Zheng Y.,Harvard University |
Lee S.,Harvard University |
Lee S.,Medical Genomics Research Center |
Liang X.,Harvard University |
And 4 more authors.
Journal of Infectious Diseases | Year: 2013
Background. Sepsis and sepsis-associated organ failure are devastating conditions. Understanding the detailed cellular/molecular mechanisms involved in sepsis should lead to the identification of novel therapeutic targets. Methods. Cecal ligation and puncture (CLP) was used as a polymicrobial sepsis model in vivo to determine mortality and end-organ damage. Macrophages were adopted as the cellular model in vitro for mechanistic studies. Results. PTRF+/- mice survived longer and suffered less organ damage after CLP. Reductions in nitric oxide (NO) and iNOS biosynthesis were observed in plasma, macrophages, and vital organs in the PTRF+/- mice. Using an acute sepsis model after CLP, we found that iNOS-/- mice had a comparable level of survival as the PTRF+/- mice. Similarly, polymerase I transcript release factor (PTRF) deficiency resulted in decreased iNOS and NO/ROS production in macrophages in vitro. Mechanistically, lipopolysaccharide (LPS) enhanced the co-localization and interaction between PTRF and TLR4 in lipid rafts. Deletion of PTRF blocked formation of the TLR4/Myd88 complex after LPS. Consistent with this, lack of PTRF impaired the TLR4 signaling, as shown by the decreased p-JNK, p-ERK, and p-p38, which are upstream factors involved in iNOS transcription. Conclusion. PTRF is a crucial regulator of TLR4 signaling in the development of sepsis. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Yun S.J.,Chungbuk National University |
Kim S.-K.,Medical Genomics Research Center |
Kim S.-K.,Korea Research Institute of Bioscience and Biotechnology |
Kim W.-J.,Chungbuk National University
Investigative and Clinical Urology | Year: 2016
High-grade T1 bladder cancer has a poor prognosis due to a higher incidence of recurrence and progression than other nonmuscle invasive bladder cancer; thus patients with high-grade T1 have to be carefully monitored and managed. If patients are diagnosed with high-grade T1 at initial transurethral resection (TUR), a second TUR is strongly recommended regardless of whether muscle layer is present in the specimen because of the possibility of understating due to incomplete resection. Since high-grade T1 disease shows diverse clinical courses, individual approaches are recommended for treatment. In cases with low risk of progression, cystectomy could represent overtreatment and deteriorate quality of life irreversibly, while, in those with high risk, bacillus Calmette– Guérin (BCG) therapy may worsen survival by delaying definitive therapy. Therefore, a strategy for predicting prognosis based on the risk of progression is needed for managing high-grade T1 disease. Molecular risk classifiers predicting the risk of progression and response to BCG may help identify the optimal management of high-grade T1 disease for each individual. © The Korean Urological Association, 2016.
Kim S.K.,Medical Genomics Research Center |
Kim S.K.,Korea Research Institute of Bioscience and Biotechnology |
Kim J.H.,Medical Genomics Research Center |
Kim J.H.,Korean University of Science and Technology |
And 4 more authors.
Bioinformatics | Year: 2014
Because cancer has heterogeneous clinical behaviors due to the progressive accumulation of multiple genetic and epigenetic alterations, the identification of robust molecular signatures for predicting cancer outcome is profoundly important. Here, we introduce the APPEX Web-based analysis platform as a versatile tool for identifying prognostic molecular signatures that predict cancer diversity. We incorporated most of statistical methods for survival analysis and implemented seven survival analysis workflows, including CoxSingle, CoxMulti, IntransSingle, IntransMulti, SuperPC, TimeRoc and multivariate. A total of 236 publicly available datasets were collected, processed and stored to support easy independent validation of prognostic signatures. Two case studies including disease recurrence and bladder cancer progression were described using different combinations of the seven workflows. © The Author 2014. Published by Oxford University Press.
Kim H.S.,Catholic University of Korea |
Kim J.O.,Catholic University of Korea |
Lee D.H.,Catholic University of Korea |
Lee H.C.,Medical Genomics Research Center |
And 6 more authors.
Oncology Reports | Year: 2011
The BRAF T1799A mutation is a heterozygous point mutation and its reported prevalence in papillary thyroid carcinoma (PTC) has varied from 29 to 83%, with an overall mean of 44%. In Korea, the reported mutation rate reached 83% in PTC and 52% in micropapillary carcinoma. We hypothesized that the differences in prevalence may be influenced by the methods of mutation analysis, the sizes of tumor and ethnic differences. Three types of DNA samples from the same PTC mass (0.4-1.6 cm, mean 0.83 cm sized) per each patient (n=17) were isolated. The first type was obtained from frozen PTC tissues using laser-captured microdissection (Frozen-laser, n=17), the second was obtained from frozen tissue by manual tumor margin dissection using a blade (Frozen-blade, n=17) and the third was obtained from formalin-fixed, paraffin-embedded tissue by manual margin dissection (Paraffin-blade, n=15, 2 failed). The mutation rates of the three-matched DNA samples were compared by the SNP mode and AQ mode of pyrosequencing, and direct DNA sequencing. Both the AQ mode of pyrosequencing and the direct DNA sequencing detected the BRAF T1799A mutation in 100% of the 'Frozen-laser' samples, but the mutation was omitted in 1/17 of the 'Frozen-blade' samples and in 5/15 of the 'Paraffin-blade' samples, while the former was more rapid and objective than the latter. The SNP mode of pyrosequencing variably detected the mutation from 40 to 100%, and it showed the lowest sensitivity. Our results indicate that the reported prevalence of the BRAF T1799A mutation in PTC can be underestimated due the mutation analysis methods, and especially in small PTCs. The BRAF T1799A mutation may be an early and essential carcinogenic event in nearly all Korean PTCs, and even in micro-PTCs. For the accurate detection of the BRAF T1799A mutation from small PTCs, fresh or frozen tissues and more cautious microdissection are required, and the AQ mode of pyrosequencing assay is preferred. Copyright © 2011 Spandidos Publications Ltd. All rights reserved.
PubMed | Medical Genomics Research Center
Type: Journal Article | Journal: Cancer letters | Year: 2012
IL-32 is a newly discovered cytokine. Recently, various reports suggest that it plays a role as a proinflammatory mediator and may be involved in several cancer carcinogenesis. However, IL-32 expression in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression and role of IL-32 in hepatocellular carcinoma, because IL-32 was identified as an upregulated gene in hepatocellular carcinoma tissues compared to nontumorous regions using DNA microarray. IL-32 was overexpressed in tissue and serum from patients with HCC and localized in the cytoplasm and nucleus of hepatocellular carcinoma tumor cells. Moreover, secreted IL-32 concentration in the serum of patients with hepatocellular carcinoma was elevated as compared with those in the normal serum using a developed sandwich ELISA. Furthermore, IL-32 suppression in hepatocellular carcinoma decreased expression of phospho-p38 MAPK, NF-B, and antiapoptotic protein Bcl-2 and induced expression of proapoptotic proteins as well as p53 and PUMA resulting in the suppression of cell growth and induction of intrinsic apoptosis. Based on our results, we suggest that IL-32 is involved in the progression of hepatocellular carcinoma and may be a useful biomarker for diagnosis and therapeutic target of hepatocellular carcinoma.