Purpose:The development of hepatocellular carcinoma is associated with the chronic inflammation of the liver caused by various factors such as hepatitis B or C virus infection. Previously, we reported DNA binding protein A (dbpA) as a candidate molecule that can accelerate inflammation-induced hepatocarcinogenesis. DbpA belongs to the Y-box binding protein family, and Y-box binding protein-1 (YB-1), the prototype member of this family, is reported to be a prognostic marker of malignant diseases other than hepatocellular carcinoma. The purpose of this study is to examine the significance of the expression of dbpA or of theT-to-G transversion in the dbpA promoter region, which enhances the promoter activity in vitro, for the progression of hepatocellular carcinoma. Experimental Design: We studied the expression of dbpA (as well as of YB-1) in 82 formalinfixed hepatocellular carcinoma tissues by immunohistochemistry and determined the sequence of the dbpA promoter region in 42 frozen hepatocellular carcinoma tissues. We examined the relationship between these findings and the clinicopathologic factors of hepatocellular carcinoma patients. Results: DbpA expression was associated with the advanced stages of hepatocellular carcinoma, and the cases with the nuclear dbpA expression had a poor prognosis. DbpA contributed more significantly to this association thanYB-1. Furthermore, theT-to-G transversion in the dbpA promoter region was related to the nuclear localization of dbpA. Conclusion: DbpA was a more significant prognostic marker of hepatocellular carcinoma than YB-1. TheT-to-G transversion in the dbpA promoter region was suggested to be a predisposing factor for the progression of hepatocellular carcinoma.

Purpose We evaluated the noninferiority of dexamethasone (DEX) on day 1, with sparing on days 2 and 3, combined with neurokinin-1 receptor antagonist (NK-RA) and palonosetron (Palo) compared with the 3-day use of DEX in highly-emetogenic chemotherapy (HEC). Patients and Methods Patients who were scheduled to receive HEC (cisplatin ≥ 50 mg/m or anthracycline plus cyclophosphamide) were randomly assigned to receive either DEX on days 1 to 3 (Arm D3) or DEX on day 1 and placebo on days 2 and 3 (Arm D1) combined with NK-RA and Palo. The primary end point was complete response (CR), defined as no emesis and no rescue medications during the overall (0 to 120 h) phase. The noninferiority margin was set at -15.0% (Arm D1 - Arm D3). Results A total of 396 patients-196 and 200 patients in Arms D3 and D1, respectively-were evaluated. CR rates during the overall period were 46.9% for Arm D3 and 44.0% for Arm D1 (95% CI, -12.6% to 6.8%; P = .007). CR rates during the acute (0 to 24 h) phase were 63.3% and 64.5% for Arms D3 and D1, respectively (95% CI, -8.1% to 10.6%; P < .001), and they were 56.6% and 51.5%, respectively, during the delayed (24 to 120 h) phase (95% CI, -14.8% to 4.6%; P = .023). Hot flushes and tremors were observed more frequently as DEX-related adverse events on days 4 and 5 in Arm D3, whereas anorexia, depression, and fatigue were observed more frequently on days 2 and 3 in Arm D1. As an indication of quality of life, global health status was similar in both arms. Conclusion Antiemetic DEX administration on days 2 and 3 can be spared when combined with NK-RA and Palo in HEC.

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Abstract.We recently reported that the expression of dbpA (DNA binding protein A) is associated with advanced stages of human hepatocellular carcinoma (HCC) and that its transcription is positively regulated by E2F1, which is also implicated in hepatocarcinogenesis. To study the in vivo effect of dbpA on hepatocarcinogenesis, we generated the dbpA-transgenic mouse that specifically expressed a transgene in hepatocytes. Here, we studied the effect of dbpA on the expression of other cellular genes by using microarray analyses. The expression profiles from livers of 31-and 32-week-old male transgenic mice [Tg(+)] that did not show any morphological changes and from livers of their male wild-type littermates [Tg(-)] were compared. Expression differences detected by microarray analyses were validated by reverse transcription-polymerase chain reaction (RT-PCR) using total RNA samples from livers of 3 pairs of Tg(+) and (-) mice. The 11 up-regulated genes included 7 carcinogenesis-related genes (Igfbp1, Tff3, Hpx, Orm2, Ctsl, Plg, Jdp1), and the 9 down-regulated genes included Car3 that is associated with the protection of cells from attack by oxygen radicals. We confirmed that the expression of Igfbp1 (insulin like growth factor binding protein 1) was reduced by siRNA targeting dbpA in the human HCC cell line. In conclusion, our present data suggested that dbpA could be positively involved in carcinogenesis by changing the expression profiles of cellular genes.