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Cho, Hyun Soo,Lee, Kyu-Yup,Choi, Hongsoo,Jang, Jeong Hun,Lee, Sang Heun S. Karger AG 2016 Audiology & neuro-otology Vol.21 No.3
<P>The aim of this study was to investigate the efficacy of preoperative and intraoperative steroid administration for inner ear protection in cochlear implantation (CI). Nineteen subjects who underwent CI were included in the study, and 10 subjects were enrolled as controls (steroid-administered group, n = 19; control group, n = 10). Dexamethasone (dexamethasone sodium phosphate, 5 mg/ml) was systemically administered preoperatively (1 ml) and topically applied during CI (0.5 ml). The extent of hearing preservation (HP) after CI and the change in the bithermal caloric response were evaluated. Hearing level was calculated using mean thresholds [(250 Hz + 500 Hz + 1,000 Hz + 2,000 Hz)/4]. Preoperative hearing thresholds were similar in the steroid-administered and control groups (100.92 +/- 12.60 vs. 103.29 +/- 14.39 dB, p = 0.650). The mean thresholds significantly increased in both groups after surgery (108.46 +/- 14.08 dB, p = 0.006, for the steroid-administered group; 117.50 +/- 6.34 dB, p = 0.027, for the control group), and the difference between the groups was also significant (p = 0.027). The postoperative shift in the hearing thresholds at frequencies of 500 and 1,000 Hz was significant in the steroid-administered group and that at the frequencies of 500, 1,000 and 2,000 Hz was significant in the control group. However, the extent of the shift in hearing threshold levels at each frequency was not significantly different between the groups. Preservation of hearing thresholds was compared between the groups, and there were significantly more subjects with complete and partial HP in the steroid-administered group than in the control group (p = 0.008). The preoperative caloric response was maintained after CI in the steroid-administered group. This study suggests that the perioperative use of a steroid could minimize the inner ear damage after CI. (C) 2016 S. Karger AG, Basel</P>
Cho, Sung-Yup,Chae, Jeesoo,Na, Deukchae,Kang, Wonyoung,Lee, Ahra,Min, Seoyeon,Kang, Jinjoo,Choi, Boram,Lee, Jieun,Sung, Chang Ohk,Chuang, Jeffrey H.,Lee, Charles,Lee, Won-Suk,Park, Hansoo,Kim, Jong-Il American Association for Cancer Research 2019 Clinical Cancer Research Vol.25 No.9
<P><B>Purpose:</B></P><P>Genomic and transcriptomic alterations during metastasis are considered to affect clinical outcome of colorectal cancers, but detailed clinical implications of metastatic alterations are not fully uncovered. We aimed to investigate the effect of metastatic evolution on <I>in vivo</I> treatment outcome, and identify genomic and transcriptomic alterations associated with drug responsiveness.</P><P><B>Experimental Design:</B></P><P>We developed and analyzed patient-derived xenograft (PDX) models from 35 patients with colorectal cancer including 5 patients with multiple organ metastases (MOMs). We performed whole-exome, DNA methylation, and RNA sequencing for patient and PDX tumors. With samples from patients with MOMs, we conducted phylogenetic and subclonal analysis and <I>in vivo</I> drug efficacy test on the corresponding PDX models.</P><P><B>Results:</B></P><P>Phylogenetic analysis using mutation, expression, and DNA methylation data in patients with MOMs showed that mutational alterations were closely connected with transcriptomic and epigenomic changes during the tumor evolution. Subclonal analysis revealed that initial primary tumors with larger number of subclones exhibited more dynamic changes in subclonal architecture according to metastasis, and loco-regional and distant metastases occurred in a parallel or independent fashion. The PDX models from MOMs demonstrated therapeutic heterogeneity for targeted treatment, due to subclonal acquisition of additional mutations or transcriptomic activation of bypass signaling pathway during tumor evolution.</P><P><B>Conclusions:</B></P><P>This study demonstrated <I>in vivo</I> therapeutic heterogeneity of colorectal cancers using PDX models, and suggests that acquired subclonal alterations in mutations or gene expression profiles during tumor metastatic processes can be associated with the development of drug resistance and therapeutic heterogeneity of colorectal cancers.</P>
Cho, Sung-Yup,Han, Jee Yun,Na, Deukchae,Kang, Wonyoung,Lee, Ahra,Kim, Jooyoung,Lee, Jieun,Min, Seoyeon,Kang, Jinjoo,Chae, Jeesoo,Kim, Jong-Il,Park, Hansoo,Lee, Won-Suk,Lee, Charles American Association for Cancer Research 2017 Molecular cancer therapeutics Vol.16 No.10
<P>Colorectal cancer is the third most commonly diagnosed cancer in the world, and exhibits heterogeneous characteristics in terms of genomic alterations, expression signature, and drug responsiveness. Although there have been considerable efforts to classify this disease based on high-throughput sequencing techniques, targeted treatments for specific subgroups have been limited. KRAS and BRAF mutations are prevalent genetic alterations in colorectal cancers, and patients with mutations in either of these genes have a worse prognosis and are resistant to anti-EGFR treatments. In this study, we have found that a subgroup of colorectal cancers, defined by having either KRAS or BRAF (KRAS/BRAF) mutations and BCL2L1 (encoding BCLXL) amplification, can be effectively targeted by simultaneous inhibition of BCL-XL (with ABT-263) and MCL1 (with YM155). This combination treatment of ABT-263 and YM-155 was shown to have a synergistic effect in vitro as well as in in vivo patient-derived xenograft models. Our data suggest that combined inhibition of BCL-XL and MCL1 provides a promising treatment strategy for this genomically defined colorectal cancer subgroup. (C) 2017 AACR.</P>
CRISPR/Cas9-coupled recombineering for metabolic engineering of <i>Corynebacterium glutamicum</i>
Cho, Jae Sung,Choi, Kyeong Rok,Prabowo, Cindy Pricilia Surya,Shin, Jae Ho,Yang, Dongsoo,Jang, Jaedong,Lee, Sang Yup Elsevier 2017 Metabolic engineering Vol.42 No.-
<P><B>Abstract</B></P> <P>Genome engineering of <I>Corynebacterium glutamicum</I>, an important industrial microorganism for amino acids production, currently relies on random mutagenesis and inefficient double crossover events. Here we report a rapid genome engineering strategy to scarlessly knock out one or more genes in <I>C. glutamicum</I> in sequential and iterative manner. Recombinase RecT is used to incorporate synthetic single-stranded oligodeoxyribonucleotides into the genome and CRISPR/Cas9 to counter-select negative mutants. We completed the system by engineering the respective plasmids harboring CRISPR/Cas9 and RecT for efficient curing such that multiple gene targets can be done iteratively and final strains will be free of plasmids. To demonstrate the system, seven different mutants were constructed within two weeks to study the combinatorial deletion effects of three different genes on the production of γ-aminobutyric acid, an industrially relevant chemical of much interest. This genome engineering strategy will expedite metabolic engineering of <I>C. glutamicum</I>.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Development of CRISPR/Cas9-based knockout in <I>C. glutamicum</I>. </LI> <LI> CRISPR/Cas9-coupled recombineering efficiency up to 100% for gene knockout. </LI> <LI> Developed a curable plasmid based on pCC1 origin for orthogonal plasmid curing. </LI> <LI> Demonstration of simultaneous, coupled deletion of two genes with one sgRNA. </LI> <LI> Generated and screened for <I>C. glutamicum</I> mutants producing high titers of GABA. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Trends in Patient Satisfaction from 1989-2003: Adjusted for Patient Characteristics
Cho, Sung-Hyun,Kim, Chang-Yup Korean Society of Nursing Science 2007 Journal of Korean Academy of Nursing Vol.37 No.2
Purpose. To identify trends in patient satisfaction adjusted for sociodemographic factors and health status from 1989-2003. Methods. Five repeated cross-sectional surveys were used. The study sample included 290,534 household members 20 years of age and over from the five survey periods of 1989, 1992, 1995, 1999, and 2003. Satisfaction was measured using a five-point scale, ranging from "very satisfied" to "very dissatisfied." Crude satisfaction rates, representing the proportion of patients satisfied (very satisfied or satisfied), were calculated for each survey period. Satisfaction rates adjusted for age, sex, marital status, education, and self-rated health status were calculated for each of the five years. Results. Crude satisfaction rates increased from 15.4% in 1989 to 40.5% in 2003. The proportions of satisfaction and dissatisfaction were reversed after 15 years had passed. However, the satisfaction trend was not linear throughout the different years, with 1992 being the year with the lowest satisfaction rate (9.7%). These trends in crude rates did not change even after adjusting for patient characteristics. The odds of satisfaction in 1992 were 38% lower (odds ratio 0.62, 95% CI 0.60 to 0.64) than the odds in 1989. In 2003, the odds of satisfaction were 4.01 times (95% CI 3.89 to 4.13) the odds for 1989. Older, female, married, and less-educated people were more likely to be satisfied. Patients who rated their health as 'very good' had the highest satisfaction rate, and those with "neutral" health ratings had the lowest. General hospitals achieved substantial improvement whereas pharmacies became the lowest-rated of all institutions. Conclusions. The Korean health system has achieved better patient satisfaction rates over the past 15 years. Increased health expenditure, resources, and quality improvement efforts may have contributed to this progress.
Cho, Sung-Yup,Sung, Chang Ohk,Chae, Jeesoo,Lee, Jieun,Na, Deukchae,Kang, Wonyoung,Kang, Jinjoo,Min, Seoyeon,Lee, Ahra,Kwak, Eunhye,Kim, Jooyoung,Choi, Boram,Kim, Hyunsoo,Chuang, Jeffrey H.,Pak, Hyo-Ky American Society of Hematology 2018 Blood Vol.131 No.17
<P>Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas (EBV1-DLBLs) tend to occur in immunocompromised patients, such as the elderly or those undergoing solid organ transplantation. The pathogenesis and genomic characteristics of EBV1-DLBLs are largely unknown because of the limited availability of human samples and lack of experimental animal models. We observed the development of 25 human EBV1-DLBLs during the engraftment of gastric adenocarcinomas into immunodeficient mice. An integrated genomic analysis of the human-derived EBV1-DLBLs revealed enrichment ofmutations in Rho pathway genes, including RHPN2, and Rho pathway transcriptomic activation. Targeting the Rho pathway using a Rho-associated protein kinase (ROCK) inhibitor, fasudil, markedly decreased tumorgrowth inEBV1-DLBL patient-derived xenograft (PDX) models. Thus, alterations in the Rho pathway appear to contribute to EBV-induced lymphomagenesis in immunosuppressed environments.</P>