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  • Author: Klaus Jung x
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Dry infectious DNA of bacteriophage ΦΧ174 was irradiated in extremely thin layers with slow protons and the differential inactivation cross section determined for various proton energies in the range from 0.8 to 50 keV. Above 5 keV the inactivation cross section is independent of proton energy, it reaches a shallow minimum between 1 and 1.5 keV, and increases slightly at still smaller energies. By comparing the experimentally determined inactivation cross sections with the cross sections for energy loss in elastic nuclear collisions and in ionizations, respectively, elastic collisions were demonstrated to destroy the ability of ΦΧ-DNA to give rise to intact bacteriophage in spheroplasts of E. coli K12.

The radiosensitivity of dry ribonuclease was determined at various temperatures between 120 °K and 440 °K using 2 MeV protons. Within this temperature range the inactivation cross section S (T) of ribonuclease may be described as a function of temperature by the expression S(T) = (1.28 + 16·e-1000/RT+14000·e-6500/7RT)·10-14 cm2 .

This result indicates that the observed radiation damage to ribonuclease is produced by three different mechanisms, one being independent of temperature, the other two having apparent activation energies of 1 kcal/mole and 6.5 kcal/mole, respectively. From these relatively small activation energies the conclusion may be drawn that radical reactions contribute to the inactivation of enzymes in the dry state. Experiments with Co gamma radiation showed that the radiosensitivity of ribonuclease at 77 °K depends on dose rate; at room temperature a dose rate effect was not observed.

Abstract

Background: MicroRNAs (miRNAs) have shown to be promising novel biomarkers in various cancers. We aimed to translate the results of an own previous tissue-based miRNA profile of prostate carcinoma (PCa) with upregulated miR-183 and downregulated miR-205 into a urine-based testing procedure for diagnosis of PCa.

Methods: Urine sediments were prepared from urine samples collected after a standardized digital-rectal examination (DRE) of patients undergoing prostate biopsy with PSA (prostate-specific antigen) values <20 μg/L in consecutive order. According to the sample-size calculation (α=0.05, power=0.95), 38 patients each with PCa and without PCa were randomly enrolled in this study. PCA3 (prostate cancer associated 3) in urine as Food and Drug Administration-approved assay was determined as reference standard for comparison. The miRNAs were measured by RT-qPCR using TaqMan assays and normalized using different approaches.

Results: Both miRNAs were correlated to the mRNA PSA concentrations in the sediments indicating a relationship to the released prostate cells after DRE. However, they had no discriminating capacity between patients with and without PCa. In contrast, PCA3 clearly differentiated between these two patients groups. There was also no significant correlation between miRNAs and standard clinicopathologic variables like Gleason score and serum PSA.

Conclusions: The data of our study show that miR-183 and miR-205 failed to detect early and aggressive PCa despite their highly dysregulated expression in cancer tissue. Our results and the critical evaluation of the few data of other studies raise serious doubts concerning the capability of urinary miRNAs to replace or improve PCA3 as predictive marker for prostate biopsy outcome.