• 대한세포병리학회지
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• 제7권1호
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• pp.97-102
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• 1996

Fine needle aspiration cytology of a pulmonary mass was performed on a 51-year-old man who had a left testicular mass. Cytologic features were composed of a homogeneous population of malignant cells associated with a background of foamy and lacelike material. The cellular features were characterized by monomorphous cell proliferation of relatively regular large cells, generally isolated or grouped. Occasionally, fine blanching stroma with large tumor cells and scanty lymphocytes were noted. The tumor cells had a round, regular nucleus, prominent round nucleoli, and a thin rim of cytoplasm containing large vacuoles or lacunae filled with glycogen. The fine needle aspiration cytologic diagnosis was highly consistent with metastatic seminoma from testis and less likely primary or other metastatic carcinoma. The diagnosis of resected testicular mass was classic seminoma. Despite the fact that cytopathologists were not familial with diagnosis of seminoma due to clinician's lack of interest in fine needle aspiration cytology of germ cell tumors including seminoma, it appears that a diagnosis of this tumor should not be problematic in cytologic material if specific histologic criteria are applied.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4031-4036
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• 2012

Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.

• Natural Product Sciences
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• 제23권1호
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• pp.21-28
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• 2017

In our program to search for new AMP-activated protein kinase (AMPK) activators from plants that exert potential anticancer property, we found that an EtOAc extract of Myristica fragrans (nutmeg) activated AMPK enzyme in human breast cancer MCF-7 cells. Two major diarylbutane-type lignans, macelignan and meso-dihydroguaiaretic acid (MDGA), were isolated as active principles from this extract. Treatment of breast cancer cells with two compounds induced cellular apoptosis, evidenced by cleavage of poly-(ADP-ribose) polymerase (PARP) and Ser 15 phosphorylation of p53. Moreover, macelignan and MDGA significantly inhibited the colony formation of MCF-7 breast cancer cells on soft agar. Intraperitoneal injection of macelignan and MDGA (20 mg/kg) suppressed the tumor growth of 4T1 mammary cancer cells. These results indicate that the chemopreventive effects of two major diarylbutane-type lignans from Myristica fragrans (nutmeg) may be associated with induction of apoptosis presumably through AMPK activation.

• International Journal of Molecular Medicine
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• 제44권3호
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• pp.949-959
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• 2019

Pistacia weinmannifolia (PW) has been used in traditional Chinese medicine to treat headaches, dysentery, enteritis and influenza. However, PW has not been known for treating respiratory inflammatory diseases, including chronic obstructive pulmonary disease (COPD). The present in vitro analysis confirmed that PW root extract (PWRE) exerts anti-inflammatory effects in phorbol myristate acetate- or tumor necrosis factor α (TNF-α)-stimulated human lung epithelial NCI-H292 cells by attenuating the expression of interleukin (IL)-8, IL-6 and Mucin A5 (MUC5AC), which are closely associated with the pulmonary inflammatory response in the pathogenesis of COPD. Thus, the aim of the present study was to evaluate the protective effect of PWRE on pulmonary inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). Treatment with PWRE significantly reduced the quantity of neutrophils and the levels of inflammatory molecules and toxic molecules, including tumor TNF-α, IL-6, IL-8, monocyte chemoattractant protein-1, neutrophil elastase and reactive oxygen species, in the bronchoalveolar lavage fluid of mice with CS- and LPS-induced pulmonary inflammation. PWRE also attenuated the influx of inflammatory cells in the lung tissues. Furthermore, PWRE downregulated the activation of nuclear factor-κB and the expression of phosphodiesterase 4 in the lung tissues. Therefore, these findings suggest that PWRE may be a valuable adjuvant treatment for COPD.

• Journal of Chest Surgery
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• 제37권8호
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• pp.691-701
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• 2004

배경: 악성종양에서 신생혈관 생성 및 당분해의 증가는 저산소 상태의 미세환경을 나타내며, 이는 종양의 침습성, 전이 등으로 환자의 예후와 관련이 있는 것으로 알려져 있다. Hypoxia-inducible factor 1(HIF-1)는 당원 수송체, 당분해 효소, 혈관내피세포 성장인자 등의 유전자의 전사를 활성화한다고 알려져 있다. 그리고 HIF-1의 전사 활성도는 HIF-1 a subunit의 표현이 조절되는 정도에 의존한다. 그러나 식도암에서 HIF-1의 발현과 혈관 생성능 및 종양세포 증식능과의 관계 및 예후에 관한 연구는 전무하다. 대상 및 방법: 고신대학교 의과대학 흉부외과학교실에서 1995년부터 2000년까지 수술치험한 77예의 식도 편평세포암 환자의 조직에서 채취한 정상 편평상피와 암조직에서 면역조직화학검사를 이용하여 HIF-1 a의 발현을 조사하고 혈관생성인자, 증식지수, p53 단백과의 상관관계, 임상-병리학적인 인자 및 생존율과의 상관관계를 분석하였다. 결과: HIF-1 a의 고발현율은 42.9% (33예/77예)였다. HIF-1 a의 고발현은 조직학적 등급(p=0.032), 병리학적 병기(p=0.002), 종양 침윤의 깊이(p=0.022), 주위 림프절 전이(p=0.002), 원격전이(p=0.049), 림프관 침윤(p=0.004)과 관련이 있었다. HIF-1 a의 고발현은 혈관내피세포 성장인자의 발현, Ki-67 증식지수와 관련이 있었으나, 미세혈관수와는 관련이 없었고, p53의 발현과는 관련이 있는 경향을 보였다. 단변량분석과 다변량분석에서 HIF-1 a의 고발현은 불량한 예후를 나타내는 인자로 보였다. 결론: 식도 편평세포암 조직에서 HIF-1 a의 발현은 종양조직내 신생혈관의 생성과 관련이 있는 것으로 나타났고, 고발현 된 경우는 림프절 전이와 수술 후 불량한 예후를 나타내었으므로 보다 강화된 치료전략이 필요할 것으로 사료된다.

• Journal of Chest Surgery
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• 제39권11호
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• pp.828-837
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• 2006

배경: 악성종양에서 신생혈관 생성 및 당분해의 증가는 저산소 상태의 미세환경을 나타내며, 이는 종양의 침습성, 전이 및 환자의 예후와 관련이 있는 것으로 알려져 있다. Hypoxia-inducible factor 1(HIF-1)는 당원 수송체, 당분해 효소, 혈관내피세포 성장인자 등의 유전자의 전사를 활성화한다고 알려져 있다. 그리고 HIF-1의 전사 활성도는 HIF-$1{\alpha}$ 아단위의 표현이 조절되는 정도에 의존한다. 비소세포 폐암에서 HIF-$1{\alpha}$의 발현이 혈관 생성능, 종양세포 증식능 및 이상형 p53의 축적 등 종양의 생물학적 특성에 미치는 영향과 환자의 수술 후 예후와의 관계를 규명하고자 한다. 대상 및 방법: 1997년부터 1999년까지 비소세포 폐암으로 진단받고 전폐절제술 혹은 폐엽절제술을 시행 받은 59명의 폐암 환자들에서 얻어진 파라핀 조직 블록을 대상으로 하였다. ABC(avidin-biotin complex) 방법에 기초한 면역조직화학검사를 이용하여 암조직과 정상조직에서 HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), p53 단백의 발현을 조사하고, Ki-67의 발현을 이용한 증식지수를 측정하였다. HIF-$1{\alpha}$ 발현과 환자의 생존기간을 포함한 임상적-병리학적 변수들과의 상관관계, VEGF, p53의 발현과 증식지수와의 상관관계를 분석하였다. 결과: HIF-$1{\alpha}$의 과발현은 40.7%(24예/59예)였다. HIF-$1{\alpha}$의 과발현은 병리학적 TNM병기(p=0.004), T병기(p=0.020), N병기(p=0.004), 림프관/혈관 침범(p=0.019) 등과 관련이 있었다. 또 혈관내피세포 성장인자의 발현(p<0.001) 및 이상형의 p53의 발현(p=0.040)과 관련성이 있었다. Kaplan-Meier 생존분석에서 HIF-$1{\alpha}$의 과발현이 있는 환자의 5년 생존울은 22%로 HIF-$1{\alpha}$의 저발현 환자의 5년 생존율 61%에 비해 불량한 생존율을 보였고, 단변량분석과 다변량분석에서 HIF-$1{\alpha}$의 발현은 불량한 예후를 나타내는 인자로 관찰되었다. 결론: 이상의 결과로 비소세포 폐암 환자에서 HIF-$1{\alpha}$의 과발현은 종양내 신생혈관의 생성과 림프절 전이와 관련이 있는 표지자로 여겨지며, 수술 후 불량한 예후를 나타내었다.

• Advances in Traditional Medicine
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• 제6권1호
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• pp.12-20
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• 2006

Some natural products are able to inhibit radiation effects and exert an antitumor effect with fewer adverse reactions; however, their antitumor effects are less than those of widely-used synthetic drugs. Propolis is a natural material that has been attracting attention, and we extracted this material with water and investigated the effect of continuous propolis administration on radioactivity-induced reduction of hemocytes, in addition to the antioxidant and antitumor effects of propolis. Following a 1-week adjustment period, water-soluble propolis was administered intraperitoneally to male ICR mice at a dose of 100 mg/kg every other day for 2 weeks. Following administration, 2 Gy whole-body irradiation was performed and the counts of leukocytes, lymphocytes, and granulocytes and monocytes in the peripheral blood were determined 1, 3, 7, 15 and 30 days after irradiation. These cells were considered since they are closely associated with immunity to radioactivity. In a second experiment, water-soluble propolis was similarly administered to the mice for 2 weeks after a 1-week adjustment period, and 2 Gy whole-body irradiation was performed. The antioxidant effects in hemocytes were then investigated using 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), a radical generator. In a third experiment, $1\;{\times}\;10^6$ Sarcoma-180 cells were inoculated into the right thigh of mice, which were divided into four groups: control, water-soluble propolis-treated, 6 Gy irradiated and water-soluble propolis-treated + 6 Gy irradiated groups, and changes in tumor size were measured for 20 days. Statistical analysis was conducted using ANOVA for multiple groups. In the three experiments, administration of water-soluble propolis inhibited the reduction of hemocytes caused by whole-body irradiation, showed antioxidant effects against radioactivity, and inhibited tumor growth, respectively. In conclusion, our data suggest that the antioxidant effect of watersoluble propolis inhibits hemocyte reduction caused by whole-body irradiation and enhances immunological inhibition of tumor growth.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2647-2650
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• 2014

Background: Colorectal cancers(CRC) are the third most common cancer in the western world, with surgery preferred for management of non-metastatic disease and post surgical treatment usually arranged according to the TNM staging system. However, there is still prognostic variation between patients who have the same stage. It is increasingly recognized that variations within disease course and clinical outcome in colorectal cancer patients are influenced by not only oncological characteristics of the tumor itself but also host response factors. Recent studies have shown correlation between the inflammatory response and clinical outcomes in various cancers. The neutrophil/lymphocyte ratio (NLR) has been described as a marker for immune response to various stimuli including cancer. Material-Methods: Two hundred eighty-one CRC patients were included in our retrospective analysis, separated into two groups according to a cut-off value for the NLR. Patient data including age, gender, vertical penetration, anatomic location, and differentiation of the tumor, TNM stage, survival rate, and disease-free survival were analyzed for correlations with the NLR. Results: Using ROC curve analysis, we determined a cut-off value of 2.2 for NLR to be best to discriminate between patient survival in the whole group. In univariate analysis, high pretreatment NLR (p=0.001, 95%CI 1.483-4.846), pathologic nodal stage (p<0.001, 95%CI 1.082-3.289) and advanced pathologic TNM stage (p<0.001, 95%CI 1.462-4.213) were predictive of shorter survival. In multivariate analysis, advanced pathologic TNM stage (p=0.001, 95%CI 1.303-26.542) and high pretreatment NLR (p=0.005, 95%CI 1.713-6.378) remained independently associated with poor survival. Conclusions: High pre-treatment NLR is a significant independent predictor of shorter survival in patients with colorectal cancer. This parameter is a simple, easily accessible laboratory value for identifying patients with poorer prognosis.

• 동의생리병리학회지
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• 제22권2호
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• pp.282-289
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• 2008

We evaluated the effect of SHBCS on adhesion and invasion of colon L5-26 adenocarcinoma cell line in vitro in vitro and experimental liver metastasis in vivo. SHBCS showed little inhibitory effect on colon 26-L5 cell proliferation. At the concentration of up to 500 mg/ml of SHBCS 80% of cells were viable. SHBCS showed no inhibitory effect on adhesion and invasion of colon 26-L5 cells, which were placed on matrigel. In a dose dependent manner, oral administration of SHBCS showed a significantly inhibitory effect on liver metastasis from colon 26-L5 injected mice. When mice were depleted of NK cells or macrophages before tumor inoculation, SHBCS significantly decreased liver metastasis fromf the tumor injected mice. Compared with the control mice, SHBCS increased the populations of macrophages and NK cells by 30%, 18%(10 mg/mouse, 50 mg/mouse) and 5%, 1% (10 mg/mouse, 50 mg/mouse) respectively. Compared with the control mice, SHBCS increased the populations of CD4 cells by 5%, 18% (10 mg/mouse, 50 mg/mouse) respectively. Spelenocytes from mice administerd with SHBCS were stimulated with LPS plus ConA, proliferation of splenocytes from mice administerd with SHBCS was 140%, 146%(10 mg/mouse, 50 mg/mouse) compared with th control mice. In conclusion, the present study suggests that SHBCS may have an inhibitory effect on liver metastasis through immunopotentiating activity which is associated with macrophages and NK cells.

• 대한두경부종양학회지
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• 제25권1호
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• pp.18-23
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• 2009

Objectives : In $CO_2$ laser surgery for supraglottic cancer, neck dissection is generally done in second stage. We investigated simultaneous neck dissection with primary resection could be available in laser supraglottic surgery. Material and Methods : We analyzed 13 patients with supraglottic cancer who were treated with transoral supraglottic laryngectomy and simultaneous neck dissection from 2001 to 2007. Tumor stage, extent of laser surgery, histological results, survival rate, local control rate, complications, and functional results were reviewed. Results : 5-year local control rate, survival rate and disease specific survival rate from the neck was 100%, 69.9%, 100% respectively. Tracheotomy was done in all 13 cases. One patient had a long tracheotomy indwelling (191 days). In the rest of 12 patients average decanulation time was 7.4 days(1-22 days). Nasogastric tube was inserted in 5 cases, and average oral intake was possible in 3.5 days(1-16 days). Average hospital days was 29.7 days. There was no serious complication associated with neck dissection. Conclusion : Simultaneous neck dissection with primary laser resection for supraglottic cancer is oncologic sound and can be performed without significant surgical morbidity.