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.

The interaction between 17␤-estradiol and estrogen receptor alpha (ER-␣) plays an important role in breast carcinogenesis and breast cancer treatment. ER-␣ is a critical growth regulatory gene in breast cancer and its expression level is tightly linked to the prognosis and treatment outcomes of breast cancer patients. Loss of ER-␣ expression in breast epithelial cells is critical for breast cancer progression. The underlying molecular mechanisms for this loss, however, are poorly defined. Histone deacetylases (HDACs) are implicated in the alteration of chromatin assembly and tumorigenesis. We show that histone deacetylase 1 (HDAC1) interacts with ER-␣ in vitro and in vivo and suppresses ER-␣ transcription activity. The interaction of HDAC1 with ER-␣ was mediated by the AF-2 and DBD domains of ER-␣. We observed an endogenous interaction of HDAC1 with ER-␣ in breast cancer cells, which was decreased in the presence of estrogen. Interestingly, overexpression of HDAC1 in stable transfected MCF-7 clones induced loss of ER-␣ and significantly increased cell proliferation and colony formation, as compared to the control MCF-7 cells, whereas treatment of stable MCF-7 clones with the HDAC specific inhibitor trichostatin A (TSA) induced re-expression of ER-␣ mRNA and protein. Our findings strongly suggest that HDAC1 affects breast cancer progression by promoting cellular proliferation in association with a reduction in both ER-␣ protein expression and transcriptional activity. Thus, HDAC1 may be a potential target for therapeutic intervention in the treatment of a subset of ER-negative breast cancers.

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.

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Low serum prealbumin level in the perioperative period is associated with a poorer prognosis in NSCLC patients and could serve as a marker for identifying patients at high risk, even at an early clinical stage.

Objective: To establish a new therapeutic approach for the treatment of esophageal cancer, we investigated an alternative mechanism of immunotherapy for sensitizing target cells to effector cells. Methods: Six human esophageal cancer cell lines were used. The expression of Fas antigen on tumor cells was determined by flow cytometry. The cytotoxic effect of cis-dichlorodiammineplatinum (CDDP) and anti-Fas antibody was evaluated using an MTT assay. The cytotoxic activity of LAK cells was measured by a ⁵¹Cr release assay. Results: Five out of six esophageal cancer cell lines expressed Fas antigen at various levels (26.2–61.5%), and Fas expression increased after CDDP treatment. The antitumor effect of anti-Fas antibody on the esophageal cancer cell line and the antitumor effect of LAK cells activated by IL-2 were enhanced by pretreatment with CDDP. After concanamycin A treatment to specifically evaluate Fas-dependent cytotoxicity, LAK cells expressing Fas ligand killed only Fas-positive cells, but not Fas-negative cells. An anti-Fas neutralizing antibody inhibited this cytotoxicity. DNA fragmentation was shown in a cell line that was treated with CDDP and anti-Fas antibody, and also in the targeted esophageal cancer cell line cocultured with LAK cells. Conclusion: Our results suggest a potential clinical application of CDDP as a Fas inducer to make esophageal tumors susceptible to Fas antigen and LAK cytotoxicity.

S100 proteins have been implicated in the progression and metastasis of several cancers. Among the S100 family, S100A9 is reportedly expressed in non-small cell lung cancer (NSCLC), though the clinical significance and prognostic value of S100A9 expression in NSCLC remains unclear. The aim of the present study was to examine the relationship between S100A9 expression and prognosis in NSCLC patients. S100A9 expression was evaluated by immunohistochemical staining. Seventy patients with NSCLC who had undergone lung resection were enrolled in the study. Overexpression of S100A9 was observed in 38 (54.3%) patients. Kaplan-Meier analysis showed that, following surgery, patients overexpressing S100A9 had a significantly lower 5-year overall survival rate than patients with weak or no expression of S100A9 (P=0.005). This finding was also observed in pathological stage IA patients (P=0.03). Multivariate Cox regression analysis revealed overexpression of S100A9 to be an independent factor predictive of poor disease outcome (hazard ratio, 0.3; 95% confidence interval, 0.1-0.8; P=0.02). Our results suggest that overexpression of S100A9 is associated with a poor prognosis among NSCLC patients and could serve as a marker identifying patients who are at high risk, even at an early pathological stage.

[Purpose] The purpose of this study was to clarify the benefits of early mobilization for mechanically ventilated patients for their survival to discharge to home from the hospital. [Subjects and Methods] Medical records were retrospectively analyzed of patients who satisfied the following criteria: age ≥ 18 years; performance status 0–2 and independent living at their home before admission; mechanical ventilation for more than 48 h; and survival after mechanical ventilation. Mechanically ventilated patients in the early mobilization (EM) group (n = 48) received mobilization therapy, limb exercise and chest physiotherapy, whereas those in the control group (n = 60) received bed rest alone. Univariate and multivariate logistic regression analyses were performed to identify clinical variables associated with discharge disposition. [Results] Early mobilization was a positive independent factor and the presence of neurological deficits was a negative factor contributing to discharge to home. Among patients surviving mechanical ventilation without neurological deficits, the rate of discharge to home was significantly higher among patients in the EM group that in the control group (76% vs. 40%). [Conclusion] Early mobilization can improve the rate of discharge to home of patients requiring mechanical ventilation because of non-neurological deficits.