• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5371-5374
• /
• 2013

Objective: Photodynamic therapy (PDT) is an emerging therapeutic procedure suitable for the treatment of cervical cancer. However, the side effects of PDT are severe, including skin ulceration, so we designed an experiment to examine the effects of multiple low-dose photodynamic therapy of 5, 10, 15, 20-tetrakis(1-methylpyridinium-4-yl) porphyrin (Tmpyp4) on tumour growth by utilizing a model in nude mice implanted with Hela cervical cancer cells. Materials and Methods: Female BALB/c nude mice (aged 5-6 weeks, weighing 18-20 g) were used. Hela cervical cancer cells were injected subcutaneously ($1{\times}10^7cells/200{\mu}L$). Ten days after injection, the mice were divided into three groups (n=6), the A group of controls without any treatment, the B group receiving a single-treatment with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation (blue laser, $108J/cm^2$), and the C group given three-treatments with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation at intervals of two days. After starting treatment, tumours were measured every two days, to assess growth. At 2 weeks after the last treatment of C group, tumour tissue and organs were collected from each mouse to evaluate tumor histology and organ damage. Results: Tumour growth in C group was significantly inhibited compared with A and B groups (P<0.05), without any injury to the skin and internal organs. Conclusion: Our novel findings demonstrated that multiple low-dose photodynamic therapy of Tmpyp4 could inhibit cervical cancer growth significantly with no apparent side effects.

• IMMUNE NETWORK
• /
• v.15 no.3
• /
• pp.135-141
• /
• 2015

Dysfunction of gut immune regulation is involved in mucosal damage in inflammatory bowel disease (IBD). However, there is still no efficacious immune-regulator for the treatment of IBD. Alloferon is a novel immune-modulatory peptide that was originally isolated from infected insects. It shows anti-inflammatory effects by the regulation of cytokine production by immune cells and their activities. Therefore, we investigated the effect of alloferon in a mouse model of colitis using dextran sulfate sodium (DSS). Colitis was induced by administration of DSS in drinking water for 7 consecutive days. It was confirmed by the presence of weight loss, diarrhea, hematochezia, and colon contraction. Alloferon was injected 4 days after DSS administration. We found that alloferon improved the pathogenesis of IBD based on the reduced disease activity index (DAI) and colon contraction. Edema, epithelial erosion, and immune cell infiltration were found in mice administered DSS, but the phenomena were reduced following alloferon treatment. The plasma level of IL-6, a classical pro-inflammatory cytokine in colitis, was also decreased by alloferon. Moreover, alloferon inhibited the TNF-${\alpha}$-induced degradation and phosphorylation of $I{\kappa}B$ in Colo205 colon cancer cells. Taken together, these results show that alloferon has anti-inflammatory effects and attenuates DSS-induced colitis.

• IMMUNE NETWORK
• /
• v.12 no.4
• /
• pp.155-164
• /
• 2012

It is well established that blocking the interaction of EGFR with growth factors leads to the arrest of tumor growth, resulting in tumor cell death. ER414 is a human monoclonal antibody (mAb) derived by guided selection of the mouse mAb A13. The ER414 exhibited a ~17-fold lower affinity and, as a result, lower efficacy of inhibition of the EGF-mediated tyrosine phosphorylation of EGFR when compared with mAb A13 and cetuximab. We performed a stepwise in vitro affinity maturation to improve the affinity of ER414. We obtained a 3D model of ER414 to identify the amino acids in the CDRs that needed to be mutated. Clones were selected from the phage library with randomized amino acids in the CDRs and substitution of amino acids in the HCDR3 and LCDR1 of ER414 led to improved affinity. A clone, H3-14, with a ~20-fold increased affinity, was selected from the HCDR3 randomized library. Then three clones, ER2, ER78 and ER79, were selected from the LCDR1 randomized library based on the H3-14 but did not show further increased affinities compared to that of H3-14. Of the three, ER2 was chosen for further characterization due to its better expression than others. We successfully performed affinity maturation of ER414 and obtained antibodies with a similar affinity as cetuximab. And antibody from an affinity maturation inhibits the EGF-mediated tyrosine phosphorylation of EGFR in a manner similar to cetuximab.

• The Korea Journal of Herbology
• /
• v.30 no.3
• /
• pp.35-40
• /
• 2015

Objectives : Zizyphus jujube (ZJ) has been used as a traditional medicine for various diseases. However, the inhibitory effect of ZJ on intestinal inflammation has not been fully understood, yet. The aim of this study is to investigate anti-colitis activity of ZJ in dextran sulfate sodium (DSS)-induced colitis mouse model. Methods : To investigate the protective effects of ZJ,the colitis mice were induced by drinking water containing 5% DSS for 7 days. Mice were randomized into groups receiving ZJ (500 mg/kg), sulfasalazine (SFZ) (150 mg/kg) as a positive control, or water as a negative control. We assayed the effects of ZJ on DSS-induced the clinical signs, measuring weight loss, colon length and disease activity index (DAI). Additionally, to find a possible explanation for the anti-inflammatory effects of ZJ, we evaluated the effects of ZJ on the production of prostaglandin $E_2$ ($PGE_2$) and expression of cyclooxygenase (COX)-2 in colitis tissue. Results : The results showed that mice treated with DSS showed considerable clinical signs, including weight loss, and reduced colon length. However, administration of ZJ significantly reduced the weight loss, shortens colon length, and improved DAI as clinical symptoms. Moreover, ZJ inhibited the $PGE_2$ production and COX-2 expression levels in DSS-treated colon tissues. Conclusions : Collectively, the findings of this study provide us with novel insights into the pharmacological actions of ZJ as a potential molecule for use in the treatment of intestinal inflammation including ulcerative colitis.

• Journal of Korean Neurosurgical Society
• /
• v.37 no.2
• /
• pp.129-136
• /
• 2005

Objective: Currently available therapies for human malignant gliomas have limited efficacy. Toxoplasma gondii, an obligate intracellular protozoan parasite, and Quil-A are nonspecific, potent immune stimulants. T. gondii is shown to have antitumor activity in some types of cancers. Therefore, this study is undertaken to evaluate the antitumor effect of Toxoplasma lysate antigen (TLA), alone or in combination with Quil-A, on human glioma U373MG and U87MG cells. Methods: The in vitro effects of TLA alone or in combination with Quil-A on the proliferation, invasion, and apoptosis of glioma cells were tested using MTT, Matrigel invasion, and DNA fragmentation assays, and the in vivo effects on the growth of gliomas were evaluated in athymic nude mice transplanted with glioma cells. Results: Treatment with TLA resulted in the suppressed proliferation and invasion of both U373MG and U87MG cells, in a dose-dependent manner. In addition, at high concentration, TLA induced glioma cell apoptosis. When TLA was administered in the mouse glioma model, malignant glioma growth was decreased. The combined treatment of TLA with Quil-A significantly inhibited the proliferation and invasion of cultured cells as well as tumor mass of implanted mice. Conclusion: TLA inhibits the proliferation and invasion of glioma cells in vitro and in vivo, and these antitumor effects of TLA are significantly enhanced by the addition of Quil-A.

• Nutrition Research and Practice
• /
• v.6 no.4
• /
• pp.322-327
• /
• 2012

This study investigated the hypothesis that a sorghum extract exerts anti-diabetic effects through a mechanism that improves insulin sensitivity via peroxisome proliferator-activated receptor gamma (PPAR-${\gamma}$) from adipose tissue. Seven C57BL/6 mice were fed an AIN-93M diet with fat consisting of 10% of total energy intake (LF) for 14 weeks, and 21 mice were fed a high-fat AIN diet with 60% of calories derived from fat (HF). From week 8, the HF diet-fed mice were orally administered either saline (HF group), 0.5% (0.5% SE group), or 1% sorghum extract (1% SE group) for 6 weeks (n = 7/group). Perirenal fat content was significantly lower in the 0.5% SE and 1% SE groups than that in the HF mice. Levels of total and low-density lipoprotein cholesterol, triglycerides, glucose, and the area under the curve for glucose were significantly lower in mice administered 0.5% SE and 1% SE than those in HF mice. Serum insulin level was significantly lower in mice administered 1% SE than that in HF mice or those given 0.5% SE. PPAR-${\gamma}$ expression was significantly higher, whereas the expression of tumor necrosis factor-${\alpha}$ was significantly lower in mice given 1% SE compared to those in the HF mice. Adiponectin expression was also significantly higher in mice given 0.5% SE and 1% SE than that in the HF mice. These results suggest that the hypoglycemic effect of SE may be related with the regulation of PPAR-${\gamma}$-mediated metabolism in this mouse model.

• BMB Reports
• /
• v.48 no.7
• /
• pp.419-425
• /
• 2015

Ginseng has been widely used for therapeutic and preventive purposes for thousands of years. However, orally administered ginseng has very low bioavailability and absorption in the intestine. Therefore, fermented ginseng was developed to enhance the beneficial effects of ginseng in the intestine. In this study, we investigated the molecular mechanisms underlying the anti-inflammatory activity of fermented wild ginseng (FWG). We found that FWG significantly alleviated the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis mouse model, and decreased expression level of pro-inflammatory cytokines in colonic tissue. Moreover, we observed that FWG suppressed the infiltration of macrophages in DSS-induced colitis. FWG also attenuated the transcriptional activity of nuclear factor-κB (NF-κB) by reducing the translocation of NF-κB into the nucleus. Our data indicate that FWG contains anti-inflammatory activity via NF-κB inactivation and could be useful for treating colitis. [BMB Reports 2015; 48(7): 419-425]

• 한국약용작물학회:학술대회논문집
• /
• 2006.04a
• /
• pp.137-149
• /
• 2006

Amyloid beta ($A{\beta}$) is believed one of the major pathogens of Alzheimer's disease (AD), and the reduction of $A{\beta}$ is considered a primary therapeutic target. Immunization with $A{\beta}$ can reduce $A{\beta}$ burden and pathological features in transgenic AD model mouse. This means $anti-A{\beta}$ autoantibodies may have a role in AD pathology. Recent findings suggest $anti-A{\beta}$ autoantibodies level decrease in AD patients. The early detection of AD is important for treatment of this disease. However, diagnosis on AD has only been possible through limited methods such as neuropsychological examination or MRI. To investigate whether it was possible to detect the presence and different levels of naturally occurring $anti-A{\beta}$ autoantibodies in the plasma of patients with AD and age-matched controls. An advanced ELISA was performed to detect levels of naturally occurring $anti-A{\beta}$ autoantibodies in the plasma. The level of $anti-A{\beta}$ auto-antibodies from patients with idiopathic Parkinson's disease or stroke and from normal controls were compared to that of AD patients. Our results showed a significantly lower $anti-A{\beta}$ autoantibodies level in AD compared to those with other neurological diseases or control. The level of $anti-A{\beta}$ autoantibodies in the serum may be used to diagnose the presence of AD.

• Proceedings of the Korean Vacuum Society Conference
• /
• 2014.02a
• /
• pp.411.1-411.1
• /
• 2014

This study evaluates the utility of an antibacterial microneedle composed of green tea extract (GT) and hyaluronic acid (HA), for the efficient delivery of GT. These microneedles have the potential to be a patient-friendly method for the conventional sustained release of drugs. In this study, a fabrication method using a mold-based technique to produce GT/HA microneedles with a maximum area of ${\sim}60mm^2$ with antibacterial properties was used to manufacture transdermal drug delivery systems. Fourier transform infrared (FTIR) spectrometry was carried out to observe the potential modifications in the microneedles, when incorporated with GT. The degradation rate of GT in GT/HA microneedles was controlled simply by adjusting the HA composition. The effects of different ratios of GT in the HA microneedles were determined by measuring the release properties. In HA microneedles loaded with 70% GT (GT70), a continuous higher release rate were sustained for 72 h. The in vitro cytotoxicity assays demonstrated that GT/HA microneedles are not generally cytotoxic to chinese hamster ovary cells (CHO-K1), human embryonic kidney cells (293T), and mouse muscle cells (C2C12), which were treated for 12 and 24 h. Antimicrobial activity of the GT/HA microneedles was demonstrated by ~95% growth reduction of gram negative [Escherichia coli (E. coli), Pseudomonas putida (P. putida) and Salmonella typhimurium (S. typhimurium)] and gram positive bacteria [Staphylococcus aureus (S. Aureus) and Bacillus subtilis (B. subtilis)], with GT70. Furthermore, GT/HA microneedles reduced bacterial growth in the infected skin wound sites and improved skin wound healing process in rat model.

• Herbal Formula Science
• /
• v.19 no.2
• /
• pp.11-22
• /
• 2011

Objectives : Hwangyeonhaedok-tang(HHDT) has been traditionally used for various clinical symptoms associated with gastrointestinal disorder, cardiovascular diseases, and inflammation in the Oriental medicine. However, little is known for antioxidant and anti-inflammatory effects of HHDT on dextran-sulfate sodium(DSS)-induced colitis in mice. Methods : In this study, we investigated an antioxidant and anti-inflammatory effects of HHDT on DSS-induced colitis in mice. An experimental colitis was induced by daily treatment with 5% DSS. HHDT was orally administrated the various concentrations(25-100 mg/kg, body weight/day) for 7 days with one time per day. Results : HHDT reduced significantly clinical sign of DSS-induced colitis, including body weight loss, shorten colon length, disease activity index(DAI), and histological colon injury. HHDT also inhibited significantly serum NO and prostaglandine $E_2(PGE_2)$ productions in DSS-induced colitis mice. Furthermore, HDDT increased significantly an superoxide anion(SOD), catalase, and glutathione peroxidase(GPx) activity of the colon tissue in DSS-induced colitis mice. Conclusions : These results suggest that HHDT administration could reduce significantly the clinical signs and inflammatory mediators, and increase antioxidant activity in DSS-induced colitis model mice and is a good candidate for further evaluation as an effective anti-ulcerative agent.