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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The role of targeted therapy in patients with lung adenosquamous carcinoma (ASC) has been controversial and it was unclear whether a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) could improve outcomes. This study was designed to evaluate the efficacy of different generations of EGFR TKI therapy in ASC patients with sensitive EGFR mutations. ⋯ Targeted therapy showed remarkable efficacy in ASC patients harboring sensitive EGFR mutations, comparable to adenocarcinoma. The application of the third-generation TKI provided an option to prolong survival.
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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.