It has been long recognized that cranial irradiation used for the treatment of primary and metastatic brain tumor often causes neurological side-effects such as intellectual impairment, memory loss and dementia, especially in children patients. Our previous study has demonstrated that whole-brain irradiation (WBI) can cause cognitive decline in rats. Minocycline is an antibiotic that has shown neuroprotective properties in a variety of experimental models of neurological diseases. However, whether minocycline can ameliorate cognitive impairment induced by ionizing radiation (IR) has not been tested. Thus this study aimed to demonstrate the potential implication of minocycline in the treatment of WBI-induced cognitive deficits by using a rat model. Sprague Dawley rats were cranial irradiated with electron beams delivered by a linear accelerator with a single dose of 20 Gy. Minocycline was administered via oral gavages directly into the stomach before and after irradiation. The open field test was used to assess the anxiety level of rats. The Morris water maze (MWM) was used to assess the spatial learning and memory of rats. The level of apoptosis in hippocampal neurons was measured using immunohistochemistry for caspase-3 and relative markers for mature neurons (NeuN) or for newborn neurons (Doublecortin (DCX)). Neurogenesis was determined by BrdU incorporation method. Neither WBI nor minocycline affected the locomotor activity and anxiety level of rats. However, compared with the sham-irradiated controls, WBI caused a significant loss of learning and memory manifest as longer latency to reach the hidden platform in the MWM task. Minocycline intervention significantly improved the memory retention of irradiated rats. Although minocycline did not rescue neurogenesis deficit caused by WBI 2 months post-IR, it did significantly decreased WBI-induced apoptosis in the DCX positive neurons, thereby resulting in less newborn neuron depletion 12 h after irradiation. Minocycline significantly inhibits WBI-induced neuron apoptosis, leading to less newborn neurons loss shortly after irradiation. In the long run, minocycline improves the cognitive performance of rats post WBI. The results indicate a potential clinical implication of minocycline as an effective adjunct in radiotherapy for brain tumor patients.

Radiotherapy is among the routine treatment options for malignant tumors. And it damages DNA and other cellular organelles in target cells by using ionizing radiation produced by various rays, killing the cells. In recent years, multiple studies have demonstrated that exosomes are mechanistically involved in regulating tumor formation, development, invasion and metastasis, and immune evasion. The latest research shows that radiation can affect the abundance and composition of exosomes as well as cell-to-cell communication. In the environment, exosome-carried miRNAs, circRNA, mRNA, and proteins are differentially expressed in cancer cells, while these molecules play a role in numerous biological processes, including the regulation of oncogene expression, mediation of signaling pathways in cancer cells, remodeling of tumor-related fibroblasts, regulation of cell radiosensitivity, and so forth. Therefore, elucidation of the mechanism underlying the role of exosomes in radiotherapy of malignant tumors is crucial for improving the efficacy of radiotherapy. This review will summarize the research advances in radiosensitivity of malignant tumors related to exosomes.

Background The aim of this study is to establish a prognostic risk assessment model for coexpressed M2 related genes and to elucidate the role of M2 macrophages within the ccRCC (Clear cell carcinoma of the kidney) immune microenvironment, which may have the potential to enhance the efficacy of ccRCC treatment.Method Transcriptome data, clinical data, and mutation data were obtained from TCGA-KIRC. CIBERSORT was used to calculate the proportion of M2 macrophage cells of each of the 539 samples. Genes associated with macrophage M2 in TCGA-KIRC with the external dataset E-MTAB-1980 from the Arrayexpress database were determined by intersection, and a coexpression network was established. Following lasso regression, a prognostic model was constructed, factors with significant findings were entered into a Cox regression analysis. Next, we used the external dataset E-MTAB-1980 from the ArrayExpress database for validation. Lastly, risk score was evaluated by stroma immune infiltration, GSEA, TMB and drug sensitivity.Results We obtained the top 46 genes most strongly correlated with macrophage M2 in TCGA-KIRC, which are enriched in immune receptor activity, leukocyte and mononuclear cell migration. A model of twelve genes related to the coexpressed macrophage M2 gene was established, we demonstrated that it has good prognostic capacity.Conclusion We proposed a twelve-gene Cox proportional hazard regression model associated with M2 ccRCC macrophage that could provide a measurement method to generate prognostic scores in patients with ccRCC. We discovered that the M2 macrophage infiltration was closely related to tumor metabolism and inversely correlated with risk score in ccRCC. The observations we report here have the potential to provide meaningful candidate biomarkers for the treatment and surveillance of ccRCC.