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1.
Melanie A. Krook Julie W. Reeser Gabrielle Ernst Hannah Barker Max Wilberding Gary Li Hui-Zi Chen Sameek Roychowdhury 《British journal of cancer》2021,124(5):880
Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.Subject terms: Cancer, Cancer 相似文献
2.
Clare Delany PhD Master MSPT BAppSc Ian Edwards PhD Grad Dip PT BAppSc Caroline Fryer PhD Grad Dip BAppSc 《Physiotherapy theory and practice》2019,35(7):663-676
The profile and reach of physiotherapy has expanded in areas of extended scope of practice, and broader engagement with population needs beyond the individual treatment encounter. These changes raise increasingly complex ethical challenges evidenced by growth in physiotherapy-based ethics studies and discussions. This paper examines how a broad cross section of Australian physiotherapists perceive, interpret, and respond to ethical challenges in their work contexts and how professional codes of conduct are used in their practice. Using an interpretive qualitative methodology, purposive sampling of 88 members of national clinical special interest groups were recruited for focus group discussions. Narrative-based and thematic data analysis identified ethical challenges as emerging from specific clinical contexts, and influenced by health organizations, funding policies, workplace relationships, and individually held perspectives. Five themes were developed to represent these findings: (1) the working environment, (2) balancing diverse needs and expectation, (3) defining ethics, (4) striving to act ethically, and (5) talking about ethics. The results portray a diverse and complex ethical landscape where therapists encounter and grapple with ethical questions emerging from the impact of funding models and policies affecting clinical work, expanding boundaries and scope of practice and changing professional roles and relationships. Codes of conduct were described as foundational ethical knowledge but not always helpful for “in the moment” ethical decision-making. Based on this research, we suggest how codes of conduct, educators, and professional associations could cultivate and nurture ethics capability in physiotherapy practitioners for these contemporary challenges. 相似文献
3.
Joseph M. Northey Kate L. Pumpa Clare Quinlan Ashley Ikin Kellie Toohey Disa J. Smee Ben Rattray 《Journal of Science and Medicine in Sport》2019,22(5):580-585
Objectives
The current study investigated the effects of two exercise interventions on cognitive function amongst breast cancer survivors.Design
Pilot randomised-controlled trial.Methods
Seventeen female cancer survivors (mean: 62.9 ± 7.8 years) were randomised into three groups: high-intensity interval training (HIIT, n = 6); moderate-intensity continuous training (MOD, n = 5); or wait-list control (CON, n = 6). The HIIT and MOD groups exercised on a cycle ergometer 3 days/week for 12-weeks. Primary outcomes were cognitive function assessments utilising CogState. Secondary outcomes were resting middle cerebral artery blood flow velocity, cerebrovascular reactivity and aerobic fitness (VO2peak). Data were analysed with General Linear Mixed Models and Cohen’s d effect sizes were calculated.Results
All 17 participants who were randomised were available for follow-up analysis and adherence was similar for HIIT and MOD (78.7 ± 13.2% vs 79.4 ± 12.0%; p = 0.93). Although there were no significant differences in the cognitive and cerebrovascular outcomes, HIIT produced moderate to large positive effects in comparison to MOD and CON for outcomes including episodic memory, working memory, executive function, cerebral blood flow and cerebrovascular reactivity. HIIT significantly increased VO2peak by 19.3% (d = 1.28) and MOD had a non-significant 5.6% (d = 0.72) increase, compared to CON which had a 2.6% decrease.Conclusions
This study provides preliminary evidence that HIIT may be an effective exercise intervention to improve cognitive performance, cerebrovascular function and aerobic fitness in breast cancer survivors. Considering the sample size is small, these results should be confirmed through larger clinical trials. 相似文献4.
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6.
Nandita M deSouza Clare M Tempany 《International journal of cancer. Journal international du cancer》2019,144(3):422-430
Recognition of <3 metastases in <2 organs, particularly in cancers with a known predisposition to oligometastatic disease (OMD) (colorectal, prostate, renal, sarcoma and lung), offers the opportunity to focally treat the lesions identified and confers a survival advantage. The reliability with which OMD is identified depends on the sensitivity of the imaging technique used for detection and may be predicted from phenotypic and genetic factors of the primary tumour, which determine metastatic risk. Whole-body or organ-specific imaging to identify oligometastases requires optimization to achieve maximal sensitivity. Metastatic lesions at multiple locations may require a variety of imaging modalities for best visualisation because the optimal image contrast is determined by tumour biology. Newer imaging techniques used for this purpose require validation. Additionally, rationalisation of imaging strategies is needed, particularly with regard to timing of imaging and follow-up studies. This article reviews the current evidence for the use of imaging for recognising OMD and proposes a risk-based roadmap for identifying patients with true OMD, or at risk of metastatic disease likely to be OM. 相似文献
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10.
F M Barker 《Journal of the American Optometric Association》1988,59(7):558-560
Since its introduction in early 1985, the Volk +90D lens has become a very popular auxiliary lens for biomicroscopic fundus evaluation. The Volk +90D lens provides a wide field of view which is accessible by simple scanning of the biomicroscope. The necessity to hand hold the lens, however, has not always provided enough stability, particularly for the novice user. This article describes a newly introduced holder for the Volk +90D lens which mounts on the base of the biomicroscope headrest providing rapid and stable lens placement. Use of this holder improves the technique of retinal examination and photography by stabilizing the image and by freeing both hands to operate the slit lamp biomicroscope. The enhanced stability afforded by this holder also gives the examiner the practical capability of viewing the posterior pole without mydriasis. 相似文献