• 제목/요약/키워드: Proliferation Resistance

검색결과 246건 처리시간 0.036초

Assessment of the material attractiveness and reactivity feedback coefficients of various fuel cycles for the Canadian concept of Super-Critical Water Reactors

  • Ibrahim, Remon;Buijs, Adriaan;Luxat, John
    • Nuclear Engineering and Technology
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    • 제54권7호
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    • pp.2660-2669
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    • 2022
  • The attractiveness for weapons usage of the proposed fuel cycle for the PT-SCWR was evaluated in this study using the Figure-of-Merit methodology. It was compared to the attractiveness of other fuel cycles namely, Low Enriched Uranium (LEU), U/Th, Re-enriched Reprocessed Uranium (RepU), and Pu/Th/U. The optimal content of natural uranium, which can be added to Pu/Th to render the produced U-233 unattractive, was found to be 9%. A ranking system to compare the attractiveness of the various fuel cycles is proposed. RepU was found to be the most proliferation resistant fuel cycle for the first 100 years,while, the least proliferation resistant fuel cycle was the originally proposed Pu/Th one. The reactivity feedback coefficients were calculated for all proposed fuel cycles. All studied reactivity coefficients have the same sign implying that all the fuel cycles will behave neutronically in a similar way. The Pu/Th/U fuel was found to have the most negative value of the Coolant Void Reactivity which will help to restore the core to a safe status faster in case of a loss-of-coolant accident. The fuel and moderator temperature coefficients did not show significant differences between the fuels studied.

Tumor bioenergetics: An emerging avenue for cancer metabolism targeted therapy

  • Kee, Hyun Jung;Cheong, Jae-Ho
    • BMB Reports
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    • 제47권3호
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    • pp.158-166
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    • 2014
  • Cell proliferation is a delicately regulated process that couples growth signals and metabolic demands to produce daughter cells. Interestingly, the proliferation of tumor cells immensely depends on glycolysis, the Warburg effect, to ensure a sufficient amount of metabolic flux and bioenergetics for macromolecule synthesis and cell division. This unique metabolic derangement would provide an opportunity for developing cancer therapeutic strategy, particularly when other diverse anti-cancer treatments have been proved ineffective in achieving durable response, largely due to the emergence of resistance. Recent advances in deeper understanding of cancer metabolism usher in new horizons of the next generation strategy for cancer therapy. Here, we discuss the focused review of cancer energy metabolism, and the therapeutic exploitation of glycolysis and OXPHOS as a novel anti-cancer strategy, with particular emphasis on the promise of this approach, among other cancer metabolism targeted therapies that reveal unexpected complexity and context-dependent metabolic adaptability, complicating the development of effective strategies.

RNA Interference to Prevent Bombyx mori Nuclear Polyhedrosis Virus Infection in Vivo

  • Hu Zhigang;Chen Keping;Gao Lu;Yao Qin
    • International Journal of Industrial Entomology and Biomaterials
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    • 제12권1호
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    • pp.15-19
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    • 2006
  • RNA interference has been used as a powerful tool in preventing virus proliferation in many species. In this study, we injected the dsRNA in vitro transcripts into Bombyx mori to investigate the resistance to B. mori nuclear polyhedrosis virus (BmNPV). Through vivisectional observation and real-time quantities PCR analysis, we found that these dsRNA can prevent the BmNPV to a certain extent, and delay the viruses' proliferation.

An Analysis of Constraints on Pyroprocessing Technology Development in ROK Under the US Nonproliferation Policy

  • Jae Soo Ryu
    • 방사성폐기물학회지
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    • 제21권3호
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    • pp.383-395
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    • 2023
  • Since 1997, the Republic of Korea (ROK) has been developing pyro-processing (Pyro) technology to reduce the disposal burden of high-level radioactive waste by recycling spent nuclear fuel (SNF). Compared to plutonium and uranium extraction process, Korean Pyro technology has relatively excellent proliferation resistance that cannot separate pure plutonium owing to its intrinsic characteristics. Regarding Pyro technology development of ROK, the Bush administration considered that Pyro is not reprocessing under the Global Nuclear Energy Partnership, whereas the Obama administration considered that Pyro is subject to reprocessing. However, the Bush and Obama administrations did not allow ROK to conduct full Pyro activities using SNF, even though ROK had faithfully complied with international nonproliferation obligations. This is because the US nuclear nonproliferation policy to prevent the spread of sensitive technologies, such as enrichment and reprocessing, has a strong effect on ROK, unlike Japan, on a bilateral level beyond the NPT regime for non-proliferation of nuclear weapons.

Inhibition of Tumoral VISTA to Overcome TKI Resistance via Downregulation of the AKT/mTOR and JAK2/STAT5 Pathways in Chronic Myeloid Leukemia

  • Kexin Ai;Mu Chen;Zhao Liang;Xiangyang Ding;Yang Gao;Honghao Zhang;Suwan Wu;Yanjie He;Yuhua Li
    • Biomolecules & Therapeutics
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    • 제32권5호
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    • pp.582-600
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    • 2024
  • Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

Synthesis of Butein Analogues and their Anti-proliferative Activity Against Gefitinib-resistant Non-small Cell Lung Cancer (NSCLC) through Hsp90 Inhibition

  • Seo, Young Ho;Jeong, Ju Hui
    • Bulletin of the Korean Chemical Society
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    • 제35권5호
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    • pp.1294-1298
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    • 2014
  • Non-small cell lung cancer (NSCLC) is the most common type of lung cancer representing 85% of lung cancer patients. Despite several EGFR-targeted drugs have been developed in the treatment of NSCLC, the clinical efficacy of these EGFR-targeted therapies is being challenged by the occurrence of drug resistance. In this regard, Hsp90 represents great promise as a therapeutic target of cancerous diseases due to its role in modulating and stabilizing numerous oncogenic proteins. Accordingly, inhibition of single Hsp90 protein simultaneously disables multiple signaling networks so as to overcome drug resistance in cancer. In this study, we synthesized a series of 11 butein analogues and evaluated their biological activities against gefitinibresistant NSCLC cells (H1975). Our study indicated that analogue 1h inhibited the proliferation of H1975 cells, down-regulated the expression of Hsp90 client proteins, including EGFR, Met, Her2, Akt and Cdk4, and upregulated the expression of Hsp70. The result suggested that compound 1h disrupted Hsp90 chaperoning function and could serve a potential lead compound to overcome the drug resistance in cancer chemotherapy.

Phosphorylation of rpS3 by Lyn increases translation of Multi-Drug Resistance (MDR1) gene

  • Woo Sung Ahn;Hag Dong Kim;Tae Sung Kim;Myoung Jin Kwak;Yong Jun Park;Joon Kim
    • BMB Reports
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    • 제56권5호
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    • pp.302-307
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    • 2023
  • Lyn, a tyrosine kinase that is activated by double-stranded DNA-damaging agents, is involved in various signaling pathways, such as proliferation, apoptosis, and DNA repair. Ribosomal protein S3 (RpS3) is involved in protein biosynthesis as a component of the ribosome complex and possesses endonuclease activity to repair damaged DNA. Herein, we demonstrated that rpS3 and Lyn interact with each other, and the phosphorylation of rpS3 by Lyn, causing ribosome heterogeneity, upregulates the translation of p-glycoprotein, which is a gene product of multidrug resistance gene 1. In addition, we found that two different regions of the rpS3 protein are associated with the SH1 and SH3 domains of Lyn. An in vitro immunocomplex kinase assay indicated that the rpS3 protein acts as a substrate for Lyn, which phosphorylates the Y167 residue of rpS3. Furthermore, by adding various kinase inhibitors, we confirmed that the phosphorylation status of rpS3 was regulated by both Lyn and doxorubicin, and the phosphorylation of rpS3 by Lyn increased drug resistance in cells by upregulating p-glycoprotein translation.

MoS2 코팅된 치과용 임플란트의 표면특성과 생체적합성 (Surface Characteristics and Biocompatibility of MoS2-coated Dental Implant)

  • 권민기;이준식;김미은;최한철
    • Corrosion Science and Technology
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    • 제23권1호
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    • pp.72-81
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    • 2024
  • The Ti-6Al-4V alloy is widely used as an implant material due to its higher fatigue strength and strengthto-weight ratio compared to pure titanium, excellent corrosion resistance, and bone-like properties that promote osseointegration. For rapid osseointegration, the adhesion between the titanium surface and cellular biomolecules is crucial because adhesion, morphology, function, and proliferation are influenced by surface characteristics. Polymeric peptides and similar coating technologies have limited effectiveness, prompting a demand for alternative materials. There is growing interest in 2D nanomaterials, such as MoS2, for good corrosion resistance and antibacterial, and bioactive properties. However, to coat MoS2 thin films onto titanium, typically a low-temperature hydrothermal synthesis method is required, resulting in the synthesis of films with a toxic 1T@2H crystalline structure. In this study, through high-temperature annealing, we transformed them into a non-toxic 2H structure. The implant coating technique proposed in this study has good corrosion resistance and biocompatibility, and antibacterial properties.

Effects of Glucagon-like Peptide-2 on Morphology, Proliferation and Enzyme Activity of Intestinal Enterocyte Cells of Weaned Piglets In vitro

  • Jia, Gang;Jiang, RongChuan;Wang, KangNing
    • Asian-Australasian Journal of Animal Sciences
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    • 제22권8호
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    • pp.1160-1166
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    • 2009
  • This study was conducted according to the single-factor design principle to investigate in vitro the effects of different glucagon-like peptide-2 (GLP-2) concentrations (0, $1{\times}10^{-11}$, $1{\times}10^{-10}$, $1{\times}10^{-9}$, $1{\times}10^{-8}$ and $1{\times}10^{-7}$ mol/L) on the morphology, proliferation and enzyme activity of intestinal enterocyte cells of 28-d-old weaned piglets. These cells were primary cultured in 4 pieces of 24-well cell culture plate. After having been grown for 48 h in culture media with hGLP-2, the ileal enterocyte cells of 28-d-old weaned piglets exhibited the typical characteristics of simple columnar epithelium. Compared with the control groups, the quantities of treated cells significantly increased (p<0.05) and their corresponding absorption values in 540 nm (MTT OD) also significantly increased (p<0.01). Likewise, lactic acid concentration, total protein content and protein retention significantly increased (p<0.05). $Na^{+}$, $K^{+}$-ATP enzyme activity was more active (p<0.05), although the activity of alkaline phosphatase, lactic acid dehydrogenase and creatine phosphokinase in culture media significantly decreased (p<0.01). To summarize, the results indicated that GLP-2 in vitro is capable of promoting the proliferation of intestinal enterocyte cells of 28-d weaned piglets, restraining their apoptosis and maintaining the integrity of their morphology.