• Title/Summary/Keyword: PD-1/PD-L1

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Anti-Cancer Activity of the Flower Bud of Sophora japonica L. through Upregulating Activating Transcription Factor 3 in Human Colorectal Cancer Cells

  • Lee, Jin Wook;Park, Gwang Hun;Eo, Hyun Ji;Song, Hun Min;Kim, Mi Kyoung;Kwon, Min Ji;Koo, Jin Suk;Lee, Jeong Rak;Lee, Man Hyo;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.28 no.3
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    • pp.297-304
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    • 2015
  • The flower buds of Sophora japonica L (SF), as a well-known traditional Chinese medicinal herb, have been used to treat bleeding-related disorders such as hematochezia, hemorrhoidal bleeding, dysfunctional uterine bleeding, and diarrhea. However, no specific anti-cancer effect and its molecular mechanism of SF have been described. Thus, we performed in vitro study to investigate if treatment of SF affects activating transcription factor 3 (ATF3) expression and ATF3-mediated apoptosis in human colorectal cancer cells. The effects of SF on cell viability and apoptosis were measured by MTT assay and Western blot analysis against cleaved poly (ADP-ribose) polymerase (PARP). ATF3 activation induced by SF was evaluated using Western blot analysis, RT-PCR and ATF3 promoter assay. SF treatment caused decrease of cell viability and increase of apoptosis in a dose-dependent manner in HCT116 and SW480 cells. Exposure of SF activated the levels of ATF3 protein and mRNA via transcriptional regulation in HCT116 and SW480 cells. Inhibition of extracellular signal-regulated kinases (ERK) 1/2 by PD98059 and p38 by SB203580 attenuated SF-induced ATF3 expression and transcriptional activation. Ectopic ATF3 overexpression accelerated SF-induced cleavage of PARP. These findings suggest that SF-mediated apoptosis may be the result of ATF3 expression through ERK1/2 and p38-mediated transcriptional activation.

Effect of Restricted Feed Intake on Early Reproductive Development in Large White Gilts

  • Gaughan, John B.
    • Asian-Australasian Journal of Animal Sciences
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    • v.14 no.11
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    • pp.1534-1541
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    • 2001
  • Forty-five Large White gilts were used to study the effect of energy intake from 28 to 176 d of age on body composition and reproductive development. From 28 to 60 d, the gilts were fed ad libitum a 16.6 MJ DE/kg, 24% crude protein and 1.3% total lysine diet. From 61 d of age three dietary treatments were used; 1) ad libitum access to feed (15.6 MJ DE/kg, 21% crude protein and 1.07% total lysine) (H), 2) feed offered at 75% (M) of the previous days intake of H, and 3) feed offered at 60% (L) of the previous days intake of H. ADG from 61 to 176 d of age was (p<0.05) affected by treatment. Although live weight at 176 d of age did not differ (p>0.1) the H gilts had higher (p<0.08) carcass weights than the M or L gilts. Back fat depths were similar (p>0.1) for all treatments at 115 d of age, however by 176 d of age M and H gilts were fatter (p<0.1) than L gilts. The mean lipid deposition (LD) from 115 to 176 d of age for L gilts (78.9 g/d) was less (p<0.05) than for M gilts (143.6 g/d) and H gilts (135.6 g/d). There were no differences between treatments for protein deposition (PD) over the same period. More (p<0.05) H gilts (n=8) attained puberty (first observed estrus) than either M gilts or L gilts (n=4 for both). Follicle numbers were similar (p>0.1) across treatments. For gilts that attained puberty, H gilts had fewer (p<0.05) follicles (13.5) than M gilts (19.7) and L gilts (21.3). For gilts with follicular development, H gilts had the heaviest (458.7 g) reproductive tract weight (RTW). However, for those that attained puberty, L gilts had the heaviest RTW. RTW were lowest for those with no follicular development. Energy restriction had a negative impact on puberty attainment, i.e. it took longer to reach puberty. However, for gilts that attained puberty, the number of follicles was greater for those on r feed intakes. It would appear that rate of fat deposition, but not necessarily the total amount of fat, plays an important role in puberty attainment.

Fermentation Process for Mass Production of Clitocybin A, a New Anti-Wrinkle Agent from Clitocybe aurantiaca and Evaluation of Inhibitory Activity on Matrix Metalloproteinase-1 Expression (Clitocybe aurantiaca 균주가 생산하는 주름개선소재 clitocybin A의 대량 발효생산 및 MMP-1 발현저해활성)

  • Kim, Kwan-Chul;Lee, Hyeok-Won;Lee, Hong-Won;Choo, Soo-Jin;Yoo, Ick-Dong;Ha, Byung-Jo
    • Microbiology and Biotechnology Letters
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    • v.42 no.2
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    • pp.194-201
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    • 2014
  • Clitocybin A is a novel anti-wrinkle cosmetic agent produced by the strain from a Korean native mushroom Clitocybe aurantiaca. In this study, fermentation, extraction, and purification conditions for a large scale production of clitocybin A were optimized, and its cytotoxicity and inhibition activity on the expression of matrix metalloproteinase-1 (MMP-1) were characterized. The mass production of anti-wrinkle agent was achieved according to the 300 L fermentation process with a fed-batch cultivation using the modified yeast-maltose (YM) broth, and a total of 12.5 kg of cell mass was obtained in a 120 L culture broth for 14 days. After extraction and purification, clitocybin A was identified by HPLC. The cytotoxicity of clitocybin A was examined by the MTT assay. When assayed at 100 and 200 ${\mu}g/ml$ concentrations, clitocybin A showed no cytotoxicity, demonstrating safety. The inhibition activity of clitocybin A on the expression of MMP-1 was examined against UV irradiation. Oleanolic acid (control group) showed a relatively low MMP-1 inhibiting activity (ca. 16.7%) at 10 ${\mu}g/ml$ and showed increased cytotoxicity at higher concentrations. In contrast, clitocybin A showed no cytotoxicity at 100 ${\mu}g/ml$, and exhibited a relatively high MMP-1-inhibiting activity (33.1%). These findings indicate that clitocybin A may be a safe and effective anti-wrinkle agent for use in functional cosmetics.

Aspect of Blood Pressure after Oral Administration of Alcohol : Effect of Dissolved Oxygen on Blood Pressure (알코올 투여에 따른 혈압의 변화 양상 : 용존산소량에 따른 혈압 변화)

  • Song, Byung-Jeong;Lee, Byung-Yo;Chae, Jung-Woo;An, Jung-Hwa;Kwon, Kwang-Il
    • Korean Journal of Clinical Pharmacy
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    • v.22 no.3
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    • pp.228-233
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    • 2012
  • Purpose: The purpose of this study was to elucidate the effect of dissolved oxygen in alcohol to blood pressure of healthy persons. Methods: Subjects (n=30) were randomized in a double blind crossover study to receive 120 mL, 240 mL, 360 mL of alcohol (Korean spirit, 19.59 v/v%, dissolved oxygen is 8 ppm and 20 ppm). Blood alcohol concentration (BAC) and blood pressure were measured applying Lion SD-400 Alcolmeter$^{(R)}$ Breathalyser and Tensoval duo control. Pharmacokinetic parameters ($C_{max}$, $T_{max}$, $AUC_{last}$, $K_{el}$, $V_d$, Clearance) were calculated using Winnonlin$^{(R)}$ program. The difference of parameters and values were analysed by student t-test using Microsoft$^{(R)}$ Excel program. Results: The $AUC_{last}$ values of 8 ppm group and 20 ppm group in 240 ml administration were $6.15{\pm}2.60cg{\cdot}min/ml$, $5.33{\pm}1.84cg{\cdot}min/ml$ (p<0.05) and those in 360 mL were $11.93{\pm}5.70cg{\cdot}min/ml$, $10.33{\pm}4.60cg{\cdot}min/ml$ (p < 0.01), respectively. Thus, the $AUC_{last}$ was significantly decreased. On the other hands, there was a significant change in systolic blood pressure (SBP) after alcohol administration. All measured value after 360 mL of alcohol administration was significantly decreased (p < 0.01). Conclusions: The dissolved oxygen in alcoholic beverage has no effect on blood pressures but the alcohol administration has an effect on blood pressure. Thus, SBP can be used as a biomarker of alcohol administration and utilized in PK/PD modeling of alcohol.

Treatment Results of CyberKnife Radiosurgery for Patients with Primary or Recurrent Non-Small Cell Lung Cancer (원발 혹은 재발성 비소세포 폐암 환자에서 사이버나이프률 이용한 체부 방사선 수술의 치료 결과)

  • Kim, Woo-Chul;Kim, Hun-Jung;Park, Jeong-Hoon;Huh, Hyun-Do;Choi, Sang-Huoun
    • Radiation Oncology Journal
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    • v.29 no.1
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    • pp.28-35
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    • 2011
  • Purpose: Recently, the use of radiosurgery as a local therapy in patients with early stage non-small cell lung cancer has become favored over surgical resection. To evaluate the efficacy of radiosurgery, we analyzed the results of stereotactic body radiosurgery in patients with primary or recurrent non-small cell lung cancer. Materials and Methods: We reviewed medical records retrospectively of total 24 patients (28 lesions) with non-small cell lung cancer (NSCLC) who received stereotactic body radiosurgery (SBRT) at Inha University Hospital. Among the 24 patients, 19 had primary NSCLC and five exhibited recurrent disease, with three at previously treated areas. Four patients with primary NSCLC received SBRT after conventional radiation therapy as a boost treatment. The initial stages were IA in 7, IB in 3, IIA in 2, IIB in 2, IIIA in 3, IIIB in 1, and IV in 6. The T stages at SBRT were T1 lesion in 13, T2 lesion in 12, and T3 lesion in 3. 6MV X-ray treatment was used for SBRT, and the prescribed dose was 15~60 Gy (median: 50 Gy) for PTV1 in 3~5 fractions. Median follow up time was 469 days. Results: The median GTV was 22.9 mL (range, 0.7 to 108.7 mL) and median PTV1 was 65.4 mL (range, 5.3 to 184.8 mL). The response rate at 3 months was complete response (CR) in 14 lesions, partial response (PR) in 11 lesions, and stable disease (SD) in 3 lesions, whereas the response rate at the time of the last follow up was CR in 13 lesions, PR in 9 lesions, SD in 2 lesions, and progressive disease (PD) in 4 lesions. Of the 10 patients in stage 1, one patient died due to pneumonia, and local failure was identified in one patient. Of the 10 patients in stages III-IV, three patients died, local and loco-regional failure was identified in one patient, and regional failure in 2 patients. Total local control rate was 85.8% (4/28). Local recurrence was recorded in three out of the eight lesions that received below biologically equivalent dose 100 $Gy_{10}$. Among 20 lesions that received above 100 $Gy_{10}$, only one lesion failed locally. There was a higher recurrence rate in patients with centrally located tumors and T2 or above staged tumors. Conclusion: SBRT using a CyberKnife was proven to be an effective treatment modality for early stage patients with NSCLC based on high local control rate without severe complications. SBRT above total 100 $Gy_{10}$ for peripheral T1 stage patients with NSCLC is recommended.

Growth Inhibition of Polysaccharide Fraction in Cell Wall Components from Enterococcus faecalis 2B4-1 against Tumor Cell Lines (Enterococcus faecalis 2B4-1 세포벽 성분 중 Polysaccharide Fraction의 종양세포 증식억제 효과)

  • Park, Sang-Jin;Kim, Jeong-Hwan;Lee, Kyung-Ho;Yang, Jong-Beom;Baek, Young-Jin;Kim, Chang-Han
    • Microbiology and Biotechnology Letters
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    • v.27 no.1
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    • pp.8-14
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    • 1999
  • This study was developed to evaluate the growth inhibition effects of cell wall components of Enterococcus faecalis 2B4-1 obtained from feces of neonates against tumor cell lines. Polysaccharide fraction (PS) shown sensitive growth inhibition effect in the cell wall components was isolated and characterized. In growth inhibition effects, residue fractin of whole cell was shown sensitive level of percent survival about 30% when administrated at ehe concentration of 100${\mu}$g/ml, and that was more effective than that of supernatant fraction against the tumor cell lines, SNU-1, 3LL, FARROW and HEC-1-B. Sensitive growth inhibition effects against SNU-1, FARROW and HEC-1-B were performed by whole cell (WC) fraction from Ent. faecalis 2B4-1. Cytoplasm fractin (CP) of WC was shown non-inhibition effect, however, the other part of WC, precipitate of disrupted cell (PD), was sensitive against the tumor cell line mentioned above. Followed by separation to peptidoglycan fraction (PG) and polysaccharide fraction (PS) were all sensitive which the latter was shown more sensitive percent survival than the former. Composed sugars of polysaccharide fraction were determined to D-glucose, L-rhamnose and D-glucosamine, and the rate fo composition was calculated to about 1:1:1 by the data of elemental analysis, IR, TLC and HPLC.

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Effects of Anti-B7.1/B7.2 Antibodies on LPS-Stimulated Macrophages

  • Won, Tae-Joon;Huh, Yoon-Joo;Lim, Young-Tae;Song, Dong-Sup;Hwang, Kwang-Woo
    • Biomolecules & Therapeutics
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    • v.18 no.4
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    • pp.463-468
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    • 2010
  • T-cell activation depends on signals received by the T-cell receptor and CD28 co-stimulatory receptor. Since B7.1 and B7.2 molecules expressed on the surface of antigen presenting cells provide co-stimulatory signals through CD28 to T-cells, an inhibitor of CD28-B7.1/B7.2 binding has been proposed as a therapeutic agent for suppression of excessive T-cell activity. Although anti-B7.1/B7.2 antibodies are known to block B7.1 and B7.2 molecules, their effects on intracellular events in antigen presenting cells remain unclear. In this study, anti-B7.1/B7.2 antibodies decreased secretion of nitric oxide and pro-inflammatory cytokines such as TNF-$\alpha$, IL-$1{\beta}$, and IL-12 in LPS-activated RAW264.7 macrophage-like cells and peritoneal macrophages. Moreover, anti-B7.1/B7.2 antibodies inhibited $I{\kappa}B{\alpha}$ phosphorylation and down-regulated expression of co-stimulatory molecules including B7.1, B7.2, and PD-L1 in LPS-stimulated peritoneal macrophages. These findings suggest that CTLA4-Ig and anti-B7.1/B7.2 antibodies may be candidates to treat chronic inflammatory diseases and autoimmune responses caused by excessive activation of both T-cells and macrophages.

The Interaction between Epidermal Growth Factor (EGF) and Follicular Stimulating Hormone (FSH) on Nuclear Maturation of Mouse Oocytes by Using Their Inhibitor

  • Cha, Soo-Kyung;Kim, Tae-Hyung;Eum, Jin-Hee;Park, Kang-Hee;Park, Eun-A;Kim, Seung-Bum;Chung, Mi-Kyung;Lee, Dong-Ryul;Ko, Jung-Jae
    • Proceedings of the Korean Society of Embryo Transfer Conference
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    • 2002.11a
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    • pp.113-113
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    • 2002
  • The stimulatory effect of EGF and FSH on oocyte maturation have been reported in various mammalian species. And some reports presented FSH enhanced the effect of EGF on oocyte maturation. But, the interaction between EGF and FSH on nuclear maturation of mammalian oocytes is not fully understood. We observed the effect of EGF and FSH on nuclear maturation during in vitro maturation of mouse oocytes. Also, we examined the interaction between EGF and FSH on nuclear maturation of mouse oocytes using the EGFR inhibitor or FSH inhibitor. Germinal vesicle (GV) stage oocytes were obtained from 3-4weeks PMSG primed BCFI hybrid mice and cultured in TCM-199 medium with 0.4%PVP supplemented with/without EGF (1ng/ml), FSH (1ug/ml), EGFR specific tyrosine kinase inhibitors: Tyrphostin AG 1478 (500nM), MAP kinase kinase inhibitor : U0126 (20uM) or PD 98059 (100uM) for 14-l5hr. Rapid staining method were used for the assessment of nuclear maturation. Nuclear maturation rates of EGF indjor FSH-treated group were significantly higher than those of control group. Treatment of EGFR inhibitor significantly block the nuclear maturation of GV oocyte in EGF-treated group, but it did not block those of GV oocyte in FSH-treated or FSH and EGF-treated group. Treatment of FSH inhibitor(U0126, PD98059) significantly block the nuclear maturation of EGF-treated group, FSH-treated and FSH and EGF-treated group. These results show that EGF has a stimulatory effect as well as different action pathway with FSH on in-vitro maturation of mouse oocyte in vitro. Therefore, further studies will be needed to find the signaling pathway of EGF associated with nuclear maturation.

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The outcome of surfactant replacement therapy in above nearterm neonates with severe pulmonary disease (준 만삭 이상아에서 폐표면 활성제 보충요법의 성적)

  • Shon, Su-Min;Lee, Bo-Young;Kim, Chun-Soo;Lee, Sang-Lak;Kwon, Tae-Chan
    • Clinical and Experimental Pediatrics
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    • v.50 no.12
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    • pp.1200-1205
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    • 2007
  • Purpose : We performed this study to investigate the outcome of surfactant replacement therapy (SRT) in above nearterm neonates who were required mechanical ventilatory care due to meconium aspiration pneumonia (MAP), respiratory distress syndrome (RDS) or other severe pneumonia (PN). Methods : 48 patients, gestational period ${\geq}36weeks$, who were admitted in NICU of Dongsan Medical Center, Keimyung University between July 1999 and June 2004 were enrolled. They were divided into three groups, MAP group (15 cases), RDS group (27 cases) and PN group (6 cases). All patients were received SRT and evaluated several clinical data (gestational age, oxygen index, duration of ventilator care) and outcome (complications and mortality rate) between pre-SRT and post-SRT. The mean dose of surfactant (modified bovine surfactant, Newfacten, Yuhan Co., Seoul, Korea) was 120 mg/kg. Results : Among each groups, mean pre-SRT OI was higher in MAP group ($21{\pm}3.2$) than other groups, mean duration (days) of ventilatory care and oxygen therapy were similar distributions. Compared with pre-SRT values, significant improvements (P<0.05) in mean values for FiO2 and oxygenation index were documented at 12 hours after SRT. Early complications (persistent pulmonary hypertension of newborm, pneumothorax) and survival rate were lower in MAP group. Within RDS group, earlier SRT (given before 12 hours of life) revealed significantly lower early complication rate than later SRT (given after 12 hours of life) (13.3% vs 58.3%, P<0.05) Conclusion : Our study suggested that SRT seems to be an effective therapy in above nearterm neonates with severe pulmonary disease, and earlier SRT tends to reduce complications in RDS group than later therapy.

MST1R as a potential new target antigen of chimeric antigen receptor T cells to treat solid tumors

  • Wen An;Ju-Seop Kang;Sukjoong Oh;Ang Tu
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.3
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    • pp.241-256
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    • 2023
  • Although chimeric antigen receptor T cell (CAR-T) is a promising immunotherapy in hematological malignancies, there remain many obstacles to CART cell therapy for solid tumors. Identifying appropriate tumor-associated antigens (TAAs) is especially critical for success. Using a bioinformatics approach, we identified common potential TAAs for CAR-T cell immunotherapy in solid tumors. We used the GEO database as a training dataset to find differentially expressed genes (DEGs) and verified candidates using the TCGA database, obtaining seven common DEGs (HM13, SDC1, MST1R, HMMR, MIF, CD24, and PDIA4). Then, we used MERAV to analyze the expression of six genes in normal tissues to determine the ideal target genes. Finally, we analyzed tumor microenvironment factors. The results of major microenvironment factor analyses showed that MDSCs, CXCL1, CXCL12, CXCL5, CCL2, CCL5, TGF- β, CTLA-4, and IFN-γ were significantly overexpressed in breast cancer. The expression of MST1R was positively correlated with TGF- β, CTLA-4, and IFN-γ. In lung adenocarcinoma, MDSCs, Tregs, CXCL12, CXCL5, CCL2, PD-L1, CTLA-4, and IFN-γ were significantly overexpressed in tumor tissues. The expression of MST1R was positively correlated with TGF- β, CTLA-4, and IFN-γ. In bladder cancer, CXCL12, CCL2, and CXCL5 were significantly overexpressed in tumor tissues. MST1R expression was positively correlated with TGF- β. Our results demonstrate that MST1R has the potential as a new target antigen for treating breast cancer, lung adenocarcinoma, and bladder cancer and may be used as a progression indicator for bladder cancer.