• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.3
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• pp.384-388
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• 2013

This study investigated the anti-inflammatory effects of extracts from Caesalpinia sappan L. (CSL) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice. Skin inflammation was detected by immunohistochemistry and the protein and mRNA expression levels of cyclooxygenase-2 (COX-2) and cytokines (IL-6, IL-$1{\beta}$ and TNF-${\alpha}$) detected by Western blotting and RT-PCR. The activation of nuclear factor-kappa B (NF-${\kappa}B$) and mitogen-activated protein kinase (MAPK) were analyzed by Western blotting. CSL extracts markedly inhibited the TPA-induced expression of COX-2 and pro-inflammatory cytokines. Also, CSL extracts significantly reduced the activation of NF-${\kappa}B$ and MAPK. These results suggest that CSL extracts may serve as therapeutic agents against skin diseases related to inflammation.

• BMB Reports
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• v.51 no.11
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• pp.572-577
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• 2018

Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

• Journal of Life Science
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• v.24 no.5
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• pp.588-593
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• 2014

Tumor angiogenesis is important in tumorigenesis and therapeutic interventions in cancer. To know inhibitor and effector of tumor angiogenesis in cancer, the specific gene of tumor and angiogenesis may develop the mechanisms of cancer suppression and therapy. Recently, we described the role of RalA-binding protein 1 (RLIP76) in tumor angiogenesis. Tumor vascular volumes were diminished, and vessels were fewer in number, shorter, and narrower in RLIP76 knockout mice than in wild-type mice. Moreover, angiogenesis in basement membrane matrix plugs was blunted in the knockout mice in the absence of tumor cells, with endothelial cells isolated from the lungs of these animals exhibiting defects in migration, proliferation, and cord formation in vitro. RLIP76 is expressed in most human tissues and is overexpressed in many tumor types. In addition, the protein regulates tumorigenesis and angiogenesis in vivo and in vitro. As the export of chemotherapy agents is a prominent cellular function of RLIP76, it is a major factor in mechanisms of drug resistance. Moreover, RLIP76 acts as a selective effector of the small GTPase, R-Ras, and regulates R-Ras signaling, leading to cell spreading and migration. Furthermore, in skin carcinogenesis, RLIP76 knockout mice are resistant, with tumors that form showing diminished angiogenesis. Thus, RLIP76 is required for efficient endothelial cell function and angiogenesis in solid tumors.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.184-194
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• 2020

Histone deacetylase (HDAC) inhibitors represent a novel class of anticancer agents, which can be used to inhibit cell proliferation and induce apoptosis in several types of cancer cells. In this study, we investigated the anticancer activity of MHY4381, a newly synthesized HDAC inhibitor, against human prostate cancer cell lines and compared its efficacy with that of suberoylanilide hydroxamic acid (SAHA), a well-known HDAC inhibitor. We assessed cell viability, apoptosis, cell cycle regulation, and other biological effects in the prostate cancer cells. We also evaluated a possible mechanism of MHY4381 on the apoptotic cell death pathway. The IC₅₀ value of MHY4381 was lower in DU145 cells (IC₅₀=0.31 µM) than in LNCaP (IC₅₀=0.85 µM) and PC-3 cells (IC₅₀=5.23 µM). In addition, the IC₅₀ values of MHY4381 measured in this assay were significantly lower than those of SAHA against prostate cancer cell lines. MHY4381 increased the levels of acetylated histones H3 and H4 and reduced the expression of HDAC proteins in the prostate cancer cell lines. MHY4381 increased G2/M phase arrest in DU145 cells, and G1 arrest in LNCaP cells. It also activated reactive oxygen species (ROS) generation, which induced apoptosis in the DU145 and LNCaP cells by increasing the ratio of Bax/Bcl-2 and releasing cytochrome c into the cytoplasm. Our results indicated that MHY4381 preferentially results in antitumor effects in DU145 and LNCaP cells via mitochondria-mediated apoptosis and ROS-facilitated cell death pathway, and therefore can be used as a promising prostate cancer therapeutic.

• Journal of Pharmaceutical Investigation
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• v.41 no.1
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• pp.31-36
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• 2011

$5HT_{2C}$ receptor among fourteen 5-HT subtypes plays important roles in several disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. The purpose of the study is to investigate pharmacokinetic parameters and bioavailability of a newly synthesized selective agonist of $5-HT_{2C}$ receptor, KOPC-20010 (KP10) in rats after intravenous and oral administration for the development of therapeutic anti-obesity agents. KP10 was administered orally (40 mg/kg) or intravenously (20 mg/kg), blood was collected via a catheter, and analyzed by GC/MSD. The calibration curve of KP10 in plasma and urine showed high linearity ($r^2$ >0.999). The retention times of KP10 in plasma and urine were 8.7 and 9.7 min, respectively. After oral administration of 40 mg/kg, pharmacokinetic parameters were calculated as follows; $C_{max}$ value was $1242.9{\pm}1195.5$ ng/mL at $1.1{\pm}0.6$ hr ($T_{max}$). $AUC_{0->24hr}$ and $AUC_{0>{\infty}}$ were $8034.2{\pm}960.7$ and $10464.1{\pm}681.5\;ng{\cdot}hr/mL$, respectively. The terminal half-life was $21.9{\pm}7.6$ hr. $AUC_{0->24hr}$ and $AUC_{0>{\infty}}$ were $4292.4{\pm}523.0$ and $6111.2{\pm}756.2\;ng{\cdot}hr/mL$, respectively, after 20 mg/kg of intravenous administration. The terminal half-life after intravenous administration was $25.1{\pm}9.4$ hr. Bioavailability of KP10 was determined to 86%. The excretion amount into the urine within 48 hr was approximately 4.7 to 6.7% of the dose administered. These data may be beneficial to the anti-obesity drug development of KP10.

• The Journal of Internal Korean Medicine
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• v.38 no.6
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• pp.863-876
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• 2017

Objectives: The aim of this experimental study was to evaluate the anti-neoplastic and anti-inflammatory effects of single and mixed extracts of Ulmus davidiana (UD) and Oldenlandia diffusa (OD) on azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colonic neoplasms in mice. Methods: AOM/DSS induces colitis-associated colonic neoplasms in mice. Mice were divided into seven groups: normal-no inducement and no treatment; control-colonic neoplasms with no treatment; UD-colonic neoplasms and treatment with UD; OD-colonic neoplasms and treatment with OD; UD1+OD1-colonic neoplasms and treatment with UD1 and OD1. UD1+OD2-colonic neoplasms and treatment with UD1 and OD2; UD2+OD1-colonic neoplasms and treatment with UD2 and OD1. Single and mixed preparations of UD and OD were applied to mice for six weeks. The colon length and weight and histopathologic changes of colon tissue were observed. Serum pro-inflammatory cytokines, including tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6), were determined by enzyme-linked immunosorbent assay. The mRNA expression levels of Bax, Bcl-2, and interferon-gamma ($INF-{\gamma}$) were measured by RT-PCR. Results: The colon length was significantly increased in OD, UD1+OD2, and UD2+OD1 mice, and the colon weight was significantly decreased in OD and UD1+OD2 mice. The morphological change of colon epithelial cells was more suppressed in complex-treatment groups than in single-treatment groups. The inhibitory effect on inflammatory cell invasion was especially shown in UD1+OD2 mice. The serum level of the pro-inflammatory $TNF-{\alpha}$ was decreased in all complex-treatment groups, and the IL-6 level was decreased in UD1+OD1 mice. Single-treatment groups had an increase in the mRNA expression of the pro-apoptosis regulator Bax, and UD2+OD1 decreased the mRNA expression of the anti-apoptosis regulator Bcl-2. The mRNA expression of $INF-{\gamma}$ associated with inflammation was decreased in OD and UD1+OD2 mice. Conclusions: This study suggests that single and mixed extracts of Ulmus davidiana and Oldenlandia diffusa have anti-neoplastic and anti-inflammatory effects on AOM/DSS-induced colonic neoplasms in mice. Therefore, we conclude that UD, OD, and a mixture of UD and OD are potential therapeutic agents for colitis-associated colonic neoplasms.

• Journal of fish pathology
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• v.20 no.2
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• pp.147-160
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• 2007

Four strains of water mold, ChS-E0511, RaT-E0511, RaT-A0512 and MaS-F0512, were isolated from salmonid fish and/or their eggs taken from culture farms in Yangyang, Milyang and Pyeongchang, Korea in 2005. Descriptions of their morphological aspects, the results of the phylogenetic analysis conducted, and the sequence of the small sub-unit 18S rRNAs of the isolates confirmed that they all belong to the species Saprolegnia parasitica. Only one species, ChS-E0511, which was isolated from fertilized eggs of the chum salmon, was classified as part of the S. parasiticaGroup 1 according to its oogonia and gemmae production. The chemotherapeutic effects of various chemicals on the ChS-E0511 strain were assessed from the inhibitory effects of growth in GY media and the relative ratio of eyed eggs to fertilized eggs of the rainbow trout. Malchite green, a prohibited substance in food animals, was better than others, such as the Opuntia ficus-indicaextract, 2-bronopol, and sodium chloride. These results suggest that the fungi isolated from salmonids and/or their eggs identified as S. parasitica were composed of more than two groups. These isolates will be useful in an intensive evaluation of therapeutic agents.

• Korean Journal of Food Science and Technology
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• v.43 no.5
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• pp.624-632
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• 2011

Water and ethanol extracts of 16 different Korean traditional oriental prescriptions used widely for prevention of degenerative arthritis were prepared and their total phenolic and total flavonoid contents were quantified. Additionally, antioxidant and anti-inflammatory activities of water, ethanol and enzyme-treated extracts were determined by in vitro assays. Total phenolic and total flavonoid contents of three extracts from the 16 different medicinal prescriptions varied from 10.03-78.03 and 0-16.24 mg/g, respectively. Among the three extracts of 16 different medicinal prescriptions tested, 'Mahangeuigamtang' showed the potent full term for DPPH ($RC_{50}$=71.26, 27.33, 63.00 ${\mu}g/mL$) and full term for ABTS ($RC_{50}$=21.11, 27.45, 152.11 ${\mu}g/mL$) radical scavenging activities, and its water and ethanol extracts exhibited significant cyclooxygenase-2 (COX-2) inhibitory activity (49.10 and 69.06%, respectively). Ethanol and enzyme-treated extracts of 'Euieuiintang' exerted the strongest COX-2 inhibitory activity (68.23 and 75.05%, respectively). 'Mahangeuigamtang' and 'Euieuiintang' may be useful as potential therapeutic agents for treatment of degenerative diseases, such as inflammation and aging.

• Korean Journal of Food Science and Technology
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• v.49 no.6
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• pp.710-713
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• 2017

This study evaluates the ability of corn silk (Zea mays L.) extract to function as a natural anti-inflammatory and anti-atopic therapeutic agent. The anti-inflammatory effects of corn silk were evaluated by measuring the inhibitory activities of nitric oxide (NO) and production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$. Anti-atopic effects were assessed by measuring the repression of thymus and activation-regulated chemokine (TARC). These results indicated that NICS-1 (corn silk ethanol extract) and NICS-3 (high maysin corn silk ethanol extract) functioned as anti-inflammatory agents by down-regulating LPS-induced NO and TNF-${\alpha}$. Additionally, two extracts showed weak repression of TARC expression levels in tumor necrosis factor TNF-${\alpha}$ plus IFN-${\gamma}$ induced HaCaT cells, respectively. These results suggest that corn silk extracts have anti-inflammatory and anti-atopic activities, and thus have the potential to reduce and alleviate the symptoms associated with atopic dermatitis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.117-122
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• 2014

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. Materials and Methods: We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively Results: A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). Conclusions: All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature.