Circ_0008500 Knockdown Improves Radiosensitivity and Inhibits Tumorigenesis in Breast Cancer Through the miR-758-3p/PFN2 Axis.

Breast cancer is one of the most common malignancies worldwide. Circular RNAs (CircRNAs) were revealed to be implicated in the development of breast cancer. In this research, we aimed to investigate the role and underlying mechanism of circ_0008500 in the development and radiosensitivity of breast cancer. Using real-time quantitative PCR (RT-qPCR) and western blot, we found that hsa_circ_0008500 (circ_0008500) and profilin 2 (PFN2) were increased, while microRNA-758-3p (miR-758-3p) was decreased in breast cancer tissues and cells. Cell viability, the number of colonies, proliferation and apoptosis were detected using CCK-8, colony formation, EdU assays and flow cytometry, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were devoted to test the interaction between miR-758-3p and circ_0008500 or PFN2. The results showed that circ_0008500 knockdown inhibited cell growth, and facilitated cell apoptosis and radiosensitivity in breast cancer cells in vitro. Moreover, circ_0008500 regulated PFN2 expression by sponging miR-758-3p. Functionally, circ_0008500 knockdown regulated cell behaviors and radiosensitivity by targeting miR-758-3p to downregulate PFN2 expression in vitro. Additionally, in vivo tumor formation assay and immunohistochemistry (IHC) assay demonstrated that circ_0008500 knockdown enhanced the radiosensitivity and repressed tumor growth in vivo. In conclusion, circ_0008500 inhibition promoted the radiosensitivity and restrained the development of breast cancer by downregulating PFN2 expression via targeting miR-758-3p.

Can internal mammary lymph nodes irradiation bring survival benefits for breast cancer patients? A systematic review and meta-analysis of 12,705 patients in 12 studies.

OBJECTIVE: To evaluate the effect of prophylactic irradiation of internal mammary lymph nodes in breast cancer patients. METHODS: The computer searched PubMed, EMBASE, Web of science, CNKI, Wanfang Medical Network, the Chinese Biomedical Literature Database to find clinical studies on internal mammary lymph node irradiation (IMNI) in breast cancer. The quality of the included literature was evaluated according to the Newcastle-Ottawa scale. Stata14 software was used for meta-analysis. RESULTS: A total of 12,705 patients in 12 articles were included for meta-analyzed. Compared with patients who unirradiated internal mammary lymph nodes (non-IMNI), the risk of death for patients after IMNI was reduced by 11% (HR 0.89, 95% CI 0.79-1.00, P = 0.0470); DFS of group mixed N+ patients (high risk group) was significantly improved after IMNI (HR 0.58, 95% CI 0.49-0.69, P < 0.001). Further subgroup analysis shows that compared with non-IMNI, DFS was significantly increased in N1or ypN1 subgroup (HR 0.65, 95% CI 0.49-0.87, P = 0.003) and N2or ypN2 subgroup (HR 0.51, 95% CI 0.37-0.70, P < 0.001) after IMNI, but there was no statistical difference in DFS between the IMNI and non-IMNI groups in N0 subgroup (HR 1.02 95% CI 0.87-1.20, P = 0.794) and N3 or ypN3 subgroup (HR 0.85, 95% CI 0.49-1.45, P = 0.547). No serious incidents were reported in all the included studies, and most of the acute and late side effects were mild and tolerable. CONCLUSION: Under modern radiotherapy techniques, IMNI can safely and effectively bring clinical benefits to N1-2 breast cancer patients, but its role in N0, N3 breast cancer patients remains to be further studied.

Relationship between WBRT total dose, intracranial tumor control, and overall survival in NSCLC patients with brain metastases - a single-center retrospective analysis.

BACKGROUND: The relationship between whole brain radiotherapy (WBRT) dose with intracranial tumor control and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) brain metastases (BM) is largely unknown. METHODS: We retrospectively analyzed 595 NSCLC BM patients treated consecutively at the Fourth Hospital of Hebei Medical University between 2013 to 2015. We assigned the patients into 4 dose groups of WBRT: none, < 30, 30-39, and ≥ 40 Gy and assessed their relationship with OS and intracranial progression-free survival (iPFS). Cox models were utilized. Covariates included sex, age, KPS, BM lesions, extracranial metastasis, BM and lung tumor resection, chemotherapy, targeted therapy, and focal radiotherapy modalities. RESULTS: Patients had a mean age of 59 years and were 44% female. Their median survival time (MST) of OS and iPFS were 9.3 and 8.9 months. Patients receiving none (344/58%), < 30 (30/5%), 30-39 (93/16%), and ≥ 40 (128/22%) Gy of WBRT had MST of OS (iPFS) of 7.3 (6.8), 6.0 (5.4), 10.3 (11.9) and 11.9 (11.9) months, respectively. Compared to none, other WBRT groups had adjusted HRs for OS - 1.23 (p > 0.20), 0.72 (0.08), 0.61 (< 0.00) and iPFS - 1.63 (0.03), 0.71 (0.06), 0.67 (< 0.01). Compared to 30-39 Gy, WBRT dose ≥40 Gy was not associated with improved OS and iPFS (all p > 0.40). Stratified analyses by 1-3 and ≥ 4 BM lesions and adjustment analyses by each prognostic index of RPA class, Lung-GPA and Lung-molGPA supported these relationships as well. CONCLUSIONS: Compared to none, WBRT doses ≥30 Gy are invariably associated with improved intracranial tumor control and survival in NSCLC BM patients.