Purpose: Estrogen receptor-a (ER-a) and-h (ER-h) play important roles in the carcinogenesis of breast tumors. Similarly, there have been several reports of ER expression in lung cancers, but the results have not been consistent, and the receptors' prognostic value remains unclear. Our goal was to investigate ER expression in non^small cell lung cancer (NSCLC) and to assess whether their expression correlates with prognosis. Experimental Design: ER expression was examined using immunohistochemical methods with sections from 132 resected NSCLC specimens. Kaplan-Meier survival curves were analyzed to determine the significance of ER expression in the prognosis of NSCLC patients. Results: ER-a was detected in the cytoplasm of 73% of the specimens analyzed, whereas ER-h was detected in the nucleus of 51%. ER-a expression correlated with poorer overall survival (P < 0.001), as did the absence of ER-h expression (P = 0.048). Likewise, at histopathologic stage I, ER-a expression (P = 0.028) or the absence of ER-h (P = 0.

Wilson's disease, an autosomal recessive disorder, is characterized by the excessive accumulation of copper in the liver. WND (ATP7B) gene, which encodes a putative copper transporting P-type ATPase, is defective in the patients. To investigate the in vivo function of WND protein as well as its intracellular localization, WND cDNA was introduced to the Long-Evans Cinnamon rat, known as a rodent model for Wilson's disease, by recombinant adenovirus-mediated gene delivery. An immunofluorescent study and a subcellular fractionation study revealed the transgene expression in liver and its localization to the Golgi apparatus. Moreover, since the synthesis of holoceruloplasmin is disturbed in the LongEvans Cinnamon rat, the plasma level of holoceruloplasmin, oxidase-active and copper-bound form, was examined to evaluate the function of WND protein with respect to the copper transport. Consequently, the appearance of holoceruloplasmin in plasma was confirmed by Western blot analysis and plasma measurements for the oxidase activity and the copper content. These findings indicate that introduced WND protein may function in the copper transport coupled with the synthesis of ceruloplasmin and that the Golgi apparatus is the likely site for WND protein to manifest its function.Wilson's disease, an autosomal recessive disorder, is characterized by the excessive accumulation of copper in the liver (1). This phenomenon is thought to be due to reduced biliary excretion of copper and disturbed incorporation of copper into ceruloplasmin (CPN).1 Hepatic copper at toxic levels causes liver cirrhosis, and extrahepatic copper toxicity occurs especially in the brain due to the released copper from the damaged liver. WND (officially designated ATP7B), identified as the gene responsible for this disease, encodes a putative copper transporting P-type ATPase (2-5). The observations of single base changes or small deletions within WND of Wilson's disease patients have already been reported (3, 6).The Long-Evans Cinnamon (LEC) rat, known as an animal model for Wilson's disease, shows some of the clinical features similar to Wilson's disease, including hepatic copper accumulation, reduced biliary copper excretion, reduced copper in plasma, and a remarkable decrease of serum CPN activity (7,8). Atp7b, the rat gene homologous to WND, has been cloned, and a partial deletion at the 3Ј end in this gene is reported in the LEC rat (9). It is also known that the expression of Atp7b mRNA is absent in the LEC rat (10).CPN, a blue copper oxidase in plasma, contains 90 -95% of plasma copper. This protein is synthesized mainly in hepatocytes and secreted into plasma with 6 atoms of copper per molecule as the oxidase active holoprotein (11-13). The reduced levels of oxidase activity of CPN in the circulation of Wilson's disease patients and LEC rats is due to the secretion of apoceruloplasmin, copper-free and oxidase-inactive form, resulting from the disturbed incorporation of copper atoms into the protein (1, 14), while the intracellular synthesis of CPN...

Lymphatic flux from a primary tumor initially flows into a tumor-draining lymph node (LN), the so-called sentinel LN (SLN). Carried by the lymph fluid are a variety of mediators produced by the tumor that can influence immune responses within the SLN, making it a good model with which to investigate tumor-related immunology. For instance, dendritic cell (DC) numbers are reduced in SLNs from melanoma and breast cancer patients. In the present study, we investigated the mechanism by which DC numbers were reduced within SLNs from patients with non-small cell lung cancer. We found that the incidence of apoptosis among DCs was higher in SLNs than in non-SLNs, as were levels of TGFβ-1. In contrast, levels of TGFβ-1 mRNA did not differ between SLNs and non-SLNs, but were 30 times higher in tumors than in either LN type. In vitro, incubation for 2 days with TGFβ-1 induced apoptosis among both cultured DCs and DCs acutely isolated from normal thoracic LNs, effects that were blocked by the TGFβ-1 inhibitor DAN/Fc chimera. Taken together, these results suggest that tumor-derived TGFβ-1 induces immunosuppression within SLNs before the movement of tumor cells into the SLNs, thereby facilitating metastasis within those nodes.

The results suggest that this formula might serve as an indication for preoperative marking of small peripheral pulmonary nodules in thoracoscopic resection.