Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma

Caveolin-1 is a major component of caveolae and plays a regulatory role in several signalling pathways. Caveolin-1 was recently identified as a metastasis-related gene in prostate cancer. The clinical effects of caveolin-1 expression in pancreatic carcinoma, however, remain unknown. In this study, we have investigated the relationship between caveolin-1 expression and the clinicopathologic variables and clinical outcome in 79 patients with pancreatic adenocarcinoma undergoing surgical resection. Caveolin-1 expression was determined by immunohistochemistry, using a polyclonal anti-caveolin-1 antibody. Patients were divided into two groups based on the extent of caveolin-1 expression: a negative expression group (immunoreactivity in less than 50% of cells) and a positive expression group. Positive caveolin-1 immunostaining was detected in 32 cases (40.5% of total), while non-neoplastic ductal epithelium showed little or no staining. Positive caveolin-1 expression was correlated with tumour diameter (P=0.0079), histopathologic grade (P=0.0272) and poor prognosis (P=0.0008). Upon multivariate analysis with Cox's proportional hazards model, positive caveolin-1 expression was shown to be an independent negative predictor for survival (P=0.0358). These results suggest that caveolin-1 overexpression is associated with tumour progression, thereby indicating a poor prognosis for certain patients undergoing surgical resection for pancreatic carcinoma

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