MicroRNA expression profiles in human cancer cells after ionizing radiation

Introduction: MicroRNAs are regulators of central cellular processes and are implicated in the pathogenesis and prognosis of human cancers. MicroRNAs also modulate responses to anti-cancer therapy. In the context of radiation oncology microRNAs were found to modulate cell death and proliferation after irradiation. However, changes in microRNA expression profiles in response to irradiation have not been comprehensively analyzed so far. The present study's intend is to present a broad screen of changes in microRNA expression following irradiation of different malignant cell lines. Materials and methods: 1100 microRNAs (Sanger miRBase release version 14.0) were analyzed in six malignant cell lines following irradiation with clinically relevant doses of 2.0 Gy. MicroRNA levels 6 hours after irradiation were compared to microRNA levels in non-irradiated cells using the "Geniom Biochip MPEA homo sapiens". Results: Hierarchical clustering analysis revealed a pattern, which significantly (p = 0.014) discerned irradiated from non-irradiated cells. The expression levels of a number of microRNAs known to be involved in the regulation of cellular processes like apoptosis, proliferation, invasion, local immune response and radioresistance (e. g. miR-1285, miR-24-1, miR-151-5p, let-7i) displayed 2 - 3-fold changes after irradiation. Moreover, several microRNAs previously not known to be radiation-responsive were discovered. Conclusion: Ionizing radiation induced significant changes in microRNA expression profiles in 3 glioma and 3 squamous cell carcinoma cell lines. The functional relevance of these changes is not addressed but should by analyzed by future work especially focusing on clinically relevant endpoints like radiation induced cell death, proliferation, migration and metastasis

Mature results of a randomized trial comparing two fractionation schedules of high dose rate endoluminal brachytherapy for the treatment of endobronchial tumors

Purpose: To determine the efficacy of high dose rate endobronchial brachytherapy (HDR-BT) for the treatment of centrally located lung tumors, two different fractionation schedules were compared regarding local tumor response, side effects and survival. Mature retrospective results with longer follow-up and more patients were analyzed. Initial results were published by Huber et al. in 1995. Methods and materials: 142 patients with advanced, centrally located malignant tumors with preferential endoluminal growth were randomized to receive 4 fractions of 3.8 Gy (time interval: 1 week, n = 60, group I) or 2 fractions of 7.2 Gy (time interval: 3 weeks, n = 82, group II) endobronchial HDR-BT. Age, gender, tumor stage, Karnofsky Performance Score and histology were equally distributed between both groups. Results: Local tumor response with 2 fractions of 7.2 Gy was significantly higher as compared to 4 fractions of 3.8 Gy (median 12 vs. 6 weeks; p <= 0.015). Median survival was similar in both groups (19 weeks in the 4 fractions group vs. 18 weeks in the 2 fractions group). Fatal hemoptysis was less frequent following irradiation with 2 x 7.2 Gy than with 4 x 3.8 Gy, although the difference did not achieve statistical significance (12.2% vs. 18.3%, respectively. p = 0,345). Patients presenting with squamous cell carcinoma were at higher risk of bleeding compared to other histology (21.9% vs. 9%, p = 0,035). Multivariate analysis with regard to overall survival, revealed histology (p = 0.02), Karnofsky Performance Score (p < 0.0001) and response to therapy (p < 0.0001) as significant prognostic factors. For patients showing complete response the median survival was 57 weeks, while for patients with progressive disease median survival time was 8 weeks, p < 0.0001. The KPS at the start of the treatment was significantly correlated with survival. Patients presenting with a KPS = 60 at the start had a significantly (p = 0,032) shorter survival time (10 weeks) than patients with a KPS &gt; 60 (29 weeks). Moreover, the Karnofsky Performance Score of most patients improved during therapy (p = 0,001), suggesting successful palliation of cancer associated symptoms. Multivariate analysis with regard to local tumor control found no significant factors. Conclusion: Endobronchial HDR-BT is an effective local treatment for advanced centrally located malignant tumors with endoluminal tumor growth. Local tumor response was significantly higher after HDR-BT with 2 x 7.2 Gy