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Sökning: WFRF:(de la Torre Manuel)

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  • Gullbo, Joachim, et al. (författare)
  • Antitumor efficacy and acute toxicity of the novel dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) in vivo.
  • 2004
  • Ingår i: Investigational new drugs. - 0167-6997. ; 22:4, s. 411-20
  • Tidskriftsartikel (refereegranskat)abstract
    • The novel alkylating dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) was evaluated for acute toxicity and antitumor activity in mice, with melphalan as a reference. To determine a safe and tolerable dose for efficacy studies the acute toxicity following intravenous injection in the tail vein was monitored using a 14-day schedule with up to four doses. The highest tested dose, 25 micromoles/kg, was considered close to this level, with minor effects on body weight gain but significant effects on hematological parameters. Melphalan and J1 appeared equitoxic with no statistically significant differences. Subsequently a mouse hollow fiber model was employed with subcutaneous implantation of fibers containing human tumor cells. Three different human tumor cell lines as well as two samples of primary human tumor cells (ovarian carcinoma and chronic lymphatic leukemia) were used as tumor models. At the dose level tested there was a marked and statistically significant decrease in both T-cell leukemia CCRF-CEM and small cell lung cancer NCI-H69 tumor cell growth and viability in response to J1 as compared with both placebo and melphalan treated groups. In primary ovarian carcinoma cells only J1 treatment resulted in significant tumor regression (net cell kill). In summary the results indicate that, despite an expected short half time in the blood circulation, the promising in vitro data from the previous studies of J1 seems translatable into the in vivo situation. At equal doses of alkylating units J1, compared to melphalan, was more active in the mouse hollow-fiber model, but showed similar general toxicity.
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  • Vialas, Vital, et al. (författare)
  • A multicentric study to evaluate the use of relative retention times in targeted proteomics
  • 2017
  • Ingår i: Journal of Proteomics. - Elsevier. - 1874-3919. ; 152, s. 138-149
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII). According to the results obtained in this study, dimensionless retention time values (iRTs) demonstrated to be a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups both intra- and inter-laboratories. iRT values also showed very low variability over long time periods. Furthermore, parallel quantitative analyses showed a high reproducibility despite the variety of experimental strategies used, either MRM (multiple reaction monitoring) or pseudoMRM, and the diversity of analytical platforms employed. Biological significance From the very beginning of proteomics as an analytical science there has been a growing interest in developing standardized methods and experimental procedures in order to ensure the highest quality and reproducibility of the results. In this regard, the recent (2012) introduction of the dimensionless retention time concept has been a significant advance. In our multicentric (28 laboratories) study we explore the usefulness of this concept in the context of a targeted proteomics experiment, demonstrating that dimensionless retention time values is a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups.
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4.
  • Gõmez-Elvira, Javier, et al. (författare)
  • Curiosity's rover environmental monitoring station : Overview of the first 100 sols
  • 2014
  • Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:7, s. 1680-1688
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>In the first 100 Martian solar days (sols) of the Mars Science Laboratory mission, the Rover Environmental Monitoring Station (REMS) measured the seasonally evolving diurnal cycles of ultraviolet radiation, atmospheric pressure, air temperature, ground temperature, relative humidity, and wind within Gale Crater on Mars. As an introduction to several REMS-based articles in this issue, we provide an overview of the design and performance of the REMS sensors and discuss our approach to mitigating some of the difficulties we encountered following landing, including the loss of one of the two wind sensors. We discuss the REMS data set in the context of other Mars Science Laboratory instruments and observations and describe how an enhanced observing strategy greatly increased the amount of REMS data returned in the first 100 sols, providing complete coverage of the diurnal cycle every 4 to 6 sols. Finally, we provide a brief overview of key science results from the first 100 sols. We found Gale to be very dry, never reaching saturation relative humidities, subject to larger diurnal surface pressure variations than seen by any previous lander on Mars, air temperatures consistent with model predictions and abundant short timescale variability, and surface temperatures responsive to changes in surface properties and suggestive of subsurface layering. Key Points Introduction to the REMS results on MSL mission Overiview of the sensor information Overview of operational constraints</p>
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5.
  • Hamilton, Victoria E., et al. (författare)
  • Observations and preliminary science results from the first 100 sols of MSL Rover Environmental Monitoring Station ground temperature sensor measurements at Gale Crater
  • 2014
  • Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 119:4, s. 745-770
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We describe preliminary results from the first 100 sols of ground temperature measurements along the Mars Science Laboratory's traverse from Bradbury Landing to Rocknest in Gale. The ground temperature data show long-term increases in mean temperature that are consistent with seasonal evolution. Deviations from expected temperature trends within the diurnal cycle are observed and may be attributed to rover and environmental effects. Fits to measured diurnal temperature amplitudes using a thermal model suggest that the observed surfaces have thermal inertias in the range of 265-375?J m-2 K-1 s-1/2, which are within the range of values determined from orbital measurements and are consistent with the inertias predicted from the observed particle sizes on the uppermost surface near the rover. Ground temperatures at Gale Crater appear to warm earlier and cool later than predicted by the model, suggesting that there are multiple unaccounted for physical conditions or processes in our models. Where the Mars Science Laboratory (MSL) descent engines removed a mobile layer of dust and fine sediments from over rockier material, the diurnal temperature profile is closer to that expected for a homogeneous surface, suggesting that the mobile materials on the uppermost surface may be partially responsible for the mismatch between observed temperatures and those predicted for materials having a single thermal inertia. Models of local stratigraphy also implicate thermophysical heterogeneity at the uppermost surface as a potential contributor to the observed diurnal temperature cycle. Key Points Diurnal ground temperatures vary with location Diurnal temperature curves are not well matched by a homogeneous thermal model GTS data are consistent with a varied stratigraphy and thermophysical properties.</p>
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6.
  • Bill-Axelson, Anna, et al. (författare)
  • Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
  • 2008
  • Ingår i: Journal of the National Cancer Institute. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-54
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up. METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided. RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P &lt; .001). CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.</p>
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7.
  • Carlsson, Jörgen, et al. (författare)
  • EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides
  • 2015
  • Ingår i: Radiology and Oncology. - 1318-2099 .- 1581-3207. ; 49:1, s. 50-58
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background. There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder canter and these methods are therefore not routinely used. Targeting radionuclides to the extracellular domain of the receptors is potentially a better possibility. Methods. EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose. Results. EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients. Conclusions. At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.</p>
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8.
  • Dyrskjøt, Lars, et al. (författare)
  • Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma : a multicenter validation study
  • 2007
  • Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:12, s. 3545-3551
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Purpose:</strong> Clinically useful molecular markers predicting the clinical course of patients diagnosed with non–muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for molecular diagnosis of disease stage and carcinoma <em>in situ</em> (CIS) and for predicting disease recurrence and progression.</p> <p><strong>Experimental Design:</strong> We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic diagnosis and clinical outcome.</p> <p><strong>Results:</strong> Classification of disease stage using a 52-gene classifier was found to be highly significantly correlated with pathologic stage (<em>P</em> &lt; 0.001). Furthermore, the classifier added information regarding disease progression of T<sub>a</sub> or T<sub>1</sub> tumors (<em>P</em> &lt; 0.001). The molecular 88-gene progression classifier was highly significantly correlated with progression-free survival (<em>P</em> &lt; 0.001) and cancer-specific survival (<em>P</em> = 0.001). Multivariate Cox regression analysis showed the progression classifier to be an independently significant variable associated with disease progression after adjustment for age, sex, stage, grade, and treatment (hazard ratio, 2.3; <em>P</em> = 0.007). The diagnosis of CIS using a 68-gene classifier showed a highly significant correlation with histopathologic CIS diagnosis (odds ratio, 5.8; <em>P</em> &lt; 0.001) in multivariate logistic regression analysis.</p> <p><strong>Conclusion:</strong> This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non–muscle-invasive bladder cancer. This information may be useful to better guide patient treatment.</p>
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