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Sökning: WFRF:(Belgrano Valerio)

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  • Belgrano, Andrea, et al. (författare)
  • Mapping and Evaluating Marine Protected Areas and Ecosystem Services: A Transdisciplinary Delphi Forecasting Process Framework
  • 2021
  • Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Marine Protected Areas (MPAs) are an important tool for management and conservation and play an increasingly recognised role in societal and human well-being. However, the assessment of MPAs often lacks a simultaneous consideration of ecological and socio-economic outcomes, and this can lead to misconceptions on the effectiveness of MPAs. In this perspective, we present a transdisciplinary approach based on the Delphi method for mapping and evaluating Marine Protected Areas for their ability to protect biodiversity while providing Ecosystem Services (ES) and related human well-being benefits – i.e., the ecosystem outputs from which people benefit. We highlight the need to include the human dimensions of marine protection in such assessments, given that the effectiveness of MPAs over time is conditional on the social, cultural and institutional contexts in which MPAs evolve. Our approach supports Ecosystem-Based Management and highlights the importance of MPAs in achieving restoration, conservation, and sustainable development objectives in relation to EU Directives such as the Marine Strategy Framework Directive (MSFD), the Maritime Spatial Planning Directive (MSPD), and the Common Fisheries Policy (CFP).
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  • Belgrano, Valerio, et al. (författare)
  • BRAF status as a predictive factor for response in isolated limb perfusion.
  • 2019
  • Ingår i: International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. - : Informa UK Limited. - 1464-5157. ; 36:1, s. 511-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Isolated limb perfusion (ILP) is a treatment option for unresectable in-transit melanoma metastases of the extremities. Approximately two-thirds of the patients have a complete response, and known predictive factors mainly regard tumor burden. In an attempt to identify subgroups with higher response rates, we retrospectively analyzed the predictive value of the BRAF V600E/K mutation for response at our institution.Between January 2012 and December 2017, 98 consecutive patients underwent first-time ILP with melphalan for melanoma in-transit metastases and were included in the study. Data was retrieved from our prospectively kept database. Tumor burden was assessed preoperatively as number of lesions and largest tumor diameter. BRAF status was determined according to clinical routine. Response rates were classified according to WHO criteria.Of the 98 patients included in the analysis, 32 patients had a BRAF V600E/K mutation (33%) and 66 patients were BRAF wild type (wt). There was no difference in age, sex or tumor burden between the groups. Comparing response between BRAF V600E/K mutation and BRAF wt, the overall response rate was 69% vs. 77% (p=.36) and the complete response rate was 47% vs. 52% (p=.67). There was no difference in survival, with a median survival of 47 months.In this consecutive series of patients, BRAF V600E/K mutation was not found to be a significant factor for response or survival following ILP.
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  • Belgrano, Valerio (författare)
  • Development of individualized surgical treatments for malignant melanoma
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Cutaneous melanoma is a malignancy with an increasing incidence worldwide, especially in northern Europe. The aim of this thesis is to scrutinize the results achieved by traditional surgery and the opportunities offered by translational research for the more advanced stages of the disease. Paper I analysed outcomes of sentinel node biopsy (SNB) performed on 769 con-secutive patients with cutaneous melanoma. Breslow thickness was the only pre-dictive factor for a positive SN. The 5-year melanoma specific survival (MSS) was 81% and in multivariate analysis the negative prognostic factors for survival were SN-status, followed by Breslow thickness and ulceration. Paper II reported on 290 consecutive patients who underwent 380 isolated limb perfusion (ILP), of which 90 were re-ILPs. The results between the 1st, the 2nd and the 3-5th were compared. Patients with a complete response at the first treat-ment were likely to have the same response at re-ILP without any increase in the risk for local toxicity or complications. Paper III BRAF mutational status as a predictive factor for response was studied in 98 patients who underwent ILP. In this consecutive series, 32 patients had a BRAF V600E/K mutation and 66 patients were BRAF wild type, and no significant correlation for response or survival was found. Paper IV was a translational study based on patient-derived xenograft models including 21 cutaneous melanoma biopsies transplanted into either NOG or IL-2 transgenic NOG (hIL2-NOG) mice. It was shown that the models reliably could be used to predict the effect of tumour-infiltrating lymphocytes against the tumours. Conclusions: The surgical approach and therapies for patients with cutaneous melanoma are becoming more targeted and personalized. A specialised multidisci-plinary approach can improve the understanding of the disease, support the deci-sion-making process towards the most advantageous treatment options for each individual patient at a specific time.
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  • Belgrano, Valerio, et al. (författare)
  • Isolated limb perfusion as a treatment option for rare types of tumours
  • 2016
  • Ingår i: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 32:6, s. 595-599
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Isolated limb perfusion (ILP) is an established and effective treatment for advanced melanoma and soft tissue sarcomas of the extremities with a high overall response rate. The aim of this study was to describe our experience of ILP for more rare types of tumours. Methods: Patients with Merkel cell carcinoma (MCC) (n = 4), squamous cell carcinoma (SCC) (n = 2), B-cell lymphoma (n = 1), desmoid tumours (n = 3), pigmented villonodular synovitis (PVNS) (n = 1) and giant cell tumour (n = 1) were treated with ILP and analysed retrospectively. Results: The four patients with in-transit MCC had three complete responses (CR) and one partial response (PR); the two patients with SCC had one CR and one stable disease (SD); the patients with desmoid tumours had two PR and one SD. A CR was also observed for the patient with a giant cell tumour, but the patient with PVNS had a SD. The patient with cutaneous metastases of B-cell lymphoma showed a CR, however with rapid systemic progression. Local toxicity according to Wieberdink was grade II in 10 patients (83%) and grade III in two patients (17%). Conclusions: These results show that ILP can be used as a treatment option also for more rare disease entities when other treatments have failed.
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  • Belgrano, Valerio, et al. (författare)
  • Response and Toxicity of Repeated Isolated Limb Perfusion (re-ILP) for Patients With In-Transit Metastases of Malignant Melanoma.
  • 2019
  • Ingår i: Annals of surgical oncology. - : Springer Science and Business Media LLC. - 1534-4681 .- 1068-9265. ; 26:4, s. 1055-1062
  • Tidskriftsartikel (refereegranskat)abstract
    • Isolated limb perfusion (ILP) is a safe and well-established treatment for in-transit metastases of melanoma. In case of relapse or disease progression, ILP can be repeated (re-ILP). This study aimed retrospectively to analyze a large consecutive series of re-ILP and compare clinical outcomes with first-time ILP.Between 2001 and 2015, 290 consecutive patients underwent 380 ILPs. Of these, 90 were re-ILPs including 68second ILPs, 16 third ILPs, 4 fourth ILPs, and two fifth ILPs. The study evaluated response (using World Health Organization [WHO] criteria), local toxicity (using the Wieberdink scale), and complications (using Clavien-Dindo).The results were compared between the first ILP, the second ILP, and the third to fifth ILP. The overall response rate was respectively 83%, 80% and 68%, with a complete response (CR) rate of 60%, 41%, and 59%. In the re-ILP group, the patients with a CR after the first ILP had a 65% CR rate after the second ILP compared with 8% for the patients without a CR (p=0.001). The risk for local toxicity or complications was not increased after re-ILP. The median overall survival periods were respectively 34, 41, and 93months (p=0.02).As a therapeutic option, ILP can be repeated safely for in-transit metastases of melanoma, achieving similar high response rates without increasing complications or toxicity. Re-ILP is mainly indicated for patients who already had a CR after the first ILP, whereas other treatment options should be considered for primary non-responders.
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  • Belgrano, Valerio, et al. (författare)
  • Sentinel node for malignant melanoma: An observational study of a consecutive single centre experience
  • 2019
  • Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 45:2, s. 225-230
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology Introduction: Sentinel node biopsy (SNB) for melanoma gives prognostic information, however the success is dependent on several factors. The aim of this study was to describe outcome data after the introduction of the technique at our centre, including analysis of false negative rate (FNR), predictive factors for positive sentinel node (SN) and non-sentinel node (NSN), as well as prognostic factors for melanoma-specific survival (MSS). Materials and methods: This is a retrospective observational study of a prospectively kept database at Sahlgrenska University Hospital. Between March 2000 and December 2013, 769 consecutive patients with cutaneous malignant melanoma undergoing SNB were included. The median follow-up time was 55 months (2–179 months). Tumour load in the SN was categorized according to the largest tumour deposit, low when ≤1 mm and high when >1 mm. Results: The FNR was 20% and the SN positivity rate was 14% with a decrease in both FNR and SN positivity rate during the study period. In multivariate analysis the only predictive factor for a positive SN was Breslow thickness. The 5-year melanoma specific survival (MSS) was 81% and in multivariate analysis the prognostic factors were SN-status (low metastatic load HR = 2.6, p = 0.001; high metastatic load HR = 2.7, p = 0.004) followed by Breslow thickness and ulceration. Conclusions: In this study Breslow thickness was the only independent predictive factor for a positive SN, no predictive factors were identified for NSN. Independent prognostic factors for MSS were SN status, Breslow thickness and ulceration. Interestingly, there was no survival difference depending on SN tumour burden when using 1 mm as cut-off.
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  • Ben-Shabat, Ilan, et al. (författare)
  • The effect of perfusate buffering on toxicity and response in isolated hepatic perfusion for uveal melanoma liver metastases
  • 2017
  • Ingår i: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 33:4, s. 483-488
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Isolated hepatic perfusion (IHP) is a treatment option for patients with liver metastases. Previous studies have found that liver toxicity is one of the limiting factors, and in an attempt to reduce the toxicity a buffering agent was added to the perfusate. The aim was to retrospectively analyse if this buffering reduced toxicity and complication rates.Methods: A retrospective review of 52 consecutive patients with uveal melanoma liver metastases treated with IHP between 2005 and 2013. Patients were followed by daily liver function tests (LFT). Toxicity was graded according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE; United States Department of Health & Human Services, Washington, D.C), complications according to Clavien-Dindo and response according to RECIST-criteria.Results: Thirty-six patients were treated with a buffered perfusate and 16 patients without buffer. There was no difference in age, gender, largest tumour size or number of tumours between the groups. There was a significantly lower mean in peak ALT, AST, PK (INR) and bilirubin when comparing buffer with no-buffer. There were five major complications without a significant difference between the groups (8.3 vs. 12.5%, p=0.33). There was a lower complete response (CR) rate (11 vs. 44%, p=0.023) and a trend for shorter time to local progression (9.2 vs. 17.6 months, p=0.096); however, not significant in multivariate analysis. There was no difference in survival (24.2 vs. 26.0 months, p=0.43) between the two groups.Conclusions: Adding buffer to the perfusate during IHP significantly reduces postoperative LFTs; however, without a reduced complication rate. Interestingly, buffering also seems to reduce the response rate; however, this did not translate into a survival difference. To address if buffering adds any clinical benefit to the patients concerning toxicity, a larger prospective trial is necessary.
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  • Georgas, K., et al. (författare)
  • Bowel vaginoplasty: a systematic review
  • 2018
  • Ingår i: Journal of Plastic Surgery and Hand Surgery. - : Medical Journals Sweden AB. - 2000-656X .- 2000-6764. ; 52:5, s. 265-273
  • Forskningsöversikt (refereegranskat)abstract
    • Among surgical procedures for constructing a neovagina, positive outcomes are reported in literature for bowel vaginoplasty for male-to-female transgenders and patients with vaginal aplasia. This systematic review shows outcomes of bowel vaginoplasty procedures, and rates the quality of evidence of the included studies. A search of the literature was performed in PubMed, Medline, Cochrane Library and SveMed in accordance with the PRISMA statement, between January 2016 and February 2018. The PICOS (patients, intervention, comparator, outcomes and study design) approach was used as inclusion criteria. Among 251 analyzed studies only 34 met inclusion criteria. Quality of evidence and methodology were rated according to GRADE and MINORS, respectively. Data from the included studies were extracted based on study characteristics, participants? specifics, type of intervention/treatment and type of outcome measures into data extraction forms. All studies were non-randomized with a high risk of bias and very low quality of evidence according to GRADE. Vaginal reconstruction with isolated bowel segments provides a self-lubricating neovagina with low rates of failure and revision, and without routine dilatation need. Furthermore, the use of laparoscopic techniques offers a better postoperative cosmetic appearance of the abdomen and a shorter hospital stay. Vaginoplasty using bowel segment is a safe and effective procedure that obtains excellent long-term results as reported by the included studies. Despite that further researches are needed improving methodology with larger populations, retrospective qualitative studies and report of outcome measurements using standardized evaluation tools as the Female Sexual Function Index.
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  • Hornborg, Sara, et al. (författare)
  • Trophic indicators in fisheries : A call for re-evaluation
  • 2013
  • Ingår i: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 9:1, s. 1050-
  • Tidskriftsartikel (refereegranskat)abstract
    • Mean trophic level (MTL) of landings and primary production required (PPR) by fisheries are increasingly used in the assessment of sustainability in fisheries. However, in their present form, MTL and PPR are prone to misinterpretation. We show that it is important to account for actual catch data, define an appropriate historical and spatial domain, and carefully consider the effects of fisheries management, based on results from a case study of Swedish fisheries during the past century.
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  • Howell, Daniel, et al. (författare)
  • Interim Report of the Working Group on Multispecies Assessment Methods (WGSAM)
  • 2018
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The pan-regional Working Group on Multispecies Assessment Methods (WGSAM) met in San Sebastian, Spain, 16–20 October 2017. In this eleventh report of the group, work focused on three of the multi-annual ToRs (B, C, D). Based on their knowledge, participants provided an updated inventory of progress of multispecies models in ICES Ecoregions (ToR A), noting those regions where no information was available. A Key Run (ToR B) of the North Sea Stochastic Multispecies Model (SMS) was presented and reviewed in detail by 4 WGSAM experts, and approved by the group following implementation of changes agreed in plenary at the meeting and verified by a subset of experts post-meeting. The Key Run is documented in detail in Annex for ToR B, with key outputs summarised in Section 5 and data files made available on the WGSAM webpage and the ICES expert group Github (https://github.com/iceseg/wg_WGSAM). Since the M2 values are used for the assessment of important North Sea stocks, it is recommended to publish the annex also on the official stock annex website. In addition, WGSAM does not recommend updating existing data series of natural mortality by simply adding the latest three new years. The timeseries as a whole shows patterns which are not retained by this procedure. Multispecies model skill assessment (ToR C) and multi-model ensemble methods (ToR D) were emphasized this year. Considerable progress has been made towards advancing both aspects of multispecies modelling. Investigation of skill assessment and ensemble methods and case studies is critical to ensure that outputs of multispecies assessment models are reliable for use in operational assessment and to inform management decisions. Progress was also made on investigations of top predator impacts on managed fish across several regions (ToR F), including the North Sea where new information was included in the SMS key run. Further progress was also made on multispecies and ecosystem level reference points and harvest control rules in mixed fisheries (ToR G).
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  • Howell, Daniel, et al. (författare)
  • Report of the Working Group on Multispecies Assessment Methods (WGSAM), 10-14 October 2016, Reykjavik, Iceland
  • 2017
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The Working Group on Multispecies Assessment Methods (WGSAM) met in Reykjavik, Iceland, 10–14 October 2016. In this tenth report of the pan-regional WGSAM, work focused on four (B, E, F, G) of the multi-annual ToRs.Based on their knowledge, participants provided an updated inventory of progress of multispecies models in ICES Ecoregions (ToR A), noting those regions where no information was available. Reporting on ToR A was scarce compared to previous years, partly because recent relevant work was reported against ToR E and G instead.A Key Run (ToR B) of the Baltic Sea Ecopath with Ecosim (NS-EwE) model was presented and reviewed in detail by 4 WGSAM experts, and approved by the group following implementation of changes agreed in plenary at the meeting and verified by the 4 experts in January. The Key Run is documented in a detail in Annex 3, with key outputs summarised in Section 3 and data files made available on the WGSAM webpage). WGSAM also conducted an informal review of the LeMans modelling framework for potential application in the Irish Sea, and recommended adjustments to the framework for further review. Because the LeMans framework is a within-model ensemble addressing parameter uncertainty, this review also related to ToR D.Multispecies model skill assessment (ToR C) and multi-model ensemble methods (ToR D) were not emphasized this year. However, plans were made to coordinate future work for ToR C, and one ToR D presentation reviewed the utility of a dynamic multimodel ensemble for making inferences about the real world. This method can infer results for individual components of aggregate groups; the ensemble model uses correlations in other ecosystem models to determine what the models that group species would have predicted for individual species. A proof of concept for the North Sea was presented.Ecosystem indicator analyses (ToR E) were presented from a wide range of ecosystems. A theoretical analysis comparing results from the Celtic and North Seas with 4 “idealized” fleets was presented to analyse the performance of selected indicators in a multispecies mixed fishery. Four indicators including the Large Fish Indicator (LFI) were examined, and shown to have mixed utility in measuring the impact of different fleet sectors, with the best indicator varying by ecosystem. A multivariate analysis of ecosystem responses to multiple drivers was conducted for four US ecosystems using gradient forest method to identify potential ecosystem thresholds. Other multivariate methods were reviewed that draw on the strengths of multiple indicators for the Northeast US shelf ecosystem. A food web based biodiversity indicator was presented with an application for the Baltic Sea. This could be extended to any ecosystem with an EwE or similar model. A community status indicator relating a species-area relationship to the LFI and mean trophic levels was presented for the Swedish west coast.Impacts of apex predators on fisheries (ToR F) were examined with one presentation and a group discussion planning further work. A multipecies production model was parameterized to simulate interactions between three fish guilds, fisheries, and one marine mammal guild, concluding that fish reference points and trajectories change with marine mammal interactions. Fishery management was also important to reduce vessel interactions with and ensure prey supply to marine mammals. 4 | ICES WGSAM REPORT 2016 Exploration of practical advice for fisheries management incorporating multispecies, mixed fishery, and environmental factors (ToR G) was evident across regions. Two approaches for incorporating species, fleet, environmental, and other interactions are in progress in the Northeast US. One presentation outlined the New England approach, and another outlined the Mid-Atlantic approach. In New England, a management strategy evaluation is in progress to evaluate harvest control rules that consider herring's role as forage in the ecosystem. The modelling framework and stakeholder workshops were discussed. In the Baltic, a Nash Equilibrium optimisation approach incorporating environmental factors was presented for the cod-herring-sprat fishery to attempt to identify a solution that would give good yield for all species simultaneously. In the North Sea a theoretical analysis using 4 “idealized” fleets was presented to analyse the potential implications of "Pretty Good Yield" ranges around MSY. The model examined the likelihood of the fishery being precautionary for the different species given the uncertainties involved, and concluded that the upper ends of MSY ranges would not guarantee precautionarity.
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  • Howell, Daniel, et al. (författare)
  • Report of the Working Group on Multispecies Assessment Methods (WGSAM), 9–13 November 2015, Woods Hole, USA
  • 2016
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Three meetings were held between 2013 and 2015 (Stockholm, London and Woods Hole), with progress being made on all the Terms of Reference. WGSAM has been making significant contributions required to enable ICES to develop its capability to give advice on the ecosystem impacts of fishing and climate change. This is a priority area identified in the ICES strategic plan and is consistent with scientific needs to support implementation of the Common Fisheries Policy and Marine Strategy Framework Directive. This final report summarises the key progress made against each ToR. A particularly important area established during this period has been the discussions that have led to guidelines on quality assurance of ecosystem models in-tended for advice giving. WGSAM prepared a specific briefing on this issue and con-tinues to work on issues related to model review processes, model validation and developing methods for generating advice from multi-model ensembles. These are all important areas of work in the evolution toward giving integrated, ecosystem-based advice to ICES clients. We recommend that ICES supports continuation of WGSAM new ToRs and considers more specifically how to support WGSAM in developing advice relevant products.
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  • Jang, Su Chul, 1984, et al. (författare)
  • Mitochondrial protein enriched extracellular vesicles discovered in human melanoma tissues can be detected in patient plasma
  • 2019
  • Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Extracellular vesicles (EVs), including exosomes and microvesicles, are secreted from all cells, and convey messages between cells in health and disease. However, the diversity of EV subpopulations is only beginning to be explored. Since EVs have been implicated in tumour microenvironmental communication, we started to determine the diversity of EVs specifically in this tissue. To do this, we isolated EVs directly from patient melanoma metastatic tissues. Using EV membrane isolation and mass spectrometry analysis, we discovered enrichment of mitochondrial membrane proteins in the melanoma tissue-derived EVs, compared to non-melanoma-derived EVs. Interestingly, two mitochondrial inner membrane proteins MT-CO2 (encoded by the mitochondrial genome) and COX6c (encoded by the nuclear genome) were highly prevalent in the plasma of melanoma patients, as well as in ovarian and breast cancer patients. Furthermore, this subpopulation of EVs contains active mitochondrial enzymes. In summary, tumour tissues are enriched in EVs with mitochondrial membrane proteins and these mitochondrial membrane proteins can be detected in plasma and are increased in melanoma, ovarian cancer as well as breast cancer.
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  • Lindqvist Bagge, Ann-Sophie, et al. (författare)
  • Health-Related Quality of Life for Patients Who have In-Transit Melanoma Metastases Treated with Isolated Limb Perfusion
  • 2016
  • Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 23:6, s. 2062-2069
  • Tidskriftsartikel (refereegranskat)abstract
    • The incidence of malignant melanoma is increasing, and up to 5 % of patients will experience in-transit metastases. Normally, the initial treatment is surgical excision, but when not possible, locoregional treatment options such as isolated limb perfusion (ILP) are an alternative. This study aimed to assess health-related quality of life (HRQoL) prospectively for patients whose in-transit metastases is treated with ILP. More specifically, the study aimed to describe HRQoL for patients with in-transit extremity melanoma metastases, to describe changes in HRQoL after ILP, and to correlate HRQoL with local toxicity and clinical response after ILP. The Functional Assessment of Cancer Therapy-Melanoma (FACT-M) consists of 51 items comprising the Functional Assessment of Cancer Therapy-General (FACT-G), the melanoma subscale , and the melanoma surgery scale. Forty-five patients answered the FACT-M questionnaire before ILP (52 procedures) and at 3, 6 and 12 months after ILP. Response and toxicity were analyzed and correlated with the changes in the HRQoL of the patients. Patients with in-transit metastasis have an HRQoL mainly influenced by tumor burden, defined as more or < 10 tumors (FACT-M: 142.5 vs. 128.4 points; p = 0.02). After ILP, there was a trend toward a decrease in FACT-G (+0.1 vs. -7.3 points; p = 0.05) and FACT-M (+1.6 vs. -8.9 points; p = 0.08) when Wieberdink classifications 1-2 and 3-4 were compared at 3 months. A significant difference in FACT-G (+1.0 vs. -13.0 points; p = 0.04) was observed 12 months after ILP as well as a trend for FACT-M (+1.7 vs. -14.6 points; p = 0.08) when the patients who had a complete response were compared with those who did not. This study found that patients with in-transit metastases have an HRQoL mainly influenced by tumor burden. After ILP, there is an initial decrease in HRQoL due to local toxicity. After 12 months, the patients with a complete response maintained an HRQoL at baseline level, strengthening the use of ILP as a palliative treatment.
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  • Longo, Catherine S., et al. (författare)
  • Role of trophic models and indicators in current marine fisheries management
  • 2015
  • Ingår i: Marine Ecology Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 538, s. 257-272
  • Tidskriftsartikel (refereegranskat)abstract
    • The previous decade has witnessed a flourishing of studies on how fisheries and marine food webs interact, and how trophicmodels and indicators can be used for assessment and management purposes. Acknowledging the importance of complex interactions among species, fishermen and the environment has led to a shift from single species to an ecosystem-wide approach in the science supporting fisheries management (e.g. Johannesburg Declaration, Magnuson-Stevens Act). Moreover, fisheries managers today acknowledge that fishing activities are linked to a range of societal benefits and services, and their work is necessarily amulti-objective practice (i.e. ecosystem-based management). We argue that the knowledge accumulated thus far points to tropho-dynamic models and indicators as key tools for such multi-dimensional assessments. Nevertheless, trophodynamic approaches are still underutilised in fisheriesmanagement. More specifically,most management decisions continue to rely on single species and sector-specific models. Here we review examples of applications of trophodynamic indicators within fisheries assessments in wellstudied ecosystems, and discuss progressmade (as well as lack thereof) towards increased integration of these metrics into marine resource management. Having clarified how trophic indicators fit within current policy and management contexts, we propose ways forward to increase their use in view of futuremanagement challenges.
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25.
  • Ny, Lars, 1967, et al. (författare)
  • Supporting clinical decision making in advanced melanoma by preclinical testing in personalized immune-humanized xenograft mouse models
  • 2020
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:2, s. 266-273
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The mouse strains usually used to generate patient-derived xenografts (PDXs) are immunocompromised, rendering them unsuitable for immunotherapy studies. Here we assessed the value of immune-PDX mouse models for predicting responses to anti-PD-1 checkpoint inhibitor therapy in patients. Patients and methods: Melanoma biopsies contained in a retrospective biobank were transplanted into NOG mice or NOG mice expressing interleukin 2 (hIL2-NOG mice). Tumor growth was monitored, and comparisons were made with clinical data, sequencing data, and current in silico predictive tools. Results: Biopsies grew readily in NOG mice but growth was heterogeneous in hIL2-NOG mice. IL2 appears to activate T-cell immunity in the biopsies to block tumor growth. Biopsy growth in hIL2-NOG mice was negatively associated with survival in patients previously treated with PD-1 checkpoint blockade. In two cases, the prospective clinical decisions of anti-PD-1 therapy or targeted BRAF/MEK inhibitors were supported by the observed responses in mice. Conclusions: Immune-PDX models represent a promising addition to future biomarker discovery studies and for clinical decision making in patients receiving immunotherapy.
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  • Pesce, S., et al. (författare)
  • Different Features of Tumor-Associated NK Cells in Patients With Low-Grade or High-Grade Peritoneal Carcinomatosis
  • 2019
  • Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Peritoneal carcinomatosis (PC) is a rare disease defined as diffused implantation of neoplastic cells in the peritoneal cavity. This clinical picture occurs during the evolution of peritoneal tumors, and it is the main cause of morbidity and mortality of patients affected by these pathologies, though cytoreductive surgery with heated intra-peritoneal chemotherapy (CRS/HIPEC) is yielding promising results. In the present study, we evaluated whether the tumor microenvironment of low-grade and high-grade PC could affect the phenotypic and functional features and thus the anti-tumor potential of NK cells. We show that while in the peritoneal fluid (PF) of low-grade PC most CD56dim NK cells show a relatively immature phenotype (NKG2A+KIR-CD57-CD16dim), in the PF of high-grade PC NK cells are, in large majority, mature (CD56dimKIR+CD57+CD16bright). Furthermore, in low-grade PC, PF-NK cells are characterized by a sharp down-regulation of some activating receptors, primarily NKp30 and DNAM-1, while, in high-grade PC, PF-NK cells display a higher expression of the PD-1 inhibitory checkpoint. The compromised phenotype observed in low-grade PC patients corresponds to a functional impairment. On the other hand, in the high-grade PC patients PF-NK cells show much more important defects that only partially reflect the compromised phenotype detected. These data suggest that the PC microenvironment may contribute to tumor escape from immune surveillance by inducing different NK cell impaired features leading to altered anti-tumor activity. Notably, after CRS/HIPEC treatment, the altered NK cell phenotype of a patient with a low-grade disease and favorable prognosis was reverted to a normal one. Our present data offer a clue for the development of new immunotherapeutic strategies capable of restoring the NK-mediated anti-tumor responses in association with the CRS/HIPEC treatment to increase the effectiveness of the current therapy.
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