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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.
Raymond J. Chan RN PhD Vivienne E. Milch MBBS MHPol Fiona Crawford-Williams PhD Oluwaseyifunmi Andi Agbejule BRadTherapy Ria Joseph MNutrDiet Jolyn Johal BND Narayanee Dick BSc Matthew P. Wallen PhD Julie Ratcliffe PhD Anupriya Agarwal MBBS Larissa Nekhlyudov MD Matthew Tieu PhD Manaf Al-Momani BPharm Scott Turnbull PhD Rahul Sathiaraj MPH Dorothy Keefe MBBS MD Nicolas H. Hart PhD 《CA: a cancer journal for clinicians》2023,73(6):565-589
Patient navigation is a strategy for overcoming barriers to reduce disparities and to improve access and outcomes. The aim of this umbrella review was to identify, critically appraise, synthesize, and present the best available evidence to inform policy and planning regarding patient navigation across the cancer continuum. Systematic reviews examining navigation in cancer care were identified in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Cumulative Index of Nursing and Allied Health (CINAHL), Epistemonikos, and Prospective Register of Systematic Reviews (PROSPERO) databases and in the gray literature from January 1, 2012, to April 19, 2022. Data were screened, extracted, and appraised independently by two authors. The JBI Critical Appraisal Checklist for Systematic Review and Research Syntheses was used for quality appraisal. Emerging literature up to May 25, 2022, was also explored to capture primary research published beyond the coverage of included systematic reviews. Of the 2062 unique records identified, 61 systematic reviews were included. Fifty-four reviews were quantitative or mixed-methods reviews, reporting on the effectiveness of cancer patient navigation, including 12 reviews reporting costs or cost-effectiveness outcomes. Seven qualitative reviews explored navigation needs, barriers, and experiences. In addition, 53 primary studies published since 2021 were included. Patient navigation is effective in improving participation in cancer screening and reducing the time from screening to diagnosis and from diagnosis to treatment initiation. Emerging evidence suggests that patient navigation improves quality of life and patient satisfaction with care in the survivorship phase and reduces hospital readmission in the active treatment and survivorship care phases. Palliative care data were extremely limited. Economic evaluations from the United States suggest the potential cost-effectiveness of navigation in screening programs. 相似文献
3.
Julie Despres Yasmina Ramdani Marine di Giovanni Magalie Bnard Abderrakib Zahid Mait Montero‐Hadjadje Florent Yvergnaux Thibaut Saguet Azeddine Driouich Marie‐Laure Follet‐Gueye 《Experimental dermatology》2019,28(8):922-932
It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing. 相似文献
4.
Thomas Ruffing Tilmann Rückauer Frederic Bludau Alexander Hofmann Markus Muhm Arnold J Suda 《Injury》2019,50(2):607-612
Introduction
Compression fractures of the cuboid bone in children and adolescents are rare. Fracture morphology, associated lesions, treatment options and long-term outcomes of this very rare injury are published in a few case reports. This study with review of the literature aims to support the understanding of fracture pattern and optimize pathways of decision making.Material and Methods
A retrospective two-center study was performed in a patient cohort treated between 2001 and 2016. All patients aged less than 18 years who sustained a cuboid fracture were included. Age, gender, mechanism of injury, fracture morphology, amount of displacement, associated injuries, and therapy were analyzed. In the follow-up (FU), the AOFAS Midfoot Scale was investigated.Results
Fractures of the cuboid bone were diagnosed in 7 boys and 9 girls. The mean age of the patients was 10 years (range: 2.2–16.1 years). According to the classification of Fenton we detected 11 (69%) type 2, 2 (12%) type 3 and 3 (19%) type 5b fractures. Other fracture types according to Fenton were not observed. All children under 10 years sustained a type 2 fracture. Open reduction and internal fixation was performed in 5 (31%) patients. Bone grafting was not necessary. FU was performed in 14/16 patients on average after 9 years (mean; range: 1.4–16.2 years). The mean AOFAS Midfoot Scale at FU for extra-articular type 2 fractures was 100 points, whereas in intra-articular fractures (Type 3) and fractures associated with mid-tarsal disruption (type 5b) worse results were found (95 and 66 points, accordingly).Conclusion
This rare injury shows inhomogenous morphologies and offers different treatment approaches. Extra-articular Fenton type 2 lesions are the most common type of cuboid fracture in children (69%). A potential loss of length of the lateral column must be considered. In contrast to adults, type 1, 4, and 5a fractures were not found in our cohort of children and adolescents. Lower scores of the AOFAS Midfoot Scale were found with either intra-articular involvement or associated midfoot lesions. 相似文献5.
6.
David M. Presby Michael C. Rudolph Vanessa D. Sherk Matthew R. Jackman Rebecca M. Foright Kenneth L. Jones Julie A. Houck Ginger C. Johnson Janine A. Higgins P. Darrell Neufer Robert H. Eckel Paul S. MacLean 《Diabetes》2021,70(4):867
Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain. 相似文献
7.
Clint R. Bellenger John B. Arnold Jonathan D. Buckley Dominic Thewlis Joel T. Fuller 《Journal of Science and Medicine in Sport》2019,22(3):294-299
Objectives
To investigate whether functional overreaching affects locomotor system behaviour when running at fixed relative intensities and if any effects were associated with changes in running performance.Design
Prospective intervention study.Methods
Ten trained male runners completed three training blocks in a fixed order. Training consisted of one week of light training (baseline), two weeks of heavy training designed to induce functional overreaching, and ten days of light taper training designed to allow athletes to recover from, and adapt to, the heavy training. Locomotor behaviour, 5-km time trial performance, and subjective reports of training status (Daily Analysis of Life Demands for Athletes (DALDA) questionnaire) were assessed at the completion of each training block. Locomotor behaviour was assessed using detrended fluctuation analysis of stride intervals during running at speeds corresponding to 65% and 85% of maximum heart rate (HRmax) at baseline.Results
Time trial performance (effect size ±95% confidence interval (ES): 0.16 ± 0.06; p < 0.001), locomotor behaviour at 65% HRmax (ES: ?1.12 ± 0.95; p = 0.026), and DALDA (ES: 2.55 ± 0.80; p < 0.001) were all detrimentally affected by the heavy training. Time trial performance improved relative to baseline after the taper (ES: ?0.16 ± 0.10; p = 0.003) but locomotor behaviour at 65% HRmax (ES: ?1.18 ± 1.17; p = 0.048) and DALDA (ES: 0.92 ± 0.90; p = 0.045) remained impaired.Conclusions
Locomotor behaviour during running at 65% HRmax was impaired by functional overreaching and remained impaired after a 10-day taper, despite improved running performance. Locomotor changes may increase injury risk and should be considered within athlete monitoring programs independently of performance changes. 相似文献8.
Julie A. Tannenbaum 《The Hastings Center report》2019,49(5):34-36
While there is not unanimity (across time or cultures), almost all who read this commentary will think that both they and a toddler have a moral status higher than that of a rat. For instance, they will think that a third party who has to choose whom to save from death should choose them over the rat, and the toddler over the rat. But what is it about humans that gives us this greater moral status? This question is particularly pressing when considering that scientists have begun creating human‐animal chimeras with brains composed partly or wholly of human cells. In “Human‐Animal Chimeras: The Moral Insignificance of Uniquely Human Capacities,” Julian Koplin focuses on the moral implications of such experiments and those that use (or plan to use) these chimeras to study diseases and treatments. How should we understand the concerns about moral status that have been raised about such chimeras? In this commentary, I interpret these concerns differently from Koplin and respond to his suggestion that the greater one's ability to draw value from certain kinds of conscious experiences, the greater one's moral status. 相似文献
9.