• Journal of Korean Neurosurgical Society
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• v.40 no.4
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• pp.217-226
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• 2006

Malignant gliomas are the most common type of primary brain tumor and are in great need of novel therapeutic approaches. Advances in treatment have been very modest, significant improvement in survival has been lacking for many decades, and prognosis remains dismal. Despite "gross total" surgical resections and currently available radio-chemotherapy, malignant gliomas inevitably recur due to reservoirs of notoriously invasive tumor cells that infiltrate adjacent and non-adjacent areas of normal brain parenchyma. In principle, the immune system is uniquely qualified to recognize and target these infiltrative pockets of tumors cells, which have generally eluded conventional treatment approaches, In the span of the last 10 years, our understanding of the cancer-immune system relationship has increased exponentially; and yet we are only beginning to tease apart the intricacies of the central nervous system and immune cell interactions. This article reviews the complex associations of the immune system with brain tumors. We provide an overview of currently available treatment options for malignant gliomas, existing gaps in our knowledge of brain tumor immunology, and strategies that might be exploited for improved design of "custom immunotherapeutics." We will also examine major new immunotherapy approaches that are being actively investigated to treat patients with malignant glioma, and identify some current and future research priorities in this area.

• Phonetics and Speech Sciences
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• v.5 no.2
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• pp.43-51
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• 2013

English native listeners have a tendency to treat strong syllables in a speech stream as the potential initial syllables of new words, since the majority of lexical words in English have a word-initial stress. The current study investigates whether Korean (L1) - English (L2) late bilinguals perceive strong syllables in English continuous speech as word onsets, as English native listeners do. In Experiment 1, word-spotting was slower when the word-initial syllable was strong, indicating that Korean listeners do not perceive strong syllables as word onsets. Experiment 2 was conducted in order to avoid any possibilities that the results of Experiment 1 may be due to the strong-initial targets themselves used in Experiment 1 being slower to recognize than the weak-initial targets. We employed the gating paradigm in Experiment 2, and measured the Isolation Point (IP, the point at which participants correctly identify a word without subsequently changing their minds) and the Recognition Point (RP, the point at which participants correctly identify the target with 85% or greater confidence) for the targets excised from the non-words in the two conditions of Experiment 1. Both the mean IPs and the mean RPs were significantly earlier for the strong-initial targets, which means that the results of Experiment 1 reflect the difficulty of segmentation when the initial syllable of words was strong. These results are consistent with Kim & Nam (2011), indicating that strong syllables are not perceived as word onsets for Korean listeners and interfere with lexical segmentation in English running speech.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.411-416
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• 2017

Paclitaxel (PTX) is a effectively chemotherapeutic agent which is extensively able to treat the non-small cell lung, pancreatic, breast and other cancers. But it is a practically insoluble drug with water solubility less than $1{\mu}g/mL$, which restricts its therapeutic application. To overcome the problem, hyaluronic acid-complexed paclitaxel nanoemulsions (HPNs) were prepared by ionic complexation of paclitaxel (PTX) nanoemulsions and hyaluronic acid (HA) to specifically target non-small cell lung cancer. HPNs were composed of ${\small{DL}}-{\alpha}$-tocopheryl acetate, soybean oil, polysorbate 80, ferric chloride, and HA and fabricated by high-pressure homogenization. The HPNs were $85.2{\pm}7.55nm$ in diameter and had a zeta potential of $-35.7{\pm}0.25mV$. The encapsulation efficiency was almost 100%, and the PTX content was 3.0 mg/mL. We assessed the in vivo antitumor efficacy of the HPNs by measuring changes in tumor volume and body weight in nude mice transplanted with CD44-overexpressing NCI-H460 xenografts and treated with a bolus dose of saline, $Taxol^{(R)}$, PTX nanoemulsions (PNs), or HPNs at a dose of 25 mg/kg. Suppression of cancer cell growth was higher in the PN- and HPN-treated groups than in the $Taxol^{(R)}$ group. In particular, HPN treatment dramatically inhibited tumor growth, likely because of the specific tumor-targeting affinity of HA for CD44-overexpressed cancer cells. The loss of body weight and organ weight did not vary significantly between the groups. It is suggest that HPNs should be used to effective nanocarrier system for targeting delivery of non-small cell lung cancer overexpressing CD44 and high solubilization of poorly soluble drug.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7785-7792
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• 2014

Background: Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In this study a library of novel derivatives of VPA was synthesized and tested. Methods: A human liver cancer cell line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic properties were evaluated in transgenic zebrafish embryos. Results: N-valproylglycine derivatives suppressed survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They also suppressed angiogenic blood vessel formation by 80% when used between $2-20{\mu}M$ in zebrafish embryos. Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034). Conclusion: The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.585-595
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• 2018

Amitriptyline, a tricyclic antidepressant, is commonly used to treat depression and neuropathic pain, but its mechanism is still unclear. We tested the effect of amitriptyline on 5-hydroxytryptamine 3 ($5-HT_3$) receptor currents and studied its blocking mechanism because the clinical applications of amitriptyline overlapped with $5-HT_3$ receptor therapeutic potentials. Using a whole-cell voltage clamp method, we recorded the currents of the $5-HT_3$ receptor when 5-HT was applied alone or co-applied with amitriptyline in cultured NCB-20 neuroblastoma cells known to express $5-HT_3$ receptors. To elucidate the mechanism of amitriptyline, we simulated the $5-HT_3$ receptor currents using Berkeley $Madonna^{(R)}$ software and calculated the rate constants of the agonist binding and receptor transition steps. The $5-HT_3$ receptor currents were inhibited by amitriptyline in a concentration-dependent, voltage-independent manner, and a competitive mode. Amitriptyline accelerated the desensitization of the $5-HT_3$ receptor. When amitriptyline was applied before 5-HT treatment, the currents rose slowly until the end of 5-HT treatment. When amitriptyline was co-applied with 5-HT, currents rose and decayed rapidly. Peak current amplitudes were decreased in both applications. All macroscopic currents recorded in whole cell voltage clamping experiments were reproduced by simulation and the changes of rate constants by amitriptyline were correlated with macroscopic current recording data. These results suggest that amitriptyline blocks the $5-HT_3$ receptor by close and open state blocking mechanisms, in a competitive manner. We could expand an understanding of pharmacological mechanisms of amitriptyline related to the modulation of a $5-HT_3$ receptor, a potential target of neurologic and psychiatric diseases through this study.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.441-449
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• 2015

Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-${\alpha}$ in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-${\kappa}B$-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-${\beta}$ (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-${\kappa}B$ nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-${\kappa}B$ activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-${\kappa}B$ activation.

• Korean Journal of Pharmacognosy
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• v.45 no.3
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• pp.194-199
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• 2014

The roots of Paeonia lactiflora (PL) has been traditionally used as analgesic, spasmolytic and tonic in Korea, China, and Japan. As part of a search for herbal medicine to treat diabetes and obesity, we confirmed hypoglycemic effect of PL through high fat diet-induced obese and diabetic mice experiments in vivo. Treatment of ethanolic extract from PL led to a significant decrease in glucose level, which is comparable to that of an antidiabetic drug metformin. In addition, PL selectively stimulates the transcriptional activities of both peroxisome proliferator-activated receptor $(PPAR){\alpha}$ and ${\gamma}$, and inhibits enzymatic activity of protein tyrosine phosphatase 1B (PTP1B), which are predicted to be therapeutic target in treatment of type2 diabetes and obesity. Especially, the n-hexane fraction (Hx) from PL ethanol extract showed more potent activities on $PPAR{\alpha}$ and than others and exihibited moderate inhibitory activity against PTP1B.

• Archives of Plastic Surgery
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• v.38 no.5
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• pp.687-690
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• 2011

Purpose: Pemphigus vulgaris, a rare autoimmune blistering disease of the skin and mucous membranes remains a challenging disease to treat. Management is focused on immunotherapy against autoimmune antibodies that target keratinocyte cell adhesion molecules, and antibiotics preventing secondary infections. There is no established dressing protocol and skin is usually manipulated the least amount possible in order to minimize irritation. The authors suggest that early initiation of aggressive bathing and debridement of skin lesions, with nutritional support, is essential in accelerating resolution. Methods: A 40 year-old male previously diagnosed with pemphigus vulgaris was admitted due to exacerbation of mucocutaneous lesions involving the epidermis and mucosa of the whole body. Steroids, immunosuppressants, intravenous immunoglobulin and antibiotics were administrated, but infection and de-epithelialization progressed, while his general condition deteriorated with a weight loss of over 20 kilograms. The plastic surgery department intervened with daily bathing, debridement of unhealthy debris and non-traumatizing coverage of growing epithelium. Total parenteral nutrition and mobilization with rehabilitation therapy was initiated as early as possible. Results: After bathing, healthy epithelium gradually covered the patient's entire body, while his general condition improved with a corresponding weight gain of 14 kgs. Conclusion: Treatment of pemphigus vulgaris focuses on immunotherapy and infection control. However, an equal amount of attention should be laid on early intervention with daily dressings including bathing and irrigation, nutritional support, and exercise as this accelerates resolution of existing infections, promotes healthy epithelialization and leads to faster recovery.

• Korean Journal of Medicinal Crop Science
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• v.27 no.3
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• pp.173-185
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• 2019

Background: Galgeun-tang used in traditional Korean medicine, is a mixture of the medicinal plants Cinnamomi Ramulus, Ephedrae Herba and Puerariae Radix, and has been prescribed for the treatment of various ailments, including fever. Although the use of traditional medicinal herbs to treat diseases has recently increased, their safety and toxicity profiles incompletely elucidated. Thus, we evaluated Galgeun-tang's toxicity in male and female Sprague-Dawley rats. Methods and Results: Galgeun-tang (1,000, 2,000 and 4,000 mg/kg) was orally administered to rats for 13 weeks, and then, they were maintained for 4 weeks without administration (recovery period). Their clinical signs, and hematological and urinary properties, were monitored. The results showed that Galgeun-tang administeration slightly increased serum creatinine, urea nitrogen and, aspartate aminotransferase levels. Additionally, 2,000 and 4,000 mg/kg Galgeun-tang significantly increased urinary bilirubn and protein levels of male and female rats, which were restored during the recovery period. Conclusions: The no-observed-adverse-effect level of orally administered Galgeun-tang was 4,000 mg/kg in both female and male rats, and no target organs were identified. In addition, 400 mg/kg was found to be the no-observed-effect level for toxicity under the study conditions.

• Journal of Medicine and Life Science
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• v.17 no.3
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• pp.80-85
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• 2020

Urinary tract infections are among the most common infectious diseases and are the major causes of mortality and morbidity. These diseases result in many severe hospitalizations each year. Severe sepsis and septic shock are common and life-threatening medical conditions, and large cases are associated with urinary tract infection. The medical term "severe sepsis" is defined as sepsis complicated by hypotension, organ dysfunction, and tissue hypoperfusion, whereas "septic shock" is defined as sepsis complicated either by hypotension that is refractory to fluid resuscitation or by hyperlacteremia. A recent multicenter-study in Korea reported that the rate of in-hospital mortality associated with severe sepsis and septic shock was > 34%. Among the causative diseases, urogenital tract infection showed a high correlation. Moreover, it is very important that clinicians detect severe sepsis and septic shock early and treat them properly. The principles of initial treatment include provision of sufficient hemodynamic resuscitation and early administration of appropriate antibiotic therapy to mitigate uncontrolled infection. Initial resuscitation includes the use of vasopressors and intravenous fluids, and it is a key to achieve the target of initial resuscitation. Supportive care in the intensive care unit, such as glucose control, stress ulcer prophylaxis, blood transfusion, deep vein thrombosis prophylaxis, and renal replacement therapy, is also significant. We have summarized the key components in the treatment of severe sepsis and septic shock in patients with urinary tract infection. Urologists should be aware that appropriate early treatment is necessary to prevent fatal outcomes in these patients.