Further developments of ß,γ-unsaturated α-ketoesters as versatile synthons in asymmetric catalysis.

ß,γ-Unsaturated α-ketoesters prove to be versatile organic synthons participating in diverse catalytic asymmetric transformations with the breathtaking development of organo-catalysis, new catalytic systems including ingenious chiral ligands as well as Lewis acid cations. The highly efficient creation of stereogenic centers with excellent enantioselectivity is not a surprise, but owes to the bidentate coordination of its unique 1,2-dicarbonyl motif to artful chiral messenger, establishing a rigid system for the precise chiral-identification of the attack. In the past five years, various reaction modes of ß,γ-unsaturated α-ketoesters have been developed, involving their multiple reaction sites, such as the carbon-carbon double bond (C=C), the carbonyl group (C=O), the entire C=C-C=O fragment, and the ester group. In this review, we summarize the state-of-the-art catalytic asymmetric reactions of ß,γ-unsaturated α-ketoesters, to provide an updated overview to chemists working in this and related fields, facilitating their discoveries in asymmetric catalysis, natural products synthesis, and drug development.

Vascular endothelial growth factor (VEGF) gene polymorphisms and breast cancer risk in a Chinese population.

Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumours. Associations between three VEGF gene polymorphisms (-634 G/C, +936 C/T, and +1612 G/A) and breast cancer risk have been extensively studied, but the currently available results are inconclusive. Our aim was to investigate associations between three VEGF gene polymorphisms and breast cancer risk in Chinese Han patients. We performed a hospital-based case-control study including 680 female incident breast cancer patients and 680 female age-matched healthy control subjects. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the three VEGF gene polymorphisms. We observed that women carriers of +936 TT genotypes [odds ratio (OR) =0.46, 95% confidence interval (CI) = 0.28, 0.76; P=0.002] or 936 T-allele (OR=0.81, 95% CI= 0.68, 0.98; P=0.03) had a protective effect concerning the disease. Our study suggested that the +1612G/A polymorphism was unlikely to be associated with breast cancer risk. The -634CC genotype was significantly associated with high tumor aggressiveness [large tumor size (OR=2.63, 95% CI=1.15, 6.02; P=0.02) and high histologic grade (OR=1.47, 95% CI= 1.06, 2.03; P=0.02)]. The genotypes were not related with other tumor characteristics such as regional or distant metastasis, stage at diagnosis, or estrogen or progesterone receptor status. Our study revealed that the VEGF -634 G/C and +936 C/T gene polymorphisms may be associated with breast cancer in Chinese Han patients.

Aspirin use and breast cancer risk: a meta-analysis.

Animal and in vitro studies suggest that the use of aspirin may be associated with reduced risk for breast cancer, but results from these studies of the association have been inconsistent. The objective of this meta-analysis was to quantitatively summarize the current evidence for such a relationship. We searched MEDLINE for studies of aspirin use and breast cancer risk that were published in any language, from January 1, 1966, to July 1, 2011. A total of 33 studies (19 cohort studies, 13 case-control studies, and 1 randomized controlled trial [RCT]) that included 1,916,448 subjects were identified. We pooled the relative risks from individual studies using a random-effects model, heterogeneity, and publication bias analyses. In a pooled analysis of all studies, aspirin use was associated with reduced risk for breast cancer (odds ratio [OR] = 0.86, 95% confidence interval [CI] = 0.81, 0.92). In the subgroup analysis by study design, results were similar except for RCT (OR = 0.98, 95% CI = 0.87, 1.09). In conclusion, this meta-analysis indicated that regular use of aspirin may be associated with reduced risk of breast cancer. More RCT were needed to confirm this association in the future.