The cohesin protein complex holds sister chromatids together after synthesis until mitosis. It also contributes to post-replicative DNA repair in yeast and higher eukaryotes and accumulates at sites of laser-induced damage in human cells. Our goal was to determine whether the cohesin subunits SMC1 and Rad21 contribute to DNA double-strand break repair in X-irradiated human cells in the G2 phase of the cell cycle. RNA interference-mediated depletion of SMC1 sensitized HeLa cells to X-rays. Repair of radiation-induced DNA double-strand breaks, measured by γH2AX/53BP1 foci analysis, was slower in SMC1- or Rad21-depleted cells than in controls in G2 but not in G1. Inhibition of the DNA damage kinase DNA-PK, but not ATM, further inhibited foci loss in cohesin-depleted cells in G2. SMC1 depletion had no effect on DNA single-strand break repair in either G1 or late S/G2. Rad21 and SMC1 were recruited to sites of X-ray-induced DNA damage in G2-phase cells, but not in G1, and only when DNA damage was concentrated in subnuclear stripes, generated by partially shielded ultrasoft X-rays. Our results suggest that the cohesin complex contributes to cell survival by promoting the repair of radiation-induced DNA double-strand breaks in G2-phase cells in an ATM-dependent pathway.

Markers predictive of treatment effect might be useful to improve the treatment of patients with metastatic solid tumors. Particularly, early changes in tumor metabolism measured by PET/CT with ¹⁸F-FDG could predict the efficacy of treatment better than standard dimensional Response Evaluation Criteria In Solid Tumors (RECIST) response. Methods: We performed PET/CT evaluation before and after 1 cycle of treatment in patients with resectable liver metastases from colorectal cancer, within a phase 2 trial of preoperative FOLFIRI plus bevacizumab. For each lesion, the maximum standardized uptake value (SUV) and the total lesion glycolysis (TLG) were determined. On the basis of previous studies, a ≤ −50% change from baseline was used as a threshold for significant metabolic response for maximum SUV and, exploratively, for TLG. Standard RECIST response was assessed with CT after 3 mo of treatment. Pathologic response was assessed in patients undergoing resection. The association between metabolic and CT/RECIST and pathologic response was tested with the McNemar test; the ability to predict progression-free survival (PFS) and overall survival (OS) was tested with the Log-rank test and a multivariable Cox model. Results: Thirty-three patients were analyzed. After treatment, there was a notable decrease of all the parameters measured by PET/CT. Early metabolic PET/CT response (either SUV- or TLG-based) had a stronger, independent and statistically significant predictive value for PFS and OS than both CT/RECIST and pathologic response at multivariate analysis, although with different degrees of statistical significance. The predictive value of CT/RECIST response was not significant at multivariate analysis. Conclusion: PET/CT response was significantly predictive of long-term outcomes during preoperative treatment of patients with liver metastases from colorectal cancer, and its predictive ability was higher than that of CT/RECIST response after 3 mo of treatment. Such findings need to be confirmed by larger prospective trials.

The structural and mechanical properties of the microenvironmental context have a profound impact on cancer cell motility, tumor invasion, and metastasis formation. In fact, cells react to their mechanical environment modulating their adhesion, cytoskeleton organization, changes of shape, and, consequently, the dynamics of their motility. In order to elucidate the role of extracellular matrix stiffness as a driving force in cancer cell motility/invasion and the effects of ionizing radiations on these processes, we evaluated adhesion and migration as biophysical properties of two different mammary cell lines, over a range of pathophysiological stiffness (1–13 kPa) in a control condition and after the exposure to two different X-ray doses (2 and 10 Gy, photon beams). We concluded that the microenvironment mimicking the normal mechanics of healthy tissue has a radioprotective role on both cell lines, preventing cell motility and invasion. Supraphysiological extracellular matrix stiffness promoted tumor cell motility instead, but also had a normalizing effect on the response to radiation of tumor cells, lowering their migratory capability. This work lays the foundation for exploiting the extracellular matrix-mediated mechanism underlying the response of healthy and tumor cells to radiation treatments and opens new frontiers in the diagnostic and therapeutic use of radiotherapy.

An adequate and balanced diet is fundamental in preserving the health of astronauts from several space-induced diseases. Therefore, the integration of a diet with fresh food, rich in bioactive compounds such as microgreens produced directly onboard, may be useful in space for human nutrition. However, ionizing radiation (IR) in space represents a significant hindrance for organisms, with potential critical outcomes on plant morpho-anatomical, eco-physiological, and biochemical aspects, depending on the plant and IR features (e.g., species, developmental stage, IR dose, and type). In this study, we analyzed the effect of different doses of X-rays (0-control, 0.3, 1, 10, 20, and 30 Gy) on the morpho-anatomical and nutritional traits of microgreens of Brassica rapa L., irradiated at the stage of germinated seeds. After the irradiation, microgreens were cultivated in controlled conditions. At harvest, the morpho-biometric traits were analyzed, along with the leaf functional anatomical traits and the phytochemical content of the aboveground biomass. The results showed that X-ray exposure does not induce detrimental effects on growth, while it stimulates the production of antioxidants, improving plant defense and nutritional value. The overall results support the idea of using this species in space as a supplemental functional food.