• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8533-8539
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• 2016

Background: B-cell chronic lymphocytic leukemia B (B-CLL), the most common type of leukemia, may be caused by apoptosis deficiency in the body. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) as providers of pro-apoptotic molecules such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can be considered as an effective anti-cancer therapy candidate. Therefore, in this study we assessed the role of tumor necrosis factor-producing mesenchymal stem cells oin apoptosis of B-CLL cells resistant to fludarabine-based chemotherapy. Materials and Methods: In this study, after isolation and culture of AD-MSCs, a lentiviral LeGO-iG2-TRAIL-GFP vector containing a gene producing the ligand pro-apoptotic with plasmid PsPAX2 and PMDG2 virus were transfected into cell-lines to generate T293HEK. Then, T293HEK cell supernatant containing the virus produced after 48 and 72 hours was collected, and these viruses were transduced to reprogram AD-MSCs. Apoptosis rates were separately studied in four groups: group 1, AD-MSCs-TRAIL; group 2, AD-MSCs-GFP; group 3, AD-MSCs; and group 4, CLL. Results: Observed apoptosis rates were: group 1, $42{\pm}1.04%$; group 2, $21{\pm}0.57%$; group 3, $19{\pm}2.6%$; and group 4, % $0.01{\pm}0.01$. The highest rate of apoptosis thus occurred ingroup 1 (transduced TRAIL encoding vector). In this group, the average medium-soluble TRAIL was 72.7pg/m and flow cytometry analysis showed a pro-apoptosis rate of $63{\pm}1.6%$, which was again higher than in other groups. Conclusions: In this study we have shown that tumor necrosis factor (TNF) secreted by AD-MSCs may play an effective role in inducing B-CLL cell apoptosis.

• Journal of Periodontal and Implant Science
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• v.39 no.sup2
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• pp.279-286
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• 2009

Purpose: Gene therapy (ex vivo) has recently been used as a means of delivering bone morphogenetic proteins (BMPs) to sites of tissue regeneration. In the present study, we investigated the effect of co-transduction of adenoviruses expressing BMP-2 and BMP-7 on osteogenesisof C2C12 cells in vitro. Methods: A replication-defective human adenovirus 5 (Ad5) containing a cDNA for BMPs in the E1 region of the virus (Ad5BMP-2 and Ad5BMP-7) was constructed by in vivo homologous recombination. Functional activity of Ad5BMP-2 and Ad5BMP-7 were evaluated in mouse stromal cells (W20-17cells). C2C12 cells are transduced with various MOI (multiplicity of infection) of Ad5BMP-2 and Ad5BMP-7 to assess most effective and stable titer. Based on this result, C2C12 cells were transduced with Ad5BMP-2 and Ad5BMP-7 alone or by combination. BMPs expression, alkaline phosphatase (ALPase) activity, cell proliferation, and mineralization were assessed. Results: Ad5BMP-2 and Ad5BMP-7 are successfully transduced to W20-17 cells, and secreted BMPs stimulated cell differentiation. Also, C2C12 cells transduced with Ad5BMPs showed expression of BMPs and increased ALPaseactivity. In all groups, cell proliferation was observed over times. At 7days, cells co-transduced with Ad5BMP-2 and Ad5BMP-7 showed lower proliferation than the others. C2C12 cells co-transduced with Ad5BMP-2 and Ad5BMP-7 had greater ALPaseactivity than that would be predicted if effect of individual Ad5BMPs were additive. Little mineralized nodule formation was detected in cells transduced with individual Ad5BMPs. In contrast, Ad5BMP-2 and Ad5BMP-7 combination stimulated mineralization after culturing for 10 days in mineralizing medium. Conclusions: Present study demonstrated that adenoviruses expressing BMPs gene successfully produced BMPs protein and these BMPs stimulated cells to be differentiated into osteoblastic cells. In addition, the osteogenic activity of Ad5BMPs can be synergistically increased by co-transduction of cells with Ad5BMP-2 and Ad5BMP-7.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3595-3604
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• 2015

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

• Applied Chemistry for Engineering
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• v.32 no.3
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• pp.312-319
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• 2021

Photothermal therapy is a treatment that necrotizes selectively the abnormal cells, in particular cancer cells, which are more vulnerable to heat than normal cells, using the heat generated when irradiating light. In this study, we synthesized a reduced graphene oxide with carboxyl groups (CRGO)-gold nanorod (AuNR) nanocomposite for photothermal treatment. Graphene oxide (GO) was selectively reduced and exfoliated at high temperature to synthesize CRGO, and the length of AuNR was adjusted according to the amount of AgNO₃, to synthesize AuNR with a strong absorption peak at 880 nm, as an ideal photothermal agent. It was determined through FT-IR, thermogravimetric and fluorescence analyses that more carboxyl groups were conjugated with CRGO over RGO. In addition, CRGO exhibited excellent stability in aqueous solutions compared to RGO due to the presence of carboxylic acid. The CRGO-AuNR nanocomposites fabricated by electrostatic interaction have an average size of ~317 nm with a narrow size distribution. It was confirmed that under radiation with a near-infrared 880 nm laser which has an excellent tissue transmittance, the photothermal effect of CRGO-AuNR nanocomposites was greater than that of AuNR due to the synergistic effect of the two photothermal agents, CRGO and AuNR. Furthermore, the results of cancer cell toxicity by photothermal effect revealed that CRGO-AuNR nanocomposites showed superb cytotoxic properties. Therefore, the CRGO-AuNR nanocomposites are expected to be applied to the field of anticancer photothermal therapy based on their stable dispersibility and improved photothermal effect.

• Korean Journal of Pharmacognosy
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• v.46 no.1
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• pp.52-58
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• 2015

Neural stem cells (NSCs), with self-renewal and neuronal differentiation capacity, are a feasible resource in cell-based therapies for various neurodegenerative diseases and neural tissue injuries. In this study, we investigated the effects of Schisandrae Fructus (SF) on proliferation and differentiation of human embryonic NSCs. Treatment with 70% ethanol extract of SF increased the viability of NSCs derived from human embryonic stem cells, which was accompanied by increased mRNA expression of cyclin D1. Whereas 70% ethanol extract of SF also decreased the mRNA expression of nestin, it increased class III ${\beta}$-tublin (Tuj-1) and MAP2 in both growth and differentiation media. Lastly, we found increased mRNA expression of BDNF in SF-treated NSCs. In conclusion, our study demonstrates for the first time that SF induced proliferation and neuronal differentiation of NSCs and increased mRNA expression of BDNF, suggesting its potential as a regulator of NSC fate in NSC-based therapy for neuronal injuries from various diseases.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.2
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• pp.111-117
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• 2006

An area of current research is investigating the app1ication of human mesenchymal stem cells or hMSCs as a cell-based regenerative therapy. In order to achieve effective bone regeneration, appropriate matrices functioning as cell-carriers must be identified and optimized in terms of function, efficacy and biocompatibility. Two methods of approaching optimization of matrices are to facilitate adhesion of the donor hMSCs and furthermore to facilitate recruitment of host progenitor cells to osteoblastic differentiation. Pleiotrophin is an extracellular matrix protein that was first identified in developing rat brains and believed to be associated with developing neuronal pathways. A recent publication by Imai and colleagues demonstrated that transgenic mice with upregulated pleiotrophin expression developed a greater volume of cortical as well as cancellous bone. The proposed mechanism of action of pleiotrophin is demonstrated here. Through either environmental stresses and/or intracellular regulation, there is an increase in pleiotrophin production. The pleiotrophin is released extracellularly into areas requiring bone deposition. A receptor-mediated process recruits host osteoprogenitor cells into these areas. Therefore, the aim of our study was to investigate the osteoconductive properties of pleiotrophin. We wanted to determine if pleiotrophin coating facilitates cellular adhesion and furthermore if this has any effect on hMSCs derived bone formation in an animal model. The results showed a dose dependent response of cellular adhesion in fibronectin samples, and cellular adhesion was facilitated with increasing pleiotrophin concentrations. Histologic findings taken after 5 weeks implantation in SCID mouse showed no presence of bone formation with only a dense fibrous connective tissue. Possible explanations for the results of the osteogenesis assay include inappropriate cell loading.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.123-129
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• 2012

Objectives : Allergy has been described as an inflammatory with hypersensitivity resulting from seasonal or perennial responses to specific allergens. The root of Platycodon grandiflorum (Jacq.) A. DC.(Platycodi Radix; Campanulaceae) has been traditionally used to treat chronic diseases such as bronchitis, asthma, pulmonary tuberculosis, inflammation and hyperlipidemia. In this study, we examined the effect of 70% ethanol extract of Platycodi Radix (PR-E) on ovalbumin (OVA)-induced airway inflammation in mice. Methods : Mice were sensitized and challenged by OVA inhalation to induced chronic airway inflammation, and then were intragastrically administered PR-E extract at doses of 50 and 200 mg/kg/day from days 21 to 30 consecutively. The levels of allergic mediators such as histamine, OVA-specific immunoglobulin (Ig) E, and cytokines such as IL-4 and IFN-${\gamma}$ were measured in the sera of mice by ELISA. The histological change of lung tissue was observed by hematoxylin and eosin (H&E) staining. Results : PR-E extract significantly decreased the serum levels of histamine, OVA-specific IgE, and Th2 cytokine, IL-4 compared with those in the OVA-induced group. PE-E extract significantly increased the serum level of Th1 cytokine, IFN-${\gamma}$. Based on lung histopathological studies, inflammatory cell infiltration and mucus hypersecretion were inhibited by PE-E extract administration compared to that in the OVA-induced group. Conclusions : These findings indicate that PE-E extract may be useful as an adjuvant therapy for the treatment of bronchial asthma.

• Journal of the Korean Burn Society
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• v.22 no.2
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• pp.45-48
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• 2019

Allogenic keratinocyte application is widely used for treatment of second degree burns. However, there is no significant body of report on application of allogenic keratinocyte to third degree burns. A geriatric patient visited our burn center showing second to third-degree burn on dorsum of her left hand. Considering the surface area and wound depth, surgery was indicated but her medical condition and age made the surgery high risk for a long operation. Therefore, chemical escharolysis, serial bedside debridement, and cultured allogenic keratinocyte (Kaloderm^®, Tegoscience, Seoul, Korea) application was done. The wound was completely epithelialized after four rounds of Kaloderm^® application. For third-degree burns where definitive surgical reconstruction is precluded due to medical comorbidity of the patient, we investigated the possibility of allogenic keratinocyte treatment which may allow to avoid high-risk anesthesia and surgery.

• Journal of Periodontal and Implant Science
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• v.33 no.3
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• pp.359-372
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• 2003

Among objectives of periodontal therapy. the principal one is the morphological and functional reconstruction of lost periodontal supporting tissues. This includes de novo formation of connective tissue attachment and the regrowth of alveolar bone. The use of enamel matrix derivative(EMD) may be a suitable means of regeneration new periodontal attachment in the infrabony defects. Implant used to replace lost tooth but, implantitis occurred after installation. The purpose of this study was to investigate the effects of EMD on differentiation and growth of osteoblast in titanium disc. Twentyfive millimeter diameter and 1mm thick Ti disc which was coated 25, 50, 100, 200${\mu}g$/ml of EMD(Emdogain(R)) used as experimental group, 25, 50, 100, 200ng/d of rhBMP-2 as positive control group, and no coat as negative control group. A human osteosarcoma cell line Saos-2 was cultured in Ti disc and cell proliferation and Alkaline phosphatase (ALP) activity were measured at 1 and 6 days. PCR was performed at 2 and 8 hours. Semi-quantitative RT-PCR for mRNA expressions of various osteoblastic differentiation markers -type I collagen, ALP, osteopontin, and bone sialoprotein - were performed at appropriate concentrations based upon the results of MTT and ALP assay. Cultured cell-disc complexes were prepared for scanning electron microscopy (SEM) at 2 hour. Data were analyzed using Mann-Whitney and repeated- measures 1-way analysis of variance(SPSS software version 10,SPSS. Chicago. IL). After culture, there was more osteoblast in EMD100${\mu}g$/ml than in EMD50, 200${\mu}g$/ml on day 6. There was significant difference in experimental and positive control group compared control group, as times go by(1 and 6 days). Alkaline phosphatase activity was different significantly in EMD100, 200${\mu}g$/ml and BMP100, 200${\mu}g$/ml on day 6. The results of reverse transcriptase-polymerase chain reaction (RT-PCR) showed that expression of mRNA for ALPase, collagen type I, osteopontin. hone sialoprotein and BMP-2 was detected at 2 hour and 8 hour in EMI 200${\mu}g$/ml subgroup and BMP100ng/ml subgroup. The results of this study suggest that application of enamel matrix derivative on osteoblast attached to titanium surface facilitate the expression of bone specific protein and the differentiation and growth of osteoblast.

• Journal of Korean Neurosurgical Society
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• v.30 no.3
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• pp.263-271
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• 2001

Objective : Glioblastomas, the most common type of primary brain tumors, are highly invasive and cause massive tissue destruction at both the tumor invading edges and in areas that are not in direct contact with glioma cells. As a result, patients with high-grade gliomas are faced with a poor prognosis. Such grim statistics emphasize the need to better understand the mechanisms that underlie glioma invasion, as these may lead to the identification of novel targets in the therapy of high grade gliomas. Protein kinase C(PKC) is a family of serine/threonine kinases and an important signal transduction enzyme that conveys signals generated by ligand-receptor interaction at the cell surface to the nucleus. PKC appears to be critical in regulating many aspects of glioma biology. The purpose of this study was to assess accurately the role of PKC in the invasion regulation of human gliomas based on hypothesis that protein kinase C(PKC) is functional in the process of glial tumor cell invasion. Method : To test this hypothesis, U-87 malignant glioma cell line intracellular PKC levels were up and down regulated and their invasiveness was tested. Intracellular PKC level was characterized using PKC activity assays. Invasion assays including barrier migration and spheroid confrontation were used to study the relationship between PKC concentration and invasiveness. Result : The cell line which were treated by PKC inhibitor tamoxifen and hypericin exhibited decreased PKC activity and decreased invasive abilities dose dependently both in matrigel invasion assay and tumor spheroid fetal rat brain aggregates(FRBA) confrontation assay. However, the cell line that was treated by PKC activator 12-O-tetradecanylphorbol-13acetate(TPA) did not exhibit increases in either PKC activity or invasive ability. Conclusion : These studies suggest that PKC may be a useful molecular target for the chemotherapy of glioblastoma and other malignancies and that a therapeutic approach based on the ability of PKC inhibitors may be helpful in preventing invasion.