Anti-metastatic mechanism of Tian-Xian Liquid (TXL) and its bioactive fractions in human colorectal cancer cells and xenograft models

Poster Session A: abstract no. 29Colorectal carcinoma is the second most prevalent cancer with an up-rising trend in Hong Kong (Hong Kong Cancer Registry). Traditional Chinese medicine acts as a complementary alternative for tumour therapy with minimal side-effects and traumatic injuries. Tian-Xian Liquid (TXL), one of the well-known natural medicinal herbal formulations, has been commercially used as an anticancer dietary supplement for a decade without known adverse effects. This study aimed to investigate the anti-metastatic property of TXL and its bioactive fractions [butanol fraction (BU), ethyl-acetate fraction (EA) and aqueous fraction (WA)] at molecular level on human colorectal cancer in vitro (HT-29 cancer cells) and in vivo (nude mice xenografts). For the cell model, TXL and its bioactive fractions have similar anti-proliferative effects by MTT assay. At 4-hour-incubation, IC50 values were obtained at 1% (V/V) TXL, 1.25% (V/V) BU, 5% (V/V) EA and 0.3125% (V/V) WA. At IC50, TXL and its bioactive fractions significantly reduced the MMP2 and MMP7 expressions at mRNA level by real-time PCR. At protein level, TXL, BU and EA correspondingly down-regulated MMP2 (active form) and MMP7 protein from 24 to 48 hours; TXL and BU also down-regulated VEGF protein expression; however, no such effect was found in WA-treated cells. Further, only TXL, EA and WA effectively inhibited the cell migration at 48 hours incubation by woundhealing assay. For the xenografts models, MMP2 and MMP7 mRNA expressions were reduced by TXL-, BU- and EA-treated xenografts; however no effects on MMP2 protein expression in all drug-treated xenografts. The VEGF protein expression was significantly down-regulated in TXL- and WA-treated xenografts. Further, TXL, BU and WA effectively inhibited the tumor growth without altering the body weight of the xenografts. In summary, the Chinese medicinal formulation, TXL, demonstrated the most effective anti-metastatic ability on human colorectal cancer in vitro and in vivo.published_or_final_versio

Genetic Variation in N-Methyl-D-Aspartate Receptor Subunit NR3A but Not NR3B Influences Susceptibility to Alzheimer's Disease

[[abstract]]Background: The administration of memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has clinically improved the cognitive function of patients with Alzheimer's disease ( AD), indicating that a disturbance in glutamatergic transmission might be involved in a predisposition to developing the disease. Aim: The potential association of polymorphisms in NMDA receptor subunits NR3A and NR3B, encoded by the GRIN3A and GRIN3B genes, with AD was investigated. Methods: We performed a case-control study. Two single nucleotide polymorphisms, 3104 G/A (rs10989563) and 3723 G/A (rs3739722), in the GRIN3A gene and 2 GRIN3B gene polymorphisms, 1210 C/T (rs4807399) and 1730 C/T (rs2240158), were studied. Results: Upon genotyping of the exonic polymorphism in the GRIN3A gene, the G allele was present at a higher rate than the A allele at position 3723 in AD patients compared with normal groups ( p < 0.05). Three haplotypes (designated Ht1-3) were identified from these 2 polymorphisms (3104 G/A and 3723 G/A), and the distribution of Ht2 (AG) differed between AD patients and controls ( p < 0.05). Additionally, from the 2 GRIN3B gene variants 1210 C/T and 1730 C/T analyzed, no strong association with AD was observed. Conclusion: These observations suggest that the genetic variation of the NR3A, but not NR3B, subunit of the NMDA receptor may be a risk factor for AD pathogenesis among the Taiwanese population. Copyright (C) 2009 S. Karger AG, Base

A Novel Genetic Variant of BMP2K Contributes to High Myopia

[[abstract]]Loss of eye growth regulation may cause myopia, because modulation of optic globe size is essential for the generation of normal optic power. Evidence has implied variations of BMP2 gene expression mediate ocular development and retinal tissue remodeling. Given BMP2 as a potential regulator involved in myopia development, we investigate whether gene BMP2-inducible kinase (BMP2K, BIKe), whose expression is up-regulated during BMP2-induced osteoblast differentiation, contributes to susceptibility of high myopia. Participants grouped into high myopia had a spherical equivalent greater than -6.00 D, compared with a control group of spherical equivalent less than -0.5 D. Genotyping of polymorphisms 1379 G/A (rs2288255) and 3171 C/G (rs-12507099), corresponding with 405 Gly/Ser and 1002 Thr/Ser variation in the BMP2K gene were determined by PCR-restriction fragment length polymorphism and associative study performed by comparing high myopic subjects and healthy controls. The frequency of A allele in the BMP2K gene 1379 G/A polymorphism showed a significant difference between cases and controls (P<0.001, OR = 2.99, 95% CI = 1.62-5.54) and subjects with either AA or AG genotype show higher risk than GG genotype (P<0.001, OR = 3.07, 95% CI = 1.59-5.92), while 3171 C/G polymorphism was not significant from this survey. These data suggest that BMP2K gene 1379 G/A variant is strongly correlated with high myopia and may contribute to a genetic risk factor for high degrees of myopic pathogenesis. J. Clin. Lab. Anal. 23:362-367, 2009. (C) 2009 Wiley-Liss, Inc

High-RI resist polymers for 193 nm immersion lithography

A critical aim within the field of 193 nm immersion lithography is the development of high refractive index immersion fluids and resists. Increases in the refractive index (RI) of the immersion fluid will result in increases in the numerical aperture and depth of focus. Increasing the RI of resist polymers will improve exposure latitude for the process. A challenge for increasing the RI of resist polymers is to do so without detrimentally affecting other properties of the polymer such as transparency, line edge roughness, adhesion and plasma etch resistance. It is well known in the literature that introducing sulfur, bromine or aromatic groups into a polymer structure will increase its RI. However, due to the relatively strong absorption of phenyl groups at 193 nm these groups have to be avoided. Furthermore, the use of bromine poses problems associated with contamination of the silicon wafer. Hence, in this study, a systematic approach has been used to increase the sulfur content of 193 nm type resist polymers, by synthesis of sulfur-containing monomers and by performing bulk modifications of the polymer. The effect of sulfur content on the RI at 193 nm was then investigated. A broad study of the relationship between molecular structure and RI dispersion from 250-180 nm has also been undertaken, and conclusions drawn using QSPR methodologies. Finally, the effect of sulfur content on other lithography parameters, such as transparency, adhesion and plasma etch resistance, was also evaluated

Synthesis of high-refractive index sulfur containing polymers for 193-nm immersion lithography: A progress report

To be able to extend the 193 nm immersion lithography technology platform, the development of high refractive index immersion fluids and resists is required. This paper reports our investigations into generating high refractive index polymers for use in photoresist formulations for 193 nm immersion lithograph. In this study a series of model compounds have been screened for refractive index and transparency at 589 nm and 193 nm. For the compounds studied this series of experiments demonstrated that sulfur-containing compounds have a positive effect on the refractive index of a molecule at 589 nm. However, the situation is complicated by the presence of absorption bands for some small molecules in the low waveleingth region. To demonstrate this, we examined the refractive index dispersion of a series of molecules based on ethyl acetate with varying degrees of sulfur substitution. These results indicated that an anomalous increase in refractive index could be expected 20 - 30 nm above the absorption maximum. The implications for design of high refractive index resists for 193 nm immersion lithography are discussed

Proprioception and flexibility profiles of elite synchronized swimmers

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Dislocations as channels for the fabrication of sub-surface porous GaN by electrochemical etching

Porosification of nitride semiconductors provides a new paradigm for advanced engineering of the properties of optoelectronic materials. Electrochemical etching creates porosity in doped layers whilst leaving undoped layers undamaged, allowing the realisation of complex three-dimensional porous nanostructures, potentially offering a wide range of functionalities, such as in distributed Bragg reflectors. Porous/non-porous multilayers can be formed by etching whole, as-grown wafers uniformly in one simple process, without any additional processing steps. The etch penetrates from the top down, through the undoped layers, leaving them almost untouched. Here, atomic-resolution electron microscopy is used to show that the etchant accesses the doped layers via nanometre-scale channels that form at dislocation cores and transport the etchant and etch products to and from the doped layer respectively. Results on AlGaN and non-polar GaN multilayers indicate the same mechanism is operating, suggesting this approach may be applicable in a range of materials

LNK (SH2B3): paradoxical effects in ovarian cancer.

LNK (SH2B3) is an adaptor protein studied extensively in normal and malignant hematopoietic cells. In these cells, it downregulates activated tyrosine kinases at the cell surface resulting in an antiproliferative effect. To date, no studies have examined activities of LNK in solid tumors. In this study, we found by in silico analysis and staining tissue arrays that the levels of LNK expression were elevated in high-grade ovarian cancer. To test the functional importance of this observation, LNK was either overexpressed or silenced in several ovarian cancer cell lines. Remarkably, overexpression of LNK rendered the cells resistant to death induced by either serum starvation or nutrient deprivation, and generated larger tumors using a murine xenograft model. In contrast, silencing of LNK decreased ovarian cancer cell growth in vitro and in vivo. Western blot studies indicated that overexpression of LNK upregulated and extended the transduction of the mitogenic signal, whereas silencing of LNK produced the opposite effects. Furthermore, forced expression of LNK reduced cell size, inhibited cell migration and markedly enhanced cell adhesion. Liquid chromatography-mass spectroscopy identified 14-3-3 as one of the LNK-binding partners. Our results suggest that in contrast to the findings in hematologic malignancies, the adaptor protein LNK acts as a positive signal transduction modulator in ovarian cancers