• Clinical and Experimental Reproductive Medicine
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• 제32권3호
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• pp.287-293
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• 2005

Objective: To evaluate the usefulness of serum concentrations of macrophage migration inhibitory factor (MIF) of patients with ovarian cysts for differential diagnosis of endometrioama. Method: From Jan. 2003 to Dec. 2004, preoperative serum MIF levels were assessed in 28 women with endometrioma, 32 with benign epithelial tumor, 23 with functional and simple cysts, 22 with benign mature cystic teratoma, and 25 women without ovarian tumor as control. MIF levels were determined using an ELISA (Quantikine Human MIF immunoassay, R&D Systems, Inc., USA). Results: Mean MIF levels were higher in all groups with benign tumors than control (all p<0.01), but there was no significant difference between benign tumor groups (p=0.95). There was no significant correlation between MIF levels and tumor volume, body mass index (BMI) (p=0.635, 0.674 respectively) Serum MIF level had significant correlation with count of WBC and neutrophils (p=0.008, 0.024 respectively), but had no correlation with count of lymhocytes and monocytes (p=0.688, 0.294 respectively). Conclusions: This study showed a marked increase in MIF concentrations in the peripheral blood of patients with endometrioma, but there was no significant difference with other benign tumors. Serum MIF level had significant correlation with count of WBC and neutrophils. These suggest serum MIF level has no usefulness for differential diagnosis of endometrioma from other benign ovarian cysts.

• 대한한방종양학회지
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• 제6권1호
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• pp.47-65
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• 2000

In order to investigate antitumor and immune response effect by Hyangsapyungwisan after Sarcoma-180 cells and methotrexate were treatred each other, the extract of Hyangsapyungwisan was orally administered to ICR mice for 14 days. To evaluate the effects of the Hyangsapyungwisan, 50% inhibition concentration($IC_{50}$), mean survival days, tumor weight for antitumor effects, hemagglutinin titer, hemolysin titer, rosette forming cells, natural killer cell activity and productivity of interleukin-2 for immune responses measured in ICR mice. The results were summarized as follows: 1. Mean survival time in Hyangsapyungwisan-treated group was slightly prolonged, as compared with control group(13.46%). 2. On the MTT assay, cell viability was significantly inhibited by $5{\mu}g/well,\;2.5{\mu}g/well,\;1.25{\mu}g/well,\;and\;0.625{\mu}g/well$ of Hyangsapyung-wisan concentration inhibited cell viability significantly. $IC_{50}$ for cell viability was $11.59{\mu}g/well$. 3. Tumor weight in Hyangsapyungwisan treated group was depressed, as compared with the control group(p<0.05). 4. Hemagglutinin titer in Hyangsapyungwisan-treated group was slightly increased with no significance, as compared with the control group. 5. Hemolysin titer in Hyangsapyungwisan-treated group was silightly increased, as compared with the control group(p<0.05). 6. Rosette forming cells in Hyangsapyungwisan-treated group was silightly increased, as compared with the control group(p<0.05). 7. Naural killer cell activity in Hyangsapyungwisan-treated group was significantly increased(p<0.05). 8. Production of interleukin-2 was significantly increased(p<0.05). According to the above results, Hyangsapygwisan had prominent antitumor effects, and enhance both cellular and humoral immunity in mice.

• Journal of Ginseng Research
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• 제47권2호
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• pp.210-217
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• 2023

Background: Effects of the major ginsenoside Rg1 on mammalian longevity and physical vitality are rarely reported. Purpose: To examine longevity, tumor, and spontaneous locomotor activity in rats consuming Rg1. Methods: A total of 138 Wistar rats were randomized into 2 groups: control (N = 69) and Rg1 (N = 69). Rg1 (0.1 mg/kg per day) were orally supplemented from 6 months of age until natural death. Spontaneous mobility was measured by video-tracking together with body composition (dual energy x-ray absorptiometry) and inflammation markers at 5, 14, 21, and 28 months of age. Results: No significant differences in longevity (control: 706 days; Rg1: 651 days, p = 0.77) and tumor incidence (control: 19%; Rg1: 12%, p = 0.24) were observed between the two groups. Movement distance in the control group declined significantly by ~60% at 21 months of age, together with decreased TNF-α (p = 0.01) and increased IL-10 (p = 0.02). However, the movement distance in the Rg1 group was maintained ~50% above the control groups (p = 0.01) at 21 months of age with greater magnitudes of TNF-α decreases and IL-10 increases. Glucose, insulin, and body composition (bone, muscle and fat percentages) were similar for both groups during the entire observation period. Conclusion: The results of the study suggest a delay age-dependent decline in physical vitality during late life by lifelong Rg1 consumption. This improvement is associated with inflammatory modulation. Significant effects of Rg1 on longevity and tumorigenesis were not observed.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2001년도 춘계학술발표대회
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• pp.47-47
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• 2001

The neuropeptide vasopressin (VP) is a nine- amino acid hormone synthesized as preprohormone in the cell bodies of hypothalamic magnocellular neurons. The tumor in magnocellular neurons of the hypothalamus is associated with disfunctions of the cell bodies, leading to the diabetes insipidus. In order to study with the diabetes insipidus caused by a defect in VP synthesis and its secretion, we have produced the transgenic mice regulated by vasopressin promoter inserted to SV40 T antigen coding sequence (pVPSV.IGR2.1). One transgenic line expressing high levels of SV40 T antigen was propagated. The founder and all transgene positive adult animals have appeared with shorten mortality or apparent phenotypic abnormalities, including immune complex disease, and eventually die between 4 and 8 months of age. The mRNA and protein of SV40T antigen transgene were detected in brain of fetus as well as in brain, spleen, lung and lymph node in moribund at the age of 20 weeks. Histological analysis of transgenic mice showed that tumor developed in brain similar to primitive neuroectodermal tumors (PNET) in man. We also detected lymphomas in spleen and lymph node, and consequent tumor formation in various tissues of the transgenic mice. In pVPSV.IGR2.1, 21% mice showed brain tumor (PNET) at 5 weeks and 100% mice showed brain tumor after 15 weeks. In addition, Expression of apoptosis related genes (Bcl-28 & Bax) was increased over their age in mice with PNET as compared to control mice. Apoptosis related gene expression might be deregulated in mice with brain tumor. However, transgenic mice were not developed with the diabetes insipidus. These mice represent the first disease model to exhibit primitive neuroectodermal tumor in brain, as well as a unique model system for exploring the cellular pathogenesis of lymphomas.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1253-1259
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• 2012

The 14-3-3 proteins are highly conserved, ubiquitous molecules involved in a variety of biologic phenomena, such as cell cycle control, and apoptosis. However, their expression in cholangiocarcinoma has not been previously characterized. In this paper, immunohistochemistry using specific anti-14-3-3 monoclonal antibodies was performed on formalin-fixed;, paraffin embedded archival tissue from 86 patients of cholangiocarcinoma. We also examined the correlation between expression and survival rate and clinicopathologic factors such as tumor location, tumor size, pathologic differentiation, lymphatic permeation, lymph node metastasis, and tumor stage. Positive 14-3-3 proteins expression was observed for 6 isoforms (${\beta}$, ${\sigma}$, ${\gamma}$, ${\theta}$, ${\delta}$, ${\eta}$) of these proteins in 86 patients of cholangiocarcinoma. ${\beta}$ and ${\sigma}$ isoform immunoreactivity was correlated with lymph node metastasis, tumor stage and patients' survival rate. In addition, ${\delta}$ isoform immunoreactivity showed trends with tumor location, tumor size, pathologic differentiation and tumor stage, while the ${\theta}$ isoform was correlated with pathologic differentiation. These results indicated that upregulated expression of some isoforms of 14-3-3 may be a common mechanism for evading apoptosis in cholangiocarcinoma, so that targeting 14-3-3 may be a novel promising strategy for the treatment of this tumor.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권2호
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• pp.66-73
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• 2009

Tumor angiogenesis is a process leading to formation of blood vessels within tumors and is crucial for maintaining a supply of oxygen and nutrients to support tumor growth and metastasis. Vascular endothelial growth factor(VEGF) plays a key role in tumor angiogenesis including induction of endothelial cell proliferation, migration, survival and capillary tube formation. VEGF binds to two distinct receptors on endothelial cells. VEGFR-2 is considered to be the dominant signaling receptor for endothelial cell permeability, proliferation, and differentiation. Bevacizumab(Avastin, Genetech, USA) is a monoclonal antibody against vascular endothelial growth factor. It is used in the treatment of cancer, where it inhibits tumor growth by blocking the formation of new blood vessels. The goal of this study is to identify the anti-tumor effect of Bevacizumab(Avastin) for oral squamous cell carcinoma cell lines. Human squamous cell carcinoma cell line(HN4) was used in this study. We examined the sensitivity of HN4 cell line to Bevacizumab(Avastin) by using in vitro proliferation assays. The results were as follows. 1. In the result of MTT assay according to concentration of Bevacizumab(Avastin), antiproliferative effect for oral squamous cell carcinoma cell lines was observed. 2. The growth curve of cell line showed the gradual growth inhibition of oral squamous cell carcinoma cell lines after exposure of Bevacizumab(Avastin). 3. In the apoptotic index, groups inoculated Bevacizumab(Avastin) were higher than control groups. 4. In condition of serum starvation, VEGFR-2 did not show any detectable autophosphorylation, whereas the addition of VEGF activated the receptor. Suppression of phosphorylated VEGFR-2 and phosphorylated MAPK was observed following treatment with Bevacizumab(Avastin) in a dose-dependent manner. 5. In TEM view, dispersed nuclear membrane, scattered many cytoplasmic vacuoles and localized chromosomal margination after Bevacizumab(Avastin) treatment were observed. These findings suggest that Bevacizumab(Avastin) has the potential to inhibit MAPK pathway in proliferation of oral squamous cell carcinoma cell lines via inhibition of VEGF-dependent tumor growth.

• Archives of Pharmacal Research
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• 제20권2호
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• pp.128-137
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• 1997

The effects of cylindan, a polysaccharide isolated from the basidiocarps of Agrocybe cylindracea, on murine sarcoma 180 tumor and murine immune cells were examined after intraperitoneal administration. Cylindan exhibited a marked life extension effect in mice against ascite forms of sarcoma 180 and Lewis lung carcinoma at a dose of 50 mg/kg/day, although it did not show any direct cytotoxicity against sarcoma 180, X5563, and MM46 murine tumor cells. Cylindan increased numbers of bone marrow stem cells as well as peritoneal exudate cells in flow cytometry using monoclonal antibodies. The tumor bearing mice group apparently showed the increase of macrophages and cytotoxic T lymphocytes in mouse spleen cells during the early stage of tumor growth. But during the later stage, the control group decreased immune cells and cylindan restored the decreased immune cells in the tumor bearing mice to the normal level. In non-specific immune response, cylindan stimulated the bacterial phagocytosis and acid phosphatase production in macrophages. It also activated components of the alternative complement pathway and natural killer activity against YAC-1 lymphoma. In number of plasma cells as token of stimulation of the differentiation of B lymphocytes. In cellular immunity, cylindan restored the depressed response of delayed type hypersensitivity in the tumor bearing mice to 60% of the normal level and increased the interleukin-2 (IL-2) responsiveness in the IL-2 dependent CTLL-2 cells. These results suggest that cylindan did not show direct cytotoxic effects on tumor cells but restored the decreased immune response of the tumor bearing mice.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.63-70
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• 2019

Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Our studies demonstrate that PD-1 expression is markedly increased in tumor-infiltrating MDSCs compared to expression in bone marrow and spleens and that it can be induced by LPS that is able to mediate $NF-{\kappa}B$ signaling. Moreover, expression of PD-L1 and CD80 on $PD-1^+$ MDSCs was higher than on $PD-1^-$ MDSCs and proliferation of MDSCs in a tumor microenvironment was more strongly induced in $PD-1^+$ MDSCs than in $PD-1^-$ MDSCs. Although we could not characterize the inducer of PD-1 expression derived from cancer cells, our findings indicate that the study on the mechanism of PD-1 induction in MDSCs is important and necessary for the control of MDSC activity; our results suggest that $PD-1^+$ MDSCs in a tumor microenvironment may induce tumor development and relapse through the modulation of their proliferation and suppressive molecules.

• 한국의학물리학회지:의학물리
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• 제26권3호
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• pp.119-126
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• 2015

본 연구에서는 불규칙적인 종양의 움직임에서 각각의 움직임 파라미터에 의해 발생되는 토모테라피 장비의 선량 오차 특성을 분석하여, 각각의 파라미터가 선량에 미치는 효과를 확인하기 위해 간소화된 이론 모델을 적용, 시뮬레이션 분석을 수행하고자 한다. 간단한 분석적인 모델이 tumor motion parameters에 의한 motion-induced dose error를 분석하기 위해 사용되었다. 분석적인 모델은 실제 tomotherapy 장비를 이용한 static dose와 Simulated tumor motion를 이용하여 dose profile을 획득하는 것이다. 본 연구에서는 Static dose를 얻기 위해 Hi-art tomotherapy unit을 이용하였다. Simulated tumor motion은 internet accessible respiratory trace generator (RTG) program을 이용하여 획득되었다. 종양의 움직임은 불규칙한 정도가 큰 케이스와 작은 케이스, 실제 환자의 종양 움직임을 모사한 케이스로 구분하였다. 불규칙도가 작은 케이스의 경우 종양의 진폭, 주기, 베이스라인 등 종양 움직임 파라미터에 10% 변동을 인가 하였으며, 불규칙도가 큰 케이스의 경우 40%의 변동을 인가 하였다. 위상변동 케이스의 경우 종양의 초기위상이 end inhale, mid exhale, end exhale, and mid inhale으로 나뉘어 졌고, 시뮬레이션을 통해 획득된 각각의 선량분포결과가 비교되었다. 또한, 환자 케이스에서는 임상과 동일한 조건에서의 종양 움직임을 인가하여 선량 오차를 획득하였다. 종양의 움직임에 의한 선량은 시뮬레이션 과정을 통해 계산되었으며 이를 종양의 움직임이 없는 케이스와 비교하여 종양 움직임이 선량에 미치는 영향을 확인했다. 진폭, 주기, 베이스라인 등 종양 움직임 파라미터가 불규칙하게 변하는 경우, 종양이 불규칙하게 움직이는 케이스의 경우 불규칙도가 큰 케이스의 경우가 불규칙도가 작은 케이스와 규칙적으로 움직이는 케이스보다 더 큰 선량오차가 발생하였다. 상쇄 효과는 종양움직임의 불규칙성에 반비례하기 때문에, 종양 움직임의 불규칙성이 큰 케이스의 경우 불규칙성이 작은 케이스, 종양의 움직임이 규칙적인 케이스에 비해 더 적은 상쇄 효과가 발생하였다. 위상변동 케이스의 경우, 불규칙한 종양의 움직임 케이스에서 규칙적인 움직임 케이스보다 더 큰 선량 차이가 관찰되었고, 또한 환자케이스에서 규칙적인 종양의 움직임의 경우보다 더 큰 선량의 차이가 발견되었다. 본 연구에서는 불규칙적인 종양의 움직임에서 각각의 움직임 변수들의 불규칙성에 따른 발생되는 토모테라피에서의 선량 오차 특성을 분석하였다. 본 연구의 결과를 통해 불균일한 종양 움직임의 불규칙성을 제어하는 것에 대한 중요성을 확인할 수 있었고, 이러한 불균일성의 제어의 경우 복부압박이나 호흡 훈련을 통해 해결이 가능할 것으로 생각된다.

• 한국의학물리학회지:의학물리
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• 제28권1호
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• pp.1-10
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• 2017

The difference between three-dimensional (3D) and four-dimensional (4D) dose could be affected by factors such as tumor size and motion. To quantitatively analyze the effects of these factors, a phantom that can independently control each factor is required. The purpose of this study is to develop a deformable lung phantom with the above attributes and evaluate the characteristics. A phantom was designed to simulate diaphragm motion with amplitude in the range 1~7 cm and period up to ${\geq}2s$ of regular breathing. To simulate different tumors sizes, custom molds were created using a 3D printer and filled with liquid silicone. The accuracy of the phantom diaphragm motion was assessed by comparing measured motion with predicted motion. Because the phantom diaphragm motion is not identical to the tumor motion, the correlation between the diaphragm and tumor motions was calculated by a curve fitting method to emulate user-intended tumor motion. Tumors of different sizes were located at same position, and tumor set-up positions were evaluated. The accuracy of phantom diaphragm motion was better than 1 mm. The diaphragm-tumor correlation showed that the tumor motion in the superior-inferior direction increased with increasing diaphragm motion. The tumor motion was larger in the $10cm^3$ tumor than in the $90cm^3$ tumor. The range of difference between the tumor set-up positions was 0 to 0.45 cm. This phantom showed independently adjusting factors such as tumor size and motion to facilitate quantitative analysis of the dosimetric impact of respiratory motion according to these factors.