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

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21.
  • 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.
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22.
  • 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>
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23.
  • Bhoo-Pathy, Nirmala, et al. (författare)
  • Intake of Coffee, Decaffeinated Coffee, or Tea Does Not Affect Risk for Pancreatic Cancer: Results From the European Prospective Investigation into Nutrition and Cancer Study
  • 2013
  • Ingår i: Clinical Gastroenterology and Hepatology. - Elsevier. - 1542-7714. ; 11:11, s. 1486-1492
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Few modifiable risk factors have been implicated in the etiology of pancreatic cancer. There is little evidence for the effects of caffeinated coffee, decaffeinated coffee, or tea intake on risk of pancreatic cancer. We investigated the association of total coffee, caffeinated coffee, decaffeinated coffee, and tea consumption with risk of pancreatic cancer. METHODS: This study was conducted within the European Prospective Investigation into Nutrition and Cancer cohort, comprising male and female participants from 10 European countries. Between 1992 and 2000, there were 477,312 participants without cancer who completed a dietary questionnaire and were followed up to determine pancreatic cancer incidence. Coffee and tea intake was calibrated with a 24-hour dietary recall. Adjusted hazard ratios (HRs) were computed using multivariable Cox regression. RESULTS: During a mean follow-up period of 11.6 y, 865 first incidences of pancreatic cancers were reported. When divided into fourths, neither total intake of coffee (HR, 1.03; 95% confidence interval [CI], 0.83-1.27; high vs low intake), decaffeinated coffee ( HR, 1.12; 95% CI, 0.76-1.63; high vs low intake), nor tea were associated with risk of pancreatic cancer ( HR, 1.22, 95% CI, 0.95-1.56; high vs low intake). Moderately low intake of caffeinated coffee was associated with an increased risk of pancreatic cancer ( HR, 1.33; 95% CI, 1.02-1.74), compared with low intake. However, no graded dose response was observed, and the association attenuated after restriction to histologically confirmed pancreatic cancers. CONCLUSIONS: Based on an analysis of data from the European Prospective Investigation into Nutrition and Cancer cohort, total coffee, decaffeinated coffee, and tea consumption are not related to the risk of pancreatic cancer.
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24.
  • Gustafson, Lars, et al. (författare)
  • A factor analytic approach to symptom patterns in dementia.
  • 2010
  • Ingår i: International Journal of Alzheimer's Disease. - Hindawi Publishing Corporation. - 2090-0252.
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous publications have shown a high diagnostic sensitivity and specificity of three short clinical rating scales for Alzheimer's disease (AD), frontotemporal dementia (FTD), and vascular dementia (VaD) validated against neuropathological (NP) diagnoses. In this study, the aim was to perform an exploratory factor analysis of the items in these clinical rating scales. The study included 190 patients with postmortem diagnoses of AD (n = 74), VaD (n = 33), mixed AD/VaD (n = 31), or FTD (n = 52). The factor analysis produced three strong factors. Factor 1 contained items describing cerebrovascular disease, similar to the Hachinski Ischemic Score. Factor 2 enclosed major clinical characteristics of FTD, and factor 3 showed a striking similarity to the AD scale. A fourth symptom cluster was described by perception and expression of emotions. The factor analyses strongly support the construct validity of the diagnostic rating scales.
25.
  • Fedirko, V., et al. (författare)
  • Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans
  • 2013
  • Ingår i: Annals of Oncology. - 0923-7534. ; 24:2, s. 543-553
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking. Patients and methods: The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset. Results: Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer. Conclusions: Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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26.
  • Giandomenico, Valeria, et al. (författare)
  • Olfactory Receptor 51E1 as a Novel Target for Diagnosis in Somatostatin Receptor Negative Lung Carcinoids
  • 2013
  • Ingår i: Journal of Molecular Endocrinology. - 0952-5041 .- 1479-6813. ; 51, s. 277-286
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Somatostatin receptors (SSTRs) may be used in lung carcinoids (LCs) for diagnosis and therapy, although additional targets are clearly warranted. This study aimed to investigate whether olfactory receptor 51E1 (OR51E1) may be a potential target for LCs. OR51E1 coding sequence was analyzed in LC cell lines, NCI-H727 and NCI-H720. OR51E1 transcript expression was investigated in LC cell lines and frozen specimens by quantitative real-time PCR. OR51E1, SSTR2, SSTR3, and SSTR5 expression was evaluated by immunohistochemistry on paraffin-embedded sections of 73 typical carcinoids (TCs), 14 atypical carcinoids (ACs) and 11 regional/distant metastases, and compared to OctreoScan data. Immunohistochemistry results were rendered semiquantitatively on a scale from 0 to 3+, taking into account the cellular compartmentalization (membrane vs. cytoplasm) and the percentage of tumor cells (&lt;50% vs. &gt;50%). Our results showed that wild-type OR51E1 transcript was expressed in both LC cell lines. OR51E1 mRNA was expressed in 9/12 TCs and 7/9 ACs (p=NS). Immunohistochemically, OR51E1, SSTR2, SSTR3 and SSTR5 were detected in 85%, 71%, 25% and 39% of TCs, and in 86%, 79%, 43% and 36% of ACs, respectively. OR51E1 immunohistochemical scores were higher or equal compared to SSTRs in 79% of TCs and 86% of ACs. Furthermore, in the LC cases where all SSTR subtypes were lacking, membrane OR51E1 expression was detected in 10/17 TCs and 1/2 ACs. Moreover, higher OR51E1 immunohistochemical scores were detected in 5/6 OctreoScan-negative LC lesions. Therefore, the high expression of OR51E1 in LCs makes it a potential novel diagnostic target in SSTR-negative tumors.</p>
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27.
  • Huang, Jiaqi, et al. (författare)
  • Risk of pancreatic cancer among individuals with hepatitis C or hepatitis B virus infection : a nationwide study in Sweden
  • 2013
  • Ingår i: British Journal of Cancer. - London, United Kingdom : Nature Publishing Group. - 0007-0920. ; 109:11, s. 2917-2923
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A few studies indicated that hepatitis C and hepatitis B virus (HCV/HBV) might be associated with pancreatic cancer risk. The aim of this nationwide cohort study was to examine this possible association.Methods: Hepatitis C virus- and hepatitis B virus-infected individuals were identified from the national surveillance database from 1990 to 2006, and followed to the end of 2008. The pancreatic cancer risk in the study population was compared with the general population by calculation of Standardized Incidence Ratios (SIRs), and with a matched reference population using a Cox proportional hazards regression model to calculate hazard ratios (HRs).Results: In total 340 819 person-years in the HCV cohort and 102 295 in the HBV cohort were accumulated, with 34 and 5 pancreatic cancers identified, respectively. The SIRHCV was 2.1 (95% confidence interval, CI: 1.4, 2.9) and the SIRHBV was 1.4 (0.5, 3.3). In the Cox model analysis, the HR for HCV infection was 1.9 (95% CI: 1.3, 2.7), diminishing to 1.6 (1.04, 2.4) after adjustment for potential confounders.Conclusion: Our results indicated that HCV infection might be associated with an increased risk of pancreatic cancer but further studies are needed to verify such association. The results in the HBV cohort indicated an excess risk, however, without statistical significance due to lack of power.
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28.
  • 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.
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29.
  • Ahlgren, Sara, 1979- (författare)
  • Molecular Radionuclide Imaging Using Site-specifically Labelled Recombinant Affibody Molecules Preparation and Preclinical Evaluation
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Radionuclide molecular imaging is an emerging multidisciplinary technique that is used in modern medicine to visualise diseases at cellular and molecular levels. This thesis is based on five papers (I-V) and focuses on the development of site-specific radiolabelled recombinant anti-HER2 Affibody molecules and preclinical evaluations <em>in vitro</em> and <em>in vivo</em> of the labelled conjugates. This work is part of a preclinical development of an Affibody molecule-based tracer for molecular imaging of HER2 expressing tumours.</p> <p>Papers I and II report the evaluation of the Affibody molecule Z<sub>HER2:2395</sub>-C, site-specifically labelled with the radiometals <sup>111</sup>In (for SPECT) and <sup>57</sup>Co (as a surrogate for <sup>55</sup>Co, suitable for PET applications) using a thiol reactive DOTA derivative as a chelator. Both conjugates demonstrated very suitable biodistribution properties, enabling high contrast imaging just a few hours after injection.</p> <p>Papers III and IV report the development and optimization of a technique for site-specific labelling of Z<sub>HER2:2395</sub>-C with <sup>99m</sup>Tc using an N<sub>3</sub>S chelating peptide sequence. <sup>99m</sup>Tc-Z<sub>HER2:2395</sub>-C demonstrated high and specific tumour uptake and rapid clearance of non-bound tracer from the blood, resulting in high tumour-to-non-tumour ratios shortly after injection, enabling high contrast imaging. In addition, in the study described in paper IV, freeze-dried kits previously developed for <sup>99m</sup>Tc-labelling were optimised, resulting in the development of a kit in which all the reagents and protein needed for labelling of Z<sub>HER2:2395</sub>-C with <sup>99m</sup>Tc were contained in a single vial.</p> <p>Paper V reports the evaluation of an anti-HER2 Affibody molecule, ABY-025, with a fundamentally re-engineered scaffold. Despite the profound re-engineering, the biodistribution pattern of <sup>111</sup>In-ABY-025 was very similar to that of two variants of the parental molecule.</p> <p>It seems reasonable to believe that these results will also be applicable to Affibody molecules towards other targets. Hopefully, this work will also be helpful in the development of other small proteinaceous tracers.</p>
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30.
  • Solberg, Arne, et al. (författare)
  • Residual Prostate Cancer in Patients Treated with Endocrine Therapy with or Without Radical Radiotherapy : A Side Study of the SPCG-7 Randomized Trial.
  • 2011
  • Ingår i: International journal of radiation oncology, biology, physics. - Elsevier. - 1879-355X. ; 80:1, s. 55-61
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>PURPOSE: The Scandinavian Prostate Cancer Group-7 randomized trial demonstrated a survival benefit of combined endocrine therapy and external-beam radiotherapy over endocrine therapy alone in patients with high-risk prostate cancer. In a subset of the study population, the incidence and clinical implications of residual prostate cancer in posttreatment prostate biopsy specimens was evaluated.</p> <p>METHODS AND MATERIALS: Biopsy specimens were obtained from 120 of 875 men in the Scandinavian Prostate Cancer Group-7 study.</p> <p>RESULTS: Biopsies were performed at median of 45 months follow-up. In 63 patients receiving endocrine treatment only and 57 patients receiving combined treatment, residual cancer was found in 66% (n = 41) and 22% (n = 12), respectively (p &lt; 0.0001). The vast majority of residual tumors were poorly differentiated (Gleason score &gt;/=8). Endocrine therapy alone was predictive of residual prostate cancer: odds ratio 7.49 (3.18-17.7), p &lt; 0.0001. In patients with positive vs. negative biopsy the incidences of clinical events were as follows: biochemical recurrence 74% vs. 27% (p &lt; 0.0001), local progression 26% vs. 4.7% (p = 0.002), distant recurrence 17% vs. 9.4% (p = 0.27), clinical recurrence 36% vs. 13% (p = 0.006), cancer-specific death 19% vs. 9.7% (p = 0.025). In multivariable analysis, biochemical recurrence was significantly associated with residual cancer: hazard ratio 2.69 (1.45-4.99), p = 0.002, and endocrine therapy alone hazard ratio 3.45 (1.80-6.62), p &lt; 0.0001.</p> <p>CONCLUSIONS: Radiotherapy combined with hormones improved local tumor control in comparison with endocrine therapy alone. Residual prostate cancer was significantly associated with serum prostate-specific antigen recurrence, local tumor progression, clinical recurrence, and cancer-specific death in univariable analysis. Residual cancer was predictive of prostate-specific antigen recurrence in multivariable analysis.</p>
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