Objective: Ras-related C3 botulinum toxin substrate1(Rac1) and epithelial mesenchymal transition (EMT) are key therapeutic targets in cancer. We investigated the clinical significance of Rac1 and markers of EMT expression in non-small cell lung cancer (NSCLC), and their possible correlation with EMT phenotype.Methods: Immunohistochemistry was used to assess the expression of Rac1, Snail1, Twist1, N-cadherin (N-cad), Vimentin (Vim), and E-cadherin (E-cad) in 153 NSCLC paraffin-embedded specimens and 45 normal specimens adjacent to tumors. The correlation of Rac1 and EMT markers with clinicopathological characteristics and the relationship between the protein levels and progression-free survival (PFS) and overall survival (OS) were analyzed.Results: Compared with non-tumor tissues, the NSCLC tissues showed marked elevation in the levels of Rac1, Snail1, Twist1, N-cad, and Vim levels, whereas the E-cad levels were significantly decreased (P < 0.05). The aberrant expression of Rac1 and EMT markers was significantly associated with TNM stage and metastasis (P < 0.05). Increased expression of Rac1 may be associated with poor OS and PFS compared with low expression (P<0.001 and P=0.004). Significant correlations were observed between the EMT markers expressed and OS or PFS(P<0.01). In addition, multivariate analysis indicated that the expression of Rac1, Snail1, Twist1, N-cad, Vim, and E-cad was an independent prognostic factor in NSCLC. Interestingly, Rac1 expression was positively correlated with Snail1, Twist1, N-cad, and Vim levels (r=0.563, r=0.440, r=0.247 r=0.536, P<0.01, respectively) and negatively correlated with E-cad levels (r=-0.464, P<0.001) in NSCLC tissues. Rac1, Twist, Snail1, Vim and N-cad were highly expressed in lung cancer patients resistant to radiotherapy, while E-cad was poorly expressed.Conclusion: Rac1 may promote NSCLC progression and metastasis via EMT, which may be considered as a potential therapeutic target.

Abstract. The aim of this study was to compare the dosimetric characteristics of left-sided whole breast irradiation among 3-dimensional conformal radiotherapy (3D-CRT), 4-field inverse-planned intensity-modulated radiotherapy (IP-IMRT) and hybrid IMRT technique (combining 3D-CRT beams and IP-IMRT beams) with respect to target coverage and irradiation of organs at risk. The 3 different planning techniques were analyzed for 8 patients with left-sided breast conserving surgery. Plans were compared on the basis of planning target volume (PTV) dose conformity, homogeneity and the volumes of normal tissues treated based on dose-volume histograms (DVHs). DVHs were calculated for the PTV, heart, and the bilateral lungs, contralateral breast, and soft tissue surrounding the breast PTV (V OB ) volume. IP-IMRT and hybrid IMRT techniques comparably improved the PTV dose homogeneity and conformity (CI) significantly, compared to the conventional 3D-CRT technique (P<0.017); the IP-IMRT technique only could additionally benefit patients by decreasing the high-dose (40 Gy) volume for heart and ipsilateral lung compared with the hybrid IMRT technique (P<0.017); the hybrid IMRT plans achieved a further improvement by compromising the increase of low-dose volume (total lung V13, contralateral lung V5, heart V10 and soft tissue surrounding the breast V5) compared with IP-IMRT plans (P<0.017). Hybrid IMRT plans achieved equivalent PTV dose uniformity to IP-IMRT plans and compromised the low-dose volume and requirement of clinic resource between IP-IMRT and 3D-CRT plans, promoting it as a standard practice of left-sided breast irradiation for patients in good-ordered cardiopulmonary health.

G-rich oligonucleotides have attracted considerable interest as therapeutic agents. In this report, we tested two G-rich aptamers selected against EGFR-transfected A549 cells, and their G-rich domains (S13 and S50) were identified to account for the binding of parental aptamers. CD spectra showed that S13 and S50 bind to their targets by forming parallel quadruplexes. Their binding, internalization and antiproliferation activity in cancer and noncancer cells were investigated by flow cytometry and MTS assay, and compared with those of nucleolin-binding AS1411 and thrombin-binding aptamer. The two truncated aptamers (S13 and S50) have good binding and internalization in cancer cells and noncancer cells; however, only S50, like AS1411, shows potent antiproliferation against cancer cells. Our data suggest that tumor-selective antiproliferation of G-rich oligonucleotides does not directly depend on the binding of the G-rich aptamer to cells.

BackgroundSingle nucleotide polymorphisms (SNPs) in DNA repair genes can alter gene expression and activity and affect response to cancer treatment and, correspondingly, survival. The present study was designed to evaluate the utility of the XRCC1 Arg399Gln and ERCC1 Cys8092Ala SNPs, measured in pretreatment biopsy samples, as predictors of response to radiotherapy in patients with non-metastatic nasopharyngeal carcinoma (NPC).Materials and methodsThe study included 75 consecutive patients with stage II-IVA-B NPC. XRCC1 Arg399Glu and ERCC1 Cys8092Ala SNPs were identified from paraffin-embedded biopsy specimens via Sanger sequencing. Expression of p53 and pAkt protein was analyzed by immunohistochemical staining. Potential relationships between genetic polymorphisms and progression-free survival (PFS) were analyzed by using a Cox proportional hazards model, the Kaplan-Meier method, and the log-rank test.ResultsMultivariate analysis showed that carriers of the ERCC1 8092 Ala/Ala genotype [hazard ratio (HR) 1.882; 95% confidence interval (CI) 1.031–3.438; P = 0.039] and heavy smokers (≥20 pack-years) carrying the XRCC1 Arg/Arg genotype (HR 2.019; 95% CI 1.010–4.036; P = 0.047) had significantly lower PFS rates. Moreover, combined positive expression of p53 and pAkt led to significantly increased PFS in subgroups carrying the XRCC1 Gln allele (HR 7.057; 95% CI 2.073–24.021; P = 0.002) or the ERCC1 Cys allele (HR 2.568; 95% CI 1.056–6.248; P = 0.038).ConclusionsThe ERCC1 Cys8092Ala polymorphism is an independent predictor of response to radiotherapy for NPC, and the XRCC1 Arg399Glu mutation combined with smoking status seems to predict PFS as well. Our results further suggest a possible correlation between these genetic polymorphisms and p53 protein status on survival.