• Title/Summary/Keyword: toxicity response

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Retrospective Study on the Therapeutic Effects of an Etoposide, Adriamycin, Cisplatin-II (EAPII) versus an Etoposide, Leucovorin, 5-Furorouracil (ELF) Combination Chemotheraphy in Unresectable Gastric Cancer (절제 불가능한 진행성 위암 환자에서 Etoposide, Adriamycin 및 Cisplatin-II (EAP-II)와 Etoposide, Leucovorin 및 5-Furorouracil (ELF) 복합 화학요법의 치료효과에 대한 후향적 연구)

  • Moon Hee-Seok;Kang Yoon-Sae;Kim Yeon-Soo;Park Ki-Oh;Lee Eum-Seok;Sung Jae-Kyu;Lee Byong-Seok;Noh Seung-Moo;Song Kyu-Sang;Cho June-Sick;Shin Kyung-Sook;Jeong Hyun-Yong
    • Journal of Gastric Cancer
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    • v.3 no.3
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    • pp.122-127
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    • 2003
  • Purpose: The incidence rate and the mortality rate of gastric cancer have decreased in developed countries over the last several decades. On the other hand, they remain high in far eastern countries such as Korea, Japan, China and in many developing countries. The cure of patients with gastric carcinomas can be achieved mostly through complete surgical resection, but most gastric cancer patients are in advanced stages when diagnosed and have poor prognoses. therefore, the development of an effective systemic therapy is essential for far advanced gastric cancer patients. Until recently, the most commonly used combination chemotherapy was based on 5-flurouracil or cisplatin, but the results were not satisfactory, so recently etoposide, adriamycin and cisplatin (EAP-II) combination chemotherapy was introduced in patients with advanced gastric cancer. Early studies showed a high response rate and the ability to convert unresectable cases to resectable ones, but later studies couldn't duplicate the result. the purpose of this study was to evaluate the relative efficacy & toxicity of EAP-II chemotherapy and ELF chemotherapy which is based on 5-flurouracil. Materials and Methods: Between July 1992 and July 2002, sixty-five patients with inoperable advanced gastric cancer were enrolled for this study. Thirty-seven patient received EAP-II chemotherapy:etoposide (20 mg/$m^{2}$ IV for $1\∼5 days$), adriamycin (20 mg/$m^{2}$ IV for $1\∼5 days$) and cisplatin (20 mg/$m^{2}$ IV for $1\∼5 days$) and Twenty-eight patients receieved ELF chemotherapy : etoposide (100 mg/$m^{2}$ IV for $1\∼3 days$), leucovorin (20 mg/$m^{2}$ IV for $1\∼5 days$) and 5-FU (500 mg/$m^{2}$ IV for $1\∼5 days$). Each treatment schedule for each group was repeated every four weeks: EAP-II means 3.4 cycles per patient..ELF means 4.1 cycles per patient Results: Total respones rates were $5.4\%$ in the ELF group and $3.6\%$ in the EAP group (P-value>0.05). The median times to progression were 144 days in the ELF group and 92 days in the EAP-II group (P-value<0.05), and themedian overall survival times were 189 days in the ELF group and 139 days in the EAP-II group (P-value>0.05). The difference in the survival curves for the two regimens was not statistically significant. Non-hematologic toxicitis & hematologic toxicitis were more frequently observed for the EAP-II regimen. Anemia: $27.6\%$ in ELF vs $54\%$ in EAP-II; Leukopenia: $8.5\%$ in ELF vs $19\%$ in EAP-II; nausea & vomiting: $45.9\%$ in ELF vs $67.8\%$ in EAP-II. Conclusion: EAP-II regimen is not superior to ELF regimen in the tratment of inoperable advanced gastric cancer (J Korean Gastric Cancer Assoc 2003;3:122-127)

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Effect of Supercritical Carbon Dioxide on Physicochemical Properties and Microbial Reduction of Freeze-Dried Bovine Liver (초임계 이산화탄소 처리가 동결 건조된 소간의 이화학적 특성 및 미생물 저감화에 미치는 영향)

  • Kim, Hye-Min;Woo, Sung-Woon;Kim, Ah-Na;Heo, Ho-Jin;Chun, Ji-Yeon;Choi, Sung-Gil
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.12
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    • pp.1847-1855
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    • 2015
  • Supercritical carbon dioxide ($SC-CO_2$) treatment has been becoming an important method for substituting the use of organic solvents for samples extraction prior to analysis due to its low toxicity, ease of handling, low cost of disposal etc. Freeze-dried bovine liver was treated with $SC-CO_2$ under different pressures (200, 300, and 450 bar) in order to investigate effects on physicochemical properties and reduction of microbial load. The yield of lipid extraction from bovine liver by $SC-CO_2$ treatment increased with increasing pressure, with values of 84, 86, and 90% in response to 200, 300, and 450 bar, respectively. Results of high performance liquid chromatography analysis showed that vitamin A and coenzyme $Q_{10}$ ($CoQ_{10}$), which is soluble in lipid, were almost removed from bovine liver by $SC-CO_2$ treatment. Saturated fatty acids ratio of bovine liver decreased with increasing pressure, whereas polyunsaturated fatty acids increased with increasing pressure. Total content of amino acids in bovine liver treated by $SC-CO_2$ was less than that of the control sample without treatment. The number of aerobic bacteria in bovine liver, which was stored at $5^{\circ}C$ for 5 days and freeze-dried, decreased from 6.2 to 4.2 log CFU/g by $SC-CO_2$ treatment at 100 bar for 3 h. Interestingly, coliform bacteria were not found in the bovine liver sample by $SC-CO_2$ at 100 bar for 3 h under all storage conditions. This indicates that $SC-CO_2$ treatment can effectively reduce coliform bacteria in the food matrix even at low moisture. In conclusion, freeze-dried bovine liver by proper $SC-CO_2$ treatment may be used as a potential high protein source, with increasing microbial safety and stability of lipid oxidation.

Effect of Sodium ion on the Anaerobic Degradation of Food Waste : Quantitative Evaluation, Inhibition Model (주방폐기물의 혐기성분해에 대한 나트륨이온의 영향: 저해 특성평가, 저해모델)

  • Shin, Hang-Sik;Song, Young-Chae;Paik, Byeong-Cheon
    • Journal of the Korea Organic Resources Recycling Association
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    • v.2 no.2
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    • pp.3-17
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    • 1994
  • The inhibitory effect of sodium ion on the anaerobic degradation of food waste was studied by an anaerobic batch toxicity assay and inhibition model. The anaerobic degradation activity of food waste spiked with over $2g\;Na^+/L$ of sodium ion was severely inhibited at the initial stage of the exposure. The inhibition response of anaerobic microorganisms on the sodium ion estimated from the methane production was differed according to the concentration of sodium ion. The relative acclimation time(RAT) and methanation rate(RMR), defined as the ratios of initial lag time and maximum methane production rate of the sample spiked with sodium ion to the control. respectively, were used to evaluate the acclimation and inhibitory effects quantitatively on the anaerobic microorganisms. When sodium ion was increased from $2g\;Na^+/L$ to $20g\;Na^+/L$, the RAT was exponentially increased from 18.9 to 90. but the RMR was linearly decreased from 0.97 to 0.02. The effects of sodium ion for the maximum methanation rate, first order kinetic constant and ultimate methane production were well evaluated by a generalized nonlinear expression model. it could be described by the uncompetitive inhibition mode. The sodium ion concentration causing 50% inhibition of methanation activity was about $11g\;Na^+/L$, and the critical sodium ion beyond to compelete inhibition was 20 to $21g\;Na^+/L$. The presented results could be used to obtain the design or operation parameters of the anaerobic process treating food waste of high salt.

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The Preliminary Results of Intensity-Modulated Radiotherapy for Tonsillar Cancer (편도암에 대한 세기조절방사선치료의 예비적 결과)

  • Park, Geum-Ju;Lee, Sang-Wook;Choi, Eun-Kyung;Kim, Jong-Hoon;Song, Si-Yeol;Youn, Sang-Min;Park, Sung-Ho;Park, Dong-Wook;Ahn, Seung-Do
    • Radiation Oncology Journal
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    • v.27 no.3
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    • pp.120-125
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    • 2009
  • Purpose: We wanted to present the preliminary results of intensity-modulated radiotherapy (IMRT) for the treatment of tonsillar cancer. Materials and Methods: We retrospectively analyzed 12 patients who underwent IMRT for tonsillar cancer at Asan Medical Center between November 2002 and February 2007. Seven patients (58%) received definitive treatment, and five (42%) were treated in the postoperative setting. Among the definitively treated patients, 6 patients received cisplatin-based chemotherapy regimens. Simultaneous modulated accelerated radiation therapy (SMART) was used in nine patients. The prescribed dose was 72 Gy at 2.4 Gy/fraction for the definitively treated cases and 61.6 Gy at 2.2 Gy/fraction for the postoperative cases. The median follow-up period was 34 months. Results: All twelve patients completed treatment without interruption, and eleven showed a complete response. One patient had persistent loco-regional disease after treatment. The three-year estimates of loco-regional control, disease-free survival and overall survival were 91.7%, 91.7%, and 100%. The worst acute mucositis was Grade 1 in four patients, Grade 2 in five patients, Grade 3 in two patients and Grade 4 in one patient. Grade 3 xerostomia was observed in six patients. Conclusion: Intensity-modulated radiotherapy was shown to be a safe and effective treatment modality for tonsillar cancer. Further studies with a larger number of patients and a longer follow-up period are needed to evaluate the ultimate tumor control and late toxicity of IMRT for treating tonsillar cancer.

Comparison of Amphotericin B and Itraconazole as Empirical Antifungal Therapy in Children with Acute Leukemia with Neutropenic Fever (발열을 동반한 호중구감소 상태의 급성백혈병 환아에서 경험적 항진균제로 투여한 Amphotericin B와 Itraconazole의 효과와 이상 반응 비교)

  • Lee, Sang-Yun;Park, Jong-Sun;Kim, Sun-Young;Yang, Keum-Jin;Park, Kyung-Deok;Kim, Hack-Ki
    • Pediatric Infection and Vaccine
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    • v.12 no.1
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    • pp.75-85
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    • 2005
  • Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.

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Influence of Toxic Heavy Metals on Germination of Rice Seeds and Growth of Rice Seedling (수도생육(水稻生育)에 대한 유해(有害) 중금속(重金屬)의 영향(影響) - 발아 및 묘대기(苗垈期) 생육(生育)에 대하여 -)

  • Kim, B.J.;Ha, Y.L.;Kim, J.O.;Han, K.H.
    • Korean Journal of Soil Science and Fertilizer
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    • v.11 no.2
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    • pp.119-126
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    • 1979
  • Rice seeds, suweon 264, were germinated under 5 levels of toxic heavy metals, Cd(0, 0.05, 0.5, 5, 20ppm), Cu(0, 0.05, 0.5, 5, 20, ppm), Cr(0, 0.5, 1, 5, 10ppm), Ni(0, 0.5, 1, 5, 10ppm), Co(0, 0.5, 1, 5, 10ppm), Zn(0, 0.5, 5, 20, 40, ppm), Pb(0, 0.5, 5, 20, 40ppm) and Mn(0, 1, 10, 25, 50, ppm) in culture solution, and then grown with supplying culture solution contained respective concentrations. Germination and growth response to the toxic heavy metals were studied. Results obtained are as follows : 1) The germination injury of rice seeds by excess concentration of toxic heave metal in culture solution occured in Cd and Cu; below 0.05 ppm, Ni; below 0.5 ppm, Mn; below 1.0 ppm, Co and Cr; 0.5-1.0 ppm, and 0.5-5 ppm, Zn and Pb. Thereby, in the order of degrees of the elements toxicity to germination, they were arranged as follows : Cd>Cu>Ni>Co>Cr>Mn>Zn$$\geq_-$$Pb. 2) Toxic heavy metal concentrations in culture solution, which result in decreasing dry weight due to the injury of excess concentration of treated elements, were Cd: below 0.05 ppm, Ni, Cr and Co; below 0.5 ppm, Cu and Zn; 0.5-5 ppm, Pb; 5-20 ppm and Mn; 10-25 ppm. The order was Ni>Cd>Cr>Co>Cu$$\geq_-$$Zn>Pb>Mn. 3) The critical contents of Cd, Ni, Pb, Cu, Zn, Mn, and Co in dry matter, Which result in decreasing dry weight, were considered to be 0.05-15.5, 1.50-25.0, 24.0-28.0, 26.5-62.5, 470-645.0, 231.0-500.0 and below 15.0 ppm, respectively. 4) The contents of Cr, Co, Cd, Pb, Ni, Cu and Zn in dry matter by 0.5 ppm treatment concentration of each heavy metals was trace, 15.0, 17.5, 24.0, 25.0, 84.5 and 470.0 ppm, respectively. Thereby, in the order of each element to uptaked by rice seedlings, they were arranged as follow; Zn>Cu>Ni>Pb>Cd>Co>Cr. 5) The hazardous concentrations of root activity by toxic heavy metals in culture solution were Cd; below 0.05, Cu; 0.05-0.5, Cr; below 0.5, Ni; 0.5-1.0, Co; 0.5-1.0, Zn; above 0.5, Pb; 0.5-5.0 and Mn; 1.0-10.0 ppm. The hazardous degree of root activity by toxic heave metals was in the order of Cd>Cu>Cr>Zn>Ni>Co>Pb>Mn.

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Determination of Target Clean-up Level and Risk-Based Remediation Strategy (위해성에 근거한 정화목표 산정 및 복원전략 수립)

  • Ryu, Hye-Rim;Han, Joon-Kyoung;Nam, Kyoung-Phile
    • Journal of Soil and Groundwater Environment
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    • v.12 no.1
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    • pp.73-86
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    • 2007
  • Risk-based remediation strategy (RBRS) is a consistent decision-making process for the assessment and response to chemical release based on protecting human health and the environment. The decision-making process described integrates exposure and risk assessment practices with site assessment activities and remedial action selection to ensure that the chosen actions are protective of human health and the environment. The general sequences of events in Tier 1 is as follows: initial site assessment, development of conceptual site model with all exposure pathways, data collection on pollutants and receptors, and identification of risk-based screening level (RBSL). If site conditions do not meet RBSL, it needs further site-specific tier evaluation, Tier 2. In most cases, only limited number of exposure pathways, exposure scenarios, and chemicals of concern are considered the Tier 2 evaluation since many are eliminated from consideration during the Tier 1 evaluation. In spite of uncertainties due to the conservatism applied to risk calculations, limitation in site-specific data collections, and variables affecting the selection of target risk levels and exposure factors, RBRS provides us time- and cost-effectiveness of the remedial action. To ensure reliance of the results, the development team should consider land and resource use, cumulative risks, and additive effects. In addition, it is necessary to develop appropriate site assessment guideline and reliable toxicity assessment method, and to study on site-specific parameters and exposure parameters in Korea.

Changes of Nitrogen Uptake, Growth and Activities of Nitrogen Metabolizing Enzymes by Different Source of Nitrogen in Tobacco (담배에서 질소 형태에 따른 흡수 양상 및 생육과 질소대사 효소의 활성 변화)

  • 이상각;심상인;강병화;배길관
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.42 no.5
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    • pp.515-521
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    • 1997
  • Tobacco plant was grown for 40 days hydroponically in nutrient solutions composed of different forms of nitrogen, like NO$_3$$^{[-10]}$ -N, NH$_4$$^{+}$-N, and a mixed formulation of NO$_3$$^{[-10]}$ -N and NH$_4$$^{+}$-N. Uptake response, nitrate reductase, and glutamine synthetase activity at growth stage were investigated to understand the basic knowledge of nitrogen metabolism. The better growth of shoot and root was observed in the mixed nutrient solution than NO$_3$$^{[-10]}$ -N or NH$_4$$^{+}$-N, alone. The plant growth in NH$_4$$^{+}$-N nutrient solution was poor due to ammonium toxicity. The pH of nutrient solution containing NO$_3$$^{[-10]}$ -N increased up to 40 days after transplanting. But the pH of solution containing NO$_3$$^{[-10]}$ -N decreased drastically to 3.42 at 20 days after transplant. The pH in the mixed formulation dropped to pH 3.64 at 30 days after transplant and showed re-increase. It is assumed that nitrogen of NH$_4$$^{+}$-N form was taken up preferentially at early stage and NO$_3$$^{[-10]}$ -N form was taken up preferentially at middle stage in the treatment with the mixed solution. The result indicates that the relative proportion of nitrogen forms affected the uptake patterns at each growth stages. The contents of chlorophyll and soluble protein were high with the mixed solution. Total nitrogen content was the highest in NH$_4$$^{+}$-N solution and the content also increased by the application of the mixed type of nitrogen. The amount of nitrate in leaves was high in NO$_3$$^{[-10]}$ -N treatment and the amount of ammonium was high in NH$_4$$^{+}$-N treatment. The activity of nitrate reductase or glutamine synthetase was highest in the leaves grown in mixed nutrient solution than in those with any other single of nitrogen form.

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Influence of Potassium Concentrations in Fertilizer Solution on the Growth, Appearance of Physiological Disorder and Tissue Nutrient Contents of Eggplant (Solanum melogena L.) (칼륨 시비농도가 가지의 생육과 생리장해 발현 및 무기원소 함량에 미치는 영향)

  • Kim, Jeong-Man;Kim, Ju;Chon, Hyong-Gwon;Park, Eun-Seok;Jeong, Jong-Seong;Choi, Jong-Myung
    • Horticultural Science & Technology
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    • v.28 no.5
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    • pp.743-749
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    • 2010
  • Objective of this research was to investigate the effect of various potassium concentrations in fertilizer solution on growth of and nutrient uptake by 'Chugyang' eggplant ($Solanum$ $melongena$ L.). Tissue analyses were conducted to determine the threshold levels of potassium in plants when disorders develop for potassium. The lower leaves of K deficient plants became spotted, yellowing in color, and finally necrosis occurred. The necrosis spread inward and upward. K toxic plants developed necrotic spot at the margin of old leaves and the surface of old leaves were twisted. The tissue K contents in the most recently fully expanded leaves and dry weight of full above ground plant tissue at 35 days after transplanting showed linear and quadratic response to elevated K concentrations with the equation of y=1.127+0.3147x ($R^2$=0.8916) and y=14.92+2.2743x-$0.1402x_2$ ($R^2$=0.8659). When 10% reduction in dry weight set to threshold levels, optimum tissue K contents are in the range from 2.1 to 5.1%. The yield through 150 days after transplanting and tissue K contents at 150 days after transplanting also showed quadratic and linear responses to elevated potassium concentrations in fertigation solution with the equation of y=153.24+345.5x-$18.46x^2$ ($R^2$=0.8620) and y=0.9921+0.3860x ($R^2$=0.9611), respectively. When the 10% reduction in yield is set to threshold levels, the tissue K contents for maximum yield should be around 3.4% to 5.9% in most recently fully expanded leaves.

Drug Interaction between Ginseng Extract (GE) and Sorafenib (쏘라페닙과 홍삼추출물간의 약물상호작용)

  • Lee, Nam-Hee;Park, Ho-Jae;Rho, Ja-Sung;Kim, Mi-Kyung;Lee, Yu-Kyoung;Cho, Eun-A;Heo, Jeong;Cho, Mong;Hwang, Tae-Ho
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1518-1525
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    • 2011
  • Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.