@article{DiessnerBruttelBeckeretal.2013,
  author    = {Diessner, Joachim and Bruttel, Valentin and Becker, Kathrin and Pawlik, Miriam and Stein, Roland and H{\"a}usler, Sebastian and Dietl, Johannes and Wischhusen, J{\"o}rg and H{\"o}nig, Arnd},
  title     = {Targeting breast cancer stem cells with HER2-specific antibodies and natural killer cells},
  series = {American Journal of Cancer Research},
  volume    = {3},
  journal   = {American Journal of Cancer Research},
  number    = {2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128633},
  pages     = {221-220},
  year      = {2013},
  abstract  = {Breast cancer is the most common cancer among women worldwide. Every year, nearly 1.4 million new cases of breast cancer are diagnosed, and about 450.000 women die of the disease. Approximately 15-25\% of breast cancer cases exhibit increased quantities of the trans-membrane receptor tyrosine kinase human epidermal growth factor receptor 2 (HER2) on the tumor cell surface. Previous studies showed that blockade of this HER2 proto-oncogene with the antibody trastuzumab substantially improved the overall survival of patients with this aggressive type of breast cancer. Recruitment of natural killer (NK) cells and subsequent induction of antibody-dependent cell-mediated cytotoxicity (ADCC) contributed to this beneficial effect. We hypothesized that antibody binding to HER2-positive breast cancer cells and thus ADCC might be further improved by synergistically applying two different HER2-specific antibodies, trastuzumab and pertuzumab. We found that tumor cell killing via ADCC was increased when the combination of trastuzumab, pertuzumab, and NK cells was applied to HER2-positive breast cancer cells, as compared to the extent of ADCC induced by a single antibody. Furthermore, a subset of \(CD44^{high}CD24^{low}HER2^{low}\) cells, which possessed characteristics of cancer stem cells, could be targeted more efficiently by the combination of two HER2-specific antibodies compared to the efficiency of one antibody. These in vitro results demonstrated the immunotherapeutic benefit achieved by the combined application of trastuzumab and pertuzumab. These findings are consistent with the positive results of the clinical studies, CLEOPATRA and NEOSPHERE, conducted with patients that had HER2-positive breast cancer. Compared to a single antibody treatment, the combined application of trastuzumab and pertuzumab showed a stronger ADCC effect and improved the targeting of breast cancer stem cells.},
  language  = {en}
}
@article{DiessnerWischnewskyBlettneretal.2016,
  author    = {Diessner, Joachim and Wischnewsky, Manfred and Blettner, Maria and H{\"a}usler, Sebastian and Janni, Wolfgang and Kreienberg, Rolf and Stein, Roland and St{\"u}ber, Tanja and Schwentner, Lukas and Bartmann, Catharina and W{\"o}ckel, Achim},
  title     = {Do Patients with Luminal A Breast Cancer Profit from Adjuvant Systemic Therapy? A Retrospective Multicenter Study},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0168730},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178217},
  year      = {2016},
  abstract  = {Background Luminal A breast cancers respond well to anti-hormonal therapy (HT), are associated with a generally favorable prognosis and constitute the majority of breast cancer subtypes. HT is the mainstay of treatment of these patients, accompanied by an acceptable profile of side effects, whereas the added benefit of chemotherapy (CHT), including anthracycline and taxane-based programs, is less clear-cut and has undergone a process of critical revision. Methods In the framework of the BRENDA collective, we analyzed the benefits of CHT compared to HT in 4570 luminal A patients (pts) with primary diagnosis between 2001 and 2008. The results were adjusted by nodal status, age, tumor size and grading. Results There has been a progressive reduction in the use of CHT in luminal A patients during the last decade. Neither univariate nor multivariate analyses showed any statistically significant differences in relapse free survival (RFS) with the addition of CHT to adjuvant HT, independent of the nodal status, age, tumor size or grading. Even for patients with more than 3 affected lymph nodes, there was no significant difference (univariate: p = 0.865; HR 0.94; 95\% CI: 0.46-1.93; multivariate: p = 0.812; HR 0.92; 95\% CI: 0.45-1.88). Conclusions The addition of CHT to HT provides minimal or no clinical benefit at all to patients with luminal A breast cancer, independent of the RFS-risk. Consequently, risk estimation cannot be the initial step in the decisional process. These findings-that are in line with several publications-should encourage the critical evaluation of applying adjuvant CHT to patients with luminal A breast cancer.},
  language  = {en}
}
@article{DiessnerWischnewskyStueberetal.2016,
  author    = {Diessner, Joachim and Wischnewsky, Manfred and St{\"u}ber, Tanja and Stein, Roland and Krockenberger, Mathias and H{\"a}usler, Sebastian and Janni, Wolfgang and Kreienberg, Rolf and Blettner, Maria and Schwentner, Lukas and W{\"o}ckel, Achim and Bartmann, Catharina},
  title     = {Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer},
  series = {BMC Cancer},
  volume    = {16},
  journal   = {BMC Cancer},
  number    = {307},
  doi       = {10.1186/s12885-016-2345-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161173},
  year      = {2016},
  abstract  = {Background The development of metastases is a negative prognostic parameter for the clinical outcome of breast cancer. Bone constitutes the first site of distant metastases for many affected women. The purpose of this retrospective multicentre study was to evaluate if and how different variables such as primary tumour stage, biological and histological subtype, age at primary diagnosis, tumour size, the number of affected lymph nodes as well as grading influence the development of bone-only metastases. Methods This retrospective German multicentre study is based on the BRENDA collective and included 9625 patients with primary breast cancer recruited from 1992 to 2008. In this analysis, we investigated a subgroup of 226 patients with bone-only metastases. Association between bone-only relapse and clinico-pathological risk factors was assessed in multivariate models using the tree-building algorithms "exhausted CHAID (Chi-square Automatic Interaction Detectors)" and CART(Classification and Regression Tree), as well as radial basis function networks (RBF-net), feedforward multilayer perceptron networks (MLP) and logistic regression. Results Multivariate analysis demonstrated that breast cancer subtypes have the strongest influence on the development of bone-only metastases (χ2 = 28). 29.9 \% of patients with luminal A or luminal B (ABC-patients) and 11.4 \% with triple negative BC (TNBC) or HER2-overexpressing tumours had bone-only metastases (p < 0.001). Five different mathematical models confirmed this correlation. The second important risk factor is the age at primary diagnosis. Moreover, BC subcategories influence the overall survival from date of metastatic disease of patients with bone-only metastases. Patients with bone-only metastases and TNBC (p < 0.001; HR = 7.47 (95 \% CI: 3.52-15.87) or HER2 overexpressing BC (p = 0.007; HR = 3.04 (95 \% CI: 1.36-6.80) have the worst outcome compared to patients with luminal A or luminal B tumours and bone-only metastases. Conclusion The bottom line of different mathematical models is the prior importance of subcategories of breast cancer and the age at primary diagnosis for the appearance of osseous metastases. The primary tumour stage, histological subtype, tumour size, the number of affected lymph nodes, grading and NPI seem to have only a minor influence on the development of bone-only metastases.},
  language  = {en}
}
@article{HaeuslerdelBarrioDiessneretal.2014,
  author    = {H{\"a}usler, Sebastian F. M. and del Barrio, Itsaso Montalb{\´a}n and Diessner, Joachim and Stein, Roland G. and Strohschein, Jenny and H{\"o}nig, Arnd and Dietl, Johannes and Wischhusen, J{\"o}rg},
  title     = {Anti-CD39 and anti-CD73 antibodies A1 and 7G2 improve targeted therapy in ovarian cancer by blocking adenosine-dependent immune evasion},
  series = {American Journal of Translational Research},
  volume    = {6},
  journal   = {American Journal of Translational Research},
  number    = {2},
  issn      = {1943-8141},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120016},
  pages     = {129-139},
  year      = {2014},
  abstract  = {The ectonucleotidases CD39 and CD73 degrade ATP to adenosine which inhibits immune responses via the \(A_{2A}\) adenosine receptor (ADORA2A) on T and NK cells. The current study investigates the potential therapeutic use of the specific anti CD39- and anti CD73-antibodies A1 (CD39) and 7G2 (CD73) as these two ectonucleotidases are overexpressed in ovarian cancer (OvCA). As expected, NK cell cytotoxicity against the human ovarian cancer cell lines OAW-42 or SK-OV-3 was significantly increased in the presence of A1 or 7G2 antibody. While this might partly be due to antibody-dependent cell-mediated cytotoxicity, a luciferase-dependent assay for quantifying biologically active adenosine further showed that A1 and 7G2 can inhibit CD39 and CD73-dependent adenosine-generation. In turn, the reduction in adenosine levels achieved by addition of A1 and 7G2 to OAW-42 or SK-OV-3 cells was found to de-inhibit the proliferation of \(CD4^+\) T cells in coculture with OvCA cells. Likewise, blocking of CD39 and CD73 on OvCA cells via A1 and 7G2 led to an increased cytotoxicity of alloreactive primed T cells. Thus, antibodies like A1 and 7G2 could improve targeted therapy in ovarian cancer not only by specifically labeling overexpressed antigens but also by blocking adenosine-dependent immune evasion in this immunogenic malignancy.},
  language  = {en}
}
@article{KleberStein1991,
  author    = {Kleber, Eduard W. and Stein, Roland},
  title     = {Lernbehinderte und CNC-Technologie : Bericht {\"u}ber einen in Deutschland laufenden Modellversuch},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40172},
  year      = {1991},
  abstract  = {Im Rahmen eines Modellversuches sollen in Hessen neue Ausbildungsg{\"a}nge im Metallbereich f{\"u}r Lernbehinderte umgesetzt und evaluiert werden. Dabei geht es insbesondere um eine Pr{\"u}fung der M{\"o}glichkeiten und Grenzen einer Ausbildung an computergesteuerten Dreh- und Fr{\"a}smaschinen. Berufsbildungswerke f{\"u}r die Ausbildung Lern- und K{\"o}rperbehinderter sowie Betriebe der freien Wirtschaft bilden im Rahmen des Versuches modellhaft Gruppen von Werkzeugmaschinenspanern aus. Ziele des p{\"a}dagogischen Rahmenprogrammes sind gr{\"o}sstm{\"o}gliche Fachkompetenz, Selbst{\"a}ndigkeit, Kooperations- und Kommunikationsf{\"a}higkeit. Von dem Projekt sind Erkenntnisse hinsichtlich der M{\"o}glichkeiten des qualifizierten Einsatzes Lernbeeintr{\"a}chtigter in Bereichen moderner industrieller Fertigung zu erwarten.},
  subject      = {Sonderp{\"a}dagogik / Zeitschrift},
  language  = {de}
}
@article{KleberStein1993,
  author    = {Kleber, Eduard W. and Stein, Roland},
  title     = {Konzentrationsprobleme: Fehldiagnose oder Zeitkrankheit?},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40116},
  year      = {1993},
  abstract  = {Konzentration ist ein psychologisches Konstrukt, das hochkomplexe Interaktions-Situations-Ph{\"a}nomene bezeichnet. Die hohe Komplexit{\"a}t l{\"a}ßt unmittelbare Folgerungen f{\"u}r therapeutische Maßnahmen nicht zu und enth{\"a}lt spezielle Probleme der Validit{\"a}t bei niedrigen Leistungswerten in Tests. Die Diagnose von Konzentrationsproblemen dient nicht selten Lehrern, Sch{\"u}lern und Eltern als Entlastung. Dabeif{\"u}hren oberfl{\"a}chliche Analysen oft zu Mißverst{\"a}ndnissen und Fehldiagnosen. Bei solchen Diagnosen werden dann Konzentration, Interesse, Motivation, Belastbarkeit, "aus dem Felde gehen" und "auswandern" konfundiert. Ohne eine sorgf{\"a}ltige und m{\"o}glichst umfassende Analyse der Aufmerksamkeitssituation k{\"o}nnen Maßnahmen zur Beseitigung oder Reduktion der Schwierigkeiten nicht effektiv ausgew{\"a}hlt werden.},
  subject      = {Sonderp{\"a}dagogik},
  language  = {de}
}
@incollection{KleberStein1991,
  author    = {Kleber, Eduard W. and Stein, Roland},
  title     = {Neue Wege f{\"u}r die Integration Lernbehinderter ins Berufsleben},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40127},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1991},
  abstract  = {No abstract available},
  subject      = {Integrationsp{\"a}dagogik / Deutsches Sprachgebiet / Kongress / Saarbr{\"u}cken <1990>},
  language  = {de}
}
@article{KleberStein1991,
  author    = {Kleber, Eduard W. and Stein, Roland},
  title     = {Neue Wege in die moderne Berufswelt},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40157},
  year      = {1991},
  abstract  = {No abstract available},
  language  = {de}
}
@article{KleberStein1991,
  author    = {Kleber, Eduard W. and Stein, Roland},
  title     = {Neue Wege in die moderne Berufswelt},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40105},
  year      = {1991},
  abstract  = {In Hessen wurde 1989 ein Modellversuch zum Einsatz neuer Technologien in der Berufsausbildung lernbehinderter Jugendlicher gestartet. Die Chancen Lernbehinderter f{\"u}r qualifizierte Arbeitspl{\"a}tze im Bereich Metall der Fachrichtungen Drehen, Fr{\"a}sen und Produktionstechnik sollen dadurch verbessert werden.},
  subject      = {Sonderp{\"a}dagogik},
  language  = {de}
}
@article{KleberSteinAmannetal.1991,
  author    = {Kleber, Eduard W. and Stein, Roland and Amann, Fritz and Brenner, G{\"u}nther},
  title     = {Neue Wege f{\"u}r die Integration Lernbehinderter in die Berufswelt? : Oder neue Wege, um niedrigere Lohngruppen zu schaffen ... ?(Bericht {\"u}ber einen 1989 angelaufenen Modellversuch)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40163},
  year      = {1991},
  abstract  = {In Hessen wurde 1989 ein Modellversuch gestartet. der die Chancen Lernbehinderter f{\"u}r qualifizierte Arbeitspl{\"a}tze im Bereich Metall verbessern soll. Ziel ist die Erarbeitung einer differenzierten Ausbildung im Berufsbild ,Werkzeugmaschinenspaner', einer reduzierten Variante des aktuellen Metallberufes ,Zerspanungsmechaniker·. Dabei geht es auch um die Integration von Arbeiten an computergesteuerten Dreh- und Fr{\"a}smaschinen. Berufsbildungswerke f{\"u}r die Ausbildung Lernund K{\"o}rperbehinderter sowie Betriebe der freien Wirtschaft bilden im Rahmen des Versuchs modellhaft Gruppen von Werkzeugmaschinenspanern aus. Ziele sind Fachkompetenz, Selbst{\"a}ndigkeit, Kooperations- und Kommunikationsf{\"a}higkeit.},
  subject      = {Sonderp{\"a}dagogik / Zeitschrift},
  language  = {de}
}