• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2002.11a
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• pp.38-50
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• 2002

질병의 정확한 진단과 적절한 치료 그리고 이에 대한 연구를 위해서는 병소에서 채취한 검체의 형태학적 소견을 관찰하는 것이 중요하다. 이러한 형태학적 변화를 관찰하기 위해서, 연구자들은 생검 조직으로 제작한 헤마톡실린-에오신 염색표본을 이용하고 있으며, 필요한 경우에는 세포의 미세구조를 관찰하기 위하여 전자현미경 검색을 시행하고 있다. 그러나, 각종질환은 점차 세분화되고, 새로운 진단기준이 소개되고 있으며, 종양의 진단에 도움을 주는 종양표지자, 그리고, 예후를 판정할 수 있는 예후인자들이 알려지고 있어서, 통상적인 헤마톡실린-에오신 염색표본이나 전자현미경 검색만으로는 이러한 종합적인 정보를 얻기가 어렵다. (중략)

• Journal of Gastric Cancer
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• v.8 no.3
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• pp.129-135
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• 2008

Purpose: The usefulness of serum tumor markers for assessing gastric carcinoma is very limited compared to that for neoplasms in other digestive organs. Many reports have shown that serum tumor markers are closely associated with the prognosis and tumor recurrence in gastric cancer patients. However, little is known about the usefulness of serum tumor markers as a predictor of distant metastasis for gastric carcinoma. Materials and Methods: With excluding the non-specific causes of elevated tumor markers, a total of 788 patients with gastric carcinoma and who were seen at our hospitals between 2004 and 2006 were included in this study. The correlation between the preoperative level of tumor makers and the clinicopathological features was analyzed. Results: CEA was significantly correlated with age, gender and nodal metastasis, but not with the depth of tumor. The CEA level was not correlated with distant metastasis, such as peritoneal or hematogenous metastasis. In contrast, the CA 19-9 level was significantly correlated not only with the depth of tumor and nodal metastasis, but also with peritoneal metastasis. Especially, the patients with over 500% elevation of the CA 19-9 level had a significant risk of peritoneal metastasis. Conclusion: CA 19-9 is useful for predicting peritoneal metastasis in gastric cancer patients. It can be used efficiently in making the diagnostic and the treatment plan, in combination with other diagnostic tools, for gastric cancer patients.

• Radiation Oncology Journal
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• v.24 no.2
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• pp.128-137
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• 2006

Purpose: We investigated whether a relationship exists between tumor control dose 50 ($TCD_{50}$) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between $TCD_{50}$, TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Materials and Methods: Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used In this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were $8{\sim}12$ weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for $TCD_{50}$, TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of $p53,\;p21^{WAF1/CIP1},\;BAX,\;Bcl-2,\;Bcl-X_L,\;Bcl-X_S$, and p34. Correlation analysis was peformed whether the level of RIA were correlated with $TCD_{50}$ or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with $TCD_{50}$, TGD, RIA. Results: The level of RIA showed a significant positive correlation (R=0.922, p=0.026) with TGD, and showed a trend to correlation (R=-0.848), marginally significant correlation with $TCD_{50}$ (p=0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of $p21^{WAF1/CIP1}$ and 34 showed a significant correlation either with $TCD_{50}$ (R=0.893, p=0.041 and R=0.904, p=0.035) or with TGD (R=-0.922, p=0.026 and R=-0.890 p=0.043). The tumors with high constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 were less radiosensitive than those with low expression. Conclusion: Radiosensitivity may be predicted with the level of RIA in murine tumors. The constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 can be used as biological markers which predict the radiosensitivity.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.45-55
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• 2008

Purpose: This study evaluates the association of estrogen receptor(ER), progesterone receptor(PR), Her-2, COX-2, and survivin with the clinicopathological features and outcomes in young Korean women with breast cancer using recently developed tissue microarray(TMA) technology. Materials and Methods: A cohort of 212 young patients with breast cancer diagnosed at the age of 45 years or younger from March 1994 to August 2005, were enrolled in this study. The age range of patients was $23{\sim}45$ years(median age, 39 years). The minimum and median follow-up periods were 24 months and 60 months, respectively. Serial sections of primary tumors were processed by the use of a TMA for immunohistochemical staining for five biomarkers. The correlation of these five biomarkers and the clinicopathological features and outcomes were analyzed by statistical methods. Results: The majority of the patients were stage T1(90 patients) or T2(101 patients), and 105 patients(49.5%) had an axillary node metastasis. The 5-year overall and relapse free survival rates for all of the patients were 90.4% and 82.3%, respectively, and 36 patients had a locoregional or distant metastasis as a first event. Positive expression of ER, PR, Her-2, COX-2, and survivin was determined in 38.2%, 45.3%, 25.9%, 41.5%, and 43.4%, of the tumor samples, respectively. Tumor stage, nodal status, age, as well as expression of ER, PR, and HER-2 status were significantly associated with the disease free survival rate. Tumor stage, nodal status, as well as expression of ER, PR, and HER-2 were significantly related with the overall survival rate. Expression of COX-2 and survivin were not single independent prognostic factors for the disease free and overall survival rate although co-expression of HER-2 and COX-2 had a tendency as a poor prognostic factor. By multivariate analysis, only T stage and lymph node status were significant prognostic factors, and ER status was a marginally significant prognostic factor(p=0.075). Conclusion: Expression of ER, PR and HER-2 were significant prognostic factors for the relapse free and overall survival rate. Expression of COX-2 and survivin were not prognostic factors for young women with breast cancer.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.4
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• pp.460-469
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• 2017

Heat shock proteins (HSPs) are induced as a self-defense mechanism of cells when exposed to various external stresses, such as high fever, infection, free radicals, and heavy metals. They affect the prognosis in the process of tumor formation. HSP is classified into four families: HSP27, HSP60, HSP90, and HSP100, depending on molecular weight. Heat shock protein 90 (HSP90), a molecular chaperone, plays an important role in the cellular protection against various stressful stimuli and in the regulation of cell cycle progression and apoptosis. In the present study, we assessed the differential expression of HSP90 family proteins in non-small cell lung cancer (NSCLC), and the correlation of their expression levels with clinicopathologic factors and patient survival rates. The result of this study can be summarized as follows; $HSP90{\alpha}$ showed higher expression in patients with no lymphovascular invasion (p=0.014). $HSP90{\beta}$ showed a higher expression of squamous cell carcinoma (p=0.003), and an over expression of glucose-related protein (GRP94) was significantly associated with poor differentiation (p=0.048). However, none of the HSP90 proteins showed a significant association with the survival status in patients with NSCLC. This study also indicates that $HSP90{\alpha}$ might contribute more to the carcinogenesis of NSCLC than $HSP90{\beta}$, and GRP94 and isoform selectivity should be considered when HSP90 inhibitors are studied or utilized in the treatment of NSCLC.

• Journal of Life Science
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• v.17 no.8 s.88
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• pp.1039-1045
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• 2007

Glioblastoma multiforme (GBM) is the most frequently occurring brain cancer. Although the existence of cancer stem cells (CSCs) in GBM has been established, there is little evidence to explain the link between CSCs and chemoresistance. In this study, we investigated that only a few cells of A172 and established GBM2 survived after 1,3-bis(2chloroethyl)-1-nitrosourea (BiCNU) exposures and these sur-vived cells resist the subsequent BiCNU treatment. In addition, these BiCNU-resistant small pop-ulations derived from GBM cells increased the phosphorylations of Erk and Akt and highly expressed CD133 stem cell surface marker. Furthermore, we observed that the BiCNU-resistant cancer cells de-rived from GBM have grown tumors when transplanted into severe combined immuno-deficient (SCID) mouse brain. These results demonstrate that BiCNU-resistant subpopulation cells derived from GBM have cancer stem-like cell properties. Therefore, it may provide provide further evidence that CSCs in GBM have chemotherapeutic drug resistance.

• Korean Journal of Head & Neck Oncology
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• v.30 no.2
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• pp.43-52
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• 2014

배경 및 목적 암-연관 섬유아세포(Cancer-associated fibroblasts, CAF)는 종양미세환경의 가장 중요한 요소의 하나다. 그래서 두경부편평세포암에 대해 CAF가 암세포의 운동성에 미치는 영향을 평가하고, CAF에 과발현되는 CD44의 역할에 대해 평가하고자 하였다. 재료 및 방법 두경부암환자의 종양조직에서 CAF를 분리하고, 비종양성 조직으로부터 정상 섬유아세포(NHF)를 분리하였다. 창상치유분석과 상하 챔버를 이용한 3차원 세포 이동 분석을 이용하여, CAF가 암세포의 이동에 미치는 영향을 분석하고, CAF에서 과발현되는 CD44를 중화항체로 CAF를 차단했을 때 암세포 이동의 변화를 관찰하였다. 결과 NHF에 비해 CAF에서 CD44가 과발현되는 것을 관찰하였다. 창상치유분석에서 CAF와 같이 배양된 암세포는 NHF와 같이 배양된 암세포에 비해 더 빠른 이동을 보였다. CD44 중화 항체를 처리했을 때는 암세포의 이동성이 저해되었다. 결론 CAF는 종양미세환경에서 암세포의 운동성을 조절하는 중요한 인자의 하나일 것으로 사료된다. CD44는 CAF의 기능을 매개하는 중요한 표지자 중 하나로 생각된다.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.4
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• pp.307-313
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• 2008

Purpose: Vascular endothelial growth factor (VEGF) and its receptor, fetal liver kinase 1 (Flk-1), play an important role in vascular permeability and tumor angiogenesis. The aim of this study is to evaluate the therapeutic efficacy of $^{131}I$ labeled anti-Flk-1 monoclonal antibody (DC101) on the growth of melanoma tumor, which is known to be very aggressive in vivo. Materials and Methods: Balb/c nude mice were injected subcutaneously with melanoma cells in the right flank. Tumors were allowed to grow up to $200-250\;mm^3$ in volume. Gamma camera imaging and biodistribution studies were performed to identify an uptake of $^{131}I$-DC101 in various organs. Mice with tumor were randomly divided into five groups (10 mice per group) and injected intravenously; control PBS (group 1), $^{131}I$-DC101 $50\;{\mu}g/mouse$ (group 2), non-labeled DC101 $50\;{\mu}g/mouse$ (group 3), $^{131}I$-DC101 $30\;{\mu}g/mouse$ (group 4) and $15\;{\mu}g/mouse$ (group 5) every 3 or 4 days for 20 days. Tumor volume was measured with caliper twice a week. Results: In gamma camera images, the uptake of $^{131}I$-DC101 into tumor and thyroid was increased with time. Biodistribution results showed that the radioactivity of blood and other major organ was gradually decreased with time whereas tumor uptake was increased up to 48 hr and then decreased. After 4th injection of $^{131}I$-DC101, tumor volume of group 2 and 4 was significantly smaller than that group 1. After 5th injection, the tumor volume of group 5 also significantly reduced. Conclusion: These results indicated that delivery of $^{131}I$ to tumor using FlK-1 antibody, DC101, effectively blocks tumor growth in aggressive melanoma xenograft model.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.1
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• pp.38-48
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• 2022

Carcinoembryonic antigen (CEA) is an oncofetal antigen primarily detected in the peripheral blood of cancer patients, particularly in those with colorectal cancer. CEA is considered a valuable target for antigen-specific immunotherapy. In this study, we induced the anti-tumor immunity for CEA through the administration of a dendritic cell (DC) vaccine. However, there was a limitation in inducing tumor regression in the DC vaccinated mice. To enhance the efficacy of anti-tumor immunity in MC38/CEA2 tumor-bearing mice, we evaluated the effects of DC vaccine in combination with cyclophosphamide (CYP). Administration of CYP 100 mg/kg in mice resulted in significant inhibition of tumor growth in the 2-day tumor model, whereas a lower inhibition of tumor growth was seen in the 10-day tumor model. Therefore, the 10-day tumor model was selected for testing chemo-immunotherapy. The combined CYP and DC vaccine not only increased tumor antigen-specific immune responses but also induced synergistic anti-tumor immunity. Furthermore, the adverse effects of CYP such as weight loss and immunosuppression by regulatory T cells and myeloid-derived suppressor cells showed a significant reduction in the combined chemo-immunotherapy treatment compared with CYP alone. Our data suggest that chemoimmunotherapy with the DC vaccine may offer a new therapeutic strategy to induce a potent anti-tumor effect and reduce the adverse effects of chemotherapy.