Favorable prognosis in colorectal cancer patients with co-expression of c-MYC and ß-catenin

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background The purpose of our research was to determine the prognostic impact and clinicopathological feature of c-MYC and β-catenin overexpression in colorectal cancer (CRC) patients. Methods Using immunohistochemistry (IHC), we measured the c-MYC and β-catenin expression in 367 consecutive CRC patients retrospectively (cohort 1). Also, c-MYC expression was measured by mRNA in situ hybridization. Moreover, to analyze regional heterogeneity, three sites of CRC including the primary, distant and lymph node metastasis were evaluated in 176 advanced CRC patients (cohort 2). Results In cohort 1, c-MYC protein and mRNA overexpression and ß-catenin nuclear expression were found in 201 (54.8 %), 241 (65.7 %) and 221 (60.2 %) of 367 patients, respectively, each of which was associated with improved prognosis (P = 0.011, P = 0.012 and P = 0.033, respectively). Moreover, co-expression of c-MYC and ß-catenin was significantly correlated with longer survival by univariate (P = 0.012) and multivariate (P = 0.048) studies. Overexpression of c-MYC protein was associated with mRNA overexpression (ρ, 0.479; P  0.05). Conclusions Co-expression of c-MYC and ß-catenin was independently correlated with favorable prognosis in CRC patient. We concluded that the expression of c-MYC and ß-catenin might be useful predicting indicator of CRC patients prognosis

Prognostic significance of natural killer cell-associated markers in gastric cancer: quantitative analysis using multiplex immunohistochemistry

Abstract Background Natural killer (NK) cells mediate the anti-tumoral immune response as an important component of innate immunity. The aim of this study was to investigate the prognostic significance and functional implication of NK cell-associated surface receptors in gastric cancer (GC) by using multiplex immunohistochemistry (mIHC). Methods We performed an mIHC on tissue microarray slides, including 55 GC tissue samples. A total of 11 antibodies including CD57, NKG2A, CD16, HLA-E, CD3, CD20, CD45, CD68, CK, SMA, and ki-67 were used. CD45 + CD3-CD57 + cells were considered as CD57 + NK cells. Results Among CD45 + immune cells, the proportion of CD57 + NK cell was the lowest (3.8%), whereas that of CD57 + and CD57- T cells (65.5%) was the highest, followed by macrophages (25.4%), and B cells (5.3%). CD57 + NK cells constituted 20% of CD45 + CD57 + immune cells while the remaining 80% were CD57 + T cells. The expression of HLA-E in tumor cells correlated with that in tumoral T cells, B cells, and macrophages, but not CD57 + NK cells. The higher density of tumoral CD57 + NK cells and tumoral CD57 + NKG2A + NK cells was associated with inferior survival. Conclusions Although the number of CD57 + NK cells was lower than that of other immune cells, CD57 + NK cells and CD57 + NKG2A + NK cells were significantly associated with poor outcomes, suggesting that NK cell subsets play a critical role in GC progression. NK cells and their inhibitory receptor, NKG2A, may be potential targets in GC

Protective effect of ultrasonication-processed ginseng berry extract on the D-galactosamine/lipopolysaccharide-induced liver injury model in rats

Background: Acute hepatic failure is a life-threatening critical condition associated with rapid deterioration of liver function and liver transplantation. Several studies have shown that Panax ginseng Mayer has antidiabetic and hepatoprotective effects. However, the hepatoprotective effect of ginseng berry is still unveiled. In this study, we evaluated the hepatoprotective effects of ultrasonication-processed ginseng berry extract (UGBE) on acute hepatic failure model in rats. Methods: Ginseng berry extract (GBE) was ultrasonically processed. The GBE, silymarin, and UGBE were orally administered to male Sprague-Dawley rats for 4 wk. Twenty-four h after the last administration, rats were challenged with D-galactosamine (D-GalN)/lipopolysaccharide (LPS). Results: After ultrasonication, the component ratio of ginsenosides Rg2, Rg3, Rh1, Rh4, Rk1, Rk3, and F4 in GBE had been elevated. Administration of UGBE significantly increased the survival rate of D-GalN/LPS-challenged rats. Pretreatment with UGBE significantly decreased serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels in D-GalN/LPS-challenged rats in a dose-dependent manner. The levels of enzymatic markers for oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and glutathione) were increased by UGBE treatment in a dose-dependent manner. Tumor necrosis factor alphalevel, inducible nitric oxide synthase activities, and nitric oxide productions were reduced by UGBE treatment. In addition, hemeoxygenase-1 levels in liver were also significantly increased in the UGBE-treated group. The protein expression of toll-like receptor 4 was decreased by UGBE administration. Hematoxylin and eosin staining results also supported the results of this study showing normal appearance of liver histopathology in the UGBE-treated group. Conclusion: UGBE showed a great hepatoprotective effect on D-GalN/LPS-challenged rats via the toll-like receptor 4 signaling pathway. Keywords: acute liver failure, ginseng berry, hepatotoxicity, toll-like receptor 4, ultrasonicatio

The Effect of DA-9701 on 5-Hydroxytryptamine-Induced Contraction of Feline Esophageal Smooth Muscle Cells

Serotonin, or 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter found in blood platelets, the gastrointestinal (GI) tract, and the central nervous system (CNS) of animals and humans. The signaling pathways of 5-hydroxytryptamine (5-HT)-induced contractions in cat esophageal smooth muscle cell (ESMC)s have been identified, but the downstream components of the 5-HT signaling pathway remain unclear. DA-9701 is the standardized extract of the Pharbitis nil Choisy seed (Pharbitidis Semen, Convolvulaceae) and the root of Corydalis yahusuo W.T. Wang (Corydalis Tuber, Papaveraceae). DA-9701 is known to have strong gastroprokinetic effects and a good safety profile. In this study, we investigated the 5-HT signaling pathway at the G-protein level, and we explored the mechanisms by which DA-9701 induces smooth muscle contraction. Freshly isolated smooth muscle cells were harvested from the feline esophagus, and cells were permeabilized to measure their length. 5-HT produced esophageal smooth muscle contractions in a dose-dependent manner. Furthermore, 5-HT produced a relatively long-acting contraction. 5-HT binds to the 5-HT2, 5-HT3 and 5-HT4 receptors to induce smooth muscle contraction in feline ESMCs. These receptors, which are located in esophageal smooth muscle, are coupled to Gαq, Gαo and Gαs. These G proteins activate PLC, which leads to Ca2+/calmodulin-dependent MLCK activation, resulting in MLC20 phosphorylation and cell contraction. Conversely, DA-9701 inhibits 5-HT-induced contraction by inhibiting MLC20 phosphorylation