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Review : Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment Strategies
( Gi Su Oh ),( Hyung Jin Kim ),( Ai Hua Shen ),( Su Bin Lee ),( Dipendra Khadka ),( Arpana Pandit ),( Hong Seob So ) 대한전해질학회 2014 Electrolytes & Blood Pressure Vol.12 No.2
Cisplatin is one of the most widely used and highly effective drug for the treatment of various solid tumors; however, it has dose-dependent side effects on the kidney, cochlear, and nerves. Nephrotoxicity is the most well-known and clinically important toxicity. Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory res-ponses, are closely associated with cisplatin-induced nephrotoxicity. Even though the establishment of cisplatin-induced nephrotoxicity can be alleviated by diuretics and pre-hydration of patients, the prevalence of cisplatin nephrotoxi- city is still high, occurring in approximately one-third of patients who have under- gone cisplatin therapy. Therefore it is imperative to develop treatments that will ameliorate cisplatin-nephrotoxicity. In this review, we discuss the mechanisms of cisplatin-induced renal toxicity and the new strategies for protecting the kidneys from the toxic effects without lowering the tumoricidal activity.
( Gi-su Oh ),( Su-bin Lee ),( Anjani Karna ),( Hyung-jin Kim ),( Aihua Shen ),( Arpana Pandit ),( Seunghoon Lee ),( Sei-hoon Yang ),( Hong-seob So ) 대한결핵 및 호흡기학회 2016 Tuberculosis and Respiratory Diseases Vol.79 No.4
Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to NAD<sup>+</sup> by various quinones and thereby elevates the intracellular NAD+ levels. In this study, we examined the effect of increase in cellular NAD<sup>+</sup> levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with モ-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor β1 (TGF-β1) and モ-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: β-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-β1, α-smooth muscle actin accumulation. In addition, β-lapachone showed a protective role in TGF-β1-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that β-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-β1-induced EMT in vitro, by elevating the NAD<sup>+</sup>/NADH ratio through NQO1 activation.
Oh, Gi-Su,Kim, Hyung-Jin,Choi, Jae-Hyuck,Shen, AiHua,Choe, Seong-Kyu,Karna, Anzani,Lee, Seung Hoon,Jo, Hyang-Jeong,Yang, Sei-Hoon,Kwak, Tae Hwan,Lee, Chul-Ho,Park, Raekil,So, Hong-Seob Springer-Verlag 2014 Kidney international Vol.85 No.3
Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors. In addition to its antitumor activity, cisplatin affects normal cells and may induce adverse effects, such as ototoxicity, nephrotoxicity, and neuropathy. Various mechanisms, such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammatory responses, are critically involved in cisplatin-induced adverse effects. As NAD<SUP>+</SUP> is a cofactor for various enzymes associated with cellular homeostasis, we studied the effects of increased NAD<SUP>+</SUP> levels by means of NAD(P)H:quinone oxidoreductase 1 (NQO1) activation using a known pharmacological activator (β-lapachone) in wild-type and NQO1<SUP>−/−</SUP> mice on cisplatin-induced renal dysfunction in vivo. The intracellular NAD<SUP>+</SUP>/NADH ratio in renal tissues was significantly increased in wild-type mice co-treated with cisplatin and β-lapachone compared with the ratio in mice treated with cisplatin alone. Inflammatory cytokines and biochemical markers for renal damage were significantly attenuated by β-lapachone co-treatment compared with those in the cisplatin alone group. Notably, the protective effects of β-lapachone in wild-type mice were completely abrogated in NQO1<SUP>−/−</SUP> mice. Moreover, β-lapachone enhanced the tumoricidal action of cisplatin in a xenograft tumor model. Thus, intracellular regulation of NAD<SUP>+</SUP> levels through NQO1 activation might be a promising therapeutic target for the protection of cisplatin-induced acute kidney injury.
Oh, Gi-Su,Lee, Su-Bin,Karna, Anjani,Kim, Hyung-Jin,Shen, AiHua,Pandit, Arpana,Lee, SeungHoon,Yang, Sei-Hoon,So, Hong-Seob The Korean Academy of Tuberculosis and Respiratory 2016 Tuberculosis and Respiratory Diseases Vol.79 No.4
Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to $NAD^+$ by various quinones and thereby elevates the intracellular $NAD^+$ levels. In this study, we examined the effect of increase in cellular $NAD^+$ levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with ${\beta}$-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor ${\beta}1$ (TGF-${\beta}1$) and ${\beta}$-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: ${\beta}$-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-${\beta}1$, ${\alpha}$-smooth muscle actin accumulation. In addition, ${\beta}$-lapachone showed a protective role in TGF-${\beta}1$-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that ${\beta}$-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-${\beta}1$-induced EMT in vitro, by elevating the $NAD^+$/NADH ratio through NQO1 activation.
Deep Neck Space Infection Caused by Keratocystic Odontogenic Tumor
Oh, Ji-Su,Kim, Su-Gwan,You, Jae-Seek,Min, Hong-Gi,Kim, Ji-Won,Kim, Eun-Sik,Kim, Cheol-Man,Lim, Kyung-Seop Korean Association of Maxillofacial Plastic and Re 2014 Maxillofacial Plastic Reconstructive Surgery Vol.36 No.2
Keratocystic odontogenic tumor (KCOT) is a benign cystic intraosseous tumor of odontogenic origin. An infection of a KCOT is not common because KCOT is a benign developmental neoplasm. Moreover, a severe deep neck space infection with compromised airway caused by infected KCOT is rare. This report presents a 60-year-old male patient with a severe deep neck space infection related to an infected KCOT due to cortical bone perforation and rupture of the exudate. Treatment of the deep neck space infection and KCOT are reported.
New Therapeutic Concept of NAD Redox Balance for Cisplatin Nephrotoxicity
Oh, Gi-Su,Kim, Hyung-Jin,Shen, AiHua,Lee, Su-Bin,Yang, Sei-Hoon,Shim, Hyeok,Cho, Eun-Young,Kwon, Kang-Beom,Kwak, Tae Hwan,So, Hong-Seob Hindawi Publishing Corporation 2016 BioMed research international Vol.2016 No.-
<P>Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors. In addition to its antitumor activity, cisplatin affects normal cells and may induce adverse effects such as ototoxicity, nephrotoxicity, and peripheral neuropathy. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammatory responses are closely associated with cisplatin-induced nephrotoxicity; however, the precise mechanism remains unclear. The cofactor nicotinamide adenine dinucleotide (NAD<SUP>+</SUP>) has emerged as a key regulator of cellular energy metabolism and homeostasis. Recent studies have demonstrated associations between disturbance in intracellular NAD<SUP>+</SUP> levels and clinical progression of various diseases through the production of reactive oxygen species and inflammation. Furthermore, we demonstrated that reduction of the intracellular NAD<SUP>+</SUP>/NADH ratio is critically involved in cisplatin-induced kidney damage through inflammation and oxidative stress and that increase of the cellular NAD<SUP>+</SUP>/NADH ratio suppresses cisplatin-induced kidney damage by modulation of potential damage mediators such as oxidative stress and inflammatory responses. In this review, we describe the role of NAD<SUP>+</SUP> metabolism in cisplatin-induced nephrotoxicity and discuss a potential strategy for the prevention or treatment of cisplatin-induced adverse effects with a particular focus on NAD<SUP>+</SUP>-dependent cellular pathways.</P>
Oh, Gi-Su,Pae, Hyun-Ock,Choi, Byung-Min,Kwon, Ji-Wung,Yun, Yeong-Ho,Choi, Jeong-Ho,Kwon, Tae-Oh,Park, Young-Chul,Chung, Hun-Teag The Korean Association of Immunobiologists 2003 Immune Network Vol.3 No.3
Background: The mushroom Phellinus linteus (PL) has been shown to have the anti-tumor and immunostimulatory effects. We hypothesized that the hot water extract of PL (WEPL) exerts its significant immunostimulatory effect by inducing production of the Th1-derived cytokine interferon-${\gamma}$ (IFN-${\gamma}$) by T lymphocytes. Methods: T lymphocytes were isolated from the mice fed with 200 mg/kg of WEPL once a day for 4 weeks, and then stimulated with the mitogen concanavaline A (Con A). IFN-${\gamma}$ gene and intracellular protein expressions were analyzed by RT-PCR and flow cytometry, respectively. The production of IFN-${\gamma}$ was measured by enzyme-linked immunosorbent assay. Results: WEPL significantly enhanced the transcription of IFN-${\gamma}$ mRNA. The effect of WEPL on IFN-${\gamma}$ expression was further supported by a concomitant increase in the number of cells with intracellular IFN-${\gamma}$ protein as well as the secretion of IFN-${\gamma}$. However, WEPL did not modulate either gene expression or protein secretion of interleukin-4, a Th2-associated cytokine, by Con A-stimulated T lymphocytes. Conclusion: Our results demonstrate that one of the potentially beneficial anti-tumor and immunostimulatory effects of WEPL may be mediated through the enhancement of IFN-${\gamma}$ secretion by T lymphocytes.
Su Gyeong Jun,Gi Eun Hwang,Gil Su Jang,Oh Hun Kwon,Tae Young Kwon,Ji Hee Kim,Jeung Keun Suh 한국인간·식물·환경학회 2014 인간식물환경학회지 Vol.17 No.1
This study was conducted to evaluate 35 units of genetic resources collected from Hungary in 1999, and identify their horticultural traits and select useful resources. A comparison with ‘Geumdang’ and ‘Superbigarim’, the two varieties of Korean origin now being marketed indicated that the durations of time involved in flowering were largely similar to each other, and that the stem length of the Korean varieties averaged 163 cm, comparing with that of Hungarian varieties that averaged 133 cm. As for the fruit shape, the sweet banana type which was similar to the Korean counterpart accounted for 83%, ranking a top, followed by smaller varieties of which the cherry type accounted for 14% of the total. The hungarian varieties averaged 34.7 g in weight, a level significantly heavier than the Korean counterparts that averaged 25 g. As regards the ASTA value, 9 resources registered 100 or over, and as regards sugar contents, 4 resources reached 15% or over. As for capsaicinoid contents, 69% of the resources reached 10 mg% or lower, and 17% reached 10~40 mg%, followed by the group of 49 mg% or over that accounted for 14%. As a rule, the resources sampled for the current study were relatively less hot in taste. 본 연구는 1999년 헝가리에서 수집한 고추 유전자원 35점을 평가하여 원예적 형질을 조사하고 유용한 자원을 선발하고자 실시하였다. 한국시판 대비 품종 ‘금당’과 ‘슈퍼비가림’과 비교했을 때 개화소요일은 거의 유사하였으며, 초장은 한국 품종이 평균 163cm이었으나 헝가리 자원은 133cm로 작게 조사되었다. 과형은 한국 품종과 유사한 sweet banana형이 83%로 가장 많았고, 소형은 cherry형이 14%였다. 과중은 대체로 한국 품종 25g에 비해 무거워 평균 34.7g이었다. ASTA 값은 100이상이 9자원이었으며, 당함량은 15% 이상이 4자원이었다. Capsaicinoids 함량은 10mg% 이하인 자원이 69%, 10~40mg%가 17%, 40mg% 이상은 14%로 대부분 매운맛 성분이 적은 자원이었다.