35 research outputs found
RCAS1 as a tumour progression marker: an independent negative prognostic factor in gallbladder cancer
Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) induces apoptosis in immune cells bearing the RCAS1 receptor. We sought to determine RCAS1 involvement in the origin and progression of gallbladder cancer, and also implications of RCAS1 for patient survival. RCAS1 expression was examined immunohistochemically in 110 surgically resected gallbladder specimens. The gallbladders represented 20 cases of cholecystitis with no associated pancreaticobiliary maljunction; 23 cases of cholecystitis with pancreaticobiliary maljunction; 14 cases of adenomyomatosis; 7 adenomas; and 46 cancers. High expression of RCAS1 (immunoreactivity in over 25% of cells) was observed in 32 of the 46 cancers (70%), but not in other diseases, including pre-cancerous conditions. RCAS1 immunoreactivity was associated with depth of tumour invasion (P = 0.0180), lymph node metastasis (P = 0.0033), lymphatic involvement (P = 0.0104), venous involvement (P = 0.0224), perineural involvement (P = 0.0351) and stage by the tumour, nodes and metastases (TNM) classification (P = 0.0026). Thus, RCAS1 expression may be a relatively late event in gallbladder carcinogenesis possibly promoting tumour progression. Cox regression multivariate analysis demonstrated RCAS1 positivity to be an independent negative predictor for survival (P = 0.0337; risk ratio, 12.690; 95% confidence interval, 1.216–132.423). High expression of RCAS1 significantly correlated with tumour progression and predicted poor outcome in gallbladder cancer. © 2001 Cancer Research Campaign http://www.bjcancer.co
Modeling of plasma-induced damage and its impacts on parameter variations in advanced electronic devices
A comprehensive model predicting the effects of plasma-induced damage (PID) on parameter variations in advanced metal–oxide–semiconductor field-effect transistors (MOSFETs) is proposed. The model focuses on the silicon recess structure (Si loss) in the source/drain extension region formed by high-energy ion bombardment during plasma etching. The model includes the following mechanisms: (1) damaged layer formation by ion impact and penetration, (2) Si recess structure formation by a subsequent wet etch, (3) MOSFET performance degradation, and (4) MOSFET parameter variation. Based on a range theory for plasma-etch damage, the thickness of the damaged layer exhibits a power-law dependence on the energy of the ion incident on the surface of Si substrate. Assuming that the damaged layer was formed during a gate or an offset spacer etch process, the depth of Si recess (dR) is a function of the depth profile of the created defect site (ndam), the wet-etch stripping time (tw), and the energy of the incident ion. It was found that dR also showed a power-law dependence on the average ion energy Ēion estimated from applied self-dc-bias voltage for various tw. As for MOSFET performance degradation, the threshold voltage (Vth) shifted and the shift (ΔVth) increased with an increase in Ēion and a decrease in gate length. This induces an increase in subthreshold leakage current (Ioff) for MOSFET. Technology computer-aided-design simulations were performed to confirm these results. By integrating the presented PID models, parameter variations could be predicted: Using a Monte Carlo method, it was demonstrated that PID increases parameter variations such as Vth and Ioff. It also was found that the variation in Ēion induces Vth and Ioff variations, comparable to that induced by other process parameter fluctuations such as dopant fluctuation and gate length. In summary, considering the effects of PID on parameter variations is vital for designing future ultralarge-scale-integrated circuits with billions of built-in MOSFETs
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Transcriptional targeting of adenovirus vectors with the squamous cell carcinoma-specific antigen-2 promoter for selective apoptosis induction in lung cancer
Squamous cell carcinoma antigens SCCA1 and SCCA2 are highly homologous serine proteinase inhibitors which have been widely utilized as serological markers for squamous cell cancers, but it has recently been demonstrated that only SCCA2 is truly specific for certain forms of lung cancer. Using a construct containing the 5'-flanking region of the SCCA2 gene between -460 and +0 bp and the luciferase reporter gene, SCCA2 promoter activity was detected in SCCA2-producing SCC cell lines (LK-2, LC-1), but not in SCCA2-nonproducing lung adenocarcinoma cell lines (A549, ABC-1, and RERF-LC-MS) or normal cells (WI-38, SAEC, and NHEK-Adult). Infection with a recombinant adenovirus vector, Ad-SCCA2-DsRed, resulted in cell-specific expression of the SCCA2 promoter-driven DsRed marker gene only in LK-2 and LC-1 cells. The same strategy was used for SCCA2-driven expression of a proapoptotic gene, (KLAKLAK)2, which can cause mitochondrial disruption by triggering mitochondrial permeabilization and swelling, resulting in the release of cytochrome c and induction of apoptosis. Infection with Ad-SCCA2-KLAKLAK2 specifically reduced the growth of the two human lung SCC cell lines compared to the SCCA2 nonproducing cell lines both in vitro and in vivo, suggesting that the SCCA2 promoter had a tumor-specific effect. These results suggest that transduction of SCCA2 promoter-controlled suicide genes by adenoviral vectors can confer transcriptionally targeted cytotoxicity in SCCA2-producing lung SCC cells, and represents a novel strategy for gene transfer specifically targeted to SCC in the lung