[Dynamics of LINE-1 Retrotransposon Methylation Levels in Circulating DNA from Lung Cancer Patients Undergoing Antitumor Therapy].

Malignant cell transformation is accompanied with abnormal DNA methylation, such as the hypermethylation of certain gene promoters and hypomethylation of retrotransposons. In particular, the hypomethylation of the human-specific family of LINE-1 retrotransposons was observed in lung cancer tissues. It is also known that the circulating DNA (cirDNA) of blood plasma and cell-surface-bound circulating DNA (csb-cirDNA) of cancer patients accumulate tumor-specific aberrantly methylated DNA fragments, which are currently considered to be valuable cancer markers. This work compares LINE-1 retrotransposon methylation patterns in cirDNA of 16 lung cancer patients before and after treatment. CirDNA was isolated from blood plasma, and csb-cirDNA fractions were obtained by successive elution with EDTA-containing phosphate buffered saline and trypsin. Concentrations of methylated LINE-1 region 1 copies (LINE-1-met) were assayed by real-time methylation-specific PCR. LINE-1 methylation levels were normalized to the concentration of LINE-1 region 2, which was independent of the methylation status (LINE-1-Ind). The concentrations of LINE-1-met and LINE-1-Ind in csb-cirDNA of lung cancer patients exhibited correlations before treatment (r = 0.54), after chemotherapy (r = 0.72), and after surgery (r = 0.83) (P < 0.05, Spearman rank test). In the total group of patients, the level of LINE-1 methylation (determined as the LINE-1-met/LINE-1-Ind ratio) was shown to increase significantly during the follow-up after chemotherapy (P < 0.05, paired t test) and after surgery compared to the level of methylation before treatment (P < 0.05, paired t test). The revealed association between the level of LINE-1 methylation and the effect of antitumor therapy was more pronounced in squamous cell lung cancer than in adenocarcinoma (P < 0.05 and P > 0.05, respectively). These results suggest a need for the further investigation of dynamic changes in levels of LINE-1 methylation depending on the antitumor therapy.

Chemotherapy and intraoperative radiation therapy for operable stage III non-small cell lung cancer.

The study was undertaken to evaluate results of combined modality treatment including intraoperative radiation therapy (IORT) in 202 patients with stage III non-small cell lung cancer. The 5-year disease-free and overall survival rates in patients who underwent 15 Gy IORT were 18. 7% and 29. 2%, respectively. The overall response rate to preoperative chemotherapy with paclitaxel/carboplatin was 43. 7%, treatment was well tolerated. Preoperative chemotherapy with paclitaxel/ carboplatin in combination with 15 Gy IORT led to a significant increase in the 5-year disease-free and overall survival rates to 31. 4% and 39. 2%, respectively (p<0. 05). The 5-year disease-free and overall survival rates were respectively 32. 6% and 40. 8% in patients who received additional administration of cisplatin combined with 10 Gy IORT. Radiosensibilization with cisplatin in patients treated with 15 Gy IORT increased the 5-year disease-free and overall survival rates to 41. 7% and 47. 9%, respectively (p<0. 05).