• Title/Summary/Keyword: Non-toxicity

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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.

The development of conductive 10B thin film for neutron monitoring (중성자 모니터링을 위한 전도성 10B 박막 개발)

  • Lim, Chang Hwy;Kim, Jongyul;Lee, Suhyun;Jung, Yongju;Choi, Young-Hyun;Baek, Cheol-Ha;Moon, Myung-Kook
    • Journal of Radiation Protection and Research
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    • v.39 no.4
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    • pp.199-205
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    • 2014
  • In the field of neutron detections, $^3He$ gas, the so-called "the gold standard," is the most widely used material for neutron detections because of its high efficiency in neutron capturing. However, from variable causes since early 2009, $^3He$ is being depleted, which has maintained an upward pressure on its cost. For this reason, the demands for $^3He$ replacements are rising sharply. Research into neutron converting materials, which has not been used well due to a neutron detection efficiency lower than the efficiency of $^3He$, although it can be chosen for use in a neutron detector, has been highlighted again. $^{10}B$, which is one of the $^3He$ replacements, such as $BF_3$, $^6Li$, $^{10}B$, $Gd_2O_2S$, is being researched by various detector development groups owing to a number of advantages such as easy gamma-ray discrimination, non-toxicity, low cost, etc. One of the possible techniques for the detection is an indirect neutron detection method measuring secondary radiation generated by interactions between neutrons and $^{10}B$. Because of the mean free path of alpha particle from interactions that are very short in a solid material, the thickness of $^{10}B$ should be thin. Therefore, to increase the neutron detection efficiency, it is important to make a $^{10}B$ thin film. In this study, we fabricated a $^{10}B$ thin film that is about 60 um in thickness for neutron detection using well-known technology for the manufacturing of a thin electrode for use in lithium ion batteries. In addition, by performing simple physical tests on the conductivity, dispersion, adhesion, and flexibility, we confirmed that the physical characteristics of the fabricated $^{10}B$ thin film are good. Using the fabricated $^{10}B$ thin film, we made a proportional counter for neutron monitoring and measured the neutron pulse height spectrum at a neutron facility at KAERI. Furthermore, we calculated using the Monte Carlo simulation the change of neutron detection efficiency according to the number of thin film layers. In conclusion, we suggest a fabrication method of a $^{10}B$ thin film using the technology used in making a thin electrode of lithium ion batteries and made the $^{10}B$ thin film for neutron detection using suggested method.

Gemcitabine-induced Cell Death in Lung Cancer Cells : the Role of p53 (폐암 세포에서 Gemcitabine에 의한 세포 사멸과 p53의 역할)

  • Kim, Doh-Hyung;Bae, Gang-U;Yong, Wha-Shim;Choi, Eun-Kyung;Kim, Youn-Seup;Park, Jae-Seuk;Jee, Young-Koo;Lee, Kye-Young
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.3
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    • pp.275-284
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    • 2002
  • Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.

The Physiological Efficacy of Aloe Gel (Aloe Gel의 생리 효과에 대한 고찰 - Gel의 다당류와 미량 성분을 중심으로 -)

  • 서화중
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.24 no.6
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    • pp.1026-1038
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    • 1995
  • Although aloe lost a lot of its previous popularity in modern clinical uses as medicine numerous scientific researches still have claimed the beneficial properties(curing and general tonic effect) of aloe gel. Whereas considerable contradictory reports have helped to confuse the aloe gel issue and continually aroused controversy about aloe gel efficacy. However health food, cosmetic and medicinal products made from aloe gel are widely available in the world market especially in U.S.A. so the growing of Aloe plant and the processing of A. vera gel have become big industries in some countries. In some previous papers the salicylic acid, one of the common trace gel components, was thought to have an analgetic and antinflammatory effect. Large amount of Mg ion in the gel was suggested to act as anesthetic, Mg-lactate as antihistamic, and Aloctin A(a glycoprotein) as wound healer by promoting the cell growth. The carboxypeptidase and bradykinase activity in the gel were proposed to have the pain relieving and antiinflammatory effect. But any of thes etheories concerining the physiological action of the trace gel components has not been demonstrated by modern pharmacology, and failed to be supported by clinical research. It was suggested by some research workers that trace amount of anthraquinone compounds in the gel play an important role to act as false substrate inhibitors for PG and TX production(antiprostanoid effect), by which, they believed, inflammation, burn and frostbite, and infected wound could be healed. This hypothesis has not been substantiated. Butthe suggested antimicrobial action, antidiabetic, and antidotic effect of aloe gel are likely to be attributed to the trace anthraquinone compounds. In a lot of recent experimental reports it has been claimed that aloe gel polysaccharides(acetylglucomannan, acetylmannan, and glycoprotein) have the antimicrobial, antinflammatory, antitumour, and infected wound healing effect by immunoenhancement. It is hoped that these effects will be soon documented in clinical studies, then the controversy on aloe gel beneficial effect will cease. In the 30 days subchronic toxicity test the lowest observed adverse effect level of acemannan(acetylmannan) on dog was 5.0 mg/kg, IP. But the aloe gel is generally agreed to be harmless and non toxic even for the internal use such as health food. In the case of idiosynrasy one must keep the delayed type hypersensitivity reaction of aloe gel in mind. In conclusion it seem to be impossible to simply refuse a lot of evidences made by research workers who have claimed aloe gel's beneficial effects and to deny the fact that there had been long therapeutic histories of Aloe plants.

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Preliminary Results of Phase I/II Study of Simultaneous Modulated Accelerated (SMART) for Nasopharyngeal Carcinoma (비인강암의 치료에서 동시차등조사가속치료를 적용한 제1상/2상 연구의 예비적 결과)

  • Park Jin-Hong;Back Geum-Mun;Yi Byong-Yong;Choi Eun-Kyung;Ahn Seung-Do;Shin Seong-Soo;Kim Jung-Hun;Kim Sang-Yoon;Lee Bong-Jae;Nam Soon-Yuhl;Choi Seung-Ho;Kim Seung-Bae;Lee Sang-Wook
    • Radiation Oncology Journal
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    • v.24 no.1
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    • pp.1-10
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    • 2006
  • Puroose: To present preliminary results of intensity-modulated radiotherapy (IMRT) using the simultaneous modulated accelerated radiation therapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). Materials and Methods: Twenty patients who underwent IMRT for non-metastatic NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. IMRT was delivered using the 'step and shoot' SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume (GTV), 60 Gy (2 Gy/day) to the clinical target volume (CTV) and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received concurrent chemotherapy using cisplatin once per week. Results: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had RTOG grade 3 mucositis, whereas nine (45%) had grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no grade 3 or 4 chronic xerostomia. All patients showed complete response. Two patients had distant metastases and loco-regional recurrence, respectively. Conclusion: IMRT using the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and may also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

Anti-inflammatory Efficacy and Liver Protective Activity of Pine Pollen according to Probe Sonicator Ultrasonic Disintegration Extraction Method (송화분의 초음파 파쇄 추출 방법에 따른 항염증 효능 및 간 보호 활성)

  • Kim, Ok Ju;Woo, Young Min;Jo, Eun Sol;Jo, Min Young;Li, Chun-Ri;Lee, Young-Ho;Ahn, Mee Young;Lee, Sang-Hyeon;Ha, Jong Myung;Kim, Andre
    • Applied Chemistry for Engineering
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    • v.30 no.5
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    • pp.569-579
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    • 2019
  • In this study, the effect anti-oxidant, anti-inflammatory, and liver protective activity was investigated via quick ultrasonic disintegration of pine pollen using a probe sonicator (PS) followed by the extraction with water, 70% ethanol, and 100% ethanol. The anti-inflammatory effect was studied by measuring the production of nitric oxide (NO) and cytokine in RAW264.7 cells induced with lipopolysaccharides (LPS). The cell toxicity was also checked with an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the experiment was conducted using non-toxic $100{\mu}g/mL$. The NO inhibition rate was highest in the 70% ethanol PS group at $85.99{\pm}0.12%$. Also an excellent efficiency was obtained from the results of interlukin-1 beta ($IL-1{\beta}$) and tumor necrosis factor alpha ($TNF-{\alpha}$), which is related to inflammation-related cytokine, with the respective inhibition rates of 63 and 22%. To examine liver protective activity, HepG2 cells were treated with Taclin, and the generation of glutamic oxaloacetic transaminase (GOT) and lactate dehydrogenase (LDH) was measured in the culture solution. From GOT and LDH generation results, the inhibition rates in the 70% ethanol PS group were 28% and 13%, respectively, which was higher compared to that of using negative control group. Our results suggest that pine pollen extracted in 70% ethanol using PS may be used to develop food products that have anti-aging, anti-inflammatory, and liver protective effects.

Risk Assessment of As, Cd, Cu and Pb in Different Rice Varieties Grown on the Contaminated Paddy Soil (중금속 오염 논토양에서 재배된 벼 품종간 위해성평가 비교)

  • Kim, Won-Il;Kim, Jin-Kyoung;Yoo, Ji-Hyock;Paik, Min-Kyoung;Park, Sang-Won;Kwon, Oh-Kyung;Hong, Moo-Ki;Yang, Jay-E;Kim, Jeong-Gyu
    • Korean Journal of Soil Science and Fertilizer
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    • v.42 no.1
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    • pp.53-57
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    • 2009
  • Heavy metal pollution may be one of the most serious challenges confront crop production and human health. Therefore, the selection of heavy metal tolerance cultivars which adapted to the contaminated fields will introduced a suitable solution for management this critical environmental risk. The objectives of this research is to assess human health risk using geochemical analyses and exposure assessment of heavy metals in rice cultivars. Risk for inhabitants in the closed mine area was comparatively assessed for As, Cd, Cu and Pb in 10 rice varieties as a major exposure pathway. The average daily dose (ADD) of each heavy metal was estimated by analyzing the exposure pathways to rice and soil. For the non-carcinogenic risk characterization, Hazard Quotient (HQ) and Hazard Index (HI) were calculated using toxicity indices provided by US-EPA IRIS. The different rice varieties revealed a wide range of HI values from 23.6 to 34.3, indicating that all rice varieties have a high potential toxic risk. The DA rice variety showed the lowest HI value while the TB rice variety the highest. The probabilities of cancer risk for As via rice consumption were varied with rice varieties ranging from 2.0E-03 to 3.5E-03 which exceeded the regulatory acceptable risk of 1 in 10,000 set by US-EPA. The DA rice variety also showed the lowest value while the TB rice variety gave the highest value. Our results indicate that risk assessment can be contribute to screen the pollution safe rice cultivars in paddy fields affected by the mining activity.

Gene Expression of Detoxification Enzymes in Tenebrio molitor after Fungicide Captan Exposure (살진균제인 캡탄 처리 후 갈색거저리의 해독효소 유전자 발현)

  • Jang, Ho am;Baek, Hyoung-Seon;Kim, Bo Bae;Kojour, Maryam Ali Mohammadie;Patnaik, Bharat Bhusan;Jo, Yong Hun;Han, Yeon Soo
    • Korean journal of applied entomology
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    • v.61 no.1
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    • pp.155-163
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    • 2022
  • The application of fungicides is indispensable to global food security, and their use has increased in recent times. Fungicides, directly or indirectly, have impacted insects, leading to genetic and molecular-level changes. Various detoxification mechanisms allow insects to eliminate reactive oxygen species (ROS) toxicity induced by agrochemicals including fungicides. In the present study, we analyzed the mRNA expression levels of detoxifying enzymes in Tenebrio molitor larvae following exposure to non-lethal doses (0.2, 2, and 20 ㎍/µL) of a fungicide captan. Transcripts of peroxidases (POXs), catalases (CATs), superoxide dismutases (SODs), and glutathione-s-transferases (GSTs) were screened from the T. molitor transcriptome database. RT-qPCR analysis showed that TmPOX5 mRNA increased significantly 24 h post-captan exposure. A similar increase was noticed for TmSOD4 mRNA 3 h post-captan exposure. Moreover, the expression of TmCAT2 mRNA increased significantly 24 h post-treatment with 2 ㎍/µL captan. TmGST1 and TmGST3 mRNA expression also increased noticeably after captan exposure. Taken together, these results suggest that TmPOX5 and TmSOD4 mRNA can be used as biomarkers or xenobiotics sensors for captan exposure in T. molitor, while other detoxifying enzymes showed differential expression.

Risk Assessment of Heavy Metals Migrated from Plastic Food Utensils, Containers, and Packaging Distributed in Korea (국내 유통 식품용 플라스틱 기구 및 용기, 포장의 중금속 위해도 평가)

  • Kyung Youn, Lee;Hyung Soo, Kim;Dae Yong, Jang;Ye Ji, Koo;Seung Ha, Lee;Hye Bin, Yeo;Ji Su, Yoon;Kyung-Min, Lim;Jaeyun, Choi
    • KOREAN JOURNAL OF PACKAGING SCIENCE & TECHNOLOGY
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    • v.28 no.3
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    • pp.175-182
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    • 2022
  • Heavy metals can be intentionally or unintentionally introduced into plastic food utensils, containers, and packaging (PFUCP) as additives or contaminants, which can be ingested with food by humans. Here, seven-heavy metals (lead, cadmium, nickel, chromium, antimony, copper, and manganese) with toxicity concerns were selected, and risk assessment was done by establishing their migration from 137 PFUCP products made of 16 materials distributed in Korea. Migration of heavy metals was examined by applying 4% acetic acid as a food simulant (70℃, 30 minutes) to the PFUCP products. Inductively coupled plasma mass spectrometry (ICP-MS) was employed for the analysis of migrated heavy metals, and the reliability of quantitative results was confirmed by checking linearity, LOD, LOQ, recovery, precision, and expanded uncertainty. As a result of monitoring, heavy metals were detected at a level of non-detection to 8.76 ± 11.87 ㎍/L and most of the heavy metals investigated were only detected at trace amounts of less than 1 ㎍/L on average. However, antimony migrated from PET products was significantly higher than other groups. Risk assessment revealed that all the heavy metals investigated were safe with a margin of exposure above 311. Collectively, we demonstrated that heavy metals migrated from PFUCP products distributed in Korea appear to be within the safe range.

Reversal of Multidrug Resistance with KR-30035: Evaluated with Biodistribution of Tc-99m MIBI in Nude Mice Bearing Human Tumor Xenografts (이종이식된 인체종양에서 KR-30035가 Tc-99m MIBI체내 분포에 미치는 영향으로 평가한 다약제내성 역전가능성)

  • Kim, Jung-Kyun;Lee, Byung-Ho;Choi, Sang-Woon;Yoo, Sung-Eun;Lee, Sang-Woo;Chun, Kyung-Ah;Ahn, Byeong-Cheol;Park, Jae-Young;Suh, Jang-Soo;Lee, Kyu-Bo;Lee, Jae-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.35 no.3
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    • pp.168-184
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    • 2001
  • Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

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