Prognostic Factors in Patients with Locally Advanced Breast Cancer Treated by Neoadjuvant Chemotherapy

PURPOSE: Neoadjuvant chemotherapy (NAC) has become the standard treatment for patients with locally advanced breast cancer. The purpose of this study was to evaluate prognosis according to molecular subtype and clinicopathologic factors in patients with locally advanced breast cancer treated by NAC. METHODS: We retrospectively analyzed the medical records of 91 patients with breast cancer who underwent NAC followed by surgery between January 2005 and January 2010. The patients were classified into four molecular subtype groups: luminal A, luminal B, HER2 enriched, and triple negative (TN). RESULTS: Thirty-five (38%) patients had luminal A, 13 (14%) patients luminal B, 22 (24%) patients HER2 enriched and 21 (21%) patients TN breast cancer. Patients with TN breast cancer tended to be more than 50 years of age and to have a higher histologic grade. There were statistically significant differences according to ypN stage (ypN0 vs. ypN1–3; p=0.019, 5-year disease-free survival [DFS]; p=0.005, 5-year overall survival [OS]) and lymphovascular invasion (LVI) (p=0.003, 5-year DFS; p=0.006, 5-year OS) in the univariate analysis. In the multivariate analysis, LVI was a significant factor in 5-year DFS (odds ratio 2.145, 95% confidence interval 1.064–4.324, p=0.033). There was no significant difference among molecular subtypes in DFS (p=0.161) or OS (p=0.084). CONCLUSION: LVI was associated with prognosis in patients with locally advanced breast cancer treated by NAC and surgery. However, molecular subtype had no effect on 5-year DFS or OS.

The effects of ecabet sodium on nuclear factor-kappa B activation and chemokine gene expression in Helicobacter pylori-infected human gastric epithelial cells / 대한내과학회지

BACKGROUND: Helicobacter pylori stimulates nuclear factor-kappa B (NF-kappa B) activation and chemokine expression of gastric epithelial cells. Although ecabet sodium (ecabet), a locally acting anti-ulcer drug, is known to have an anti-H. pylori activity, there is little known how ecabet acts anti-inflammatory effects in gastric epithelial cells infected with H. pylori. We investigated the effects of ecabet on chemokine gene expression and NF-kappa B activation of human gastric epithelial cells infected with H. pylori. METHODS: After the infection of Hs746T and MKN-45 gastric epithelial cell lines with cagA+cytotoxin+ H. pylori in the presence of ecabet, mRNA expression of chemokine such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) was assessed by quantitative RT-PCR, and chemokine secretion was measured by ELISA. NF-kappa B signals were assayed by electrophoretic mobility shift assay. The activation of NF-kappa B and IL-8 reporter genes was measured by luciferase assay. RESULTS: The treatment of ecabet (5 microgram/mL) decreased the transcription and secretion of chemokine IL-8 and MCP-1 from the gastric epithelial cells infected with H. pylori in a dose-dependent manner. In addition, ecabet inhibited NF-kappa B activation of gastric epithelial cells induced by H. pylori infection. Moreover, the inhibited NF-kappa B signal by ecabet was comprised of heterodimers of p65/p50 predominantly. CONCLUSION: These results suggest that ecabet can inhibit H. pylori-induced IL-8 and MCP-1 gene transcription via suppression of NF-kappa B signal.

Expression of Cyclooxygenase-2 in Human Intestinal Epithelial Cells Stimulated with Bacteroides fragilis Enterotoxin

A ~20 kDa heat-labile toxin (BFT) produced by enterotoxigenic B. fragilis induces chemokine responses that may be associated with mucosal inflammation. To determine whether epithelial cells can contribute to BFT-induced inflammation, we assessed the expression of cyclooxygenase (COX)-2 in BFT-stimulated human intestinal epithelial cells. Human intestinal epithelial cell lines, HT-29 and Caco-2, were incubated with purified BFT. COX-2 mRNA and protein expression were measured by quantitative RT-PCR and Western blot analysis, respectively. BFT increased expression of COX-2, not that of COX-1, in human intestinal epithelial cell lines. Up-regulated COX-2 expression was paralleled by increased prostaglandin E2 (PGE2) production measured by the radioimmunoassay. PGE2 was predominantly secreted from the basolateral surface of BFT-treated epithelial cells, whereas lactate dehydrogenase was released predominantly from the apical surface. Moreover, the COX-2 expression and PGE2 production were significantly suppressed when NF-kappaB activity was inhibited. The basolateral secretion of PGE2 by up-regulated COX-2 in the BFT-stimulated colon epithelial cells seems to contribute to the inflammatory response in the underlying intestinal mucosa.

Nuclear Factor - kappa B Activation and Signal Transduction Pathway in Human Intestinal Epithelial Cells Stimulated with Bacteroides fragilis Enterotoxin

No abstract available.

Expression of Cyclooxygenase - 2 in Intestinal Epithelial Cells in Response to Invasive Bacterial Infection and its Role of Epithelial Cell Apoptosis

Invasion of enteric bacteria, such as Salmonella and invasive E. coli, into intestinal epithelial cells induces proinflammatory gene responses and finally epithelial cell apoptosis. In this study, we asked whether invasive bacterial infection of human intestinal epithelial cells could upregulate cyclooxygenase-2 (COX-2) gene expression and whether increased COX-2 expression could influence intestinal epithelial cell apoptosis. Expression of COX-2 mRNA and prostaglandin (PG) E production were upregulated in HT-29 colon epithelial cells which were infected with S. dublin or invasive E. coli, as examined by quantitative RT-PCR and radioimmunoassay. Inhibition of COX-2 expression and PGE2 production using NS-398, a specific COX-2 inhibitor, showed a significant increase af epithelial cell apoptosis and caspase-3 activation in HT-29 cells infected with invasive bacteria. However, the addition of valerylsalicylate, a specific COX-1 inhibitor, did not change apoptosis in S. dublin-infected HT-29 cells. These results suggest that upregulated COX-2 expression and PGE2 production in response to invasive bacterial infection could contribute to host defense by inhibiting apoptosis of intestinal epithelial cells.