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Träfflista för sökning "AMNE:(MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology) srt2:(2010-2014);srt2:(2014)"

Sökning: AMNE:(MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology) > (2010-2014) > (2014)

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  • Hofmarcher, Thomas, et al. (författare)
  • Access to high-quality oncology care across Europe
  • 2014
  • Rapport (övrigt vetenskapligt)abstract
    • Oncology care in Europe is facing challenging circumstances. The report aims to derive evidence-based policy recommendations on how to optimize access to oncology care and how to achieve a high-quality standard that is both achievable and sustainable. The report looks at the full cancer patient pathway encompassing primary prevention, screening, diagnostics and treatment. Special emphasis is placed on access to effective screening programs as well as on access to innovative drug treatments. Barriers that prevent access to effective oncology care are identified and determinants of a high-quality standard in care established. The analysis focuses on three common cancer types - colorectal, lung and prostate cancer - and four EU member states - France, Germany, Poland and Sweden. The health-economic burden of cancer is reviewed and countries’ performance on the established access and quality principles assessed and compared. This report was commissioned and funded by Janssen Pharmaceutica NV and based on independent research delivered by IHE. Janssen has had no influence or editorial control over the content of this report, and the views and opinions of the authors are not necessarily those of Janssen.
  • Borné, Yan, et al. (författare)
  • Cadmium exposure and incidence of diabetes mellitus - results from the malmö diet and cancer study.
  • 2014
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Cadmium is a pollutant with multiple adverse health effects: renal dysfunction, osteoporosis and fractures, cancer, and probably cardiovascular disease. Some studies have reported associations between cadmium and impaired fasting glucose and diabetes. However, this relationship is controversial and there is a lack of longitudinal studies.
  • Sjögren, Erik, et al. (författare)
  • Pharmacokinetics of an injectable modified-release 2-hydroxyflutamide formulation in the human prostate gland using a semiphysiologically based biopharmaceutical model.
  • 2014
  • Ingår i: Molecular pharmaceutics. - 1543-8392. ; 11:9, s. 3097-111
  • Tidskriftsartikel (refereegranskat)abstract
    • The local distribution of 2-hydroxyflutamide (2-HOF) in prostate tissue after a single intraprostatic injection of a novel parenteral modified-release (MR) formulation in patients with localized prostate cancer was estimated using a semiphysiologically based biopharmaceutical model. Plasma concentration-time profiles for 2-HOF were acquired from a phase II study in 24 patients and the dissolution of the MR formulation was investigated in vitro. Human physiological values and the specific physicochemical properties of 2-HOF were obtained from the literature or calculated via established algorithms. A compartmental modeling approach was adopted for tissue and blood in the prostate gland, where the compartments were modeled as a series of concentric spherical shells contouring the centrally positioned depot formulation. Discrete fluid connections between the blood compartments were described by the representative flow of blood, whereas the mass transport of drug from tissue to tissue and tissue to blood was described by a one-dimensional diffusion approximation. An empirical dissolution approach was adopted for the release of 2-HOF from the formulation. The model adequately described the plasma concentration-time profiles of 2-HOF. Predictive simulations indicated that the local tissue concentration of 2-HOF within a distance of 5 mm from the depot formulation was approximately 40 times higher than that of unbound 2-HOF in plasma. The simulations also indicated that spreading the formulation throughout the prostate gland would expose more of the gland and increase the overall release rate of 2-HOF from the given dose. The increased release rate would initially increase the tissue and plasma concentrations but would also reduce the terminal half-life of 2-HOF in plasma. Finally, an in vitro-in vivo correlation of the release of 2-HOF from the parenteral MR formulation was established. This study shows that intraprostatic 2-HOF concentrations are significantly higher than systemic plasma concentrations and that increased distribution of 2-HOF throughout the gland, using strategic imaging-guided administration, is possible. This novel parenteral MR formulation, thus, facilitates good pharmacological effect while minimizing the risk of side effects.
  • Femel, Julia, 1986- (författare)
  • Therapeutic Cancer Vaccines Targeting Molecules Associated with Tumor Angiogenesis
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Induction of an endogenous antibody response by therapeutic vaccination could provide an alternative to cost-intensive monoclonal antibody-based treatments for cancer. Since the target of a cancer vaccine will most likely be a self-antigen, self-tolerance of the immune system must be circumvented. Using fusion proteins consisting of the self-antigen to be targeted and a part derived from a foreign antigen, it is possible to break tolerance against the self-antigen. Furthermore, a potent adjuvant is required to support an immune response against a self-molecule. Currently no adjuvant suitable for this purpose is approved for use in humans.</p><p>This thesis describes the development of a therapeutic vaccine targeting the vasculature of tumors. As tumor cells have developed strategies to escape immune surveillance, targeting of molecules associated with the tumor stroma is an interesting alternative. The alternatively spliced extra domain-A and B (ED-A and ED-B) of fibronectin and the glycan-binding protein galectin-1 are selectively expressed during events of tumor angiogenesis. We have designed recombinant proteins to target ED-B, ED-A and galectin-1, containing bacterial thioredoxin (TRX) as a non-self part, resulting in TRX-EDB, TRX-EDA and TRX-Gal-1. Vaccination against ED-B induced anti-ED-B antibodies and inhibited growth of subcutaneous fibrosarcoma. Immunization against ED-A decreased tumor burden and reduced the number of lung metastases in the MMTV-PyMT model for metastatic mammary carcinoma in a therapeutic setting. Analysis of the tumor tissue from ED-B and ED-A-immunized mice indicated an attack of the tumor vasculature by the immune system. Finally, we show that galectin-1 immunization reduced tumor burden and increased leukocyte numbers in the tumor tissue. Galectin-1 is pro-angiogenic and immunosuppressive, and therefore allows simultaneous targeting of fundamental characteristics of tumorigenesis. We furthermore show that the biodegradable squalene-based Montanide ISA 720 combined with CpG oligo 1826 (M720/CpG) is at least as potent as Freund’s adjuvant with respect to breaking self-tolerance, when comparing several immunological parameters. Freund’s is a potent but toxic adjuvant used in the majority of preclinical studies.</p><p>The work presented in this thesis shows that therapeutic cancer vaccines targeting the tumor vasculature are a feasible and promising approach for cancer therapy.</p>
  • Leenders, Max, et al. (författare)
  • Fruit and vegetable intake and cause-specific mortality in the EPIC study
  • 2014
  • Ingår i: European Journal of Epidemiology. - Springer. - 1573-7284. ; 29:9, s. 639-652
  • Tidskriftsartikel (refereegranskat)abstract
    • Consumption of fruits and vegetables is associated with a lower overall mortality. The aim of this study was to identify causes of death through which this association is established. More than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition study were included, of which 25,682 were reported deceased after 13 years of follow-up. Information on lifestyle, diet and vital status was collected through questionnaires and population registries. Hazard ratios (HR) with 95 % confidence intervals (95 % CI) for death from specific causes were calculated from Cox regression models, adjusted for potential confounders. Participants reporting consumption of more than 569 g/day of fruits and vegetables had lower risks of death from diseases of the circulatory (HR for upper fourth 0.85, 95 % CI 0.77-0.93), respiratory (HR for upper fourth 0.73, 95 % CI 0.59-0.91) and digestive system (HR for upper fourth 0.60, 95 % CI 0.46-0.79) when compared with participants consuming less than 249 g/day. In contrast, a positive association with death from diseases of the nervous system was observed. Inverse associations were generally observed for vegetable, but not for fruit consumption. Associations were more pronounced for raw vegetable consumption, when compared with cooked vegetable consumption. Raw vegetable consumption was additionally inversely associated with death from neoplasms and mental and behavioral disorders. The lower risk of death associated with a higher consumption of fruits and vegetables may be derived from inverse associations with diseases of the circulatory, respiratory and digestive system, and may depend on the preparation of vegetables and lifestyle factors.
  • Zamora-Ros, R, et al. (författare)
  • Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
  • 2014
  • Ingår i: British Journal of Cancer. - 0007-0920. ; 111:9, s. 1870-1880
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods:A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases.Results:During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC.Conclusions:Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.British Journal of Cancer advance online publication, 14 August 2014; doi:10.1038/bjc.2014.459 www.bjcancer.com.
  • Gatto, Francesco, 1987-, et al. (författare)
  • Chromosome 3p loss of heterozygosity is associated with a unique metabolic network in clear cell renal carcinoma
  • 2014
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 111:9, s. E866-E875
  • Tidskriftsartikel (refereegranskat)abstract
    • Several common oncogenic pathways have been implicated in the emergence of renowned metabolic features in cancer, which in turn are deemed essential for cancer proliferation and survival. However, the extent to which different cancers coordinate their metabolism to meet these requirements is largely unexplored. Here we show that even in the heterogeneity of metabolic regulation a distinct signature encompassed most cancers. On the other hand, clear cell renal cell carcinoma (ccRCC) strongly deviated in terms of metabolic gene expression changes, showing widespread down-regulation. We observed a metabolic shift that associates differential regulation of enzymes in one-carbon metabolism with high tumor stage and poor clinical outcome. A significant yet limited set of metabolic genes that explained the partial divergence of ccRCC metabolism correlated with loss of von Hippel-Lindau tumor suppressor (VHL) and a potential activation of signal transducer and activator of transcription 1. Further network-dependent analyses revealed unique defects in nucleotide, one-carbon, and glycerophospholipid metabolism at the transcript and protein level, which contrasts findings in other tumors. Notably, this behavior is recapitulated by recurrent loss of heterozygosity in multiple metabolic genes adjacent to VHL. This study therefore shows how loss of heterozygosity, hallmarked by VHL deletion in ccRCC, may uniquely shape tumor metabolism.
  • Salander, Pär, 1948-, et al. (författare)
  • The creation of hope in patients with lung cancer
  • 2014
  • Ingår i: Acta Oncologica. - Informa Healthcare. - 0284-186X .- 1651-226X. ; 53:9, s. 1205-1211
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Lung cancer is associated with biomedical and psychological symptoms as well as a generally poor prognosis. When healthcare staff communicate with lung cancer patients it is essential that they consider the patients' own views of the situation to avoid putting unnecessary strain upon the patients' shoulders. The purpose of the present study is to better understand how a group of patients with lung cancer reflects upon their new life situation after diagnosis and primary treatment. METHOD: Fifteen patients with non-small cell lung cancer were consecutively included and, where possible, repeatedly interviewed during the course of the disease process. The 29 interviews were conducted in a thematically structured narrative form that facilitated a dialog between the interviewer and the patient. The interviews covered experiences with health care, living an everyday life, and thoughts about the future. FINDINGS AND REFLECTIONS: By focusing on how the patients more or less preconsciously elaborated mentally with their vulnerable situation, it was possible to detect different mental manoeuvres that they used as a way of creating hope. The patients distanced themselves from their disease, relied on a feeling of a sound body, idealised treatment possibilities, relied on healthy behaviour, focused on a concrete project, found that they were better off than others, and took solace in the fact that there were patients who had successfully managed the disease. DISCUSSION: The patients were not passive victims in the face of their diagnosis, but were actively trying to find ways of looking at their despairing situation in a positive light. A creative process for psychological survival had thus been initiated by the patients. We suggest that acknowledging this process should be the starting point from which physicians can engage in hope work with their patients.</p>
  • Schleiermacher, Gudrun, et al. (författare)
  • Emergence of New ALK Mutations at Relapse of Neuroblastoma
  • 2014
  • Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 32:25, s. 2727-2734
  • Tidskriftsartikel (refereegranskat)abstract
    • In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated the potential role of ALK mutations in neuroblastoma clonal evolution.
  • Spetz, Johan, et al. (författare)
  • Effects of internal irradiation from 177Lu-octreotate on transcriptional expression in GOT1 midgut carcinoid in nude mice
  • 2014
  • Ingår i: SweRays Workshop, Malmö, Sweden, Aug 20-22.
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Introduction: Neuroendocrine (NE) tumors expressing somatostatin receptors (SSTR) are often treated with 177Lu-octreotate. The treatment is highly successful in animal models, but low cure rates in clinical studies suggests optimization of treatment protocol is needed. Little is known about which cellular responses play a crucial role in neuroendocrine tumors after irradiation. It is therefore important to identify the effects of 177Lu-octreotate on biological functions for future optimization of treatment parameters and the identification of biomarkers predicting treatment response. The aim of this study was to investigate the transcriptional response of GOT1 midgut carcinoid in nude mice following 177Lu-octreotate treatment. Methods: GOT1 bearing BALB/c nude mice were i.v. injected with 15 MBq 177Lu-octreotate and tumor size was measured twice a week using calipers. Animals were killed after 1, 3, 7 or 41 days and tumor samples excised and snap frozen in liquid nitrogen. Total RNA was extracted from tumor samples and subjected to Illumina microarray expression analysis. Differential transcriptional profiles were identified by comparing treated and untreated tumor samples using Nexus Expression 3.0 software. Associated biological functions and biological pathways (according to Gene Ontology terms) were compared using Nexus Expression 3.0 and Ingenuity IPA. Results: The mean tumor volume was clearly reduced after 177Lu-octreotate treatment. Microarray analysis showed clear difference in regulation pattern between the time points. The analysis of associated biological functions revealed clear effect on cell death and survival, and cell cycle after 1, 3, and 7 days, while cellular movement and cellular development were clearly influenced after 41 days. Cellular growth and proliferation was also affected after 1 day but not at the other time points studied. Conclusions: : Analysis of the transcriptional regulation in GOT1 tumors in nude mice following 177Lu-octreotate treatment revealed responses in different cellular functions that were distinct for each time point. These findings indicate potential venues for increasing clinical effectiveness of midgut carcinoid therapy with 177Lu-octreotate.
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