Peripheral lymphocyte subset variation predicts prostate cancer carbon ion radiotherapy outcomes.

The immune system plays a complementary role in the cytotoxic activity of radiotherapy. Here, we examined changes in immune cell subsets after heavy ion therapy for prostate cancer. The lymphocyte counts were compared with acute radiotherapy-related toxicity, defined according to the Common Terminology Criteria for Adverse Events, and short-term local efficacy, defined based on prostate-specific antigen concentrations. Confirmed prostate cancer patients who had not received previous radiotherapy were administered carbon ion radiotherapy (CIR) in daily fractions of 2.74 GyE with a total dose of 63-66 GyE. Lymphocyte subset counts were investigated before, during and after radiotherapy, and at a 1 month follow-up. Most notable among our findings, the CD4/CD8 ratio and CD19+ cell counts were consistently higher in patients with a complete response (CR) or partial response (PR) to CIR than in those classified in the stable disease (SD) group (P<0.05 for both). But CD3+ and CD8+ cell counts were lower in the CR and PR groups than in the SD group. These results indicate that variations in peripheral lymphocyte subpopulations are predictive of outcome after CIR for prostate cancer.

Photo-thermal effect enhances the efficiency of radiotherapy using Arg-Gly-Asp peptides-conjugated gold nanorods that target αvß3 in melanoma cancer cells.

BACKGROUND: Thermotherapy has been known to be one of the most effective adjuvants to radiotherapy (RT) in cancer treatment, but it is not widely implemented clinically due to some limitations, such as, inadequate temperature concentrations to the tumor tissue, nonspecific and non-uniform distribution of heat. So we constructed arginine-glycine-aspartate peptides-conjugated gold nanorods (RGD-GNRs) that target the alpha(v) beta(3) Integrin (αvß3) and investigate whether the photo-thermal effect of RGD-GNRs by near infrared radiation (NIR) could enhance the efficiency of RT in melanoma cancer cells. RESULTS: RGD-GNRs could be seen both on the surface of the cell membranes and cytoplasm of A375 cells with high expression of αvß3. After exposed to 808 nm NIR, RGD-GNRs with various concentrations could be rapidly heated up. Compared to other treatments, flow cytometric analysis indicated that RT + NIR + RGD-GNRs increased apoptosis (p < 0.001) and decreased the proportion of cells in the more radioresistant S phase (p = 0.014). Treated with NIR + RGD-GNRs, the radiosensitivity was also significantly enhanced (DMFSF2: 1.41). CONCLUSION: Results of the current study showed the feasibility of using RGD-GNRs for synergetic RT with photo-thermal therapy. And it would greatly benefit the therapeutic effects of refractory or recurrent malignant cancers.

Circulating microRNAs in esophageal squamous cell carcinoma: association with locoregional staging and survival.

Locoregional staging and prognostic information play a critical role in esophageal squamous cell carcinoma (ESCC) treatment strategies. Although microRNA (miRNA) is a promising marker for cancer detection, the relationship between circulating plasma miRNAs and ESCC remains unclear. Our study aims to investigate the association between circulating plasma miRNAs and tumor diagnosis or prognosis in ESCC patients. Plasma levels of miR-16, miR-21, miR-22, miR-126, miR-148b, miR-185, miR-221, miR-223, and miR-375 were evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays from 38 ESCC patients prior to treatment and 19 healthy subjects. Differences in selected miRNAs and their diagnostic and prognostic value were examined. Levels of four of the selected miRNAs were found to be significantly higher in ESCC patients than in controls; namely, miR-16, miR-21, miR-185, and miR-375 (P < 0.050). In addition, the area under the receiver operating characteristic (ROC) curve (AUC) for miR-375 was 0.921 (95% confidence interval [CI] 0.817-0.976). Moreover, the expression levels of miR-16 were higher in patients with T3-4 tumors than in patients with T1-2 tumors (P = 0.020). Kaplan-Meier survival analysis showed that high expression levels of miR-16 and miR-21 in the plasma correlated significantly with shortened progression-free survival (PFS; P = 0.031 and P = 0.038, respectively) and overall survival (OS; P = 0.022 and P = 0.041, respectively) in ESCC patients. Four plasma miRNAs were identified that could potentially serve as novel diagnostic biomarkers for ESCC. Moreover, specific miRNAs, such as miR-16 and miR-21, can predict poor survival in ESCC.

Correlation of dynamic changes in γ-H2AX expression in peripheral blood lymphocytes from head and neck cancer patients with radiation-induced oral mucositis.

BACKGROUND: To evaluate the role of γ-H2AX in peripheral blood lymphocytes (PBLs) as a predictive biomarker of the severity of oral mucositis (OM) in head and neck cancer (HNC) patients with receiving radiotherapy. METHODS: In vitro assays for evaluating DNA damage and repair kinetics were performed on blood samples withdrawn from 25 HNC patients undergoing radiotherapy or chemoradiotherapy before radiotherapy. As for the in vivo study, blood samples were also withdrawn before radiotherapy, and 1 hour after radiotherapy on the fourth and last days. Flow cytometry was used to assess the expression of γ-H2AX in PBLs. OM was assessed using the World Health Organization (WHO) scores twice a week and correlated with the expression of γ-H2AX. RESULTS: The in vitro assay results showed that patients with severe OM had higher γ-H2AX-specific relative fluorescence at various irradiation doses in the damage kinetics assay, with significantly higher γ-H2AX expression at 8 Gy (p = 0.039), and also at 24 hours after irradiation at a dose of 2 Gy in the repair kinetics assay, compared to the patients with mild OM (p = 0.008). The optimal cutoff value for relative fluorescence of γ-H2AX was 0.960, 24 hours post-irradiation. However, there were no significant differences in γ-H2AX expression at different times between the two groups, as assessed with the in vivo assay. CONCLUSIONS: These results suggest that the damage and repair kinetics of γ-H2AX from PBLs in the in vitro study may have predictive value for identifying the grades of OM among HNC patients prior to radiotherapy.