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The effects of suberoylanilide hydroxamic acid ( SAHA), a histone deacetylase inhibitor, have not been studied in esophageal squamous cell cancer ( ESCC). Cell viability assay; flow cytometry for cell cycle and annexin V apoptosis assays; assays for cell migration, invasion, and adhesion to extracellular matrix ( ECM); and immunoblotting and immunofluorescence staining were performed in three ESCC cell lines. Tumor xenograft with semiquantitative immunohistochemistry was used to study the effects of SAHA in vivo. SAHA effectively inhibited growth of ESCC cells with half-inhibitory concentrations ( IC50) ranging from 2.6 to 6.5 μmol/L. SAHA restored acetylation of histone 3 lysine 9 ( H3K9Ac) and histone 4 lysine 12 ( H4K12Ac) with an induction of G1 or G2 cell cycle arrest and apoptosis. Expression of cell cycle checkpoint regulatory proteins including cyclin-dependent kinases ( CDKs) and cyclins was decreased, whereas expression of cell cycle suppressors, p21, p27, and Rb was increased in ESCC cells after SAHA treatment. SAHA inhibited migration, invasion, and ECM adhesion in ESCC cells with an induction of E-cadherin expression. SAHA significantly inhibited growth of ESCC tumors with increased expression of p21, p27, Rb, and E-cadherin while decreasing expression of CDK4 and cyclin D1 within the murine tumors. In conclusion, SAHA had antigrowth activity against ESCC cells in vitro and in vivo while inhibiting cell migration, cell invasion, and ECM adhesion, suggesting its potential as an epigenetic therapeutic agent for ESCC. [ABSTRACT FROM AUTHOR]

Aim: To develop a faster and easier in vivo method to screen compounds for anti-oxidant activity using a microbial system. Methods and Results: Bacterial redox sensor-based assay systems were applied. The activities of SoxR and OxyR, the bacterial redox sensors, were monitored to probe the intracellular redox status through two reporter strains, Escherichia coli soxSp- lacZ and oxySp- lacZ fusions, which specifically respond to paraquat, a superoxide generator, and H2O2, respectively, with practically no cross reactivity. For the test screening, 27 natural compounds including phenolics and flavonoids that are putatively considered anti-oxidant nutritional supplements were collected and assayed for their capability to alleviate oxidative stress in these bacterial systems. Among them, rutin, kaempferol and quercetin had significant anti-H2O2 activity, and betaine, glycyrrhizic acid and baicalin had weak anti-superoxide activity. While rutin, kaempferol and quercetin significantly reduced the H2O2 stress at low concentrations, betaine, glycyrrhizic acid and baicalin required higher concentration for their anti-superoxide effects. In vitro, only quercetin protected DNA in a metal-catalysed oxidation system, suggesting that the other compounds might indirectly exert their anti-oxidant activities through other biological functions. Finally, quercetin, rutin and kaempferol significantly restored the viability of a superoxide dismutase mutant that has limited viability because of defective defence against oxidative stress. Conclusion: These bacterial systems could provide a more efficient method for measuring the activity of compounds affecting cellular oxidative stress and viability. Significance and Impact of the Study: The demand for anti-oxidant and anti-ageing activities is increasing in one of the fastest growing segments of the functional food market, but the screening for these activities is currently very laborious, expensive and time consuming. This study suggests a basis for a high throughput screening method for these activities. [ABSTRACT FROM AUTHOR]

Ciglitizone, a class of thiazolidinediones, acts as a potent activator of the adipose differentiation program in established preadipose cell lines. Thiazolidinediones have also been investigated in diabetic patients and have been reported to act as peroxisome proliferator-activated receptor-γ ligands. Intramuscular adipogenesis or marbling through transdifferentiation of satellite cells in cattle was successfully conducted earlier. In this report, the effects of ciglitizone on the differentiation pathway of porcine myogenic satellite cells was investigated. Semitendinosus muscle was aseptically taken from 10-d-old piglets under general anesthesia, and porcine satellite cells were obtained and grown to near confluence. Postconfluent cells (d 0) were further cultured in differentiation medium containing an adipogenic mixture plus ciglitizone (10 µM) for 48 h. From d 2 onward, the cells were cultured only in the presence of ciglitizone until d 10. Controls were cultured in differentiation medium only. Exposure of porcine satellite cells to the adipogenic mixture plus ciglitizone generated lipid droplets on d 2, and subsequently, exposure of cells to ciglitizone alone helped in cytoplasmic lipid filling, providing them with the acquisition of adipocyte morphology. An increase (P < 0.05) in the fusion (structures containing 2 to 3 nuclei) of satellite cells was observed, and myosin heavy chain appeared with greater intensity (immunohistochemistry) in the control group from d 2 onward. Adipocyte-specific transcriptional factors (i.e., CCAAT/enhancer binding protein-α and peroxisome proliferator-activated receptor-γ) were predominant during transdifferentiation and were observed with immuhistochemistry, Western blot (-47.2 and -60.4 kDa, respectively), and real-time PCR. Ciglitizone appeared to convert the differentiation pathway of satellite cells into that of adipoblasts. [ABSTRACT FROM AUTHOR]

The article presents a study on the effects of randomized clinical test of splenectomy versus splenic preservation on proximal gastric cancer patients. The researchers found that gastrectomy combined with splenectomy indicated connection with slightly higher morbidity and mortality rates. However, they concluded that obtained results did not support the application of prophylactic splenectomy to take away macroscopically negative lymph nodes near the spleen.

To understand moIecular genetic characteristics of Korean pigs, the genetic relationships of nine pig breeds including two Korean pigs (Korean native pig and Korean wild pig), three Chinese pigs (Mm pig, Xiang pig, and Wuzhishan pig), and four European breeds (Berkshire, Duroc, Landrace, and Yorkshire) were characterized from a 16-microsatellite loci analysis. The mean heterozygosity within breeds ranged from 0.494 to 0.703. Across multiple loci, significant deviation from Hardy-Weinberg equilibrium was observed in most pig breeds, except for two Chinese pigs (Mm pig and Wuzhishan pig). This deviation was in the direction of heterozygote deficit. Across population loci, 36 of 144 significantly deviated (P< 0.05) from Hardy-Weinberg equilibrium. The mean FST, a measure of genetic divergence among sub-populations, of all loci indicated that 26.1% of total variation could be attributed to the breed difference. Relationship trees based on the Nei's DA genetic distance and scatter diagram from principal component analysis consistently displayed pronounced genetic differentiation among the Korean wild pig, Xiang pig, and Wuzhishan pig. Individual assignment test using a Bayesian method showed 100% success in assigning Korean and Chinese individual pigs into their correct breeds of origin and 100% exclusion success from all alternative reference populations at P < 0.001. These findings indicate that the Korean native pig has been experiencing progressive interbreeding with Western pig breeds after originating from a North China pig breed with a black coat color. Considering the close genetic relationship of Korean pigs to the Western breeds such as Berkshire and Landrace, our findings can be used as valuable genetic information for the preservation and further genetic improvement of the Korean native pig. [ABSTRACT FROM AUTHOR]

Background: Body-weight loss has been reported as a poor prognostic factor for some malignancies. The purpose of this study was to evaluate the prognostic value of postoperative body-weight loss in patients with gastric cancer. Methods: In 564 patients who underwent curative resection for gastric cancer, usual body-weight, body-weight at the time of resection and that 6 and 12 months after resection were recorded prospectively. Results: The 5-year survival rate of patients who lost more than 5 per cent of their 6-month postoperative weight by 12 months after resection was 63 per cent while that of patients who maintained 95 per cent or more of their 6-month postoperative weight was 84 per cent (P < 0·001). Multivariate analysis revealed that serosal invasion, nodal metastasis, body-weight loss during the second 6-month interval after resection and extent of gastric resection were independent prognostic indicators. Conclusion: When a patient loses body-weight during the second 6-month interval after curative resection for gastric cancer, recurrent disease should be suspected. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated that inhibitors of cyclooxygenase (COX) attenuate various neuronal injuries and age-dependent demented conditions. From these findings, we proposed to test the effect of age on COX activity and its possible suppression by the antiaging action of dietary restriction in the rat brain. The status of reactive oxygen species (ROS) was also assessed to correlate with COX activity to delineate the underlying mechanism of the altered COX activity during aging. These results showed that COX activity significantly increased in 24-month-old rats compared with 6-month-old rats in an ad libitum group. Interestingly, mRNA and protein levels of COX-2 showed little corresponding age-related change. The formation of ROS was found to increase gradually with age in ad libitum fed rats. However, dietary restriction suppressed the increase at the age of 24 months. To substantiate the relationship between ROS and COX activity when the rats were 24 months of age, we conducted in vitro experiments with a C6 glioma cell line. Together, it is concluded that increased COX activity with age is due to the activation of COX catalytic reaction by ROS without increased gene expression of COX-2 and that it is related to the increased pro-oxidant status in aged rats. [ABSTRACT FROM AUTHOR]

Cyclooxygenase (COX) is the key rate-limiting enzyme in the prostaglandin synthetic pathway. Two isoforms of COX have been identified: a constitutive COX-1 and an inducible COX-2, which is activated in response to various stimuli. We investigated the changes of COX-1 and COX-2 in rat heart during aging. We measured the age-related changes in the mRNA and protein levels of COX by using reverse-transcription polymerase chain reaction and Western blotting, respectively. COX-2 mRNA and protein levels increased with age, whereas those of COX-1 showed no change. The COX activity determined by prostaglandin E(2) production increased with age. Because the COX-catalyzed arachidonate cascade is an important source of reactive oxygen species (ROS) generation, changes in ROS generation and lipid peroxidation were also assessed. The amount of ROS generated by the COX pathway increased with age, as did the total ROS generation and lipid peroxidation. These results show that COX-2 activity increases with age, partially because of elevated transcriptional expression and protein content, and they suggest that increased COX-2 can play a role in oxidative alterations in the aged heart. [ABSTRACT FROM AUTHOR]

When a T cell hybridoma, 707.7, was treated with a Ca2+ ionophore (A23187), apoptotic cell death was induced. Interestingly, we observed that the expression of Tcf-1, a T cell-specific transcription factor, mRNA was reduced by 5-fold in the A23187-treated apoptotic cells compared to an ethanol-treated control. The hybridoma cells, however, did not display such a reduced expression of Tcf-1 mRNA upon treatment with buthionine sulfoxide, which is known to induce a necrosis-like cell death. When another T cell hybridoma, KMIs-8.3.5, was treated with A23187 and phorbol myristate acetate, which leads to activation-induced apoptosis, Tcf-1 expression was again greatly reduced. However, a mutant line (KCIT1-8.5) derived from KMIs-8.3.5, which produces IL-2 upon activation and is resistant to apoptosis, did not show such reduction in Tcf-1 expression. We also showed that the reduced expression level of CD3ε mRNA and surface TCR-CD3 complex in apoptotic T cells is caused by the reduced expression of Tcf-1. When 70.7 cells were transfected with a plasmid DNA pSVtcf-1, in which Tcf-1 gene expression is driven by the SV40 promoter, such reduction of the Tcf-1 mRNA and the surface expression of the TCR-CD3 complex were not observed upon apoptosis induction. Our results suggest that the reduced expression of Tcf-1 is specific for the apoptotic, but not for the activating, process of T cells and is also responsible for the reduced surface expression of the TCR-CD3 in apoptotic T cells. [ABSTRACT FROM PUBLISHER]