Oncofetal gene SALL4 in aggressive hepatocellular carcinoma

Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment.

Clinical and testing protocols for the analysis of epidermal growth factor receptor mutations in East Asian patients with non-small cell lung cancer:a combined clinical-molecular pathological approach

Several randomized phase III studies in advanced stage non-small cell lung cancer (NSCLC) confirmed the superior response rate and progression-free survival of using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor as first-line therapy compared with chemotherapy in patients with activating EGFR mutations. Despite the need for EGFR mutation tests to guide first-line therapy in East Asian NSCLC, there are no current standard clinical and testing protocols.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Large-scale association analysis identifies new risk loci for coronary artery disease

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2)

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis

BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in the United States. Increased level of interleukin-8 (IL-8) and CXCR2 on tumours and in the tumour microenvironment has been associated with CRC growth, progression and recurrence in patients. Here, we aimed to evaluate the effects of tissue microenvironment-encoded IL-8 and CXCR2 on colon cancer progression and metastasis.

METHODS: A novel immunodeficient, skin-specific IL-8-expressing transgenic model was generated to evaluate colon cancer growth and metastasis. Syngeneic mouse colon cancer cells were grafted in CXCR2 knockout (KO) mice to study the contribution of CXCR2 in the microenvironment to cancer growth.

RESULTS: Elevated levels of IL-8 in the serum and tumour microenvironment profoundly enhanced the growth of human and mouse colon cancer cells with increased peri-tumoural angiogenesis, and also promoted the extravasation of the cancer cells into the lung and liver. The tumour growth was inhibited in CXCR2 KO mice with significantly reduced tumour angiogenesis and increased tumour necrosis.

CONCLUSION: Increased expression of IL-8 in the tumour microenvironment enhanced colon cancer growth and metastasis. Moreover, the absence of its receptor CXCR2 in the tumour microenvironment prevented colon cancer cell growth. Together, our study demonstrates the critical roles of the tumour microenvironment-encoded IL-8/CXCR2 in colon cancer pathogenesis, validating the pathway as an important therapeutic target.

Population density and refractive error among Chinese children.

PURPOSE: China is urbanizing rapidly, and the prevalence of myopia is high. This study was conducted to identify the reasons for observed differences in the prevalence of myopia among urban versus rural Chinese children. METHODS: All children with uncorrected acuity of 6/12 or worse and a 50% random sample of children with vision better than 6/12 at all secondary schools in mixed rural-urban Liangying Township, Guangdong, underwent cycloplegic refraction, and provided data on age, gender, parental education, weekly near work and time outdoors, and urban development level of respondents' neighborhoods (12-item questionnaire). Population density of 32 villages and urban zones in Liangying was calculated from census figures (mean population density, 217 persons/km(2); range, 94-957; mean for Guangdong, 486). RESULTS: Among 5844 eligible children, 4612 (78.9%) had parental consent and completed examinations; 2957 were refracted per protocol, and 2480 (83.9%) of these had questionnaire data. Those with completed examinations were more likely to be girls (P < 0.001), and questionnaire respondents were more myopic (P = 0.02), but otherwise did not differ significantly from nonrespondents. In multivariate models, older age (P < 0.001), more near work (P = 0.02), and higher population density (P = 0.003), but not development index, parental education, or time outdoors were significantly associated with more myopic refractive error. CONCLUSIONS: Higher population density appears to be associated with myopia risk, independent of academic activity, time spent outdoors, familial educational level, or economic development, factors that have been thought to explain higher myopia prevalence among urban children. Mechanisms for this apparent association should be sought.

A Concert of Works by Ross Lee Finney, 1966

Concert Program for A Concert of Works by Ross Lee Finney, 1966

An exploratory study of how a Korean chaebol’s learning culture facilitates customer service

This paper explains how the organizational learning concept is used by managers in a global Korean company to promote group work, information sharing and an open communication style in order to produce a high level of customer service. Previously collected data from a set of in-depth personal interviews undertaken with three senior managers in a Korean electronics company were analyzed and interpreted using the grounded theory approach, and a number of propositions are put forward. The research findings show that managers in a chaebol deploy organizational learning to identify skilled and knowledgeable staff, and improve the organization’s capability by placing emphasis on developing harmonious, mutually oriented relationships that permeate throughout the organization. Top management demand that staff identify with government economic objectives and align the organization’s strategy accordingly so that the products produced are marketable. To achieve this, the organization fosters continual interaction among managers throughout the organization’s hierarchy. The chaebol’s organizational learning model encapsulates a “corollary” (continual communication) and “tools” (cultural influence and relationship management), and manifests in a unique strategy that allows management systems to evolve naturally.