The nuclear retinoic acid receptor may play a critical role in the process of lung carcinogenesis. Alteration or loss of nuclear retinoic acid receptors (RARs) has been associated with progression in premalignant and malignant tissues and it is associated with malignant transformation in human cells. Vitamin A derivates, such as retinoic acid, have emerged as adjuvant to therapy in several types of cancer with favorable effects. Retinoic acid regulates the expression of target genes through the binding and activation of RARs, inhibiting growth proliferation. Diverse studies have evaluated different retinoids alone or in combination with chemotherapy in lung cancer, from which results have been controversial with benefits observed only in the subpopulation with high levels of triglycerides. Additionally, several large randomized trials using retinoids to prevent tobacco-related cancer have failed; due to the latter the use of retinoids in clinical trials remains controversial. However they could reduce the risk of cancer development in non-smokers. There is evidence that retinoids have different effects on lung cancer; still the identification of biomarkers could determinate their benefits as preventive or therapy agents. This review describes the RAR alterations during the development of Non-Small Cell Lung Cancer and sets out the importance of several cancer treatments with retinoid compounds.

No abstract

(OS) in lung adenocarcinoma patients. Results: All tested cancer cell lines expressed AQP11 and correlation analysis revealed significant association of AQP11 expression with cisplatin resistance (Spearman's r¼0.82, p¼0.008). Analysis of stress markers showed that cisplatin-treated cells with higher AQP11 expression had lower stress. Using shRNA, we knocked down AQP11 in cispaltin resistant A549 and HCC827 cells and cisplatin sensitive H460 cells. Resulting knockdown A549 and HCC827 cells became 2.6-to 2.9-fold more sensitive to cisplatin compared to parental and control vector transduced cells. In sensitive H460 cells, knocking down AQP11 did not change sensitivity to cisplatin. Results suggest that high expression AQP11 contributes to cisplatin resistance. TCGA database analysis of previously untreated lung adenocarcinoma, detected 13% tumors with elevated AQP11 mRNA expression (6.18±0.55 vs. 4.28±0.77, p<0.001). Increased AQP11 expression was significantly associated with decreased OS. These patients showed lower median survival rate of 34.47 versus 52.5 months in patients with low AQP11 expression (longrank test p<0.05). Conclusion: AQP11 is the cispaltin non-DNA target that may significantly contribute to the development of resistance. High AQP11 level is a pro-survival factor protecting tumor cells from cisplatin-induced stress. High AQP11 expression associates with lower OS in lung adenocarcinoma patients and with cispaltin resistance in lung cancer cell lines. With further validation, AQP11 level might be a predictor of cisplatin resistance and overall survival in lung cancer.

Background: The aim of the study is to demonstrate the relationship between clinicopathological variables and brain metastasis in patients with resected lung adenocarcinoma. Methods:The clinicopathological characteristics of 748 patients of resected lung adenocarcinoma at Taipei

compare survival between these six cohorts. Result: 98,069 patients were included. Treatment in ACs had superior 2YS compared to treatment in CCs, increasing from 16.1% versus 10.3% for those diagnosed in 2004(+5.8%), to 23.7% versus 16.2% for those diagnosed in 2013(+7.5%). Our multivariable model found growth in 2YS disparity of 0.34%-per-year (95% CI 0.18% to 0.50%, p<0.001). This was histology-related: Difference in adenocarcinoma 2YS rose from 7% in 2004 to 9% in 2013(p¼0.0023), while squamous carcinoma 2YS difference was 2.7% in 2004 and 0.8% in 2013(p¼0.6). 9047 patients were treated at ICs. In the 2004-2008 cohort treatment at ICs had similar outcomes to CCs, however by 2011-2015 ICs had superior histology-related survival, suggesting treatment-related improvements in ICs over CCs (Table 1). Conclusion: Survival disparities in metastatic lung cancer between academic and community-based centers in the US continued to widen through 2015. Treatment at integrated centers, a group of facilities with at least one hospital that can include community and academic centers, may help to bridge the divide. Treatment related disparities in other health systems warrant further study globally.