Human mesenchymal stem cells (hMSCs) have generated a great deal of interest in clinical applications. The reason is that they may have the plasticity needed to differentiate into multiple lineages and the ability to expand ex vivo. For the therapeutic applications of hMSCs to be of practical use, it is crucial to assess the efficacy and safety of hMSCs in long-term ex vivo expansion. In this study, we cultured hMSCs by population doubling (PD) 60, and investigated their growth, osteogenic and adipogenic differential abilities, change of surface markers, telomerase activity, telomere length, and gene expression related to tumorigenesis. An in vivo tumorigenesis assay was also carried out. In long-term expanded hMSCs, the cells became aged above PD 30 and their adipogenic and osteogenic differentiation potential decreased. Telomerase activity unchanged whereas telomere length decreased and karyotypes were not changed. Gene expressions related to tumorigenesis decreased in proportion as the PD of hMSCs increased. In vivo transplantation of long-term cultured hMSCs to nude mice did not result in tumor formation. These findings suggest that diverse tests for cellular therapy should be considered during the ex vivo culture of hMSCs, particularly when a prolonged and extended propagation period is required.

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Purpose: Screening in cervical cancer is now progressing to discover candidate genes and proteins that may serve as biological markers and that play a role in tumor progression. W e examined the protein expression patterns of the squamous cell carcinoma (SCC) tissues from Korean women with using two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometer.Materials and Methods: Normal cervix and SCC tissues were solubilized and 2-DE was performed using pH 3～10 linear IPG strips of 17 cm length. The protein expression was evaluated using PDQuest 2-D software TM . The differentially expressed protein spots were identified with a MALDI-TOF mass spectrometer, and the peptide mass spectra identifications were performed using the Mascot program and by searching the Swiss-prot or NCBInr databases.Results: A total of 35 proteins were detected in SCC.17 proteins were up-regulated and 18 proteins weredownregulated. Among the proteins that were identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, α-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase and apolipoprotein a1) were protein previously known to be involved in tumor, and 21 proteins were newly identified in this study. Conclusion

Background/Aims: Chronic gastritis is a common finding during endoscopy and it is very important to describe it correctly. This study was designed to evaluate the distribution of endoscopic gastritis and the differences according to age, sex or area. Materials and Methods: A clinical analysis was conducted on 25,536 subjects who had undergone an upper endoscopy for routine health check-up. Endoscopic gastritis was classified into four types, superficial gastritis, erosive gastritis, atrophic gastritis and intestinal metaplasia. The distribution of the four types of gastritis was evaluated according to sex, age and area. Results: 51.6% of the patients had experienced at least one of the symptoms (epigastric pain or discomfort, soarness, dyspepsia, abdominal pain) on at least a few occasions during the previous year. The incidence of normal gastric finding was 3,593 (14.1%). 21,943 (85.9%) subjects have at least more than one of endoscopic gastritis. The number of cases with superficial gastritis was 7,983 (31.3%), erosive gastritis 6,054 (23.7%), atrophic gastritis 6,918 (27.1%), and intestinal metaplasia 1,181 (7.1%). Erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men than women (P＜0.001) and in the older age group (≥60 years) than younger age group (P＜0.001). Conclusions: The prevalence of endoscopic gastritis was very common, 85.9%. In addition, erosive gastritis, atrophic gastritis and intestinal metaplasia were more frequent in men and in the older age group, which is similar to gastric cancer or peptic ulcer.

Abstract. As 2 O 3 has been reported to induce apoptosis and inhibit the proliferation of various human cancer cells. We evaluated the ability of a novel arsenic compound, As 4 O 6 , along with As 2 O 3 in vitro and in vivo. To examine the levels of apoptosis of HPV 16-positive SiHa cervical cancer cell, flow cytometry and Western blotting were employed at various time intervals after two arsenic compound treatments. Ingenuity Pathway Analysis (IPA) was applied to investigate the differential cell death pathway of As 4 O 6 and As 2 O 3 . The results showed that As 4 O 6 was more effective in suppressing SiHa cell growth in vitro and in vivo compared to As 2 O 3 . In addition, the cell cycle was arrested at the sub-G 1 phase by As 4 O 6 . Western blot analysis showed that the proliferating cell nuclear antigen (PCNA) and Bcl-X L with sequence homology to Bcl-2 were significantly suppressed by As 4 O 6 . However, the apoptosis-related proteins such as p21 and Bax were overexpressed by As 4 O 6 . IPA suggested that there is a significant difference between As 2 O 3 -and As 4 O 6 -induced cell death pathways. Taken together, As 4 O 6 has a specific cell death pathway and possesses more potent anti-tumor effects on human cervical cancer cells in vitro and in vivo.

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The financial environment affects the level of R&D activity of a country. Using the proxy measures of macroeconomic financial environment variables, we show that cross-country differences in R&D activity, including expenditures, researchers, and patents etc., are correlated with the stock market turnover ratio. In particular, we found that the relationship was in direct relation to R&D expenditures or the number of researchers but indirect in relation to R&D outputs such as patents. These results imply that finance structure of an economy could enhance R&D activity through providing efficient resource allocation function. Other proxy measures of the financial environment such as banking sector size or stock market capitalization are not found to be significant. The size of the finance industry does not seem to change the national portfolio toward more high-risk innovative sectors. Financial quality, not size, determines the level of R&D intensity.Keywords: R&D; financial development; stock turnover ratio. * Corresponding author. 381 Rev. Pac. Basin Finan. Mark. Pol. 2010.13:381-401. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 08/17/15. For personal use only. 382 • Young-Soon Hwang, Hong-Ghi Min & Seung-Hun Han Rev. Pac. Basin Finan. Mark. Pol. 2010.13:381-401. Downloaded from www.worldscientific.com by UNIVERSITY OF CALIFORNIA @ SAN DIEGO on 08/17/15. For personal use only.

Human epithelial cells undergo morphological and molecular changes leading to terminal differentiation and replicative senescence after a finite number of cell divisions during serial subculture. However, the target genes and their functional significance in the senescence and differentiation in normal human oral keratinocytes have been poorly defined. Here, we demonstrated normal human oral keratinocytes transcriptional signature profiling to senescence and differentiation. Using microarray analysis, our findings indicated that the gene expression profiles induced by serial subculture are distinct classes of gene. The greatest number of these altered genes was identified as being related to biological pathways of transport, cell proliferation, cell cycle, defense and immune response, cell death, transcription, apoptosis, and inflammatory response, suggesting that the serial subculture is able to induce a multitude of specific gene expression changes during senescence and differentiation. Several highly upregulated genes (IL-1β, S100A8, S100A9, MMP1, MMP9, IL-8, BHLHB2, HES1, and TWIST1) in response to the serial subculture in normal human oral keratinocytes were observed. In vitro and in vivo studies also exhibited a close relationship between senescence and differentiation of primary oral keratinocytes and expression of inflammatory molecules. These results suggest a new approach to determine the biological events underlying the pathogenesis of oral keratinocyte aging.