Identifying therapeutic targets for cancer treatment relies on consistent changes within particular types or sub-types of malignancy. The ability to define either consistent changes or sub-types of malignancy is often masked by tumor heterogeneity. To elucidate therapeutic targets in cutaneous squamous cell carcinoma (cSCC), the most frequent skin neoplasm with malignant potential, we have developed an integrated approach to gene expression profiling beginning with primary keratinocytes in culture. Candidate drivers of cSCC development were derived by first defining a set of in vitro cancer genes and then comparing their expression in a range of clinical data sets containing normal skin, cSCC and the benign hyper-proliferative condition psoriasis. A small interfering RNA (siRNA) screen of the resulting 21 upregulated genes has yielded targets capable of reducing xenograft tumor volume in vivo. Small-molecule inhibitors for one target, Polo-like kinase-1 (PLK1), are already in clinical trials for other malignancies, and our data show efficacy in cSCC. Another target, C20orf20, is identified as being overexpressed in cSCC, and siRNA-mediated knockdown induces apoptosis in vitro and reduces tumor growth in vivo. Thus, our approach has shown established and uncharacterized drivers of tumorigenesis with potent efficacy as therapeutic targets for the treatment of cSCC.

Introduction For many years, erectile dysfunction (ED) has been considered as a complication of cardiovascular disease (CVD) or regarded as a late consequence of generalized arterial disease. However, a growing body of evidence suggests that ED is an early manifestation of atherosclerosis and a precursor to systemic vascular disease. Aim We conducted a meta-analysis to evaluate the association between ED and the risk of CVD events. Methods Relevant studies published between January 1966 and September 2009 were identified by searching Medline, Embase, and The Cochrane Library. Studies were selected using a prior defined criteria. The strength of the relationship between ED and CVD events was assessed by adjusted relative risks (RRs). Main Outcome Measures The adjusted RRs of CVD events. Results A total of 45,558 participants from seven cohort studies (eight full-text articles) were identified in this meta-analysis. The studies provided adjusted RRs estimates for ED subjects comparing with health subjects, leading to a pooled adjusted RR of 1.47 (95% confidence interval [CI], 1.29–1.66, P <0.001; P for heterogeneity=0.152; I† = 36.2%) for CVD events. The risks of CVD, all-cause mortality and myocardial infarction were 1.41 (95% CI, 1.22–1.64 P <0.001), 1.23 (95% CI, 1.02–1.48; P = 0.034), and 1.43 (95% CI, 1.10–1.85 P = 0.007), respectively. The overall adjusted RR decreased significant from 1.63 (<7 years) to 1.37 (≥7 years) along with the elongation of follow-up. Conclusions There is evidence of an increased risk of CVD events for patients with ED. Patients who are discovered to have ED are supposed to be thoroughly assessed for cardiovascular risk and occult systemic vascular disease.

Abstract. The long non-coding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) is an oncogenic lncRNA in bladder cancer, and its upregulation is associated with enhanced cell invasion. However, the underlying mechanism remains to be elucidated. The present study demonstrated that UCA1 was positively associated with cell invasion ability and promoted epithelial-mesenchymal transition (EMT) of bladder cancer cells by inducing high mobility group box 1 (HMGB1). Furthermore, bioinformatics and luciferase reporter assays demonstrated binding sites of the tumor suppressive miR-143 within UCA1 and the 3'untranslated region of HMGB1. UCA1 negatively regulated miR-143 expression in a dose-dependent manner in bladder cancer cells. In addition, UCA1 and HMGB1 were upregulated and miR-143 was downregulated in bladder cancer specimens. Overall, the data suggested that UCA1 may promote the invasion and EMT of bladder cancer cells by regulating the miR-143/HMGB1 pathway, which exhibits an important regulatory role in the pathology of bladder cancer.

Summary We present a web server, GenCLiP 3, which is an updated version of GenCLiP 2.0 to enhance analysis of human gene functions and regulatory networks, with the following improvements: i) accurate recognition of molecular interactions with polarity and directionality from the entire PubMed database; ii) support for Boolean search to customize multiple-term search and to quickly retrieve function related genes; iii) strengthened association between gene and keyword by a new scoring method; and iv) daily updates following literature release at PubMed FTP. Availability The server is freely available for academic use at: http://ci.smu.edu.cn/genclip3/. Supplementary information Supplementary data are available at Bioinformatics online.