Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1.

In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene; P=8.82×10(-9)), rs10474352 at 5q14.

New multi-target-directed small molecules against Alzheimer's disease: a combination of resveratrol and clioquinol.

Alzheimer's disease (AD) is currently one of the most difficult and challenging diseases to treat. Based on the ‘multi-target-directed ligands’ (MTDLs) strategy, we designed and synthesised a series of new compounds against AD by combining the pharmacophores of resveratrol and clioquinol. The results of biological activity tests showed that the hybrids exhibited excellent MTDL properties: a significant ability to inhibit self-induced β-amyloid (Aβ) aggregation and copper(II)-induced Aβ aggregation, potential antioxidant behaviour (ORAC-FL value of 0.

Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression.

Pregnancy during breast cancer: does a mother's parity status modify an offspring's mortality risk?

To assess whether children born to primiparous women around the time of a breast cancer diagnosis have an increased mortality risk. From the merged Swedish Multi-Generation and Cancer Registers, we identified 49,750 eligible children whose mother was diagnosed with breast cancer between 1958 and 2010. Mortality rates in offspring were compared to the background population using standardized mortality ratios (SMR), adjusted for calendar year of birth, attained age, and sex, and calculated for each category of timing of delivery (before, around, or after mother's diagnosis) and mother's parity status.

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study.

Introduction: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.

Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium.

Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

Background: In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia.

Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify carriers in those with presumed low risk by family history.

Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered more than 20 years ago, there remains a gap in the availability of genetic counselling and genetic testing in Asian countries because of cost, access and inaccurate reporting of family history of cancer. In order to improve access to testing, we developed a rapid test for recurrent mutations in our Asian populations. In this study, we designed a genotyping assay with 55 BRCA1 and 44 BRCA2 mutations previously identified in Asian studies, and validated this assay in 267 individuals who had previously been tested by full sequencing.

Synthesis, structure, and catalytic activity of novel trinuclear rare-earth metal amido complexes incorporating μ-η5:η1 bonding indolyl and μ3-oxo groups.

The reactions of different pyrrolyl-functionalized indoles with rare-earth metal(III) amides [(Me3Si)2N]3RE(III)(μ-Cl)Li(THF)3 (RE = Yb, Er, Dy, Eu, Y) produced different kinds of rare-earth metal amido complexes. Reactions of N-((1H-pyrrol-2-yl)methylene)-2-(1H-indol-3-yl)ethanamine with rare-earth metal amides [(Me3Si)2N]3RE(III)(μ-Cl)Li(THF)3 (RE = Yb, Er, Dy, Eu, Y) in toluene or THF at temperatures of 75-80 °C afforded the novel trinuclear rare-earth metal amido complexes incorporating the indolyl ligand in μ-η(5):η(1) bonding modes and a μ3-O group, which is believed to originate from cleavage of the THF ring based on experimental results. Reactions of 2-(1H-indol-3-yl)-N-((1-methyl-1H-pyrrol-2-yl)methylene)ethanamine with rare-earth metal(III) amides [(Me3Si)2N]3RE(III)(μ-Cl)Li(THF)3 (RE = Yb, Dy) produced mononuclear ytterbium and dysprosium amides having the indolyl ligand in an η(1) bonding fashion.

Fine-scale mapping of the FGFR2 breast cancer risk locus: putative functional variants differentially bind FOXA1 and E2F1.

The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry studies (n = 2,028) from the Breast Cancer Association Consortium. We identified three statistically independent risk signals within the locus.

Clinical outcome of childhood lymphoblastic lymphoma in Shanghai China 2001-2010.

Background: This retrospective cohort study analysed the clinical characteristics and outcomes of patients with childhood lymphoblastic lymphoma (LBL) treated in Shanghai, China.

Procedure: From 2001 to 2010, 108 evaluable patients ≤16 years of age who were newly diagnosed with biopsy-proven LBL were treated with one of three treatment protocols: CCCG-99, SCMC-T-NHL-2002, or LBL-CHOF-2006.

Results: Two patients had Stage I disease, 5 had Stage II, 55 had Stage III, and 46 had Stage IV.

[Application of excitation-emission matrix spectrum combined with parallel factor analysis in dissolved organic matter in East China Sea].

Using excitation-emission matrix spectrum(EEMs) combined with parallel factor analysis (PARAFAC) examine the fluorescent components feature of dissolved organic matter (DOM) sampled from East China Sea in the summer and autumn was examined. The type, distribution and origin of the fluorescence dissolved organic matter were also discussed. Three fluorescent components were identified by PARAFAC, including protein-like component C1 (235, 280/330), terrestrial or marine humic-like component C2 (255, 330/400) and terrestrial humic-like component C3 (275, 360/480).

Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers.

Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element.

Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls.

In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously.

Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS).

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants.

Large-scale genotyping identifies 41 new loci associated with breast cancer risk.

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping.

Birth rates among female cancer survivors: a population-based cohort study in Sweden.

Background: More women of fertile age are long-term survivors of cancer. However, population-based data on birth rates of female cancer survivors are rare.

Methods: A total of 42,691 women ≤ 45 years with a history of cancer were identified from the Swedish Multi-Generation Register and the Swedish Cancer Register, for whom relative birth rates were calculated as compared to the background population, ie, standardized birth ratios (SBRs).

Preparation of 3D network Na2Ti2O4(OH)2 nanotube film and study on formation mechanism of nanotubes and light absorption properties.

The 3D network Na2Ti2O4(OH)2 nanotube film was prepared by combining interface chemical reaction with hydrothermal reaction. It can be readily indexed based on an orthorhombic system Na2Ti2O4(OH)2 (JCPDS, 47-0124), corresponding with (200), (110), (600), and (020). The nanotubes are commonly multiwalled with a diameter about 40 nm, and a length more than 2000 nm.

Gene polymorphisms of ABC transporters are associated with clinical outcomes in children with acute lymphoblastic leukemia.

Introduction: Genetic variability affects clinical outcome in pediatric acute lymphocytic leukemia (ALL) patients. Evaluating gene polymorphisms in ABC transporters could help identify relapse risk and predict outcome.

Material And Methods: The SNaPshot SNP technique was used to analyze single-nucleotide polymorphisms (SNPs) in the multidrug transporter 1 (MDR1), multidrug resistance associated proteins (MRP1, MRP2) and breast cancer resistance protein (BCRP) genes of 82 pediatric ALL patients.

A small molecule agonist of EphA2 receptor tyrosine kinase inhibits tumor cell migration in vitro and prostate cancer metastasis in vivo.

During tumor progression, EphA2 receptor can gain ligand-independent pro-oncogenic functions due to Akt activation and reduced ephrin-A ligand engagement. The effects can be reversed by ligand stimulation, which triggers the intrinsic tumor suppressive signaling pathways of EphA2 including inhibition of PI3/Akt and Ras/ERK pathways. These observations argue for development of small molecule agonists for EphA2 as potential tumor intervention agents.

[Fluorescence characteristics of dissolved organic matter in the sea nearby Zhangzi island].

Fluorescence excitation-emission matrix spectroscopy (EEMs) was parsed, using parallel factor analysis (PARAFAC) to parse the model, to examine the fluorescent components and their distributing variations of dissolved organic matter (DOM) sampled from the nearby sea area of Zhangzi island. The identified components in different seasons were almost similar, including humic-like components C1(265/440 nm), C2(410-450/520-550 nm) and protein-like component C3(230, 280/330 nm), and the good linearity proved that they had the same sources or some relationships. Furthermore, all of the 3 components in different water layers and different seasons showed higher fluorescence intensity around the Zhangzi island.

A phantom-based calibration method for digital x-ray tomosynthesis.

Objective: The purpose of this study was to develop a phantom-based experimental calibration method to minimize the reconstruction artifacts for the geometric misalignments of the digital tomosynthesis prototype.

Methods: A calibration phantom with ten fiducial markers was designed. Using this calibration phantom, the projection matrices of an experimental digital tomosynthesis prototype were acquired from each projection view under a series of misalignment conditions.

[Preparation and luminescent performance of Tb3+ doped SiO2 core-shell nanoparticles].

The authors synthesized the core-shell nanoparticles of SiO2-coated SiO2:Tb3+ by using sol-gel method (SiO2:Tb3+ @SiO2), and studied the influence of core-shell ratio and preparation craftwork on its luminescence properties. The photograph of TEM and EDS showed that SiO2:Tb3+ were coated successfully by SiO2. The authors found that the samples of SiO2:Tb3+ @SiO2 prepared by mixing of core and shell after shell aging with the ratio of core/shell being 1.

Dynamic porous coordination polymer based on 2D stacked layers exhibiting high sorption selectivity for CO2.

A new dynamic porous coordination polymer (PCP) [Ni(dcpy)(bipy)(0.5)(H(2)O)]·1.5H(2)O (1) was synthesized by assembly of 3-(2',5'-dicarboxylphenyl)pyridine (dcpy), 4,4'-bipyridine (bipy) and NiSO(4)via solvothermal, hydrothermal and microwave methods, displaying a wavelike 2D stacked layer framework.

NMR structure of a heterodimeric SAM:SAM complex: characterization and manipulation of EphA2 binding reveal new cellular functions of SHIP2.

The sterile alpha motif (SAM) for protein-protein interactions is encountered in over 200 proteins, but the structural basis for its interactions is just becoming clear. Here we solved the structure of the EphA2-SHIP2 SAM:SAM heterodimeric complex by use of NMR restraints from chemical shift perturbations, NOE and RDC experiments. Specific contacts between the protein surfaces differ significantly from a previous model and other SAM:SAM complexes.