Over the last two decades, entrepreneurship has emerged as a mainstream business discipline in the United States. Even after the collapse of the dotcom phenomenon, the global explosion of e-business and new business opportunities created by advances in information and telecommunication technologies (ICT) have widely popularized entrepreneurship for new venture creation. But while entrepreneurship is becoming more prevalent throughout the world, its education by country differs according to cultural context. This paper presents the results of a study on the impact of entrepreneurship education in the U.S. and Korea.

Purpose: To identify epigenetic molecular makers in plasma for the early detection of colorectal cancer. Experimental Design: We retrospectively analyzed the methylation status of 10 genes in fresh-frozen tissues and corresponding plasma samples from 243 patients with stage I and II sporadic colorectal cancer, 276 healthy individuals, and plasma from 64 colorectal adenoma patients using methylation-specific PCR. The methylation score (M score) was used to find molecular markers with high sensitivity and specificity. Results: Of the 243 colorectal cancer tissues, methylation was detected in 18% for p14, 34% for p16, 27% for APC, 34% for DAPK, 32% for HLTF, 21% for hMLH1, 39% for MGMT, 24% for RARβ2, 58% for RASSF2A, and 74% for Wif-1. Receiver operator characteristic curve analysis in plasma from 243 patients with cancer and 276 healthy individuals showed that the M score of any single gene had a sensitivity of <40% after controlling for age, sex, and tumor location. The specificity of the M score was not different between multigene and single gene analyses, but the sensitivity of the M score was significantly increased by multigene analysis. For all patients, the M score in a model including APC, MGMT, RASSF2A, and Wif-1 genes had a sensitivity of 86.5% and a specificity of 92.1% when 1.6 was used as a cutoff. In this model, the M score had a positive predictive value of 90.6% and a negative predictive value of 88.8%. Conclusion: The present study suggests that tumor-specific methylation of APC, MGMT, RASSF2A, and Wif-1 genes might be a valuable biomarker in plasma for the early detection of colorectal cancer. (Clin Cancer Res 2009;15(19):6185-91)

Key words: RUNX3; methylation; colon cancerColorectal cancer (CRC) is one of the leading causes of cancerrelated deaths in the United States. In its early stages, colon carcinogenesis is associated with alterations in molecular signaling pathways and then progresses as a result of a sequential accumulation of events that either activate oncogenes or inactivate tumor suppressor genes. 1 Some alterations participating in multistep colon carcinogenesis affect APC, K-Ras, p53 and elements of the TGF-␤ signaling pathway, such as TGF␤RII and SMAD4. The TGF-␤ signaling pathway serves as a major tumor suppressor in a variety of human gastrointestinal tumors, including colon, gastric and pancreatic cancer. 2 The downstream transcriptional targets of the TGF-␤ signaling pathways are key mediators for regulating cellular proliferation, extracellular matrix production and immune surveillance, and also dictate gastrointestinal epithelial development.The runt-domain related (RUNX) transcription factors are mammalian homologues of the Drosophila genes runt and lozenge, and are heterodimeric proteins composed of 2 highly conserved DNA binding subunits, ␣ and ␤. 3 RUNX transcription factors are one of the important targets of TGF-␤ superfamily signaling and play critical functions in mammalian development. RUNX proteins have been shown to interact with downstream SMAD proteins in mediating the growth suppressive effects of TGF-␤ and play an important role in development and oncogenesis. 3 Three mammalian runt-related genes, RUNX1, RUNX2 and RUNX3 have been described. RUNX1 is an indispensable factor in hematopoiesis and angiogenesis, and anomalies in this gene are involved in about 30% of the cases of human acute leukemia. 4 RUNX2 collaborates with c-myc and Pim-1, and its over-expression in mice predisposes to the development of T-cell lymphoma. 5,6 RUNX3 is a putative tumor suppressor gene localized to chromosome 1p36, a region that exhibits frequent loss of heterozygosity (LOH) events in colon, gastric, breast and ovarian cancers. More recently, silencing of RUNX3 has been reported in gastrointestinal cancers in mice as well as humans. 7-10 Li and colleagues 8 demonstrated that the gastric mucosa of the RUNX3-null mouse exhibited hyperplasia due to stimulated proliferation and suppressed apoptosis of the epithelial cells. These cells were resistant to growth-inhibitory effects of TGF-␤, indicating that RUNX3 regulates the growth of gastric epithelial cells. 8 Physical interactions between the C-terminus of RUNX3 and SMAD that mediate transmission of TGF-␤ induced growth inhibitory signals to the nucleus have been already described. 11 Because the TGF-␤ mediated signaling pathway regulates cell growth in the human colon, it is possible that RUNX3 plays an important tumor suppressor role. In our study, we determined the prevalence of RUNX3 expression and its promoter methylation in human colon cancer cell lines and primary cancers, and defined the association of these events with MSI and TGF␤RII status. We further demonstrate t...

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Entrepreneurship has been emphasized in many countries as a way of boosting economic growth and job creation. As entrepreneurship is becoming popular around the world, its education should be customized according to each country's unique cultural context. The purpose of this paper is to identify differences among the selected nations in terms of factors that are important to enhance the pedagogical effect of entrepreneurship education. This is an empirical study based on the data collected from university students in the US, Korea, China and Fiji representing nations with significantly different cultural contexts. The results imply that customized approaches based on unique cultural context are needed for effective entrepreneurship education in each country.