• Title/Summary/Keyword: CPT-11

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Anti-epidermal growth factor receptor (EGFR) monoclonal antibody and DNA topoisomerase inhibitor reduce growth of salivary adenoid cystic carcinoma in a murine model (항-표피성장인자수용체 단클론항체와 DNA 토포이소머라제 억제제에 의한 마우스 모델에서의 타액선 선낭암종 성장 억제)

  • Park, Young-Wook;Lee, Hee-Su
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.36 no.3
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    • pp.177-185
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    • 2010
  • Introduction: Epidermal growth factor receptor (EGFR) is expressed in human epithelial tumors including salivary cancers, and known to be correlated with tumor progression and poor clinical courses in some epithelial tumors. In this study, we determined the therapeutic effect of the anti-EGFR monoclonal antibody Erbitux (C225, cetuximab) in combination with the DNA topoisomerase I inhibitor irinotecan (CPT-11) on human salivary adenoid cystic carcinoma (SACC) cells growing in nude mice. Materials and Methods: At first, immunocytochemical analysis for the expression of EGFR and phosphorylated EGFR (pEGFR) on a human salivary ACC cell line (ACC3). To determine the in vivo effects of Erbitux and CPT-11, nude mice with orthotopic parotid tumors were randomized to receive intraperitoneal Erbitux (1 mg) two times per week, intraperitoneal Irinotecan (50 mg/kg) once per week, Erbitux plus CPT-11, or placebo. (control) Tumor volume and weight were measured. And mechanisms of in vivo activity of Erbitux and/or CPT-11 were determined by immunohistochemical/ immunofluorescent analyses. Results: Immunocytochemical staining of ACC3 demonstrated that EGFR was expressed and phosphorylated. CPT-11 inhibited ACC tumor growth in nude mice. Tumors of mice treated with CPT-11 and CPT-11 plus Erbitux exhibited increased tumor cell apoptosis and decreased microvessel density, which correlated with a decrease in the tumor volume in nude mice. But, CPT-11 seems not to be synergistic with Erbitux in our ACC3 model system. Conclusion: These results suggest that anti-EGFR monoclonal antibody and the DNA topoisomerase I inhibitor will be effective in the treatment of recurred or metastatic lesions of salivary ACC.

RELATIONSHIP BETWEEN CHANGES IN EVENT-RELATED POTENTIALS AND CHANGES IN CONTINUOUS PERFORMANCE TEST UNDER THE INFLUENCE OF METHYLPHENIDATE IN ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (주의력 결핍 ${\cdot}$ 과잉행동장애 아동에서 Methylphenidate에 의한 사건관련전위와 연속과제수행 변화사이의 상관성)

  • Choi, Young;Lee, Mu-Suk;Lee, Mi-Suk
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.8 no.2
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    • pp.273-286
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    • 1997
  • Objective:This study was designed to evaluate effects of methylphenidate(MPH) on event-related potentials(ERP) and continuous performance test(CPT) in attention-deficit hyperactivity disorder (ADHD) and to see the correlation between changes in ERP and changes in performance. Method:ERP and CPT were used to examine the acute effects of MPH(0.5mg/kg) in eleven ADHD boys(89-103 months old). Results:1) After MPH administration, P3 latency to nontarget stimuli at Fz was significantly decreased (p<0.01) and P2 amplitudes to target stimuli at Pz and at Oz and P3 amplitude to target stimuli at Cz were significantly increased(p<0.05). 2) Commission error and omission error in the CPT-X and commission error in the CPT-AX were decreased(p<0.01), and hits and perceptual sensitivity(d') in the CPT-X and d′ in the CPT-AX were increased(p<0.01). 3) The change of P3 latency to nontarget stimuli at Fz and the change of d′ in the CPT-X were negatively correlated(p<0.05), and the change of P2 amplitude to target stimuli at Pz and d′ in the CPT-AX were positively correlated(p<0.05). Conclusion:MPH improves change orienting reaction, the delivery of task relevant information, accuracy and perceptual sensitivity in ADHD. And the increase of ability to discriminate targets from non-targets reflects reduced evaluation time in large memory component task and enhanced change orienting reaction in simple task.

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Effects of Cheongpyesagan-tang and YKK012 on in vitro and in vivo Colon Cancer Cell Growth with and without CPT-11 (청폐사간탕(淸肺瀉肝湯)과 YKK012의 항암제 CPT-11과 병용투여 시 대장암 성장억제에 미치는 효과)

  • Ahn, Hun-Mo;Han, Sang-Yong;Kim, Ji-Hoon;Rho, Tae-Won;Chong, Myong-Soo;Kim, Yun-Kyung
    • The Korea Journal of Herbology
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    • v.30 no.1
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    • pp.33-42
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    • 2015
  • Objectives : The aim of this study was to evaluate the antitumor effects of Cheongpyesagan-tang(CST) and YKK012 on colon cancer. Methods : MTT assay was used to evaluate the cytotoxicity of Single herbs and combinations of CST and YKK012 on murine colon cancer cells, Colon 38. To explain effects of apoptosis in colon cancer, we performed the western blot. Effects of CST and YKK012 on antitumor activity of CPT-11 using the murine colon38 allograft tumor in BDF1 mice. Results : Single herbs and combinations of CST and YKK012 was tested in vitro, Rhei Radix (RH) and Scutellariae Radix (SC) and YKK012 showed dose-response cytotoxicity on Colon 38. This might be due to the apoptosis, as we see Bax and Caspase-3, which are apoptotic factors, was expressed in RH and SC treated cells. YKK012 also showed increased expression of Caspase-3. In mouse colorectal cancer xenograft model of colon38 cells, herbal combinations showed tendencies of tumor regression, but was not significant. Furthermore, because toxicity was observed in CST group, we reduced the dose of CST for the next experiment. The anti-tumor effects of herbal combinations were insufficient to be used as single anti-tumor agent. With simultaneous usage of CPT-11, contrary to that CST showed no synergistic effects, YKK012 which was composed by the combination of four $ER{\beta}$ selective herbs, significantly reduced the size of tumor and Bax expression was increased. Conclusions : We suggest YKK012 can be a effective cancer adjuvant therapy with CPT-11 on colon cancer.

Synthesis and Antitumor Activity of Phthalimide-Based Polymers Containing Camptothecin

  • Lee, Neung-Ju
    • Macromolecular Research
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    • v.11 no.1
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    • pp.47-52
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    • 2003
  • The objective of this study was to develop a polymeric drug delivery system for camptothecin (CPT), capable of improving its therapeutic index and reducing its side effects. A monomeric conjugate, 3,6-endo-methylene-1,2,3,6-tetrahydrophthalimidoethanoylcamptothecin in (ETECPT) between CPT and 3,6-endo-methylene-1,2,3,6-tetrahydrophthalimidoethanoic acid was synthesized. Its homo-and copolymer with acrylic acid (AA) were prepared by photopolymerization using 2,2-dimethoxy-2-phenylacetophenone (DMP) as a photoinitiator. The monomer and its polymers were characterized by IR, $^1$H- and $^{13}$ C-NMR spectra. The ETECPT content in poly(ETECPT-co-AA) obtained by elemental analysis was 82 wt%. The number-average molecular weights of the polymers determined by gel permeation chromatography were as follows: M$_{n}$ = 11,400 for poly(ETECPT), M$_{n}$ = 17,900 for poly(ETECPT-co-AA). The $IC_{50}$/ values of ETECPT and its polymers against cancer cells were much larger than that of CPT. Our results from the in vivo antitumor activity indicated that all polymers show high antitumor activity than CPT at a dose of 100 mg/kg./kg.

Cryptotanshinone inhibits TNF-α-induced LOX-1 expression by suppressing reactive oxygen species (ROS) formation in endothelial cells

  • Ran, Xiaoli;Zhao, Wenwen;Li, Wenping;Shi, Jingshan;Chen, Xiuping
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.4
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    • pp.347-355
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    • 2016
  • Cryptotanshinone (CPT) is a natural compound isolated from traditional Chinese medicine Salvia miltiorrhiza Bunge. In the present study, the regulatory effect and potential mechanisms of CPT on tumor necrosis factor alpha ($TNF-{\alpha}$) induced lectin-like receptor for oxidized low density lipoprotein (LOX-1) were investigated. Human umbilical vein endothelial cells (HUVECs) were cultured and the effect of $TNF-{\alpha}$ on LOX-1 expression at mRNA and protein levels was determined by Real-time PCR and Western blotting respectively. The formation of intracellular ROS was determined with fluorescence probe $CM-DCFH_2-DA$. The endothelial ox-LDL uptake was evaluated with DiI-ox-LDL. The effect of CPT on LOX-1 expression was also evaluated with SD rats. $TNF-{\alpha}$ induced LOX-1 expression in a dose- and time- dependent manner in endothelial cells. $TNF-{\alpha}$ induced ROS formation, phosphorylation of $NF-{\kappa}B$ p65 and ERK, and LOX-1 expression, which were suppressed by rotenone, DPI, NAC, and CPT. $NF-{\kappa}B$ inhibitor BAY11-7082 and ERK inhibitor PD98059 inhibited $TNF-{\alpha}-induced$ LOX-1 expression. CPT and NAC suppressed $TNF-{\alpha}-induced$ LOX-1 expression and phosphorylation of $NF-{\kappa}B$ p65 and ERK in rat aorta. These data suggested that $TNF-{\alpha}$ induced LOX-1 expression via ROS activated $NF-{\kappa}B/ERK$ pathway, which could be inhibited by CPT. This study provides new insights for the anti-atherosclerotic effect of CPT.

Diagnostic Significance of Comprehensive Attention Test in Children and Adolescents with Attention-Deficit Hyperactivity Disorder (주의력결핍 과잉행동장애 아동에서 종합주의력검사의 진단적 유용성)

  • Seo, Jong-Man;Lee, Jung-Sun;Kim, Seong-Yoon;Kim, Hyo-Won
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.22 no.4
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    • pp.246-252
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    • 2011
  • Background : The objective of this study was to evaluate the diagnostic efficiency of the Comprehensive Attention Test (CAT) by comparing the results of the continuous performance test (CPT) and the CAT in children and adolescents with attention-deficit hyperactivity disorder (ADHD). Method : A total of 110 children and adolescents with ADHD (mean age : 11.2${\pm}$2.9 years, 76 boys) and 36 children and adolescents without ADHD (mean age : 12.0${\pm}$2.7 years, 25 boys) completed the CAT. We compared the specificity and sensitivity of the CPT and CAT at two different cut-off points via the McNemar test. The areas under the receiver operating characteristic curves (AUC) between the two groups were compared using Medcalc software. Results : The sensitivity and specificity of the CPT were .419 and .806, respectively. The sensitivity of the CAT was .827, which was significantly higher than that of the CPT (p<.001), and the specificity of CAT is .444, which was significantly lower than that of CPT (p<.001). The AUC of the CPT and CAT was .664 and .692, respectively, and there were no significant difference between the two groups on the paired comparison (p=.513). Conclusions : The results of this study suggest that the CAT has moderate specificity and high sensitivity. The CAT can be used as a useful tool to evaluate the neuropsychological function of children and adolescents with ADHD.

Clinical Observations on Associations Between the UGT1A1 Genotype and Severe Toxicity of Irinotecan

  • Lu, Yan-Yan;Huang, Xin-En;Wu, Xue-Yan;Cao, Jie;Liu, Jin;Wang, Lin;Xiang, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3335-3341
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    • 2014
  • Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean, $12.75{\mu}mol/L$) with compared to TA6/6 (mean, $9.92{\mu}mol/L$) with p<0.05. Conclusions: Our study support the conclusion that patients with a $UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the $UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.

Modeling for Prediction of the Turnip Mosaic Virus (TuMV) Progress of Chinese Cabbage (배추 순무모자이크바이러스(TuMV)병 진전도 예측모형식 작성)

  • 안재훈;함영일
    • Korean Journal Plant Pathology
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    • v.14 no.2
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    • pp.150-156
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    • 1998
  • To develop a model for prediction of turnip mosaic virus(TuMV) disease progress of Chinese cabbage based on weather information and number of TuMV vector aphids trapped in Taegwallyeong alpine area, data were statistically processed together. As the variables influenced on TuMV disease progress, cumulative portion(CPT) above 13$^{\circ}C$ in daily average temperature was the most significant, and solar radiation, duration of sunshine, vector aphids and cumulative temperature above $0^{\circ}C$ were significant. When logistic model and Gompertz model were compared by detemining goodness of fit for TuMV disease progress using CPT as independent variable, regression coefficient was higher in the logistic model than in the Gompertz model. Epidemic parameters, apparent infection rate and initial value of logistic model, were estimated by examining the relationship between disease proportion linearized by logit transformation equation, In(Y/Yf-Y) and CPT. Models able to describe the progression of TuMV disease were formulated in Y=100/(1+128.4 exp(-0.013.CPT.(-1(1/(1+66.7.exp(-0.11.day). Calculated disease progress from the model was in good agreement with investigated actual disease progress showing high significance of the coefficient of determination with 0.710.

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A Characteristics of the Strength Recovery of the Soil Adjacent to the Pile Depending on the Construction Methods of a Environment-friendly Screw Concrete Pile for a Noise- and Vibration-free Method (무소음·무진동을 위한 환경친화적인 스크류콘크리트말뚝의 시공법에 따른 말뚝 인접 지반의 강도 회복 특성)

  • Kim, Dong-Chul;Choi, Youngkyu
    • Journal of the Korean Geotechnical Society
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    • v.29 no.1
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    • pp.71-80
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    • 2013
  • Before and after the test constructions, and after an 11-month hiatus from the pilot pile installations, the in-situ tests (CPT, SPT) were carried out at the ground adjacent to the noise- and vibration-free screw concrete piles installed by 2 kinds of construction methods (i.e., the toe-jetting shoe type, the pre-digging type). In the toe-jetting shoe type construction methods, after construction, the soil strength within 3.5D (where, D = pile diameter) from the pile center decreased greatly by about 46% of the original ground and, after an 11-month hiatus, a strength recovery adjacent to the piles appeared about 71% of the original ground. In the pre-digging type construction methods, a strength recovery adjacent to the piles appeared 100% of the strength of the original ground.

Current Treatments for Breast Cancer-Related Lymphoedema: A Systematic Review

  • Li, Lun;Yuan, Liqin;Chen, Xianyu;Wang, Quan;Tian, Jinhui;Yang, Kehu;Zhou, Enxiang
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.11
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    • pp.4875-4883
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    • 2016
  • Background and objective: Breast cancer-related lymphoedema (BCRL) is a disabling complication with long term impact on quality on life after breast cancer treatment. Its management remains a major challenge for patients and health care professionals; the goal of this overview was to summarize effects of different treatment strategies for patients with BCRL. Methods: A thorough search was undertaken to allow a systematic review or meta-analysis of treatments for BCRL. Two investigators independently selected studies and abstracted the data. Results: Combined physical therapy (CPT) with different combinations of surgery, oral pharmaceuticals, low-level laser therapy, weight reduction, mesenchymal stem cell therapy, kinesio tex taping, and acupuncture might be effective in reducing lymphoedema, but exercise demonstrated no obvious benefit. The results of direct comparisons showed CPT might be more effective than standard physiotherapy (ST). Manual lymphatic drainage (MLD) may not offer additional benefits to ST for swelling reduction, but could facilitate compression bandaging. MLD seemed to have similar effects with self-administered simple lymphatic drainage (SLD) or using an intermittent pneumatic compression pump (IPC). IPC might also not be associated with additional effectiveness for CPT. Efficacy of stem cell therapy vs. compression sleeve or CPT, as well as the effects of daflon and coumarin could not be established. Conclusion: Although many treatments for BCRL might reduce lymphoedema volume, their effects were not well established. The quality of many of the original studies in the included reviews was not optimal, so that in future randomized control trials are a high priority.