Dissymmetric pyridyl-substituted 3,5-bis(arylidene)-4-piperidones as anti-hepatoma agents by inhibiting NF-κB pathway activation.

To get new anti-hepatoma agents with anti-inflammatory activity and hypotoxicity, a series of dissymmetric pyridyl-substituted 3,5-bis(arylidene)-4-piperidones (BAPs, 25-82) were designed and synthesized. Many of them exhibited potential anti-hepatoma properties against human hepatocellular carcinoma cell lines (HepG2, QGY-7703, SMMC-7721) and hypotoxicity for human normal heptical cell line (HHL-5, LO2), and prominently inhibited lipopolysaccharides (LPS) induced IL-6, TNF-α secretion to exert its anti-inflammatory effect. Combining the data of cytotoxicity, cytocompatibility and anti-inflammatory activity, 3-pyridyl and -CF3 substituted 67 may be the potential anti-hepatoma agent. 67 effectively promoted cell apoptosis through up-regulating cleaved caspase-3 and Bax expression and down-regulating Bcl-2 expression. Furthermore, 67 prominently inhibited NF-κB pathway activation by blocking the phosphorylation of IκBα, p65 and the nuclear translocation of NF-κB induced by TNF-α and LPS. In addition, 67 could reasonably bind to the active site of Bcl-2 and NF-κB/p65 protein proved by Molecular docking analyses. Moreover, 67 significantly suppressed the growth and inflammatory response of HepG2 xenografts in nude mice and was relatively nontoxic to mice. These results suggest that 67 may be effective and hypotoxicity anti-hepatoma agent for the clinical treatment of liver cancers.

The Role of Axillary Lymph Node Dissection in Tubular Carcinoma of the Breast: A Population Database Study.

BACKGROUND The aim of this study was to investigate the role of axillary lymph node dissection on the outcome of patients with tubular carcinoma of the breast. MATERIAL AND METHODS Patients diagnosed with tubular carcinoma of the breast between 2000-2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Statistical analysis of the data was undertaken, including analysis of breast cancer-specific survival (BCSS). RESULTS Of the 5,645 patients identified on the SEER database with tubular carcinoma of the breast, 5,032 (89.4%) patients had undergone axillary lymph node dissection, with significantly increased rates after 2002 compared with rates between 2000-2001 (p <0.001), which stabilized between 2002-2013 (p=0.330). Axillary lymph node metastases were present in 6.1% of all patients and in 5.3% of patients with a tumor size ≤2 cm. Lymph node-positive disease was associated with patient age ≤65 years, intermediate-grade or high-grade tumors, and tumor size >2.0 cm. Axillary lymph node dissection was an independent prognostic indicator. The 10-year BCSS was 97.3% and 96.6% in patients with and without axillary lymph node dissection, respectively (p=0.002). The number of removed lymph nodes was not related to breast cancer-specific survival. CONCLUSIONS In patients with tubular carcinoma of the breast, lymph node status was not associated with significant breast cancer-specific survival. However, axillary lymph node dissection may still be considered for patients with for tubular carcinoma of the breast even in patients with a small tumor size.