류마티스 관절염 활액막에서 Cyclooxygenase-1, 2의 발현 양상

이영호 ( Young Ho Lee ),최성재 ( Seong Jae Choi ),지종대 ( Jong Dae Ji ),김애리 ( Ae Ree Kim ),김철환 ( Chul Hwan Kim ),송관규 ( Gwan Gyu Song ) 대한류마티스학회 1998 대한류마티스학회지 Vol.5 No.2

목적: 류마티스 관절염 환자의 활액막에서 COX-1과 COX-2의 발현양상을 알아보고자 하였다. 방법: 류마티스 관절염 환자 9명의 활액막과 대조군으로 골관절염 환자 5명의 활액막 조직을 COX-1과 COX-2 특이항체를 이용하여 면역조직화학법으로 염색하여 관찰하였고 H&E 염색상 조직학적 소견 조사하였다. 결과: 1. COX-1은 류마티스 관절염 활액막조직에서 기질 유섬유아세포에서 강하게 염색되었고, 활액내막세포, 염증성 단핵세포와 혈관내피세포에서도 발현되었으며, 골관절염 활액막조직의 COX-1 염색소견과 유사하였다. 2. COX-2는 류마티스 관절염 활액막조직에서 염증성 단핵세포에서 강하게 염색되었고, 기질 유섬유아세포, 혈관내피세포와 활액내막세포에서 발현되었으며, 골관절염 활액막조직의 COX-2 발현소견과 의의 있는 차이를 보이지 않았다. 3. 류마티스 관절염 활액막에서 COX-1과 COX-2의 발현양상간에 있어서 의의 있는 차이는 관찰되지 않았다. 결론: COX-1도 COX-2처럼 류마티스 관절염 활액막에서 증가되어 있고 COX-1도 COX-2처럼 류마티스 관절염 활액막의 염증반응에 기여할 가능성이 있다. Objective: To investigate expression and localization of cyclooxygenase-1(COX-1) and cyclooxygenase-1(COX-2) in synovial tissues from patients with rheumatoid arthritis(RA). Methods: We examined expression and localization of COX-1 and COX-2 staining in synovial tissues from patients with RA, compared with osteoarthritis(OA) as control by immunohistochemical staining using polyclonal COX-1 and COX-2 antibodies and also scored histologic features of inflammation. Results: COX-1 in synovial tissues from RA was stained most strongly in stromal fibroblast-like cells and expressed in synovial lining cells, inflammatory mononuclear cells and vascular endothelial cells. COX-1 expression in RA synovial tissues was comparable to that in OA synovial tissues. COX-2 in synovial tissues from RA was stained most strongly in inflammatory mononuclear cells and expressed in stromal fibroblast-like cells, vascular endothelial cells and synovial lining cells. COX-2 expression in RA synovial tissues was not significantly different from that in OA synovial tissues. In addition, no significant difference between COX-1 and COX-2 stainings in synovial tissues from RA was observed. Conclusions: Our data suggest that COX-1 expression may be up regulated like COX-2 expression in chronic RA and COX-1, like COX-2, might contribute to synovial inflammation in RA.

TCDD에 노출된 갑상샘 유두암종 세포주에서 선택적 Cyclooxygenase 2 억제제의 효과

김해성,안광성,이정현,채양석,원남희,최종상,김철환 대한병리학회 2011 Journal of Pathology and Translational Medicine Vol.45 No.1

Background: Cyclooxygenase 2 (COX-2) is related to carcinogenesis and progression of cancer. COX-2 has been detected in thyroid cancer. This suggests that COX-2 inhibitor may be useful to control the growth of thyroid cancer cells as well as the progression of thyroid cancer. Tetrachlorodibenzodioxin (TCDD), acting as an inflammatory cytokine, directly induces the expression of COX-2. We examine whether TCDD controls the effect of COX-2 inhibitor on thyroid cancer cells. Methods: The effects of TCDD and celecoxib on thyroid papillary carcinoma cell line (SNU790) were examined using cell proliferation and fluorescence-activated cell sorting analysis. Western blot analysis was performed to determine the expressed COX-2 levels and the cell cycle-related proteins. The matrix metalloproteinase-2 (MMP-2) expression and gelatinolytic activity were examined using real time-polymerase chain reaction and zymography. Results: TCDD directly induced the growth of SNU790 and the expression of cyclin D1, cyclin A, cyclin E, p21 and COX-2. Celecoxib suppressed the growth of SNU790 and the expression of cyclin D1 and cyclin E. Celecoxib reduced the MMP-2 expression and the gelatinolytic activity, but those effects were decreased in the SNU790 by either pre-treatment with TCDD or co-treatment with TCDD and celecoxib. Conclusions: Celocoxib effect is directly reduced depending on the exposure to TCDD. TCDD exposure should be considered in the treatment with Celecoxib.

Cyclooxygenase-2 Overexpression in Chronic Inflammation Associated with Benign Prostatic Hyperplasia: Is It Related to Apoptosis and Angiogenesis of Prostate Cancer?

김병훈,김천일,장혁수,최미선,정혜라,김덕윤,박철희 대한비뇨의학회 2011 Investigative and Clinical Urology Vol.52 No.4

Purpose: This study was performed to investigate the relationship between cyclooxygenase-2 (COX-2) expression and apoptosis/angiogenesis in inflammatory and noninflammatory benign prostatic hyperplasia (BPH) and prostate cancer (PC). Materials and Methods: This study involved 64 BPH and 57 PC patients. The BPH histopathologies were classified by the presence of chronic inflammation as follows: noninflammatory BPH (NI-BPH; n=23) and inflammatory BPH (I-BPH; n=41). The association between the expression of COX-2, expression of Bcl-2, the apoptotic index (AI), expression of vascular endothelial growth factor (VEGF), and microvascular density (MVD) in the prostate was investigated. Results: An overexpression of COX-2, Bcl-2, and VEGF was observed in cases of PC compared with cases of BPH. In PC, the AI was lower and MVD was higher than in BPH. In NI-BPH, I-BPH, and PC, the overexpression of COX-2, Bcl-2, and VEGF gradually increased. The AI was high in I-BPH, but did not differ significantly between the NI-BPH and I-BPH groups or between the NI-BPH and PC groups. MVD was significantly high in PC, but no significant difference was found between NI-BPH and I-BPH. A significant correlation was shown between the overexpression of COX-2 and Bcl-2, and COX-2 and VEGF. However, the AI was not correlated with the overexpression of COX-2 or Bcl-2. MVD was correlated with the overexpression of COX-2 and VEGF. Conclusions: COX-2 overexpression in PC is correlated with a decrease in apoptosis and an increase in angiogenesis. Chronic inflammation in BPH causes an overexpression of COX-2, which induces the increased expression of Bcl-2 and VEGF. It is likely that chronic inflammation plays a role in the intermediate step of carcinogenesis in the prostate. Purpose: This study was performed to investigate the relationship between cyclooxygenase-2 (COX-2) expression and apoptosis/angiogenesis in inflammatory and noninflammatory benign prostatic hyperplasia (BPH) and prostate cancer (PC). Materials and Methods: This study involved 64 BPH and 57 PC patients. The BPH histopathologies were classified by the presence of chronic inflammation as follows: noninflammatory BPH (NI-BPH; n=23) and inflammatory BPH (I-BPH; n=41). The association between the expression of COX-2, expression of Bcl-2, the apoptotic index (AI), expression of vascular endothelial growth factor (VEGF), and microvascular density (MVD) in the prostate was investigated. Results: An overexpression of COX-2, Bcl-2, and VEGF was observed in cases of PC compared with cases of BPH. In PC, the AI was lower and MVD was higher than in BPH. In NI-BPH, I-BPH, and PC, the overexpression of COX-2, Bcl-2, and VEGF gradually increased. The AI was high in I-BPH, but did not differ significantly between the NI-BPH and I-BPH groups or between the NI-BPH and PC groups. MVD was significantly high in PC, but no significant difference was found between NI-BPH and I-BPH. A significant correlation was shown between the overexpression of COX-2 and Bcl-2, and COX-2 and VEGF. However, the AI was not correlated with the overexpression of COX-2 or Bcl-2. MVD was correlated with the overexpression of COX-2 and VEGF. Conclusions: COX-2 overexpression in PC is correlated with a decrease in apoptosis and an increase in angiogenesis. Chronic inflammation in BPH causes an overexpression of COX-2, which induces the increased expression of Bcl-2 and VEGF. It is likely that chronic inflammation plays a role in the intermediate step of carcinogenesis in the prostate.

Phenethyl Isothiocyanate가 Toll-Like Receptor Agonists에 의해 유도된 Nuclear Factor-κB 활성과 Cyclooxygenase-2, Inducible Nitric Oxide Synthase 발현에 미치는 효과

김수정 ( Soo Jung Kim ),박혜정 ( Hye Jeong Park ),신화정 ( Hwa Jeong Shin ),김지수 ( Ji Soo Kim ),안희진 ( Hee Jin Ahn ),민인순 ( In Soon Min ),윤형선 ( Hyung Sun Youn ) 한국응용생명화학회(구 한국농화학회) 2011 Journal of Applied Biological Chemistry (J. Appl. Vol.54 No.4

염증의 중요한 분자학적 기전에는 cyclooxygenase-2 (COX-2)에 의한 prostaglandins (PGs) 생성과 inducible nitric oxide synthase (iNOS)에 의한 nitric oxide (NO) 생성이 있다. 많은 종류의 박테리아나 바이러스가 전사요소인 nuclear factor-κB(NF-κB)를 활성화시켜 여러 타깃 유전자의 발현을 조절해 PGs나 NO와 같은 염증물질을 유도하게 된다. 우리는 이번 실험을 통하여 phenethyl isothiocyanate (PEITC)가 toll-like receptor (TLR) agonists에 의해 유도된 NF-κB활성과 COX-2, iNOS 발현에 어떠한 영향을 미치는지 알아 보았다. PEITC는 lipopolysaccharide (LPS)와 polyinosinic-polycytidylic acid (poly[I:C])에 의해 유도된 NF-κB활성을 억제시켰다. 또한 PEITC는 LPS와 Poly[I:C]에 의해 유도된 iNOS의 발현도 억제시켰다. 하지만 PEITC는 TLR agonists들인 LPS, Poly[I:C], 2kDa macrophage-activating lipopeptide (MALP-2), oligodeoxynucleotide 1668 (ODN1668)에 의한 COX-2 발현은 억제시키지 못하였다. 즉 PEITC가 TRIF-dependent 신호전달체계만을 조절하여 TRIF-dependent 신호전달체계에 의해 조절되는 iNOS는 억제하지만 MyD88-dependent 신호전달 체계에 의해 조절되는 COX-2는 억제하지 못한다는 것을 설명해준다. 이러한 결과는 iNOS와 COX-2가 서로 다른 메커니즘에 의해 조절된다는 것을 암시하며, PEITC가 여러 병원균들로부터 유도되는 염증반응이나 만성적인 질병들을 조절할 수 있음을 제시하는 중요한 결과이다. Toll-like receptors (TLRs) play an important role in induction of innate immune responses. The activation of TLRs triggers inflammatory responses that are essential for host defense against invading pathogens. Phenethyl isothiocyanate (PEITC) extracted from cruciferous vegetables has an effect on anti-inflammatory therapy. Dysregulated activation of nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) has been shown to play important roles in the development of certain inflammatory disease. To evaluate the therapeutic potential of PEITC, NF-κB activation and COX-2 and iNOS expression induced by lipopolysaccharide (LPS, TLR4 agonist), polyinosinic-polycytidylic acid (Poly[I:C], TLR3 agonist), 2 kDa macrophageactivating lipopeptide (MALP-2, TLR2 and TLR6 agonist) or oligodeoxynucleotide 1668 (ODN1668, TLR9 agonist) were examined. PEITC inhibits the activation of NF-κB induced by LPS or Poly[I:C] but not by MALP-2 or ODN1668. PEITC also suppressed the iNOS expression induced by LPS or Poly[I:C]. However, PEITC did not suppress COX-2 expression induced by LPS, Poly[I:C], MALP-2, or ODN1668. These results suggest that PEITC has the specific mechanism for antiinflammatory responses.

선택적 Cyclooxygenase-2 억제제인 Celecoxib가 상이한 Cylooxygenase-2 발현량을 가진 인간 암세포주들에 대하여 유도하는 방사선 감수성 증진 작용

표홍렬(Hongryull Pyo),신유근(You Keun Shin),김현석(Hyun Seok Kim),성진실(Jinsil Seong),서창옥(Chang Ok Suh),김귀언(Gwi Eon Kim) 대한방사선종양학회 2003 Radiation Oncology Journal Vol.21 No.3

목 적: Cyclooxygenase-2 (COX-2)를 과발현하는 A549 인간폐암세포주와 발현하지 않는 MCF-7 인간 유방암 세포주에서 선택적 COX-2 억제제인 celecoxib의 방사선 감수성 증진 작용을 관찰하고자 하였다. 대상 및 방법 : A549 세포와 MCF-7 세포에 대해서 방사선 혹은 방사선과 celecoxib를 병용 투여한 후에 clonogenic radiationsurvival실험을 시행하였다.같은 실험을 각각 10%와 1%의 FBS를 포함한 배지에서 반복하였다.각 세포에 방사선과 celecoxib를 동시 혹은 단독 투여한 후에 각 실험 그룹의 세포사멸을 측정하였다. 결 과: 약물 투여기간 동안 10%의 혈청을 포함한 배지조건에서 배양된 A549 세포에서는, 3 0μM과 50μM 농도의celecoxib가 투여된 상태에서 surviving fraction=0.1에서의 Radiation enhancement ratio (RER)가 각각 1.58과 1.81로 celecoxib가 A549 세포의 방사선 감수성을 증가시켰다. 이러한 방사선 감수성의 증가는 세포를 1%의 혈청을 포함한 배지에서 배양하였을때는 소실되었다. MCF-7 세포에서는 10%와 1% 혈청을 포함한 각각의 배지조건 하에서 celecoxib에 의한 방사선 감수성의 변화가 관찰되지 않았다. A549와 MCF-7 세포의 각 그룹에서 세포사멸을 측정한 결과 celecoxib와 방사선이 병용 투여되었을 때 유도되는 세포사멸은 상호 상승적이지 않은 것으로 나타났다. 결 론: COX-2 선택적 억제제인 celecoxib는 COX-2를 과발현하는 A549 세포에서 선택적으로 방사선 감수성을 증진시켰으며, 저 농도의 혈청을 포함한 배지조건에서는 이러한 효과가 소실되었다. COX-2를 발현하지 않는 MCF-7 세포주에서는 celecoxib에 의해서 방사선 감수성이 변화되지 않았으며, 이러한 celecoxib의 방사선 감수성 증진 작용 기전에 세포 사멸은 관여하지 않는 것으로 보인다. Purpose To investigate the modulation of radiosensitivity by celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on cancer cells over-and under-expressing COX-2. Materials and Methods: A clonogenic radiation survival analysis was performed on A549 human lung and MCF-7 human breast cancer cell lines incubated in both 1 and 10% fetal bovine serum (FBS) containing media. The apoptosis in both cell lines was measured after treatment w ith radiation and/or celecoxib. Results Celecoxib enhanced the radiation sensitivity of the A 5 49 cells in the medium containing the 10% FBS, with radiation enhancement ratios of 1.58 and 1.81 respectively, at surviving fractions of 0.1, with 30M and 50M celecoxib. This enhanced radiosensitivity disappeared in the medium containing the 1% FBS. Celecox ib did not change the radiation sensitivity of the MCF-7 cells in either media. The induction of apoptosis by celecoxib and radiation was not synergistic in either cell line. Conclusion Celecoxib, a selective COX-2 inhibitor, preferentially enhanced the effect of radiation on COX-2 over-expressing cancer cells compared to the cells with a low expression, and this effect disappeared on incubation of the cells during drug treatment in the medium with suboptimal serum concentration. Apoptosis did not appear to be the underlying mechanism of this radiation enhancement effect due to celecoxib on the A549 cells. These findings suggest radiosensitization by a selective COX-2 inhibitor is COX-2 dependent.

정상 자궁내막, 자궁내막 증식증, 자궁 내막암에서의 cyclooxygenase-2,p53 발현율 비교 연구

유상욱,이낙우,이규완,김옥경,송재윤,홍순철 대한부인종양학회 2006 Journal of Gynecologic Oncology Vol.16 No.3

Objective: The purpose of this study is to compare the expression rate of cyclooxygenase-2(COX-2), p53 in endometrial hyperplasia ,endometrial cancer and normal endometrium and to correlate COX-2 with the clinicopathological factors and p53 in endometrial cancer. Materials and methods: Immunohistochemical stain of COX-2, p53 was performed on samples from a series of 19 cases of normal proliferative endometrium, 20 cases of complex endometrial hyperplasia and 19 cases of endometrial cancer. And then we analyzed the expression of COX-2 correlated the findings with clinicopathological factors and p53. Expression of COX-2 was scored according to the proportion of positive-staining cells: negative, no staining; 1+, <10%; 2+, 10-50%; 3+, >50. For p53 overexpression, when there were at least 10% of tumor cells stained , it was considered as positive. Results: Overexpression of COX-2(≥2+) was seen in 5(26.3%) of the endometrial cancers, 6(30%) of the complex endometrial hyperplasia, and 4(21.1%) of the normal endometria. The expression rates of COX-2 in endometrial cancer, hyperplasia and normal endometrium were not different statistically significant(p=0.93). COX-2 was not correlated with clinicopathological factors but correlated with p53 significantly (p=0.021). Conclusion: In this study, the immunohistochemical analysis showed no difference statistically in COX-2 expression between endometrial cancer and hyperplasia compared to normal endometria. COX-2 was significantly correlated with p53. This finding may represent that tumor suppressor p53 upregulates COX-2 expression 목적: Cyclooxygenase-2(COX-2) 과발현이 대장암, 자궁 경부암, 유방암, 방광암등 여러 암에서 보고되고 있고, 최근에는 자궁내막암에서 COX-2발현 양상에 관한 연구가 이루어지고 있다. 여러 보고에서 COX-2와 p53의 상관관계와 기전에 대한 연구가 이루어지고 있다. 이에 본 연구에서는 자궁내막증식증과 자궁내막암에서의 COX-2 발현율을 정상 자궁내막과 비교하고 임상예후인자로서의 가능성을 확인하며 COX-2 발현이 p53과 관련성이 있는지에 관하여 살펴보았다. 연구 방법: 2000년 1월부터 2005년 10월까지 고려대학교 안암병원 산부인과학 교실에서 자궁 내막 생검 또는 자궁 적출술을 통해 외과적으로 절제된 정상 증식기 자궁 내막 19예, 복합성 자궁 내막 증식증(complex endometrial hyperplasia) 20예, 자궁 내막암으로 확진된 19예 등 58예를 대상으로 하였다. 자궁내막 조직에 COX-2, p53으로 면역 조직 화학 염색을 시행하여 그 결과를 COX-2는 염색 강도에 따라 음성, 1+,2+3+로 판독하였고, p53은 음성과 양성 두군으로 판독하였다. 세 군에서의 COX-2, p53염색 결과를 비교하였고, COX-2와 p53의 관계를 알아보았다. 결과: 세 군에서의 COX-2 양성율을 비교한 결과 정상 자궁 내막, 복합성 자궁내막 증식증, 자궁내막암 세군 간에 유의한 차이는 보이지 않았다. COX-2 강양성(2+이상)으로 판독한 결과 정상 자궁내막 4/19예(21.1%), 복합성 자궁내막 증식증 6/20예(30%), 자궁 내막암 5/19예(26.3%)로 정상 자궁내막에 비해 복합성 자궁내막증식증과 자궁내막암에서 COX-2 강양성율이 높았으나 통계학적으로 유의하지는 않았다(p=0.930). COX-2면역조직 화학 염색 결과와 p53 면역 조직 화학 염색 결과와의 관련성을 비교한 결과 p53에서 양성을 보인 10/10예(100%)에서 COX-2 양성을 보였으며(p=0.021), p53 양성과 COX-2 강양성(2+이상) 사이의 상관관계도 유의한 결과를 나타났다(p=0.013) 결론: 결론적으로, 복합성 자궁내막증식증, 자궁내막암에서 정상 자궁 내막에서의 COX-2 발현율은 통계학적으로 유의한 차이를 보이지 않았고 자궁내막암의 임상적 예후 인자와도 관련성을 입증하지는 못하였으나 COX-2 발현은 p53 발현과 유의한 상관관계를 보였다. 이는 아마도 p53이 COX-2발현을 증가시킨 결과로 판단된다.

생쥐에서 사구체내 Cyclooxygenase-2 과발현이 Puromycin에 의한 발세포 손상에 미치는 영향

조영일 ( Young Il Jo ) 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.2

목적: Cyclooxygenase-2 (COX-2) 억제제 치료가 단백뇨를 감소시키는 것으로 알려진 이후 COX-2가 발세포(podocyte) 손상에 관여할 가능성이 제기되었지만, COX-2가 발세포 손상에 어떤 역할을 하는지는 명확하지 않다. 한편, 생쥐는 발세포에 독성을 가진 puromycin (PAN)을 투여해도 발세포 손상과 단백뇨가 잘 유발되지 않는다. 저자는 COX-2가 발세포 손상에 관여한다면 사구체에 COX-2를 과발현시킨 생쥐는 PAN에 의해 단백뇨가 발생할 것이라고 가정하고, COX-2 유전자 도입 생쥐에 PAN 및 선택적 COX-2 억제제를 투여하여 COX-2가 발세포 손상에 어떤 영향을 미치는지를 알아보고자 하였다. 방법: Wild-type 생쥐 (B6/D2 strain)와 COX-2 유전자 도입 생쥐에 PAN을 투여하였고, 다른 한 군에는 PAN과 함께 선택적 COX-2 억제제 (SC58236)를 투여하였다. PAN은 실험 1일 (15 mg/100 g BW) 및 3일 (30 mg/100 g BW)의 시작 시점에 정맥 주사하였고, SC58236은 PAN을 주사한 직후부터 식용수에 용해시켜 실험기간 내내 경구 투여하였다. 생쥐는 실험 3일 및 10일 종료 시점에 희생시켰으며, 알부민뇨, 족돌기 소실 그리고 사구체내 COX-2와 nephrin의 발현 정도를 조사하였다. 결과: COX-2 유전자 도입 생쥐만 PAN을 투여한 후에 알부민뇨가 발생하였고, 알부민뇨는 선택적 COX-2 억제에 의해 유의하게 억제되었다. 알부민뇨는 3일째에 유의하게 증가하였고 이후에는 정상수준으로 점차 감소하였다. PAN 투여로 알부민뇨가 발생한 COX-2 유전자 도입 생쥐에서 사구 체내 COX-2 발현은 증가하였고 nephrin은 발현이 감소하는 양상을 보였으며, 이러한 변화는 COX-2 억제제 투여로 완화되었다. 이와는 달리, wild-type 생쥐는 PAN 투여 후에도 유의한 변화를 보이지 않았다. 결론: PAN에 반응을 보이지 않는 wild-type 생쥐와는 달리, COX-2 유전자 도입 생쥐는 PAN에 의해 알부민뇨, 발세포 손상 및 COX-2 발현 증가가 나타났고, 이는 선택적 COX-2 억제제에 의해 완화되었다. 이러한 결과는 COX-2가 생쥐에서 PAN에 의한 발세포 손상의 유발인자로 작용하며, COX-2 억제제가 발세포 손상을 완화시킬 수 있음을 시사한다. Purpose: The aim of this study is to investigate the effect of glomerular cyclooxygenase-2 (COX-2) overexpression on podocyte injury by puromycin aminonucleoside (PAN) in nephrin-driven COX-2 transgenic mice. Methods: We administrated PAN intravenously on day-1 (15 mg/100 g body weight) and day-3 (30 mg/100 g body weight) in wild type (male B6/D2 mice) and COX-2 transgenic mice. An additional group received a selective COX-2 inhibitor (SC58236) with PAN. The animals from each group were sacrificed at the end of day-3 and 10. We investigated albuminuria, foot process effacement and glomerular COX-2 and nephrin expression. Results: PAN induced albuminuria only in COX-2 transgenic mice, with the peak on day-3. Selective COX-2 inhibition significantly reduced albuminuria. EM examination demonstrated foot process effacement, which was improved partially by selective COX-2 inhibition, in COX-2 transgenic mice treated with PAN on day-3. Glomerular COX-2 expression increased significantly on day-3 in COX-2 transgenic mice treated with PAN, whereas expression of nephrin showed a tendency to decrease on day-3. These changes of expression of COX-2 and nephrin were partly attenuated by selective COX- 2 inhibition. Unlike COX-2 transgenic mice, wild-type mice did not show any changes even after PAN treatment. Conclusion: In COX-2 transgenic mice, PAN induced albuminuria, podocyte injury and up-regulation of glomerular COX-2, which were ameliorated by selective COX-2 inhibitor. These results suggest that COX-2 may play an important role in increasing susceptibility of podocytes to injury and selective COX-2 inhibition may ameliorate podocyte injury.

Upregulation of Cyclooxygenase­2 in Squamous Cell Carcinomas of the Head and Neck

Lee, Dong Wook,Yoon, Tae Young,Park, Kyu Hyung 충북대학교 의학연구소 2002 忠北醫大學術誌 Vol.12 No.2

연구목적 : Cyclooxygenase-2(COX-2)는 대장암을 비롯한 여러 종양의 암화과정에 중요한 역할을 하는 것으로 추정되고 있다. 본 연구는 인체 두경부의 편평상피암에서 COX-2의 발현양상을 알아보고자 시행하였다. 대상 및 방법: 면역조직화학검사와 Western blotting을 이용하여 두경부 편평상피암 조직과 세포주에서 COX-2의 발현 정도를 측정하였다. 결과: COX-2의 발현 정도는 면역조직화학검사상 정상 조직에서보다 두경부 편평상피암 조직에서 유의하게 증가되어 있었고, 정상 세포주에서는 COX-2 단백질이 거의 발현되지 않지만 두경부암 세포주에서는 COX-2가 잘 발현되고 있음을 Western blot을 통하여 확인할 수 있었다. 결론: COX-2가 두경부암의 암화과정에서 중요한 역할을 담당할 가능성이 크다는 결론을 도출할 수 있었으며, 임상적으로는 COX-2의 억제제가 두경부암의 예방 및 치료에 기여하리라고 생각된다. Purpose: Cyclooxygenase-2 (COX-2) has been found to be involved in carcinogenic process in many human cancers including colorectal carcinoma. the aim of this study was to examine the expression of COX-2 in human squamous cell carcinoma of the head and neck (SCCHN). Materials and Methods: We investigated the expression of COX-2 in human head and neck cancer tissues an dcell lines using immunohistochemistry and Western blot analysis, respectively. Result: Immunostaining revealed a significantly increased COX-2 expression in tumor tissues compared with normal controls (p<0.05). Western blotting analysis using a COX-2 antibody indicated that seven SCCHN cancer cell lines tested constitutively expressed COX-2 protein. Conclusion: Our study showed that COX-2 could be a participant in carcinogenesis of SCCHN and COX-2 inhibitors would be a potential tool for the management of SCCHN.

결장직장암에서의 Cyclooxygenase-2와 Inducible Nitric Oxide Synthase의 발현

양근호,배병노,김정연,김기환,한세환,김홍주,김영덕 대한대장항문학회 2003 Annals of Coloproctolgy Vol.19 No.3

후두 편평세포암종에서 Cyclooxygenase 1과 2의 발현

김경환,조강한,이규석,임도형,백상흠,양훈식,홍영호,김미경 대한이비인후과학회 2001 대한이비인후과학회지 두경부외과학 Vol.44 No.9