• 제목/요약/키워드: dose-effect relationship

검색결과 226건 처리시간 0.027초

Effect of Paclitaxel-loaded Nanoparticles on the Viability of Human Hepatocellular Carcinoma HepG2 Cells

  • Hou, Zhi-Hong;Zhao, Wen-Cui;Zhang, Qi;Zheng, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권5호
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    • pp.1725-1728
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    • 2015
  • Objective: To explore effects of paclitaxel-loaded poly lactic-co-glycolic acid (PLGA) particles on the viability of human hepatocellular carcinoma (HCC) HepG2 cells. Materials and Methods: The viability of HepG2 cells was assessed using MTT under different concentrations of prepared paclitaxel-loaded particles and paclitaxel (6.25, 12.5, 25, 50, and 100 mg/L), and apoptosis was analyzed using Hochest33342/Annexin V-FITC/PI combined with an IN Cell Analyzer 2000. Results: Paxlitaxel-loaded nanoparticles were characterized by narrow particle size distribution (158.6 nm average particle size). The survival rate of HepG2 cells exposed to paclitaxel-loaded PLGA particles decreased with the increase of concentration and time period (P<0.01 or P<0.05), the dose- and time-dependence indicating sustained release (P<0.05). Moreover, apoptosis of HepG2 cells was induced, again with an obvious dose- and time-effect relationship (P<0.05). Conclusions: Paclitaxel-loaded PLGA particles can inhibit the proliferation and induce the apoptosis of HCC HepG2 cells. This new-type of paclitaxel carrier body is easily made and has low cost, good nanoparticle characterization and sustained release. Hence, paclitaxel-loaded PLGA particles deserve to be widely popularized in the clinic.

방사선에 전신 조사된 마우스 음와 세포의 아포토시스 유도를 이용한 생물학적 선량 측정 모델 개발 연구 (Mouse model system based on apoptosis induction to crypt cells after exposure to ionizing radiation)

  • 김태환
    • 대한수의학회지
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    • 제41권4호
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    • pp.571-578
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    • 2001
  • 방사선 피폭선량의 예측을 위한 방사선 민감 지표 모델 개발의 일환으로 apoptotic fragment assay법이 방사선에 피폭된 후 체내 피폭선량을 예측할 수 있는 지표로의 이용 가능성을 평가하기 위하여 코발트-60 감마선과 의료용 싸이크로트론 50MeV($p{\rightarrow}Be^+$) fast neutron 을 0.25Gy에서 1Gy의 선량을 마우스에 각각 전신 조사한 후 소장 음와세포내 apoptotic crypt cell의 수적 변화를 관찰하였다. 저선량 조사군에서 apoptotic crypt cell의 출현 빈도가 1Gy까지 급격하게 증가한 것으로 보아 방사선이 stem cell 지역에 있는 crypt cell의 형태학적 변화를 유발하는 것으로 나타났다. 이상의 결과는 아포토시스가 손상된 세포를 제거하므로 손상된 방사선 민감 표적 장기의 항상성 유지에 중요한 역할을 하는 것으로 판단되었다. Apoptotic fragments의 발생빈도에 대한 선량-반응 곡선에 있어서 음와세포는 중성자조사군이 $y=0.18+(9.728{\pm}0.887)D+(-4.727{\pm}1.033)D^2$ ($r^2=0.984$)으로, 반면에 감마선조사군은 $y=0.18+(5.125{\pm}0.601)D+(-2.652{\pm}0.7000)D^2$ ($r^2=0.970$)의 식을 얻었다. 이와 같이 중성자조사군과 감마선조사군은 공히 linear quadratic model 로 관찰되었다. apoptotic fragments 의 발생빈도와 조사 선량간에 유의한 효과가 있는 것으로 확인되었다. 이상의 결과에서 조사선량의 증가에 비례하여 방사선 민감 세포의apoptotic fragments 가 수적으로 증가하였으며, 고준위 방사선과 저준위 방사선은 선량 반응 관계식과 시간 경과에 따른 영향이 매우 유사하였으며, 마우스 음와세포의 apoptosis 유도에 대한 중성자선의 방사선 생물학적 효과비(RBE)는 2.072이였다. 그리고 모든 방사선조사군에서 방사선피폭 후 4시간과 6시간에 apoptosis 유도가 가장 많았으며, 음와세포의 형태학적 소견은 정상 대조군에서 관찰되지 않는 전형적인 apoptotic fragments 가 나타났다. 따라서 음와 세포에서의 아포토시스 유도는 방사선 피폭으로 발생된 세포 손상의 생물학적 영향 평가검색, 방사선 방호제의 민감도 검사, 방사성 동위원소의 체내 오염에 대한 체내 피폭선량 예측의 지표 및 방사선 민감 표적장기의 손상정도 파악에 이용 가능할 것임. Apoptotic fragment assay 법은 0.25Gy에서 1Gy 까지의 선량에서 간편하고 빠르며 재현성이 있는 지표로서 방사선 민감 표적 장기의 선량 반응 평가와 방사선 피폭후 조기 피폭선량 예측을 위한 방사선 생물학적 선량측정법의 좋은 지표로 사용할 수 있을 것으로 사료됨.

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공기 중 벤젠과 소변 중 뮤콘산과의 상관성 연구 (Study of correlation between airborne benzene and urinary trans,trans-muconic acid in Petrochemical industry processes)

  • 주귀돈;이종성;최성봉;신재훈
    • 한국산업보건학회지
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    • 제16권4호
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    • pp.356-363
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    • 2006
  • To investigate the exposure effect of benzene, we measured airborne benzene as external doses, uninary tt-muconic acid as an internal dose of benzene exposure and analyzed the relationship between tt-muconic acid concentration and benzene exposure. The study population of eight businesses included 157 workers(87 workers in field; exposure group, 70 workers in board; control group) who produce or use benzene in petrochemical industry. The concentrations of airborne benzene were evaluated by personal samples and urine was sampled at the pre and end shift. Urinary t,t-muconic acid as internal dose was to analyze the relationship with airborne benzene. The geometric means(GM) of airborne benzene was 0.0231 ppm(range ND-1.0471 ppm) in exposure group and 0.0147 ppm(range ND-0.3162 ppm) in control group. The geometric means(GM) of urinary t,t-muconic acid at end-shift was $196.8{\pm}2.23{\mu}g/g$ creatinine in exposure group and $149.2{\pm}2.08{\mu}g/g$ creatinine in control group. There was significant correlation between the airborne concentration of benzene and the urinary concentration of t,t-muconic acid( r=0.711, p<0.01). From the results of stepwise multiple regression analysis about t,t-muconic acid at end-shift, significant independents was airborne benzene. In this study, there were significant correlation between the urinary concentration of t,t-muconic acid and the airborne concentration of benzene. More extensive studies ruling out healthy worker effect is needed.

투약에 대한 흥미도와 약물계산역량 간의 관계에서 약물계산자신감의 매개효과: Kolb의 학습양식유형을 적용하여 (The Mediating Effect of Drug Calculation Confidence in the Relationship between Interest in Medication and Drug Calculation Competency)

  • 박형숙;조규영;김동희;김상희;김명수
    • Journal of Korean Biological Nursing Science
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    • 제15권4호
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    • pp.155-163
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    • 2013
  • Purpose: The purpose of this study was to identify the mediating effect of confidence for drug calculation in the relationship between interest in medication and drug calculation competency using learning style. Methods: Participants in this study were 421 nursing students from Busan and Kyungnam province. The scales of learning style, interest in medication, importance of perception, confidence for drug calculation, and drug calculation competency for nursing students were used in this study. Descriptive statistics, $X^2$-test, t-test, Pearson correlation coefficient, and stepwise multiple regression were used for data analysis. Results: Learning styles of the participants were diverger 19.0%, accommodator 30.9%, converger 21.1%, and assimilator 29.0%. The drug dose calculation competency of participants was relatively low with a mean score 66.73. There were significant positive correlations among drug dose calculation competency, interest in medication (r=.31, p<.001), and confidence for drug calculation (r=.44, p<.001). Confidence for drug calculation was a moderator between interests in medication and drug calculation competency. Conclusion: Based on the result of this study, confidence for drug calculation promoting strategy such as medication reconciliation and various learning technology for improving drug calculation competency are needed.

Nerve Growth Factor Stimulates Glioblastoma Proliferation through Notch1 Receptor Signaling

  • Park, Jun Chul;Chang, In Bok;Ahn, Jun Hyong;Kim, Ji Hee;Song, Joon Ho;Moon, Seung Myung;Park, Young-Han
    • Journal of Korean Neurosurgical Society
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    • 제61권4호
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    • pp.441-449
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    • 2018
  • Objective : Notch receptors are heterodimeric transmembrane proteins that regulate cell fate, such as differentiation, proliferation, and apoptosis. Dysregulated Notch pathway signaling has been observed in glioblastomas, as well as in other human malignancies. Nerve growth factor (NGF) is essential for cell growth and differentiation in the nervous system. Recent reports suggest that NGF stimulates glioblastoma proliferation. However, the relationship between NGF and Notch1 in glioblastomas remains unknown. Therefore, we investigated expression of Notch1 in a glioblastoma cell line (U87-MG), and examined the relationship between NGF and Notch1 signaling. Methods : We evaluated expression of Notch1 in human glioblastomas and normal brain tissues by immunohistochemical staining. The effect of NGF on glioblastoma cell line (U87-MG) was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. To evaluate the relationship between NGF and Notch1 signaling, Notch1 and Hes1 expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. To confirm the effects of NGF on Notch1 signaling, Notch1 and Hes1 small interfering RNAs (siRNAs) were used. Results : In immunohistochemistry, Notch1 expression was higher in glioblastoma than in normal brain tissue. MTT assay showed that NGF stimulates U87-MG cells in a dose-dependent manner. RT-PCR and Western blot analysis demonstrated that Notch1 and Hes1 expression were increased by NGF in a dose-dependent manner. After transfection with Notch1 and Hes1 siRNAs, there was no significant difference between controls and 100 nM $NGF-{\beta}$, which means that U87-MG cell proliferation was suppressed by Notch1 and Hes1 siRNAs. Conclusion : These results indicate that NGF stimulates glioblastoma cell proliferation via Notch1 signaling through Hes 1.

Reduced Ovarian Cancer Incidence in Women Exposed to Low Dose Ionizing Background Radiation or Radiation to the Ovaries after Treatment for Breast Cancer or Rectosigmoid Cancer

  • Lehrer, Steven;Green, Sheryl;Rosenzweig, Kenneth E
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권6호
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    • pp.2979-2982
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    • 2016
  • Background: High dose ionizing radiation can induce ovarian cancer, but the effect of low dose radiation on the development of ovarian cancer has not been extensively studied. We evaluated the effect of low dose radiation and total background radiation, and the radiation delivered to the ovaries during the treatment of rectosigmoid cancer and breast cancer on ovarian cancer incidence. Materials and Methods: Background radiation measurements are from Assessment of Variations in Radiation Exposure in the United States, 2011. Ovarian cancer incidence data are from the Centers for Disease Control and Prevention. Standardized incidence ratios (SIR) of ovarian cancer following breast cancer and rectosigmoid cancer are from Surveillance, Epidemiology, and End Results (SEER) data. Obesity data by US state are from the Centers for Disease Control and Prevention. Mean ages of US state populations are from the United States Census Bureau. Results: We calculated standardized incidence ratios (SIR) from Surveillance, Epidemiology, and End Results (SEER) data, which reveal that in 194,042 cases of breast cancer treated with beam radiation, there were 796 cases of ovarian cancer by 120+ months of treatment (0.41%); in 283, 875 cases of breast cancer not treated with radiation, there were 1,531 cases of ovarian cancer by 120+ months (0.54%). The difference in ovarian cancer incidence in the two groups was significant (p < 0.001, two tailed Fisher exact test). The small dose of scattered ovarian radiation (about 3.09 cGy) from beam radiation to the breast appears to have reduced the risk of ovarian cancer by 24%. In 13,099 cases of rectal or rectosigmoid junction cancer treated with beam radiation in the SEER data, there were 20 cases of ovarian cancer by 120+ months of treatment (0.15%). In 33,305 cases of rectal or rectosigmoid junction cancer not treated with radiation, there were 91 cases of ovarian cancer by 120+ months (0.27%). The difference in ovarian cancer incidence in the two groups was significant (p = 0.017, two tailed Fisher exact test). In other words, the beam radiation to rectum and rectosigmoid that also reached the ovaries reduced the risk of ovarian cancer by 44%. In addition, there was a significant inverse relationship between ovarian cancer in white women and radon background radiation (r = - 0.465. p = 0.002) and total background radiation (r = -0.456, p = 0.002). Because increasing age and obesity are risk factors for ovarian cancer, multivariate linear regression was performed. The inverse relationship between ovarian cancer incidence and radon background was significant (${\beta}=-0.463$, p = 0.002) but unrelated to age (${\beta}=-0.080$, p = 0.570) or obesity (${\beta}=-0.180$, p = 0.208). Conclusions: The reduction of ovarian cancer risk following low dose radiation may be the result of radiation hormesis. Hormesis is a favorable biological response to low toxin exposure. A pollutant or toxin demonstrating hormesis has the opposite effect in small doses as in large doses. In the case of radiation, large doses are carcinogenic. However, lower overall cancer rates are found in U.S. states with high impact radiation. Moreover, there is reduced lung cancer incidence in high radiation background US states where nuclear weapons testing was done. Women at increased risk of ovarian cancer have two choices. They may be closely followed (surveillance) or undergo immediate prophylactic bilateral salpingo-oophorectomy. However, the efficacy of surveillance is questionable. Bilateral salpingo-oophorectomy is considered preferable, although it carries the risk of surgical complications. The data analysis above suggests that low-dose pelvic irradiation might be a good third choice to reduce ovarian cancer risk. Further studies would be worthwhile to establish the lowest optimum radiation dose.

예쁜꼬마선충을 이용한 레오누린과 그 합성 분절 유도체의 수명연장 효과 연구 (Study on Lifespan Extension Effect of Leonurine and its Synthetic Fragmental Analogs on Caenorhabditis elegans)

  • 차동석;한영택
    • 약학회지
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    • 제60권3호
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    • pp.141-145
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    • 2016
  • The current study was conducted to evaluate the lifespan extension effects of leonurine and its synthetic fragmental analogs using Caenohabditis elegans model system. Leonurine significantly prolonged the lifespan of C. elegans in a dose-dependent manner. To dissect the structure-activity relationship between leonurine and lifespan extension activity, seven novel fragmental analogs were synthesized and evaluated. Our study revealed that benzoate part of leonurine is responsible for its lifespan extension property rather than quanidine moiety.

Styrene-Mediated Oxidative Stresses in Rat Sperm Cells

  • Chun Young-Jin;Lee Hyun Min;Han Jee Hye;Oh Young Kun
    • Toxicological Research
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    • 제21권2호
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    • pp.129-134
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    • 2005
  • Styrene is a commercially important chemical used mainly in the production of plastics. A toxic effect exerted by styrene exposure may cause infertility, congenital anomalies or death in offspring. Treatment with styrene for 0, 50, 100, and 500 mg/kg for 5 days in Sprague-Dawley rats significantly decreased sperm motilities and sperm counts while sperm abnormalities were significantly increased. To determine the relationship between changes in sperm motilities and roles of reactive oxygen species (ROS), we determined the effect of styrene on ROS production and mRNA expression of antioxidant enzymes in rats. ROS production was enhanced by styrene treatment in a dose-dependent manner. The mRNA expression of catalase and superoxide dismutase (SOD) 2 was strongly suppressed by styrene treatment although SOD1 or glutathione peroxidase (GPX) 4 expressions were not significantly changed. Taken together, these results indicate that styrene may cause toxic effect in rat sperm cells by enhancing oxidative stresses.

창출이 가토의 혈압에 미치는 영향 (Effect of atractylis on the blood pressure of the rabbit)

  • 고석태;문영희;김성오
    • 약학회지
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    • 제17권2호
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    • pp.103-110
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    • 1973
  • In this study the effect of alcohol extract of atractlis (AAE) on the blood pressure of the rabbit was investigated. The results of the experiment are as follows. AAE elicited hypotension with doses ranging from 3 to 30 mg/kg, i.v., exhibiting a linear dose-relationship. This effect of AAE was abolished by atropine and potentiated by physostigmine, while not affected by diphenhydramine, hexamethonium, propranolol and cyproheptadine. AAE did not influence the pressor responses to norepinephrine and the depressor to isoproterenol. The above results indicate that AAE produced the hypotension by stimulating the parasympathetic nervous system related to acetylcholine.

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사물탕의 용량별 투여가 임신 랫드와 태자에 미치는 독성학적 연구 (Toxicological Effect of Samultang (Herbal Medicine) Administration in the Pregnant Rats and Fetuses - Focusing on dose-response Relationship -)

  • 전성진;신헌태;김경태;박해모;이선동
    • 대한예방한의학회지
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    • 제14권3호
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    • pp.1-12
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    • 2010
  • Objective : Samulatang (herbal description) is much used for women's disease in Korean Traditional Medicine. The aim of this study is to evaluate reproductive toxic effect by Samultang in pregnant rats and fetuses, and ascertain a dose-response relationship Method : Pregnant Sprague-Dawley rats were administered with the Samultang at single, double and quadruple dose for 20 days, orally. Pregnant rats were sacrificed at 20th day of gestation, and observed internal and reproductive organs. Live fetuses of gestation were randomly selected and fixed in 95% ethanol. Fetuses were stained with alcian blue and alizarin red S. We observe maternal body weight,, index associated pregnancy, and skeletal malformations in fetus Result : Maternal body weight of Samultang treated group has increased, side effect was not found in maternal body compared to that of control group. There were no significant difference in internal and reproductive organs. Double concentration administered group had lowest value in number of implantation, live fetuses, implantation rate and delivery rate, Also double concentration administered group showed higher early and late resorption rate than the other group. But, these are not significant. In the sex ratio, number of females, bigger than number of males in all Samultang administered groups. The fetuses of dams treated with Samultang didn't showed external and skeletal malformation. Vertebral and sternal variations were observed in single, double and quadruple concentration administered group but, compared to the control, those variations were insignificant. There were no significant changes in number of ribs, cervical, thoracic, lumber, sacral and caudal vertebrae Conclusion : Samultang is not expected to affect on pregnant rats and fetus about maternal body weight and number of live fetuses. There were no significant changes in organ weight, reproductive organs. Although skeletal variations were showed in vertebrae and sternum, treated groups were shown insignificant changes in skeletal variation