• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4037-4043
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• 2012

Despite progress in elucidating mechanisms associated with colorectal cancer and improvement of treatment methods, it remains a frequent cause of death worldwide. New and more effective therapies are therefore urgently needed. Recent studies have shown that immunogenicity of whole ovarian tumor cells and subsequent T cell response were potentiated by oxidation modification with hypochlorous acid (HOCl) in vitro and ex vivo. These results prompted us to investigate the protective antitumor response with an HOCl treated CT26 colorectal cancer cell vaccine in an in vivo mouse model. Administration of HOCl modified vaccine triggered robust antitumor immunity to autologous tumor cells in mice and prolonged survival period significantly. In addition, increased necrosis and apoptosis were found in tumor tissue from the oxidation group. Interestingly, ELISPOT assays showed that specific T cell responses were not elicited in response to the immunizing cellular antigen, in contrast to raising sera antibody titer and antibody binding activity shown by ELISA assay and flow cytometry. Further evaluation of the mechanisms underlying HOCl modified vaccine mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results combined with previous studies suggest that HOCl oxidation modified whole cell vaccine has wide applicability as a cancer vaccine because it can target both T cell- and B cell-specific responses. It may thus represent a promising approach for the immunotherapy of colorectal cancer.

• Radiation Oncology Journal
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• 제21권4호
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• pp.283-290
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• 2003

목적: 자궁경부암의 방사선치료 후의 재발이나 병소의 지속을 발견하기 위한 종양표지자로서의 Squamous cell carcinoma (SCC) 항원의 의의를 장기간의 경과관찰을 통해서 확인하고자 하였다. 대상 및 방법: 1995년 10월부터 2001년 5월까지 단국대학병원 방사선종양학과에서 원발성 자궁경부암으로 근치적 방사선치료를 시행 받은 환자 중 치료 전후에 혈중 SCC 항원치를 주기적으로 측정한 48예를 대상으로 하였다. 결과: 방사선치료 전에 측정한 SCC 항원치는 전체의 79.2$\%$에서 정상치 보다 높았다. 치료 후에 SCC 항원치는 유의하게 감소하였으며 치료 후 3개월 경에는 23.0$\%$에서 정상치 보다 높았다. 병소의 완전 관해가 이루어지고 치료실패가 일어나지 않은 경우는 6개월 이후의 장기적인 관찰 중 SCC 항원치는 결국 정상범위가 되었다. 치료 후의 장기적인 경과 관찰 중에 SCC 항원치가 재상승하여 지속적으로 높은 값을 나타낸 경우는 치료실패를 아주 잘 예측하였으며 SCC 항원치의 재상승과 임상적 치료실패 확인 사이의 시간간격(lead time)의 평균은 4개월이었다 재발과 관련된 SCC 항원치의 지속적 상승의 민감도는 85.7$\%$, 특이도는 100.0$\%$이었다. 첫 번째 치료실패가 폐 전이로 나타났던 4예 중 3예에서는 SCC 항원치의 재상승이 일어나기 전에 흉부단순 촬영 소견에서 폐 전이가 나타났으나 그 외의 모든 임상적 재발 시에는 SCC 항원치의 재상승이 동반되거나 선행되었다. 결론: 본 연구에서 치료 전 SCC 항원치가 높았던 경우에 치료 후 SCC 항원치의 지속적 상승은 치료 실패를 정확하게 예견하게 해 주는 좋은 예후인자였으며 SCC 항원치 상승과 치료실패 사이의 시간간격은 평균 4개월이었다. 그러나 치료 전 SCC 항원치가 높은 경우의 치료실패 양상 중, 폐 전이 초기와 같이 종양부피가 작은 경우는 처음에는 일시적으로 SCC항원치가 정상범위로 관찰될 수 있으므로 경과 관찰 시 반드시 흉부단순 촬영을 병행하여 폐 전이 여부를 함께 관찰하여야 할 것으로 생각된다.

• Radiation Oncology Journal
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• 제29권1호
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• pp.11-19
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• 2011

목적: 수술 전 항함화학방사선치료는 국소 진행된 직장암에서 표준치료로 알려져 있다. 이 연구는 동시 항암화학 방사선치료를 받은 국소 진행된 직장암 환자의 생존율 및 병기하향률에 영향을 미치는 인자들을 분석하였다. 대상 및 방법: 2004년 3월부터 2008년 8월까지 수술 전 항암화학방사선치료를 받은 국소 진행된 직장암 환자 33명을 대상으로 하였다. 모든 환자는 전 골반 방사선조사를 시행하였으며 28명(84.8%)은 동시적 소조사야 추가 방사선치료, 5명(15.2%)은 조사영역축소 방사선치료를 실시하였다. 총 방사선량은 50.4 Gy이었으며, 5-fluorouracil를 동시 투여하였다. 추적관찰 기간은 중앙값 24.2개월(9.8~64.7개월)이었다. 결과: 33명 중 31명(93.9%)에서 수술이 시행되었으며, 24명(72.7%)은 항문괄약근보존술, 7명(21.2%)은 복회음부 절제술이 시행되었다. 3년 생존율과 무병생존율은 각각 78.8%, 63.4% 이었다. 무병생존율에 영향을 미치는 인자로 수술 후 병리학적 소견이 중요하였다. 병리학적 N 병기(p=0.001), 절제면 침윤 여부(p=0.029) 및 분화도(p=0.030)가 통계학적으로 의미 있게 영향을 미치는 인자였다. 종양 크기 (p=0.081), 림프혈관과 신경주위 침윤여부(p=0.073) 모두 영향을 마치는 인자로서의 경향성을 보였다. 한편, 수술 전 임상 소견으로는 임상적 T 병기만이 유의한 결과를 보였다(p=0.018). 병리학적 완전관해율은 9.1%였으며, T병기하향률은 30.3%, N 병기하향률은 72.7%로 나타났다. 단변량 분석에서 항암화학방사선치료 후 수술까지의 기간 및 임상적 T 병기가 의미 있는 병기하향의 예측인자로 분석되었다(p=0.029, 0.027). 치료 전 carcinoembryonic antigen 수치는 예측인자의 경향성을 보였다(p=0.068). 결론: 국소 진행된 직장암 환자의 생존율은 임상적 병기보다 수술 후 병리학적 소견에 더 의존되었다. 그러므로 수술전 항암화학방사선치료로 병기하향을 얻는 것이 의미가 있으며, 수술까지의 기간, 임상적 T 병기가 이러한 병기하향을 예측하는 인자였음을 알 수 있었다.

• Journal of Korean Medical Science
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• 제33권47호
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• pp.303.1-303.10
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• 2018

Background: Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with oncogenic activities in human cancers; however, the clinical significance of CDC6 in prostate cancer (PCa) remains unclear. Therefore, we investigated whether the CDC6 mRNA expression level is a diagnostic and prognostic marker in PCa. Methods: The study subjects included 121 PCa patients and 66 age-matched benign prostatic hyperplasia (BPH) patients. CDC6 expression was evaluated using real-time polymerase chain reaction and immunohistochemical (IH) staining, and then compared according to the clinicopathological characteristics of PCa. Results: CDC6 mRNA expression was significantly higher in PCa tissues than in BPH control tissues (P = 0.005). In addition, CDC6 expression was significantly higher in patients with elevated prostate-specific antigen (PSA) levels (> 20 ng/mL), a high Gleason score, and advanced stage than in those with low PSA levels, a low Gleason score, and earlier stage, respectively. Multivariate logistic regression analysis showed that high expression of CDC6 was significantly associated with advanced stage (${\geq}T3b$) (odds ratio [OR], 3.005; confidence interval [CI], 1.212-7.450; P = 0.018) and metastasis (OR, 4.192; CI, 1.079-16.286; P = 0.038). Intense IH staining for CDC6 was significantly associated with a high Gleason score and advanced tumor stage including lymph node metastasis stage (linear-by-linear association, P = 0.044 and P = 0.003, respectively). Conclusion: CDC6 expression is associated with aggressive clinicopathological characteristics in PCa. CDC6 may be a potential diagnostic and prognostic marker in PCa patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3877-3880
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• 2013

Objective: To explore the expression and significance of tumor specific growth factor (TSGF), carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP) in cancer tissue and serum of patients with colon cancer. Materials and Methods: Radical surgery for colon cancer was performed on 43 patients with laparoscopu under conditions of general anesthesia. The Elisa method was used to detect the levels of serum TSGF, CEA and AFP before and after radical operation, and cancer tissue underwent TSGF, CEA and AFP immunohistochemistry staining after laparoscopic surgery. The decreased conditions of serum TSGF, CEA and AFP in patients with colon cancer at different levels of differentiation and clinical stagings were analyzed, and the relationships of expression rates between histological types, colon cancer morphology, lymph node metastasis and TSGF, CEA as well as AFP in cancer tissue were assessed. Results: Compared with before radical surgery, the levels of serum TSGF, CEA and AFP decreased notably in patients after operations (p<0.01). The decreased degree of TSGF and CEA was the largest in patients with poorly differentiated cancer tissue (p<0.01), while that of AFP was noted in patients with moderately differentiated cancer tissue (p<0.01). The decreased degree of TSGF and AFP was the largest in patients at phase Dukes A (p<0.01), while that of CEA in patients at phase Dukes C (p<0.01). There were no significant differences among the positive expression rates of TSGF, CEA and AFP with different histological types and colon cancer morphologies (p>0.05). The positive expression rates of TSGF and CEA in patients with lymph node metastasis were significantly higher than those without lymph node metastasis (p<0.01). Conclusions: TSGF, CEA and AFP can be used to evaluate the effect of radical operation for colon cancer, and the changed levels of different markers are associated with tumor differentiation, clinical stating and presence or absence of lymph node metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10209-10215
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• 2015

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 1993년도 제27차 학술대회 초록집
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• pp.83-83
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• 1993

정상 p53 유전자는 17번 염색체의 short arm에 위치하는 항암 유전자이나 point mutation에 의한 p53 유전자의 변이는 반감기가 긴 p53단백을 합성하여 핵내에 축적되고 변이형 p53은 암의 발생을 일으키는 것으로 알려졌다. 최근 p53에 대한 단크론성 항체가 개발되어 조직에서 변이형 p53의 검색이 가능하여 여러종류의 종양조직에서 면역세포화학적 방법으로 p53에 대한 표현 양상이 연구되었다. 이에 설 및 편도의 편평상피세포암 조직에서 면역세포화학적 방법으로 p53의 표현 양상을 검색하고 p53의 표현 양상과 임상적, 병리적 소견과의 관계를 알아보고자 29례의 편평상피세포암(설암 19례, 편도암 10례)의 진단시 채취한 생검조직에서 p53에 대한 단크론성 항체를 사용하여 p53의 표현양상과 병리조직학적 분화도, 종양의 원발부위, 원발종양의 크기, 경부 임파전이 여부와의 관계를 비교 분석하여 다음과 같은 결과를 얻었다. 1. p53은 대조군과 실험군의 모든 비종양핵에서는 음성반응을 보였고, 29례의 실험군 중 4례의 종양핵에서 양성반응을 보여 양성율은 13.8%이었다. 2. p53의 양성반응은 종양의 크기가 4cm 이상인 예에서 4cm 미만인 예에서 보다 양성인 예가 많았다(p<0.05). 3. p53의 양성반응은 종양의 병리조직학적 분화도, 종야의 원발부위, 경부 임파전이 여부와 유의한 관계가 없었다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5973-5981
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• 2013

At present, the most common cause of cancer-related death in women is breast cancer. In a large proportion of breast cancers, there is the overexpression of human epidermal growth factor receptor 2 (HER2). This receptor is a 185 KDa growth factor glycoprotein, also known as the first tumor-associated antigen for different types of breast cancers. Moreover, HER2 is an appropriate cell-surface specific antigen for passive immunotherapy, which relies on the repeated application of monoclonal antibodies that are transferred to the patient. However, vaccination is preferable because it would stimulate a patient's own immune system to actively respond to a disease. In the current study, several bioinformatics tools were used for designing synthetic peptide vaccines. PEPOP was used to predict peptides from HER2 ECD subdomain III in the form of discontinuous-continuous B-cell epitopes. Then, T-cell epitope prediction web servers MHCPred, SYFPEITHI, HLA peptide motif search, Propred, and SVMHC were used to identify class-I and II MHC peptides. In this way, PEPOP selected 12 discontinuous peptides from the 3D structure of the HER2 ECD subdomain III. Furthermore, T-cell epitope prediction analyses identified four peptides containing the segments 77 (384-391) and 99 (495-503) for both B and T-cell epitopes. This work is the only study to our knowledge focusing on design of in silico potential novel cancer peptide vaccines of the HER2 ECD subdomain III that contain epitopes for both B and T-cells. These findings based on bioinformatics analyses may be used in vaccine design and cancer therapy; saving time and minimizing the number of tests needed to select the best possible epitopes.

• IMMUNE NETWORK
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• 제7권1호
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• pp.31-38
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• 2007

Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1715-1717
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• 2014

The overall incidence and mortality of renal cell carcinoma (RCC), the most common kidney cancer, are steadily increasing for reasons that are not fully explained. Our aim was to explore the expression of membrane MHC class I chain-related gene A (mMICA) in human RCC cell lines and tissue specimens, and to determine expression of soluble MICA (sMICA) in serum of patients with renal cell carcinoma, we used flow cytometry (FCM) and immunohistochemistry as well as an enzyme linked immunosorbent assay (ELISA). The results showed that percentage of mMICA expression was significantly increased in human kidney cancer tissues and RCC cell lines (786-O and Ketr-3) than that in healthy adults and human embryonic kidney 293 (HEK293) cell line individuality (P<0.05). sMICA content in healthy adults was negative, but in renal cancer patients was significantly elevated (P<0.05). Our research showed that high expression of MICA in human kidney cancer, this results show that MICA might serve as potential tumor-associated antigen (TAA) in RCC.