• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.56-78
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• 1998

Objective: Chronic hepatitis B infection (CHB) occurs in 6% to 10% of population in Korea. In ethinic communities where prevalence of chronic infection is high such as Korea, transmission of hepatitis B infection is either vertical (ie, by perinatal infection) or by close family contact (usually from mothers or siblings) during the first 5 years of life. The development of chronic hepatitis B infection is increasingly more common the earlier a person is exposed to the virus, particularly in fetal and neonatal life. And it progress to cirrhosis and hepatocellular carcinoma, especially in severe liver damage and perinatal infection. Histopathology of CHB is important when evaluating the final outcomes. A numerical scoring system which is a semiquantitatively assessed objective reproducible classification of chronic viral hepatitis, is a valuable tool for statistical analysis when predicting the outcome and evaluating antiviral and other therapies. In this study, a numerical scoring system (Ludwig system) was applied and compared with the conventional histological classification of De Groute. And the comparative analysis of cinical findings, family history, serology, and liver function test by histopathological findings in chronic hepatitis B of children was done. Methods: Ninety nine patients [mean age=9 years (range=17 months to 16 years)] with clinical, biochemical, serological and histological patterns of chronic HBV infection included in this study. Five of these children had hepatocelluar carcinoma. They were 83 male and 16 female children. They all underwent liver biopsies and histologic evaluation was performed by one pathologist. The biopsy specimens were classified, according to the standard criteria of De Groute as follows: normal, chronic lobular hepatitis (CLH), chronic persistent hepatitis (CPH), mild to severe chronic active hepatitis (CAH), or active cirrhosis, inactive cirrhosis, hepatocellular carcinoma (HCC). And the biopsy specimens were also assessed and scored semiquantitatively by the numerical scoring Ludwig system. Serum HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc (IgG, IgM), and HDV were measured by radioimunoassays. Results: Male predominated in a proportion of 5.2:1 for all patients. Of 99 patients, 2 cases had normal, 2 cases had CLH, 22 cases had CPH, 40 cases had mild CAH, 19 cases had moderate CAH, 1 case had severe CAH, 7 cases had active cirrhosis, 1 case had inactive cirrhosis, and 5 cases had HCC. The mean age, sex distribution, symptoms, signs, and family history did not differ statistically among the different histologic groups. The numerical scoring system was correlated well with the conventional histological classification. The histological activity evaluated by both the conventional classification and the scoring system was more severe as the levels of serum aminotransferases were higher. In contrast, the levels of serum aminotransferases were not useful for predicting the degree of histologic activity because of its wide range overlapping. When the histological activity was more severe and especially the cirrhosis more progressing, the prothrombin time was more prolonged. The histological severity was inversely related with the duration of seroconversion of HBeAg. Conclusions: The histological activity could not be accurately predicted by clinical and biochemical findings, but by the proper histological classification of the numerical scoring system for the biopsy specimen. The numerical scoring system was correlated well with the conventional histological classification, and it seems to be a valuable tool for the statistical analysis when predicting the outcome and evaluating effects of antiviral and other therapies in chronic hepatitis B in children.

• Journal of Microbiology and Biotechnology
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• v.26 no.1
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• pp.197-206
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• 2016

Listeria monocytogenes is a foodborne pathogen of considerable genetic diversity with varying pathogenicity. Initially, we found that the strain M7 was far less pathogenic than the strain Lm850658 though both are serovar 4a strains belonging to the lineage III. Comparative genomic approaches were then attempted to decipher the genetic basis that might govern the strain-dependent pathotypes. There are 2,761 coding sequences of 100% nucleotide identity between the two strains, accounting for 95.7% of the total genes in Lm850658 and 92.7% in M7. Lm850658 contains 33 specific genes, including a novel 20K prophage whereas strain M7 has 130 specific genes, including two large prophages (38K and 44K). To examine the roles of these specific prophages in pathogenicity, the 20K and 38K prophages were deleted from their respective strains. There were virtually no differences of pathogenicity between the deletion mutants and their parent strains, although some putative virulent factors like VirB4 are present in the 20K region or holin-lysin in the 38K region. In silico PCR analysis of 29 listeria genomes show that only strain SLCC2540 has the same 18 bp integration hotspot as Lm850658, whereas the sequence identity of their 20K prophages is very low (21.3%). The 38K and 44K prophages are located in two other different hotspots and are conserved in low virulent strains M7, HCC23, and L99. In conclusion, the 20K and 38K prophages of L. monocytogenes serovar 4a strains Lm850658 and M7 are not related to virulence but contribute to genetic diversity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6651-6661
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• 2015

Breast cancer is a global health concern and is a major cause of death among women. In Oman, it is the most common cancer in women, with an incidence rate of 15.6 per 100,000 Omani females. Various anticancer remedies have been discovered from natural products in the past and the search is continuing for additional examples. Cytotoxic natural compounds may have a major role in cancer therapy either in potentiating the effect of chemotherapy or reducing its harmful effects. Recently, a few studies have reported advantages of using crude camel milk in treating some forms of cancer. However, no adequate data are available on the lyophilised camel's milk responsibility for triggering apoptosis and oxidative stress associated with human breast cancer. The present study aimed to address the role of the lyophilised camel's milk in inducing proliferation repression of BT-474 and HEp-2 cells compared with the non-cancer HCC1937 BL cell line. Lyophilized camel's milk fundamentally repressed BT-474 cells growth and proliferation through the initiation of either the intrinsic and extrinsic apoptotic pathways as indicated by both caspase-3 mRNA and its action level, and induction of death receptors in BT-474 but not the HEp-2 cell line. In addition, lyophilised camel's milk enhanced the expression of oxidative stress markers, heme-oxygenase-1 and reactive oxygen species production in BT-474 cells. Increase in caspase-3 mRNA levels by the lyophilised camel's milk was completely prevented by the actinomycin D, a transcriptional inhibitor. This suggests that lyophilized camel's milk increased newly synthesized RNA. Interestingly,it significantly (p<0.003) repressed the growth of HEp-2 cells and BT-474 cells after treatment for 72 hours while 24 hours treatment repressed BT-474 cells alone. This finding suggests that the lyophilised camel's milk might instigate apoptosis through initiation of an alternative apoptotic pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6073-6080
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• 2015

Background: Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24), a unique tumor suppressor gene, has killing activity in a broad spectrum of cancer cells. Herein, plasmids producing mda-7 proteins fused to different RGD peptides (full RGD4C and shortened RGD, tRGD) were evaluated for apoptosis induction with a hepatocellular carcinoma cell line, Hep-G2. The study aim was to improve the apoptosis potency of mda-7 by tethering to RGD peptides. Materials and Methods: Three plasmids including mda-7, mda-7-RGD and mda-7-tRGD genes beside a control vector were transfected into Hep-G2 cells. After 72 hours incubation, cell viability was evaluated by MTT assay. In addition, the rate of apoptosis was analyzed by flow cytometry using PI/annexin staining. To detect early events in apoptosis, 18 hours after transfection, expression of the BAX gene was quantified by real time PCR. Modeling of proteins was also performed to extrapolate possible consequences of RGD modification on their structures and subsequent attachment to receptors. Results and Conclusions: In MTT assays, while all mda-7 forms showed measurable inhibition of proliferation, unmodified mda-7 protein exhibited most significant effect compared to control plasmid (P<0.001). Again, flow cytometry analysis showed a significant apoptosis induction by simple mda-7 gene but not for those RGD-fused mda-7 proteins. These findings were also supported by expression analysis of BAX gene (P<0.001). Protein modelling analysis revealed that tethering RGD at the end of IL-24/Mda7 disrupt attachment to cognate receptor, IL-20R1/IL-20R2. In conclusion, fusion of RGD4C and shortened RGD peptides to carboxyl terminal of mda7, not only reduce apoptosis property in vitro but also disrupt receptor attachment as demonstrated by protein modelling.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2006.02a
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• pp.83-89
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• 2006

Cellular functions are carried out by a concerted action of biochemical pathways whose components have genetic interactions. Abnormalities in the activity of the genes that constitute or modulate these pathways frequently have oncogenic implications. Therefore, identifying the upstream regulatory genes for major biochemical pathways and defining their roles in carcinogenesis can have important consequences in establishing an effective target-oriented antitumor strategy We have analyzed the gene expression profiles of human liver cancer samples using cDNA microarray chips enriched in liver and/or stomach-expressed cDNA elements, and identified groups of genes that can tell tumors from non-tumors or normal liver, or classify tumors according to clinical parameters such as tumor grade, age, and inflammation grade. We also set up a high-throughput cell-based assay system (cell chip) that can monitor the activity of major biochemical pathways through a reporter assay. Then, we applied the cell chip platform for the analysis of the HCC-associated genes discovered from transcriptome profiling, and found a number of cancer marker genes having a potential of modulating the activity of cancer-related biochemical pathways such as E2F, TCF, p53, Stat, Smad, AP-1, c-Myc, HIF and NF-kB. Some of these marker genes were previously blown to modulate these pathways, while most of the others not. Upon a fast-track phenotype analysis, a subset of the genes showed increased colony forming abilities in soft agar and altered cell morphology or adherence characteristics in the presence of purified matrix proteins. We are currently analyzing these selected marker genes in more detail for their effects on various biological Processes and for Possible clinical roles in liver cancer development.

• Development and Reproduction
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• v.4 no.2
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• pp.187-193
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• 2000

Gonad and blood samples were taken from the cultured female Korean sea bass, Lateolabrax japonicus from October to February between 1997 and 1999. Gonadosomatic index began to increase in November and reached the highest value in December (12.8$\pm$1.5) and January (14.8$\pm$3.5), and then decreased sharply in February (2.6$\pm$1.5, p<0.05). The ovarian oocytes developed to tertiary yolk stage and reached fully-Brown stage in December and January, and then underwent atresia without maturation and ovulation in February. The plasma estradio3-17 $\beta$ level increased from November, and reached the highest value in December (1,152.3$\pm$107.2 pg/ml) and January (1,315.4$\pm$99.5 pg/ml), after then decreased in February (P<0.05). The concentration of plasma 17 $\alpha$ ,20 $\beta$-dihydroxy-4-pregnen-3-one was not significantly changed at low levels (86.6$\pm$6.5∼93.8$\pm$2.8 pg/ml) during the experimental period (P<0.05). All the fish with fully-grown oocytes in the ovary were matured and ovulated by HCG injection. The number of floating eggs were 325,000$\pm$26,000 at HCG 1,000 luhg and 195,000$\pm$35,000 at 2,000 lUikg. There was no difference in fertilization rate and hatching rate of the eggs (P<0.05). Considering these results, we could infer that the ovarian oocyte of the cultured Korean sea bass were not matured and ovulated because of the lack of gonadotropin surge. Moreover, HCG injection could induce oocyte maturation and ovulation in the cultured fish, and the effective dose was 1,000 IU/kg.

• The Korean Journal of Nuclear Medicine Technology
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• v.18 no.1
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• pp.89-93
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• 2014

Purpose: We investigated the quantitative evaluation of PET/CT images for evaluation after treatment in the treatment of liver metastasis of cancer with $^{90}YSIR$-Sphere. Materials and Methods: Confirmed the correlation between the measured counts was expressed by setting a region of interest from the image and a measure of the dose calibrator to see a correlation diagram of an image in a PET of $^{90}Y$. A portion uptake coefficients between PET images were acquired for 20 minutes LIST mode in 15 patients treated for liver metastasis of cancer using $^{90}Y$ SIR-Spheres high, intermediate portion, a lower portion, three measuring the coefficient of the region of interest is divided into parts, we studied the conditions for proper image acquisition. Results: Coefficient of sites that set the region of interest of the PET image and the measured counts of $^{90}Yappears$ that there is a correlation diagram statistically, ($R^2=0.956$), correlation diagram from the PET image of $^{90}Yis$, PET coefficient the coefficients of all regions of interest were increased in proportion to the image acquisition time, partial ROI coefficients of the PET image is higher about 10 minutes on average, about 14 minutes on average, the central portion is lower part 19 minute average in, confirmed the equilibrium of the standard deviation. Conclusion: Using the isotope $^{90}Y$, it is suitable to obtain a PET image, to obtain the time of proper image, the evaluation of PET/CT images, using the $^{90}Y$ SIR-Spheres and that in the treatment of liver metastases of cancer, it is useful for assessing treatment.