Ziele: Die Strahlenexposition der Bevölkerung aufgrund von Röntgenanwendungen beträgt nach Abschätzungen des BfS im Mittel 1,8 mSv pro Einwohner und Jahr. Nach allgemeiner Einschätzung ist ein erheblicher Anteil der Kollektivdosis auf Röntgenanwendungen bei Krebspatienten zurückzuführen, von denen viele aufgrund ihres Lebensalters und ihrer reduzierten Lebenserwartung einen möglicherweise strahleninduzierten Sekundärtumor nicht erleben. Ziel dieser Studie war es, den Beitrag der Krebsdiagnostik zur Kollektivdosis abzuschätzen. Methode: Nach einer Statistik des Robert-Koch-Instituts entfallen 75% aller Krebserkrankungen auf zehn Tumorarten (definiert über ICD-Codes). Für alle Patienten mit den entsprechenden Codes, die in den Jahren 2000–2005 am Klinikum der Ludwig-Maximilians-Universität, Großhadern, behandelt wurden, wurden die folgenden Angaben aus dem KIS/RIS ermittelt: Patientennummer und Alter sowie Datum und Aufnahmeparameter für jede durchgeführte diagnostische und interventionelle Röntgenanwendung. Aus den Angaben wurde dann getrennt für jeden Tumortyp die mittlere effektive Dosis pro Patient und Jahr berechnet. Desweiteren wurde die Anzahl der Patienten pro Jahr ermittelt, denen im Krankenhaus der jeweilige ICD-Code zugewiesen wurde (Inzidenz), sowie die Anzahl der Patienten mit dem jeweiligen ICD-Code, die pro Jahr geröntgt wurden (Prävalenz für Röntgenanwendungen). Ergebnis: Insgesamt wurden Expositionsdaten für 15.866 Patienten (Alter: 61,9 +- 12,9 Jahre) erhoben, bei denen 151.439 Röntgenanwendungen durchgeführt wurden. Die über alle Krebserkrankungen gemittelte Dosis pro Patient und Jahr stieg zwischen 2000 und 2005 von 13,6 auf 18,2 mSv an. Dieser Anstieg resultierte aus einer Zunahme der „CT-Dosis“ von 9,9 auf 14,9 mSv. Die mittlere jährliche Dosis pro Patient hing erheblich von der Art der Tumorerkrankung ab (Blasentumoren: 7,1 mSv; Pankreastumoren: 40,4 mSv). Unter der Annahme, dass die für die zehn untersuchten Krebserkrankungen bestimmten mittleren Dosiswerte und Inzidenz/Prävalenz-Verhältnisse für Deutschland repräsentativ sind, wurde abgeschätzt, dass Röntgenanwendungen bei Krebspatienten zu einer Kollektivdosis von etwa 14.400 Sv führen (im Mittel zu 0,17 mSv pro Einwohner und Jahr). Schlussfolgerung: Da Röntgenanwendungen der Patienten in anderen Einrichtungen nicht berücksichtigt wurden, stellt die berechnete Kollektivdosis eine Minimalschätzung dar. Tatsächlich dürften in Deutschland zwischen 15% und 20% der Kollektivdosis aus Röntgenanwendungen auf Krebspatienten entfallen.

Human intestinal lamina propria T lymphocytes (LPT), when investigated ex vivo, exhibit functional properties profoundly different from those of peripheral blood T lymphocytes (PBT). One prominent feature represents their enhanced sensitivity to CD2 stimulation when compared to PBT. Given that LPT are hyporesponsive to T cell receptor (TCR)/CD3 stimulation, an alternative activation mode, as mimicked by CD2 triggering in vitro, may be functional in mucosal inflammation in vivo. This study provides insight into signalling events associated with the high CD2 responsiveness of LPT. When compared to PBT, LPT show an increased activation of the phosphoinositide 3/protein kinase B/glycogen synthase kinase 3beta (PI3-kinase/AKT/GSK-3beta) pathway in response to CD2 stimulation. Evidence is provided that up-regulation of this pathway contributes to the enhanced CD2-induced cytokine production in LPT. Given the importance of TCR-independent stimulation for the initiation of intestinal immune responses analysis of signalling pathways induced by 'co-stimulatory' receptors may provide valuable information for therapeutic drug design.

We analysed the effects of murine polyomavirus-like particles (PLPs) on bone marrow-derived dendritic cells (BMDCs) and T cells in vitro. BMDCs activated with PLPs up-regulated CD40, CD80, CD86 and major histocompatibility complex (MHC) class II surface markers and produced proinflammatory cytokines. Chimeric PLPs [expressing the ovalbumin (OVA)-peptides OVA 257–264 or OVA 323–339 ], but not wildtype PLPs, activated OVA-specific CD8 T cells and OVA-specific CD4 T cells, respectively, indicating both MHC class I and II presentation of the peptides by antigen-presenting cells. Our results suggest that PLPs may be used as vaccine adjuvants priming dendritic cells to induce potent T cell responses.

Success in cancer immunotherapy depends on the identification and efficient targeting of specific tumor-associated antigens. Two pivotal strategies to prime patients' immune system against malignant cells are tumor-specific adoptive T-cell therapy and tumor-specific vaccination. Here, we will focus on immunotherapeutic vaccination and discuss the advantages and disadvantages of different strategies to deliver tumor-specific T-cell epitopes. A particular focus will be put on virus-like particles (VLPs) as vehicle to deliver tumor-specific epitopes in the context of full-length proteins, as multi-epitope constructs or as individual tumor-associated T-cell epitopes. VLPs represent non-infectious and non-replicating antigen delivery systems devoid of any nucleic acid. They constitute innovative immunotherapeutic agents against cancer due to their superior, adjuvant-like antigenicity. We will present various tumor-associated antigens currently in different stages of development including survivin, as promising candidates for targeted tumor therapies.

A novel identification technology for livestock based on the principles of peptide-keyhole limpet hemocyanin immunisation is described allowing traceability of labelled animals and derived meat products throughout the complete production chain. Strong and long-lasting anti-peptide-immunoglobulin G responses were induced in pigs and beef cattle via immunisations with different peptide–KLH derivatives. Subsequently, anti-peptide antibodies are reproducibly detectable in serum and meat of pigs and cattle by means of ELISA. In respect of origin verification and compliance marking in quality meat programs, especially for pigs, the bioactive labelling technology meets all necessary requirements for greater transparency in the meat production chain.

This paper describes a novel antibody‐based livestock movement control tool and method of meat allocation, both in livestock husbandry as well as during the meat‐processing chain. Immuno Track® fulfills diverse prerequisites and meets regulatory demands which are substantial for a successful monitoring technology: (i) the induction of long‐lasting antibody responses detectable onsite throughout the whole mast period of pigs, (ii) a single immunization injection with protein derivatives is sufficient to evoke a strong epitope‐specific antibody response, and (iii) the complete degradation of the protein markers after the antibody response has been triggered in meatproducing animals such as cattle or pigs. There are diverse fields of application for the Immuno‐Track marker technology, such as in quality meat programs, as compliance markers for animal vaccines or as a tool for verification of origin. Combination of this monitoring technology with the husbandry and identification databases for cattle and pigs within the European Community will lead to greater transparency in meat production, thereby regaining consumers' trust in concomitant structures of the meat‐producing industry.

Highly immunogenic capsomers (pentamers) and virus‐like particles (VLPs) were generated through insertion of foreign B cell epitopes into the surface‐exposed loops of the VP1 protein of murine polyomavirus and via heterologous expression of the recombinant fusion proteins in E. coli. Usually, complex proteins like the keyhole limpet hemocyanin (KLH) act as standard carrier devices for the display of such immunogenic peptides after chemical linkage. Here, a comparative analysis revealed that antibody responses raised against the carrier entities, KLH or VP1 pentamers, did not significantly differ up to 18 weeks, demonstrating the highly immunogenic nature of VP1‐based particulate structures. The carrier‐specific antibody response was reproducibly detected in the meat juice after processing. More importantly, chimeric VP1 pentamers and VLPs carrying peptides of 12 and 14 amino acids in length, inserted into the BC2 loop, induced a strong and long‐lasting humoral immune response against VP1 and the inserted foreign epitope. Remarkably, the epitope‐specific antibody response was only moderately decreased when VP1 pentamers were used instead of VLPs. In conclusion, we identified polyomavirus VP1‐based structures displaying surface‐exposed immunodominant B cell epitopes as being an efficient carrier system for the induction of potent peptide‐specific antibodies. The application of this approach in vaccine marker technology in livestock holding and the meat production chain is discussed.

Biological protein-based entities that form nanostructures ranging from 8 to 50 nm in size represent promising candidates in the development of novel immunotherapeutics against cancer and microbial pathogens. These recombinant nanoparticles usually consist of major coat or core proteins derived from viruses like for instance papillomavirus, polyomavirus, parvovirus or hepatitis B virus that spontaneously assemble into these highly ordered, supramolecular, icosahedral structures. By genetic engineering of permissive sites or cross-linking to surface-exposed subunit domains these nanoparticles successfully serve as carrier matrix with per se adjuvant activity for the delivery of appropriate guest peptides, protein fragments and complete proteins. Using this nanobiotechnology, potent humoral and cell-mediated immunity with emphasis on CD4 and CD8 T cell responses are induced against self or non-self foreign antigens representing appropriate immunostimulatory epitopes or complete proteins of microbial pathogens or tumor-associated antigens. Breaking of T and B cell tolerance required for therapeutic interventions against cancer represents the hallmark of such an outstanding antigen delivery system. In combination with the increasing identification of validated target antigens from pathogens or tumors, and promising progress in bioprocess development, such nanostructures offer novel homologous or heterologous treatment and prevention opportunities against a variety of malignant and infectious diseases.

Protein-based nanosystems ranging from 8 to 50 nm in size offer novel immunotherapeutic opportunities in the treatment of cancer and chronic infectious diseases. Consisting of viral major coat or core proteins derived from viruses such as papillomavirus, polyomavirus, parvovirus, or hepatitis B virus, recombinant virus-like-particles spontaneously assemble into highly ordered, supramolecular structures. Employing genetic engineering or biochemical cross-linking, these nanostructures successfully serve as carrier matrix for the delivery of epitopes, protein fragments or complete proteins, with the added value of a strong inherent adjuvant activity. Therapeutic intervention against cancer relies on the breaking of T and B cell tolerance, which represents one of the key features of virus-like-particles serving as antigen delivery system. An ever increasing identification of validated target antigens from pathogens and tumors is paralleled by significant progress in bioprocess development. Virus-like-particles are ideal vehicles for the development of novel treatment concepts against many malignant and infectious diseases.

Large discrepancies in medical research between industrial and developing countries concerning number of scientific contributions[1] are evident also for genito-urology.

Radiotherapy (RT) is uptoday essential for oncological urogenital (UG) diseases. Two physiological approaches are of importance for pathogenesis of treatment.