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排序方式: 共有696条查询结果,搜索用时 125 毫秒
1.
Haonan Guo Rui Zhang Justice Afrifa Yuanyuan Wang Jingcui Yu 《Pathology, research and practice》2019,215(6):152403
PurposeWe previously demonstrated that the functional inactivation of DAL-1 and TOB1 promotes an aggressive phenotype in gastric cancer cells, but the links between both genes and the survival of patients with gastric cancer are unknown. Here, we investigated the correlations of the expression levels of DAL-1 and TOB1 with the progression of gastric cancer.MethodsA total of 270 patients who underwent resectable gastrectomy were included. The expression of DAL-1 and TOB1 was detected by immunohistochemistry.ResultsLow expression of DAL-1 in cancer tissue was significantly associated with tumor site (p < 0.05), histological grade (p < 0.01), depth of invasion (p < 0.05), lymph node metastasis status (p < 0.05), Lauren classification (p < 0.001), and clinical stage (p < 0.01). A lower level of TOB1 was observed in gastric cancer patients with diffuse type disease compared to patients with either intestinal or mixed type disease (p < 0.001). Additionally, Spearman’s correlation analysis revealed that decreased expression of DAL-1 was positively correlated with low TOB1 expression (r=0.304, p < 0.001). The survival analysis showed that low levels of DAL-1 and TOB1 were significantly associated with poor survival of gastric cancer patients (p <0.001 and p < 0.05, respectively).ConclusionThe downregulation of DAL-1 and TOB1 expression is associated with shorter survival of gastric cancer patients. Hence, DAL-1 and TOB1 may be considered potential novel markers for predicting the outcomes of patients with gastric cancer. 相似文献
2.
Mood disorders are often characterised by alterations in circadian rhythms, sleep disturbances and seasonal exacerbation. Conversely, chronobiological treatments utilise zeitgebers for circadian rhythms such as light to improve mood and stabilise sleep, and manipulations of sleep timing and duration as rapid antidepressant modalities. Although sleep deprivation (“wake therapy”) can act within hours, and its mood‐elevating effects be maintained by regular morning light administration/medication/earlier sleep, it has not entered the regular guidelines for treating affective disorders as a first‐line treatment. The hindrances to using chronotherapeutics may lie in their lack of patentability, few sponsors to carry out large multi‐centre trials, non‐reimbursement by medical insurance and their perceived difficulty or exotic “alternative” nature. Future use can be promoted by new technology (single‐sample phase measurements, phone apps, movement and sleep trackers) that provides ambulatory documentation over long periods and feedback to therapist and patient. Light combinations with cognitive behavioural therapy and sleep hygiene practice may speed up and also maintain response. The urgent need for new antidepressants should hopefully lead to reconsideration and implementation of these non‐pharmacological methods, as well as further clinical trials. We review the putative neurochemical mechanisms underlying the antidepressant effect of sleep deprivation and light therapy, and current knowledge linking clocks and sleep with affective disorders: neurotransmitter switching, stress and cortico‐limbic reactivity, clock genes, cortical neuroplasticity, connectomics and neuroinflammation. Despite the complexity of multi‐system mechanisms, more insight will lead to fine tuning and better application of circadian and sleep‐related treatments of depression. 相似文献
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Francesco Pignatti Bertil Jonsson Gideon Blumenthal Robert Justice 《Molecular oncology》2015,9(5):1034-1041
Drug licensing and approval decisions involve the balancing of benefits against the risks (harms) in the presence of uncertainty. Typically, the benefits are estimated from primary efficacy endpoints from confirmatory (phase III) clinical trials although exceptions where promising early data from single‐arm studies have led to accelerated approvals are not uncommon, particularly for cancer drugs.The challenge for regulators is to balance early evidence of efficacy that might support approval versus the need to establish clinical benefit based on conclusive evidence. Targeted agents offer the promise that knowledge about the mechanism of the disease will help identify patients with tumors likely to respond, resulting in higher efficacy and less toxicity, and earlier regulatory decisions based on convincing evidence of clinical benefit.In this paper, we describe methods and examples of benefit‐risk assessment of targeted drugs, recent initiatives from EMA and FDA on improving communication about benefits and risks, and discuss future steps. 相似文献
5.
Jamie N. Justice Christy S. Carter Hannah J. Beck Rachel A. Gioscia-Ryan Matthew McQueen Roger M. Enoka Douglas R. Seals 《Age (Dordrecht, Netherlands)》2014,36(2):583-595
Motor function in humans can be characterized with tests of locomotion, strength, balance, and endurance. The aim of our project was to establish an analogous test battery to assess motor function in mice. Male C57BL/6 mice were studied at 3 (n = 87), 20 (n = 48) and 26 (n = 43) months of age. Tests assessed locomotion, strength, balance/coordination, and endurance capacity in mice. Motor function was reduced in the older groups of mice for the locomotion, strength, and endurance subdomains (p < 0.001). As indicated with a summary score, motor function declined by 7.4 % from 3 to 20 months and by 13.5 % from 20 to 26 months. Based on comparison with previously published data in humans, the magnitude and relative time course of changes were similar in mice and humans in each subdomain except balance/coordination. Power calculations confirmed that the age-associated differences depicted by several of the individual tests and domain summary scores would be sufficient to assess the efficacy of interventions aimed at prevention or treatment of motor dysfunction with aging. The current study describes a mouse model that characterizes age-associated changes in clinically relevant domains of motor function and indicates that the preclinical model can be used to test strategies to attenuate age-associated declines in motor function.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-013-9589-9) contains supplementary material, which is available to authorized users. 相似文献6.
7.
On the Homogeneity of Metallocene Ethylene–Propylene Copolymers as Investigated by Multiple Fractionation Techniques 下载免费PDF全文
Mohau Justice Phiri Anita Dimeska Harald Pasch 《Macromolecular chemistry and physics.》2015,216(15):1619-1628
The chemical heterogeneity of ethylene–propylene copolymers by multiple fractionation techniques is addressed. Three metallocene copolymer samples with different ethylene contents, ranging from 30 to 50 mol% are analyzed using bulk methods to confirm their molecular heterogeneity. In a second step, the samples are fractionated by temperature rising elution fractionation (TREF) to obtain fractions at 30, 60, 90, and 130 °C. These fractions are subsequently analyzed regarding their thermal and molecular properties. Differential scanning calorimetry, crystallization analysis fractionation, and high‐temperature high performance liquid chromatography (HT‐HPLC) results reveal that the TREF fractions collected at 130 °C are mainly due to polypropylene homopolymer, which is rather unexpected considering the high ethylene contents of the bulk samples. Most importantly, HT‐HPLC reveals a remarkably high chemical heterogeneity of the fractions and thus the bulk samples. Solution 13C NMR provides the comonomer contents and sequence distributions of the fractions. These indicate that the same TREF fractions from different samples have distinctively different chemical compositions.
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Ellen C. Caniglia James M. Robins Lauren E. Cain Caroline Sabin Roger Logan Sophie Abgrall Michael J. Mugavero Sonia Hernández-Díaz Laurence Meyer Remonie Seng Daniel R. Drozd George R. Seage III Fabrice Bonnet Fabien Le Marec Richard D. Moore Peter Reiss Ard van Sighem William C. Mathews Inma Jarrín Belén Alejos Steven G. Deeks Roberto Muga Stephen L. Boswell Elena Ferrer Joseph J. Eron John Gill Antonio Pacheco Beatriz Grinsztejn Sonia Napravnik Sophie Jose Andrew Phillips Amy Justice Janet Tate Heiner C. Bucher Matthias Egger Hansjakob Furrer Jose M. Miro Jordi Casabona Kholoud Porter Giota Touloumi Heidi Crane Dominique Costagliola Michael Saag Miguel A. Hernán 《Statistics in medicine》2019,38(13):2428-2446
Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the “no direct effect” assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/μl compared with 500 cells/μl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The “no direct effect” assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size. 相似文献
10.
Richard O. Phillips Fred S. Sarfo Mohammed K. Abass Justice Abotsi Tuah Wilson Mark Forson Yaw A. Amoako William Thompson Kingsley Asiedu Mark Wansbrough-Jones 《Antimicrobial agents and chemotherapy》2014,58(2):1161-1166
Buruli ulcer, an ulcerating skin disease caused by Mycobacterium ulcerans infection, is common in tropical areas of western Africa. We determined the clinical and microbiological responses to administration of rifampin and streptomycin for 2 weeks followed by administration of rifampin and clarithromycin for 6 weeks in 43 patients with small laboratory-confirmed Buruli lesions and monitored for recurrence-free healing. Bacterial load in tissue samples before and after treatment for 6 and 12 weeks was monitored by semiquantitative culture. The success rate was 93%, and there was no recurrence after a 12-month follow-up. Eight percent had a positive culture 4 weeks after antibiotic treatment, but their lesions went on to heal. The findings indicate that rifampin and clarithromycin can replace rifampin and streptomycin for the continuation phase after rifampin and streptomycin administration for 2 weeks without any apparent loss of efficacy. 相似文献