Interstitial therapy using biodegradable polymeric device loaded with anticancer agent can deliver the drug to the tumor site at high concentration, resulting in an increase of therapeutic efficacy. 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) is most commonly used as chemotherapeutic agent for brain tumors. The design of implantable device is regarded as an important factor lot the efficient delivery of antitumor agent to targeting site. In order to control the release profile of drug, the release pattern of BCNU with the changes of various dimension and additives was investigated. The PLGA wafers containing 3.85, 10, 20 and 30% of BCNU were prepared in various shape (diameter of 3, 5 and 10 mm, thickness of 0.5, 1 and 2 mm) by direct compression method. In vitro drug release profile of BCNU-loaded PLGA wafers could be controlled by changing the dimension of wafers such as initial drug content, weight, diameter, thickness, volume and surface area of wafers, as well as PLGA molecular weight and additives. Drug release from BCNU-loaded PLGA wafers was facilitated with an increase of BCNU-loading amount or presence of poly(N-vinylpyrrolidone)(PVP) or sodium chloride (NaCl). The effects of various geometric factors and additives on the BCNU release pattern were confirmed by the investigation of mass loss and morphology of BCNU-loaded PLGA wafers.
Objective : Despite advances in the understanding of tumor biology and the tumor immunology, there has been no effective treatment. The Intercellular adhesion molecule-1(ICAM-1) has been shown to be important in interaction involving cells of the immune system and to be upregulated in a number of cell culture systems by cytokines, including immune interferon($IFN-{\gamma}$) and tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$). ICAM-1 has been identified as one of the ligands for lymphocyte function-associated antigen-1(LFA-1). The effectiveness of various cytokines to ICAM-1 induction on cultured human glioblastoma cell lines and potential efficacy of immunotherapy were studied. Method : Human glioblastoma cell lines, U-251 MG, U-373 MG were trypsinized and suspended at $1{\times}10^5cells/ml$ and grown on 8 well chamber slide, the cells were incubated in 0.3ml medium alone or medium containing $IFN-{\gamma}$(1000U/ml) or $TNF-{\alpha}$(250U/ml) or $IFN-{\gamma}$ plus $TNF-{\alpha}$ for 6, 12, 24, 48 and 72 hours. The coverslip were then removed and stained with a 1/30 dilution of anti-ICAM-1 antibody. Result : Surface antigen expression of ICAM-1 was increased by incubating glioblastoma cell lines with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\gamma}$ and $TNF-{\alpha}$ has induced more ICAM-1 expression on glioblastoma cell lines. Upregulation of ICAM-1 expression in an established glioblastoma cell line was of greater magnitude and more rapid following incubation with $IFN-{\gamma}$ plus $TNF-{\alpha}$. Surface antigen expression of ICAM-1 was increased for up to 48 hours after cytokine treatment on both cell lines(p<0.05). There was no difference on both cell lines(p>0.05). Conclusion : The results of the present study indicate that ICAM-1 expression in glioblastoma cell lines, U-251 MG and U-373 MG, are induced and enhanced after treatment with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\alpha}$ and $TNF-{\gamma}$ is stronger and more rapid than $IFN-{\gamma}$ or $TNF-{\alpha}$ alone.
Lee, Hyesook;Park, Cheol;Kwon, Da Hye;Hwangbo, Hyun;Kim, So Young;Kim, Min Yeong;Ji, Seon Yeong;Kim, Da Hye;Jeong, Jin-Woo;Kim, Gi-Young;Hwang, Hye-Jin;Choi, Yung Hyun
Nutrition Research and Practice
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v.15
no.6
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pp.686-702
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2021
BACKGROUND/OBJECTIVES: Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages. MATERIALS/METHODS: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E2 (PGE2), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model. RESULTS: The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae. CONCLUSIONS: Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage.
Background: Accurate mediastinal lymph node staging is vital for the optimal therapy and prognostication of patients with lung cancer. This study aimed to determine the preoperative risk factors for pN2 disease, as well as its incidence and long-term outcomes, in patients with clinical N0-1 non-small cell lung cancer. Methods: We retrospectively analyzed patients who were treated surgically for primary non-small cell lung cancer from November 2005 to December 2014. Patients staged as clinical N0-1 via chest computed tomography (CT) and positron emission tomography (PET)-CT were divided into two groups (pN0-1 and pN2) and compared. Results: In a univariate analysis, the significant preoperative risk factors for pN2 included a large tumor size (p=0.083), high maximum standard uptake value on PET (p<0.001), and central location of the tumor (p<0.001). In a multivariate analysis, central location of the tumor (p<0.001) remained a significant preoperative risk factor for pN2 status. The 5-year overall survival rates were 75% and 22.9% in the pN0-1 and pN2 groups, respectively, and 50% and 78.2% in the patients with centrally located and peripherally located tumors, respectively. In a Cox proportional hazard model, central location of the tumor increased the risk of death by 3.4-fold (p<0.001). Conclusion: More invasive procedures should be considered when preoperative risk factors are identified in order to improve the efficacy of diagnostic and therapeutic plans and, consequently, the patient's prognosis.
The cytidine analog decitabine (DEC) acts as a nucleic acid synthesis inhibitor, whereas ammonium pyrrolidine dithiocarbamate (PDTC) is an inhibitor of nuclear factor-${\kappa}B$. The aim of this study was to investigate the possible synergistic inhibitory effect of these two inhibitors on proliferation of human gastric cancer AGS cells. The inhibitory effect of PDTC on AGS cell proliferation was significantly increased by DEC in a concentration-dependent manner, and this inhibition was associated with cell cycle arrest at the G2/M phase and the induction of apoptosis. This induction of apoptosis by the co-treatment with PDTC and DEC was related to the induction of DNA damage, as assessed by H2AX phosphorylation. Further studies demonstrated that co-treatment with PDTC and DEC induced the disruption of mitochondrial membrane potential, increased the generation of intracellular reactive oxygen species (ROS) and the expression of pro-apoptotic Bax, and down-regulated the expression of anti-apoptotic Bcl-2, ultimately resulting in the release of cytochrome c from the mitochondria into the cytoplasm. Co-treatment with PDTC and DEC also activated caspase-8 and caspase-9, which are representative caspases of the extrinsic and intrinsic apoptosis pathways. Co-treatment also activated caspase-3, which was accompanied by proteolytic degradation of poly (ADP-ribose) polymerase. Taken together, these data clearly indicated that co-treatment with PDTC and DEC suppressed the proliferation of AGS cells by increasing DNA damage and activating the ROS-mediated extrinsic and intrinsic apoptosis pathways.
The aims of this study was to investigate the effect of the Tele-rehabilitation service on health promotion and quality of life for individuals with disability. The subjects were 3 men who agreed with participating in service and were assessed of health promotion level with physical/psychological scales and quality of life. The service consists of 20 sessions for 13 weeks. The results are as follows: First, all participants improved psychosocial health promotion (subjective health level) factor. Second, physical health promotion (upper limb function, strength, range of motion) maintained and improved, but there was little change. Third, the quality of life was higher than before. In addition, qualitative research showed that participants experienced a positive change in subjective health status, emotional stability, benefit, and self efficacy, and they were satisfied with the service. Based on the results, it was shown that participation helps improve the health and quality of life of the individuals with disability in the community. This study can be used it as a basic data for establishing a Tele-rehabilitation service for individuals with disability in local community.
Lee, Mi Rim;Bae, Su Ji;Kim, Ji Eun;Song, Bo Ram;Choi, Jun Young;Park, Jin Ju;Park, Ji Won;Kang, Mi Ju;Choi, Hyeon Jun;Choi, Young Whan;Kim, Kyung Mi;Hwang, Dae Youn
Laboraroty Animal Research
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v.34
no.4
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pp.288-294
/
2018
A few clues about correlation between endoplasmic reticulum (ER) stress and mulberry (Morus alba) leaves were investigated in only the experimental autoimmune myocarditis and streptozotocin-induced diabetes. To investigate whether a novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) could suppress ER in fatty liver, alterations in the key parameters for ER stress response were measured in high fat diet (HFD)-induced obese C57L/6 mice treated with EMfC for 12 weeks. The area of adipocytes in the liver section were significantly decreased in the HFD+EMfC treated group as compared to the HFD+Vehicle treated group, while their level was higher in HFD+Vehicle treated group than No treated group. The level of the eukaryotic initiation factor 2 alpha ($eIF2{\alpha}$) and inositol-requiring enzyme 1 beta ($IRE1{\alpha}$) phosphorylation and CCAAT-enhancer-binding protein homologous protein (CHOP) expression were remarkably enhanced in the HFD+Vehicle treated group. However, their levels were restored in the HFD+EMfC treated group, although some differences were detected in the decrease rate. Similar recovery was observed on the ER stress-induced apoptosis. The level of Caspase-3, Bcl-2 and Bax were decreased in the HFD+EMfC and HFD+orlistat (OT) treated group compared to the HFD+Vehicle treated group. The results of the present study therefore provide first evidence that EMfC with the anti-obesity effects can be suppressed ER stress and ER stress-induced apoptosis in the hepatic steatosis of HFD-induced obesity model.
Purpose: To evaluate the efficacy of antibiotic-loaded cement spacers (ALCSs) for the treatment of diabetic foot infections with osteomyelitis as a salvage procedure and to analyze the risk factors of treatment failure. Materials and Methods: This study reviewed retrospectively 39 cases of diabetic foot infections with osteomyelitis who underwent surgical treatment from 2009 to 2017. The mean age and follow-up period were $62{\pm}13years$ and $19.2{\pm}23.3months$, respectively. Wounds were graded using the Wagner and Strauss classification. X-ray, magnetic resonance imaging (or bone scan) and deep tissue cultures were taken preoperatively to diagnose osteomyelitis. The ankle-brachial index, toe-brachial index (TBI), and current perception threshold were checked. Lower extremity angiography was performed and if necessary, percutaneous transluminal angioplasty was conducted preoperatively. As a surgical treatment, meticulous debridement, bone curettage, and ALCS placement were employed in all cases. Between six and eight weeks after surgery, ALCS removal and autogenous iliac bone graft were performed. The treatment was considered successful if the wounds had healed completely within three months without signs of infection and no additional amputation within six months. Results: The treatment success rate was 82.1% (n=32); 12.8% (n=5) required additional amputation and 5.1% (n=2) showed delayed wound healing. Bacterial growth was confirmed in 82.1% (n=32) with methicillin-resistant Staphylococcus aureus being the most commonly identified strain (23.1%, n=9). The lesions were divided anatomically into four groups; the largest number was the toes: (1) toes (41.0%, n=16), (2) metatarsals (35.9%, n=14), (3) midfoot (5.1%, n=2), and (4) hindfoot (17.9%, n=7). A significant difference in the Strauss wound score and TBI was observed between the treatment success group and failure group. Conclusion: The insertion of ALCSs can be a useful treatment option in diabetic foot infections with osteomyelitis. Low scores in the Strauss classification and low TBI are risk factors of treatment failure.
Journal of the Korean Applied Science and Technology
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v.36
no.1
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pp.208-216
/
2019
The purpose of this study was to investigated the biological activities such as cytotoxic, anti-oxidant and anti-inflammatory using Mentha arvensis L. extracts. Mentha arvensis L. was prepared by extracting with DW and 80% ethanol, after cell viability was assessed by MTT assay using RAW 264.7 cells. Antioxidant activities, and Anti-inflammatory activities measured through changes in the levels of reactive oxygen species (ROS), nitric oxide (NO), leukotrien B4 (LTB4), and anti- or in-flammatory cytokines($IL-1{\beta}$, IL-6, tumor necrosis factor $(TNF)-{\alpha}$, and IL-10) on LPS-induced RAW 264.7 cells. All test measured by ELISA reader and Luminex. Mentha arvensis L. was no cytotoxic in water and 80% ethanol extracts, and Concentration of 100 ug/ml of 80% ethanol extract was suppressed the productions of ROS in LPS-induced RAW 264.7 cells. Also, Productions of NO, LTB4, inflammatory or anti-inflammatory cytokines showed efficacy change that dose-independent of all extracts. In other words, Mentha arvensis L. showed significant biological activities showing anti-inflammatory, and anti-oxidant. These results may be developed as a raw material for new health food and therapeutics to ease the symptoms mentioned above.
Kim, Jun-Hoe;Phi, Ji Hoon;Lee, Ji Yeoun;Kim, Kyung Hyun;Park, Sung-Hye;Choi, Young Hun;Cho, Byung-Kyu;Kim, Seung-Ki
Brain Tumor Research and Treatment
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v.6
no.2
/
pp.60-67
/
2018
Background Recently, modern technology such as diffusion tensor imaging (DTI), neuro-navigation and intraoperative neurophysiological monitoring (IOM) have been actively adopted for the treatment of thalamic tumors. We evaluated surgical outcomes and efficacy of the aforementioned technologies for the treatment of pediatric thalamic tumors. Methods We retrospectively reviewed clinical data from 37 children with thalamic tumors between 2004 and 2017. There were 44 operations (27 tumor resections, 17 biopsies). DTI was employed in 17 cases, neuro-navigation in 23 cases and IOM in 14 cases. All diagnoses were revised according to the 2016 World Health Organization Classification of Tumors of the Central Nervous System. Progression-free survival (PFS) and overall survival (OS) rates were calculated, and relevant prognostic factors were analyzed. The median follow-up duration was 19 months. Results Fifteen cases were gross total resections (GTR), 6 subtotal resections (STR), and 6 partial resections (PR). Neurological status did not worsen after 22 tumor resections. There were statistically significant differences in terms of the extent of resection between the groups with DTI, neuro-navigation and IOM (n=12, GTR or STR=12) and the group without at least one of the three techniques (n= 15, GTR or STR=9, p=0.020). The mean PFS was $87.2{\pm}38.0$ months, and the mean OS $90.7{\pm}36.1$ months. The 5-year PFS was 37%, and the 5-year OS 47%. The histological grade ($p{\leq}0.001$) and adjuvant therapy (done vs. not done, p=0.016) were significantly related to longer PFS. The histological grade (p=0.002) and the extent of removal (GTR/STR vs. PR/biopsy, p=0.047) were significantly related to longer OS. Conclusion Maximal surgical resection was achieved with acceptable morbidity in children with thalamic tumors by employing DTI, neuro-navigation and IOM. Maximal tumor resection was a relevant clinical factor affecting OS; therefore, it should be considered the initial therapeutic option for pediatric thalamic tumors.
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