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Background: Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease mainly characterized by dryness, fatigue, and pain. Current therapies for SS in Western medicine are limited. The purpose of this clinical study was to explore the efficacy and safety of using a traditional Chinese medicine (TCM) formula on patients with primary SS.Methods: We performed a 12-week, randomized, double-blinded, placebo-controlled clinical trial at Chung Shan Medical University Hospital. We included 42 patients with SS between the ages of 20 and 80 years who met the classification criteria of the American and European Consensus Group (AECG). Patients who had other severe systemic manifestations or diseases were excluded from this trial. After screening, patients were randomly assigned to the TCM treatment group or placebo group (ratio of 2:1). We treated the TCM group with 6 g of Gan-Lu-Yin granules after breakfast and 6 g of Jia-Wei-Xiao-Yao-San combined with 1 g of Suan-Zao-Ren-Tang and 1 g of Ye-Jiao-Teng every night after dinner. Patients in the control group were treated with a placebo with the same appearance and flavor but only one-tenth the dosage of that received by the treatment group. The European League Against Rheumatism Sjogren's Syndrome Patient-Reported Index (ESSPRI) was used as the primary endpoint at week 12. Secondary endpoints were the Sjogren's Syndrome Disease Activity Index (SSDAI), physician global assessment (PGA), visual analogue scale (VAS), Multidimensional Fatigue Inventory, Medical Outcomes Survey Short Form-36, and the Pittsburgh Sleep Quality Score (PSQI). Adverse events were also recorded.Results: Of the 42 randomized patients, 28 patients were assigned to the TCM treatment group and 14 patients were assigned to the controlled group. During the study period, 5 patients withdrew from the TCM group and 7 withdrew from the control group. At week 12, the ESSPRI scores of both groups had improved. The ESSPRI score of the treatment group decreased by 0.62 (95% CI P = 0.557) and that of the placebo group decreased by 0.91 (P = 0.557). However, no significant difference was observed between the two groups. Sleep duration in the PSQI was −0.61, which exhibited an improvement of more than the −0.21 compared with the placebo group (P = 0.914).Conclusion: At week 12, the ESSPRI scores did not reveal that the use of the TCM formula was efficacious for treating patients with Sjogren's syndrome. However, the PSQI scores indicated that this formula could prolong patient sleep duration. We also found that this formula could decrease the blood pressure of patients.

The concept that lung adenocarcinoma is less related to smoking behavior than lung squamous cell carcinoma may be due to the fact that a considerable number of LAC patients do not have smoking habit. However, this argument may mislead the effect of tobacco smoke on LAC because it ignores the potential effects of environmental smoking that cause second hand smoking in non-smokers. In Taiwan, 70% of female LAC patients would encounter heavy smokers either at home or in working place, suggesting that environmental smoke may have substantial effects than we thought. Transcriptional deregulation at the chromosome 15q25 locus revealed an association between the gene encoding CHRNA5 with lung adenocarcinoma risk. It has been showed that overexpression of the genes encoded in this locus in mice increased the sensitivity to nicotine. In this report, we found that nAChR α5, but neither nAChR α7 or nAChR α9 that have been respectively shown to mediate tumorigenic alterations in lung SCC and breast cancer cells, was differentially expressed between tumor and non-tumor specimens of LAC patient specimens. Knockdown of nAChR α5 in LAC cell lines resulted in decreased cell proliferation rate as well as cell migrating and invasive capabilities. In these nAChR α5-knockdown cells, low dose (10 nM) nicotine was not able to significantly increase cell proliferation and motility, while low dose nicotine enhanced both abilities of cells when nAChR α5 expressed. Colony formation assay indicated that nAChR α5 maintained cell survival and prevent contact inhibition in LAC cells when encountering low serum stress condition. Through molecular analysis, we showed that nAChR α5 positively regulates epithelial-mesenchymal transition factors such as Snail and Slug, and negatively regulates E-cadherin. Animal experiment showed a severely suppressed tumor growth in mice transplanted with LAC cells with nAChR α5 being knocked down, in comparison to mice transplanted with parental cells. These data demonstrated a crucial role of nAChR α5 in low-dose nicotine-dependent regulation of tumorigenesis in LAC. It is, for the first time, a study of mechanism in response to low dose nicotine that implies the regulatory pathway underlying the effect of environmental nicotine. Citation Format: Mong-Lien Lotus Wang, Yi-Fan Hsu, Chih-Hsuan Liu, Cheng-Wen Wu. Nicotinic acetylcholine receptor α5 mediates low-dose nicotine-dependent regulation of tumorigenesis in lung adenocarcinoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4992. doi:10.1158/1538-7445.AM2015-4992

Background Cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), increases survival in patients with advanced EGFR-positive non-small cell lung cancer when administrated in combination with chemotherapy. In this study, we investigated the role of complement activation in the antitumor mechanism of this therapeutic drug. Results EGFR-expressing lung cancer cell lines were able to bind cetuximab and initiate complement activation by the classical pathway, irrespective of the mutational status of EGFR. This activation led to deposition of complement components and increase in complement-mediated cell death. The influence of complement activation on the activity of cetuximab in vivo was evaluated in xenografts of A549 lung cancer cells on nude mice. A549 cells express wild-type EGFR and have a KRAS mutation. Cetuximab activity against A549 xenografts was highly dependent on complement activation, since complement depletion completely abrogated the antitumor efficacy of cetuximab. Moreover, cetuximab activity was significantly higher on A549 cells in which a complement inhibitor, factor H, was genetically downregulated. Conclusions We demonstrate for the first time that the in vivo antitumor activity of cetuximab can be associated with a complement-mediated immune response. These results may have important implications for the development of new cetuximab-based therapeutic strategies and for the identification of markers that predict clinical response.