Showing papers by "Qiang Liu published in 2006"

RUNX3 Is Frequently Inactivated by Dual Mechanisms of Protein Mislocalization and Promoter Hypermethylation in Breast Cancer

Abstract: A tumor suppressor function has been attributed to RUNX3, a member of the RUNX family of transcription factors. Here, we examined alterations in the expression of three members, RUNX1, RUNX2, and RUNX3, and their interacting partner, CBF-beta, in breast cancer. Among them, RUNX3 was consistently underexpressed in breast cancer cell lines and primary tumors. Fifty percent of the breast cancer cell lines (n = 19) showed hypermethylation at the promoter region and displayed significantly lower levels of RUNX3 mRNA expression (P < 0.0001) and protein (P < 0.001). In primary Singaporean breast cancers, 9 of 44 specimens showed undetectable levels of RUNX3 by immunohistochemistry. In 35 of 44 tumors, however, low levels of RUNX3 protein were present. Remarkably, in each case, protein was mislocalized to the cytoplasm. In primary tumors, hypermethylation of RUNX3 was observed in 23 of 44 cases (52%) and was undetectable in matched adjacent normal breast epithelium. Mislocalization of the protein, with or without methylation, seems to account for RUNX3 inactivation in the vast majority of the tumors. In in vitro and in vivo assays, RUNX3 behaved as a growth suppressor in breast cancer cells. Stable expression of RUNX3 in MDA-MB-231 breast cancer cells led to a more cuboidal phenotype, significantly reduced invasiveness in Matrigel invasion assays, and suppressed tumor formation in immunodeficient mice. This study provides biological and mechanistic insights into RUNX3 as the key member of the family that plays a role in breast cancer. Frequent protein mislocalization and methylation could render RUNX3 a valuable marker for early detection and risk assessment.

RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer by protein mislocalization (vol 65, pg 7743, 2005)

Abstract: Loss of RUNX3 expression is suggested to be causally related to gastric cancer as 45% to 60% of gastric cancers do not express RUNX3 mainly due to hypermethylation of the RUNX3 promoter. Here, we examined for other defects in the properties of RUNX3 in gastric cancers that express RUNX3. Ninety-seven gastric cancer tumor specimens and 21 gastric cancer cell lines were examined by immunohistochemistry using novel anti-RUNX3 monoclonal antibodies. In normal gastric mucosa, RUNX3 was expressed most strongly in the nuclei of chief cells as well as in surface epithelial cells. In chief cells, a significant portion of the protein was also found in the cytoplasm. RUNX3 was not detectable in 43 of 97 (44%) cases of gastric cancers tested and a further 38% showed exclusive cytoplasmic localization, whereas only 18% showed nuclear localization. Evidence is presented suggesting that transforming growth factor-beta is an inducer of nuclear translocation of RUNX3, and RUNX3 in the cytoplasm of cancer cells is inactive as a tumor suppressor. RUNX3 was found to be inactive in 82% of gastric cancers through either gene silencing or protein mislocalization to the cytoplasm. In addition to the deregulation of mechanisms controlling gene expression, there would also seem to be at least one other mechanism controlling nuclear translocation of RUNX3 that is impaired frequently in gastric cancer.

Corner-pumped Yb: yttrium aluminum garnet slab laser emitted up to 1kW

Abstract: We have developed a slab laser design based on conduction cooling and a novel pumping geometry called corner pumping. The design uses a slab crystal configuration with the pump light incident from the slab corners. A maximum output power of over 1kW was achieved from a 1mm thick Yb:YAG/YAG (YAG=yttrium aluminum garnet) structure with a 0.5at.%-doped Yb:YAG. The slope efficiency and optical-to-optical efficiency with respect to the total pump power were 42.8% and 33.6%, respectively. At this pump power the electrical-to-optical conversion efficiency of the system was 16.8%.

Linearly-polarized single-transverse-mode high-energy multi-ten nanosecond fiber amplifier with 50W average power.

Abstract: A linearly polarized single-transverse-mode Yb-doped double clad polarization-maintaining fiber amplifier at 1064nm is reported, which delivers 53.1W average power at 40kHz repetition rate, with pulse energy >1mJ, duration 30ns, polarization extinction ratio 13dB, and M2<1.2. Stimulated Brillouin scattering (SBS) phenomenon during amplification is discussed, and a new SBS suppression approach using linewidth broadening induced by self-phase modulation (SPM) is demonstrated.

Efficient corner-pumped Yb:YAG/YAG composite slab laser.

Abstract: A high efficiency Yb:YAG/YAG composite slab laser is presented, in which the corner-pumped scheme is adopted. The slab is a composite crystal of Yb:YAG bonded thermally with undoped YAG at both edges. The pump light from diode arrays is coupled into the slab through four chamfers at the four corners independently. The pump absorption efficiency is studied, and an analysis method has been developed as a guide to optimize the geometric parameters of the composite slab, to obtain higher pump absorption efficiency and uniformity. The influence of the internal thermal lens on the laser resonator is analyzed. A 1016 W continuous-wave output has been obtained with the slope efficiency and optical-to-optical efficiency of 42.8% and 34.4%, respectively.

Inhibitory effect of blocking expression of human augmenter of liver regeneration (hALR) on proliferation of hepatocellular carcinoma cell line HepG2

Abstract: BACKGROUND & OBJECTIVE Human augmenter of liver regeneration (hALR) is highly expressed in hepatocellular carcinoma (HCC), but rarely expressed in normal liver cells. ALR could stimulate the proliferation of HCC cell line in vitro, but has no effect on normal hepatocytes. This study was to investigate the inhibitory effect of blocking the expression of hALR on the proliferation of HCC cell line HepG2 using small interfering RNA (siRNA) targeting ALR and anti-ALR monoclonal antibody (McAb). METHODS RNA interference (RNAi) plasmid pSIALR-A targeting hALR cDNA and control plasmid pSIALR-B were constructed and transfected into HepG2 cells, respectively. After transfection, the expression of green fluorescent protein was observed under a fluorescent microscope to calculate transfection efficiency, the protein level of hALR was measured by immunocytochemistry, meanwhile, the expression of hALR mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). (3)H-TdR incorporation approach was performed to detect the proliferation of HepG2 cells after transfection and after neutralization with anti-hALR McAb. RESULTS hALR was expressed in HepG2 cells. Plasmids pSIALR-A and pSIALR-B were successfully constructed. Both immunocytochemistry and RT-PCR showed that pSIALR-A inhibited the expression of hALR in HepG2 cells significantly by 83% as compared with pSIALR-B. pSIALR-A specifically inhibited the growth of HepG2 cells after transfection. (3)H-TdR incorporation of pSIALR-A/HepG2 cells was significantly lower than that of pSIALR-B/HepG2 cells (67 687+/-6 548 vs. 104 807+/-5 713, P<0.05). Anti-hALR McAb markedly inhibited the autonomous growth of HepG2 cells (P<0.05). CONCLUSIONS hALR is highly expressed in HepG2 cells. The short interfering RNA targeting hALR gene could specifically suppress the expression of hALR, and subsequently inhibit the growth of HepG2 cells. Anti-hALR McAb could partially inhibit the autonomous growth of HepG2 cells.

Liquid analysis based on fiber micro-drop sensors

Abstract: The fiber micro-drop sensor is a potential tool in different application areas. With the help of a group of fibers, the information of the forming and dripping of a liquid drop is monitored. The fingerprint drop trace provides the information of the liquid to be tested. Some liquids of different types are tested to show the different drop trace. The alcohol solutions of different concentrations are paid more attention to dig the information hiding in the drop trace.