Sulindac prevents esophageal adenocarcinomas induced by gastroduodenal reflux in rats

PURPOSE: It is known that cyclooxygenase (COX)-2 expression is increased in Barrett's esophagus and esophageal adenocarcinomas. We studied COX-2 expression and the effect sulindac has on the genesis of Barrett's esophagus and adenocarcinoma in rats undergoing esophagogastroduodenal anastomosis (EGDA). MATERIALS AND METHODS: Fifty-one rats were divided into a control group (n=27), a 500 ppm sulindac-treated group (n=15) and 1000 ppm sulindac-treated group (n=9). Randomly selected rats were killed by diethyl ether inhalation at 20 and 40 weeks after surgery. RESULTS: At 40 weeks, rats treated with 1000 ppm sulindac showed narrower esophageal diameter and milder inflammation than the control rats. At 40 weeks, the incidence of Barrett's esophagus was similar between control and sulindac-treated groups, but the incidence of adenocarcinoma was significantly lower in the 1000 ppm sulindac-treated group than either the control or 500 ppm sulindac-treated groups. COX-2 was significantly increased in the lower esophagus of control rats killed at 40 weeks. Cyclin D1 expression was negligible in the sulindac- treated group compared with the control group. CONCLUSION: We suggest that the chemopreventive effect of sulindac is related to decreased COX-2 and cyclin D1 expression, which may be influenced by reduced inflammation.     

Analysis of prognostic factors and treatment modality changes in breast cancer: a single institution study in Korea

PURPOSE: To determine the effects of new breast cancer treatments and to provide a baseline for monitoring the development of breast cancer in Korean women, we conducted an analysis at our institution to determine long-term clinicopathological features, survival rates, and prognostic factors. MATERIALS AND METHODS: This study retrospectively analyzed 2,403 patients between Sep 1994 and Dec 2002, who underwent breast cancer surgery at Samsung Medical Center in Korea. Demographic data, pathologic records and surgical records were collected. RESULTS: After a median follow-up duration of 121.9 (range: 2-158.1) months, the 5-year disease free survival (DFS) was 82.8% and the 10-year DFS was 74.7%. The 5-year and 10-year overall survival (OS) rates were 89.4% and 82.9%, respectively. Using multivariate analyses, we determined that the nodal status (p < 0.001), angioinvasion (p < 0.001), positive PR (p < 0.001), and C-erb-B2 (p < 0.001) were independent prognostic factors for OS. The frequency of breast conserving surgery was 33.9% before Dec 1999, and increased up to 44.1% by year Dec 2002. CONCLUSION: Most of the prognostic variables and clinical characteristics of the Korean breast cancer patients were similar to those reported for Western populations. However, the age distribution in Korean patients seemed to be different from that in patients from Western countries.     

Positive-thinking and life satisfaction amongst Koreans

PURPOSE: The present study examined the positive-thinking and life satisfaction of the general Korean population. In particular, we examined the role of positive-thinking on participants' life satisfaction. MATERIALS AND METHODS: We conducted a telephone survey of 409 respondents (194 males, 215 females). The participants provided self-reports on their positive thinking, life satisfaction and demographic information. RESULTS: The results showed that age, education, occupation, and family income had an influence on positive- thinking as well as life satisfaction in Korea. Specifically, younger respondents and persons with high incomes or higher education degrees were more likely to have higher positive scores and thus higher life satisfaction scores. However, after controlling for the demographic variables, positive thinking significantly affected life satisfaction(R(2) Change=0.170, F= 88.56, p < 0.001). CONCLUSION: We provided empirical evidence that positive thinking may indeed play a significant role in life satisfaction. Therefore, positive thinking would offer important direction for the growth of life satisfaction and interventions aiming to remediate the effects of demographic variables on life satisfaction.     

Influence of combined methionine synthase (MTR 2756A > G) and methylenetetrahydrofolate reductase (MTHFR 677C > T) polymorphisms to plasma homocysteine levels in Korean patients with ischemic stroke

PURPOSE: Methionine synthase (MTR) and 5,10-methylenetetrahydrofolate reductase (MTHFR) are the main regulatory enzymes for homocysteine metabolism. The present case- control study was conducted to determine whether there is an association between the MTR 2756A > G or MTHFR 677C > T polymorphism and plasma homocysteine concentration in Korean subjects with ischemic stroke. MATERIALS AND METHODS: DNA samples of 237 patients who had an ischemic stroke and 223 age and sex-matched controls were studied. MTR 2756A > G and MTHFR 677C > T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Frequencies of mutant alleles for MTR and MTHFR polymorphisms were not significantly different between the controls and cases. The patient group, however, had significantly higher homocysteine concentrations of the MTR 2756AA and MTHFR 677TT genotypes than the control group (p=0.04 for MTR, p=0.01 for MTHFR). The combined MTR 2756AA and MTHFR 677TT genotype (p= 0.04) and the homocysteine concentrations of the patient group were also higher than those of the controls. In addition, the genotype distribution was significant in the MTHFR 677TT genotype (p=0.008) and combined MTR 2756AA and MTHFR 677TT genotype (p=0.03), which divided the groups into the top 20% and bottom 20% based on their homocysteine levels. CONCLUSION: The results of the present study demonstrate that the MTR 2756A > G and MTHFR 677C > T polymorphisms interact with elevated total homocysteine (tHcy) levels, leading to an increased risk of ischemic stroke.     

Influence of substratum surface chemistry/energy and topography on the human fetal osteoblastic cell line hFOB 1.19: Phenotypic and genotypic responses observed in vitro

Time-dependent phenotypic response of a model osteoblast cell line (hFOB 1.19, ATCC, and CRL-11372) to substrata with varying surface chemistry and topography is reviewed within the context of extant cell-adhesion theory. Cell-attachment and proliferation kinetics are compared using morphology as a leading indicator of cell phenotype. Expression of (alpha2, alpha3, alpha4, alpha5, alphav, beta1, and beta3) integrins, vinculin, as well as secretion of osteopontin (OP) and type I collagen (Col I) supplement this visual assessment of hFOB growth. It is concluded that significant cell-adhesion events-contact, attachment, spreading, and proliferation-are similar on all surfaces, independent of substratum surface chemistry/energy. However, this sequence of events is significantly delayed and attenuated on hydrophobic (poorly water-wettable) surfaces exhibiting characteristically low-attachment efficiency and long induction periods before cells engage in an exponential-growth phase. Results suggest that a 'time-cell-substratum-compatibility-superposition principle' is at work wherein similar bioadhesive outcomes can be ultimately achieved on all surface types with varying hydrophilicity, but the time required to arrive at this outcome increases with decreasing cell-substratum-compatibility. Genomic and proteomic tools offer unprecedented opportunity to directly measure changes in the cellular machinery that lead to observed cell responses to different materials. But for the purpose of measuring structure-property relationships that can guide biomaterial development, genomic/proteomic tools should be applied early in the adhesion/spreading process before cells have an opportunity to significantly remodel the cell-substratum interface, effectively erasing cause and effect relationships between cell-substratum-compatibility and substratum properties. IMPACT STATEMENT: This review quantifies relationships among cell phenotype, substratum surface chemistry/energy, topography, and cell-substratum contact time for the model osteoblast cell line hFOB 1.19, revealing that genomic/proteomic tools are most useful in the pursuit of understanding cell adhesion if applied early in the adhesion/spreading process.     

Activation of non-canonical NF-kappaB pathway mediated by STP-A11, an oncoprotein of Herpesvirus saimiri

Although Saimiri Transforming Protein (STP)-A11, an oncoprotein of Herpesvirus saimiri, has been known to activate NF-kappaB signaling pathway, the detailed mechanism has not been reported yet. We herein report that STP-A11 activates non-canonical NF-kappaB pathway, resulting in p100 processing to p52. In addition, translocation of p52 protein (NF-kappaB2) into the nucleus is observed by the expression of STP-A11. STP-A11-mediated processing of p100 to p52 protein requires proteosome-mediated proteolysis because MG132 treatment clearly blocked p52 production in spite of the expression of STP-A11. Analysis of STP-A11 mutants to activate NF-kappaB2 pathway discloses the requirement of TRAF6-binding site not Src-binding site for STP-A11-mediated NF-kappaB2 pathway. Blockage of STP-A11-mediated p52 production using siRNA against p52 enhanced a chemotherapeutic drug-mediated cell death, suggesting that p52 production induced by the expression of STP-A11 would contribute to cellular transformation, which results from a resistance to cell death.     

Matrix metalloproteinase-9 activity is associated with poor prognosis in T3-T4 node-negative colorectal cancer

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a novel membrane-anchored matrix metalloproteinase (MMP) inhibitor. RECK, MMP-2, and MMP-9 are believed to play crucial roles in tumor progression. This study was designed to examine the prognostic value of RECK, MMP-2, and MMP-9 in conjunction with other clinicopathologic factors in patients of T3-T4 node-negative colorectal cancer. RECK and MMP expression was observed using immunohistochemical analysis of the primary tumor from 89 patients with curatively resected T3-4 N0 colorectal cancer retrospectively. High RECK expression was observed in 51 cases, whereas expression was low in the other 38 cases. MMP-2 and MMP-9 expression was positive in cancer cells in 24 and 33 cases, respectively. RECK and MMP-2 expression was not significantly associated with any clinicopathologic factors. However, expression of MMP-9 was correlated with tumor location. A statistically significant inverse correlation was found between RECK and MMP-2 expression, and a statistically significant correlation was found between MMP-2 and MMP-9 expression. However, no association between RECK and MMP-9 expression was observed. Univariate analysis demonstrated that rectal tumor location, preoperative carcinoembryonic antigen more than 5 ng/mL, positive lymphatic invasion, less than 12 dissected lymph nodes, and positive MMP-9 expression were poor prognostic factors of disease-free survival. A multivariate analysis confirmed that enhanced MMP-9 expression was an independent and significant factor for prediction of a poor prognosis. In addition, positive lymphatic invasion and less than 12 dissected lymph nodes were significant negative prognostic factors. In conclusion, MMP-9 status represents a novel prognostic factor in evaluation of T3-T4 node-negative colorectal cancer.     

Toxicity of Myristica fagrans seed compounds against Blattella germanica (Dictyoptera: Blattellidae)

The insecticidal constituents of hexane-soluble fraction from a methanolic extract of the seeds from Myristica fragrans (Myristicaceae) against adult females of Blattella germanica (L.) (Dictyoptera: Blattellidae) were analyzed by gas chromatography and gas chromatography-mass spectrometry. The insecticidal activity of 13 Myristica seed compounds against female B. germanica was examined by using the filter-paper contact toxicity and vapor phase toxicity bioassays. Results were compared with those of the other 23 known compounds of Myristica seed and currently used insecticides: dichlorvos, deltamethrin, permethrin, and propoxur. In contact toxicity tests using female B. germanica, (IS)-(-) -beta-pinene (0.06 mg/cm2) was the most toxic insecticide, based on 24-h LD50 values. The insecticidal activity of this compound was comparable with that of permethrin (0.05 mg/cm2). (1R)-(+) -Camphor, (1S)-(-) -camphor, dipentene, (1R)-(+) -3-pinene, and (+)-alpha-terpineol (0.10-0.14 mg/cm2) were more toxic than propoxur (0.19 mg/cm2). (E)-Sabinene hydrate and propoxur were almost equitoxic. Potent insecticidal activity also was observed with (R)-(+) -citronellal, (S)-(-) -citronellal, (R)-(-) -alpha-phellandrene, (1S)-(-) -alpha-pinene, (1R)-(+) -alpha-pinene, and safrole (0.27-0.48 mg/cm2). In vapor phase toxicity tests, the compounds tested were effective in closed but not in open containers. These results indicate that the effect of these compounds was largely a result of action in the vapor phase. Myristica seed compounds described merit further study as potential insecticides or as leads for the control of cockroaches.     

Increased expression of Gab2, a scaffolding adaptor of the tyrosine kinase signalling, in gastric carcinomas

AIMS: Mounting evidence indicates that alterations of protein kinase signalling pathways play crucial roles in the pathogenesis of cancers. Gab2 (Grb2-associated binding protein 2), a member of the family of Gab scaffolding adaptors, transmits and amplifies the signals from receptor tyrosine kinases. A recent study demonstrated that Gab protein was over-expressed in breast cancers, and the over-expressed Gab2 increased proliferation and invasion of the cells, indicating that Gab2 is an oncogenic protein. However, the roles of Gab in other cancers are largely unknown. METHODS: In this study, to see whether Gab2 expression could be a characteristic of gastric cancers, we analysed the expression of Gab2 in 60 gastric adenocarcinomas by immunohistochemistry using a tissue microarray. RESULTS: In the normal gastric mucosal epithelial cells, Gab2 protein was expressed in parietal and zymogen cells, but not in other mucosal epithelial cells. In the cancer cells, Gab2 expression was detected in 40 (67%) of the 60 gastric adenocarcinomas. The Gab2 expression was observed in 12 (60%) of the 20 early gastric carcinomas and 28 (70%) of the 40 advanced gastric carcinomas. There was no significant association of Gab2 expression with clinocopathological characteristics, including invasion, metastasis and stage. CONCLUSION: Our data indicate that Gab2 over-expression is a feature not only of breast cancers, but also of gastric cancers. Increased expression of Gab2 in malignant gastric cells compared with normal epithelial cells suggests that Gab2 expression may play a role in gastric cancer development.