A Powerful Chiral Super Brønsted C-H Acid for Asymmetric Catalysis.

A new type of chiral super Brønsted C-H acids, BINOL-derived phosphoryl bis((trifluoromethyl)sulfonyl) methanes (BPTMs), were developed. As compared to widely utilized BINOL-derived chiral phosphoric acids (BPAs) and N-triflyl phosphoramides (NTPAs), BPTMs displayed much higher Brønsted acidity, resulting in dramatically improved activity and excellent enantioselectivity as demonstrated in catalytic asymmetric Mukaiyama-Mannich reaction, allylic amination, three-component coupling of allyltrimethylsilane with 9-fluorenylmethyl carbamate and aldehydes, and protonation of silyl enol ether. These new strong Brønsted C-H acids have provided a platform for expanding the chemistry of asymmetric Brønsted acid catalysis.

The long non-coding RNA HOTTIP promotes progression and gemcitabine resistance by regulating HOXA13 in pancreatic cancer.

BACKGROUND: The human genome encodes many long non-coding RNAs (lncRNAs). However, their biological functions, molecular mechanisms, and the prognostic value associated with pancreatic ductal adenocarcinoma (PDAC) remain to be elucidated. Here, we identify a fundamental role for the lncRNA HOXA transcript at the distal tip (HOTTIP) in the progression and chemoresistance of PDAC. METHODS: High-throughput microarrays were performed to detect the expression profiles of lncRNAs and messenger RNAs in eight human PDAC tissues and four pancreatic tissues. Quantitative real-time PCR was used to determine the levels of HOTTIP and HOXA13 transcripts in PDAC cell lines and 90 PDAC samples from patients. HPDE6 cells (immortalized human pancreatic ductal epithelial cells) and corresponding adjacent non-neoplastic tissues were used as controls, respectively. The functions of HOTTIP and HOXA13 in cell proliferation, invasion, and epithelial-mesenchymal transition were evaluated by targeted knockdown in vitro. CCK-8 assays, colony formation assays, and xenografts in nude mice were used to investigate whether targeted silencing of HOTTIP could sensitize pancreatic cancer cells to gemcitabine. Immunohistochemistry was performed to investigate the relationship between HOXA13 expression and patient outcome. RESULTS: Microarray analyses revealed that HOTTIP was one of the most significantly upregulated lncRNAs in PDAC tissues compared with pancreatic tissues. Quantitative PCR further verified that HOTTIP levels were increased in PDAC cell lines and patient samples compared with controls. Functionally, HOTTIP silencing resulted in proliferation arrest by altering cell-cycle progression, and impaired cell invasion by inhibiting epithelial-mesenchymal transition in pancreatic cancer. Additionally, inhibition of HOTTIP potentiated the antitumor effects of gemcitabine in vitro and in vivo. Furthermore, knockdown of HOXA13 by RNA interference (siHOXA13) revealed that HOTTIP promoted PDAC cell proliferation, invasion, and chemoresistance, at least partly through regulating HOXA13. Immunohistochemistry results revealed that higher HOXA13 expression was correlated with lymph node metastasis, poor histological differentiation, and decreased overall survival in PDAC patients. CONCLUSIONS: As a crucial tumor promoter, HOTTIP promotes cell proliferation, invasion, and chemoresistance by modulating HOXA13. Therefore, the HOTTIP/HOXA13 axis is a potential therapeutic target and molecular biomarker for PDAC.

Green tea consumption and risk of pancreatic cancer: a meta-analysis.

Emerging laboratory and animal studies indicate that green tea inhibits development and progression of pancreatic cancer, but evidence from epidemiologic studies appears inconsistent and inconclusive. A meta-analysis summarizing published case-control and cohort studies was performed to evaluate the association of green tea consumption with risk of pancreatic cancer. Pertinent studies were identified by a search of PubMed and EMBASE up to April 2014. A random-effects model was assigned to compute summary risk estimates. A total of three case-control studies and five prospective studies were included, comprising 2317 incident cases and 288209 subjects. Of them, three studies were from China and the reminders were conducted in Japan. Overall, neither high vs. low green consumption (odds ratio (OR) = 0.99, 95% confidence interval [CI] = 0.78-1.25), nor an increase in green tea consumption of two cups/day (OR = 0.95, 95% CI = 0.85-1.06) was associated with risk of pancreatic cancer. The null association persisted when the analysis was stratified by sex or restricted to non-smokers. In the stratification by study location, the summary OR for the studies from China and for those from Japan was 0.77 (95% CI = 0.60-0.99) and 1.21 (95% CI = 0.94-1.54), respectively (P for differences = 0.04). Cumulative epidemiologic evidence suggests that green tea consumption is not associated with pancreatic cancer.