Publications by authors named "Rachel Giles"

Article Synopsis
  • Immune-oncology strategies are improving treatment for renal cell carcinoma (RCC), especially with the introduction of immunotherapy in the perioperative setting.
  • Adjuvant therapy with pembrolizumab has shown benefits in disease-free survival post-surgery but there's limited support for neoadjuvant therapies outside trials; both strategies have their risks and challenges.
  • While adjuvant immunotherapy is now a standard treatment, understanding the optimal use of neoadjuvant approaches is still unclear and requires further research in biomarker development and clinical trials.
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While the centrality of posttranscriptional modifications to RNA biology has long been acknowledged, the function of the vast majority of modified sites remains to be discovered. Illustrative of this, there is not yet a discrete biological role assigned for one of the most highly conserved modifications, 5-methyluridine at position 54 in tRNAs (mU54). Here, we uncover contributions of mU54 to both tRNA maturation and protein synthesis.

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The endothelial linings of capillaries, such as those in the kidney and small intestines, possess fenestrae that facilitate fluid and exchange of small molecules. Alterations in the size and number of endothelial fenestrae have been implicated in the pathogenesis of various diseases. The re-creation of fenestrated endothelium using human induced pluripotent stem cells (hiPSCs) provides a promising avenue to investigate the involvement of fenestrae in disease mechanisms and pharmacodynamics.

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Vascular smooth muscle cells (VSMCs) play a pivotal role in vascular homeostasis, with dysregulation leading to vascular complications. Human-induced pluripotent stem-cell (hiPSC)-derived VSMCs offer prospects for personalized disease modeling and regenerative strategies. Current research lacks comparative studies on the impact of three-dimensional (3D) substrate properties under cyclic strain on phenotypic adaptation in hiPSC-derived VSMCs.

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Background: There is inconsistency in outcomes collected in renal cell cancer (RCC) intervention effectiveness studies and variability in their definitions. This makes critical summaries of the evidence base difficult and sub-optimally informative for clinical practice guidelines and decision-making by patients and healthcare professionals. A solution is to develop a core outcome set (COS), an agreed minimum set of outcomes to be reported in all trials in a clinical area.

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RNAs are central to protein synthesis, with ribosomal RNA, transfer RNAs and messenger RNAs comprising the core components of the translation machinery. In addition to the four canonical bases (uracil, cytosine, adenine, and guanine) these RNAs contain an array of enzymatically incorporated chemical modifications. Transfer RNAs (tRNAs) are responsible for ferrying amino acids to the ribosome, and are among the most abundant and highly modified RNAs in the cell across all domains of life.

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Context: Outcomes in renal cell carcinoma (RCC) are reported inconsistently, with variability in definitions and measurement. Hence, it is difficult to compare intervention effectiveness and synthesise outcomes for systematic reviews and to create clinical practice guidelines. This uncertainty in the evidence makes it difficult to guide patient-clinician decision-making.

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In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER).

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The fifth edition of the World Health Organization (WHO) classification of urogenital tumours published in 2022 will be implemented in the European Association of Urology guidelines on renal cell carcinoma for 2023. Here we provide an update summarising changes in the new WHO classification of renal tumours from a clinician perspective.

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Article Synopsis
  • - CIViC is a public, crowd-sourced database that compiles peer-reviewed research on the clinical significance of cancer variants to aid in cancer management.
  • - It offers structured data in real-time to facilitate global access and is designed to keep up with evolving variant interpretation guidelines and enhance collaboration with other resources.
  • - The platform has successfully expanded to include new Evidence Types related to cancer variants and now features contributions from over 300 experts, covering more than 3200 variants across 470 genes from over 3100 published studies.
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Over the past decade, only minor changes have been introduced in the TNM staging system for renal cancer. Conversely, many milestones and modifications in management of the disease have been achieved, especially for patients with locally advanced and metastatic cancers. The European Association of Urology guidelines panel proposes a new TNM classification scheme for staging of renal cell carcinoma to reflect these breakthrough clinical improvements.

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Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery.

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As guidelines, therapies, and literature on cancer variants expand, the lack of consensus variant interpretations impedes clinical applications. CIViC is a public domain, crowd-sourced, and adaptable knowledgebase of evidence for the Clinical Interpretation of Variants in Cancer, designed to reduce barriers to knowledge sharing and alleviate the variant interpretation bottleneck.

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Background: Clinical pathways are care plans established to describe essential steps in the care of patients with a specific clinical problem. They translate (inter)national guidelines into local applicable protocols and clinical practice. The purpose of this article is to establish a multidisciplinary integrated care pathway for specialists and allied health care professionals in caring for individuals with von Hippel-Lindau (VHL) disease.

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Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome where individuals are predisposed to tumor development in the brain, adrenal gland, kidney, and other organs. It is caused by pathogenic variants in the VHL tumor suppressor gene. Standardized disease information has been difficult to collect due to the rarity and diversity of VHL patients.

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The SARS-CoV-2 virus is responsible for the COVID-19 global public health emergency, and the disease it causes is highly variable in its clinical presentation. Clinical phenotypes are heterogeneous both in terms of presentation of symptoms in the host and response to therapy. Several studies and initiatives have been established to analyse and review host genetic epidemiology associated with COVID-19.

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Context: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC.

Objective: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC.

Evidence Acquisition: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases.

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Unlabelled: The International Kidney Cancer Coalition (IKCC) is a federation of 46 affiliated patient organisations representing 1.2 million patients worldwide that is committed to reducing the global burden of kidney cancer. A large-scale global survey of patients with renal cell carcinoma (RCC) to capture real-world experiences has never been undertaken.

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Article Synopsis
  • The biopharmaceutical industry needs to better include patients and their families when developing new medicines to make sure they actually help people.
  • A study interviewed patient organization representatives to find out what they think about measuring the success of these patient engagement projects.
  • They found that patients feel proud and involved when working with medicine companies, and made suggestions to improve how the success of these projects is measured.
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Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by the development of multi-organ neoplasms. Among the manifestations of VHL are pancreatic neuroendocrine neoplasms (panNENs). In order to detect these lesions in a timely manner, patients are enrolled in a surveillance program, in accordance with the several existing VHL guidelines.

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Pseudouridine (Ψ) is a ubiquitous RNA modification incorporated by pseudouridine synthase (Pus) enzymes into hundreds of noncoding and protein-coding RNA substrates. Here, we determined the contributions of substrate structure and protein sequence to binding and catalysis by pseudouridine synthase 7 (Pus7), one of the principal messenger RNA (mRNA) modifying enzymes. Pus7 is distinct among the eukaryotic Pus proteins because it modifies a wider variety of substrates and shares limited homology with other Pus family members.

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