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  • 1
    Online Resource
    Online Resource
    DNA hypermethylation biomarkers to predict therapy response of antiangiogenic therapy in metastatic renal cell carcinoma patients.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 4_suppl ( 2014-02-01), p. 459-459
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 4_suppl ( 2014-02-01), p. 459-459
    Abstract: 459 Background: Antiangiogenic therapy has demonstrated to increase progression-free (PFS) as well as overall survival (OS) in RCC patients. Clinical scoring systems like the Memorial Sloan Kettering Cancer Center (MSKCC) help to stratify patients for treatment options. However, identification of molecular phenotypes of RCC patients would improve stratification of specific targeted therapies. We investigated whether DNA hypermethylation based markers can predict the PFS following first-line therapy. Methods: We examined primary tumors from formalin-fixed paraffin embedded tissue specimens obtained from 18 patients receiving anti-VEGF based targeted therapy. Quantitative methylation-specific PCRs were carried out following bisulphite conversion of DNA for CpG island methylation analysis of the five candidate genes, CST6, GATA5, LAD1, hsa-miR124-3 and hsa-miR9.1 identified in advance as potential prognosticators for RCC. For Kaplan Meier survival analysis relative methylation values were uniformly dichotomized and logrank statistics calculated. The analyses of sensitivity and specificity were carried out using a cutoff of 6 months for PFS to categorize for therapy failure and response, as described in the literature. Results: Hypermethylation of CST6 and LAD1 shows a highly significant association with a shortened PFS following first-line therapy (p=0.009, p=0.004, logrank test). The median survival observed for the high and low methylation group was 2.0 and 11.4 months for CST6 and LAD1. Moreover, LAD1 methylation showed a specificity of 1.0 (0.65-1.0, 95%CI) and a sensitivity of 0.73 (0.43-0.90, 95%CI) for detection of therapy failure. For CST6 methylation analysis a specificity of 0.86 (0.49-0.97, 95%CI) and a sensitivity of 0.82 (0.52-0.95, 95%CI) was detected. Conclusions: The analysis of our discovery cohort revealed that CGI methylation of CST6 and LAD1 predicts a shortened PFS of patients after anti-VEGF therapy. Provided, these results can be confirmed in an independent larger evaluation cohort, detection of hypermethylated loci in primary RCC would allow, to our knowledge for the first time, a molecular-based clinical management of patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.4_suppl.459
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Body composition parameter as risk predictor in metastatic renal cell carcinoma (mRCC)?
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e16506-e16506
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e16506-e16506
    Abstract: e16506 Background: Imaging-derived data for patient’s (pts) prognostication in advanced/metastatic (m)RCC remains scarce. Recently, imaging body composition parameters such as muscle radiation attenuation (MA) and skeletal muscle index (SMI) as prognostic markers for cancer became a matter of interest. Here, impact of MA and SMI in mRCC pts, treated in our tertiary center, were retrospectively investigated. Methods: During the observation period 01/03 – 05/16, 401 pts mRCC receiving first line medical treatment were identified and analyzed. Pts were included for MA- and SMI-analysis based on Computed tomography (CT) scan data and recorded height and bodyweight, respectively. SMI and MA were assessed by a self-designed software-module using MeVisLab. SMI- and MA-subgroups were established by cutoff points, established using an optimum risk stratification method. Descriptive statistics and overall survival (OS) with Log-rank analysis were administered. Parameters with differences in MA-subgroups (p 〈 0.2) were analyzed with univariable and multivariable Cox-Regression, once p 〈 0.2 at each subsequent step. Results: 133 pts were eligible for MA-, 123 pts for SMI-analysis. The median age was 62 (range: 39-84) years, and 65.4% of pts showed an ECOG = 0. 87/133 (65.4%) and 71/123 (57.7%) pts showed low MA and low SMI, respectively. At time of mRCC diagnosis pts with low MA were significantly older (mean: 65 vs. 58 years, p 〈 0,001), while T-, N-, and M-status, as well as MSKCC did not differ. Low MA was associated with a median OS of 27 (95% CI: 17,1-36.3) mo., compared to 60 (95% CI: 36.7-83.3) mo. for high MA (Log-Rank p = 0.001). Multivariable analysis identified low MA as an independent risk factor for OS (HR 2.07; 95% CI 1.24-3.48; p = 0.006). SMI did not reach significance (p = 0.1) (Tab.1). Conclusions: Here, MA provided a robust prognostic parameter regarding OS in mRCC pts. Interestingly, SMI showed no prognostic impact. CT-derived MA could be a promising addition to existing risk-scores. Further research is needed to validate these finding.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e16506
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Endoscopic Approach to the Quadrilateral Plate (EAQUAL): a New Endoscopic Approach for Plate Osteosynthesis of the Pelvic Ring and Acetabulum – a Cadaver Study
    Georg Thieme Verlag KG ; 2019
    In:  Zeitschrift für Orthopädie und Unfallchirurgie Vol. 157, No. 01 ( 2019-02), p. 22-28
    Details
    In: Zeitschrift für Orthopädie und Unfallchirurgie, Georg Thieme Verlag KG, Vol. 157, No. 01 ( 2019-02), p. 22-28
    Abstract: Background Dislocated pelvic fractures which require surgical repair are usually operated on via open surgery. Approach-related morbidity is reported with a frequency of up to 30%. The aim of this anatomical study was to prove the feasibility of endoscopic visualisation of the relevant anatomical structures in pelvic surgery and to perform completely endoscopic plate osteosynthesis of the acetabulum with available standard laparoscopic instruments. Method In four human cadavers, we established an endoscopic preparation of the complete pelvic ring, from the symphysis to the iliosacral joint, including the quadrilateral plate and the sciatic nerve, and performed endoscopic plate osteosynthesis along the iliopectineal line. Results The endoscopic preparation of the complete pelvic ring and the quadrilateral plate was demonstrated step-by-step, followed by completely endoscopic plate osteosynthesis along the pelvic brim. Endoscopic, radiographic, and schematic pictures are used to illustrate the technique. Conclusion The completely endoscopic preparation of the pelvic brim and the quadrilateral plate is feasible with available standard laparoscopic instruments. Moreover, plate osteosynthesis could be performed endoscopically. Further research on reduction techniques is necessary when planning to implement this technique into a clinical scenario.
    Type of Medium: Online Resource
    ISSN: 1864-6697 , 1864-6743
    URL: Article
    DOI: 10.1055/a-0621-9570
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2019
    detail.hit.zdb_id: 2280747-0
    detail.hit.zdb_id: 2304338-6
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  • 4
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    Online Resource
    Criteria for the multiple use of isolated perfused hearts in electrophysiological and metabolic experiments / Kriterien für die Mehrfachnutzung von isoliert perfundierten Schweineherzen für elektrophysiologische und metabolische Untersuchungen
    Walter de Gruyter GmbH ; 2008
    In:  Biomedizinische Technik/Biomedical Engineering Vol. 53, No. 1 ( 2008-02), p. 16-24
    Details
    In: Biomedizinische Technik/Biomedical Engineering, Walter de Gruyter GmbH, Vol. 53, No. 1 ( 2008-02), p. 16-24
    Type of Medium: Online Resource
    ISSN: 0013-5585 , 1862-278X
    URL: Article
    DOI: 10.1515/BMT.2008.003
    RVK:
    XA 10000
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2008
    detail.hit.zdb_id: 2234381-7
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  • 5
    Online Resource
    Online Resource
    An isolated pig heart for the development, validation and translation of novel magnetic resonance techniques
    Springer Science and Business Media LLC ; 2010
    In:  Journal of Cardiovascular Magnetic Resonance Vol. 12, No. S1 ( 2010-1)
    Details
    In: Journal of Cardiovascular Magnetic Resonance, Springer Science and Business Media LLC, Vol. 12, No. S1 ( 2010-1)
    Type of Medium: Online Resource
    ISSN: 1532-429X
    URL: Article
    DOI: 10.1186/1532-429X-12-S1-O17
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2578881-4
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  • 6
    Online Resource
    Online Resource
    Pathogenicity, Fungicide Resistance, and Genetic Variability of Phytophthora rubi Isolates from Raspberry ( Rubus idaeus ) in the Western United States
    Scientific Societies ; 2014
    In:  Plant Disease Vol. 98, No. 12 ( 2014-12), p. 1702-1708
    Details
    In: Plant Disease, Scientific Societies, Vol. 98, No. 12 ( 2014-12), p. 1702-1708
    Abstract: Root rot of raspberry (Rubus idaeus), thought to be primarily caused by Phytophthora rubi, is an economically important disease in the western United States. The objectives of this study were to determine which Phytophthora species are involved in root rot, examine the efficacy of different isolation methods (cane, root, and root/soil baiting with young raspberry plants), and determine if pathogenicity, fungicide resistance, and/or genetic variation exists among P. rubi isolates collected from raspberry fields in Washington, Oregon, and California. Of 275 samples, direct isolation from cane material resulted in a greater number of P. rubi isolates (39%), whereas root/soil baiting yielded the least (11%). Sequencing of the internal transcribed spacer region of 210 of the total 597 collected Phytophthora isolates showed that all but one isolate (identified as P. bisheria) were P. rubi. Results of the pathogenicity and fungicide resistance to mefenoxam comparing 14 total isolates from Washington, Oregon, and California showed that isolates were similarly virulent against red raspberry and the EC 50 frequency distributions showed no significant difference. These results, combined with amplified fragment length polymorphism results show that P. rubi isolates from Washington, Oregon, and California represent one large mixed population. This work provides novel insights into the isolation and biology of P. rubi in western U.S. raspberry production systems.
    Type of Medium: Online Resource
    ISSN: 0191-2917 , 1943-7692
    URL: Article
    DOI: 10.1094/PDIS-11-13-1130-RE
    Language: English
    Publisher: Scientific Societies
    Publication Date: 2014
    detail.hit.zdb_id: 2042679-3
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  • 7
    Online Resource
    Online Resource
    Positron emission tomography with [ 18 F]FDG in the diagnosis of Creutzfeldt-Jakob disease (CJD)
    Springer Science and Business Media LLC ; 2002
    In:  Journal of Neurology Vol. 249, No. 6 ( 2002-6-1), p. 699-705
    Details
    In: Journal of Neurology, Springer Science and Business Media LLC, Vol. 249, No. 6 ( 2002-6-1), p. 699-705
    Type of Medium: Online Resource
    ISSN: 0340-5354 , 1432-1459
    URL: Article
    DOI: 10.1007/s00415-002-0695-3
    RVK:
    XA 10000
    Language: Unknown
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2002
    detail.hit.zdb_id: 1421299-7
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  • 8
    Online Resource
    Online Resource
    Renal cell carcinoma in kidney transplant recipients: descriptive analysis and overview of a major German transplant center
    Future Medicine Ltd ; 2019
    In:  Future Oncology Vol. 15, No. 32 ( 2019-11), p. 3739-3750
    Details
    In: Future Oncology, Future Medicine Ltd, Vol. 15, No. 32 ( 2019-11), p. 3739-3750
    Abstract: Aim: Elevated risk of malignancy-related death after renal transplantation is reported and renal malignancy was ranked as the third most frequent site of malignancy-related death. However, there is a lack of data characterizing renal cell carcinoma associated with end-stage renal disease and kidney transplantation. Patients & methods: We retrospectively identified 5250 patients who underwent kidney transplantation at the Hannover Medical School since 1970. Results: 124 patients with renal cell carcinoma (incidence 2.36%) were identified. Among all patients, metastatic recurrence was noted in 4.8%. In multivariate analysis, tumor stage and hemoglobin were identified as independent prognostic markers of OS, while tumor grading was predictive for disease recurrence. Conclusion: Apart from showing the prognostic value of tumor staging and hemoglobin, our data suggest that a risk adapted approach for early transplantation is feasible.
    Type of Medium: Online Resource
    ISSN: 1479-6694 , 1744-8301
    URL: Article
    DOI: 10.2217/fon-2019-0397
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2019
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  • 9
    Online Resource
    Online Resource
    Prediction of therapy failure after VEGF-based first-line treatment of kidney cancer patients by DNA hypermethylation biomarkers.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e22076-e22076
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e22076-e22076
    Abstract: e22076 Background: Kidney Cancer (RCC) is one of the top ten causes of cancer dependent death. Anti-VEGF targeted therapy has demonstrated increased progression-free (PFS) and overall survival in RCC patients, though the clinical outcome is still poor overall. Stratification of patient treatment currently depends on different clinical scoring systems such as the Memorial Sloan Kettering Cancer Center score. However, identification of molecular phenotypes of RCC patients could improve stratification of targeted therapies and prediction of clinical course. We investigated whether DNA hypermethylation-based markers can predict the PFS following first-line therapy. Methods: We examined primary tumor tissues obtained from 18 patients receiving anti-VEGF targeted therapy. Quantitative methylation-specific PCRs were carried out for CpG island (CGI) methylation analysis of 5 candidate genes CST6, GATA5, LAD1, hsa-miR124-3 and hsa-miR9.1 identified in advance as potential prognosticators for RCC. For Kaplan Meier survival analysis relative methylation values were uniformly dichotomized and logrank statistics calculated. The analyses of sensitivity and specificity were carried out using a cutoff of 6 months for PFS to categorize for therapy failure and response. Results: Hypermethylation of CST6 and LAD1 shows a highly significant association with a shortened PFS following first-line therapy (p=0.009, p=0.004, logrank test). The median survival observed for the high and low methylation group was 2.0 and 11.4 months for CST6 and LAD1. Moreover, LAD1 methylation showed a specificity of 1.0 (0.65-1.0, 95%CI) and a sensitivity of 0.73 (0.43-0.90, 95%CI) for detection of therapy failure. For CST6a specificity of 0.86 (0.49-0.97, 95%CI) and a sensitivity of 0.82 (0.52-0.95, 95%CI) was detected. Conclusions: The analysis of our discovery cohort revealed that CGI methylation of CST6 and LAD1 predicts a shortened PFS of patients after anti-VEGF therapy. Provided, these results can be confirmed in an independent larger evaluation cohort, detection of hypermethylated loci in primary RCC would allow, to our knowledge for the first time, a molecular-based clinical management of patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.e22076
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    An isolated perfused pig heart model for the development, validation and translation of novel cardiovascular magnetic resonance techniques
    Springer Science and Business Media LLC ; 2010
    In:  Journal of Cardiovascular Magnetic Resonance Vol. 12, No. 1 ( 2010-12)
    Details
    In: Journal of Cardiovascular Magnetic Resonance, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2010-12)
    Abstract: Novel cardiovascular magnetic resonance (CMR) techniques and imaging biomarkers are often validated in small animal models or empirically in patients. Direct translation of small animal CMR protocols to humans is rarely possible, while validation in humans is often difficult, slow and occasionally not possible due to ethical considerations. The aim of this study is to overcome these limitations by introducing an MR-compatible, free beating, blood-perfused, isolated pig heart model for the development of novel CMR methodology. Methods 6 hearts were perfused outside of the MR environment to establish preparation stability. Coronary perfusion pressure (CPP), coronary blood flow (CBF), left ventricular pressure (LVP), arterial blood gas and electrolyte composition were monitored over 4 hours. Further hearts were perfused within 3T (n = 3) and 1.5T (n = 3) clinical MR scanners, and characterised using functional (CINE), perfusion and late gadolinium enhancement (LGE) imaging. Perfusion imaging was performed globally and selectively for the right (RCA) and left coronary artery (LCA). In one heart the RCA perfusion territory was determined and compared to infarct size after coronary occlusion. Results All physiological parameters measured remained stable and within normal ranges. The model proved amenable to CMR at both field strengths using typical clinical acquisitions. There was good agreement between the RCA perfusion territory measured by selective first pass perfusion and LGE after coronary occlusion (37% versus 36% of the LV respectively). Conclusions This flexible model allows imaging of cardiac function in a controllable, beating, human-sized heart using clinical MR systems. It should aid further development, validation and clinical translation of novel CMR methodologies, and imaging sequences.
    Type of Medium: Online Resource
    ISSN: 1532-429X
    URL: Article
    DOI: 10.1186/1532-429X-12-53
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2578881-4
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