[Progress in the study of small molecule inhibitors of HSP90].

HSP90, which is the biomarker of cell stress and endogenous protective protein, functions as a molecular chaperone. Many client proteins of HSP90, including EGFR, Met, Raf-1, IKK and p53, play important roles in the occurrence and development of tumor. Binding of HSP90 inhibitors triggers the deactivation of HSP90, resulting in client protein degradation, and hence inhibits the tumor growth by blocking multiple targets involved in signaling of tumor proliferation. This review summarizes recent development of small molecule inhibitors bound to N-terminal of HSP90.

miR-202 suppresses cell proliferation in human hepatocellular carcinoma by downregulating LRP6 post-transcriptionally.

MicroRNAs have emerged as important regulators of carcinogenesis. In the current study, we observed that microRNA-202 (miR-202) is downregulated in hepatocellular carcinoma (HCC) cells and tissues, indicating a significant correlation between miR-202 expression and HCC progression. Overexpression of miR-202 in HCC cells suppressed cell proliferation and tumorigenicity, while downregulation of miR-202 enhanced the cells' proliferative capacity. Furthermore, we identified low-density lipoprotein receptor-related protein 6 (LRP6) as a direct target of miR-202. miR-202 suppresses the expression of LRP6 by binding to the 3'-untranslated region (UTR) of its mRNA. Finally, we found that silencing the expression of LRP6 is the essential biological function of miR-202 during HCC cell proliferation. Collectively, our findings reveal that miR-202 is a potential tumor suppressive miRNA that participates in carcinogenesis of human HCC by suppressing LRP6 expression.

Serum C-reactive protein and risk of lung cancer: a case-control study.

Recent advances in lung cancer biology presuppose their inflammatory origin. Thus, CRP is regarded to play a key role in the development of lung cancer. Nevertheless, this interesting hypothesis and the role of inflammation in tumor biology remain complex and incompletely sure. Meanwhile, the association between CRP and risk of lung cancer was not stable in many published results. This study was conducted to evaluate the association between serum CRP and SNPs in the aspect of lung cancer risks, in order to assess its possible diagnostic and prognostic importance. We conducted a case-control study of 96 patients newly diagnosed of lung cancer and 124 controls in this research. Controls were individuals matched to lung cancer cases on age, gender and tobacco use. In order to increase the statistical power, never smokers were matched to patients by using a 3:1 ratio, whereas former and current smokers were matched equal to the patients. CRP concentrations were measured using a chemiluminescent immunoassay, and SNPs were assessed at five loci within the CRP gene (rs1417938, rs1800947, rs1205, rs2808630 and rs3093077) as part of a Golden Gate assay. Logistic regression was used to calculate OR and 95 % CI for lung cancer. CRP concentrations tended to be in positive association with lung cancer risk in our research (Q4 vs Q1: OR = 2.11, 95 % CI, 1.66-2.91, p trend < 0.01). Although CRP SNPs were related to CRP levels, they were not associated with lung cancer risk. In combined analyses, we observed a significant interaction (p (interaction) = 0.02) that positive associations were suggestive in younger (Q4 vs Q1: OR = 1.65, 95 % CI, 1.02-2.67, p trend = 0.18) and older individuals (Q4 vs Q1: OR = 2.66, 95 % CI, 1.45-3.98 p trend = 0.42). The risks of lung cancer were higher with elevated CRP levels among former smokers and current smokers. High levels of CRP were associated with increasing lung cancer risk, suggesting that CRP could be used as surrogate biomarker of angiogenesis and prognosis in lung cancer.

ScafBank: a public comprehensive Scaffold database to support molecular hopping.

AIM: The search for molecules whose bioactivities are similar to those of given compounds or to optimize the initial lead compounds from high throughput screening has attracted increasing interest in recent years. Our goal is to provide a publically searchable database of scaffolds out from a large collection of existing chemical molecules. RESULTS: Although a number of in silico methods have emerged to facilitate this process, which has become known as "scaffold hopping" or "molecular hopping", there is an urgent need for a database system to provide such valuable data in the drug design field. Here we have systematically analyzed a collection of commercially available small molecule databases and a bioactive compound database to identify unique scaffolds and we have built a publically searchable database. The analysis of approximately 4,800,000 of these compounds identified 241,824 unique scaffolds, which are stored in a relational database (http://202.127.30.184:8080/db.html). Each entry in the database is associated with a molecular occurrence and includes its distribution of molecular properties, such as molecular weight, logP, hydrogen bond acceptor number, hydrogen bond donor number, rotatable bond number and ring number. More importantly, for scaffolds derived from the bioactive compounds database, it also contains the original compounds and their target information. CONCLUSION: This Web-based database system could help researchers in the fields of medicinal and organic chemistry to design novel molecules with properties similar to the original compounds, but built on novel scaffolds.