Prognostic significance of CD44s expression in resected non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; <it>n </it>= 82) and squamous cell carcinoma (SCC; <it>n </it>= 77). Additionally, the immunoreactivity of cyclooxygenase (COX)-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically.</p> <p>Results</p> <p>High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7%) than in those with AC histology (<it>P <</it>0.001). Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (<it>P </it>= 0.021). In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (<it>P </it>< 0.001), high-grade tumor differentiation (<it>P = </it>0.046), and high CD44s expression (<it>P = </it>0.014). For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (<it>P = </it>0.015). No significant association was found between CD44s and clinical outcome (<it>P </it>= 0.311).</p> <p>Conclusions</p> <p>High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.</p

Single nucleotide polymorphisms in bone turnover-related genes in Koreans: ethnic differences in linkage disequilibrium and haplotype

<p>Abstract</p> <p>Background</p> <p>Osteoporosis is defined as the loss of bone mineral density that leads to bone fragility with aging. Population-based case-control studies have identified polymorphisms in many candidate genes that have been associated with bone mass maintenance or osteoporotic fracture. To investigate single nucleotide polymorphisms (SNPs) that are associated with osteoporosis, we examined the genetic variation among Koreans by analyzing 81 genes according to their function in bone formation and resorption during bone remodeling.</p> <p>Methods</p> <p>We resequenced all the exons, splice junctions and promoter regions of candidate osteoporosis genes using 24 unrelated Korean individuals. Using the common SNPs from our study and the HapMap database, a statistical analysis of deviation in heterozygosity depicted.</p> <p>Results</p> <p>We identified 942 variants, including 888 SNPs, 43 insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557 (63%) had been previously identified and 331 (37%) were newly discovered in the Korean population. When compared SNPs in the Korean population with those in HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations and 20% of those in Caucasian and African subpopulations were significantly differentiated from the Hardy-Weinberg expectations. In addition, an analysis of the genetic diversity showed that there were no significant differences among Korean, Han Chinese and Japanese populations, but African and Caucasian populations were significantly differentiated in selected genes. Nevertheless, in the detailed analysis of genetic properties, the LD and Haplotype block patterns among the five sub-populations were substantially different from one another.</p> <p>Conclusion</p> <p>Through the resequencing of 81 osteoporosis candidate genes, 118 unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the Korean population. In addition, using the common SNPs between our study and HapMap, an analysis of genetic diversity and deviation in heterozygosity was performed and the polymorphisms of the above genes among the five populations were substantially differentiated from one another. Further studies of osteoporosis could utilize the polymorphisms identified in our data since they may have important implications for the selection of highly informative SNPs for future association studies.</p

AKT1 polymorphisms are associated with risk for metabolic syndrome

Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin, insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that make up metabolic syndrome. We studied a 12-kb region including the first exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n = 574; age 23.7 ± 5.7 years), Strong Heart Study (SHS) (n = 2,134; age 55.5 ± 7.9 years), Dynamics of Health, Aging and Body Composition (Health ABC) (n = 3,075; age 73.6 ± 2.9 years), and Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) (n = 175; age 40–65 years)]. We identified a three SNP haplotype that we call H1, which represents the ancestral alleles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. In older African-American and European American subjects (Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p < 0.001). In middle-aged European Americans with insulin resistance (STRRIDE) studied by intravenous glucose tolerance test (IVGTT), H1 carriers showed increased insulin resistance due to the Sg component (p = 0.021). The 12-kb haplotype is a risk factor for metabolic syndrome and insulin resistance that needs to be explored in further populations

Stability comparison of anterior cruciate ligament between double- and single-bundle reconstructions

The purpose of this study was to evaluate the intra-operative stability during double-bundle anterior cruciate ligament (ACL) reconstructions (20 knees) using a navigation system and compare the results with those obtained from single-bundle reconstructions (20 knees). After registering the reference points during ACL reconstruction, antero-posterior and rotational stability tests with 30° knee flexion using a navigation system were measured before and after reconstructions on both groups. The change of antero-posterior translation after and before reconstruction was 12.5 mm in the double-bundle group and 10.5 mm in the single-bundle group, showing significant inter-group difference (p=0.014, from 17.5 mm to 5.1 mm in the double-bundle and from 16.6 mm to 6.1 mm in the single-bundle group). The mean rotational stability of the double-bundle group also showed more significant improvement after reconstruction compared to that of the single-bundle group (9.8° in the double- and 5.6° in the single-bundle groups, p<0.001). These findings suggest that a double-bundle ACL reconstruction restores greater knee stability with respect to the antero-posterior and rotational stability than a single-bundle reconstruction

A meta-analysis of the relationship between density and travel behavior

To generalize the relationship between density and travel behavior, previous research proceeded with three approaches: metropolitan-level studies describing tendencies on an international scale, area-specific studies extrapolating their outcomes to other areas, and research syntheses pooling descriptive or quantitative outcomes of the studies. However, little research investigated the contextual effect of study areas on the density–travel relationship. Thus, this study conducts meta-analysis to investigate how the magnitude of the relationship differs between two areas that have been frequently studied: the United States and Europe. A pre-test shows that the way of measuring density and travel behavior does not affect the variation in study outcomes, whereas a post-test or sensitivity analysis indicates that the rigor of research designs and statistical techniques affects the variation. The main test finds that the density–travel relationship is significantly stronger in Europe than in the United States. The magnitude difference between the areas is maintained after controlling for confounders, including research design and technical rigor