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- Tobias, J., et al.
(författare)
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A New Strategy Toward B Cell-Based Cancer Vaccines by Active Immunization With Mimotopes of Immune Checkpoint Inhibitors
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic monoclonal antibodies (mAbs), targeting tumor antigens, or immune checkpoints, have demonstrated a remarkable anti-tumor effect against various malignancies. However, high costs for mono- or combination therapies, associated with adverse effects or possible development of resistance in some patients, warrant further development and modification to gain more flexibility for this immunotherapy approach. An attractive alternative to passive immunization with therapeutic antibodies might be active immunization with mimotopes (B-cell peptides) representing the mAbs' binding epitopes, to activate the patient's own anti-tumor immune response following immunization. Here, we identified and examined the feasibility of inducing anti-tumor effectsin vivofollowing active immunization with a mimotope of the immune checkpoint programmed cell death 1 (PD1), alone or in combination with a Her-2/neu B-cell peptide vaccine. Overlapping peptides spanning the extracellular domains of human PD1 (hPD1) were used to identify hPD1-derived mimotopes, using the therapeutic mAb Nivolumab as a proof of concept. Additionally, forin vivoevaluation in a tumor mouse model, a mouse PD1 (mPD1)-derived mimotope was identified using an anti-mPD1 mAb with mPD1/mPDL-1 blocking capacity. The identified mimotopes were characterized byin vitroassays, including a reporter cell-based assay, and their anti-tumor effects were evaluated in a syngeneic tumor mouse model stably expressing human Her-2/neu. The identified PD1-derived mimotopes were shown to significantly block the mAbs' capacity in inhibiting the respective PD1/PD-L1 interactions. A significant reduction in tumor growthin vivowas observed following active immunization with the mPD1-derived mimotope, associated with a significant reduction in proliferation and increased apoptotic rates in the tumors. Particularly, combined vaccination with the mPD1-derived mimotope and a multiple B-cell epitope Her-2/neu vaccine potentiated the vaccine's anti-tumor effect. Our results suggest active immunization with mimotopes of immune checkpoint inhibitors either as monotherapy or as combination therapy with tumor-specific vaccines, as a new strategy for cancer treatment.
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- Stokes, Chris R., et al.
(författare)
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On the reconstruction of palaeo-ice sheets : Recent advances and future challenges
- 2015
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 125, s. 15-49
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Forskningsöversikt (refereegranskat)abstract
- Reconstructing the growth and decay of palaeo-ice sheets is critical to understanding mechanisms of global climate change and associated sea-level fluctuations in the past, present and future. The significance of palaeo-ice sheets is further underlined by the broad range of disciplines concerned with reconstructing their behaviour, many of which have undergone a rapid expansion since the 1980s. In particular, there has been a major increase in the size and qualitative diversity of empirical data used to reconstruct and date ice sheets, and major improvements in our ability to simulate their dynamics in numerical ice sheet models. These developments have made it increasingly necessary to forge interdisciplinary links between sub-disciplines and to link numerical modelling with observations and dating of proxy records. The aim of this paper is to evaluate recent developments in the methods used to reconstruct ice sheets and outline some key challenges that remain, with an emphasis on how future work might integrate terrestrial and marine evidence together with numerical modelling. Our focus is on pan-ice sheet reconstructions of the last deglaciation, but regional case studies are used to illustrate methodological achievements, challenges and opportunities. Whilst various disciplines have made important progress in our understanding of ice-sheet dynamics, it is clear that data-model integration remains under-used, and that uncertainties remain poorly quantified in both empirically-based and numerical ice-Sheet reconstructions. The representation of past climate will continue to be the largest source of uncertainty for numerical modelling. As such, palaeo-observations are critical to constrain and validate modelling. State-of-the-art numerical models will continue to improve both in model resolution and in the breadth of inclusion of relevant processes, thereby enabling more accurate and more direct comparison with the increasing range of palaeo-observations. Thus, the capability is developing to use all relevant palaeo-records to more strongly constrain deglacial (and to a lesser extent pre-LGM) ice sheet evolution. In working towards that goal, the accurate representation of uncertainties is required for both constraint data and model outputs. Close cooperation between modelling and data-gathering communities is essential to ensure this capability is realised and continues to progress.
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- Boele, Florien, et al.
(författare)
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Inequalities in access to neuro-oncology supportive care and rehabilitation: A survey of healthcare professionals' perspectives
- 2024
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Ingår i: NEURO-ONCOLOGY PRACTICE. - 2054-2577 .- 2054-2585.
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Tidskriftsartikel (refereegranskat)abstract
- Background Neuro-oncology patients and caregivers should have equitable access to rehabilitation, supportive-, and palliative care. To investigate existing issues and potential solutions, we surveyed neuro-oncology professionals to explore current barriers and facilitators to screening patients' needs and referral to services.Methods Members of the European Association of Neuro-Oncology and the European Organisation for Research and Treatment of Cancer Brain Tumor Group (EORTC-BTG) were invited to complete a 39-item online questionnaire covering the availability of services, screening, and referral practice. Responses were analyzed descriptively; associations between sociodemographic/clinical variables and screening/referral practice were explored.Results In total, 103 participants completed the survey (67% women and 57% medical doctors). Fifteen professions from 23 countries were represented. Various rehabilitation, supportive-, and palliative care services were available yet rated "inadequate" by 21-37% of participants. Most respondents with a clinical role (n = 94) declare to screen (78%) and to refer (83%) their patients routinely for physical/cognitive/emotional issues. Survey completers (n = 103) indicated the main reasons for not screening/referring were (1) lack of suitable referral options (50%); (2) shortage of healthcare professionals (48%); and (3) long waiting lists (42%). To improve service provision, respondents suggested there is a need for education about neuro-oncology-specific issues (75%), improving the availability of services (65%) and staff (64%), developing international guidelines (64%), and strengthening the existing evidence-base for rehabilitation (60%).Conclusions Detecting and managing neuro-oncology patients' and caregivers' rehabilitation, supportive,- and palliative care needs can be improved. Better international collaboration can help address healthcare disparities.
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- Fuchs, Margret C., et al.
(författare)
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Exploring the potential of luminescence methods for dating Alpine rock glaciers
- 2013
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Ingår i: Quaternary Geochronology. - : Elsevier BV. - 1871-1014 .- 1878-0350. ; 18, s. 17-33
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Tidskriftsartikel (refereegranskat)abstract
- Rock glaciers contain valuable information about the spatial and temporal distribution of permafrost. The wide distribution of these landforms in high mountains promotes them as useful archives for the deciphering of the environmental conditions during their formation and evolution. However, age constraints are needed to unravel the palaeoclimatic context of rock glaciers, but numerical dating is difficult. Here, we present a case study assessing the potential of luminescence techniques (OSL, IRSL) to date the inner sand-rich layer of active rock glaciers. We focus on the signal properties and the resetting of the signal prior to deposition by investigating single grains. While most quartz shows low signal intensities and problematic luminescence characteristics, K-feldspar exhibits much brighter and well-performing signals. Most signals from plagioclases do not show suitable properties. Luminescence signals far below saturation indicate distinct but differential bleaching. The finite mixture model was used to determine the prominent populations in the equivalent dose distributions. The luminescence ages represent travel times of grains since incorporation into the rock glacier and hence, minimum ages of rock glacier formation. Luminescence ages between 3 ka and 8 ka for three rock glaciers from the Upper Engadine and Albula region (Swiss Alps) agree well with independent age estimates from relative and semi-quantitative approaches. Therefore, luminescence seems to have the potential of revealing age constraints about processes related to the formation of rock glaciers, but further investigations are required for solving some of the problems remaining and reducing the dating uncertainties.
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- Guralnik, B., et al.
(författare)
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OSL-thermochronometry using bedrock quartz : A note of caution
- 2015
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Ingår i: Quaternary Geochronology. - : Elsevier BV. - 1871-1014 .- 1878-0350. ; 25, s. 37-48
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Tidskriftsartikel (refereegranskat)abstract
- Optically stimulated luminescence (OSL) thermochronometry is an emerging application, whose capability to record sub-Million-year thermal histories is of increasing interest to a growing number of subdisciplines of Quaternary research. However, several recent studies have encountered difficulties both in extraction of OSL signals from bedrock quartz, and in their thermochronometric interpretation, thus highlighting the need for a methodological benchmark. Here, we investigate the characteristic OSL signals from quartz samples across all major types of bedrock and covering a wide range of chemical purities. High ratios of infrared to blue stimulated luminescence (IRSL/BLSL), an insensitive 'fast' OSL component, and anomalously short recombination lifetimes seen in time-resolved luminescence (TROSL), are often encountered in quartz from crystalline (magmatic and metamorphic) bedrock, and may hamper successful OSL dating. Furthermore, even when the desirable signal is present, its concentration might be indistinguishable from its environmental steady-state prediction, thus preventing its conversion to a cooling or heating history. We explore the saturation properties and the thermal activation parameters of various OSL signals in quartz to outline the capabilities and limitations for their use in low-temperature thermochronometry.
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| 9. |
- Hoang-Xuan, Khê, et al.
(författare)
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European Association of Neuro-Oncology (EANO) guidelines for treatment of primary central nervous system lymphoma (PCNSL)
- 2023
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 25:1, s. 37-53
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Tidskriftsartikel (refereegranskat)abstract
- The management of primary central nervous system (PCNSL) is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the limited number of controlled studies available. In 2021, given recent advances and the publication of practice-changing randomized trials, the European Association of Neuro-Oncology (EANO) created a multidisciplinary task force to update the previously published evidence-based guidelines for immunocompetent adult patients with PCNSL and added a section on immunosuppressed patients. The guideline provides consensus considerations and recommendations for the treatment of PCNSL, including intraocular manifestations and specific management of the elderly. The main changes from the previous guideline include strengthened evidence for the consolidation with ASCT in first-line treatment, prospectively assessed chemotherapy combinations for both young and elderly patients, clarification of the role of rituximab even though the data remain inconclusive, of the role of new agents, and the incorporation of immunosuppressed patients and primary ocular lymphoma. The guideline should aid the clinicians in everyday practice and decision making and serve as a basis for future research in the field.
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| 12. |
- Schmidt, C., et al.
(författare)
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THE ASSESSMENT OF RADIONUCLIDE DISTRIBUTION IN SILEX BY AUTORADIOGRAPHY IN THE CONTEXT OF DOSE RATE DETERMINATION FOR THERMOLUMINESCENCE DATING
- 2013
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Ingår i: Archaeometry. - : Wiley. - 0003-813X .- 1475-4754. ; 55, s. 407-422
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Tidskriftsartikel (refereegranskat)abstract
- A combination of two autoradiography methods was applied to investigate the radionuclide distribution patterns in a range of different silices. We obtained greyscale images (-radiation) and -track patterns for qualitative assessment, and used a statistical approach to quantify the degree of uniformity of the radiation fields. It was found that almost all samples are poor in potassium, thorium and uranium, and that locally high concentrations are present only in dark-coloured veins and inclusions. Statistical analyses reveal evidence of radionuclide clustering in more than half of the 21 specimens. Concerning thermoluminescence dating of burnt lithics, such gradients should be taken into account to improve precision and accuracy in cases where the external radiation is not strongly dominating for the sample under consideration.
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| 13. |
- Weller, Michael, et al.
(författare)
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EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood.
- 2021
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Ingår i: Nature reviews. Clinical oncology. - : Springer Science and Business Media LLC. - 1759-4782 .- 1759-4774. ; 18, s. 170-186
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Forskningsöversikt (refereegranskat)abstract
- In response to major changes in diagnostic algorithms and the publication of mature results from various large clinical trials, the European Association of Neuro-Oncology (EANO) recognized the need to provide updated guidelines for the diagnosis and management of adult patients with diffuse gliomas. Through these evidence-based guidelines, a task force of EANO provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. The diagnostic component is based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System and the subsequent recommendations of the Consortium to Inform Molecular and Practical Approaches to CNS Tumour Taxonomy - Not Officially WHO (cIMPACT-NOW). With regard to therapy, we formulated recommendations based on the results from the latest practice-changing clinical trials and also provide guidance for neuropathological and neuroradiological assessment. In these guidelines, we define the role of the major treatment modalities of surgery, radiotherapy and systemic pharmacotherapy, covering current advances and cognizant that unnecessary interventions and expenses should be avoided. This document is intended to be a source of reference for professionals involved in the management of adult patients with diffuse gliomas, for patients and caregivers, and for health-care providers.
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