereegranskat)abstract
- River-dominated coastal areas are typically sites of active biogeochemical cycling, with productivity enhanced by terrestrial inputs of nutrients and organic matter. To examine the spatial variability and relationship between river discharge, phytoplankton, and organic carbon distributions, we analyzed surface water and sediment from the Louisiana shelf adjacent to the Mississippi River. Samples were collected during April and October 2000 to capture high and low river discharge, and were analyzed for dissolved and particulate organic carbon (DOC and POC), nutrients, and phytoplankton pigments. Pigments, determined by high performance liquid chromatography (HPLC), were also analyzed from sediment to evaluate marine carbon inputs to the seafloor. DOC in surface waters was generally within 200-300 mu M, ranging up to 399 mu M. Chlorophyll a ranged from below the limits of detection (BLD) up to 31 nM in surface waters, with higher values located further from the river mouth during high flow. Although community diversity increased during low discharge, diatoms dominated the phytoplankton population (50-80% of the community throughout the study) and consequently made more important contributions than other species to both the DOC and POC pools. Chlorophyll and degradation products (indicative of zooplankton grazing) observed in surface sediment indicated a transfer of autochthonous carbon from the highly productive photic zone to the sediment, coupling phytoplankton-derived POC in surface waters with organic carbon deposition in surface sediment. Cross-shelf changes in chlorophyll indicated a westward transport of phytoplankton that was directly and indirectly linked with river discharge and pigment decay dynamics. (c) 2006 Elsevier Ltd. All rights reserved.
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