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Radiotherapy is an important modality for the treatment of cancer, e.g., X-ray, Cs-137 γ-ray (peak energy: 662 keV). An important therapy pathway of radiation is to generate the double strand breaks of DNA to prohibit the proliferation of cancer cells. In addition, the excessive amount of reactive oxygen species (ROS) is induced to damage the organelles, which can cause cellular apoptosis or necrosis. Gold nanoparticles (GNPs) have been proven potential as a radiosensitizer due to the high biocompatibility, the low cytotoxicity and the high-Z property (Z = 79) of gold. The latter property may allow GNPs to induce more secondary electrons for generating ROS in cells as irradiated by high-energy photons. In this paper, the radiobiological effects on A431 cells with uptake of 55-nm GNPs were studied to investigate the GNPs-enhanced production of ROS on these cells as irradiated by Cs-137 γ-ray. The fluorescence-labeling image of laser scanning confocal microscopy (LSCM) shows the excessive expression of ROS in these GNPs-uptake cells after irradiation. And then, the follow-up disruption of cytoskeletons and dysfunction of mitochondria caused by the induced ROS are observed. From the curves of cell survival fraction versus the radiation dose, the radiosensitization enhancement factor of GNPs is 1.29 at a survival fraction of 30%. This demonstrates that the tumoricidal efficacy of Cs-137 radiation can be significantly raised by GNPs. Because of facilitating the production of excessive ROS to damage tumor cells, GNPs are proven to be a prospective radiosensitizer for radiotherapy, particularly for the treatment of certain radioresistant tumor cells. Through this pathway, the tumoricidal efficacy of radiotherapy can be raised.

Imaging probes/biomarkers that are correlated with molecular or microenvironmental alterations in tumors have been used not only in diagnosing cancer but also in assessing the efficacy of cancer treatment. We evaluated the early response of hepatocellular carcinoma (HCC) to radiation treatment using T2-weighted magnetic resonance imaging (MRI), diffusion-weighted (DW) MRI, and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Orthotopic HCC tumors were established in the right liver lobe of Balb/c mice. Mice were longitudinally scanned using T2-weighted/DW MRI and 18F-FDG PET 1 day before and on days 1, 3, 6, 9 and 13 after irradiation with 15 Gy to the right liver lobe to determine tumor size, apparent diffusion coefficient (ADC) value, and maximum standardized uptake value. Immunohistochemical (IHC) staining was performed to validate the tumor microenvironment. Irradiation markedly retarded tumor growth in the orthotopic HCC model and led to increaes in ADC values as early as on day 1 after irradiation. Irradiation also resulted in increases in 18F-FDG uptake on day 1 that were sustained until the end of the observation period. IHC staining revealed a decrease in the number of proliferative cells and a continuous macrophage influx into irradiated tumors, which dramatically altered the tumor microenvironment. Lastly, in vitro coculture of HCC cells and macrophages led to interaction between the cells and enhanced the cellular uptake of 18F-FDG. ADC values and 18F-FDG uptake measured using DW MRI and 18F-FDG PET serve as potential biomarkers for early assessment of HCC tumor responses to radiation therapy.

Cervical cancer is the fourth most common cancer in women worldwide. Increasing evidence has shown that miRNAs are related to the progression of cervical cancer. However, the mechanisms that affect the prognosis of cancer are still largely unknown. In the present study, we sought to identify miRNAs associated with poor prognosis of patient with cervical cancer, as well as the possible mechanisms regulated by them. The miRNA expression profiles and relevant clinical information of patients with cervical cancer were obtained from The Cancer Genome Atlas (TCGA). The selection of prognostic miRNAs was carried out through an integrated bioinformatics approach. The most effective miRNAs with synergistic and additive effects were selected for validation through in vitro experiments. Three miRNAs (miR-216b-5p, miR-585-5p, and miR-7641) were identified as exhibiting good performance in predicting poor prognosis through additive effects analysis. The functional enrichment analysis suggested that not only pathways traditionally involved in cancer but also immune system pathways might be important in regulating the outcome of the disease. Our findings demonstrated that a synergistic combination of three miRNAs may be associated, through their regulation of specific pathways, with very poor survival rates for patients with cervical cancer.