Oral Fluoropyrimidines (Capecitabine or S-1) and Cisplatin as First Line Treatment in Elderly Patients with Advanced Gastric Cancer: A Retrospective Study

Seol, Y. M.,Song, M. K.,Choi, Y. J.,Kim, G. H.,Shin, H. J.,Song, G. A.,Chung, J. S.,Cho, G. J. Oxford University Press 2009 Japanese journal of clinical oncology Vol.39 No.1

<P>BACKGROUND: This study aimed to evaluate the safety and efficacy of oral fluoropyrimidines and cisplatin therapy in elderly patients with untreated advanced gastric cancer (AGC) retrospectively. In addition, we evaluated the relative activity and toxicity of these agents in this patient population. METHODS: Clinical data from 72 patients with previously untreated AGC, who were treated with capecitabine/cisplatin and S-1/cisplatin, were reviewed. Oral fluoropyrimidines were administered orally twice a day on Days 1-14. The dose of capecitabine was 1250 mg/m(2) and that of S-1 was 50 mg [body surface area (BSA) < 1.5 m(3)] or 60 mg (BSA > 1.5 m(3)) twice a day. Cisplatin was administered intravenously on Day 1 (before the first dose of capecitabine or S-1) at a dose of 70 mg/m(2) over a 2 h period. The chemotherapy cycle was of 3 weeks (with oral capecitabine or S-1). RESULTS: Thirty-two and 40 patients received the S-1 and capecitabine regimens, respectively, and were included in the analysis. The S-1 protocol had a response rate of 40.6%, a median time-to-progression (TTP) of 5.4 months and a median survival of 9.6 months. The capecitabine had a response rate of 55%, a median TTP of 5.9 months and a median survival of 10.2 months. Each protocol had a similar incidence of Grade 3 or 4 adverse events. However, there was a higher rate of the hand-foot syndrome (6 versus 37%) and diarrhea (25 versus 32%) in the capecitabine group. CONCLUSION: Oral fluoropyrimidines and cisplatin in elderly patients with untreated AGC showed encouraging results. The treatment was well tolerated with a manageable toxicity profile. The comparison of S-1 with capecitabine showed that capecitabine had a slightly higher response rate (statistically not significant) in addition to a higher rate of adverse events such as the hand-foot syndrome and diarrhea. These data should be warranted with further prospective studies.</P>

S-1 plus irinotecan and oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: a prospective phase II study and pharmacogenetic analysis

Kim, S Y,S Hong, Y,K Shim, E,Kong, S-Y,Shin, A,Baek, J Y,Jung, K H Nature Publishing Group 2013 The British journal of cancer Vol.109 No.6

<P><B>Background:</B></P><P>S-1 is an oral fluoropyrimidine that mimics infusional 5-fluorouracil. The aim of this phase II trial was to explore the clinical efficacy of the triplet regimen TIROX, which consists of S-1, irinotecan and oxaliplatin.</P><P><B>Methods:</B></P><P>Forty-two chemo-naive patients with metastatic colorectal cancer (mCRC) were planned to be enrolled and be treated with irinotecan 150 mg m<SUP>−2</SUP> followed by oxaliplatin 85 mg m<SUP>−2</SUP> on day 1 and S-1 80 mg m<SUP>−2</SUP> per day from day 1 to 14 every 3 weeks. Polymorphisms in the <I>UGT1A1</I>, <I>UGT1A6</I>, <I>UGT1A7</I> and <I>CYP2A6</I> genes were analysed.</P><P><B>Results:</B></P><P>Between July 2007 and February 2008, 43 patients were enrolled. An objective response was noted in 29 patients (67.4%, 95% confidence interval: 53.4–81.4), of which 2 achieved durable complete responses. The median progression-free survival was 10.0 months and the median overall survival was 19.2 months. Significant grade 3 or 4 adverse events were neutropenia (45.2%), febrile neutropenia (9.5%), diarrhoea (7.1%) and vomiting (9.5%). Increased gastrointestinal toxicities were associated with the presence of <I>UGT1A6*2</I> or <I>UGT1A7*3</I> and an improved tumour response was noted in those without variant alleles of <I>CYP2A6</I> or <I>UGT1A1*60</I>.</P><P><B>Conclusion:</B></P><P>The combination of S-1, irinotecan and oxaliplatin showed favourable efficacy and tolerability in untreated patients with mCRC.</P>

Differential effects of triterpene glycosides, frondoside A and cucumarioside A₂-2 isolated from sea cucumbers on caspase activation and apoptosis of human leukemia cells

Jin, J.O.,Shastina, V.V.,Shin, S.W.,Xu, Q.,Park, J.I.,Rasskazov, V.A.,Avilov, S.A.,Fedorov, S.N.,Stonik, V.A.,Kwak, J.Y. North-Holland Pub ; Elsevier Science Ltd 2009 FEBS letters Vol.583 No.4

Frondoside A is a pentaoside having an acetyl moiety at the aglycon ring and xylose as a third monosaccharide residue. Cucumarioside A<SUB>2</SUB>-2 is a pentaoside having glucose as a third monosaccahride unit. We compared the effects of frondoside A and A<SUB>2</SUB>-2 for cell death-inducing capability with close attention paid to structure-activity relationships. Both frondoside A and A<SUB>2</SUB>-2 strongly induced apoptosis of leukemic cells. Frondoside A-induced apoptosis was more potent and rapid than A<SUB>2</SUB>-2-induced apoptosis. A<SUB>2</SUB>-2-induced but not frondoside A-induced apoptosis was caspase-dependent. This suggests that holothurians may induce apoptosis of leukemic cells caspase-dependently or -independently, depending on the holothurian structure.

早期破膜에 關한 臨床的 考察

許湘,吳文愛,安東源,申吳永 대한산부인과학회 1972 Obstetrics & Gynecology Science Vol.15 No.7

β-Amyloid induces nuclear protease-mediated lamin fragmentation independent of caspase activation

Ramasamy, V.S.,Islam, Md.I.,Haque, Md.A.,Shin, S.Y.,Park, I.S. Elsevier Biomedical Press 2016 Biochimica et biophysica acta, Molecular cell rese Vol.1863 No.6

β-Amyloid (Aβ), a hallmark peptide of Alzheimer's disease, induces both caspase-dependent apoptosis and non-apoptotic cell death. In this study, we examined caspase-independent non-apoptotic cell death preceding caspase activation in Aβ42-treated cells. We first determined the optimal treatment conditions for inducing cell death without caspase activation and selected a double-treatment method involving the incubation of cells with Aβ42 for 4 and 6h (4+6h sample). We observed that levels of lamin A (LA) and lamin B (LB) were reduced in the 4+6h samples. This reduction was decreased by treatment with suc-AAPF-CMK, an inhibitor of nuclear scaffold (NS) protease, but not by treatment with z-VAD-FMK, a pan-caspase inhibitor. In addition, suc-AAPF-CMK decreased the changes in nuclear morphology observed in cells in the 4+6h samples, which were different from nuclear fragmentation observed in STS-treated cells. Furthermore, suc-AAPF-CMK inhibited cell death in the 4+6h samples. LA and LB fragmentation occurred in the isolated nuclei and was also inhibited by suc-AAPF-CMK. Together, these data indicated that the fragmentation of LA and LB in the Aβ42-treated cells was induced by an NS protease, whose identity is not clearly determined yet. A correlation between Aβ42 toxicity and the lamin fragmentation by NS protease suggests that inhibition of the protease could be an effective method for controlling the pathological process of AD.

Antibiotic susceptibility and resistance of Streptococcus iniae and Streptococcus parauberis isolated from olive flounder (Paralichthys olivaceus)

Park, Y.K.,Nho, S.W.,Shin, G.W.,Park, S.B.,Jang, H.B.,Cha, I.S.,Ha, M.A.,Kim, Y.R.,Dalvi, R.S.,Kang, B.J.,Jung, T.S. Elsevier Scientific Pub. Co 2009 Veterinary microbiology Vol.136 No.1

The rates of antibiotic susceptibility and resistance were investigated in Streptococcus iniae and Streptococcus parauberis isolates obtained from diseased olive flounders (Paralichthys olivaceus) collected from fish farms in Jeju Island, Korea. Isolates of S. iniae (n=65) were susceptible to cefotaxime, erythromycin, ofloxacin, penicillin, tetracycline and vancomycin, as demonstrated by the minimum inhibitory concentration (MIC) test. Isolates of S. parauberis (n=86) were highly resistant to erythromycin (58% of the 86 isolates tested) and tetracycline (63% of the 86 isolates tested). Fifty-four isolates of tetracycline-resistant S. parauberis contained the tet(M/O/S) genes, of which 39 and 12 isolates contained the tet(M) and tet(S) genes, respectively, whereas 3 isolates contained both the tet(M) and tet(S) genes. Among the erythromycin-resistant isolates of S. parauberis (n=50) only 14 contained the erm(B) gene. These results suggest that the tet(S) and erm(B) genes of S. parauberis are involved in the acquisition of high-level resistance to erythromycin and tetracycline. Our findings reveal a high rate of antibiotic resistance among strains of S. parauberis and emphasize the need to develop an appropriate vaccine to reduce the use of antibiotics.

서울지역 4년제 간호대학생들의 임상실습 유,무에 따른 진로태도성숙

권혜진,김보람,김소연,김수임,성정아,신영미,윤서진,이경진,홍영선,이자형,정덕유,신혜원 이화여자대학교 간호과학대학 2009 이화간호학회지 Vol.- No.43

This study was conducted to investigate the differences in the degrees of career attitude maturity according to the clinical practice experience of the college of nursing students. The convenience sample was 275 students attending the college of nursing in Seoul. Data was obtained through a questionnaire from December 1st to 12th, 2008. The instrument used to measure the career attitude maturity in this study was "A barometer of maturity in career attitudes" developed by Ki-hak, Lee(1997). The collected data were analyzed by descriptive statistics, Chronbach's alpha, t-test and ANOVA with the SPSS 16.0 program. Below is the result of this study. 1. The average score for career attitude maturity of nursing students who experienced clinical practices was 135.56(±12.17): higher than the average score of inexperienced students, 134.37(±12.44). However it could not show meaningful differences in the statistics(F=-.805, p=.422). 2. Determinacy, one of five subordinate concepts of career attitude maturity, was statistically significative. On average, the group comprised of students with clinical practices scored 27.60(±3.81): higher than that of unpracticed students, 26.63(±4.26)(F=-1.976, p=.049). 3. The more academic years they have, except for junior year students, the points of career attitude maturity relative to general characteristics were increasingly higher. The points were 132.60(±11.99) for freshmen, 135.93(±12.72) for sophomores, 133.50(±12.57) for juniors and 138.11(±11.24) for seniors(F=2.714, p=.045). 4. According to the age of the group, the grade of career attitude maturity became higher. The scores were 133.21(±12.34) for 18-19yrs., 134.05(±12.16) for 20-22yrs., 138.43(±10.96) for 23-26yrs. and 148.71(±12.76) for 27-32yrs. (F=5.118, p=.002). 5. The average total score for career attitude maturity of nursing students was 135.00(±12.30). Of the five subdivisions―readiness, conviction, determinacy, independence and finality― readiness demonstrated the highest result with 32.33(±4.46) followed by conviction, determinacy, independence and finality respectively. Based on the results, there are some proposals for further researches. As this research was only for college of nursing in Seoul, it is necessary to compare career attitude maturity with 3-year colleges and other departments. In addition, alongside clinical practices there is a growing need to develop programs that will not only provide guidelines but also prepare students for the maturity of their career attitude.

Novel stem-loop RNA and drug-bearing DNA hybrid nanostructures specific to LNCaP prostate carcinoma

Shin, S.,Song, W.,Kim, A.,Cho, S. W.,Kim, D. I.,Um, S. Royal Society of Chemistry 2014 Biomaterials Science Vol.2 No.1

Advances in nanotechnology have resulted in the introduction of new materials for therapeutic and diagnostic purposes. In particular, DNA and RNA are viewed as representative and generic nano-blocks because of their physiochemical characteristics of specificity and nanoscopic-level accuracy. In addition, the intrinsic biocompatibility of DNA and RNA and their immune stimulation effects make these molecules ideal candidates for the rational design of novel bio-drug molecules. Recently, we reported novel RNA-DNA hybrid stem-loop structures that target and are endocytosed by LNCaP prostate cancer cells with high specificity. To effectively ligate the DNA and RNA modules in this research, we thoroughly evaluated and optimized several ligation parameters, and observed that we could enhance the ligation efficacy by changing the overhang sequences. A change in sequence information (GCAT) resulted in a 4-fold increase in ligation efficiency in comparison with other ligation factors. To determine the in vitro cellular targeting ability of the nanostructures, RNA-DNA hybrid constructs were complexed with gold nanorods (AuNRs), and the ability of these nanorods to target prostate cancer cells was highest at a 2 : 10 molar ratio of LNCaP cancer-specific looped A10 RNA to stem-DNA. Furthermore, doxorubicin (Dox) as a representative anti-prostate cancer therapeutic was loaded into the DNA-RNA hybrid nanostructures. Our results indicate that RNA-DNA hybrid constructs are effective anti-prostate cancer drug delivery platforms and can be employed for both discovery and delivery.

OGLE-2015-BLG-1482L: The First Isolated Low-mass Microlens in the Galactic Bulge

Chung, S.-J.,Zhu, W.,Udalski, A.,Lee, C.-U.,Ryu, Y.-H.,Jung, Y. K.,Shin, I.-G.,Yee, J. C.,Hwang, K.-H.,Gould, A.,Albrow, M.,Cha, S.-M.,Han, C.,Kim, D.-J.,Kim, H.-W.,Kim, S.-L.,Kim, Y.-H.,Lee, Y.,Park, American Astronomical Society 2017 The Astrophysical Journal Vol.838 No.2

<P>We analyze the single microlensing event OGLE-2015-BLG-1482 simultaneously observed from two ground-based surveys and from Spitzer. The Spitzer data exhibit finite-source effects that are. due to the passage of the lens close to or directly over. the surface of the source star as seen from Spitzer. Such finite-source effects generally yield measurements of the angular Einstein radius, which when combined with the microlens parallax derived from a comparison between the ground-based and the Spitzer light curves. yields the lens mass and lens-source relative parallax. From this analysis, we find that the lens of OGLE-2015-BLG-1482 is a very low-mass star with a. mass 0.10 +/- 0.02 M-circle dot or a brown dwarf with a. mass 55 +/- 9MJ, which are. located at D-LS = 0.80 +/- 0.19 kpc and D-LS = 0.54 +/- 0.08 kpc, respectively,. where DLS is the distance between the lens and the source, and thus it is the first isolated low-mass microlens that has been decisively located in the Galactic bulge. The degeneracy between the two solutions is severe ( Delta chi(2) = 0.3). The fundamental reason for the degeneracy is that the finite-source effect is seen only in a single data point from Spitzer, and this single data point gives rise to two solutions for rho, the angular size of the source in units of the angular Einstein ring radius. Because the rho degeneracy can be resolved only by relatively high-cadence observations around the peak, while the Spitzer cadence is typically similar to 1 day(-1), we expect that events for which the finite-source effect is seen only in the Spitzer data may frequently exhibit this rho degeneracy. For OGLE-2015-BLG-1482, the relative proper motion of the lens and source for the low-mass star is mu(rel) = 9.0 +/- 1.9 mas yr(-1), while for the brown dwarf it is 5.5 +/- 0.5 mas yr(-1). Hence, the degeneracy can be resolved within similar to 10 years from direct-lens imaging by using next-generation instruments with high spatial resolution.</P>

Genetic identification of a novel locus, ACCELERATED FLOWERING 1 that controls chromatin modification associated with histone H3 lysine 27 trimethylation in Arabidopsis thaliana

Lee, S.,Shin, K.,Lee, I.,Song, H.R.,Noh, Y.S.,Lee, R.A.,Lee, S.,Kim, S.Y.,Park, S.K.,Lee, S.,Soh, M.S. Elsevier Scientific Publishers Ireland Ltd 2013 Plant science Vol.208 No.-

Flowering on time is a critically important for successful reproduction of plants. Here we report an early-flowering mutant in Arabidopsis thaliana, accelerated flowering 1-1D (afl1-1D) that exhibited pleiotropic developmental defects including semi-dwarfism, curly leaf, and increased branching. Genetic analysis showed that afl1-1D mutant is a single, dominant mutant. Chromosomal mapping indicates that AFL1 resides at the middle of chromosome 4, around which no known flowering-related genes have been characterized. Expression analysis and double mutant studies with late flowering mutants in various floral pathways indicated that elevated FT is responsible for the early-flowering of afl1-1D mutant. Interestingly, not only flowering-related genes, but also several floral homeotic genes were ectopically overexpressed in the afl1-1D mutants in both FT-dependent and -independent manner. The degree of histone H3 Lys27-trimethylation (H3K27me3) was reduced in several chromatin including FT, FLC, AG and SEP3 in the afl1-1D, suggesting that afl1-1D might be involved in chromatin modification. In support, double mutant analysis of afl1-1D and lhp1-4 revealed epistatic interaction between afl1-1D and lhp1-4 in regard to flowering control. Taken together, we propose that AFL1 regulate various aspect of development through chromatin modification, particularly associated with H3K27me3 in A. thaliana.