위암에서 발견된 돌연변이형 Fas 단백의 기능적 결함

박원상,조용구,김창재,박조현,김영실,김수영,남석우,이석형,유남진,이정용,Park Won Sang,Cho Young Gu,Kim Chang Jae,Park Cho Hyun,Kim Young Sil,Kim Su Young,Nam Suk Woo,Lee Sug Hyung,Yoo Nam Jin,Lee Jung Young 대한위암학회 2003 대한위암학회지 Vol.3 No.4

Purpose: The balance between cell proliferation and apoptosis is crucial for homeostatic maintenance in a cell population. Decreased apoptosis or uncontrolled proliferation can lead to cancer. The Fas receptor signal through a cytoplasmic death domain is very important in the apoptotic pathway. To identify the effect of the death domain of the Fas gene in the development and/or progression of gastric cancer, we examined the apoptotic potential of five known Fas mutants detected in gastric cancers. Materials and Methods: A wild-type Fas gene was cloned with cDNA from normal liver tissue and full length Fas was sequenced. Mutants of the gene were generated with sitedirected mutagenesis by using the wild-type gene and specific primers. Wild- and mutant-type genes were transfected to HEK293 cells. Forty-eight hours after transfection the cells were stained with DAPI and cell death was counted under fluorescent microscopy. Results: In wild-type Fas-transfected cells, the percentage of apoptotic cells was $85.9\pm3.6\%$, and significant cell death and classic morphologic signs of apoptosis were observed. However, the percentages of apoptotic cells transfected with N239D, E240G, D244V, and R263H of tumor-derived mutant Fas were $29.5\pm2.08\%,\;28.5\pm3.34\%,\;25.225\pm2.06\%,\;and\;36.625\pm4.49\%$, respectively. Conclusion: These results suggest that inactivation of Fas caused by mutations in the death domain of the Fas gene may be one of the possible escape mechanisms against Fas-mediated apoptosis and that inactivating mutation of the Fas may contribute to the development or progression of gastric cancers.

위 선종 및 선암에서 Trefoil Factor Family 1 단백의 발현 양상

박원상,김영실,유남진,박조현,유진영,이연수,이정용,Park Won Sang,Kim Young Sil,Yoo Nam Jin,Park Cho Hyun,Yoo Jin Young,Lee Youn Soo,Lee Jung Young 대한위암학회 2001 대한위암학회지 Vol.1 No.1

Purpose: The trefoil factor family 1 (TFF1) has a protective effect against gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs or ethanol. In addition, a TFF1 knockout mouse model has exhibited circumferential adenomas with high-grade dysplasia, of which $30\%$ progressed into frankly invasive carcinomas. We tried to determine whether the expression pattern of the TFF1 could be involved in the development of sporadic gastric carcinomas. Materials and Methods: We examined TFF1 expression in a series of 43 sporadic gastric carcinomas and 18 gastric adenomas by immunohistochemistry. Results: Strong positive TFF1 staining was identified primarily in the normal gastric mucosa, mainly in the cytoplasm of the superficial and foveolar epithelium. We found TFF1 expression in $55.8\%$ (24 out of 43) of the gastric carcinomas and in $16.7\%$ (3 out of 18) of the gastric adenomas. Statistically, TFF1 immunoreactivity was significantly higher in diffuse-type ($82.4\%$) than in intestinal-type ($38.5\%$) carcinomas(p=0.0058, Fisher's exact test). Conclusion: Our findings provide sufficient evidence that the expression of TFF1 in gastric cancer may simply disclose gastric-type differentiation of neoplastic cells and provide further support for the existence of at least two pathways of malignant transformation of the gastric mucosa: one via intestinal metaplasia and adenomatous dysplasia, leading to glandular carcinomas with intestinal-type differentiation, and the other via hyperplastic changes or de novo changes, leading to diffuse carcinomas and to a subset of glandular carcinomas displaying gastric-type differentiation.

구척(狗脊)이 흰쥐의 척수압박에 의한 신경세포 손상에 미치는 영향

박원상 ( Won Sang Park ),김은석 ( Eun Seok Kim ),신정원 ( Jung Won Shin ),김범회 ( Bum Hoi Kim ),김성준 ( Seong Joon Kim ),강희 ( Hee Kang ),손낙원 ( Nak Won Sohn ) 한방재활의학과학회 2010 한방재활의학과학회지 Vol.20 No.2

Objectives: This study was performed to evaluate the effects of root of Cibotii rhizoma(CR) ethanol extract on the tissue and neuronal damage of the spinal cord injury(SCI). Methods :SCI was induced by mechanical contusion following laminectomy of 10th thoracic vertebra in Sprague-Dawley rats. CR was orally given once a day for 7 days after SCI. Tissue damage and nerve fiber degeneration were examined with cresyl violet and luxol fast blue(LFB) histochemistry. HSP72(as neuronal damage marker), MAP2(as nerve fiber degeneration marker), c-Fos(immediate early gene), and Bax(pro-apoptotic molecule) expressions were examined using immuno-histochemistry. Individual immuno-positive cells expressing HSP72, MAP2, c-Fos and Bax were observed on the damaged level and the upper thoracic and lower lumbar spinal segments. Results :1. CR reduced degeneration of nerve fibers and motor neuron shrinkage in the ventral horn of the lower lumbar spinal segment, but generally it did not seem to ameliorate the tissue injury following SCI. 2. CR reduced demyelination in the ventral and lateral funiculus of the lower lumbar spinal segment. 3. CR reduced HSP72 expression on the neurons in the peri-central canal gray matter adjacent to the damaged region. 4. CR strengthened MAP2 expression on the motor neurons in the ventral horn and on nerve fibers in the lateral funiculus of the lower lumbar spinal segment. 5. CR reduced c-Fos positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. 6. CR reduced Bax positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. Conclusions :These results suggest that CR plays an inhibitory role against secondary neuronal damage and nerve fiber degeneration following SCI.

보존적 치료를 통해 호전된 요추 추간판탈출증 환자의 자기공명영상으로 추적 관찰한 증례 4례 보고

박원상 ( Won Sang Park ),하인혁 ( In Hyuk Ha ),권혁준 ( Hyeok Joon Kwon ),우인 ( In Woo ),윤유석 ( You Suk Youn ),송주혀 ( Joo Hyun Song ) 한방재활의학과학회 2007 한방재활의학과학회지 Vol.17 No.4

Objectives :This study is designed to observe the effect of conservative oriental medicine treatment for HIVD of lumbar spine by MRI. Methods : 4 patients who were diagnosed as lumbar spine herniated intervertebral disc was evaluated after conservative oriental medicine treatment by Visual Analog Scale(VAS), Numeric Rating Scale(NRS), Oswestry Disability Index(ODI), Straight Leg Rasing Test(SLR) six times four week for 6 months. Results : 1. Visual Analog Scale(VAS), Numeric Rating Scale(NRS), Oswestry Disability Index(ODI), Straight Leg Rasing Test(SLR) was significantly improved after conservative oriental medicine treatment for six months.2. Also it was observed that herniated disc was decreased after six months by MRI reexamination. Conclusions : This study suggested that conservative oriental medicine treatment can be effective for decreasing pain and improving functional recovery also decreasing the volume of herniated disc

제1형 다발성 내분비종양 1예

천성원(Sung Won Chun),문인성(In Sung Moon),김준기(Jun Gi Kim),박우배(Woo Bae Park),전정수(Jung Soo Chun),박원상(Won Sang Park),이교영(Kyo Yung Lee),강창석(Chang Suck Kang) 대한외과학회 1991 Annals of Surgical Treatment and Research Vol.40 No.5

위선암 발생에서 인터루킨-1β 유전자 다형성의 역할

강원경 ( Won Kyung Kang ),박원상 ( Won Sang Park ),진형민 ( Hyung Min Chin ),박조현 ( Cho Hyun Park ) 대한소화기학회 2004 대한소화기학회지 Vol.44 No.1

총명탕과 초콜릿 첨가 총명탕의 학습 및 기억장애에 대한 효능 비교연구

김성준,박원상,최현,김범회,신정원,손영주,손낙원,정혁상,Kim, Seong-Joon,Park, Won-Sang,Choi, Hyeon,Kim, Bum-Hoi,Shin, Jung-Won,Sohn, Young-Joo,Sohn, Nak-Won,Jung, Hyuk-Sang 대한한의학방제학회 2008 大韓韓醫學方劑學會誌 Vol.16 No.1

With tablets and powder, decoction has been a widely-used method of medicine formula. However, for these formulas have unique bitter tastes and flavors of herbal component materials as it is, the compliance of herbal medicine is severly decreased especially for female and younger patients. Consequently, expected treatment effects can't be acquired completely. If loathsome tastes and flavors of decoction were effectively reduced while pharmacological activity were kept intact, the compliance could be promoted Chong-Myung-Tang has been widely prescribed for student patients with memory This study shows that Chong-Myung-Tang+chocolate have no difference from Chong-Myung-Tang in terms of pharmacological activity. Sensory difference with net chocolate was also surved. In order to observe the difference of Chong-Myung-Tang+chocolate and Chong-Myung-Tang, memory impairment was induced by intraventricular injection of $A{\beta}_{25-35}$ peptides on mice and Chong-Myung-Tang and Chong-Myung-Tang+chocolate were administered orally for 14 days. In water maze task, improvement of learning ability during acquisition period and significant increase of memory score during retention period resulted from the treatment of Chong-Myung-Tang and Chong-Myung-Tang+chocolate with respect to the $A{\beta}-injected$ control animals. Furthermore, the $A{\beta}_{25-35}$ toxicity on the hippocampus was assessed with immunohistochemistry (Bax, TUNEL), and differences in antioxidant activity was observed through TBARS and DPPH test. We employed sensory tests using chocolate flavor, herb flavor, and bitter taste & hardness as standards to show sensory differences with net chocolate. In this study, it is demonstrated that Chong-Myung-Tang+chocolate do not disturb the pharmacological activity of Chong-Myung-Tang, and have no sensory difference with net chocolate. Chong-Myung-Tang+chocolate can be used to enhance the compliance remarkably and thought of as an effective, functional formula to maximize expected treatment.

위암의 BAD 단백질의 발현

유남진,이종우,박원상,이정용,이석형,Yoo, Nam-Jin,Lee, Jong-Woo,Park, Won-Sang,Lee, Jung-Young,Lee, Sug-Hyung 대한위암학회 2003 대한위암학회지 Vol.3 No.2

Purpose: Evidence exists that dysregulation of apoptosis is involved in the pathogenesis of cancer development. The Bcl-$x_{L}$/Bcl-2-associated death promoter (BAD), a member of the Bcl-2 family, is a critical regulatory component of the intrinsic cell-death pathway that exerts its pro-apoptotic effect upon heterodimerization with anti-apoptotic proteins Bcl-2 and Bcl-$X_{L}$. Expression of the BAD protein has been reported in several cancer types, but not in stomach cancer. The aim of this study was to explore the expression status of the BAD protein in gastric carcinomas. Materials and Methods: In the current study, we analyzed the expression of the BAD protein in 60 advanced gastric adenocarcinomas by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the BAD protein in 57 ($95\%$) of the 60 cancers. Normal gastric mucosal cells showed weaker expressions of the BAD protein than gastric carcinomas. Conclusion: Taken together, these results suggest that stomach cancer cells in vivo may need BAD protein expression for apoptosis. Also, the higher expression of the BAD protein in stomach cancer cells than in normal gastric mucosal cells suggests that apoptosis might be easily triggered in susceptible stomach cancer cells, thereby producing selective pressure to make more apoptosis-resistant cells during tumor development.

위암의 Fas-associated Death Domain Protein 단백질의 발현

이석형,이종우,박원상,이정용,유남진,Lee, Sug-Hyung,Lee, Jong-Woo,Park, Won-Sang,Lee, Jung-Young,Yoo, Nam-Jin 대한위암학회 2003 대한위암학회지 Vol.3 No.2

Purpose: Evidence exists that dysregulation of apoptosis is involved in the pathogenesis of cancer development. Fasassociated death domain (FADD) protein, an adaptor protein of death receptors, is a critical regulatory component of the extrinsic cell- death pathway that exerts its pro-apoptotic effect upon binding with death receptors. Expression of the FADD protein has not been reported in stomach cancer. The aim of this study was to explore the expression status of the FADD protein in stomach cancers. Materials and Methods: In the current study, we analyzed the expression of the FADD protein in 60 advanced stomach cancer by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the FADD protein in 23 ($38\%$) of the 60 cancers. Normal gastric mucosal cells showed expression of the FADD protein. Conclusion: Taken together, these results indicate that decreased expression of the FADD protein is a frequent event in stomach cancers and suggest that to avoid apoptosis, stomach cancer cells in vivo may need loss of FADD expression, which might contribute to tumor development.

위암의 Phosphorylated Akt 단백질의 발현

이석형,이종우,박원상,이정용,유남진,김수영,Lee Sug Hyung,Lee Jong Woo,Park Won Sang,Lee Jung Young,Yoo Nam Jin,Kim Su Young 대한위암학회 2003 대한위암학회지 Vol.3 No.2

Purpose: Mounting evidence suggests that alterations of Akt/protein kinase B (PKB) play an important role in tumorigenesis. Phosphorylated Akt regulates many of the key effector molecules involved in apoptosis, angiogenesis, and cell-cycle progression during tumorigenesis. The expression of phosphorylated Akt has been described in some human malignancies, but not in primary human gastric cancer. The purpose of this study was to explore the expression status of phosphorylated Akt protein in gastric carcinomas. Materials and Methods: In the current study, we analyzed the expression of phosphorylated Akt protein in 60 advanced gastric adenocarcinomas by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the phosphorylated Akt in 42 ($70\%$) of the 60 cancers. Normal gastric mucosal cells showed no or weak expression of phosphorylated Akt protein. Conclusion: Taken together, these results indicate that Akt is frequently activated in gastric adenocarcinoma cells and suggest that phosphorylayed Akt may play a role in the development of human gastric adenocarcinomas.