During tumor progression various immunosuppressive cells are recruited to a tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are particularly abundant in TME. Based on their function, macrophages are categorized into two phenotypes: tumoricidal M1 and tumor-supportive M2. Generally, TAMs closely resemble M2-macrophages and lead to tumor growth. However, their phenotype can be changed by immune activator from M2 to M1 and thus promote tumor immunotherapy. Ginseng extracts are well known for its anti-tumor and anti-inflammatory effects from numerous reported studies. However, the mechanism of their effects is still not clear. Recently, some studies suggested that ginseng extracts induced immune activation as well as anti-tumor activities by a repolarization of activated macrophage from M2 phenotype to M1 phenotype. But, further verification about the mechanism as to how ginseng extracts can stimulate the immune response is still needed. In this study, we investigated whether ginseng extracts can alter the phenotype from M2 macrophages to M1 macrophages in mice by using a radiolabeled liposome. And we also evaluated the potential of radiolabeled liposome as a nuclear imaging agent to monitor the transition of phenotype of TAMs. In conclusion, the ginseng extracts seem to change the phenotype of macrophages from M2 to M1 like as lipopolysaccharide (LPS) in mice.
Diblock copolymers with different poly($\varepsilon$-caprolactone) (PCL) block lengths were synthesized by ringopening polymerization of $\varepsilon$-caprolactone in the presence of monomethoxy poly(ethylene glycol) (mPEG-OH, MW 2000) as initiator. The self-aggregation behaviors of the diblock copolymer nanoparticle, prepared by the diafiltration method, were investigated by using $^1H$ NMR, dynamic light scattering (DLS), and fluorescence spectroscopy. The PEG-PCL block copolymers formed the nano-sized self-aggregate in an aqueous environment by intrsa- and/or intermolecular association between hydrophobic PCL chains. The critical aggregation concentrations (cac) of the block copolymer self-aggregate became lower with increasing hydrophobic PCL block length. On the other hand, reverse trends of mean hydrodynamic diameters were measured by DLS owing to the increasing bulkiness of the hydrophobic chains and hydrophobic interaction between the PCL microdomains. The hydrodynamic diameters of the block copolymer nanoparticles, measured by DLS, were in the range of 65-270 nm. Furthermore, the size of the nanoparticles was scarcely affected by the concentration of the block copolymers in the range of 0.125-5 mg/mL owing to the negligible interparticular aggregation between the self-aggregated nanoparticles. Considered with the fairly low cac and nanoparticle stability, the PEG-PCL nanoparticles can be considered a potential candidate for biomedical applications such as drug carrier or imaging agent.
Purpose: Most patients with acute low back pain visit emergency room (ER). They mostly need beds, and if their length of stay is longer, it can become difficult to accommodate new patients at the ER. We analyzed the treatment process of patients with back pain and tried to find method for shortening of the length of stay at the ER. Methods: We retrospectively analyzed the medical records of patients with back pain who visited at our ER for one year. Patients were divided into two groups according to their length of stay at ER and were compared the charateristcs of between two groups. Results: A total of 274 patients were included in the study. Eigthy-nine patients (32.5%) were in the group with less than 3 hours and 185 patients (67.5%) were in the other group. In the comparison of the two groups according to the medical departments, the number of patients who were in group with more than 3 hours were 25 (14.0%) in the emergency department, 94 (50.5%) in neurosurgery, 66 (35.5%) in orthopedic surgery. Length of stay was significantly increased in orthopedic surgery and neurosurgery (p=0.014). In addition, the length of stay was longer when computed tomography and magnetic resonance imaging examinations were performed (p=0.000). Regardless of the type of analgesic agent, the median time to the analgesic treatment was shorter in the group with less than 3 hours (p=0.034). Conclusions: In patients with back pain who visit the ER, the emergency medicine doctor will early control the pain and do not unnecessary image examination to reduce a length of stay at the ER.
Purpose: The present study was conducted in order to examine claustrophobia, noise sensitivity and vital signs according to anxiety sensitivity level in patients who have Magnet Resonance Imaging(MRI). Methods: With 100 outpatients, we measured anxiety sensitivity, claustrophobia, noise sensitivity and vital sign before and after MRI. Measuring tools were ASI, CLQ-M, and NSI. Data were collected from February to March, 2008. Results: The ASI score was higher in women than in men(p < .05), and no statistically significant difference was observed according to age, region of scanning, experience in MRI, and the use of contrast agent. Both men and women patients showed the same ASI score and decrease in CLQ M and NSI between before and after MRI. In women, ASI, CLQ M and NSI were in positive correlation with one another(p < .001), and in men, there was no correlation between ASI and CLQ M, and positive correlation was observed with NSI(p < .05). In comparison according to ASI level, blood pressure and pulse rate were not different in men and women. CLQ M was not different in men, but was different in women(p < .001). NSI was different in both men and women(men p < .05; women p < .001). Conclusion: MRI may cause claustrophobia in patients with high anxiety sensitivity, and noise appears to aggravate anxiety. In particular, claustrophobia was more serious in women than in men. Therefore, it is necessary to develop nursing interventions to reduce anxiety sensitivity particularly for female patients, and to make plans to educate and lower noise before MRI in order to reduce claustrophobia.
Background: In the past few years, a considerable number of preclinical studies have been proposed metformin as a potential anticancer agent, but some of these studies suffer from a number of methodological limitations such as assessment of cytotoxicity in the presence of supraphysiological glucose concentrations or applying suprapharmacological levels of the drug. These objections have limited the translation of published preclinical data to the clinical setting. The present study aimed to investigate direct anticancer effects of metformin on different molecular subtypes of breast cancer with pharmacological concentrations and under normoglycemic conditions in vitro. Materials and Methods: Breast cancer cell lines from luminal A, luminal B, ErbB2 and triple-negative molecular subtypes were treated with a pharmacological concentration of metformin (2mM) at a glucose concentration of 5.5mM. Time-dependant cell viability was assessed by dye exclusion assay. MTTbased cytotoxicity assays were also performed with metformin alone or in combination with paclitaxel. Results: Metformin did not show any growth inhibitory effects or time-dependant cytotoxicity on breast cancer cell lines in the presence of normal glucose concentrations at the therapeutic plasma level. No augmentation of the antineoplastic properties of paclitaxel was apparent under the tested conditions. Conclusions: Metformin is probably unable to exert cytotoxic or cytostatic effects on breast cancer subtypes at pharmacological concentrations and normal plasma glucose levels. These results highlight the importance of establishing a higher steady-state plasma concentration of metformin in the clinical setting for assessment of anticancer effects in normoglycemic patients.
Kim, Min-Su;Yu, Dong-Woo;Jung, Young-Jin;Kim, Sang Woo;Chang, Chul-Hoon;Kim, Oh-Lyong
Journal of Korean Neurosurgical Society
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제52권6호
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pp.517-522
/
2012
Objective : Meningiomas represent 18-20% of all intracranial tumors and have a 20-50% 10-year recurrence rate, despite aggressive surgery and irradiation. Hydroxyurea, an inhibitor of ribonucleotide reductase, is known to inhibit meningioma cells by induction of apoptosis. We report the long-term follow-up result of hydroxyurea therapy in the patients with recurrent meningiomas. Methods : Thirteen patients with recurrent WHO grade I or II meningioma were treated with hydroxyurea (1000 $mg/m^2/day$ orally divided twice per day) from June 1998 to February 2012. Nine female and 4 male, ranging in age from 32 to 83 years (median age 61.7 years), were included. Follow-up assessment included physical examination, computed tomography, and magnetic resonance imaging (MRI). Standard neuro-oncological response criteria (Macdonald criteria) were used to evaluate the follow-up MRI scans. The treatment was continued until there was objective disease progression or onset of unmanageable toxicity. Results : Ten of the 13 patients (76.9%) showed stable disease after treatment, with time to progression ranging from 8 to 128 months (median 72.4 months; 6 patients still accruing time). However, there was no complete response or partial response in any patients. Three patients had progressive disease after 88, 89, 36 months, respectively. There was no severe (Grade III-IV) blood systemic disorders and no episodes of non-hematological side effects. Conclusion : This study showed that hydroxyurea is a modestly active agent against recurrent meningiomas and can induce long-term stabilization of disease in some patients. We think that hydroxyurea treatment is well tolerated and convenient, and could be considered as an alternative treatment option in patients with recurrent meningiomas prior to reoperation or radiotherapy.
Background: It was previously found that Korean Red Ginseng water extract (KRGE) inhibits the histamine-induced itch signaling pathway in peripheral sensory neurons. Thus, in the present study, we investigated whether KRGE inhibited another distinctive itch pathway induced by chloroquine (CQ); a representative histamine-independent pathway mediated by MrgprA3 and TRPA1. Methods: Intracellular calcium changes were measured by the calcium imaging technique in the HEK293T cells transfected with both MrgprA3 and TRPA1 ("MrgprA3/TRPA1"), and in primary culture of mouse dorsal root ganglia (DRGs). Mouse scratching behavior tests were performed to verify proposed antipruritic effects of KRGE and ginsenoside Rg3. Results: CQ-induced $Ca^{2+}$ influx was strongly inhibited by KRGE ($10{\mu}g/mL$) in MrgprA3/TRPA1, and notably ginsenoside Rg3 dose-dependently suppressed CQ-induced $Ca^{2+}$ influx in MrgprA3/TRPA1. Moreover, both KRGE ($10{\mu}g/mL$) and Rg3 ($100{\mu}M$) suppressed CQ-induced $Ca^{2+}$ influx in primary culture of mouse DRGs, indicating that the inhibitory effect of KRGE was functional in peripheral sensory neurons. In vivo tests revealed that not only KRGE (100 mg) suppressed CQ-induced scratching in mice [bouts of scratching: $274.0{\pm}51.47$ (control) vs. $104.7{\pm}17.39$ (KRGE)], but also Rg3 (1.5 mg) oral administration significantly reduced CQ-induced scratching as well [bouts of scratching: $216.8{\pm}33.73$ (control) vs.$115.7{\pm}20.94$ (Rg3)]. Conclusion: The present study verified that KRGE and Rg3 have a strong antipruritic effect against CQ-induced itch. Thus, KRGE is as a promising antipruritic agent that blocks both histamine-dependent and -independent itch at peripheral sensory neuronal levels.
Kim Jin Hwa;Lee Bum Chun;Kim Jin Hui;Sim Gwan Sub;Lee Dong Hwan;Lee Kyung Eun;Yun Yeo Pyo;Pyo Hyeong Bae
Archives of Pharmacal Research
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제28권2호
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pp.195-202
/
2005
Free radicals and reactive oxygen species (ROS) caused by UV exposure or other environmental factors are critical players in cellular damage and aging. In order to develop a new antiphotoaging agent, this work focused on the antioxidant effects of the extract of tinged autumnal leaves of Acer palmatum. One compound was isolated from an ethyl acetate soluble fraction of the A. palmatum extract using silica gel column chromatography. The chemical structure was identified as apigenin-8-C-beta-D-glucopyranoside, more commonly known as vitexin, by spectral analysis including LC-MS, FT-IR, UV, $^{1}H-$, and $^{13}C-NMR$. The biological activities of vitexin were investigated for the potential application of its anti-aging effects in the cosmetic field. Vitexin inhibited superoxide radicals by about $70\%$ at a concentration of $100\;{\mu}g/mL$ and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals by about $60\%$ at a concentration of $100\;{\mu}g/mL$. Intracellular ROS scavenging activity was indicated by increases in dichlorofluorescein (DCF) fluorescence upon exposure to UVB $20\;mJ/cm^2$ in cultured human dermal fibroblasts (HDFs) after the treatment of vitexin. The results show that oxidation of 5-(6-)chloromethyl-2',7'-dichlo-rodihydrofluorescein diacetate ($CM-H_{2}DCFDA$) is inhibited by vitexin effectively and that vitexin has a potent free radical scavenging activity in UVB-irradiated HDFs. In ROS imaging using a confocal microscope we visualized DCF fluorescence in HDFs directly. In conclusion, our findings suggest that vitexin can be effectively used for the prevention of UV-induced adverse skin reactions such as free radical production and skin cell damage.
A 6-year-old, intact male, mongrel dog with yellowish urine, anorexia, depression was referred to the Veterinary Medical Teaching Hospital of the Chungnam National university. Immune mediated hemolytic anemia (IMHA) was diagnosed by clinical signs, physical examination, laboratory tests (CBC, serum chemistry, Coombs' test, autoagglutination test and urinalysis) and diagnostic imaging (X-ray and ultrasonography). Clinical signs were improved after combined immune-suppressive therapy (prednisolone and cyclosporine) and prophylactic heparin therapy. A thrombus ($4cm{\times}1cm$) was observed in the right ventricle by autopsy. Combined therapy and supportive care (antithrombolytic agent and acupuncture) were effective in a dog with IMHA.
Biodistribution studies has been carried out to elucidate the cause of poor bone imagings often encountered in using $methylenediphosphonate(MDP)-^{99m}Tc$ and to establish effective conditions in using the popular bone imaging agent. After 150 minutes from the I.V. injection of $MDP-^{99m}Tc$ to mice, the radioactivities accumulated at bone(B), liver(L), and stomach(S) were counted. The radiochemical purity (RCP), the volume, the radioactivity concentration and the amount of radioactivity of $MDP-^{99m}Tc$ were controlled. Data were expressed either in %cpm/g organ or % cpm/organ. The organ distribution ratios(B/L and B/S) were correlated with the RCP, the volume of injection, the radioactivity concentration etc. Results indicated that the RCP plays a major role in biodistributions. High radioactivity concentration and injection of a small amount is recommended. Negligible effect was observed with the amount of radioactivity. It has been confirmed that the up-to-date methods of RCP determinations cannot sensitively detect the sharply affecting trace impurities. A particular biodistribution pattern of crossed B/L and B/S lines was observed in case of using $MDP-^{99m}Tc$ of low RCP. In such a case, rather a higher dosage would be effective for improving the contrast between bone and liver.
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