Identification of tumor suppressor genes (TSG) silenced by methylation uncovers mechanisms of tumorigenesis and identifies new epigenetic tumor markers for early cancer detection. Both nasopharyngeal carcinoma (NPC) and esophageal carcinoma are major tumors in Southern China and Southeast Asia. Through expression subtraction of NPC, we identified Deleted in Liver Cancer 1 (DLC1)/ARHGAP7 (NM_006094) -an 8p22 TSG as a major downregulated gene. Although expressed in all normal tissues, DLC1 was silenced or downregulated in 11/12 (91%) NPC, 6/15 (40%) esophageal, 5/8 (63%) cervical and 3/9 (33%) breast carcinoma cell lines. No genetic deletion of DLC1 was detected in NPC although a hemizygous deletion at 8p22-11 was found by 1-Mb array-CGH in some cell lines. We then located the functional DLC1 promoter by 5 0 -RACE and promoter activity assays. This promoter was frequently methylated in all downregulated cell lines and in a large collection of primary tumors including 89% (64/72) NPC (endemic and sporadic types), 51% (48/94) esophageal, 87% (7/8) cervical and 36% (5/14) breast carcinomas, but seldom in paired surgical marginal tissues and not in any normal epithelial tissue. The transcriptional silencing of DLC1 could be reversed by 5-aza-2 0 -deoxycytidine or genetic double knock-out of DNMT1 and DNMT3B. Furthermore, ectopic expression of DLC1 in NPC and esophageal carcinoma cells strongly inhibited their colony formation. We thus found frequent epigenetic silencing of DLC1 in NPC, esophageal and cervical carcinomas, and a high correlation of methylation with its downregulation, suggesting a predominant role of epigenetic inactivation. DLC1 appears to be a major TSG implicated in the pathogenesis of these tumors, and should be further tested as a molecular biomarker in patients with these cancers. Oncogene (2007) 26, 934-944.
Genetic alterations of 16q21-q22, the locus of a 6-cadherin cluster, are frequently involved in multiple tumors, suggesting the presence of critical tumor suppressor genes (TSGs). Using 1 Mb array comparative genomic hybridization (aCGH), we refined a small hemizygous deletion (∼1 Mb) at 16q21-22.1, which contains a single gene Cadherin-11 (CDH11, OB-cadherin). CDH11 was broadly expressed in human normal adult and fetal tissues, while its silencing and promoter CpG methylation were frequently detected in tumor cell lines, but not in immortalized normal epithelial cells. Aberrant methylation was also frequently detected in multiple primary tumors. CDH11 silencing could be reversed by pharmacologic or genetic demethylation, indicating an epigenetic mechanism. Ectopic expression of CDH11 strongly suppressed tumorigenecity and induced tumor cell apoptosis. Moreover, CDH11 was found to inhibit Wnt/β-catenin and AKT/Rho A signaling, as well as actin stress fiber formation, thus further inhibiting tumor cell migration and invasion. CDH11 also inhibited epithelial-to-mesenchymal transition and downregulated stem cell markers. Thus, our work identifies CDH11 as a functional tumor suppressor and an important antagonist of Wnt/β-catenin and AKT/Rho A signaling, with frequent epigenetic inactivation in common carcinomas.
Chinese eyes had smaller ACD, smaller ACW and greater iris thickness than Caucasians. ACD was the most influential parameter in determining the angle width in both ethnic groups.
TIA is prevalent and an estimated 23.9 million people in China may have experienced a TIA. Public knowledge on TIA is very limited. TIA appears to be largely undiagnosed and untreated in China. There is an urgent need to develop strategies to improve the identification and appropriate management of TIA.
We present submillimeter spectral line and dust continuum polarization observations of a remarkable hot core and multiple outflows in the high-mass star-forming region W43-MM1 (G30.79 FIR 10), obtained using the Submillimeter Array (SMA). A temperature of ∼ 400 K is estimated for the hot-core using CH 3 CN (J=19-18) lines, with detections of 11 K-ladder components. The high temperature and the mass estimates for the outflows indicate high-mass star-formation. The continuum polarization pattern shows an ordered distribution, and its orientation over the main outflow appears aligned to the outflow. The derived magnetic field indicates slightly super-critical conditions. While the magnetic and outflow energies are comparable, the B-field orientation appears to have changed from parsec scales to ∼ 0.1 pc scales during the core/star-formation process.
Using depth-sensing indentation with sub-nanometer displacement resolution, the plastic deformation of a range of materials, including a metallic glass, amorphous selenium, Ni 3 Al, pure Nb, Al, Cu, and Zn metals, and an Al-Mg alloy, has been investigated at room temperature. In amorphous selenium, even the sub-nanometer displacement resolution of the nanoindentation technique cannot reveal any strain burst during deformation at room temperature. In all other metals studied, what may appear to be smooth load-displacement curves at macroscopic scale during indentation deformation in fact turn out to consist of a continuous series of random bursts of the nanometer scale. The occurrence probability of the bursts is found to decrease at increasing burst size. In all of the crystalline metals and alloys studied, the size distribution of the strain bursts seems to follow an exponential law with a characteristic length scale. The absence of the self-organized critical behavior is likely a result of the small size of the strained volume in the nanoindentation situation, which gives rise to a constraint of a characteristic strain. In the metallic glass sample, due to the limited range of the burst sizes encountered, whether the deformation bursts follow an exponential or a power-law behavior corresponding to self-organized criticality is inconclusive. From a theoretical viewpoint based on the Shannon entropy, the exponential distribution is the most likely distribution at a given mean burst size, and this is thought to be the reason for its occurrence in different materials.
Axial length or spherical error is a significant predictor for ABP with both GDx VCC and GDx ECC. Caution should be exercised in interpreting the results of scanning laser polarimetry in eyes with a long axial length or myopia.
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