@article{AlJanabiTaubertLohseFischeretal.2014,
  author    = {Al-Janabi, Omar and Taubert, Helge and Lohse-Fischer, Andrea and Fr{\"o}hner, Michael and Wach, Sven and St{\"o}hr, Robert and Keck, Bastian and Burger, Max and Wieland, Wolf and Erdmann, Kati and Wirth, Manfred P. and Wullich, Bernd and Baretton, Gustavo and Magdolen, Viktor and Kotzsch, Mathias and F{\"u}ssel, Susanne},
  title     = {Association of Tissue mRNA and Serum Antigen Levels of Members of the Urokinase-Type Plasminogen Activator System with Clinical and Prognostic Parameters in Prostate Cancer},
  series = {Biomed Research International},
  journal   = {Biomed Research International},
  number    = {972587},
  issn      = {2314-6141},
  doi       = {10.1155/2014/972587},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117967},
  year      = {2014},
  abstract  = {The objective was to determine the mRNA expression and protein levels of uPA system components in tissue specimens and serum samples, respectively, from prostate cancer (PCa) patients and to assess their association with clinicopathological parameters and overall survival (OS). The mRNA expression levels of uPA, its receptor (uPAR), and its inhibitor type 1 (PAI-1) were analyzed in corresponding malignant and adjacent nonmalignant tissue specimens from 132 PCa patients by quantitative PCR. Preoperative serum samples from 81 PCa patients were analyzed for antigen levels of uPA system members by ELISA. RNA levels of uPA system components displayed significant correlations with each other in the tumor tissues. A significantly decreased uP AmRNA expression in PCa compared to the corresponding nonmalignant tissue was detected. High uPA mRNA level was significantly associated with a high Gleason score. Elevated concentration of soluble uPAR (suPAR) in serum was significantly associated with a poor OS of PCa patients (P = 0.022). PCa patients with high suPAR levels have a significantly higher risk of death (multivariate Cox's regression analysis; IIR - 7.12, P - 0.027). The association of high suPAR levels with poor survival of PCa patients suggests a prognostic impact of suPAR levels in serum of cancer patients.},
  language  = {en}
}
@article{AltieriSbieraDellaCasaetal.2017,
  author    = {Altieri, Barbara and Sbiera, Silviu and Della Casa, Silvia and Weigand, Isabel and Wild, Vanessa and Steinhauer, Sonja and Fadda, Guido and Kocot, Arkadius and Bekteshi, Michaela and Mambretti, Egle M. and Rosenwald, Andreas and Pontecorvi, Alfredo and Fassnacht, Martin and Ronchi, Cristina L.},
  title     = {Livin/BIRC7 expression as malignancy marker in adrenocortical tumors},
  series = {Oncotarget},
  volume    = {8},
  journal   = {Oncotarget},
  number    = {6},
  doi       = {10.18632/oncotarget.14067},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171887},
  pages     = {9323-9338},
  year      = {2017},
  abstract  = {Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R. The mRNA expression of livin, its isoforms α and β, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG). Livin protein expression was assessed by immunohistochemistry in 270 paraffin-embedded tissues (192 ACC, 58 ACA, 20 NAG). Livin, CASP3 and cleaved caspase-3 were evaluated in NCI-H295R after induction of livin overexpression. Relative livin mRNA expression was significantly higher in ACC than in ACA and NAG (0.060 ± 0.116 vs 0.004 ± 0.014 and 0.002 ± 0.009, respectively, p < 0.01), being consistently higher in tumors than in adjacent NAG and isoform β more expressed than α. No significant differences in CASP3, XIAP and DIABLO levels were found among these groups. In immunohistochemistry, livin was localized in both cytoplasm and nuclei. The ratio between cytoplasmic and nuclear staining was significantly higher in ACC (1.51 ± 0.66) than in ACA (0.80 ± 0.35) and NAG (0.88 ± 0.27; p < 0.0001). No significant correlations were observed between livin expression and histopathological parameters or clinical outcome. In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability. In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy.},
  language  = {en}
}
@article{ArdeltEbbingAdamsetal.2015,
  author    = {Ardelt, Peter U. and Ebbing, Jan and Adams, Fabian and Reiss, Cora and Arap, Wadih and Pasqualini, Renata and Bachmann, Alexander and Wetterauer, Ulrich and Riedmiller, Hubertus and Kneitz, Burkard},
  title     = {An anti-ubiquitin antibody response in transitional cell carcinoma of the urinary bladder},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0118646},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143711},
  pages     = {e0118646},
  year      = {2015},
  abstract  = {Background To use combinatorial epitope mapping ("fingerprinting") of the antibody response to identify targets of the humoral immune response in patients with transitional cell carcinoma (TCC) of the bladder. Methods A combinatorial random peptide library was screened on the circulating pool of immunoglobulins purified from an index patient with a high risk TCC (pTa high grade plus carcinoma in situ) to identify corresponding target antigens. A patient cohort was investigated for antibody titers against ubiquitin. Results We selected, isolated, and validated an immunogenic peptide motif from ubiquitin as a dominant epitope of the humoral response. Patients with TCC had significantly higher antibody titers against ubiquitin than healthy donors (p<0.007), prostate cancer patients (p<0.0007), and all patients without TCC taken together (p<0.0001). Titers from superficial tumors were not significantly different from muscle invasive tumors (p = 0.0929). For antibody response against ubiquitin, sensitivity for detection of TCC was 0.44, specificity 0.96, positive predictive value 0.96 and negative predictive value 0.41. No significant titer changes were observed during the standard BCG induction immunotherapy. Conclusions This is the first report to demonstrate an anti-ubiquitin antibody response in patients with TCC. Although sensitivity of antibody production was low, a high specificity and positive predictive value make ubiquitin an interesting candidate for further diagnostic and possibly immune modulating studies.},
  language  = {en}
}
@article{ArgentieroSolimandoKrebsetal.2020,
  author    = {Argentiero, Antonella and Solimando, Antonio Giovanni and Krebs, Markus and Leone, Patrizia and Susca, Nicola and Brunetti, Oronzo and Racanelli, Vito and Vacca, Angelo and Silvestris, Nicola},
  title     = {Anti-angiogenesis and immunotherapy: novel paradigms to envision tailored approaches in renal cell-carcinoma},
  series = {Journal of Clinical Medicine},
  volume    = {9},
  journal   = {Journal of Clinical Medicine},
  number    = {5},
  issn      = {2077-0383},
  doi       = {10.3390/jcm9051594},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205846},
  year      = {2020},
  abstract  = {Although decision making strategy based on clinico-histopathological criteria is well established, renal cell carcinoma (RCC) represents a spectrum of biological ecosystems characterized by distinct genetic and molecular alterations, diverse clinical courses and potential specific therapeutic vulnerabilities. Given the plethora of drugs available, the subtype-tailored treatment to RCC subtype holds the potential to improve patient outcome, shrinking treatment-related morbidity and cost. The emerging knowledge of the molecular taxonomy of RCC is evolving, whilst the antiangiogenic and immunotherapy landscape maintains and reinforces their potential. Although several prognostic factors of survival in patients with RCC have been described, no reliable predictive biomarkers of treatment individual sensitivity or resistance have been identified. In this review, we summarize the available evidence able to prompt more precise and individualized patient selection in well-designed clinical trials, covering the unmet need of medical choices in the era of next-generation anti-angiogenesis and immunotherapy.},
  language  = {en}
}
@phdthesis{Behrmann2020,
  author    = {Behrmann, Christoph},
  title     = {MicroRNA-221 sensitiviert Prostatakarzinomzellen gegen{\"u}ber TRAIL durch Inhibition von SOCS-3 und PIK3R1},
  doi       = {10.25972/OPUS-19920},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199205},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {MicroRNA-221 (miR-221) f{\"u}hrt in Prostatakarzinomzellen zu einer Induktion einer TRAIL-supprotiven Signatur als Folge einer Interferonaktivierung mit Heraufregulation von STAT-1 und den TRAIL-relevanten, interferonsensitiven Genen TNFSF-10 und XAF-1. Ferner f{\"u}hrt die Inhibierung des bekannten Zielgenes SOCS-3 sowie die Inhibierung des neu beschriebenen Zielgenens PIK3R1 zu einer TRAIL-Sensitivierung in den untersuchten Prostatakarzinomzellen.},
  subject      = {microrna},
  language  = {de}
}
@phdthesis{Bendig2003,
  author    = {Bendig, Ines Doris},
  title     = {Expression von VEGF (vascular endothelial growth factor) beim Urothelkarzinom der Harnblase - eine vergleichende Untersuchung histologischer Pr{\"a}parate nach Transurethraler Resektion und nach Cystektomie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-9087},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {Zur Absch{\"a}tzung der Wachstums- und Progressionstendenz des Harnblasenkarzinoms ist die Erforschung neuer diagnostischer Marker notwendig. Kriterien wie Staging und Grading erweisen sich oftmals als unzureichend, da Tumoren mit {\"a}hnlichen Stadien unterschiedliche klinische Verl{\"a}ufe zeigen k{\"o}nnen. Der VEGF (Vascular Endothelial Growth Factor) wurde als wichtiger angiogenese-stimulierender Mediator beim Harnblasenkarzinom identifiziert. Bisher konnte zeigt werden, dass die Expression von VEGF im Harnblasenkarzinom gegen{\"u}ber unauff{\"a}lligem Blasengewebe erh{\"o}ht ist. Um die Expession von VEGF in verschieden Tumorstadien zu evaluieren, wurde Tumormaterial von 52 Harnblasenkarzinompatienten untersucht, das durch transurethrale Resektion (TUR-B) und durch Cystektomie gewonnen wurde. Die Tumoren zeigten invasives Wachstum und eine urotheliale Differenzierung. Die Schnitte wurden mit einem polyklonalen Antik{\"o}rper gegen die Splicing-Varianten VEGF189, 165, 121 gef{\"a}rbt, und die VEGF-positiven Tumorzellen ausgez{\"a}hlt. Im Stadium pT1 und pT4 wurden die h{\"o}chsten Werte VEGF-positiver Zellen gefunden. Im Stadium pT2 wurde der niedrigste Wert ermittelt. G2-Tumoren unterscheiden sich statistisch nicht signifikant von den G3-Tumoren. Bei Tumoren mit lymphogener Metastasierung lag der Wert VEGF-positiver Zellen niedriger als bei denen ohne Lymphknotenmetastasen. Tumoren mit h{\"a}matogener Metastasierung wiesen h{\"o}here Werte auf als die ohne Fernmetastasen. Vergleiche der Ergebnisse der Tumorpr{\"a}parate gewonnen durch TUR-B und Cystektomie ergeben f{\"u}r die Stadien pT1 und pT2 vergleichbare Werte. Deutliche Unterschiede ergeben sich f{\"u}r das Stadium pT3 und pT4. Durch Interpretation der Ergebnisse muss davon ausgegangen werden, dass die Auswertung der VEGF-Protein-Expression keinen unabh{\"a}ngigen prognostischen Indikator darstellt. VEGF scheint beim Blasenkarzinom nicht der alleinige Mediator in der Tumorausdehnung und Filialisierung zu sein.},
  language  = {de}
}
@article{BluemelLinkeHerrmannetal.2016,
  author    = {Bluemel, Christina and Linke, Fraenze and Herrmann, Ken and Simunovic, Iva and Eiber, Matthias and Kestler, Christian and Buck, Andreas K. and Schirbel, Andreas and Bley, Thorsten A. and Wester, Hans-Juergen and Vergho, Daniel and Becker, Axel},
  title     = {Impact of \(^{68}\)Ga-PSMA PET/CT on salvage radiotherapy planning in patients with prostate cancer and persisting PSA values or biochemical relapse after prostatectomy},
  series = {EJNMMI Research},
  volume    = {6},
  journal   = {EJNMMI Research},
  number    = {78},
  doi       = {10.1186/s13550-016-0233-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147798},
  year      = {2016},
  abstract  = {Background Salvage radiotherapy (SRT) is clinically established in prostate cancer (PC) patients with PSA persistence or biochemical relapse (BCR) after prior radical surgery. PET/CT imaging prior to SRT may be performed to localize disease recurrence. The recently introduced \(^{68}\)Ga-PSMA outperforms other PET tracers for detection of recurrence and is therefore expected also to impact radiation planning. Forty-five patients with PSA persistence (16 pts) or BCR (29 pts) after prior prostatectomy, scheduled to undergo SRT of the prostate bed, underwent \(^{68}\)Ga-PSMA PET/CT. The median PSA level was 0.67 ng/ml. The impact of \(^{68}\)Ga-PSMA PET/CT on the treatment decision was assessed. Patients with oligometastatic (≤5 lesions) PC underwent radiotherapy (RT), with the extent of the RT area and dose escalation being based on PET positivity. Results Suspicious lesions were detected in 24/45 (53.3 \%) patients. In 62.5 \% of patients, lesions were only detected by 68Ga-PSMA PET. Treatment was changed in 19/45 (42.2 \%) patients, e.g., extending SRT to metastases (9/19), administering dose escalation in patients with morphological local recurrence (6/19), or replacing SRT by systemic therapy (2/19). 38/45 (84.4 \%) followed the treatment recommendation, with data on clinical follow-up being available in 21 patients treated with SRT. All but one showed biochemical response (mean PSA decline 78 ± 19 \%) within a mean follow-up of 8.12 ± 5.23 months. Conclusions \(^{68}\)Ga-PSMA PET/CT impacts treatment planning in more than 40 \% of patients scheduled to undergo SRT. Future prospective studies are needed to confirm this significant therapeutic impact on patients prior to SRT.},
  language  = {en}
}
@article{BrumbergBecklDierksetal.2020,
  author    = {Brumberg, Joachim and Beckl, Melanie and Dierks, Alexander and Schirbel, Andreas and Krebs, Markus and Buck, Andreas and K{\"u}bler, Hubert and Lapa, Constantin and Seitz, Anna Katharina},
  title     = {Detection Rate of \(^{68}\)Ga-PSMA Ligand PET/CT in Patients with Recurrent Prostate Cancer and Androgen Deprivation Therapy},
  series = {Biomedicines},
  volume    = {8},
  journal   = {Biomedicines},
  number    = {11},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines8110511},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219301},
  year      = {2020},
  abstract  = {Prostate-specific membrane antigen (PSMA) ligand PET/CT enables the localization of tumor lesions in patients with recurrent prostate cancer, but it is unclear whether androgen deprivation therapy (ADT) influences diagnostic accuracy. The aim of this study was to evaluate the effect of ADT on the detection rate of \(^{68}\)Ga-PSMA ligand PET/CT. Thus, 399 patients with initial radical prostatectomy and 68Ga-PSMA ligand PET/CT during PSA relapse were retrospectively evaluated. Propensity score matching was used to create two balanced groups of 62 subjects who either did or did not receive ADT within six months before imaging. All \(^{68}\)Ga-PSMA ligand PET/CT were evaluated visually and with semiquantitative measures. The detection rate of tumor recurrence was significantly higher in the group with ADT (88.7\% vs. 72.6\%, p = 0.02) and improved with increasing PSA-levels in both groups. In subjects with pathological PET/CT and ADT, whole-body total lesion PSMA (p < 0.01) and PSMA-derived tumor volume (p < 0.01) were significantly higher than in those without ADT. More PSMA-positive lesions and higher PSMA-derived volumetric parameters in patients with ADT suggest that a better detection rate is related to a (biologically) more advanced disease stage. Due to high detection rates in patients with PSA-levels < 2 ng/mL, the withdrawal of ADT before PSMA ligand PET/CT cannot be recommended.},
  language  = {en}
}
@article{D'AndreaSoriaGrotenhuisetal.2021,
  author    = {D'Andrea, David and Soria, Francesco and Grotenhuis, Anne J. and Cha, Eugene K. and Malats, Nuria and Di Stasi, Savino and Joniau, Steven and Cai, Tommaso and Rhijn, Bas W. G. van and Irani, Jaques and Karnes, Jeffrey and Varkarakis, John and Baniel, Jack and Palou, Joan and Babjuk, Marek and Spahn, Martin and Ardelt, Peter and Colombo, Renzo and Serretta, Vincenzo and Dalbagni, Guido and Gontero, Paolo and Bartoletti, Riccardo and Larr{\´e}, Stephane and Malmstrom, Per-Uno and Sylvester, Richard and Shariat, Shahrokh F.},
  title     = {Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Gu{\´e}rin immunotherapy for T1G3/HG bladder cancer},
  series = {World Journal of Urology},
  volume    = {39},
  journal   = {World Journal of Urology},
  number    = {9},
  doi       = {10.1007/s00345-021-03653-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-344486},
  pages     = {3337-3344},
  year      = {2021},
  abstract  = {Purpose To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Gu{\´e}rin (BCG) for T1G3/HG urinary bladder cancer (UBC). Materials and methods We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95\% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression. Results A total of 2170 (82\%) males and 465 (18\%) females were available for analysis. Overall, 1090 (50\%) males and 244 (52\%) females experienced recurrence, and 391 (18\%) males and 104 (22\%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95\%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95\%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95\%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95\%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95\%CI 0.78-1.60, p = 0.55). Conclusion Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.},
  language  = {en}
}
@phdthesis{Eckel2021,
  author    = {Eckel, Nils},
  title     = {Die microRNA-Expression des klarzelligen Nierenzellkarzinoms},
  doi       = {10.25972/OPUS-24560},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245604},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Die Arbeit befasst sich mit der experimentellen Untersuchung der MicroRNA-Expression in klarzelligen Nierenzellkarzinomen. Dabei konnte gezeigt werden, dass Tumoren gegen{\"u}ber normalem Nierengewebe {\"u}ber ein spezifisches Expressionsprofil verf{\"u}gt. Unter den differententiell exprimierten MicroRNAs fand sich auch miR-21. Aufgrund der durch sie regulierten Gene konnte gezeigt werden, dass ein m{\"o}glicher Zusammenhang zwischen der Expression von miR-21 und der Genese der klarzelligen Nierenzellkarzinoms besteht.},
  subject      = {miRNS},
  language  = {de}
}
@article{EckhardtSbieraKrebsetal.2022,
  author    = {Eckhardt, Carolin and Sbiera, Iuliu and Krebs, Markus and Sbiera, Silviu and Spahn, Martin and Kneitz, Burkhard and Joniau, Steven and Fassnacht, Martin and K{\"u}bler, Hubert and Weigand, Isabel and Kroiss, Matthias},
  title     = {High expression of Sterol-O-Acyl transferase 1 (SOAT1), an enzyme involved in cholesterol metabolism, is associated with earlier biochemical recurrence in high risk prostate cancer},
  series = {Prostate Cancer and Prostatic Diseases},
  volume    = {25},
  journal   = {Prostate Cancer and Prostatic Diseases},
  number    = {3},
  issn      = {1476-5608},
  doi       = {10.1038/s41391-021-00431-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271819},
  pages     = {484-490},
  year      = {2022},
  abstract  = {Background Prostate cancer (PCa) is the most frequent cancer in men. The prognosis of PCa is heterogeneous with many clinically indolent tumors and rare highly aggressive cases. Reliable tissue markers of prognosis are lacking. Active cholesteryl ester synthesis has been associated with prostate cancer aggressiveness. Sterol-O-Acyl transferases (SOAT) 1 and 2 catalyze cholesterol esterification in humans. Objective To investigate the value of SOAT1 and SOAT2 tissue expression as prognostic markers in high risk PCa. Patients and Methods Formalin-fixed paraffin-embedded tissue samples from 305 high risk PCa cases treated with radical prostatectomy were analyzed for SOAT1 and SOAT2 protein expression by semi-quantitative immunohistochemistry. The Kaplan-Meier method and Cox proportional hazards modeling were used to compare outcome. Main Outcome Measure Biochemical recurrence (BCR) free survival. Results SOAT1 expression was high in 73 (25\%) and low in 219 (75\%; not evaluable: 13) tumors. SOAT2 was highly expressed in 40 (14\%) and at low levels in 249 (86\%) samples (not evaluable: 16). By Kaplan-Meier analysis, we found significantly shorter median BCR free survival of 93 months (95\% confidence interval 23.6-123.1) in patients with high SOAT1 vs. 134 months (112.6-220.2, Log-rank p < 0.001) with low SOAT1. SOAT2 expression was not significantly associated with BCR. After adjustment for age, preoperative PSA, tumor stage, Gleason score, resection status, lymph node involvement and year of surgery, high SOAT1 but not SOAT2 expression was associated with shorter BCR free survival with a hazard ratio of 2.40 (95\% CI 1.57-3.68, p < 0.001). Time to clinical recurrence and overall survival were not significantly associated with SOAT1 and SOAT2 expression CONCLUSIONS: SOAT1 expression is strongly associated with BCR free survival alone and after multivariable adjustment in high risk PCa. SOAT1 may serve as a histologic marker of prognosis and holds promise as a future treatment target.},
  language  = {en}
}
@phdthesis{Feiden2018,
  author    = {Feiden, Anna Marie Elisabeth},
  title     = {Die Bedeutung der miR-146b beim Prostatakarzinom - eine molekularbiologische Funktionsanalyse anhand von LNCaP-Zellen sowie eine klinische Analyse an zwei Prostatakarzinomkollektiven},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161909},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Die miR-146b Expression war signifikant supprimiert im Prostatakarzinomgewebe im Vergleich zum benignen Prostatahyperplasiegewebe. Dies konnte anhand eines Prostatakarzinompatientenkollektivs signifikant nachgewiesen werden. Nach ektoper Steigerung der miR-146b Expression in LNCaP-Zellen mittels transienter Transfektion zeigte sich eine signifikante Proliferationsinhibierung. N-Ras konnte als direktes Target der miR-146b nachgewiesen werden: mittels qRT-PCR zeigte sich eine inverse Expression von miR-146b und N-Ras in transfizierten LNCaP-Zellen. Der Luciferase-Assay best{\"a}tigte N-Ras als direktes Target der miR-146b. Die Targetbeziehung von N-Ras und miR-146b konnte auch in vivo (Prostatakarzinompatientenkollektiv) best{\"a}tigt werden.},
  subject      = {Prostatakarzinom},
  language  = {de}
}
@phdthesis{Finkl2022,
  author    = {Finkl, Sophia},
  title     = {Untersuchungen zur Funktion und Expression von miR-200b im Prostatakarzinom unter besonderer Beachtung von miR-200b als Prognosemarker bei Hochrisiko-Erkrankten und des Enzyms SOAT1 als Zielstruktur von miR-200b},
  doi       = {10.25972/OPUS-25741},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257418},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Die miR-200b zeigte sich in zwei unabh{\"a}ngigen Prostatakarzinomkollektiven herabreguliert und in dem verwendeten Hochrisiko Kollektiv erwies sich miR-200b zudem in uni- und multivariaten Analysen in einem retrospektiven Versuchsansatz als geeigneter Marker zur Absch{\"a}tzung der Prognose des Prostatakarzinoms. Mittels in vitro Experimenten konnten tumorsuppressive Funktionen von miR-200b best{\"a}tigt werden, da miR-200b {\"u}berexprimierende Prostatakarzinom Zelllinien eine geringere Proliferation und eine geringere Autophagie zeigten. Zus{\"a}tzlich konnte auf funktioneller Ebene, SOAT1 als Zielgen von miR-200b definiert werden. Die funktionelle Bedeutung der miR-200b vermittelten Regulation der SOAT1 Expression konnte in weiteren Experimenten best{\"a}tigt werden, indem eine Sensitivierung gegen{\"u}ber der antiproliferativen Wirkung von SOAT1 Inhibitoren in miR-200b {\"u}berexprimierenden Prostatakarzinom-Zellen beobachtet werden konnte. Mit diesen Ergebnissen konnte ein Model entwickelt werden, welches einen m{\"o}glichen Erkl{\"a}rungsansatz der Bedeutung, der von miR-200b vermittelten SOAT1 Regulation f{\"u}r den Fettstoffwechsel des Prostatakarzinoms liefern k{\"o}nnte.},
  subject      = {Prostatakrebs},
  language  = {de}
}
@article{FussOtherHeinzeetal.2021,
  author    = {Fuss, Carmina Teresa and Other, Katharina and Heinze, Britta and Landwehr, Laura-Sophie and Wiegering, Armin and Kalogirou, Charis and Hahner, Stefanie and Fassnacht, Martin},
  title     = {Expression of the chemokine receptor CCR7 in the normal adrenal gland and adrenal tumors and its correlation with clinical outcome in adrenocortical carcinoma},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {22},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13225693},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250112},
  year      = {2021},
  abstract  = {Background: The chemokine receptor CCR7 is crucial for an intact immune function, but its expression is also associated with clinical outcome in several malignancies. No data exist on the expression of CCR7 in adrenocortical tumors. Methods: CCR7 expression was investigated by qRT-PCR and immunohistochemistry in 4 normal adrenal glands, 59 adrenocortical adenomas, and 181 adrenocortical carcinoma (ACC) samples. Results: CCR7 is highly expressed in the outer adrenocortical zones and medulla. Aldosterone-producing adenomas showed lower CCR7 protein levels (H-score 1.3 ± 1.0) compared to non-functioning (2.4 ± 0.5) and cortisol-producing adenomas (2.3 ± 0.6), whereas protein expression was variable in ACC (1.8 ± 0.8). In ACC, CCR7 protein expression was significantly higher in lymph node metastases (2.5 ± 0.5) compared to primary tumors (1.8±0.8) or distant metastases (2.0 ± 0.4; p < 0.01). mRNA levels of CCR7 were not significantly different between ACCs, normal adrenals, and adrenocortical adenomas. In contrast to other tumor entities, neither CCR7 protein nor mRNA expression significantly impacted patients' survival. Conclusion: We show that CCR7 is expressed on mRNA and protein level across normal adrenals, benign adrenocortical tumors, as well as ACCs. Given that CCR7 did not influence survival in ACC, it is probably not involved in tumor progression, but it could play a role in adrenocortical homeostasis.},
  language  = {en}
}
@phdthesis{Hahner2008,
  author    = {Hahner, Maximilian},
  title     = {Organerhaltung in der modernen Nierentumorchirurgie: W{\"u}rzburger Ergebnisse 1997-2002},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-35657},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {Hintergrund: Die operative Resektion von Nierenzellkarzinomen stellt die einzige Therapie mit kurativem Ansatz dar. Zunehmend etabliert sich die parenchymschonende Tumorresektion mit dem Ziel des Erhalts der Nierenfunktion neben der Radikalen Tumornephrektomie bei lokal begrenzten Nierentumoren. Methode: In unserer Untersuchung erfolgte die Gegen{\"u}berstellung von insgesamt 155 Patienten mit einem T1-Nierenzellkarzinom, die sich zwischen 1997 und 2002 entweder einer parenchymschonenden Tumorresektion oder einer Radikalen Nephrektomie an der Urologischen Universit{\"a}tsklinik W{\"u}rzburg unterzogen haben. In die Auswertung gelangten nur die Patienten, bei denen eine vollst{\"a}ndige Nachsorgehistorie eruierbar war. Zus{\"a}tzlich durfte nur ein organbegrenzter T1M0N0-Status vorliegen. Es erfolgte die Gegen{\"u}berstellung beider Operationsmethoden. Innerhalb der parenchymschonend operierten Patientengruppe erfolgte ein Vergleich von elektiven gegen{\"u}ber imperativen Indikationen. Zentraler Fokus war neben der tumorspezifischen {\"U}berlebensrate der Erhalt der Nierenfunktion und die Rate an perioperativen Komplikationen. Ergebnisse: Insgesamt ergaben sich signifikante Unterschiede beim Vergleich der postoperativen Nierenfunktion mit Hilfe der MDRD-Formel, die postoperativ bei den parenchymschonend operierten Patienten deutlich h{\"o}her lag. Wie zu erwarten fand sich hier aber eine etwas h{\"o}here Bluttransfusionsrate, sowie eine gering h{\"o}here perioperative Rate an Komplikationen. Die tumorassoziierte Gesamt{\"u}berlebensrate lag bei den parenchymschonend operierten Patienten bei 92,96\% und den radikal nephrektomierten Patienten bei 91,67\%, das onkologische Outcome bezeichnen wir deshalb als gleich. Statistisch d{\"u}rfen wir aufgrund der Zahlen nur von einem Trend sprechen. Schlussfolgerungen: In Zusammenschau aller Auswertungen sollte eine parenchymschonende Nierentumorresektion unter dem Aspekt der Erhaltung der Nierenfunktion insbesondere bei lokal begrenzten Tumoren immer erwogen werden. Im Hinblick auf das onkologische Outcome ergibt sich kein Nachteil. Der Vorteil der Radikalen Tumornephrektomie bleibt den fortgeschrittenen Tumorstadien vorbehalten.},
  subject      = {Nierentumor},
  language  = {de}
}
@article{HailerGrunewaldOrthetal.2014,
  author    = {Hailer, Amelie and Grunewald, Thomas G. P. and Orth, Martin and Reiss, Cora and Kneitz, Burkhard and Spahn, Martin and Butt, Elke},
  title     = {Loss of tumor suppressor mir-203 mediates overexpression of LIM and SH3 Protein 1 (LASP1) in high-risk prostate cancer thereby increasing cell proliferation and migration},
  series = {Oncotarget},
  volume    = {5},
  journal   = {Oncotarget},
  number    = {12},
  issn      = {1949-2553},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120540},
  pages     = {4144-53},
  year      = {2014},
  abstract  = {Several studies have linked overexpression of the LIM and SH3 domain protein 1 (LASP1) to progression of breast, colon, liver, and bladder cancer. However, its expression pattern and role in human prostate cancer (PCa) remained largely undefined. Analysis of published microarray data revealed a significant overexpression of LASP1 in PCa metastases compared to parental primary tumors and normal prostate epithelial cells. Subsequent gene-set enrichment analysis comparing LASP1-high and -low PCa identified an association of LASP1 with genes involved in locomotory behavior and chemokine signaling. These bioinformatic predictions were confirmed in vitro as the inducible short hairpin RNA-mediated LASP1 knockdown impaired migration and proliferation in LNCaP prostate cancer cells. By immunohistochemical staining and semi-quantitative image analysis of whole tissue sections we found an enhanced expression of LASP1 in primary PCa and lymph node metastases over benign prostatic hyperplasia. Strong cytosolic and nuclear LASP1 immunoreactivity correlated with PSA progression. Conversely, qRT-PCR analyses for mir-203, which is a known translational suppressor of LASP1 in matched RNA samples revealed an inverse correlation of LASP1 protein and mir-203 expression. Collectively, our results suggest that loss of mir-203 expression and thus uncontrolled LASP1 overexpression might drive progression of PCa.},
  language  = {en}
}
@article{HartrampfBundschuhWeinzierletal.2022,
  author    = {Hartrampf, Philipp E. and Bundschuh, Ralph A. and Weinzierl, Franz-Xaver and Serfling, Sebastian E. and Kosmala, Aleksander and Seitz, Anna Katharina and K{\"u}bler, Hubert and Buck, Andreas K. and Essler, Markus and Werner, Rudolf A.},
  title     = {mCRPC patients with PSA fluctuations under radioligand therapy have comparable survival benefits relative to patients with sustained PSA decrease},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {49},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {13},
  doi       = {10.1007/s00259-022-05910-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324562},
  pages     = {4727-4735},
  year      = {2022},
  abstract  = {Introduction In men with metastatic castration-resistant prostate cancer (mCRPC) scheduled for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), biochemical response is assessed based on repeated measurements of prostate-specific antigen (PSA) levels. We aimed to determine overall survival (OS) in patients experiencing sustained PSA increase, decrease, or fluctuations during therapy. Materials and methods In this bicentric study, we included 176 mCRPC patients treated with PSMA-directed RLT. PSA levels were determined using blood samples prior to the first RLT and on the admission days for the following cycles. We calculated relative changes in PSA levels compared to baseline. Kaplan-Meier curves as well as log-rank test were used to compare OS of different subgroups, including patients with sustained PSA increase, decrease, or fluctuations (defined as change after initial decrease or increase after the first cycle). Results Sixty-one out of one hundred seventy-six (34.7\%) patients showed a sustained increase and 86/176 (48.8\%) a sustained decrease in PSA levels. PSA fluctuations were observed in the remaining 29/176 (16.5\%). In this subgroup, 22/29 experienced initial PSA decrease followed by an increase (7/29, initial increase followed by a decrease). Median OS of patients with sustained decrease in PSA levels was significantly longer when compared to patients with sustained increase of PSA levels (19 vs. 8 months; HR 0.35, 95\% CI 0.22-0.56; P < 0.001). Patients with PSA fluctuations showed a significantly longer median OS compared to patients with sustained increase of PSA levels (18 vs. 8 months; HR 0.49, 95\% CI 0.30-0.80; P < 0.01), but no significant difference relative to men with sustained PSA decrease (18 vs. 19 months; HR 1.4, 95\% CI 0.78-2.49; P = 0.20). In addition, in men experiencing PSA fluctuations, median OS did not differ significantly between patients with initial decrease or initial increase of tumor marker levels (16 vs. 18 months; HR 1.2, 95\% CI 0.38-4.05; P = 0.68). Conclusion Initial increase or decrease of PSA levels is sustained in the majority of patients undergoing RLT. Sustained PSA decrease was linked to prolonged survival and men with PSA fluctuations under treatment experienced comparable survival benefits. As such, transient tumor marker oscillations under RLT should rather not lead to treatment discontinuation, especially in the absence of radiological progression.},
  language  = {en}
}
@article{HartrampfHeinrichSeitzetal.2020,
  author    = {Hartrampf, Philipp E. and Heinrich, Marieke and Seitz, Anna Katharina and Brumberg, Joachim and Sokolakis, Ioannis and Kalogirou, Charis and Schirbel, Andreas and K{\"u}bler, Hubert and Buck, Andreas K. and Lapa, Constantin and Krebs, Markus},
  title     = {Metabolic Tumour Volume from PSMA PET/CT Scans of Prostate Cancer Patients during Chemotherapy — Do Different Software Solutions Deliver Comparable Results?},
  series = {Journal of Clinical Medicine},
  volume    = {9},
  journal   = {Journal of Clinical Medicine},
  number    = {5},
  issn      = {2077-0383},
  doi       = {10.3390/jcm9051390},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205893},
  year      = {2020},
  abstract  = {(1) Background: Prostate-specific membrane antigen (PSMA)-derived tumour volume (PSMA-TV) and total lesion PSMA (TL-PSMA) from PSMA PET/CT scans are promising biomarkers for assessing treatment response in prostate cancer (PCa). Currently, it is unclear whether different software tools for assessing PSMA-TV and TL-PSMA produce comparable results. (2) Methods: \(^{68}\)Ga-PSMA PET/CT scans from n = 21 patients with castration-resistant PCa (CRPC) receiving chemotherapy were identified from our single-centre database. PSMA-TV and TL-PSMA were calculated with Syngo.via (Siemens) as well as the freely available Beth Israel plugin for FIJI (Fiji Is Just ImageJ) before and after chemotherapy. While statistical comparability was illustrated and quantified via Bland-Altman diagrams, the clinical agreement was estimated by matching PSMA-TV, TL-PSMA and relative changes of both variables during chemotherapy with changes in serum PSA (ΔPSA) and PERCIST (Positron Emission Response Criteria in Solid Tumors). (3) Results: Comparing absolute PSMA-TV and TL-PSMA as well as Bland-Altman plotting revealed a good statistical comparability of both software algorithms. For clinical agreement, classifying therapy response did not differ between PSMA-TV and TL-PSMA for both software solutions and showed highly positive correlations with BR. (4) Conclusions: due to the high levels of statistical and clinical agreement in our CRPC patient cohort undergoing taxane chemotherapy, comparing PSMA-TV and TL-PSMA determined by Syngo.via and FIJI appears feasible.},
  language  = {en}
}
@article{HartrampfKrebsPeteretal.2022,
  author    = {Hartrampf, Philipp E. and Krebs, Markus and Peter, Lea and Heinrich, Marieke and Ruffing, Julia and Kalogirou, Charis and Weinke, Maximilian and Brumberg, Joachim and K{\"u}bler, Hubert and Buck, Andreas K. and Werner, Rudolf A. and Seitz, Anna Katharina},
  title     = {Reduced segmentation of lesions is comparable to whole-body segmentation for response assessment by PSMA PET/CT: initial experience with the keyhole approach},
  series = {Biology},
  volume    = {11},
  journal   = {Biology},
  number    = {5},
  issn      = {2079-7737},
  doi       = {10.3390/biology11050660},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271191},
  year      = {2022},
  abstract  = {Simple Summary The calculation of PSMA-positive tumor volume (PSMA-TV) of the whole body from PSMA PET scans for response evaluation remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative tumor lesions. Changes in the whole-body PSMA-TV of 65 patients were comparable to the changes in PSMA-TV after including only the ten largest lesions. Moreover, changes in PSMA-TV correlated well with changes in PSA levels, as did the changes in PSMA-TV with the reduced number of lesions. We conclude that a response assessment using PSMA-TV with a reduced number of lesions is feasible and could lead to a simplified process for evaluating PSMA PET/CT. Abstract (1) Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-derived parameters, such as the commonly used standardized uptake value (SUV) and PSMA-positive tumor volume (PSMA-TV), have been proposed for response assessment in metastatic prostate cancer (PCa) patients. However, the calculation of whole-body PSMA-TV remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative lesions. (2) Methods: Sixty-five patients classified into different disease stages were assessed by PSMA PET/CT for staging and restaging after therapy. Whole-body PSMA-TV and whole-body SUV\(_{max}\) were calculated. We then repeated this calculation only including the five or ten hottest or largest lesions. The corresponding serum levels of prostate-specific antigen (PSA) were also determined. The derived delta between baseline and follow-up values provided the following parameters: ΔSUV\(_{maxall}\), ΔSUV\(_{max10}\), ΔSUV\(_{max5}\), ΔPSMA-TV\(_{all}\), ΔPSMA-TV\(_{10}\), ΔPSMA-TV\(_{5}\), ΔPSA. Finally, we compared the findings from our whole-body segmentation with the results from our keyhole approach (focusing on a limited number of lesions) and correlated all values with the biochemical response (ΔPSA). (3) Results: Among patients with metastatic hormone-sensitive PCa (mHSPC), none showed a relevant deviation for ΔSUV\(_{max10}\)/ΔSUV\(_{max5}\) or ΔPSMA-TV\(_{10}\)/ΔPSMA-TV\(_{5}\) compared to ΔSUV\(_{maxall}\) and ΔPSMA-TV\(_{all}\). For patients treated with taxanes, up to 6/21 (28.6\%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only up to 2/21 (9.5\%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). For patients treated with radioligand therapy (RLT), up to 5/28 (17.9\%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only 1/28 (3.6\%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). The highest correlations with ΔPSA were found for ΔPSMA-TV\(_{all}\) (r ≥ 0.59, p ≤ 0.01), followed by ΔPSMA-TV\(_{10}\) (r ≥ 0.57, p ≤ 0.01) and ΔPSMA-TV\(_{5}\) (r ≥ 0.53, p ≤ 0.02) in all cohorts. ΔPSA only correlated with ΔSUV\(_{maxall}\) (r = 0.60, p = 0.02) and with ΔSUV\(_{max10}\) (r = 0.53, p = 0.03) in the mHSPC cohort, as well as with ΔSUV\(_{maxall}\) (r = 0.51, p = 0.01) in the RLT cohort. (4) Conclusion: Response assessment using PSMA-TV with a reduced number of lesions is feasible, and may allow for a simplified evaluation process for PSMA PET/CT.},
  language  = {en}
}
@article{HartrampfLapaSerflingetal.2021,
  author    = {Hartrampf, Philipp E. and Lapa, Constantin and Serfling, Sebastian E. and Buck, Andreas K. and Seitz, Anna Katharina and Meyer, Philipp T. and Ruf, Juri and Michalski, Kerstin},
  title     = {Development of Discordant Hypermetabolic Prostate Cancer Lesions in the Course of [\(^{177}\)Lu]PSMA Radioligand Therapy and Their Possible Influence on Patient Outcome},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {17},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13174270},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245168},
  year      = {2021},
  abstract  = {Simple Summary Discordant FDG-positive but PSMA-negative (FDG+/PSMA-) metastases constitute a negative prognostic marker of overall survival in patients undergoing PSMA radioligand therapy (RLT). The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA- lesions, which occur during or after PSMA RLT. In a retrospective bicentric analysis of 32 patients undergoing PSMA RLT and follow-up dual tracer staging with PSMA and FDG PET/CT, FDG+/PSMA- lesions occurred in a limited number of patients. However, the presence of FDG+/PSMA- lesions appears not to have a significant impact on the OS, but further studies are needed to establish the clinical relevance of such lesions. Abstract Introduction: Positron emission tomography/computer tomography (PET/CT) targeting the prostate-specific membrane antigen (PSMA) is crucial for the assessment of adequate PSMA expression in patients with metastatic castration-resistant prostate cancer (mCRPC) prior to PSMA radioligand therapy (PSMA RLT). Moreover, initial dual tracer staging using combined PSMA and [\(^{18}\)F]fluorodeoxyglucose (FDG) PET/CT provides relevant information, since discordant FDG-positive but PSMA-negative (FDG+/PSMA-) lesions constitute a negative prognostic marker of overall survival (OS) after PSMA RLT. However, little is known about the prognostic implications of dual tracer imaging for restaging at follow-up. The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA- lesions during or after PSMA RLT. Methods: This bicentric analysis included 32 patients with mCRPC who underwent both FDG and PSMA PET/CT imaging after two or four cycles of PSMA RLT. Patients with FDG+/PSMA- lesions prior to PSMA RLT were not considered. The presence of FDG+/PSMA- lesions was assessed with follow-up dual tracer imaging of patients after two or four cycles of PSMA RLT. Patients with at least one new FDG+/PSMA- lesion were compared to patients without any FDG+/PSMA- lesions at the respective time points. A log-rank analysis was used to assess the difference in OS between subgroups. Results: After two cycles of PSMA RLT, four of 32 patients (13\%) had FDG+/PSMA- metastases. No significant difference in OS was observed (p = 0.807), as compared to patients without FDG+/PSMA- lesions. Follow-up dual tracer imaging after the 4th cycle of PSMA RLT was available in 18 patients. Of these, four patients presented with FDG+/PSMA- findings (n = 2 already after two cycles). After the fourth cycle of PSMA RLT, no significant difference in OS was observed between patients with and without FDG+/PSMA- lesions (p = 0.442). Conclusion: This study shows that FDG+/PSMA- lesions develop in a limited number of patients undergoing PSMA RLT. Further studies are needed to establish the clinical relevance of such lesions.},
  language  = {en}
}