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Molecular Pathogenesis of Gastric Cancer
박원상 대한의사협회 2010 대한의사협회지 Vol.53 No.4
In this article, I will survey the major genetic susceptibility and somatic genetic alterations involved in gastric cancer and adenoma. These include germline and somatic genetic alterations in oncogenes, tumor suppressor genes, and apoptosis-related genes. A small proportion of gastric cancers arise as a consequence of hereditary predisposition caused by specific germline mutations in E-cadherin, mismatch repair genes, adenomatous polyposis coli,and STK11. Aberrant expression of activation induced cytidine deaminase, triggered by Helicobacter pylori infection, accumulates with genetic mutations of oncogenes and tumor suppressor genes, including p53 and CTNNB1. Inactivation of trefoil factor family 1, which is a gastric specific tumor suppressor, occurs in gastric adenomas and cancers. Ectopic expression of CDX2 leads to intestinal metaplasia and defective Cdx2 expression accelerates the transformation of metaplastic cells to gastric cancer. Genetic alterations of p53 and genes related to Wnt signaling pathway and microsatellite instability occur early in the development of gastric carcinoma, indicating that detection of certain genetic alterations in adenomas may be indicative of malignant transformation. In addition, inactivation of apoptosis-inducing gene caused by mutations may be an escaping mechanism against apoptotic cell death and contribute to the progression of gastric cancer. Although the results of many studies are contradictory with one another, genetic alterations in oncogenes and tumor suppressor genes are present even in gastric adenoma and increase in frequency during multistep gastric carcinogenesis. Genetic alterations described herein, and from as yet unidentified target genes in gastric cancer cells, will guide us towards more effective risk assessment, diagnosis, and treatment.
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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.
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경운방법 및 파종시기가 남부지역 논 재배 옥수수와 후작 양파의 생육과 수량에 미치는 영향
박원상,김감곤,정용현,최나영,나채인 한국작물학회 2021 한국작물학회지 Vol.66 No.4
The present study investigated the effects of tillage practices (deep cultivation [DC] and conventional tillage [CT]) and extended planting dates (mid-June to July) for maize-onion rotation in paddy fields. The silage corn (Zea mays L.) cultivar ‘Kwangpyeongok’ and the waxy corn cultivar ‘Ilmichal’ were planted on June 14, July 3, and July 15 in 2019. In both maize, the plant height of June 14 planted was up to 100 cm greater than that of July 15 planted on August 16 and up to 40 cm on August 30. At 30 Days after planting, the leaf area index (LAI) of silage corn planted on July 3 and 15 greater than that of corn planted on June 14 due to high temperature in the early season; however, there were no differences in the LAI of waxy corn according to the planting date. Despite favorable temperature, plants sown on July 3 and 15 experienced high moisture stress during the seedling stage due to consistent rainfall, and waxy corn was highly sensitive to high moisture stress. The total yield of silage corn was 1,232 (845 in TDN), 860 (598 in TDN), and 765 (508 in TDN) DW kg・10a-1 for plants sown on June 14, July 3, and July 15, respectively. The fresh marketable ear yield of waxy corn was 872, 814, and 525 FW kg・10a-1 for plants sown on June 14, July 3, and July 15, respectively. After the completion of maize cultivation, onion seedlings (Allium cepa L.) were transplanted on November 12, 2019, and harvested on May 27, 2020. Neither summer tillage nor maize planting date affected onion growth or yield. The marketable onion yield was 8,305 and 7,848 kg・10a-1 with DC and CT, respectively. In conclusion, DC did not improve maize growth or yield under paddy conditions. Mid-June to early July is a practical window for maize planting for growers in this region. 본 연구는 남부지역 논 토양에서 옥수수(사료용 및 간식용) 재배 시 경운방법과 파종시기의 차이가 작물의 생육 및수량에 미치는 영향을 구명하고, 여름 재배기간을 거친 후겨울 소득작물인 양파에 미치는 영향을 구명하여 전・후작물 모두 적절한 수량을 얻을 수 있는 경운방법과 파종시기및 파종한계기를 구명하고자 실시하였다. 1. 옥수수의 경우 경운처리에 따라서는 생육 및 수량에 유의한 차이가 없었다. 파종시기에 따라서는 광평옥, 일미찰 모두 파종시기가 늦을수록 생육이 저조하였고 착수고의 경우 생육의 차이에 의해 7월 15일 파종 처리구가비교적 낮았다. LAI의 경우 광평옥은 7월 3일, 7월 15일파종 처리구에서 초기 생육기 온도가 높음에 따라 엽의발달이 빨랐고 시간이 경과됨에 따라서 유의한 차이는없어졌다. 일미찰의 경우는 파종시기에 따라 LAI에 유의한 차이가 없었다. 일미찰은 습해에 약한 품종으로 7 월 3일, 7월 15일 파종 처리구는 생육 초기 고온임에도불구하고 장마에 의한 과습의 피해로 엽의 발달에 차이가 없었다. 2. 광평옥 수량구성요소의 경우 파종시기가 늦을수록 이삭장 및 단위면적당 이삭수가 적었고, 이삭 및 간엽의 건물수량과 TDN도 낮았다. 일미찰 또한 수량구성요소 및수량이 파종시기가 늦을수록 낮게 나타났다. 3. 본 실험에서 실시된 심경처리의 경우 옥수수의 생육에는크게 영향이 없는 것으로 나타났다. 파종시기에 따라서는 파종이 지연됨에 따라 특히 7월 15일 파종 처리구에서 옥수수의 생육 및 수량이 부진하였으므로 파종시기는7월 3일 파종 처리구와 시기가 비슷한 7월 초까지가 적절할 것으로 판단된다. 4. 양파의 경우 여름작물인 옥수수에 실시된 경운방법 및파종시기 처리에 따라 생육 및 수량에 유의한 차이가 없었으며 양호한 생육과 수량을 보였다. 이는 2019년도 여름 재배기간을 거치고 겨울작물 재배 준비를 위한 포장정지작업이 이루어짐에 따라 양파 파종까지 4개월 이상이 경과되어 경운 및 파종시기 처리의 효과가 상쇄되어양파의 생육에 영향이 없었던 것으로 판단된다.
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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.
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박원상,조장,이화성,송재휘,윤정환,박용규,남석우,이정용 대한병리학회 2010 Journal of Pathology and Translational Medicine Vol.44 No.4
Background : Osteoarthritis (OA) is a common disease characterized by degenerating joint cartilage in the knee, hip, and hand. A functional single nucleotide polymorphism (SNP) +104-T/C; rs143383 in the 5′untranslated region of the growth differentiation factor 5 (GDF5) gene was recently associated with susceptibility to OA in the Japanese and Chinese populations. Methods : To investigate whether this association is present in the Korean population, the frequency of the polymorphism was investigated in 276 patients with knee OA and 298 healthy subjects as controls. Polymorphism analysis was performed by amplifying the core promoter region of the GDF5 gene and digesting it with the BsiEI restriction enzyme. Results : The frequency of the TT, CT, and CC genotypes was 54.3% (150/276), 41.7% (115/276), and 4.0% (11/276), respectively, in patients with OA, and 53.4% (159/298), 37.9% (113/298), and 8.7% (26/298), respectively, in healthy controls. No significant differences in genotypic or allelic frequencies of the +104T/C SNP of the GDF5 gene were observed between patients with OA and controls. Also, no significant differences in allelic and genotypic frequencies were found when the individuals were stratified by age and gender. Conclusions : The results suggest that the +104T/C; rs143383 GDF5 core promoter polymorphism is not a risk factor for OA in the Korean population.
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