1,587,210 research outputs found

    Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial

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    Oral capecitabine (Xeloda<sup>®</sup>) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings £3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings £1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK

    Combination of 5-FU and MDM2/4 peptide inhibitors as a promising strategy to enhance 5-FU induced nucleolar stress.

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    The inactivation of tumor suppressor p53 is crucial for tumor onset and progression. Half of colorectal cancer cases carry wild-type p53 that is inactivated by the overexpression of MDM2 and MDM4, the main negative regulators of p53 activity [1]. Hence, the reactivation of p53 by inhibiting MDM2/4-p53 interaction represents a useful strategy to enhance the p53-depemdent cancer cell response to chemotherapeutic drugs. Recently, it has been demonstrated that 5-Fluoruracil (5-FU), the standard first-line treatment for colorectal cancer therapy, exerts its cytotoxic effect through the activation of p53-dependent nucleolar stress response [2]. It has been recently discovered that Pep3, a 12-mer peptide, is able to disrupt the MDM2/4 heterodimer producing a more efficient p53 reactivation [3]. In this study, we developed a library of sixteen Pep3 derivatives with sequence lengths ranging from 5- to 8-mer. Intriguingly, the newly truncated peptides displayed lower IC50 values than Pep3; among which the most active peptides were VLP-13 and VLP-24. We incorporated them, alone or in association with 5-FU, in novel biodegradable nanoparticles, and we analyzed their cytotoxic activity against p53 proficient colon cancer cells. We found that the cytotoxic activity of VLP-24 was higher than VLP-13 alone or in association with 5-FU. Notably, the combined treatment with 5-FU and VLP-24 caused a significant unbalance of ribosomal RNA precursor levels associated to a strong increase of p53 and p21 expression levels leading to the activation of apoptosis. In conclusion, our data demonstrate that VLP-24 is a promising strategy to enhance 5-FU mediated activation of p53-dependent nuclear stress response. [1] Liebl MC et al. Cancers (2021); 13, 2125. [2] Pecoraro A et al. Int J Mol Sci. (2021); 22, 5496. [3] Pellegrino M et al. Cancer Res. (2015); 75; 4560-72

    Kinetic modeling of 5-FU-loaded SLNs.

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    The present study aimed to prepare solid lipid-based nanoparticles (SLNs) using Precirol® ATO 5 as solid lipid and Poloxamer 188 and Tween 80 as surfactant and co-surfactant respectively, and SLNs-derived gel for sustained delivery, enhanced in-vitro cytotoxicity, enhanced cellular uptake of 5-FU and enhanced permeation of 5-FU across the skin. The 5-FU-loaded SLNs were prepared by the hot melt encapsulation method and converted into SLN-derived gel using a gelling agent (Carbopol 940). The 5-FU-loaded SLNs had a particle size in the range of 76.82±1.48 to 327±4.46 nm, zeta potential between -11.3±2.11 and -28.4±2.40 mV, and entrapment efficiency (%) in range of 63.46±1.13 and 76.08±2.42. The FTIR analysis depicted that there was no chemical interaction between 5-FU and formulation components. Differential scanning calorimetric analysis showed thermal stability of 5-FU in the nanoparticles and powdered X-ray diffraction analysis revealed successful incorporation of 5-FU in nanoparticles. The in-vitro release study of 5-FU-loaded SLNs showed biphasic release behavior with initial burst release followed by sustained release over 48 hr. The 5-FU-loaded SLNs showed a greater cytotoxic effect on skin melanoma (B16F10 cells) and squamous cell carcinoma (A-431 cells) as compared to free 5-FU drug solution after 48 hr. Flow cytometry and fluorescence microscopy displayed enhanced quantitative and qualitative cellular uptake of SLNs. The SLNs formulation showed acceptable safety and biocompatible profile after an acute toxicity study in Wistar rats. Moreover, ex-vivo permeation studies depicted 2.13±0.076 folds enhanced flux of 5-FU-loaded SLN derived gel compared to 5-FU plain gel, and skin retention studies revealed target efficiency (%) 2.54±0.03 of 5-FU-loaded SLN derived gel compared to 5-FU plain gel.</div

    Fu Describing About the Author Himself: A Focus on Ban Gu "You tong fu"

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    From Later Han dynasty onwards, the number of fu describing about the author himself has increased. There are several possible reasons for this, but the most important reason is probably that there was no other genre through which one could express oneself except for fu in this period. For instance, the fiveword poetry was still in the middle way of establishing its own style at that moment. Moreover, in Former Han, there were few opportunities for authors to talk about themselves in detail in fu, because the main readers were emperors and kings of countries. In Later Han, the readers had become more diverse. That is probably the reason why more fu began to mention about the authors themselves in this period. Ban Gu (32-92), who is a representative scholar of Later Han and also a man of letters, expressed his aim by writing "You tong fu". Its main content is that though one's encounter with a disaster or felicity is not always derived from our behavior, we have to have a strong will and take action to overcome disasters. This idea is supported by Ban Gu's experiences of not attaining his aim. Such experiences are common in Chinese authors. One of the earliest examples is Chu Ci. Also, Chu Ci is the one of the origins of fu. It is surprising that authors expressed things about themselves mostly in fu describing journeys. It may be easier to understand this tendency if we think they substituted the heaven wander in Chu Ci with a ground journey. Chu Ci was a model for authors to express their aim which could not come true, even if the journey on the ground and the wander in heaven are different

    O kung Fu e o desenvolvimento infantil : desenvolvimento motor

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    Este trabalho busca elementos para verificar a ligação do Kung Fu, uma arte marcial chinesa, com o desenvolvimento motor infantil, baseando-se no conceito do desenvolvimento motor de GALLAHUE, D. L.; OZMUN, J. C e MEINEL, K., e assim poder associar estes conceitos a pratica desta, que atualmente é uma das artes marciais mais praticadas no mundo. Mas antes de apresentar o desenvolvimento motor, passa-se por uma revisão da história do Kung Fu, e uma revisão sobre o desenvolvimento, para que se possa desenvolver com clareza a idéia da ligação das duas coisas. Durante a pesquisa foi realizado como forma de busca de dados, um sistema de diário de observação de alunos praticantes de Kung Fu em diversos níveis de aprendizagem e treinamento, respeitando a faixa etária proposta pelo trabalho, para poder apresentar conclusões consistentes. Sem aprofundar-se no tipo de treinamento realizado e nos estilos existentes da modalidade esportiva, mas se atentando exclusivamente as crianças no treinamento, com os dados coletados, foi possível observar uma grande relação entre o Kung Fu e a melhora do desenvolvimento de capacidades como coordenação motora geral, equilíbrio, lateralidade, noção de direita e esquerda, posição e sentido.This paper searches for elements to verify the connection of Kung Fu, a Chinese martial art, with the motor development of children, based on the concept of motor development of GALLAHUE, D. L.; OZMUN, J. C e MEINEL, K., and this way be able to associate these concepts to it, which is currently one of the most practiced martial arts in the world. But before presenting the motor development, it will go through a review of the history of Kung Fu, and a review about the development, so that it can develop a clear idea of the connection of both things. During the research it was conducted as a way of data searching, a system of observation journal of students practicing Kung Fu at different levels of learning and training, respecting the age proposed for the work, to present consistent conclusions. Without going too deep into the kind of training conducted and in the different existing styles of the sport, but exclusively paying attention to the children in training, with the collected data, it was possible to observe a strong relation between Kung Fu and the improvement of capacities as general motor coordination, balance, laterality, sense of right and left, position and direction

    Kung-Fu Exhibition program, May 5, 1984

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    1984Established in 1963, the Seattle Kung Fu Club offers traditional martial arts classes for adults and children in Seattle's International District neighborhood. The program pictured here is from a Kung-Fu exhibition presented by the club on May 5, 1984, at the Seattle Center Arena (now KeyArena)"Caption information source: https://www.seattlekungfuclub.com.1 program (28 p." 8.5 x 11 in

    Kung Fu Idol

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    This is one of hundreds of 60-second radio spots created by the Center for East Asian Studies (CEAS) for Kansas Public Radio (KPR). The purpose of this outreach program is to introduce the people of Kansas to the culture and current issues of East Asia.Broadcast Transcript: First there was Pop Idol. Then there was American Idol. Soon there will be Kung Fu Idol. Well, technically this is not the title of the show but it might as well be. The show's goal is to find the greatest kung fu master in China and to star this person in a kung fu movie to be produced by the Shaolin monks. Shaolin is well known for its Zen practices and excellence in martial arts. In fact, Shaolin's brand of martial arts has influenced movies from Kill Bill to The Matrix and spawned at least one TV show. Soon showbiz began to define Shaolin's mission rather than vice versa. Kung fu idol aims to give Shaolin back the control. We can only hope that there will be more than "the sound of one hand clapping" as the credits roll. #ceas #china #hacker #tsutsu

    Paratrichocladius tridens Fu et Wang

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    Paratrichocladius tridens Fu et Wang (Fig. 12 A–B) Paratrichocladius tridens Fu et Wang, 2008: 728. Material examined. CHINA: Tibet Autonomous Region, Chayu County, Xiachayu Town, Baantong Village (28 ° 37 ’N, 97 ° 29 ’E), alt. 1600m, sweeping, holotype male, 13. vi. 1988, Chengyu Deng (BDN No. 1723). Paratypes: CHINA: Tibet Autonomous Region, Rikaze County, China – Nepal Friendship Bridge (29 ° 36 ’N, 91 °06’E), alt. 1800m, sweeping, 2 males, 14. vi. 1988, Chengyu Deng (BDN No. 1199, 07871). Diagnostic characters. The species can be separated from all other members of the genus by having 13 sensilla chaetica on ta 1 of P 3; humeral pit developed and reniform; the femur of middle and hind legs dark brown on apical 1 / 3, other parts yellow; setae on tergites relatively short, posterior of tergites V–VII in pale coloration; phallapodeme with two different colors, the deeper colored part like a fork with three tines; inferior volsella elongate and bilobed, with rounded apex, and superior volsella rounded and well developed; gonostylus slender, without distinct crista dorsalis. Correction to description (n = 3). “Gonostylus 225–285, 260 µm long” should be corrected to “Gonostylus 128–136, 132 µm long”. Distribution. The species was collected in subtropical area in Tibet Autonomous Region (Oriental China).Published as part of Fu, Yue, Saether, Ole A. & Wang, Xinhua, 2012, A review of Paratrichocladius Santos Abreu from the Sino-Indian Region (Diptera: Chironomidae: Orthocladiinae), pp. 453-482 in Zootaxa 3478 on pages 474-475, DOI: 10.5281/zenodo.20936

    Mutation frequencies following the 5-FU-, 4NQO-, and CPT-treatment.

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    A), C), and E) The frequencies of overall Lys+ mutations following treatments with 5-FU (10 μM), CPT (100 μM), or 4NQO (0.2 μg/mL), respectively, for 24 hrs. B), D), and F) The frequencies of the uracil-dependent A>C and T>G mutations following treatments with 5-FU, CPT and 4NQO, respectively. Error bars indicate 95% confidence intervals. The number of cultures used to determine the frequencies of mutations and the numerical values of the median mutation frequencies and the confidence intervals represented as graphs in this figure are listed in S4 Table.</p

    Aquatica leii Fu et Ballantyne

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    Aquatica leii (Fu et Ballantyne) Figs 19–24, 77, 78, 91 Luciola leii Fu & Ballantyne, 2006 a: 339. Fu et al. 2006 b: 860; 2007: 117; 2009: 155. Material examined. CHINA: Sixteen fifth instars bred from an original population of nine males and four females collected from Huazhong Agricultural University, Wuhan City, Hubei Province, May 14, 2010 (NHMHAU). Diagnosis. Protergum with two small pale areas at anterolateral corners; remaining terga lacking pale markings (paler or darker markings in this species are in the membranous areas not the dorsal tergal plates); lateral margins of protergum rounded; median line narrow (Figs 77, 78); glands with 2–6 marginal spines, lacking median spine (Fu et al. 2009; Fig 1 A); pygopodia arising from 6 basal stalks; rings of recurved hooks completely surrounding each stalk (Figs 61, 62, 91); antennal segment 3 with closely adpressed finger like projections subequal in length to adjacent sense cone (Figs 19, 21–23); mandibles lacking retinaculum; palpi with terminal sense organs (Figs 20, 22, 24). Remarks. The dorsal colouration of the larva depicted in Fu and Ballantyne (2006 a; Fig. 8) differs from that depicted here in having much larger anterolateral pale areas on the protergum, and pale margins on the terminal tergum (Fig. 77).Published as part of Fu, Xinhua, Ballantyne, Lesley & Lambkin, Christine, 2012, The external larval morphology of aquatic and terrestrial Luciolinae fireflies (Coleoptera: Lampyridae), pp. 1-34 in Zootaxa 3405 on page 14, DOI: 10.5281/zenodo.21130
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