Biosensor Cell-Fit-HD for correlation of single-cell fate and microscale energy deposition in complex ion beams.

We present a protocol for the biosensor Cell-Fit-HD. It enables long-term monitoring and correlation of single-cell fate with subcellular-deposited energy of ionizing radiation. Cell fate tracking using widefield time-lapse microscopy is uncoupled in time from confocal ion track imaging.

Radioresistance and Transcriptional Reprograming of Invasive Glioblastoma Cells.

Purpose: Infiltrative growth pattern is a hallmark of glioblastoma (GBM). Radiation therapy aims to eradicate microscopic residual GBM cells after surgical removal of the visible tumor bulk. However, in-field recurrences remain the major pattern of therapy failure.

Simultaneous targeting of TGF-β/PD-L1 synergizes with radiotherapy by reprogramming the tumor microenvironment to overcome immune evasion.

Localized radiotherapy (RT) induces an immunogenic antitumor response that is in part counterbalanced by activation of immune evasive and tissue remodeling processes, e.g., via upregulation of programmed cell death-ligand 1 (PD-L1) and transforming growth factor β (TGF-β).

Carbon ion dosimetry on a fluorescent nuclear track detector using widefield microscopy.

Fluorescent nuclear track detectors (FNTDs) are solid-state dosimeters used in a wide range of dosimetric and biomedical applications in research worldwide. FNTDs are a core but currently underutilized dosimetry tool in the field of radiation biology which are inherently capable of visualizing the tracks of ions used in hadron therapy. The ions that traverse the FNTD deposit their energy according to their linear energy transfer and transform colour centres to form trackspots around their trajectory.

Large scale in vivo micro-RNA loss of function screen identified miR-29a, miR-100 and miR-155 as modulators of radioresistance and tumor-stroma communication.

Micro RNAs (miR) are master regulators of cellular transcriptome. We aimed to investigate the role of miR regulation on tumor radiosensitivity and development of local tumor recurrence by a novel large-scale in vivo loss of function screen. For stable miR silencing, human A431 tumor cells were transduced with lentiviral constructs against 170 validated human miR (miRzip library).

Combined external beam radiotherapy with carbon ions and tumor targeting endoradiotherapy.

External beam radiotherapy (EBRT) with carbon ions and endoradiotherapy using radiolabeled tumor targeting agents are emerging concepts in precision cancer therapy. We report on combination effects of these two promising strategies. Tumor targeting I-labelled anti-EGFR-antibody (Cetuximab) was used in the prototypic EGFR-expressing A431 human squamous cell carcinoma xenograft model.

Deciphering the Acute Cellular Phosphoproteome Response to Irradiation with X-rays, Protons and Carbon Ions.

Radiotherapy is a cornerstone of cancer therapy. The recently established particle therapy with raster-scanning protons and carbon ions landmarks a new era in the field of high-precision cancer medicine. However, molecular mechanisms governing radiation induced intracellular signaling remain elusive.