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타목시펜 내성 유방암세포(T47D:A18/4-OHT)에서 EGFR 및 HER2 억제 효과
원용성(Yong Sung Won),주종호(Jong Ho Joo),김정수(Jeong Soo Kim),오세정(Se Jung Oh),송병주(Byung Joo Song),전해명(Hae Myung Jeon),정상설(Sang Seol Jung),박우찬(Woo Chan Park) 대한외과학회 2008 Annals of Surgical Treatment and Research(ASRT) Vol.74 No.4
Purpose: Tamoxifen has been prescribed as a very effective hormonal agent not only for the treatment of breast cancer, but also for the prevention of the disease. The development of resistance to tamoxifen is one of the most important obstacles to hormonal therapy of breast cancer. HER2 or EGFR expression has been reported to be associated with the development of tamoxifen resistance. This study was performed to evaluate the effect of HER2 and EGFR inhibition on tamoxifen resistance using tamoxifen-resistant breast cancer cells (T47D:A18/4-OHT cells). Methods: Tamoxifen-resistant T47D:A18/4-OHT cells were established by long-term treatment of 1μM 4-hydroxytamoxifen on T47D:A18 human breast cancer cells. The effect of HER2 and EGFR inhibition was investigated by the use of a cell proliferation assay with treatment of trastuzumab, a monoclonal antibody to the extracellular domain of the human HER2 receptor, and ZD1839, an ERFR tyrosine kinase inhibitor. Results: In contrast to T47D:A18 cells, T47D:A18/4-OHT cells showed estrogen-independent proliferation and partial regulation by treatment with tamoxifen. With a single treatment of trastuzumab or ZD1839, T47D:A18/4-OHT cell growth was reduced to 77.8% (P=0.15) or 74.4% (P=0.034) respectively, as compared to untreated cells. Combinational treatment with 1 nM estradiol resulted in a further reduction of T47D:A17 cell proliferation by 83.6% (P=0.002) for trastuzumab and 77.7% (P=0.047) for ZD1839, as compared to the single treatments. Conclusion: Tamoxifen resistance could be partially regulated by inhibition of HER2 or EGFR in T47D:A18/4-OHT cells, especially in combination with a low dose of estradiol. This effect may provide an important clue to overcome tamoxifen resistance in the treatment of breast cancer.
전경화,원용성,신은영,조현민,임명구,진형민,박우배,Jun, Kyong-Hwa,Won, Yong-Sung,Shin, Eun-Young,Cho, Hyun-Min,Im, Myoung-Goo,Chin, Hyung-Min,Park, Woo-Bae The Korean Gastric Cancer Association 2006 대한위암학회지 Vol.6 No.4
목적: 유전자 메틸화는 유전자의 서열에 영향을 주지 않으면서 유전자의 발현을 억제하고 세포분열 후 그대로 보존되는 후성적 변화이다. 위암조직과 정상위조직에서 hMLH1, p16, p14, COX-2, MGMT, E-cadherin 유전자와 MINT (MINT1, 2, 12, 25, 31)의 메틸화 상태를 검사하여 위암의 발생 과정에서의 작용과 CIMP 및 Helicobacter pylori균 감염을 포함한 임상병리학적인자와의 연관성을 알아보고자 하였다. 대상 및 방법: 위암과 정상위 신선 동결 조직 각각 36예를 대상으로 MSP (methylation-specific PCR)방법을 이용하여 메틸화 상태를 분석하였고 CIMP의 분석은 MINT1, MINT2, MINT12, MINT25, MINT31의 5개 marker를 대상으로 시행하였다. Helicobacter pylori균 감염여부는 Warthin-Starry silver 염색을 통하여 분류하였다. 결과: 위암 관련 유전자인 p14, p16, MGMT, COX-2, E-cadherin, hMLH1의 메틸화는 각각 14예(38.9%), 13예(36.1%), 8예(22.2%), 10예(27.8%), 21예(58.3%), 6예(16.7%)였다. MINT1과 MINT25의 메틸화는 위암조직에서 정상위조직에서보다 통계학적으로 유의하게 높게 관찰되었다. CIMP 양성률은 위암조직에서 44.4%로 높게 나타났으며 CIMP-H 위암은 환자의 연령과 종양크기와 연관이 있었다. CIMP 양성 위암은 p16 유전자의 메틸화와 연관이 있었고 p16 유전자의 메틸화는 조직학적으로 저분화, 미만형, 궤양형성하는 위암에서 낮게 나타났다. MINT1의 메틸화는 Helicobacter pylori균과 연관성이 있었다. 결론: 위암에서 hMLH1, p16, p14, COX-2, MGMT, E-cadherin, MINT (MINT1, 2, 12, 25, 31)의 불활성화에 DNA 메틸화가 작용함을 알 수 있었고, Helicobacter pylori균에 의한 위암발생에 MINT1의 메틸화가 연관이 있음을 알 수 있었다. Purpose: Methylation of gene regulatory elements plays an important role in gene inactivation without genetic alteration. Gastric cancer is one of the tumors that exhibit a high frequency of CpG island hypermethylation. The purpose of this study was to investigate the occurrence of CpG island hypermethylation in gastric carcinoma in relation to H. pylori infection, CIMP and clincopathologic variables. Materials and Methods: We investigated the promoter methylation Status of six genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin) and CIMP in 36 gastric carcinoma tissues as well as in nontumor tissues. CIMP status was investigated by examining the methylation status of MINT 1, 2, 12, 25 and 31. The methylation status of the promoter was examined by methylation-specific PCR (MSP) and H. pylori infection was examined by histological diagnosis after staining with Warthin-Starry silver. Results: Among the 36 gastric carcinoma tissues, DNA hypermethylation was detected in the following frequencies: 14 (38.9%) for p14, 13 (36.1%) for p16, 8 (22.2%) for MGMT, 10 (27.8%) for COX-2, 21 (58.3%) for E-cadherin, and 6 (16.7%) for hMLH1. The frequencies for MINT1 and MINT25 hypermethylation were significantly higher in tumor tissues than in nontumor tissues. 16 (44.4%) of the 36 gastric carcinoma tissues were positive for the CIMP CIMP-H tumors were associated with older patients and larger tumor size than CIMP-L tumors. We found a significant association between the presence of the CIMP and hypermethylation of p16. Hypermethylation of p16 and MINT2 were significantly different when compared by age. MINT1 gene methylation was significantly associated with H. pylori infection (P=0.004). Conclusion: Our results suggest that aberrant hypermethylation of multiple tumor related genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin, MINT1, 2, 12, 25, 31) occurs frequently in gastric carcinoma tissues. The hypermethylation of MINT1 was significantly higher in the tumor tissues and was associated with H. pylori infection.
von Recklinghausen ` s Disease 환자의 위에서 동시 발생한 신경 섬유종 및 평활근종
한석원(Suk Won Han),지영희(Young Hee Jee),김욱(Wook Kim),박태훈(Tae Hoon Park),원종만(Jong Man Won),원용성(Yong Sung Won),한남익(Nam Ick Han),장은덕(Eun Duk Jang) 대한소화기학회 1991 대한소화기학회지 Vol.23 No.2
Neurofibromatosis, first described by von Recklinghausen in 1882, is a dominantly inherited mesodermal and ectodermal dysplasia with a broad spectrum of clinical findings. Most clinicians know that von Recklinghausens neurofibromatosis denotes more than the dermatologic curiosity of cafe-au-lait spots. In this disease, neurofibroma can be found everywhere in the body, but gastrointestinal neurofibroma associated with von Recklinghausens disease is infrequently reported. Patients with this disease may experienee gastrointestinal hemorrhage, small bowel obstruction, malignant degeneration of neurofibromas. Recently, the authors experienced a case of simultaneously developed gastric neurofibroma and leiomyoma in a patient with von Recklinghausens disease and associated literatures were reviewed.
임명구,전경화,원용성,정지한,진형민,박우배,전정수,Im, Myoung-Goo,Jun, Kyong-Hwa,Won, Yong-Sung,Jung, Ji-Han,Chin, Hyung-Min,Park, Woo-Bae,Chun, Chung-Soo 대한위암학회 2007 대한위암학회지 Vol.7 No.2
횡문근양 종양은 윌름씨 종양의 횡문근육종 형태의 드문 변종 아형으로 여겨져 왔으나, 1989년에 신장에서 발생한 황문근양 종양이 처음으로 기술된 이후 위장관에서도 드물게 보고되고 있다. 적절한 치료는 근치적 절제술이여 술후 보조 항암요법의 효과는 보고되지 않았다. 신장외 횡문근양 종양은 신장에서 발생한 횡문근양 종양과는 경과가 다르며 불량한 예후를 보인다. 신장외 횡문근양 종양 중에서도 횡문근양 형태의 미분화 위 선암은 매우 드물며 예후가 불량하다. 63세 남자 환자가 위 체부의 대만부에 발생한 종괴로 위전절제술을 시행받았으며, 병리조직 결과에서 횡문근양 형태의 미분화 위 선암이 진단되었다. 이에 본 저자들은 면역조직화학적으로 진단된 횡문근양 형태를 보이는 미분화 위 선암을 경험하여 증례를 보고하는 바이다. Rhabdoid tumor has been considered to be a rare subtype of Wilm's tumor with Rhabdomyoma features. Since rhabdoid tumor that developed in the kidney was described for the first time in 1989, it has been reported in the gastrointestinal tract, although this is rare. The appropriate treatment is radical resection, and the effect of adjuvant chemotherapy has not yet been reported on. The outcome of extra-renal rhabdoid tumor is different from renal rhabdoid tumor and the former shows a poor prognosis. Among extra-renal rhabdoid tumors, undifferentiated gastric adenocarcinoma with rhabdoid features is very rare and its prognosis is poor. A 63 years old male patient underwent total gastrectomy for a tumor that developed in the greater curvature of the gastric body and this was diagnosed as undifferentiated gastric adenocarcinoma with rhabdoid features, according to the histopathology. We experienced an undifferentiated gastric adenocarcinoma with rhabdoid features that was diagnosed by immunohistochemical staining and we report here on this case.
이희재,서영진,원용성,이윤복,김준기,전정수,Hui-Jae Lee,Young-Jin Suh,Yong-Sung Won,Yun-Bok Lee,M.D. and Jun-Gi Kim,Chung- Soo Chun,M.D. 대한갑상선-내분비외과학회 2003 The Koreran journal of Endocrine Surgery Vol.3 No.2
Purpose: The advent of laparoscopic abdominal surgery made it possible to perform a laparoscopic adrenalectomy (LA). We have successfully performed 10 such operations since November 21, 1995. We retrospectively compared the effectiveness and the safety of a laparoscopic adrenalectomy with the effectiveness and the safety of an open adrenalectomy (OA). Methods: The 45 patients with adrenal diseases who underwent an adrenalectomy from March 1990 to January 1998 were included in this study. Ten (10) laparoscopic cases comprised the study group, and 17 of the 32 open adrenalectomy cases, performed by anterior approach, comprised the control group. Results: No one died from an adrenalectomy. Nine cases (45%) from the OA group needed transfusions (average: 661 ml), but one patient from the LA group, who had required a conversion to a celiotomy, required a transfusion (400 ml). The operating times were, on average, 191 minutes in the OA group and 230 minutes in the LA group (p=0.0384). The average size of the masses was 6.5 cm. The first days of walking after the operation was 3.4 days for the OA group and 1.3 days for the LA group (p=0.0002). The patients' former regular diets were started on days 6.9 and 3.2 for the OA and LA groups, respectively (p=0.0001). Postoperative in-hospital days were 17.5 for the OA group and 7.9 for the LA group (p=0.0001). Conclusion: In comparison with an open adrenalectomy, a laparoscopic adrenalectomy showed better convalescent features: that is, less chance of transfusion, earlier recovery, faster resumption of the former diet, shorter postoperative hospital stays, and cosmesis. We think and suggest that a laparoscopic adrenalectomy is a safe and effective procedure, and hopefully it will become the standard choice of operation for various adrenal diseases. (Korean J Endocrine Surg 2003;3:172-177)