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Neuroblastoma is thought to originate from neural crest-derived cells. CD57 defines migratory neural crest cells in normal development and is expressed in neuroblastomas. We therefore investigated the role of CD57 expression in neuroblastoma cells in vitro, in vivo and in situ. Compared to CD57low neuroblastoma cells, CD57high cells developed tumors with decreased latency after orthotopic transplantation into adrenal glands of immunodeficient mice. In addition, CD57high neuroblastoma cells were also more clonogenic, induced more spheres, were less lineage-restricted and showed enhanced invasiveness. After tail vein injection more CD57high cells homed to liver and lung and formed metastases than CD57low cells. In stroma-poor neuroblastoma of patients CD57high cells were associated with undifferentiated tumor cells across all stages and tended to be more frequent after chemotherapy. We thus conclude that strong expression of CD57 is associated with some aggressive attributes of neuroblastoma cells and is linked with undifferentiated neuroblastoma cells in patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1438. doi:1538-7445.AM2012-1438

Blinatumomab, a CD19/CD3-bispecific BiTE antibody has shown high response rates and durable remissions in patients with relapsed or refractory acute lymphocytic leukemia and non-Hodgkin's lymphoma. For treatment of patients with prostate cancer (PCa), we have developed a novel BiTE antibody, MT112/BAY2010112, that is bispecific for prostate-specific membrane antigen (PSMA) and the CD3 epsilon subunit of the T cell receptor complex. MT112/BAY 2010112 binds PSMA and CD3 of human and macaque origin allowing for assessment of safety, pharmacodynamics and pharmacokinetics in a relevant animal species. PSMA expressing human PCa cell lines VCaP, 22Rv1, MDA PCa 2b, C4-2, PC3-PSMA and LNCaP were lysed by freshly isolated, unstimulated human T cells redirected by MT112/BAY2010112 at EC50 values ranging between 0.1 and 4 ng/ml (1.8-72 pM). Efficacy of lysis correlated with levels of surface expressed PSMA. No lysis was observed in PSMA-negative PCa cell lines PC3 and DU145, showing the target antigen-specific activity of MT112/BAY2010112. The relevance of cynomolgus monkeys for further nonclinical safety evaluation of MT112/BAY 2010112 was demonstrated by in vitro side-by-side comparison of the BiTE antibody's pharmacological characteristics in human and cynomolgus monkey assay systems. For studying the activity of MT112/BAY 2010112 after subcutaneous (s.c.) administration, human 22Rv1 PCa xenografts were grown s.c. in mice to sizes of >200 mm3 in the absence of human T cells. Three days prior to treatment with BiTE, ex-vivo expanded human T cells were intraperitoneally injected. Animals were treated s.c. at 2.5 mg/kg/d or intravenously (i.v.) at 0.5 mg/kg/d for 28 consecutive days. S.c. administration of MT112/BAY 2010112 resulted in a similar drug exposure, rapid shrinkage and complete remission of established PCa xenografts as seen upon i.v. administration of the BiTE antibody. Treatment with human T cells or vehicle alone had no effect on tumor growth. Compared to i.v. administration, the relative bioavailability of the PSMA BiTE in serum after s.c. injection in mice was approximately 18%. Initial results will be presented showing that 14C-labeled MT112/BAY 2010112 accumulates in s.c. implanted LNCaP PCa tumors of mice after tail vein injection. Based on these preclinical in vivo pharmacology results, treatment of PCa patients with s.c. administered MT112/BAY2010112 appears to be justified. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3526. doi:1538-7445.AM2012-3526

Die vorliegende Arbeit prasentiert eine neue Methode zur Geschlechtsdiagnose, eine uni-, di- und multivariate Analyse der Pars petrosa, eines Teiles des Schlafenbeines — angeregt durch das haufige Auftreten dieser Struktur in Leichenbranden. Wie der Vergleich der Irrtumswahrscheinlichkeiten zweier Diskriminanzfunktionen zeigt, erweist sich die Einbeziehung aller erhobenen Variablen als vorteilhaft. Schon die Berucksichtigung von nur drei Masen fuhrt zu einer geringeren Fehlerquote bei der Geschlechtszuweisung als bei einigen konventionellen Verfahren. Abschliesend wird das Problem der Schrumpfung fur die Ubertragbarkeit der Methode auf Leichenbrandmaterial erortert, und schrumpfungskorrigierte Mittelwerte der Variablen 1 bis 3 sowie ein neuer Trennwert errechnet. Aber selbst ohne Schrumpfungskorrektur besitzen die erarbeiteten Werte und Funktionen bei direkter Anwendung auf Brandknochen eine grose Zuverlassigkeit.

The Neolithic site of Schletz in Lower Austria comprises a fortified settlement from the end of the Linearbandkeramik (LBK) culture. Large numbers of human bones were found at the base of the fortification ditches, and many of the excavated bones and skulls showed evidence of trauma which most likely originates from violence. This remarkable deposit of human remains has been considered evidence for an abrupt end to the Early Neolithic settlement at Schletz. In order to investigate this interpretation, radiocarbon accelerator mass spectrometry (AMS) measurements of human bone samples from this site were performed at VERA. The χ2 test of the results from specimens with clearly identified lesions suggests that these may be contemporaneous. Further, it may be concluded that all individuals with evidence of trauma from Schletz were probably the victims of a single event: a massacre at the end of the LBK. Similar evidence is found at Early Neolithic sites at Talheim and Herxheim in the western part of Germany. Analysis of the 14C ages of bones from both sites suggests that the Talheim event may have been coeval with the massacre of Schletz, whereas an event at Herxheim might have happened some time earlier. For Herxheim, the massacre theory is still under discussion, and a change in the burial rite is also considered as an alternative interpretation.