| 1. |
- Engert, Andreas, et al.
(author)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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In: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Journal article (peer-reviewed)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 2. |
- Schnitzbauer, Andreas A, et al.
(author)
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A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma.
- 2010
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In: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10
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Journal article (peer-reviewed)abstract
- The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.
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| 3. |
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| 4. |
- Eckhardt, C. L., et al.
(author)
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The Fc gamma receptor IIa R131H polymorphism is associated with inhibitor development in severe hemophilia A
- 2014
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In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 12:8, s. 1294-1301
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Journal article (peer-reviewed)abstract
- Background: The development of factor (F) VIII neutralizing alloantibodies (inhibitors) is a major complication of treatment with FVIII concentrates in hemophilia A and the etiology is still poorly understood. The low-affinity Fc gamma receptors (Fc gamma R), which are expressed on immune cells, provide an important link between cellular and humoral immunity by interacting with IgG subtypes. Genetic variations of the genes encoding Fc gamma Rs (FCGR genes) have been associated with susceptibility to infectious and autoimmune diseases. Objectives: The aim of this study was to investigate the association between genetic variation of FCGR and inhibitor development in severe hemophilia A. Patients/Methods: In this case-control study samples of 85 severe hemophilia A patients (siblings from 44 families) were included. Single nucleotide polymorphisms and copy number variation of the FCGR2 and FCGR3 gene cluster were studied in an FCGR-specific multiplex ligation-dependent probe amplification assay. Frequencies were compared in a generalized estimating equation regression model. Results: Thirty-six patients (42%) had a positive history of inhibitor development. The polymorphism 131R > H in the FCGR2A gene was associated with an increased risk of inhibitor development (odds ratio [OR] per H-allele, 1.8; 95% confidence interval [CI], 1.1-2.9). This association persisted in 29 patients with high titer inhibitors (OR per H-allele, 1.9; 95% CI, 1.2-3.2) and in 44 patients with the F8 intron 22 inversion (OR per H-allele, 2.6; 95% CI, 1.1-6.6). Conclusions: Hemophilia A patients with the HH genotype of the FCGR2A polymorphism 131R > H have a more than 3-fold increased risk of inhibitor development compared with patients with the RR genotype.
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| 6. |
- Geissler, F., et al.
(author)
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Group theoretical and topological analysis of the quantum spin Hall effect in silicene
- 2013
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In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 15
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Journal article (peer-reviewed)abstract
- Silicene consists of a monolayer of silicon atoms in a buckled honeycomb structure. It was recently discovered that the symmetry of such a system allows for interesting Rashba spin-orbit effects. A perpendicular electric field is able to couple to the sublattice pseudospin, making it possible to electrically tune and close the band gap. Therefore, external electric fields may generate a topological phase transition from a topological insulator to a normal insulator (or semimetal) and vice versa. The contribution of the present paper to the study of silicene is twofold. Firstly, we perform a group theoretical analysis to systematically construct the Hamiltonian in the vicinity of the K points of the Brillouin zone and find an additional, electric field induced spin-orbit term, that is allowed by symmetry. Subsequently, we identify a tight-binding model that corresponds to the group theoretically derived Hamiltonian near the K points. Secondly, we start from this tight-binding model to analyze the topological phase diagram of silicene by an explicit calculation of the Z(2) topological invariant of the band structure. To this end, we calculate the Z(2) topological invariant of the honeycomb lattice in a manifestly gauge invariant way which allows us to include S-z symmetry breaking terms-like Rashba spin-orbit interaction-into the topological analysis. Interestingly, we find that the interplay of a Rashba and an intrinsic spin-orbit term can generate a non-trivial quantum spin Hall phase in silicene. This is in sharp contrast to the more extensively studied honeycomb system graphene where Rashba spin-orbit interaction is known to compete with the quantum spin Hall effect in a detrimental way.
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| 7. |
- Geissler, Jan, et al.
(author)
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Improving Patient Involvement in Medicines Research and Development: : A Practical Roadmap
- 2017
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In: Therapeutic Innovation and Regulatory Science. - : Sage Publications. - 2168-4790 .- 2168-4804. ; 51:5, s. 612-619
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Journal article (peer-reviewed)abstract
- The value of patient involvement (PI) in medicines research and development (R&D) is increasingly recognized by all health stakeholders. Despite numerous ongoing PI initiatives, PI so far lacks structure and consistency in approach. Limited formal documentation of PI activities further hampers the sharing of experience and learnings, preventing timely and systematic implementation. This article summarizes the outcomes of several multistakeholder discussions during 2013-2016 in a practical roadmap for PI in medicines R&D. The roadmap highlights specific opportunities for PI along the 4 key stages of the medicines R&D life cycle and is illustrated with concrete examples. This roadmap's aim is to provide a tool to facilitate PI during medicines research and development and is being shared to encourage implementation and further refinement.
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| 8. |
- Lawler, Mark, et al.
(author)
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A Catalyst for Change: The European Cancer Patient's Bill of Rights.
- 2014
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In: The Oncologist. - : Oxford University Press (OUP). - 1549-490X .- 1083-7159.
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Journal article (peer-reviewed)abstract
- The European Cancer Concord is a unique patient-centered partnership that will act as a catalyst to achieve improved access to an optimal standard of cancer care and research for European citizens. In order to provide tangible benefits for European cancer patients, the partnership proposes the creation of a “European Cancer Patient's Bill of Rights,” a patient charter that will underpin equitable access to an optimal standard of care for Europe's citizens.
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| 9. |
- Lawler, Mark, et al.
(author)
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European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.
- 2023
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In: The Lancet. Oncology. - 1474-5488 .- 1470-2045. ; 24:1
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Journal article (peer-reviewed)abstract
- Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average survival for all European cancer patients by 2035.
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| 10. |
- Schnitzbauer, Andreas A., et al.
(author)
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mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors
- 2020
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In: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 272:5, s. 855-862
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Journal article (peer-reviewed)abstract
- Objective: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). Summary and Background Data: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov:NCT00355862), the effect of sirolimus on the recurrence of HCC after LTwas investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. Patients and Methods: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. Results: Sirolimus use for >= 3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) >= 10 ng/mL and having used sirolimus for >= 3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49- 0.59, P = 0.0079- 0.0245). Conclusions: mTOR-inhibitor treatment with sirolimus for >= 3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. Clinical Trial Registration: EudraCT: 2005-005362-36 Clinicaltrials.gov: NCT00355862.
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| 11. |
- Sullivan, Richard, et al.
(author)
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Delivering affordable cancer care in high-income countries
- 2011
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In: The Lancet Oncology. - London : Lancet Oncology. - 1470-2045 .- 1474-5488. ; 12:10, s. 933-980
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Journal article (peer-reviewed)abstract
- The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.
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