• Title/Summary/Keyword: Dose-response

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Evaluation of response to stereotactic radiosurgery in patients with radioresistant brain metastases

  • Sayan, Mutlay;Mustafayev, Teuta Zoto;Sahin, Bilgehan;Kefelioglu, Erva Seyma Sare;Wang, Shang-Jui;Kurup, Varsha;Balmuk, Aykut;Gungor, Gorkem;Ohri, Nisha;Weiner, Joseph;Ozyar, Enis;Atalar, Banu
    • Radiation Oncology Journal
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    • v.37 no.4
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    • pp.265-270
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    • 2019
  • Purpose: Renal cell carcinoma (RCC) and melanoma have been considered 'radioresistant' due to the fact that they do not respond to conventionally fractionated radiation therapy. Stereotactic radiosurgery (SRS) provides high-dose radiation to a defined target volume and a limited number of studies have suggested the potential effectiveness of SRS in radioresistant histologies. We sought to determine the effectiveness of SRS for the treatment of patients with radioresistant brain metastases. Materials and Methods: We performed a retrospective review of our institutional database to identify patients with RCC or melanoma brain metastases treated with SRS. Treatment response were determined in accordance with the Response Evaluation Criteria in Solid Tumors. Results: We identified 53 radioresistant brain metastases (28% RCC and 72% melanoma) treated in 18 patients. The mean target volume and coverage was 6.2 ± 9.5 mL and 95.5% ± 2.9%, respectively. The mean prescription dose was 20 ± 4.9 Gy. Forty lesions (75%) demonstrated a complete/partial response and 13 lesions (24%) with progressive/stable disease. Smaller target volume (p < 0.001), larger SRS dose (p < 0.001), and coverage (p = 0.008) were found to be positive predictors of complete response to SRS. Conclusion: SRS is an effective management option with up to 75% response rate for radioresistant brain metastases. Tumor volume and radiation dose are predictors of response and can be used to guide the decision-making for patients with radioresistant brain metastases.

Adaptive Response in CHO Cells by Bleomycin, Mitomycin C and Cadmium (Bleomycin, Mitomycin C 및 Cadmium에 의한 CHO 세포의 적응반응)

  • 김양지;한정호;정해원
    • Journal of Environmental Health Sciences
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    • v.18 no.2
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    • pp.117-124
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    • 1992
  • Pretreatment with low concentration of Bleomycin and Cadmium rendered Chinese Hamster Ovary Cells more resistant to the induction of chromosome aberration by subsequent high concentration of same agent, however Mitomycin C did not function in that way. The cells pre-exposed to low dose of Cadmitim did not show cross-resistance to challenge dose of Mitomycin C for the induction of chromosome aberration, but cells pre-exposed to Bleomycin showed cross resistance. And the cells pre-exposed to low dose of Mitomycin C showed cross resistance to challenge of Bleomycin, but Cadmium did not.

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Induction of Cardiovascular Anaphylaxis and Basic Pharmacological Analysis of Involved Mediators in Pithed Rats

  • Park, Kwan-Ha
    • Biomolecules & Therapeutics
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    • v.16 no.4
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    • pp.299-305
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    • 2008
  • Active cardiovascular anaphylactic response was induced in ovalbumin-sensitized, pithed Sprague-Dawley and Wistar rats. On intravenous administration of the antigen, ovalbumin, marked tachycardia and pressor responses were immediately elicited. Thereafter, a delayed long-lasting severe hypotensive response was observed. These anaphylactic cardiovascular responses were maximal 2-3 weeks after the sensitization, and the response was slightly diminished 6 weeks after sensitization. The immediate pressor response was blocked by a non-selective serotonin antagonist methysergide at a dose-dependent manner, but not by histamine receptor antagonists mepyramine (pyrilamine) or cimetidine. The delayed hypotension was reduced either by histamine $H_1$ receptor antagonist mepyramine or $H_2$ receptor antagonist cimetidine, both in a dose-dependent manner. The tachycardic response was not influenced by serotonin or histamine receptor antagonists examined in this study. Differently from the cardiovascular responses, there was no observable bronchial contraction in Sprague-Dawley rat trachea in contrast to Wistar rat where the trachea contracted to in vitro antigen challenge. The cardiovascular anaphylactic model seems to be useful for studying cardiovascular events that occur exclusively in peripheral heart-blood vessel systems. The involvement of two major anaphylactic mediators, serotonin and histamine, is partially demonstrated.

Thermoluminescent Characteristics of Newly Developed LiF:Mg,Cu,Na,Si TL Detectors

  • Lee J. I.;Kim J. L.;Chang S. Y.
    • Nuclear Engineering and Technology
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    • v.36 no.1
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    • pp.47-52
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    • 2004
  • Recently, a new sintered pellet-type LiF:Mg,Cu,Na,Si TL detector which has a high sensitivity and good reusability, named KLT-300(KAERI LiF:Mg,Cu,Na,Si TL detector), was developed by the variation of the dopants concentrations and the parameters of the preparation procedure at KAERI (Korea Atomic Energy Research Institute). In this study, the thermoluminescent characteristics of the newly developed TL detectors were investigated. The sensitivity of the TL detector was compared with that of the TLD-100 by light integration. The dose linearity of the detector was tested from $10^{-6}$ Gy up to 30 Gy. The dose response was very linear up to 10 Gy and a sublinear response was observed at higher doses. The energy response of the detector was studied for photon energies from 20 keV to 662 keV. The result shows that a maximum response of 1.004 at 53 keV and a minimum response of 0.825 at 20 keV were observed. The reproducibility study for the TL detector was also carried out. The coefficients of variation for each detector separately did not exceed 0.016, and for all the 10 detectors collectively was 0.0054. Lower limit of detection for the detector was investigated at 70 nGy by the Harshaw 4500 TLD Reader and the residual signal of the TL detector was found to be $0.57\%$.

Optimal Scheduling of Drug Treatment for HIV Infection: Continuous Dose Control and Receding Horizon Control

  • Hyungbo Shim;Han, Seung-Ju;Chung, Chung-Choo;Nam, Sang-Won;Seo, Jin-Heon
    • International Journal of Control, Automation, and Systems
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    • v.1 no.3
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    • pp.282-288
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    • 2003
  • It is known that HIV (Human Immunodeficiency Virus) infection, which causes AIDS after some latent period, is a dynamic process that can be modeled mathematically. Effects of available anti-viral drugs, which prevent HIV from infecting healthy cells, can also be included in the model. In this paper we illustrate control theory can be applied to a model of HIV infection. In particular, the drug dose is regarded as control input and the goal is to excite an immune response so that the symptom of infected patient should not be developed into AIDS. Finite horizon optimal control is employed to obtain the optimal schedule of drug dose since the model is highly nonlinear and we want maximum performance for enhancing the immune response. From the simulation studies, we found that gradual reduction of drug dose is important for the optimality. We also demonstrate the obtained open-loop optimal control is vulnerable to parameter variation of the model and measurement noise. To overcome this difficulty, we finally present nonlinear receding horizon control to incorporate feedback in the drug treatment.

Optimal Scheduling of Drug Treatment for HIV Infection;Continuous Dose Control and Receding Horizon Control

  • Shim, H.;Han, S.J.;Jeong, I.S.;Huh, Y.H.;Chung, C.C.;Nam, S.W.;Seo, J.H.
    • 제어로봇시스템학회:학술대회논문집
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    • 2003.10a
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    • pp.1951-1956
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    • 2003
  • It is known that HIV (Human Immunodeficiency Virus) infection, which causes AIDS after some latent period, is a dynamic process that can be modeled mathematically. Effects of available anti-viral drugs, which prevent HIV from infecting healthy cells, can also be included in the model. In this paper we illustrate control theory can be applied to a model of HIV infection. In particular, the drug dose is regarded as control input and the goal is to excite an immune response so that the symptom of infected patient should not be developed into AIDS. Finite horizon optimal control is employed to obtain the optimal schedule of drug dose since the model is highly nonlinear and we want maximum performance for enhancing the immune response. From the simulation studies, we find that gradual reduction of drug dose is important for the optimality. We also demonstrate the obtained open-loop optimal control is vulnerable to parameter variation of the model and measurement noise. To overcome this difficulty, we finally present nonlinear receding horizon control to incorporate feedback in the drug treatment.

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Whether Alzheimer's Disease is Responsive to a Single Oral Dose of Donepezil and this Response is Predictive Factor in Alzheimer's Disease (일회 Donepezil 투약이 알쯔하이머병 환자에 미치는 영향 및 반응군 예측 인자로서의 가능성)

  • Kwak, Yong-Tae;Yang, Young-Soon;Noh, Yong-Woo
    • Korean Journal of Biological Psychiatry
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    • v.18 no.1
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    • pp.36-45
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    • 2011
  • Objectives : Though a proportion of Alzheimer's disease(AD) patients treated with donepezil have shown positive response on cognition, but the responders' characteristics are still uncertain. This study attempts to identify whether a single oral dose of donepezil(5mg) can change cognition and the relationship between single dose responder items and long-term responder are examined. Methods : Twenty-three AD patients for single donepezil challenge study group and eleven AD patients for controls were participated in the study. Seven days after baseline study for neuropsychological test and EEG, same studies were rechecked after donepezil medication in study group. In donepezil study groups, 12 weeks after donepezil medication, neuropsychological test and EEG were rechecked. Results : After single donepezil challenge, forward digit span, Rey-Osterrieth Complex Figure Test copy, SVLT delayed recall were significantly improved, and beta spectra power in anterior, theta spectra power in posterior field were significantly decreased. According to linear regression analysis, forward digit span after single donepezil challenge was significantly positive correlated with long-term responders. Conclusions : This study suggests that single donepezil medication can significantly change cognitive functions and EEG in AD patients. Among these responsive items, forward digit span was significantly correlated with long-term responder.

Application plan for radiological exposure model using virtual reality-based radiological exercise system

  • Lee, Dewhey;Lee, Byung Il;Park, Younwon;Kim, Dohyung
    • Nuclear Engineering and Technology
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    • v.50 no.5
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    • pp.745-750
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    • 2018
  • New exercise technology such as the virtual reality (VR)-based exercise system is required to meet soaring demand for target participants in exercises and to alleviate the difficulties in personnel mobilization through an alternative approach to the exercise system. In a previous study, event tree methodologies were introduced in setting up an exercise scenario of a VR-based radiological exercise system. In the scenario, the locations at which major events occur are rephrased as nodes, routes as paths, and public response actions as protective actions or contents of an exercise at individual locations. In the study, a model for estimating effective doses to the participants is proposed to evaluate the exercise system, using the effective dose rates at particular times and locations derived from a computer program. The effective dose received by a student when she/he follows a successful route is about a half of the dose received when she/he does not follow the exercise guide directions. In addition, elapsed time to finish an exercise when following a successful route is less than one-third of the time spent to finish an exercise when following the guide's directions.

Toxicogenomics Study on ${\alpha}-Naphthylisothiocyanate\;(ANIT)$ Induced Hepatotoxictiy in Mice

  • Hwang, Ji-Yoon;Lim, Jung-Sun;Jeong, Sun-Young;Park, Han-Jin;Cho, Jae-Woo;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.2 no.1
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    • pp.48-53
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    • 2006
  • [ ${\alpha}-Naphthylisothiocyanate$ ] (ANIT) induces intrahepatic cholestasis, involving damage to biliary epitheial cells. This study investigates hepatic gene expression and histopathological alterations in response to ANIT treatment in order to elucidate early time response of ANIT-induced hepatotoxicity. ANIT was treated with single dose (3, 6, and 60 mg/kg) in corn oil by oral gavage. Serum biochemical and histopathological observation were performed for evaluation of hepatotoxicity level. Affymetrix oligo DNA chips were used for gene expression profile by ANIT-induced hetpatoxicity. Hepatic enzyme levels (ALT, AST, and ALP) were increased in 24 hr high dose group. In microscopic observations, moderate hepatocellular necrosis, were confirmed 24 hr high dose groups. We found that gene expression patterns were dependent on time and dose. Our selected genes were related inflammation and immunomodulation. In this study, ANIT-induced hepatotoxicity was involved in acute phase responses and provides evidence for role of neutrophil could be mechanism associated with ANIT-mediated hepatotoxicity.

Intra-tracheal Administration of the Disinfectant Chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) in a Mouse Model to Evaluate a Causal Association with Death (마우스의 기도 내 점적을 통한 가습기살균제 CMIT/MIT와 사망 간의 원인적 연관성에 관한 연구)

  • Kim, Hayoung;Chung, Yonghyun;Park, Yeongchul
    • Journal of Environmental Health Sciences
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    • v.43 no.4
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    • pp.247-256
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    • 2017
  • Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.