Mol Diagn Ther
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In November 2019 givosiran became the second small interfering RNA (siRNA)-based drug to receive US Food and Drug Administration (FDA) approval, it has been developed for the treatment of acute intermittent porphyria (AIP), a disorder characterized by life-threatening acute neurovisceral attacks. The porphyrias are a group of disorders in which enzymatic deficiencies in heme production lead to toxic accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), which are involved in the neurovisceral attacks. Givosiran acts as a conventional siRNA to trigger RNA interference (RNAi)-mediated gene silencing on delta-ALA synthase 1 (ALAS1), thus returning ALA and PBG metabolites to the physiological level to attenuate further neurotoxicity. ⋯ This siRNA is being analyzed in ENVISION (NCT03338816), a phase III, multicenter, placebo-controlled randomized controlled trial. In preliminary results, givosiran achieved clinical endpoints for AIP, reducing urinary ALA levels, and presented a safety profile that enabled further drug development. The clinical performance of givosiran revealed that suppression of ALAS1 by GalNac-decorated siRNAs represents an additional approach for the treatment of patients with AIP that manifests recurrent acute neurovisceral attacks.
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Review Meta Analysis
Evolving Concepts in Chronic Obstructive Pulmonary Disease Blood-Based Biomarkers.
In recent years, there has been a great deal of interest in the identification and validation of blood-based biomarkers for clinical use in chronic obstructive pulmonary disease (COPD). We now have panels of blood biomarkers that potentially hold great promise as they show statistically significant associations with COPD, but biomarkers for the diagnosis of COPD remain elusive. In fact, they are yet to demonstrate sufficient accuracy to be accepted in clinical use, and many are not specific to COPD but more related to inflammation (e.g. interleukin-6) or associated with other chronic diseases such as diabetes (e.g. soluble receptor for advanced glycation endproducts [sRAGE]). Although no single blood-based biomarker has demonstrated clinical utility for either the diagnosis or progression of COPD, it has been suggested that combinations of individual markers may provide important diagnostic or prognostic information; however, the interpretation of COPD biomarker results still requires thought and many questions remain unanswered.
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The present era of precision medicine sees "cancer" as a consequence of molecular derangements occurring at the commencement of the disease process, with morphological changes happening much later in the process of tumourigenesis. Conventional imaging techniques, such as computed tomography (CT), ultrasound (US) and magnetic resonance imaging (MRI) play an integral role in the detection of disease at the macroscopic level. However, molecular functional imaging (MFI) techniques entail the visualisation and quantification of biochemical and physiological processes occurring during tumourigenesis. ⋯ Despite the emergence of novel imaging biomarkers, the majority of these require validation before clinical translation is possible. In this two part review, we discuss the systematic collaboration across structural, anatomical and molecular imaging techniques that constitute MFI. Part I reviews positron emission tomography, radiogenomics, AI, and optical imaging, while part II reviews MRI, CT and ultrasound, their current status, and recent advances in the field of precision oncology.
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The present era of precision medicine sees 'cancer' as a consequence of molecular derangements occurring at the commencement of the disease process, with morphologic changes happening much later in the process of tumorigenesis. Conventional imaging techniques, such as computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI), play an integral role in the detection of disease at a macroscopic level. However, molecular functional imaging (MFI) techniques entail the visualisation and quantification of biochemical and physiological processes occurring during tumorigenesis, and thus has the potential to play a key role in heralding the transition from the concept of 'one size fits all' to 'precision medicine'. ⋯ Despite the emergence of novel imaging biomarkers, a majority of these require validation before clinical translation is possible. In this two-part review, we discuss the systematic collaboration across structural, anatomical, and molecular imaging techniques that constitute MFI. Part I reviews positron emission tomography, radiogenomics, AI, and optical imaging, while part II reviews MRI, CT and ultrasound, their current status, and recent advances in the field of precision oncology.
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Earlier identification of aggressive melanoma remains a goal in the field of melanoma research. With new targeted and immune therapies that have revolutionized the care of patients with melanoma, the ability to predict progression and monitor or predict response to therapy has become the new focus of research into biomarkers in melanoma. In this review, promising biomarkers are highlighted. ⋯ This is followed by a discussion of important genetic mutations, microRNA, and epigenetic modifications that can provide therapeutic and prognostic material. Finally, emerging serologic biomarkers are reviewed, including circulating melanoma cells and exosomes. Overall the goal is to identify biomarkers that aid in the earlier identification and improved treatment of aggressive melanoma.