48,100 research outputs found
Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial
No full textOral 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
j-fu/VoronoiFVM.jl: v0.5.2
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Combination of 5-FU and MDM2/4 peptide inhibitors as a promising strategy to enhance 5-FU induced nucleolar stress.
No full textThe 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
j-fu/VoronoiFVM.jl: v0.6.4
No full textA changelog is being generated, please check back in a few minutes
O kung Fu e o desenvolvimento infantil : desenvolvimento motor
No full textEste 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
j-fu/ExtendableSparse.jl: v0.2.5
No full textA changelog is being generated, please check back in a few minutes
The Influence of Material Modification and Residues on Space Charge Accumulation in XLPE for DC Power Cable Application
No full textThe effects of material modification and cross-linking by-products (residues) quantity on space charge accumulation and decay in XLPE have been investigated using the pulsed electro-acoustic technique. The threshold stress for space charge generation during voltage-ramping was found to show considerable variation and to depend upon the material and the amount of residue present. However, the modified XLPE material was found to exhibit a higher threshold for space charge accumulation than the reference XLPE whatever the conditions. De-gassed samples were found to exhibit the highest threshold stress, with that of the modified de-gassed XLPE accumulating no space charge at all even after 24 hours stressing at 70kV. In general heterocharge regions were formed when the residues were present and homocharge or no charge was formed when the residues were removed by degassing. Differences were also found in the space charge decay following short-circuit (volts-off), with the decay of heterocharge being rapid, whereas that of homocharge was slow. A tentative explanation is offered to explain these features
Oleoylethanolamide, an endogenous PPAR-alpha agonist, lowers body weight and hyperlipidemia in obese rats
No full textThe fatty-acid ethanolamide, oleoylethanolamide (OEA), is a naturally occurring lipid that regulates feeding and body weight [Rodriguez de Fonseca, F., Navarro, M., Gomez, R., Escuredo, L., Nava, F., Fu, J., Murillo-Rodriguez, E., Giuffrida, A., LoVerme, J., Gaetani, S., Kathuria, S., Gall, C., Piomelli, D., 2001. An anorexic lipid mediator regulated by feeding. Nature 414, 209-212], and serves as an endogenous agonist of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) [Fu, J., Gaetani, S., Oveisi, F., Lo Verme, J., Serrano, A., Rodriguez De Fonseca, F., Rosengarth., A., Luecke, H., Di Giacomo, B., Tarzia, G., Piomelli, D., 2003. Oleoylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 425, 90-93], a ligand-activated transcription factor that regulates several aspects of lipid metabolism [. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr. Rev. 20, 649-688]). OEA reduces food intake in wild-type mice, but not in mice deficient in PPAR-alpha (PPAR-alpha(-/-)), an effect that is also observed with the PPAR-alpha agonists Wy-14643 and GW7647 [Brown, P.J., Chapman, J.M., Oplinger, J.A., Stuart, L.W., Willson, T.M. and Wu, Z., 2000. Chemical compounds as selective activators of PPAR-alpha. PCT Int. Appl., 32; . The PPARs: from orphan receptors to drug discovery. J. Med. Chem. 43, 527-550]. By contrast, specific agonists of PPAR-delta/beta (GW501516) or PPAR-gamma (ciglitazone) have no such effect. In obese Zucker rats, which lack functional leptin receptors, OEA reduces food intake and lowers body-weight gain along with plasma lipid levels. Similar effects are seen in diet-induced obese rats and mice. In the present study, we report that subchronic OEA treatment (5mgkg(-1), intraperitoneally, i.p., once daily for two weeks) in Zucker rats initiates transcription of PPAR-alpha and other PPAR-alpha target genes, including fatty-acid translocase (FAT/CD36), liver fatty-acid binding protein (L-FABP), and uncoupling protein-2 (UCP-2). Moreover, OEA decreases neutral lipid content in hepatocytes, as assessed by Oil red O staining, as well as serum cholesterol and triglyceride levels. The results suggest that OEA regulates lipid metabolism and that this effect may contribute to its anti-obesity propertie
Fu Describing About the Author Himself: A Focus on Ban Gu "You tong fu"
No full textFrom 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
β-carotene as a novel adjuvant in the therapy with 5-FU of p53 deleted colon cancer cells
No full textColon cancer is one of the leading causes of cancer-related death worldwide. The main cause of failure in colon cancer therapy is represented by drug resistance in the course of treatment which has become very common. Despite recent therapeutic advancements, resistance to 5- Fluoruracil (5-FU) is still a major obstacle to successful treatments of this disease. Consequently, how to overcome 5-FU resistance is a key issue for cancer management. In order to study novel therapeutic approaches taking advantage from natural compounds showing anticancer effects we focused our interest on beta-carotene and its potential antiproliferative effects to overcome drug resistance. This compound is the most abundant carotenoid in the human diet and a well-known precursor of retinoids which, as regulator of cell proliferation and differentiation, has been shown to inhibit colon cancer progression [1]. In this study we assessed the potential role of beta-carotene as adjuvant of 5-FU in the treatment with 5-FU of p53 deleted colon cancer cells.
Our results led us to propose beta-carotene in combination with 5-FU as a promising cancer therapy by examining p53 profiles in tumors to yield a better clinical outcomes.
1. Lee NY, Kim Y, Kim YS, Shin JH, Rubin LP, Kim Y. β-Carotene exerts anti-colon cancer effects by regulating M2 macrophages and activated fibroblasts. J Nutr Biochem. 2020 Aug;82:108402. doi: 10.1016/j.jnutbio.2020.108402. Epub 2020 Apr 24. PMID: 32450500
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