• Journal of Gastric Cancer
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• 제5권1호
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• pp.34-39
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• 2005

목적: KLF6는 모든 조직에서 발현되고 있는 zinc finger를 가진 종양억제유전자로 인체 여러 암에서 불활성화되어 있다. 연구자들은 KLF6 단백의 발현 변화가 위암의 발생에 관여하는 지를 알아보고자 하였다. 대상 및 방법: 85예의 파라핀 포매된 위암조직에서 암세포들으 각각 3군데에서 펀치하여 새로운 파라핀 블록으로 옮겨 위암의 tissue microarray를 제작하였다. Tissue microarray 절편에서 KLF6 단백에 대한 항체로 면역화학염색을 실시한 후 발현 양상을 병리 지표들인 조직학적 소견, 침습 정도, 림프절 전이 및 복막파종 등과의 연관성을 조사하였다. 결과: KLF6 단백은 위점막의 표면과 소와 상피세포에서 주로 발현되고 있었고 85예 중 28예($28.9\%$)에서 발현 소실이 관찰되었다. 흥미롭게도 KLF6 단백의 발현 소실은 림프절 전이와 통계적으로 연관성이 있었으나 조직학적 소견, 침습 정도와 복막파종과는 연관성이 없었다. 결론: 이러한 소견들은 KLF6 단백의 발현 소실이 위장관 상피세포의 비정상적인 성장과 분화를 유도하고 위암의 발생 및 진행에 관여한다는 것을 의미한다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5875-5878
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• 2012

Background: Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) is a ligand dependent transcription factor involved in various processes, including carcinogenesis. We aimed to investigate any possible association of the $PPAR{\gamma}$ Pro12Ala (rs1801282) polymorphism with risk of developing gastric cancer (GC). Patients and Methods: A hospital based case control study was designed covering 50 patients with GC and 120 healthy controls. The frequencies of $PPAR{\gamma}$ Pro12Ala (rs1801282) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: The Ala12 allele of the $PPAR{\gamma}$ Pro12Ala G gene was associated with a 1.95 fold increased risk of GC development (p: 0.022; 95% CI: 1.58-2.40). Subgroup analyses showed that the same allele was also associated with metastasis (p: 0.000; OR:4.09; 95%CI:2.273-7.368) and differentiation (p: 0.004; OR:1.95; 95%CI:1.335-2.875) in patients with GC. Conclusion: This study suggests that the $PPAR{\gamma}$ Pro12Ala G (Ala12) allele might be associated with development, differentiation and metastatic process of GC in the Turkish population. Further studies conducted in larger study groups and in different ethnic populations will be needed to clarify the exact role of the $PPAR{\gamma}$ Pro12Ala polymorphism in GC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10231-10236
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• 2015

This study aimed to evaluate the prevalence of preoperative thrombocytosis and its prognostic significance in Thai patients with endometrial cancer. We retrospectively reviewed the medical records of 238 cases who had undergone surgical staging procedures between January 2005 and December 2008. Associations between clinicopathological variables and preoperative platelet counts were analyzed using Pearson's chi square or two-tailed Fisher's exact tests. Survival analysis was performed with Kaplan-Meier estimates. Univariate and Cox-regression models were used to evaluate the prognostic impact of various factors including platelet count in terms of disease-free survival and overall survival. The mean preoperative platelet count was $315,437/{\mu}L$ (SD $100,167/{\mu}L$). Patients who had advanced stage, adnexal involvement, lymph node metastasis, and positive peritoneal cytology had significantly higher mean preoperative platelet counts when compared with those who had not. We found thrombocytosis (platelet count greater than $400,000/{\mu}L$) in 18.1% of our patients with endometrial cancer. These had significant higher rates of advanced stage, cervical involvement, adnexal involvement, positive peritoneal cytology, and lymph node involvement than patients with a normal pretreatment platelet count. The 5-year disease-free survival and overall survival were significantly lower in patients who had thrombocytosis compared with those who had not (67.4% vs. 85.1%, p=0.001 and 86.0% vs. 94.9%, p=0.034, respectively). Thrombocytosis was shown to be a prognostic factor in the univariate but not the multivariate analysis. In conclusion, presence of thrombocytosis is not uncommon in endometrial cancer and may reflect unfavorable prognostic factors but its prognostic impact on survival needs to be clarified in further studies.

• Journal of Gastric Cancer
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• 제20권4호
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• pp.408-420
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• 2020

Purpose: Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). Materials and Methods: We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. Results: CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively). Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. Conclusions: CLDN18.2 expression was reduced in patients with PM but significantly intact in those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.

• Journal of Gastric Cancer
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• 제13권4호
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• pp.226-231
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• 2013

Purpose: The role of metastasectomy has been debatable and unclear in the treatment for patients with metastatic gastric cancer. Therefore, this study was designed to evaluate the role of metastasectomy on the overall survival of these patients. Materials and Methods: In 2,406 patients who underwent gastrectomy for gastric cancer between 1998 and 2010, 188 (7.8%) patients had their first surgery for metastatic gastric cancer. To minimize the bias of systemic chemotherapy, 99 patients who received postoperative chemotherapy (fewer than 2 cycles) were excluded. The primary gastrectomy or metastasectomy had not been enforced in the following cases. Patients with far advanced peritoneal dissemination, multiple liver and lung metastasis (more than 2), and a poor general condition (Eastern Cooperative Oncology Group>2) were excluded. Based on the metastasectomy, the patients were classified into two groups, gastrectomy with metastasectomy and gastrectomy only group. Results: There was no significant difference between both groups in clinicopathological characteristics except for the mean age (P=0.047). The univariate analysis for overall survival show statistical significances in metastasectomy (P=0.026), distal gastrectomy (P=0.047), and combined resection of another organ (P=0.047) group. With a multivariate analysis, metastasectomy was a significant factor in patient survival after surgery (odds ratio 1.679; P=0.034). Conclusions: Based on our results, we assume that a detailed strategy for surgery is needed to improve the overall survival of patients with metastatic gastric cancer. Therefore, we suggest that a metastasectomy can help prolong overall survival in some patients with metastatic gastric cancer.

• Journal of Gastric Cancer
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• 제2권4호
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• pp.195-199
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• 2002

Purpose: Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors that are secreted by tumor cells. Vascular endothelial growth factor (VEGF) is the most significant angiogenic factor and a selective mitogen for endothelial cells. VEGF, also known as the vascular permeability factor, acts on endothelial cells to increase microvascular permeability and directly stimulate the growth of new blood vessels. Several studies have reported that the expression of VEGF is correlated with hematogenous recurrence via angiogenesis in gastric carcinomas. This research evaluated the relationship between the expression of VEGF and hepatic and peritoneal recurrence in gastric carcinomas. Materials and Methods: Thirty specimens resected from patients with primary gastric carcinomas who had undergone curative resections were divided into three group: Group I, early gastric carcinomas without recurrence; Group II, advanced gastric carcinomas with hepatic recurrence; and Group III, advanced gastric carcinomas with peritoneal recurrence. The expression of VEGF and the density of the microvessel count were examined using immunohistochemistry. Results: 1) The expression of VEGF in Group II and Group III ($63.2\pm\24.3\%$) was stronger than that in Group I ($7\pm\4.2\%$). The expression of VEGF in Group II ($76.5\pm\13.2\%$) was stronger than that of the Group III ($50\pm\14.2\%$) (P<0.05). 2) The microvessel count in Group II ($49.9\pm14.5$) was more than that in Group I ($8.6\pm2.6$) and Group III ($29.1\pm18.1$) (P<0.05). 3) The microvessel count was increased significantly with increasing the expression of VEGF. Conclusions: The expression of VEGF is associated with advanced stomach cancer and hepatic recurrence has a higher expression of VEGF than peritoneal recurrence with neovascularization. Thus the expression of VEGF can be considered to be a useful indicator of recurrence in gastric carcinoma and especially in hepatic recurrence.

• 한국임상수의학회지
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• 제38권2호
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• pp.85-88
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• 2021

A 9-year-old, intact female Shih-tzu dog presented with a three-week history of anorexia, lethargy, and weight loss. Abdominal radiography revealed a mass in the right cranial quadrant of the abdomen that was displacing the right kidney caudally. Ultrasonography showed a large, irregular, heterogeneous hepatic mass and a small amount of peritoneal fluid. On computed tomography (CT), a large hypoattenuating mass with heterogeneous contrast enhancement occupied the right lateral lobe, and parts of the right medial and caudate lobes of the liver. There was no evidence of regional lymph node or pulmonary metastasis. Lobectomy of the right medial, right lateral and caudate liver lobes was performed, however, the patient did not recover from surgery. Hepatoblastoma was confirmed by histological examination. Hepatoblastoma is rare in dogs, and this is the first report describing CT imaging of hepatoblastoma in a dog.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.519-522
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• 2015

Background: We aimed to investigate whether the tumor free distance (the distance between the uterine serosa and the tumor at its deepest point) is useful in surgical staging and in predicting prognosis. Materials and Methods: Data from patients who underwent complete surgical staging for endometrial cancer between January 2006 and June 2011 were reviewed retrospectively. All demographic findings, surgical stages, histological type and grade, myometrial invasion, lymphovascular space invasion as well as abdominal cytology, cervical, adnexal, and omental involvement, and lymph node metastasis were recorded. The relations between myometrial invasion and tumor free distance from uterine serosa with prognostic factors were investigated. Results: Seventy patients were included in the study. Sixty-four (91.5%) had endometrioid type cancers and forty-four (62.9%) were grade 1. The deepest myometrial invasion was less than 1/2 in 42 patients (60%). In 18 patients (25.8%) lymphovascular invasion was noted. Eight (11.4%) were found to have cervical involvement, five (7.1%) had adnexal involvement and in 4 cases (5.7%) the peritoneal washings included malignant cells. Four patients had pelvic and one para-aortic node metastasis. We recognized that an invasion of more than 1/2 was correlated significantly with lymphovascular space involvement, histological grade, positive abdominal washing cytology, nodal and cervical involvement, but not with adnexal involvement. Tumor-free myometrial thickness was negative and statistically significant correlated with surgical stage, histological grade, lymphovascular space involvement, positive abdominal washing cytology, cervical and adnexal involvement. The importance of tumor-free myometrial thickness in determinating the lymphovascular space invasion was found to be highest in terms of sensitivity and specificity when crossing the ROC curve at 11 millimeters. Conclusions: Depth of myometrial invasion is more valuable for predicting lymph node metastasis than tumor-free myometrial thickness. The tumor-free myometrial thickness provides a better prediction for adnexal involvement.

• 한국식품과학회지
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• 제53권3호
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• pp.304-312
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• 2021

참당귀로부터 열수추출 및 에탄올 침전법을 이용해 조다당을 분리하고 DEAE-Sepharose FF와 Sephadex G-100을 이용하여 얻은 정제 다당 AGE-2c-I을 대상으로 선천 면역 활성 및 항종양 전이 효과를 확인하고자 하였다. 인체의 초기 면역 반응에 있어 중추적인 역할을 수행하는 보체계 활성화 및 활성화 경로를 확인한 결과, AGE-2c-I은 운지버섯 유래 시판 면역증강제인 PSK에 준하는 우수한 활성을 나타내는 것으로 확인되었으며. 본 활성은 주로 고전경로를 통하여 활성화되며 일부 부경로를 경유하는 것으로 최종 확인되었다. 또한 AGE-2c-I은 mouse 복강 유래 대식세포에 대해 직접적인 독성을 나타내지 않으며 종양세포주 YAC-1 및 B16BL6에 대한 직접적인 독성 또한 나타나지 않음을 확인함으로써 시료의 직접적인 독성에 근거한 항암 효과는 없는 것으로 확인되었다. 반면에 비장으로부터 분리한 림프구는 8 ㎍/mL의 AGE-2c-I 처리에 의해 증식능이 관찰되었다. AGE-2c-I이 대식세포의 cytokine 분비능에 미치는 효과를 확인한 결과, 우수한 IL-6, IL-12 및 TNF-α 분비능을 보였으며 시료를 200 ㎍ 및 1,000 ㎍의 고농도로 처리한 실험군에서 IL-10이 분비된 것으로 보아 AGE-2c-I은 immune-stimulator의 역할뿐만 아니라 immune-suppressor로서의 작용 또한 가능한 것으로 확인되었다. 한편 종양 및 암세포에 대하여 직접적인 살해 활성을 나타내는 NK cell 활성을 확인한 실험에서는 농도 의존적인 종양 세포 살해능을 확인할 수 있었으며 100 ㎍/mouse 농도에서 NC 대비 약 1.5배 높은 NK cell 활성을 나타냈을 뿐만 아니라, 폐에 대한 고전이성 종양세포주인 B16BL6 melanoma 세포를 이용한 실험동물 종양 전이 모델에선 100 ㎍/mouse 농도로 처리한 실험군이 NC 대비 58%의 colony가 감소한 것을 확인할 수 있었다. 이상의 결과로 부터 참당귀 유래 RG-I 구조의 다당은 높은 선천면역계 자극 활성, 특히 보체계, 대식세포, 림프구 증식, NK cell의 활성화를 통해 우수한 항종양 전이 효과를 갖는 것으로 최종 확인되었으며 건강기능성식품 소재로의 개발가치가 우수한 것으로 판단되었다.

• Journal of Gastric Cancer
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• 제9권4호
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• pp.231-237
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• 2009

목적: 진행성 위암 중 수술 소견에서 복강 내 원격전이가 존재하거나 주위 장기에 침윤이 심하여 절제가 불가능한 경우에 위 배출구 폐색을 동반하지 않더라도 예방적 위공장 우회술을 시행하는 경우가 있어, 단순 개복술 시행과 비교하여 그 의의를 알고자 하였다. 대상 및 방법: 1984년부터 2007년까지 고려대학교 의료원에서 수술을 시행 받은 진행성 위암 환자 중 위 배출구 폐색이 없고 절제 불가능한 4기 위암 환자 167예를 대상으로, 후향적 방법을 이용하여 임상병리학적 특성 및 치료성적, 그리고 예후 인자 분석을 시행하였다. 결과: 위 공장 우회술을 시행과 단순 개복술 시행을 비교한 결과, 나이, 성별, 간 전이 여부, 술 후 재원일, 재입원 횟수에서는 유의한 차이를 없었지만, 병소의 위치(P$\leq$0.014), 복막 파종(P=0.001)에서는 유의한 차이를 보였다. 예후 인자 분석에서는 위 공장 우회술을 시행한 군의 생존기간이 1~35.7개월(6.3개월), 시행하지 않은 군이 1~33.4개월(median 4.3개월)로 유의한 차이가 있었으며(P=0.031), 복막전이가 있는 경우 1~31.0개월(median 3.4개월), 없는 경우 1~33.3개월(median 5.8개월)로 유의한 차이를 보였다(P<0.001). 다변량 분석을 통한 독립적 예후 인자로는 복막 전이 여부만이 의미가 있었다(P=0.002). 결론: 절제 불가능한 4기 위암 환자에서 폐색 증상이 없는 경우, 예방적 위 공장 우회술은 생존기간의 연장에서 큰 의의를 가지지 못하는 것으로 생각한다.