• 대한한방내과학회지
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• 제24권2_4호
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• pp.1067-1074
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• 2003

Objectives : This study was designed to evaluate the effects of traditional oriental therapies(TOT) on advanced gastric cancer(AGC) patient with metastasis to liver. Methods : We retrospectively analyzed the medical record of a case of AGC patient in stage IV with metastasis to liver who had been treated with TOT for 5 months continuously in East-West Cancer Center of Oriental Hospital of Daejeon University from 5 March 2003 through 22 July 2003. Results : After treated with TOT for the 5 months, most of symptoms were disappeared or improved and tumor size was decreased on abdominal CT compared with the previous result. The hematological results and tumor markers were not increased. Conclusions : From the above results, it could be suggested that TOT have effects on improving symptoms and quality of life as a supportive or curative therapy for AGC patients.

• Journal of Microbiology and Biotechnology
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• 제28권3호
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• pp.367-374
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• 2018

RNA interference provides an effective tool for developing antitumor therapies. Cell-penetrating peptides (CPPs) are delivery vectors widely used to efficiently transport small-interfering RNA (siRNA) to intracellular targets. In this study, we investigated the efficacy of the cancer-specific CPP carrier BR2 to specifically transport siRNA to cancer-target cells. Our results showed that BR2 formed a complex with anti-vascular endothelial growth factor siRNA (siVEGF) that exhibited the appropriate size and surface charge for in vivo treatment. Additionally, the BR2-VEGF siRNA complex exhibited significant serum stability and high levels of gene-silencing effects in vitro. Moreover, the transfection efficiency of the complex into a cancer cell line was higher than that observed in non-cancer cell lines, resulting in downregulated intracellular VEGF levels in HeLa cells and comprehensively improved antitumor efficacy in the absence of significant toxicity. These results indicated that BR2 has significant potential for the safe, efficient, and specific delivery of siRNA for diverse applications.

• Tuberculosis and Respiratory Diseases
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• 제78권3호
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• pp.239-245
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• 2015

Background: Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. Methods: In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only $5{\times}10^4$ MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. Results: The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice. Conclusion: This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3457-3460
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• 2014

Background: Thymomas and thymic carcinomas are rare malignancies and devising clinically effective molecular targeted therapies is a major clinical challenge. The aim of the study was to analyze BLC2 and vascular endothelial growth factor receptor (VEGFR) expression and KRAS and EGFR mutational status and to correlate them with the clinical characteristics of patients with thymomas and thymic carcinomas. Materials and Methods: A total of 62 patients (mean age: $50.4{\pm}13.2$ years) with thymomas and thymic carcinomas were enrolled. The expression of BLC2 and VEGFR in tumor cells and normal tissues was evaluated by RT-PCR. The mutational status of the KRAS and EGFR genes was investigated by PCR with sequence specific primers. Results: The BLC2 and VEGFR expression levels did not differ significantly between tumor and normal tissues. Moreover, there were no clearly pathogenic mutations in KRAS or EGFR genes in any tumor. None of the molecular markers were significantly related to clinical outcomes. Conclusions: Changes in levels of expression of BLC2 and VEGFR do not appear to be involved in thymic tumorigenesis. Moreover, our data suggest that KRAS and EGFR mutations do not play a major role in the pathogenesis of thymomas and thymic carcinomas.

• 동의생리병리학회지
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• 제32권6호
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• pp.396-402
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• 2018

Hataedock (HTD) treatment is a traditional preventive therapy for the fetal toxicosis- the acute allergic disease after childbirth, mainly manifested by a variety of skin allergies such as scab, phlegm. The aim of this study was to investigate the efficacy of HTD treatments for the alleviation of inflammation in Dermatophagoides farinae-induced obese NC/Nga mice. 20 mg/kg of Coptidis Rhizoma, Glycyrrhizae Radix (CRGR) extracts as a remedy of HTD treatments were orally administered to NC/Nga mice. We induced obesity in the mice by high-fat diet. To induce skin allergies, the extracts of Dermatophagoides farinae were topically applied on the NC/Nga mice at 4th-6th and 8th-10th weeks. Structural and molecular changes in the skin tissues were measured by immunohistochemical staining. HTD treatment decreased the atopic dermatitis (AD)-like symptoms including hemorrhage, erythema, erosion, edema, and dryness. HTD treatment suppressed the mast cell activation confirmed by reduction of $Fc{\varepsilon}RI$, substance P, and serotonin. The expression of several inflammatory mediators including nuclear factor-kappa B ($NF-{\kappa}B$) p65, inducible nitric oxide synthase (iNOS), vascular endothelial growth factors (VEGFs) was also decreased by HTD treatment. HTD treatment suppressed the allergic, inflammatory responses in the skin tissues of the NC/Nga mice by reducing mast cells and down-regulating several inflammatory mediators.

• 대한두개안면성형외과학회지
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• 제20권4호
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• pp.239-245
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• 2019

Background: Lidocaine spray is a local anesthetic that improves random-pattern skin flap survival. The fractional ablative carbon dioxide laser (FxCL) produces vertical microchannels that delivers topically applied drugs to the skin. In this study, we hypothesized that FxCL therapy would enhance the lidocaine effect to improve random-pattern skin flap survival in rats. Methods: McFarlane random-pattern skin flaps were elevated in 48 rats, which were divided into four groups according to treatment: FxCL+lidocaine, FxCL, lidocaine, and nontreatment (control). On postoperative day 7, necrotic flap areas, the number of capillary vessels, and neutrophil count were evaluated. Anti-rat vascular endothelial growth factor (VEGF) and CD31 antibody activity were also evaluated by immunohistochemical staining. Results: Flap survival rate was $53.41%{\pm}5.43%$, $58.16%{\pm}4.80%$, $57.08%{\pm}5.91%$, and $69.08%{\pm}3.20%$ in the control, lidocaine, FxCL, and FxCL+lidocaine groups, respectively. Mean neutrophil count in the intermediate zone excluding the necrotic tissue was $41.70{\pm}8.40$, $35.43{\pm}6.41$, $37.23{\pm}7.15$, and $27.20{\pm}4.24cells/field$ in the control, lidocaine, FxCL, and FxCL+lidocaine groups, respectively. Anti-rat VEGF and CD31 antibody activity were the highest in the FxCL+lidocaine group. Conclusion: FxCL with lidocaine had a positive effect on random-pattern skin flap survival in rats. Thus, FxCL with lidocaine spray should be considered as a new treatment option to improve flap viability.

• Molecules and Cells
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• 제46권7호
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• pp.420-429
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• 2023

Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.

• 한국식품영양과학회지
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• 제43권3호
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• pp.374-380
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• 2014

본 연구에서는 야관문 추출물의 마우스 대식세포에 대한 항염증 활성과 창상유발 동물실험 모델을 통한 창상치유 효과를 조사하였다. RAW264.7 세포에서 야관문 추출물은 0.2 mg/mL 이하 농도에서 세포생존에 영향을 주지 않았으며, 염증반응이 활성화된 대식세포에 대해 농도 의존적으로 유의적인 NO 생성 감소를 나타내었다. 창상유발 동물실험 모델에서 야관문 추출물을 함유한 화장품 조성물의 창상치유효과에 대해 육안적으로 관찰한 결과, SCO군과 CCO군보다 야관문 추출물을 함유한 SSP군에서 약 20~30% 빠른 상처면적 감소 효과를 나타내었으며, 반흔 크기 역시 약 12% 작게 형성되었다. 또한 SSP군 조직의 외피와 진피 재생회복속도가 빨라진 것을 Masson's trichrome 염색을 통해 확인할 수 있었으며, VEGF 및 TGF-${\beta}1$ 유전자 발현이 SCO군과 비교 시 각각 감소 및 증가하였다. 이러한 결과는 야관문 추출물이 항염증 및 교원질 생성 유도를 통한 조직재생 활성에 기여하여 창상치유 속도를 가속화하고 반흔 면적을 감소시킬 수 있는 피부 창상치유와 관련한 코스메슈티컬 소재로써 산업적 활용이 가능함을 보여준다.

• Clinical and Experimental Pediatrics
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• 제49권9호
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• pp.977-982
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• 2006

목 적 : M. pneumoniae는 기도 점막의 상피세포에서 증식하면서 호흡기 질환을 일으키며 기관지 천식의 발생이나 악화와 관계된다고 알려져 있다. IL-6은 급성 염증을 유도하는 사이토카인으로 B 세포의 분화에 관여하며 Th2 염증반응을 촉진시키며, IL-8은 기도에서 염증부위로의 세포이동을 매개하는 케모카인으로 알레르기 염증 반응에 밀접한 관련을 가진다. 기도 상피세포에서 생성되는 NO는 기도 염증과 기도과민성의 조절에 중요하다. VEGF는 천식에서 기도개형에 주된 역할을 담당한다. 본 연구에서는 기관지 상피세포에 M. pneumoniae를 감염시켰을 때 IL-6, IL-8, NO 및 VEGF의 발현을 살펴보았다. 방 법 : M. pneumoniae를 기관지 상피 세포주인 A549 세포에 감염시킨 후 여러 시간 간격으로 배양하여 세포와 배양 상층액을 수거하였다. 면역 형광 염색과 M. pneumoniae 16S ribosomal RNA gene의 oligonucleotide primers를 이용한 중합효소 연쇄반응을 시행하여 감염을 확인하였다. IL-6, IL-8, VEGF 단백질 생성은 ELISA kit를 이용하여 정량하였고, NO는 Griess 반응을 이용하여 측정하였다. 역전사 중합효소 연쇄반응을 이용하여 IL-6, IL-8, VEGF의 mRNA 발현을 관찰하였다. 결 과 : 기관지 상피세포에 M. pneumoniae를 감염시킨 후 시간이 지남에 따라 IL-6, IL-8, NO, VEGF의 생성이 증가하였고, IL-6, IL-8, VEGF mRNA 발현이 증가됨을 관찰하였다. 결 론 : M. pneumoniae 감염은 IL-6, IL-8, NO, VEGF 등의 매개물질의 발현을 증가시켜 기관지 천식의 알레르기 염증반응에 관여할 것으로 사료된다.

• 대한한방내과학회지
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• 제35권4호
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• pp.416-427
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• 2014

Objectives: The purpose of this study was to investigate the antineoplastic effect of several herbal medicine mixtures (compositions of Astragalus membranaceu, Angelica gigas, Trichosanthes kirilowii, Panax ginseng, Rhus verniciflua Stokes) on the SNU-80 anaplastic thyroid carcinoma cell line. Methods: MTT assay was used to examine whether our herbal medicine mixtures decreased cell growth rate of SNU-80. Wound healing assay and Transwell invasion assay was performed to investigate whether our herbal medicine mixtures affect the migration and invasion of anaplastic cancer cells, SNU-80. ELISA assay was performed to know if our herbal medicine mixtures suppressed the expression of pro-invasive molecules, such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) secreted from SNU-80. Results: MTT assay demonstrated that A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas :T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 strongly suppressed the growth of SNU-80. Wound healing assay demonstrated that A. membranaceus:A. gigas=3:1, A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 inhibited the migration of SNU-80. Transwell invasion assay demonstrated that A. membranaceus:A. gigas=1:1, A. membranaceus:A. gigas:T. kirilowii =1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng=1:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng :R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 inhibited the invasion of SNU-80. ELISA assay demonstrated that A. membranaceus :A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 suppressed the expression of VEGF. Also, A. membranaceus:A. gigas=1:1, A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus :A. gigas:T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes =1:1:1:1:1 or 3:1:1:1:1 suppressed the expression of MMP-2. Conclusions: The results obtained in this study suggest that several herbal medicine mixtures suppresse the growth and inhibit the migration and invasion of SNU-80, which is anaplastic thyroid cancer cells. Especially, A. membranaceus:A. gigas: T. kirilowii=1:1:1 mixture had a stronger anti-cancer effect.