• 제목/요약/키워드: PD-1/PD-L1

검색결과 308건 처리시간 0.027초

Impact of Various Tumor Markers in Prognosis of Gastric Cancer -A Hospital Based Study from Tertiary Care Hospital of Kathmandu Valley

  • Mittal, Ankush;Gupta, Satrudhan Pd.;Jha, Dipendra Kumar;Sathian, Brijesh;Poudel, Bibek
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권3호
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    • pp.1965-1967
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    • 2013
  • Background: To obtain the maximum additional information about the prognosis of gastric cancer, we compared CA-50 with other previously defined markers. Materials and Methods: This hospital based study was carried out in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between $1^{st}$ July 2012 and $31^{st}$ December 2012. The variables collected were age, gender, AFP, CEA, CA19-9, and CA50, assayed with ELISA reader for all cases. The cut off values for serum AFP, CEA, CA19-9, and CA-50 were 10 ${\mu}g/l$, 10 ${\mu}g/l$, 37 U/ml, and 20 U/ml, respectively according to the manufacturer's instructions. Approval for the study was obtained from the institutional research ethical committee. Results: Of the 40 examined patients, 13 patients had tumors located in the upper third of the stomach, 6 patients had tumors in the middle third, 16 patients had tumors in the lower third, and 5 patients had tumors occupying two-thirds of the stomach or more. The distribution of lymph node staging of the patients was as follows: 7 patients belonged to N0, 9 patients to N1 stage, 10 patients to N2 stage, and 14 patients to N3 stage. The statistical method of Cox proportional hazards using multivariate analysis also illustrated that tumor markers including CEA (2.802), CA19-9 (2.690), CA50 (2.101), were independent prognostic factors, as tumor size (1.603), and lymph node stage (1.614). Conclusions: The tumour markers now available, like CEA, CA 19-9 and CA 50, chiefly perceive advanced gastric cancer. The preoperative rise in those tumour marker level have a prognostic significance and may be clinically helpful in choosing patients for adjuvant management.

Toxoplasma gondii IST suppresses inflammatory and apoptotic responses by inhibiting STAT1-mediated signaling in IFN-γ/TNF-α-stimulated hepatocytes

  • Seung-Hwan Seo;Ji-Eun Lee;Do-Won Ham;Eun-Hee Shin
    • Parasites, Hosts and Diseases
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    • 제62권1호
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    • pp.30-41
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    • 2024
  • The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.

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
    • 한국자원식물학회지
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    • 제28권3호
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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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    • 제14권11호
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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.

Clitocybe aurantiaca 균주가 생산하는 주름개선소재 clitocybin A의 대량 발효생산 및 MMP-1 발현저해활성 (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)

  • 김관철;이혁원;이홍원;추수진;유익동;하병조
    • 한국미생물·생명공학회지
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    • 제42권2호
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    • pp.194-201
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    • 2014
  • 본 연구에서는 국내 자생버섯의 일종인 Clitocybe aurantiaca KCTC11143BP 균주가 생산하는 주름개선 화장품 신소재 clitocybin A의 발효생산 최적조건, 추출정제조건, 세포독성 및 자외선 조사에 따른 MMP-1 발현 저해활성을 규명하였다. C. aurantiaca 균주를 5 L 발효조를 이용하여 회분식으로 배양하였을 경우, PD 액체배지보다 YM 액체배지에서 양호하게 생육하는 것을 확인하였다. 300 L 용량의 대형 발효조에서 modified된 YM 배지를 이용한 유가식 배양으로 14일간 배양한 결과, 12.5 kg/120 L의 총 균체량을 얻었다. 발효 추출물로부터 항노화 소재인 clitocybin A를 추출정제를 한 후 HPLC를 실시하여 배양 4일째부터 clitocybin A가 생산되고 있음을 확인하였다. Clitocybin A 화합물의 세포독성을 확인하기 위하여 MTT assay를 실시한 결과, 100 ${\mu}g/ml$ 농도로 처리하였을 경우 $134.6{\pm}10.4%$로 오히려 세포가 증식하여 안전한 소재임을 확인하였다. 반면, 대조군으로 사용한 oleanolic acid는 25 ${\mu}g/ml$ 농도에서도 강한 세포독성을 나타냈다. 또한, clitocybin A는 100 ${\mu}g/ml$ 처리시 33.1%의 MMP-1 발현 저해활성 보여 주름개선 기능성화장품 소재로 매우 우수한 화합물임을 확인하였다.

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

  • 송병정;이병요;채정우;안정화;권광일
    • 한국임상약학회지
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    • 제22권3호
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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.

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

  • 김우철;김헌정;박정훈;허현도;최상현
    • Radiation Oncology Journal
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    • 제29권1호
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    • pp.28-35
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    • 2011
  • 목 적: 초기 비소세포성 폐암 환자에서 수술적 절제 이외의 국소 치료로 최근 방사선 수술의 사용이 늘고 있다. 이에 저자들은 초기 혹은 재발한 비소세포성 폐암 환자를 대상으로 시행한 체부 방사선 수술의 치료 결과를 분석하여 그 유용성을 알아 보고하고자 한다. 대상 및 방법: 비소세포성 폐 종양에 대하여 방사선 수술이 시행되었던 24명의 환자, 28 lesion에 대하여 후향적 분석을 시행하였다. 이 중 원발성 종양은 19명 재발한 환자는 5명이었고 재발한 환자 5명 중 3명이 이전 치료 부위에서 재발한 환자 이었다. 원발성 종양 19명 중에서 4명은 외부 방사선 치료 후 추가로 방사선 수술을 시행 받았다. 24명의 초기 병기는 IA, IB, IIA, IIB, IIIA, IIIB, IV가 각각 7, 3, 2, 2, 3, 1, 6명이었고, 방사선 수술 당시의 T 병기는 T1 lesion이 13곳, T2가 12곳, T3가 3곳이었다. 방사선 수술은 6 MV X-ray를 이용하였고 planning target volume 1 (PTV1)에 총 방사선량 15~60 Gy(median, 50 Gy)를 3회 혹은 5회에 걸쳐 처방하여 시행하였다. 중앙 추적관찰기간은 469일이었다. 결 과: 28곳의 GTV는 0.7~108.7 mL (median, 22.9 m L)이었고, PTV1 은 5.3~184.8 mL (median, 65.4 m L)이었다. 3개월 반응률은 complete response (CR) 14곳, partial response (PR) 11곳, stable disease (SD) 3곳이었고, 마지막 추적에서의 치료반응은 CR 13곳, PR 9곳, SD 2곳, progressive disease (PD) 4곳이었다. 원발종양으로 초기 병기 IA, IB 10명에서는 50일만에 1명이 폐렴으로 사망하였고 1명이 국소재발 하였으나 나머지 환자는 6개월에서 2년간 국소재발 없이 추적관찰 되고 있으며, IIA-IIB 환자는 4명으로 환자 수가 적어서 뚜렷한 결론을 내리기 어려웠고, 재발성 폐암 환자 5명을 포함하는 10명의 IIIA-IV 병기에서는 사망 3명, 국소재발 1명, loco-regional failure 1명, regional failure 2명으로 좋지 않은 치료 결과를 보였다. 이 중에서 방사선 수술을 시행한 장소에서 재발한 경우는 총 28 1esion 중 4곳으로 85.8%의 국소제어율을 보였다. 방사선치료 양은 biologically equivalent dose (BEd) 100 $Gy_{10}$ 이하인 8 lesion 중에서 3 lesion에서 국소 재발하여 100 $Gy_{10}$ 이상인 20 lesion 중에서는 1 lesion에서만 재발한 경우보다 나빴다. 또한 중앙부의 종양과 방사선수술 당시의 병기가 T2 이상인 경우가 재발이 많았다. 결 론: 비소세포성 폐암환자에서 사이버나이프를 이용한 체부 방사선 수술은 부작용이 적으면서 높은 국소제어율을 얻을 수 있는 치료이며, 주변부의 T1 병기의 폐암에 대해서 BED 100 $Gy_{10}$ 이상의 방사선 치료가 국소제어율을 높이는데 도움이 된다고생각된다.

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

  • 박상진;김정환;이경호;양종범;백영진;김창한
    • 한국미생물·생명공학회지
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    • 제27권1호
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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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    • 제18권4호
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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
    • 한국수정란이식학회:학술대회논문집
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    • 한국수정란이식학회 2002년도 국제심포지엄
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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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