AIMS:To investigate the association of several single nucleotide polymorphisms (SNPs) within nucleotide excision repair (NER) gene and additional gene- gene and gene- smoking interaction with non-melanoma skin cancer (NMSC) risk in a Chinese population.METHODS:A total of 1322 participants (939 males, 383 females) were selected, including 660 NMSC patients and 662 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association between 4 SNPs within NER gene, additional gene- gene and gene- smoking interaction on NMSC risk.RESULTS:NMSC risk was significantly higher in carriers with G allele of rs2228527 than those with AA genotype (AG + GG versus AA), adjusted OR (95%CI) =1.76 (1.24-2.37), and higher in carriers with the G allele of rs2228529 than those with AA genotype (AG + GG versus AA), adjusted OR (95%CI) = 1.66 (1.24-2.13). However, we did not find any direct association of the rs4134822 and rs1799793 with NMSC risk after covariates adjustment. GMDR model indicated a significant interaction combination (p=0.0010), including rs2228529 and current smoking. Overall, the cross-validation consistency of this model was 9/ 10, and the testing accuracy was 60.72%. Current smokers with rs2228529- GA or GG genotype have the highest NMSC risk, compared to never- smokers with rs2228529- AA genotype, OR (95%CI) = 2.92 (1.61-4.29).CONCLUSIONS:We found that the G allele of rs2228527 and the G allele of rs2228529 within NER gene, interaction between rs2228529 and current smoking were all associated with increased NMSC risk.

Objective To evaluate effects of thalidomide on proliferative activity of as well as expressions of collagenⅠα1 andⅢα1 mRNAs and collagenⅠα1 protien in human dermal fibroblasts(HDFs), and to preliminarily explore the potential role of thalidomide in the fight against dermal fibrosis. Methods HDFs were isolated from the foreskin of a healthy young man, and subjected to primary culture. The fourth?passage HDFs were used in the following experiment. Some HDFs were divided into 3 groups to be treated with 10?3, 10?4 and 10?5 mol/L thalidomide respectively, and other HDFs treated with DMEM alone served as the blank control group. After 24?hour culture, cell counting kit?8 (CCK?8)assay was performed to evaluate the proliferative activity of HDFs, fluorescence?based quantitative PCR to measure the mRNA expressions of collagen Ⅰα1 and Ⅲα1, and Western?blot analysis to determine the protein expression of collagenⅠα1. Results Compared with the blank control group, the 10?3?and 10?4?mol/L thalidomide groups both showed significantly decreased cell survival rates(77.40%± 4.25%and 88.56%± 6.43%vs. 100.00%± 6.74%, both P<0.05), but the 10?5?mol/L thalidomide group showed no significant difference(96.66%± 1.098%, P>0.05). Compared with the blank control group, the 10?3?, 10?4?and 10?5?mol/L thalidomide groups all showed significantly lower mRNA and protein expressions of collagen Ⅰα1(mRNA:0.279 ± 0.025, 0.427 ± 0.040 and 0.658 ± 0.032 vs. 1.016 ± 0.003;protein:0.279 ± 0.020, 0.926 ± 0.048 and 1.523 ± 0.027 vs. 1.773 ± 0.059;all P<0.05). In addition, the mRNA expressions of collagenⅢα1 were also significantly weaker in the 10?3?, 10?4?and 10?5?mol/L thalidomide groups compared with the blank control group(0.551 ± 0.039, 0.756 ± 0.025 and 0.826 ± 0.018 vs. 0.988 ± 0.012, all P<0.05). Conclusion Thalidomide within a certain range of concentrations can inhibit the proliferation of HDFs, as well as expressions of collagenⅠα1 mRNA and protein and collagenⅢα1 mRNA.

Melanoma is the deadliest form of skin cancer, and BRAFV600E is a driver mutation that promotes melanoma growth and survival. PLX4032 is the first effective compound in clinical use for the treatment of patients with mutant BRAFV600. However, resistance to PLX4032 develops quickly within months. Activation of a series of receptor tyrosine kinases, including the platelet-derived growth factor receptor (PDGFR), has been identified to be the underlying mechanism for development of resistance to PLX4032. In this work, we investigated the anticancer activity of tyrphostin AG1296, a PDGFR inhibitor, in melanoma, especially PLX4032-resistant melanoma. We found that tyrphostin AG1296 could effectively reduce the viability of both PLX4032-sensitive and PLX4032-resistant melanoma cells. There is an additive effect between tyrphostin AG1296 and PLX4032 in reducing cell viability. Tyrphostin AG1296 induced dramatic apoptosis in PLX4032-resistant cells, and also dramatically inhibited migration of PLX4032-resistant cells. Importantly, tyrphostin AG1296 significantly suppressed A375R tumor growth in vivo. This is the first report on the anticancer activity of tyrphostin AG1296 in melanoma. Tyrphostin AG1296 is a promising compound in the treatment of melanoma, especially for those who have developed resistance towards BRAF inhibitors, and might shed new light on melanoma therapy.

Actinic keratosis (AK) is a precancerous state of the skin, which shows epidermal dysplasia of different degrees. The cellular DNA content and proliferative activity of the skin lesions in 27 cases of AK were analyzed with flow cytometry. The results showed that the PI (proliferating index) in AK was higher than that in normal skin (P\u003c0.05). Among 27 eases of AK, the cellular DI (DNA index) of 8 cases of severely dysplastie AK was higher than the rest 19 cases (P\u003c0.05). The results suggest that the cells in the skin lesions of AK proliferate actively, and the higher the degree of dysplasia showed in AK the more the significance of aberration of DNA content.\r\n\r\nKey words: \r\nKeratosis actinic; DNA