Adenosine triphosphate-based chemotherapy response assay-guided chemotherapy in unresectable colorectal liver metastasis

Hur, H,Kim, N K,Kim, H G,Min, B S,Lee, K Y,Shin, S J,Cheon, J H,Choi, S H Nature Publishing Group 2012 The British journal of cancer Vol.106 No.1

<P><B>Background:</B></P><P>This study aims to evaluate the effectiveness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided neoadjuvant chemotherapy for increasing resectability in patients with unresectable colorectal liver metastasis.</P><P><B>Patients and methods:</B></P><P>Patients were randomised into two groups: Group A was treated by conventional chemotherapy regimen and Group B was treated by chemotherapy regimen according to the ATP-CRA. Three chemotherapeutic agents (5-fluorouracil, oxaliplatin and irinotecan) were tested by ATP-CRA and more sensitive agents were selected. Either FOLFOX or FOLFIRI was administered. Between Group A and B, treatment response and resectability were compared.</P><P><B>Results:</B></P><P>Between November 2008 and October 2010, a total 63 patients were randomised to Group A (<I>N</I>=32) or Group B (<I>N</I>=31). FOLFOX was more preferred in Group A than in Group B (26 out of 32 (81.3%) <I>vs</I> 20 out of 31 (64.5%)). Group B showed better treatment response than Group A (48.4% <I>vs</I> 21.9%, <I>P</I>=0.027). The resectability of hepatic lesion was higher in Group B (35.5% <I>vs</I> 12.5%, <I>P</I>=0.032). Mean duration from chemotherapy onset to the time of liver resection was 11 cycles (range 4–12) in Group A and 8 cycles (range 8–16) in Group B.</P><P><B>Conclusion:</B></P><P>This study showed that tailored-chemotherapy based on ATP-CRA could improve the treatment response and resectability in initially unresectable colorectal liver metastasis.</P>

The Use of Collagen Content as Determined by Spectral Domain Polarization-Sensitive Optical Coherence Tomography to Assess Colon Anastomosis Healing in a Rat Model

Son, K.H.,Jeong, H.-W.,Jung, W.-W.,Kim, H.-S.,Lee, S.K.,Kim, K.T.,Ahn, C.B.,Park, K.Y.,Kim, B.-M.,Lee, S.H. S. Karger AG 2014 European surgical research Vol.52 No.1

<P>Abstract</P><P><B><I>Background/Purpose:</I></B> Many studies have been undertaken to prevent anastomosis leakage of the colon, and several methods have been used to assess anastomosis healing, such as measurement of bursting pressure or hydroxyproline (a marker of collagen) content at the anastomosis site. However, these methods are inappropriate for comparing anastomosis healing at two time points in the same animals. In the present study, we measured the collagen level by spectral domain polarization-sensitive optical coherence tomography (SD-PS-OCT) to assess anastomosis healing. <B><I>Methods:</I></B> Sprague-Dawley rats were divided into groups C (saline-administered controls; study group) and M [a 5-fluorouracil (5-FU)-administered experimental group]. Immediately after end-to-end anastomosis of the colon, SD-PS-OCT images of anastomoses were taken (baseline). Animals were administered saline or 5-FU for 7 days. On the 7th postoperative day, SD-PS-OCT images were acquired, a histopathologic exam was performed, and hydroxyproline levels as well as mRNA expressions of collagen-1 and collagen-3 were measured at the anastomosis site. <B><I>Results:</I></B> Fibroblast proliferation and inflammatory cell infiltration were greater in group C than in group M. The mRNA expressions of collagen-1 and collagen-3 were substantially higher in group C. Hydroxyproline levels were higher in group M than in group C. Though collagen levels measured by SD-PS-OCT at 7 days were elevated compared with baseline in group C, no such changes were observed for group M. <B><I>Conclusion:</I></B> Collagen levels at the colon anastomosis site, measured with SD-PS-OCT, were not increased at 7 days postoperatively versus baseline when 5-FU was injected, but were increased in saline-treated controls. The measurement of collagen content by SD-PS-OCT was found to provide a good means of assessing anastomosis healing, because it allows in situ assessment of collagen contents at baseline and during the postoperative period.</P><P>© 2014 S. Karger AG, Basel</P>

棚素施肥水準과 刈取管理가 Alfalfa(Medicago sativa L.)의 生育과 收量및 飼料價値에 미치는 영향

金雲植,文相鎬,全炳台,李相武 建國大學校 附設 自然科學硏究所 1991 建國自然科學硏究誌 Vol.2 No.-

本 實驗은 硼砂施肥水準과 刈取管理가 알팔파의 生育과 收量 및 飼料價値에 미치는 影響을 糾明하여 실질적인 栽培技術과 利用性提高를 目的으로 硼砂施肥水準(0,15,60Kg/ha)을 主區로 하고 生育段階를 細區로(Bud, 10% bloom, 100% bloom)하여 1989년 3월∼1990년 9월까지 建國大學校 自然科學大學 附屬 實習農場內 試料圃場에서 실시한 바, 그 結果를 要約하면 다음과 같다. 1. 草長에 있어서 硼砂施肥의 效果는 나타나지 않았으나, 初年度의 1, 2次 刈取와 2次 年度의 1次 刈取에서 生育이 진행됨에 따라 높게 나타났다. 2. 硼砂施肥에 따른 B??·B₁·B₂區의 收量에는 有意差가 없었으며, 生育이 진행됨에 따라 乾物收量은 높게 나타나 有意性이 (p<0.01, 0.05) 인정되었다. 3. 粗蛋白質 및 NDF, ADF 成分에 대한 硼砂 影響은 없었으며 生育이 진행됨에 따라 粗蛋白質含量은 떨어지고 NDF, ADF含量은 높아졌다. 4. 硼砂施肥에 의한 粗蛋白質收量은 有意差가 없었으며, 生育이 진행됨에 따라 粗蛋白質收量은 높게 나타나 그 有意性이 (p<0.05) 인정되었다. 5. 硼砂施肥에 따른 嗜好性은 B??·B₁·B₂區가 같은 傾向을 보였으며, 生育段階에 따른 嗜好性은 많은 차이를 보여 初年度의 1次 刈取時 Bud >10% bloom >100% bloom期 순으로 높게 나타났다. The purpose of the experiment was carried out to determine the effects of boron application and cutting management on the growth, yield and feeding value for the purpose of practical culture and utilization techniques. The trial was performed at different borax application level(main treatments ; 0, 15, 30kg/ha) and growth stage(sub treatments : Bud, 10% bloom and 100% bloom stage) from 1989 to 1990 in experimental field college of Natural Science, Kon Kuk University. The results obtained are summarized as follows : 1. The effect of borax application in the plant length was shown, but plant length in the first and second cutting time of the first year and first cutting time of the second year after sown was high by the progression of growth. 2. There was not significant among main treatments(B??·B₁·B₂)in dry matter yield, but was shown significantly high (p<0.01, 0.05) by the progression of growth in first cutting time. 3. The content of chemical composition, NDF and ADF were not affected by boron application, and content of crude protein was decreased and those of curde fiber, NDF and ADF were increased by the progression of growht in first cutting time. 4. There was not significant among main treatments(B??·B₁·B₂) in crude protein yield but was significant (p<0.05) by the progression of growth in first cutting time. 5. There was not significant among main treatments(B??·B₁·B₂) in palatability, but palatability by growth stage was the highest at bud stage in first cutting time of first year after sown.

<i>CYP2A6</i> and <i>ERCC1</i> polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients

Park, S R,Kong, S-Y,Nam, B-H,Choi, I J,Kim, C G,Lee, J Y,Cho, S J,Kim, Y W,Ryu, K W,Lee, J H,Rhee, J,Park, Y-I,Kim, N K Nature Publishing Group 2011 The British journal of cancer Vol.104 No.7

<P><B>Background:</B></P><P>We evaluated the association between polymorphisms of cytochrome P450 2A6 (<I>CYP2A6</I>)/excision repair cross-complementation group 1 (<I>ERCC1</I>)/X-ray repair cross-complementing group 1(<I>XRCC1</I>) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.</P><P><B>Methods:</B></P><P>Among MGC patients (<I>n</I>=108), who received S-1 (40 mg m<SUP>−2</SUP> b.i.d., days 1–14) and cisplatin (60 mg m<SUP>−2</SUP>, day 1) every 3 weeks, we analysed the wild-type allele (<I>W</I>) and variants (<I>V</I>) of <I>CYP2A6</I> (<I>*4</I>, <I>*7, *9, *10</I>), and the polymorphisms of <I>ERCC1</I> (rs11615, rs3212986) and <I>XRCC1</I> (rs25487).</P><P><B>Results:</B></P><P>Patients having fewer <I>CYP2A6</I> variants had better response rates (<I>W</I>/<I>W vs W</I>/<I>V</I> other than <I>*1/*4 vs V</I>/<I>V</I> or <I>*1/*4</I>=66.7 <I>vs</I> 58.3 <I>vs</I> 32.3% <I>P</I>=0.008), time to progression (TTP) (7.2 <I>vs</I> 6.1 <I>vs</I> 3.5 months, <I>P</I>=0.021), and overall survival (23.2 <I>vs</I> 15.4 <I>vs</I> 12.0 months, <I>P</I>=0.004). <I>ERCC1 19442C</I>><I>A</I> (rs3212986) was also associated with response rate (<I>C/C</I>, 46.7% <I>vs C/A</I>, 55.3% <I>vs A/A</I>, 87.5%) (<I>P</I>=0.048) and TTP (4.4 <I>vs</I> 7.6 <I>vs</I> 7.9 months) (<I>P</I>=0.012). Patients carrying both risk genotypes of <I>CYP2A6</I> (<I>V</I>/<I>V</I> or <I>1/*4</I>) and <I>ERCC1 19442C</I>><I>A</I> (<I>C/C</I>) <I>vs</I> those carrying none showed an adjusted odds ratio of 0.113 (<I>P</I>=0.004) for response, and adjusted hazard ratios of 3.748 (<I>P</I>=0.0001) for TTP and 2.961 (<I>P</I>=0.006) for death.</P><P><B>Conclusion:</B></P><P>Polymorphisms of <I>CYP2A6</I> and <I>ERCC1 19442C</I>><I>A</I> correlated with the efficacy of S-1/cisplatin.</P>

Caspase-3 activation as a key factor for HBx-transformed cell death

Kim, A.,Kwon, O. S.,Kim, S. O.,He, L.,Bae, E. Y.,Lee, M. S.,Jeong, S. J.,Shim, J. H.,Yoon, D. Y.,Kim, C. H.,Moon, A.,Kim, K. E.,Ahn, J. S.,Kim, B. Y. Blackwell Publishing Ltd 2008 Cell proliferation Vol.41 No.5

<P>Abstract. </P><P><I>Objectives</I>: Nuclear factor-kappa B (NF-&kgr;B) activation has been associated with the tumorigenic growth of hepatitis B virus X protein (HBx)-transformed cells. This study was aimed to find a key target for treatment of HBx-mediated cancers. <I>Materials and methods</I>: NF-&kgr;B activation, endoplasmic reticulum-stress (ER-stress), caspase-3 activation, and cell proliferation were evaluated after Chang/HBx cells permanently expressing HBx viral protein were treated with inhibitors of NF-&kgr;B, proteasome and DNA topoisomerase. <I>Results</I>: Inhibition of NF-&kgr;B transcriptional activity by transient transfection with mutant plasmids encoding Akt1 and glycogen synthase kinase-3&bgr; (GSK-3&bgr;), or by treatment with chemical inhibitors, wortmannin and LY294002, showed little effect on the survival of Chang/HBx cells. Furthermore, I&kgr;Bα (S32/36A) mutant plasmid or other NF-&kgr;B inhibitors, 1-pyrrolidinecarbonidithioic acid and sulphasalazine, were also shown to have little effect on the cell proliferation. By contrast, proteasome inhibitor-1 (Pro1) and MG132 enhanced the HBx-induced ER-stress response and the subsequent activation of caspase-12, -9 and -3 and reduced cell proliferation. Camptothecin (CPT), however, triggered activation of caspase-3 without induction of caspase-12, and reduced cell proliferation. In addition, CPT-induced cell death was reversed by pre-treatment with z-DEVD, a caspase-3-specific inhibitor. <I>Conclusions</I>: Detailed exploitation of the regulators of caspase-3 activation could open the gate for finding an efficient target for development of anticancer therapeutics against HBx-transformed hepatocellular carcinoma.</P>

20대 여성의 신발종류에 따른 족저압 영역별 비교 연구

김용재,지진구,김정태,홍준희,이중숙,이훈식,박승범 한국운동역학회 2004 한국운동역학회지 Vol.14 No.3

Y. J. KIM, J. G. JI, J. T. KIM, J. H. HONG, J. S. LEE, H. S. LEE, S. B. PARK. A comparison study for mask plantar pressure measures to the difference of shoes in 20 female. Korean Journal of Sport Biomechanics, Vol. 14, No. 3, pp. 83-98, 2004. The purpose of this study was to investigate the test-retest of plantar pressures using the F-Scan system over speeds and plantar regions. 6 healthy female subjects in 20's were recruited for the study. Plantar pressure measurements during locomotor activities can provide information concerning foot function, particularly if the timing and magnitude of the loading profile can be related to the location of specific foot structures such as the metatarsal heads. The Tekscan F-Scan system consists of a flexible, 0.18mm thick sole-shape having 1260 pressure sensors, the sensor insole was trimmed to fit the subjects' right. left shoes - sneakers shoes & dress shoes. It was calibrated by the known weight of the test subject standing on one foot. The Tekscan measurements show the insole pressure distribution as a function of the time. This finding has important implications for the development of plantar pressure test protocols where the function of the forefoot is important. According to the result of analysis it is as follows : 1) Center of force trajectory in women's dress shoes display direct movement, compare with center of force trajectory in Sneaker shoes displays a little bit curved slow pronation movement. Sneaker shoes in forefoot part display very quick supination movement, therefore, this shoes effects negative effectiveness for ankle's stability. Considering center of force trajectory analyzing, the more center of force close straight line, the more movement can be quick movement for locomotion. For foot pressure distribution, center of force trajectory in locomotion is better to curved trajectory with pronation movement. So sneaker shoes style is good shoes considering center of pressure distribution trajectory compare with women's dress shoes. 2) Women's dress shoes increased peak pressure in medial, this is effected by high hill's height. The more increased women's dress shoes's height, the more women's peak pressure will increase, pronation can increase compare with before. Supination movement increase, this focused pressure in lateral, also, supination increased more. If the supination movement increased, foot pressure focused in lateral, therefore, it is appeared force distribution in gait direction. This is bad movement in foot's stability. 3) Women's dress shoes in landing phase displayed a long time, this is when women's dress shoes wear, gait movement is unbalance, so, landing phase displayed a long time. For compensation in gait, swing phase quick movement. 4) Women's dress shoes displayed peak pressure distribution in lateral of rearfoot part, Sneakers shoes displayed peak pressure distribution in medial of forefoot part. Its results has good impact absorption compare with women's dress shoes. In forefoot part, sneakers shoes has good propulsive force compare with women's dress shoes.

Bacillus cereus and Bacillus thuringiensis spores in Korean rice: Prevalence and toxin production as affected by production area and degree of milling

Kim, B.,Bang, J.,Kim, H.,Kim, Y.,Kim, B.s.,Beuchat, L.R.,Ryu, J.H. Academic Press 2014 FOOD MICROBIOLOGY Vol.42 No.-

We determined the prevalence of and toxin production by Bacillus cereus and Bacillus thuringiensis in Korean rice as affected by production area and degree of milling. Rough rice was collected from 64 farms in 22 agricultural areas and polished to produce brown and white rice. In total, rice samples were broadly contaminated with B. cereus spores, with no effect of production area. The prevalence and counts of B. cereus spores declined as milling progressed. Frequencies of hemolysin BL (HBL) production by isolates were significantly (P @? 0.01) reduced as milling progressed. This pattern corresponded with the presence of genes encoding the diarrheal enterotoxins. The frequency of B. cereus isolates positive for hblC, hblD, or nheB genes decreased as milling progressed. Because most B. cereus isolates from rice samples contained six enterotoxin genes, we concluded that B. cereus in rice produced in Korea is predominantly of the diarrheagenic type. The prevalence of B. thuringiensis in rice was significantly lower than that of B. cereus and not correlated with production area. All B. thuringiensis isolates were of the diarrheagenic type. This study provides information useful for predicting safety risks associated with B. cereus and B. thuringiensis in rough and processed Korean rice.

Paenibacillus pueri sp. nov., isolated from Pu'er tea

Kim, B.-C.,Jeong, W.-J.,Kim, D. Y.,Oh, H.-W.,Kim, H.,Park, D.-S.,Park, H.-M.,Bae, K. S. Microbiology Society 2009 International journal of systematic and evolutiona Vol.59 No.5

<P>Pu'er tea is a fermented drink made from the leaves of the tea plant, Camellia sinensis. Two novel bacteria, designated strains b09i-3(T) and b13i-1, were isolated during the process of fermentation of this tea. These isolates were Gram-positive, endospore-forming, motile rods that grew at 25-42 degrees C and pH 5.5-10.4. The DNA G+C content was 56.6-58.4 mol%, the predominant isoprenoid quinone was MK-7 and the predominant cellular fatty acid was anteiso-C(15 : 0) (49.0-50 % of the total). Phylogenetic analysis based on 16S rRNA gene sequences showed that strains b09i-3(T) and b13i-1 shared 99.9 % similarity and were affiliated with a cluster within the family Paenibacillaceae. Strains b09i-3(T) and b13i-1 were related most closely to Paenibacillus ginsengihumi DCY16(T) (97 % 16S rRNA gene sequence similarity). Levels of DNA-DNA relatedness between the two novel isolates and P. ginsengihumi DCY16(T) were below 56 %. The phylogenetic and phenotypic characteristics of these novel isolates allowed them to be distinguished clearly from recognized species of the genus Paenibacillus. Based on these data, strains b09i-3(T) and b13i-1 are considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus pueri sp. nov. is proposed. The type species is b09i-3(T) (=KCTC 13223(T)=CECT 7360(T)).</P>

ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding

Jeon, B.N.,Yoon, J.H.,Han, D.,Kim, M.K.,Kim, Y.,Choi, S.H.,Song, J.,Kim, K.S.,Kim, K.,Hur, M.W. Elsevier Science 2017 Biochimica et biophysica acta. Gene regulatory mec Vol.1860 No.9

Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed to severe DNA damage, p53 activates PUMA (p53-upregulated modulator of apoptosis) transcription. Interestingly, apoptosis due to transcriptional activation of PUMA by p53 is attenuated by ZNF509S1. Thus we investigated the molecular mechanism(s) underlying the transcriptional attenuation and anti-apoptotic effects of ZNF509S1. We show that ZNF509S1 modulation of p53 activity is important in PUMA gene transcription by modulating post-translational modification of p53 by p300. ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding at the p53 response element 1 of the PUMA promoter. ZNF509S1 may play a role not only in cell cycle arrest, by activating RB expression, but also in rescuing cells from apoptotic death by repressing PUMA expression in cells exposed to severe DNA damage.

<i>S100A9</i> and <i>EGFR</i> gene signatures predict disease progression in muscle invasive bladder cancer patients after chemotherapy

Kim, W. T.,Kim, J.,Yan, C.,Jeong, P.,Choi, S. Y.,Lee, O. J.,Chae, Y. B.,Yun, S. J.,Lee, S. C.,Kim, W. J. Oxford University Press 2014 Annals of Oncology Vol.25 No.5

<P>In our previous gene expression profile analysis, IL1B, S100A8, S100A9, and EGFR were shown to be important mediators of muscle invasive bladder cancer (MIBC) progression. The aim of the present study was to investigate the ability of these gene signatures to predict disease progression after chemotherapy in patients with locally recurrent or metastatic MIBC. Patients with locally advanced MIBC who received chemotherapy were enrolled. The expression signatures of four genes were measured and carried out further functional analysis to confirm our findings. Two of the four genes, S100A9 and EGFR, were determined to significantly influence disease progression (P = 0.023, 0.045, respectively). Based on a receiver operating characteristic curve, a cut-off value for disease progression was determined. Patients with the good-prognostic signature group had a significantly longer time to progression and cancer-specific survival time than those with the poor-prognostic signature group (P < 0.001, 0.042, respectively). In the multivariate Cox regression analysis, gene signature was the only factor that significantly influenced disease progression [hazard ratio: 4.726, confidence interval: 1.623-13.763, P = 0.004]. In immunohistochemical analysis, S100A9 and EGFR positivity were associated with disease progression after chemotherapy. Protein expression of S100A9/EGFR showed modest correlation with gene expression of S100A9/EGFR (r = 0.395, P = 0.014 and r = 0.453, P = 0.004). Our functional analysis provided the evidence demonstrating that expression of S100A9 and EGFR closely associated chemoresistance, and that inhibition of S100A9 and EGFR may sensitize bladder tumor cells to the cisplatin-based chemotherapy. The S100A9/EGFR level is a novel prognostic marker to predict the chemoresponsiveness of patients with locally recurrent or metastatic MIBC.</P>