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Proton beams used for radiotherapy have potential for superior sparing of normal tissue, although range uncertainties are among the main limiting factors in the accuracy of dose delivery. The aim of this study was to benchmark an N-vinylpyrrolidone based polymer gel to perform three-dimensional measurement of geometric proton beam characteristics and especially to test its suitability as a range probe in combination with an anthropomorphic phantom. For single proton pencil beams as well as for 3 × 3 cm2 mono-energy layers depth dose profiles, lateral dose distribution at different depths and proton range were evaluated in simple cubic gel phantoms at different energies from 75 to 115 MeV and different dose levels. In addition, a 90 MeV mono-energetic beam was delivered to an anthropomorphic 3D printed head phantom, which was filled with gel. Subsequently, all phantoms underwent magnetic resonance imaging using an axial pixel size of 0.68–0.98 mm and with slice thicknesses of 2 or 3 mm to derive a 3-dimensional distribution of the T 2 relaxation time, which correlates with radiation dose. Indices describing lateral dose distribution and proton range were compared against predictions from a treatment planning system (TPS, for cubic and head phantoms) and Monte Carlo simulations (MC, for the head phantom) after manual rigid co-registration with the T 2 relaxation time datasets. For all pencil beams, the FWHM agreement with TPS was better than 1 mm or 7%. For the mono-energetic layer, the agreement with TPS in this respect was even better than 0.3 mm in each case. With respect to range, results from gel measurements differed no more than 0.9 mm (1.6%) from values predicted by TPS. In case of the anthropomorphic phantom, deviations with respect to a nominal range of about 61 mm as well as in FWHM were slightly higher, namely within 1.0 mm and 1.1 mm respectively. Average deviations between gel and TPS/MC were similar (−0.3 mm ± 0.4 mm/−0.2 ± 0.5 mm). In conclusion, polymer gel dosimetry was found to be a valuable tool to determine geometric proton beam properties three-dimensionally and with high spatial resolution in simple cubic as well as in a more complex anthropomorphic phantom. Post registration range errors of the order of 1 mm could be achieved. The additional registration uncertainty (95%) was 1 mm. [ABSTRACT FROM AUTHOR]

Background: The urokinase plasminogen activator (uPA) system is one of the best-investigated protease systems, both under physiological and pathological conditions, including various types of cancer. However, effects of co-expression of members of the uPA system in soft-tissue sarcoma (STS) patients at the protein level in both tumour tissue and serum have not been investigated yet.Methods: We examined 82 STS patients for protein levels of uPA, PAI-1and uPAR in tumour tissue and serum by ELISA.Results: A significant correlation between high antigen levels of uPA, PAI-1 or uPAR in tumour tissue, and of uPAR in serum, with poor outcome of STS patients was found for the first time. Most strikingly, we observed an additive effect of combined uPA, PAI-1 or uPAR levels in tumour tissue extracts with uPAR levels in serum on patients' prognosis. High uPA/uPAR, PAI-1/uPAR and uPAR/uPAR antigen levels in tumour tissue/serum were associated with a 5.9-fold, 5.8-fold and 6.2-fold increased risk of tumour-related death (P=0.003, 0.001 and 0.002, respectively) compared with those patients who displayed low levels of the respective marker combination.Conclusion: As expression of members of the uPA system in tumour tissue and serum is additively correlated with prognosis of STS patients, our results suggest that combinations of these biomarkers can identify STS patients with a higher risk of tumour-related death. [ABSTRACT FROM AUTHOR]

Piwi proteins and their interaction with piRNAs have rapidly emerged as important contributors to gene regulation, indicating their crucial function in germline and stem cell development. However, data on the Hiwi 1 (Hiwi) gene, one of the four human Piwi homologues, are still scarce. Therefore, we investigated the Hiwi mRNA expression in microdissected PDAC tissues from patients with ductal adenocarcinoma of the pancreas (PDAC) by quantitative real-time PCR and the protein expression by immunohistochemistry. Elevated levels of Hiwi mRNA transcripts were measured in 40 out of 56 tissues and a positive immunostaining of Hiwi was detected in tumours of 21 out of 78 patients. There was no general impact of elevated Hiwi mRNA transcript levels or protein expression on survival, as tested by multivariate Cox regression and Kaplan-Meier analysis. However, men showed a significantly increased risk for tumour-related death in case of down- or upregulated expression of Hiwi mRNA (relative risk (RR)=2.78; P=0.034). In summary, we report the first analysis of Hiwi expression in PDAC and its impact on prognosis. We suggest that alterations in mRNA expression of Hiwi can increase the risk of tumour-related death in male PDAC patients. [ABSTRACT FROM AUTHOR]