• Nuclear Engineering and Technology
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• 제39권2호
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• pp.149-160
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• 2007

The IAEA launched the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) and developed the INPRO Methodology to provide guidelines and to assess the characteristics of a future innovative nuclear energy system in areas such as safety, economics, waste management, and proliferation resistance. The proliferation resistance area of the INPRO Methodology is reviewed here, and modifications for further improvements are proposed. The evaluation metrics including the evaluation parameters, evaluation scales and acceptance limits are developed for a practical application of the methodology to assess the proliferation resistance. The proliferation resistant characteristics of the DUPIC fuel cycle are assessed by applying the modified INPRO Methodology based on the developed evaluation metrics and acceptance criteria. The evaluation procedure and the metrics can be utilized as a reference for an evaluation of the proliferation resistance of a future innovative nuclear energy system.

• 한국방사성폐기물학회:학술대회논문집
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• 한국방사성폐기물학회 2009년도 학술논문요약집
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• pp.53-54
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• 2009

The preliminary quantitative analysis of proliferation resistance for the five nuclear fuel cycles demonstrated that the thermal MOX fuel cycle is most vulnerable to proliferation due to the presence of pure $PuO_2$ in the fuel cycle, while the once-through fuel cycle has the highest proliferation resistance. The innovative next generation fuel cycles such as Pyro-SFR and Wet-SFR were found to have similar levels of proliferation resistance to that of the DUPIC fuel cycle which is believed to have proliferation resistance strong enough for commercial deployment. The sensitivity analysis also demonstrated the effectiveness of the proposed methodology in applying to existing and/or newly developing nuclear fuel cycles so as to improve the proliferation resistance characteristic of the fuel cycle systems.

• 한국방사성폐기물학회:학술대회논문집
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• 한국방사성폐기물학회 2009년도 학술논문요약집
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• pp.73-73
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• 2009

There are many factors to evaluate nuclear fuel cycle such as safety, public acceptance, economics, etc.. Transparency, proliferation, environment issues, public acceptance and safety are essential to expansion of nuclear industry and proliferation resistance is one of key constraints in the deployment of advanced nuclear energy systems. Proliferation resistance is being considered as one of the most important factors in assessing advanced and innovative nuclear systems. IAEA defmes proliferation resistance as characteristics of nuclear energy system that impedes the diversion or undeclared production of nuclear material [1]. Barriers to proliferation is consist of intrinsic and extrinsic barriers(institutional measures). Intrinsic barriers are characterized in material barriers and technical barriers in general. Material barriers is intrinsic, or inherent, qualities of materials that reduce the inherent desirability or attractiveness of the material as an explosive. Isotopic, chemical, radiological, mass and bulk, detectability barriers are considered as material barriers attributes [2]. Proliferation resistance is examined for several nuclear fuel cycles based on previous study which is focused on the intrinsic barriers [3-4]. Pyroprocessing and DUPIC are considered as reprocessing technologies in Korea and the PWR direct disposal is considered. Comparative assessments of the proliferation attributes and merits of different fuel cycle systems will be performed and the optimal back-end fuel cycle and strategy will be proposed.

• Biomolecules & Therapeutics
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• 제30권3호
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• pp.257-264
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• 2022

Colorectal cancer (CRC) is one of the most common malignant tumor. 5-FU is commonly used for the treatment of CRC. However, the development of drug resistance in tumor chemotherapy can seriously reduce therapeutic efficacy of 5-FU. Recent data show that FoxM1 is associated with 5-FU resistance in CRC. FoxM1 plays a critical role in the carcinogenesis and drug resistance of several malignancies. It has been reported that urushiol V isolated from the cortex of Rhus verniciflua Stokes is cytotoxic to several types of cancer cells. However, the underlying molecular mechanisms for its antitumor activity and its potential to attenuate the chemotherapeutic resistance in CRC cells remain unknown. Here, we found that urushiol V could inhibit the cell proliferation and induced S-phase arrest of SW480 colon cancer cells. It inhibited protein expression level of FoxM1 through activation of AMPK. We also investigated the combined effect of urushiol V and 5-FU. The combination treatment reduced FoxM1 expression and consequently reduced cell growth and colony formation in 5-FU resistant colon cancer cells (SW480/5-FUR). Taken together, these result suggest that urushiol V from Rhus verniciflua Stokes can suppress cell proliferation by inhibiting FoxM1 and enhance the antitumor capacity of 5-FU. Therefore, urushiol V may be a potential bioactive compound for CRC therapy.

• Biomolecules & Therapeutics
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• 제25권5호
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• pp.490-496
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• 2017

Imatinib resistance has become a major clinical problem for chronic myeloid leukemia. The aim of the present study was to investigate the involvement of MEG3, a lncRNA, in imatinib resistance and demonstrate its underlying mechanisms. RNAs were extracted from CML patients' peripheral blood cells and human leukemic K562 cells, and the expression of MEG3 was measured by RT-qPCR. Cell proliferation and cell apoptosis were evaluated. Western blotting was used to measure the protein expression of several multidrug resistant transporters. Luciferase reporter assay was performed to determine the binding between MEG3 and miR-21. Our results showed that MEG3 was significantly decreased in imatinib-resistant CML patients and imatinib-resistant K562 cells. Overexpression of MEG3 in imatinib-resistant K562 cells markedly decreased cell proliferation, increased cell apoptosis, reversed imatinib resistance, and reduced the expression of MRP1, MDR1, and ABCG2. Interestingly, MEG3 binds to miR-21. MEG3 and miR-21 were negatively correlated in CML patients. In addition, miR-21 mimics reversed the phenotype of MEG3-overexpression in imatinib-resistant K562 cells. Taken together, MEG3 is involved in imatinib resistance in CML and possibly contributes to imatinib resistance through regulating miR-21, and subsequent cell proliferation, apoptosis and expression of multidrug resistant transporters.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1391-1396
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• 2014

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most common cause of lung cancer death. Currently, the epidermal growth factor receptor inhibitor gefitinib is used for its treatment; however, drug resistance is a major obstacle. Expression of Met has been associated with both primary and acquired resistance to gefitinib, but the mechanisms regulating its expression are not fully understood. Recently, miRNAs such as miR-130a have been shown to play a role in gefitinib resistance, but importance in NSCLC and relationships with Met have not been fully explored. Here we show that miR-130a is over-expressed in gefitinibsensitive NSCLC cell lines, but is low in gefitinib-resistant NSCLC cell lines. Moreover, miR-130a expression was negatively correlated with that of Met. Further analysis revealed that over-expression of miR-130a increased cell apoptosis and inhibited proliferation of NSCLC cells treated with gefitinib, whereas lowering the expression of miR-130a decreased cell apoptosis and promoted cell proliferation after treatment with gefitinib in both gefitinib-sensitive and -resistant NSCLC cell lines, suggesting that miR-130a overcomes gefitinib resistance. We also demonstrated that miR-130a binds to the 3'-UTR of Met and significantly suppresses its expression. Finally, our results showed that over-expressing Met could "rescue" the functions of miR-130a regarding cell apoptosis and proliferation after cells are treated with gefitinib. These findings indicate that the miR-130a/Met axis plays an important role in gefitinib resistance in NSCLC. Thus, the miR-130a/Met axis may be an effective therapeutic target in gefitinib-resistant lung cancer patients.

• Preventive Nutrition and Food Science
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• 제9권4호
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• pp.367-373
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• 2004

The prevalence of type-2 diabetes increases remarkably in post-menopausal women, possibly because insulin secretion fails to compensate for the insulin resistance induced in various tissues by estrogen insufficiency. However, this has not been fully defined. Therefore, the present study investigated whether an ovariectomy (OVX) would increase insulin resistance and decrease the $\beta$-cell function and mass in female rats with and without a $90\%$ pancreatectomy (Px). Female rats aged 15 weeks were divided into four groups: 1) OVX + Px, 2) SOVX (sham operation of OVX) + Px, 3) OVX + SPx (sham operation of Px), and 4) SOVX + SPx, and given a $30\%$ fat diet for 8 weeks. At the end of the experimental period, the islet function and insulin resistance were determined using a hyperglycemic clamp and a euglycemic hyperinsulinemic clamp, respectively. The OVX only increased the body weight in the SPx rats, which was partially related to the food intake. Yet, the OVX did increase the peripheral insulin resistance, while the Px increased this resistance further. The OVX and Px both exacerbated the islet function, as measured by the insulin secretion pattern, while delaying and decreasing the first-phase insulin secretion. The OVX only decreased the proliferation of $\beta$-cells in the Px rats, while increasing apoptosis in both the Px and SPx rats. As a result, the OVX decreased the $\beta$-cell mass in the Px rats, but increased the mass in the SPx rats. In conclusion, an OVX was found to accelerate the development and progression of diabetes by increasing the insulin resistance and decreasing the $\beta$-cell mass. Therefore, menopause can be a risk factor for type-2 diabetes, mainly due to a deceased proliferation of $\beta$-cells.

• Nuclear Engineering and Technology
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• 제37권1호
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• pp.91-100
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• 2005

Kyung-hee Thorium Fuel (KTF), a heterogeneous thorium-based seed and blanket design concept for pressurized light water reactors, is being studied as an alternative to enhance proliferation resistance and fuel cycle economics of PWRs. The proliferation resistance characteristics of the KTF assembly design were evaluated through parametric studies using neutronic performance indices such as Bare Critical Mass (BCM), Spontaneous Neutron Source rate (SNS), Thermal Generation rate (TG), and Radio-Toxicity. Also, Fissile Economic Index (FEI), a new index for gauging fuel cycle economy, was suggested and applied to optimize the KTF design. A core loaded with optimized KTF assemblies with a seed-to-blanket ratio of 1: 1 was tested at the Korea Next Generation Reactor (KNGR), ARP-1400. Core design characteristics for cycle length, power distribution, and power peaking were evaluated by HELIOS and MASTER code systems for nine reload cycles. The core calculation results show that the KTF assembly design has nearly the same neutronic performance as those of a conventional $UO_2$ fuel assembly. However, the power peaking factor is relatively higher than that of conventional PWRs as the maximum Fq is 2.69 at the M$9^{th}$ equilibrium cycle while the design limit is 2.58. In order to assess the economic potential of a heterogeneous thorium fuel core, the front-end fuel cycle costs as well as the spent fuel disposal costs were compared with those of a reference PWR fueled with $UO_2$. In the case of comprising back-end fuel cycle cost, the fuel cycle cost of APR-1400 with a KTF assembly is 4.99 mills/KWe-yr, which is lower than that (5.23 mills/KWe-yr) of a conventional PWR. Proliferation resistance potential, BCM, SNS, and TG of a heterogeneous thorium-fueled core are much higher than those of the $UO_2$ core. The once-through fuel cycle application of heterogeneous thorium fuel assemblies demonstrated good competitiveness relative to $UO_2$ in terms of economics.

• Nuclear Engineering and Technology
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• 제50권5호
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• pp.794-800
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• 2018

The proliferation resistance (PR) of Th/U and Th/Pu fuels used in CANada Deuterium Uranium for the deep geological repository was assessed by combining the multiattribute utility analysis proposed by Chirayath et al., 2015 with the transport model of radionuclides in the repository and comparing with that of the used natural U fuel case. It was found that there was no significant advantage for Th/U and Th/Pu fuels from the viewpoint of the PR in the repository. It was also found that the PR values for used nuclear fuels in the repository of Th/U, Th/Pu, and natural U was comparable with those for enrichment and reprocessing facilities in the pressurized water reactor (PWR) nuclear fuel cycle. On the other hand, the PR values considering the transport of radionuclides in the repository were found to be slightly smaller than those without their transport after the used nuclear fuels started dissolving after 1,000 years.

• 대한핵의학회지
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• 제36권4호
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• pp.209-223
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• 2002

By considering the biological properties of a tumor, it should be possible to realize better results in cancer therapy. PET imaging offers the opportunity to measure tumor growth non-invasively and repeatedly as an early assessment of response to cancer therapy. Measuring cellular growth instead of energy metabolism showed offer significant advantages in evaluating therapy. Thymidine and its derivative nucleoside compounds can be changed to mono, di- and tri- phosphate compounds by thymidine kinase and then be incorporated into DNA. Their bindings are increased in highly proliferating cells due to the high DNA synthesis rate. To evaluate cell proliferation, many kinds of thymidine and uridine derivatives have been labeled with positron emitter and radioactive iodine. Compared to radiopharmaceuticals which have radioisotope labeled base ring such as pyirmidine, the radiopharmacuticals which have radioisotope labeled sugar ring are more stable in vivo and have metabolic resistance. The biological properties such as DNA incorporation ratios are highly dependent on their chemical structures and metabolic processes. This overview describes synthesis of radiopharmaceuticals and their biological properties for imaging of tumor cell proliferation.