GlcNAcylation, a dynamic posttranslational modification, is involved in a wide range of biological processes and some human diseases. Although there is emerging evidence that some tumor-associated proteins are modified by GlcNAcylation, the role of GlcNAcylation in tumor progression remains unclear. Here, we show that GlcNAcylation enhances the migration/invasion of breast cancer cells in vitro and lung metastasis in vivo. The decrease of cell surface E-cadherin is the molecular mechanism underlying GlcNAcylation-induced breast cancer metastasis. p120 and β-catenin, but not E-cadherin, are GlcNAcylated; the GlcNAcylation of p120 and β-catenin might play roles in the decrease of cell surface E-cadherin. Moreover, immunohistochemistry analysis indicated that the global GlcNAcylation level in breast tumor tissues is elevated significantly as compared with that in the corresponding adjacent tissues; further, GlcNAcylation was significantly enhanced in metastatic lymph nodes compared with their corresponding primary tumor tissues. This is the first report to clearly elucidate the roles and mechanisms whereby GlcNAcylation influences the malignant properties of breast cancer cells. These results also suggest that GlcNAcylation might be a potential target for the diagnosis and therapy of breast cancer. Cancer Res; 70(15);

a b s t r a c tSyndrome differentiation (Bian Zheng) in traditional Chinese medicine (TCM) is the comprehensive analysis of clinical information gained by the four main diagnostic TCM procedures: observation, listening, questioning, and pulse analysis, and it is used to guide the choice of treatment either by acupuncture and/or TCM herbal formulae, that is, Fufang. TCM syndrome differentiation can be used for further stratification of the patients' conditions with certain disease, identified by orthodox medical diagnosis, which could help the improvement of efficacy of the selected intervention. In modern TCM research it is possible to integrate syndrome differentiation with orthodox medical diagnosis leading to new scientific findings in overall medical diagnosis and treatment. In this review, the focus is to screen published evidence on the role of syndrome differentiation in modern TCM research with particular emphasis on basic and clinical research as well as, pharmacological evaluation of TCM herbal formulary for drug discovery.

No abstract

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.T he incidence of chromosomal abnormalities is as high as 1 in 160 live births in the United States (1) or 1 in 60 in China (2). The incidence increases with maternal age and can reach 2.5% with maternal age over 35 in China (2). Among autosomal abnormalities, Down syndrome (trisomy 21), Edward syndrome (trisomy 18), and Patau syndrome (trisomy 13) are most compatible with survival and therefore the most clinically significant. Sex chromosome aneuploidies occur in 1 in 500 male births and 1 in 850 female births in the United States (3-6) and 1 in 450 in China (2). Turner's syndrome (45,X), Klinefelter's syndrome (47, XXY), and 47,XYY syndrome are common sex chromosome aneuploidies that are associated with fetal loss, infertility, and language developmental delays, among other defects (7-9). Fetuses with aneuploidy account for 6-11% of all stillbirths and neonatal deaths (10). The incidence of Down syndrome increases significantly with maternal age, occurring in 25 in 100,000 births with maternal age over 35 and 30 in 100,000 births with maternal age over 40 in China. There were an estimated 27,000 babies with Down syndrome born in China in 2006, which caused an economic burden of $10,000 per capita, $48,300 per family, and a total of $2.1 billion per year (11). Diagnosis of fetal chromosomal aneuploidies is the most common indication for an invasive prenatal testing procedure such as chorionic villus sampling or amniocentesis. Curren...

Noninvasive prenatal testing (NIPT) using sequencing of fetal cellfree DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/ duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer.noninvasive prenatal testing | NIPT | maternal plasma DNA | cell-free DNA | semiconductor sequencing G enomic disorders are defined by loss, gain, or translocation of chromosomal material. Deletion/duplication syndromes are known to be associated with a wide range of structural and functional abnormalities (1), such as Cri du Chat Syndrome (5p deletion) (2) and DiGeorge Syndrome (22q11.2 deletion) (3). Such deletion/duplication syndromes can be reliably diagnosed prenatally from the DNA of fetal cells; fetal DNA may be assessed for chromosomal abnormalities by karyotyping, FISH, comparative genomic hybridization (CGH), and array-based technologies (4). G-banded karyotyping is the predominant technique for diagnosis of chromosomal abnormalities, but it is limited to resolution of 5-10 Mb (5, 6). Genomic disorders of a smaller size are more reliably detected by chromosomal microarray analysis (CMA), of which array CGH (aCGH) is an example.According to The American Society of Human Genetics, CMA has replaced the standard metaphase karyotype in postnatal assessment of individuals with developmental delay, intellectual disability, congenital anomalies, and autism (7). In December of 2013, The American Congress of Obstetricians and Gynecologists and the Society of Maternal Fetal-Medicine recommended pr...