Previous studies identified microRNAs (miRNAs) and messenger RNAs with significantly different expression between normal pancreas and pancreatic cancer (PDAC) tissues. Due to technological limitations of microarrays and real-time PCR systems these studies focused on a fixed set of targets. Expression of other RNA classes such as long intergenic non-coding RNAs or sno-derived RNAs has rarely been examined in pancreatic cancer. Here, we analysed the coding and non-coding transcriptome of six PDAC and five control tissues using next-generation sequencing. Besides the confirmation of several deregulated mRNAs and miRNAs, miRNAs without previous implication in PDAC were detected: miR-802, miR-2114 or miR-561. SnoRNA-derived RNAs (e.g. sno-HBII-296B) and piR-017061, a piwi-interacting RNA, were found to be differentially expressed between PDAC and control tissues. In silico target analysis of miR-802 revealed potential binding sites in the 3′ UTR of TCF4, encoding a transcription factor that controls Wnt signalling genes. Overexpression of miR-802 in MiaPaCa pancreatic cancer cells reduced TCF4 protein levels. Using Massive Analysis of cDNA Ends (MACE) we identified differential expression of 43 lincRNAs, long intergenic non-coding RNAs, e.g. LINC00261 and LINC00152 as well as several natural antisense transcripts like HNF1A-AS1 and AFAP1-AS1. Differential expression was confirmed by qPCR on the mRNA/miRNA/lincRNA level and by immunohistochemistry on the protein level. Here, we report a novel lncRNA, sncRNA and mRNA signature of PDAC. In silico prediction of ncRNA targets allowed for assigning potential functions to differentially regulated RNAs.

Objectives: The present study aimed to compare the tumor growth delay between conventional radiotherapy (CRT) and the spatially fractionated modalities of microbeam radiation therapy (MRT) and minibeam radiation therapy (MBRT). In addition, we also determined the influence of beam width and the peak-to-valley dose ratio (PVDR) on tumor regrowth. Methods: A549, a human non-small-cell lung cancer cell line, was implanted subcutaneously into the hind leg of female CD1-Foxn1^nu mice. The animals were irradiated with sham, CRT, MRT, or MBRT. The spatially fractionated fields were created using two specially designed multislit collimators with a beam width of 50 μm and a center-to-center distance (CTC) of 400 μm for MRT and a beam width of 500 μm and 2000 μm CTC for MBRT. Additionally, the concept of the equivalent uniform dose (EUD) was chosen in our study. A dose of 20 Gy was applied to all groups with a PVDR of 20 for MBRT and MRT. Tumor growth was recorded until the tumors reached at least a volume that was at least three-fold of their initial value, and the growth delay was calculated. Results: We saw a significant reduction in tumor regrowth following all radiation modalities. A growth delay of 11.1 ± 8 days was observed for CRT compared to the sham, whereas MBRT showed a delay of 20.2 ± 7.3 days. The most pronounced delay was observed in mice irradiated with MRT PVDR 20, with 34.9 ± 26.3 days of delay. Conclusions: The current study highlights the fact that MRT and MBRT modalities show a significant tumor growth delay in comparison to CRT at equivalent uniform doses.

Glioblastoma (GBM) constitutes the most common primary brain tumor and it remains incurable despite therapeutic advances. The high infiltration/invasion potential of GBM cells is considered to be one of the reasons for the inevitable recurrence of the disease. Radiotherapy (RT) is part of the standard care for patients with GBM, and its benefits on overall survival are extensively reported. However, numerous preclinical studies show that X-ray irradiation can enhance the motility of GBM cells. In the present review, we bring together state-of-the-art research on the impact of radiation on GBM cell motility. The mechanisms through which irradiation impacts the brain tumor microenvironment and the tumor cells themselves, leading to more aggressive/invasive tumors, are described. Finally, we summarize potential pharmacological strategies to overcome this problem. Clinical data validating the occurrence of these processes are urgently needed as they could be of great value for patient outcomes. With this comprehensive review, we expect to highlight the need for methods which allow for monitoring the post-irradiation invasive behavior of GBM in patients.

Background: Microbeam radiation therapy (MRT) is an advanced preclinical approach in radiotherapy that utilizes spatially fractionated dose distributions by collimating x-rays into micrometer-wide, planar beams. While the benefits of temporal fractionation are well established and widely incorporated into conventional radiotherapy protocols, the interplay between MRT and temporal dose fractionation remains largely unexplored. In this study, we investigate the effects of combining temporal and spatial dose fractionation by assessing clonogenic cell survival following temporally fractionated MRT with varying irradiation angles, compared to conventional broad-beam (BB) irradiation. Methods: A lung tumor cell line (A549) and a normal lung cell line (MRC-5) were irradiated with a total number of four fractions with a 24 h interval between each fraction. We compared a temporally fractionated BB regime to two temporally fractionated MRT schemes with either overlapping MRT fields or MRT fields with a 45° rotation per fraction. Subsequently, the clonogenic cell survival assay was used by analyzing the corresponding survival fractions (SFs). Results: The clonogenic survival of A549 tumor cells differed significantly between microbeam radiation therapy with rotation (MRT + R) and overlapping MRT. However, neither MRT + R nor overlapping MRT showed statistically significant differences compared to the broad-beam (BB) irradiation for A549. In contrast, the normal tissue cell line MRC-5 exhibited significantly higher clonogenic survival following both MRT + R and overlapping MRT compared to BB. Conclusions: This study demonstrates that combining temporal and spatial fractionation enhances normal tissue cell survival while maintaining equivalent tumor cell kill, potentially increasing the therapeutic index. Our findings support the feasibility of delivering temporally fractionated doses using different MRT modalities and provide clear evidence of the therapeutic benefits of temporally fractionated MRT.