The promise of retinoids as chemopreventive agents in breast cancer is based on the differentiation and apoptosis induced upon their binding to the retinoic acid (RA) receptor B (RARB). We have previously shown that HOXA5 induces apoptosis in breast cancer cells. In this study, we investigated whether RA/ RARB and HOXA5 actions intersect to induce apoptosis and differentiation in breast cancer cells. We found that HOXA5 expression can be induced by RA only in RARB-positive breast cancer cells. We have, for the first time, identified the RA response element in HOXA5, which was found to be located in the 3 ¶ end of the gene. Chromatin immunoprecipitation assays showed that RARB binds directly to this region in vivo. Overexpression of RARb strongly enhances RA responsiveness, and knocking down RARb expression abolishes RA-mediated induction of HOXA5 expression in breast cancer cells. In addition, there is coordinated loss of both HOXA5 and RARb expression during neoplastic transformation and progression in the breast epithelial cell model, MCF10A. Knockdown of HOXA5 expression partially abrogates retinoid-induced apoptosis and promotes cell survival upon RA treatment. These results strongly suggest that HOXA5 acts directly downstream of RARb and may contribute to retinoid-induced anticancer and chemopreventive effects. [Cancer Res 2007;67(17):8007-13]

These data suggest that mutation of AXIN1 gene is a frequent and late event for HCC associated with cirrhosis, and is correlated significantly with abnormal expression of axin and beta-catenin. Therefore, activation of Wnt signaling through AXIN1 rather than beta-catenin mutation might play an important role in liver carcinogenesis.

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Sputum cytology is a non-invasive test for evaluating lung cancer. But, its sensitivity is yet lower than other tests. ThinPrep (TP) is an automated cytopreparatory method that has mucolytic and hemolysing effects. We compared 955 sputum specimens that were prepared by both TP and conventional preparation (CP). The nuclear details were more preserved on the TP slides, while the obscuring materials were more eliminated on the TP slides as compared with the CP. The cytologic rates of TP were 2.7% unsatisfactory, 4.7% normal, 81.0% benign, 2.4% suspicious, and 9.1% malignancy. The rates of CP were 7.9% unsatisfactory, 1.6% normal, 84.8% benign, 1.8% suspicious, and 4.0% malignancy. The false negative rates, relative to the histologic data for 352 cases which the tissue diagnosis was available, were 49.6% (TP) and 69.4% (CP). Sputum cytology using the TP method improves the diagnostic accuracy for evaluating lung cancer by reducing the unsatisfactory and false-negative rates.

We investigated the patterns of pretreatment expression of the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) by immunohistochemical staining and determined their correlation with treatment response and survival in 44 patients with esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). The definitive CCRT consisted of a median dose of 54 Gy (range: 40.0-68.4 Gy) and two cycles of concurrent administration of mostly 5-fluorouracil + cisplatinum. High expression of EGFR, VEGF, and COX-2 was found in 79.5%, 31.8%, and 38.6%, respectively. The Cox regression analysis for overall survival (OS) showed that both the treatment response and COX-2 expression were significant. The 3-yr OS rates of patients that achieved a complete response and those that did not were 46.7% and 5.3%, respectively (P = 0.006). The logistic regression analysis for treatment response with various parameters showed that only a high expression of VEGF was significantly associated with a complete response. Unlike other well-known studies, higher expression of VEGF was significantly correlated with a complete response to CCRT in this study. However, higher expression of COX-2 was significantly associated with shorter survival. These results suggest that VEGF might be a predictive factor for treatment response and COX-2 a prognostic factor for OS in patients with ESCC after definitive CCRT.