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국산 백굴채 엑스의 급성 경구독성과 항암작용에 관한 연구
김정훈,김영옥,박찬봉,채병숙,강태욱,안영근 원광대학교 식품약품안전성연구소 1995 食品藥品安全性硏究 Vol.8 No.-
The MeOH and H_2O extracts of Chelidoni Herba were examined for acute oral toxicity in mice, and MeOH extract of Chelidoni Herba was examined for anti inflammatroy activities in rats. The results of this study were summarized as follows: (1) The median lethal doses of the total MeOH and H_2O extracts of Chelidoni Herba were 12.5 and 10.1 g/㎏. respectively. (2) Major symptoms of this acute oral toxicity were eye extrusion. hair erection. trembling of head. paralysis. rapid running or moving before death, and depression of respiration. (3) The total MeOH extract of Chelidoni Herba was shown to have significant anti-inflammatory activity on toe paw edema induced by carrageenin.
( Chan Young Ock ),( Bhumsuk Keam ),( Tae Min Kim ),( Doo Hee Han ),( Tae Bin Won ),( Se Hoon Lee ),( J. Hun Hah ),( Tack Kyun Kwon ),( Dong Wan Kim ),( Dong Young Kim ),( Chae Seo Rhee ),( Hong Gyun 대한내과학회 2016 The Korean Journal of Internal Medicine Vol.31 No.3
Background/Aims: The role of induction chemotherapy (IC) for eyeball preservation has not been established in head and neck squamous cell carcinoma (HNSCC) of the paranasal sinus and nasal cavity (PNSNC). Periorbital involvement frequently leads to eyeball exenteration with a margin of safety. We evaluated the treatment outcomes, including survival and eyeball preservation, of patients who received IC for HNSCC of the PNSNC. Methods: We reviewed 21 patients diagnosed with HNSCC of the PNSNC who were treated with IC. We analyzed response, eyeball preservation rate, and overall survival. Results: Tumors were located in the paranasal sinus (n = 14) or nasal cavity (n = 7). Most patients had stage T4a (n = 10) or T4b (n = 7) disease. More than half of the patients received a chemotherapy regimen of docetaxel, fluorouracil, and cisplatin (n = 11). Thirteen patients (61.9%) achieved a partial response after IC and 15 patients (71.4%) achieved T down-staging. Among 17 patients with stage T4 disease, which confers a high risk of orbital exenteration, 14 (82.4%) achieved preservation of the involved eye. The 3-year overall survival (OS) rate of patients who achieved a partial response to IC was 84.6%. The 3-year OS rate of patients with stable disease or disease progression after IC was 25.0% (p = 0.038). Conclusions: IC could be considered for down-staging patients with advanced T-stage disease. It could also be a reasonable option for eyeball preservation in locally advanced HNSCC of the PNSNC.
( Chan-young Ock ),( Shin-hye Yoo ),( Bhumsuk Keam ),( Miso Kim ),( Tae Min Kim ),( Yoon Kyung Jeon ),( Dong-wan Kim ),( Doo Hyun Chung ),( Dae Seog Heo ) 대한내과학회 2019 The Korean Journal of Internal Medicine Vol.34 No.5
Background/Aims: Although crizotinib is standard chemotherapy for advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), clinical factors affecting progression-free survival (PFS) have not been reported. The purpose of this study was to identify clinical factors affecting PFS of crizotinib and develop a prognostic model for advanced ALK-positive NSCLC. Methods: Clinicopathologic features of patients enrolled in PROFILE 1001, 1005, 1007, and 1014 (training cohort) were reviewed. We conducted multivariate Cox analysis for PFS and overall survival (OS) in the training cohort (n = 159) and generated a proportional hazards model based on significant clinicopathologic factors, and then validated the model in an independent validation cohort (n = 40). Results: In the training cohort, the objective response rate was 81.5%. Median PFS and OS from the start of crizotinib were 12.4 and 31.3 months, respectively. Multivariate Cox analysis showed poor performance status, number of metastatic organs (≥ 3), and no response to crizotinib independently associated shorter PFS. Based on a score derived from these three factors, median PFS and OS of patients with one or two factors were significantly shorter compared to those without these factors (median PFS, 22.4 months vs. 10.5 months vs. 6.5 months; median OS, not reached vs. 29.1 months vs. 11.8 months, respectively; p < 0.001 for each group). This model also had validated in an independent validation cohort. Conclusions: Performance status, number of metastatic organs, and response to crizotinib affected PFS of crizotinib in ALK-positive NSCLC. Based on these factors, we developed a simple and useful prediction model for PFS.
Prevention of colitis-associated colorectal cancer with 8-hydroxydeoxyguanosine.
Ock, Chan Young,Kim, Eun-Hee,Hong, Hua,Hong, Kyung Sook,Han, Young-Min,Choi, Ki-Seok,Hahm, Ki-Baik,Chung, Myung-Hee American Association for Cancer Research, Inc 2011 CANCER PREVENTION RESEARCH Vol.4 No.9
<P>Colitis-associated cancer (CAC) is one of clear examples of inflammation-carcinogenesis sequence, by which the strict control of colitis with potent anti-inflammatory or antioxidative agent offers the chance of cancer prevention. Supported with the facts that Rac1 binds and activates STAT3, which are significantly upregulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) paradoxically can block Rac1 activation and subsequent NADPH oxidase (NOX) inactivation in various inflammation models, we hypothesized that attenuated Rac1-STAT3 and COX-NF-관B pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS)-induced colitis and can prevent CAC. Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can alleviate IBD, for which interleukin (IL)-10 knockout mice were designed to ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSS-induced colitis as well as various inflammatory mediators such as TNF-관, IL-6, COX-2, and iNOS in a dose-dependent manner. To document the cancer prevention effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS for 1 week, after which 8-OHdG-containing diets were given for 20 weeks. As results, mice that consumed 8-OHdG-containing diet significantly reduced both tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level were significantly attenuated in the 8-OHdG-treated group. Significantly decreased levels of malondialdehyde, monocyte chemotactic protein-1, matrix metalloproteinasess, COX-2, NOX4, and 관-catenin nuclear accumulation were responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we clearly showed cancer-preventive effect of exogenous 8-OHdG against CAC.</P>
Ock, Chan-Young,Kim, Eun-Hee,Choi, Duck Joo,Lee, Ho Jae,Hahm, Ki-Baik,Chung, Myung Hee WJG Press 2012 World journal of gastroenterology Vol.18 No.4
<P>Reactive oxygen species (ROS) attack guanine bases in DNA easily and form 8-hydroxydeoxyguanosine (8-OHdG), which can bind to thymidine rather than cytosine, based on which, the level of 8-OHdG is generally regarded as a biomarker of mutagenesis consequent to oxidative stress. For example, higher levels of 8-OHdG are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer. However, we have found that exogenous 8-OHdG can paradoxically reduce ROS production, attenuate the nuclear factor-관B signaling pathway, and ameliorate the expression of proinflammatory mediators such as interleukin (IL)-1, IL-6, cyclo-oxygenase-2, and inducible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1, NOX organizer-1 and NOX activator-1 in various conditions of inflammation-based gastrointestinal (GI) diseases including gastritis, inflammatory bowel disease, pancreatitis, and even colitis-associated carcinogenesis. Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative-stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases, as well as the prevention of inflammation-associated GI cancer. In this editorial review, the novel fact that exogenous 8-OHdG can be a functional molecule regulating oxidative-stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced.</P>
Young-Ock Kim,Chun-Geon Park,Kang-Hyo Lee,Won-Sik Kong,Kyung-Hun Park,Hyung-Don Kim,Yu-Su Shin,Chan-Heum Park,Ji-Yeon Lee,Young Sub Ahn 한국버섯학회 2016 버섯 Vol.20 No.1
Pleurotus cornucopiae (PC) mushrooms is found in the field and commonly known in Japan as Tamogidake mushrooms. Recently it has been reported that PC also alleviating the toxicity of heavy metals. However little is known about mechanism of the action of PC on osteoblast differentiation, especially in transcription factor. Inhibitor of DNA binding-1 (Id-1) function has been linked to the proliferation, migration, and senescence of cells, and studies about relationship between Id-1 and biological function. Therefore, this study was aimed to investigate the effect of PC on osteoblast differentiation and expression of Id-1 and Id-2. PC treatment increased ALP, Col 1 and OCN. PC treatment up-regulated the mRNA levels of Id-1 and Id-2 genes. This PC–induced osteoblast differentiation is more effective in lower doses rather than high doses. This study shows that expression of Id-1 and Id-2 was increased in a dose-dependent manner during PC-induced osteoblast differentiation.
OCK, Chan Young,LIM, Yun Jeong,KIM, Yoon Jae,CHUNG, Jun Won,KWON, Kwang An,KIM, Ju Hyun,HAHM, Ki Baik Blackwell Publishing Asia 2011 Journal of digestive diseases Vol.12 No.2
<P><B>OBJECTIVE: </B> Heat shock proteins (HSPs) are crucial for the maintenance of cellular integrity during normal cell growth as well as pathophysiological conditions. While acting as molecular chaperones with their folding activities, HSPs play a cytoprotective role to rescue epithelial cells from several gastric damages including non‐steroidal anti‐inflammatory drugs (NSAIDs) and <I>Helicobacter pylori</I>. Since the exact relationship between HSP27 phosphorylation and biological function remains unknown in NSAID‐induced gastropathy, we hypothesized that revaprazan, a novel acid pump antagonist, can secure significant cytoprotection from NSAID damages through HSP27 accentuation.</P><P><B>METHODS: </B> We evaluated protective actions of revaprazan against either <I>in vivo</I> animal model of indomethacin induced gastropathy or <I>in vitro</I> cell model focused on HSP27 expression and activation.</P><P><B>RESULTS: </B> Indomethacin induced significant cytotoxicities accompanied with phosphorylated HSP27 and attenuated levels of HSP27 in the <I>in vitro</I> cell experiment and revaprazan administration protected stomach from indomethacin‐induced gastric damages in accordance with HSP27 dephosphorylation in the <I>in vivo</I> animal experiment. HSP27 siRNA abolished these cytoprotective privileges of revaprazan. Indomethacin, 40 mg/kg, <I>po</I>, administration provoked significant levels of gastric damages accompanied with decrement in HSP27, while rats administrated with revaprazan prior to indomethacin imposed the accentuation of HSP27, of which levels were significantly correlated with the prevention of the indomethacin‐induced gastric damages.</P><P><B>CONCLUSION: </B> HSP27 phosphorylation with resultant decrease in HSP27 level was one of the mechanisms of indomethacin‐induced cytotoxicity, of which post‐translational modifications were prevented with revaprazan administration in the presence of indomethacin. Therefore, acid pump antagonist could be a choice for the prevention of NSAID‐induced gastropathy backed up with distinctive cytoprotective action beyond acid suppressor.</P>
( Chan Young Ock ),( Bhumsuk Keam ),( Tae Min Kim ),( Doo Hee Han ),( Tae Bin Won ),( Se Hoon Lee ),( J Hun Hah ),( Tack Kyun Kwon ),( Dong Wan Kim ),( Dong Young Kim ),( Chae Seo Rhee ),( Hong Gyun W 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1
Background: The role of induction chemotherapy in head and neck squamous cell carcinoma (HNSCC) has been suggested but poorly established in the paranasal sinus and nasal cavity (PNS-NC). Periorbital involvement is frequently observed and need of eyeball exenteration for safe margin is concerned in HNSCC of PNS-NC. We evaluated the treatment outcome of patients with induction chemotherapy focused on eyeball preservation in HNSCC of PNS-NC. Methods: Medical records were reviewed for 21 patients diagnosed with HNSCC of PNS-NC and treated with induction chemotherapy in Seoul National University Hospital from August 2005 to March 2012. Overall survival, response rate, and eyeball preservation rate were analyzed. Results: Of total 21 patients, median age was 57 years old and 15 were male. Tumors were located in paranasal sinus (N=14) and nasal cavity (N=7). Most patients had T4 stage, consists of 10 patients of T4a and 7 patients of T4b. Induction chemotherapy regimens were DFP (Docetaxel plus fiourouracil plus Cisplatin, N=11), FP (N=8), and DP (N=2). Median follow-up duration was 83.1 (range 28.8-109.1) months, and overall survival rate at 3 years was 61.5%. Thirteen patients (61.9%) had partial response by induction chemotherapy, and 15 patients (71.4%) achieved T down-staging. Among patients with T4 stage, which is high risk of orbital exenteration, 14 out of 17 patients (82.4%) eventually preserved the involved eye. Three-year overall survival rate of patients who had partial response to induction chemotherapy was 76.2% compared with 37.5% in those with stable disease or progression to induction chemotherapy. Conclusions: In this single center retrospective analysis, induction chemotherapy could be active for downstaging of T stage, and reasonable option for eyeball preservation in HNSCC of PNS-NC.