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Clinical Biochemistry Jul 2021Since prostate cancer (PCa) relies on limited diagnosis and therapies, more effective alternatives are needed. Aptamers are versatile tools that may be applied for...
Since prostate cancer (PCa) relies on limited diagnosis and therapies, more effective alternatives are needed. Aptamers are versatile tools that may be applied for better clinical management of PCa patients. This review shows the trends on aptamer-based applications for PCa to understand their future development. We searched articles reporting aptamers applied in PCa on the Pubmed, Scopus and Web of Science databases over the last decade. Almost 80% of the articles used previously selected aptamers in novel approaches. However, cell-SELEX was the most applied technique for the selection of new aptamers allowing their binding to targets in their native configuration. ssDNA aptamers were 24% more common than RNA aptamers. The most studied PCa-specific aptamers were the DNA PSA-specific aptamer PSap4#5 and the PSMA-specific RNA aptamers A10 and A9, being PSA and PSMA the most reported targets. Thus, researchers still prefer the ease of use of DNA aptamers. Blood-based liquid biopsies represented 24% of all samples, being the most promising clinical samples. Especially noteworthy, electro-analytical methods accounted for more than 40% of the diagnostic techniques and treatment approaches with drug delivery systems or transcriptional modifiers were reported in 70% of the articles. Although all these articles showed clinically relevant aptamers for PCa and there are good prospects for their use, the development of all these strategies was in its early stages. Thus, the aptamers are not completely validated and we foresee that the completion of clinical studies will allow the implementation of these aptamer-based technologies in the clinical practice of PCa.
Topics: Animals; Antigens, Surface; Aptamers, Nucleotide; Glutamate Carboxypeptidase II; Humans; Male; Precision Medicine; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 33794195
DOI: 10.1016/j.clinbiochem.2021.03.014 -
Clinical Pharmacology and Therapeutics Dec 2021Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease characterized by loss of motor neurons and muscle atrophy. Untreated infants with type 1 SMA...
Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease characterized by loss of motor neurons and muscle atrophy. Untreated infants with type 1 SMA do not achieve major motor milestones, and death from respiratory failure typically occurs before 2 years of age. Individuals with types 2 and 3 SMA exhibit milder phenotypes and have better functional and survival outcomes. Herein, a systematic literature review was conducted to identify factors that influence the prognosis of types 1, 2, and 3 SMA. In untreated infants with type 1 SMA, absence of symptoms at birth, a later symptom onset, and a higher survival of motor neuron 2 (SMN2) copy number are all associated with increased survival. Disease duration, age at treatment initiation, and, to a lesser extent, baseline function were identified as potential treatment-modifying factors for survival, emphasizing that early treatment with disease-modifying therapies (DMT) is essential in type 1 SMA. In patients with types 2 and 3 SMA, factors considered prognostic of changes in motor function were SMN2 copy number, age, and ambulatory status. Individuals aged 6-15 years were particularly vulnerable to developing complications (scoliosis and progressive joint contractures) which negatively influence functional outcomes and may also affect the therapeutic response in patients. Age at the time of treatment initiation emerged as a treatment-effect modifier on the outcome of DMTs. Factors identified in this review should be considered prior to designing or analyzing studies in an SMA population, conducting population matching, or summarizing results from different studies on the treatments for SMA.
Topics: Cholestenones; Humans; Muscular Atrophy, Spinal; Observational Studies as Topic; Oligonucleotides; Prognosis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33792051
DOI: 10.1002/cpt.2247 -
AJNR. American Journal of Neuroradiology May 2021Spinal muscular atrophy is a progressive neurodegenerative disorder that can be treated with intrathecal antisense oligonucleotide therapy (nusinersen). However,...
BACKGROUND
Spinal muscular atrophy is a progressive neurodegenerative disorder that can be treated with intrathecal antisense oligonucleotide therapy (nusinersen). However, administration is often complicated by posterior spinal fusion and neuromuscular scoliosis, necessitating a transforaminal approach.
PURPOSE
To assess the safety profile of the transforaminal approach for intrathecal access.
DATA SOURCES
Searches of the PubMed, Web of Science, and SCOPUS databases.
STUDY SELECTION
Thirteen articles were selected based on inclusion of transforaminal access and appropriate clinical information about the procedure.
DATA ANALYSIS
Complications were taken from the included articles and aggregated based on Cardiovascular and Interventional Radiological Society of Europe scale adverse event grading.
DATA SYNTHESIS
Total number of complications and grade of complications were analyzed, by year and in total.
LIMITATIONS
Selection bias in publication, small patient population size, and variability of the procedure limits the available data.
CONCLUSIONS
Transforaminal approach is a safe alternative for intrathecal access in patients with spinal muscular atrophy and may be applicable to a larger patient population.
Topics: Europe; Humans; Injections, Spinal; Male; Muscular Atrophy, Spinal; Oligonucleotides; Postoperative Complications
PubMed: 33632735
DOI: 10.3174/ajnr.A7009 -
Cancers Jan 2021Transforming growth factor β (TGFβ) is a pleiotropic cytokine that participates in a wide range of biological functions. The alterations in the expression levels of... (Review)
Review
Transforming growth factor β (TGFβ) is a pleiotropic cytokine that participates in a wide range of biological functions. The alterations in the expression levels of this factor, or the deregulation of its signaling cascade, can lead to different pathologies, including cancer. A great variety of therapeutic strategies targeting TGFβ, or the members included in its signaling pathway, are currently being researched in cancer treatment. However, the dual role of TGFβ, as a tumor suppressor or a tumor-promoter, together with its crosstalk with other signaling pathways, has hampered the development of safe and effective treatments aimed at halting the cancer progression. This systematic literature review aims to provide insight into the different approaches available to regulate TGFβ and/or the molecules involved in its synthesis, activation, or signaling, as a cancer treatment. The therapeutic strategies most commonly investigated include antisense oligonucleotides, which prevent TGFβ synthesis, to molecules that block the interaction between TGFβ and its signaling receptors, together with inhibitors of the TGFβ signaling cascade-effectors. The effectiveness and possible complications of the different potential therapies available are also discussed.
PubMed: 33498521
DOI: 10.3390/cancers13030379 -
Brain Imaging and Behavior Oct 2021While C9orf72-specific imaging signatures have been proposed by both ALS and FTD research groups and considerable presymptomatic alterations have also been confirmed in... (Review)
Review
While C9orf72-specific imaging signatures have been proposed by both ALS and FTD research groups and considerable presymptomatic alterations have also been confirmed in young mutation carriers, considerable inconsistencies exist in the literature. Accordingly, a systematic review of C9orf72-imaging studies has been performed to identify consensus findings, stereotyped shortcomings, and unique contributions to outline future directions. A formal literature review was conducted according to the STROBE guidelines. All identified papers were individually reviewed for sample size, choice of controls, study design, imaging modalities, statistical models, clinical profiling, and identified genotype-associated pathological patterns. A total of 74 imaging papers were systematically reviewed. ALS patients with GGGGCC repeat expansions exhibit relatively limited motor cortex involvement and widespread extra-motor pathology. C9orf72 positive FTD patients often show preferential posterior involvement. Reports of thalamic involvement are relatively consistent across the various phenotypes. Asymptomatic hexanucleotide repeat carriers often exhibit structural and functional changes decades prior to symptom onset. Common shortcomings included sample size limitations, lack of disease-controls, limited clinical profiling, lack of genetic testing in healthy controls, and absence of post mortem validation. There is a striking paucity of longitudinal studies and existing presymptomatic studies have not evaluated the predictive value of radiological changes with regard to age of onset and phenoconversion. With the advent of antisense oligonucleotide therapies, the meticulous characterisation of C9orf72-associated changes has gained practical relevance. Neuroimaging offers non-invasive biomarkers for future clinical trials, presymptomatic ascertainment, diagnostic and prognostic applications.
Topics: Amyotrophic Lateral Sclerosis; C9orf72 Protein; DNA Repeat Expansion; Frontotemporal Dementia; Humans; Magnetic Resonance Imaging; Proteins
PubMed: 33398779
DOI: 10.1007/s11682-020-00429-w -
Restorative treatments of dystrophin expression in Duchenne muscular dystrophy: A systematic review.Annals of Clinical and Translational... Sep 2020To evaluate the effect of pharmacological treatments that increase the synthesis of dystrophin in Duchenne muscular dystrophy (DMD). Systematic searches were carried out... (Meta-Analysis)
Meta-Analysis
To evaluate the effect of pharmacological treatments that increase the synthesis of dystrophin in Duchenne muscular dystrophy (DMD). Systematic searches were carried out in MEDLINE, EMBASE, and Web of Science, and in gray literature from inception to December 2019. Clinical trials addressing the effect of restorative treatments of dystrophin expression in children and adolescents with DMD on functional outcomes {(6-minute walking distance [6MWD], other timed functional tests [TFTs], The North Star Ambulatory Assessment)}, dystrophin expression, cardiorespiratory function, and biochemical tests were included. The DerSimonian-Laird method was used to calculate the pooled estimates for functional outcomes. Eleven studies were included in the systematic review and five in the meta-analysis. Eteplirsen showed a significant effect on 6MWD, Δ6MWD = 67.3 m (95% CI: 27.32, 107.28), and Δ6MWD = 151.0 m (95% CI: 36.15, 265.85) at 48 weeks and 3 years, respectively. In the systematic review, analyzing individually the clinical trials using Ataluren and Drisapersen showed a nonsignificant effect on 6MWD. However, the meta-analysis showed a significant effect on 6MWD for Ataluren and Drisapersen, Δ6MWD = 18.3 m (95% CI: 1.0, 35.5) and Δ6MWD = 21.5 m (95% CI: 4.7, 38.3), respectively. There were no significant differences according to baseline age for Drisapersen. Similarly, the meta-analysis showed effect in TFT with Ataluren. All drugs induced a partial synthesis of dystrophin, and exon skipping was obtained with Eteplirsen and Drisapersen. Eteplirsen also improved forced vital capacity (Δ%pFVC = 1.8%) and maximal inspiratory pressure (Δ%pMIP = 4.4%). Eteplirsen and Ataluren could modestly reduce disease progression. However, more trials are needed to confirm its efficacy, as well as quality of life and cost-utility studies.
Topics: Dystrophin; Humans; Morpholinos; Muscular Dystrophy, Duchenne; Oligonucleotides; Outcome Assessment, Health Care; Oxadiazoles
PubMed: 33325654
DOI: 10.1002/acn3.51149 -
Journal of Neurochemistry Mar 2021The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization...
The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate-limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence-specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac-conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood-brain barrier, but its half-life is short and liver failure a potential side effect. Amyloid-directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR-amyloidosis has become a model disease for pathophysiology-based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood-brain barrier permeability.
Topics: Amyloid; Amyloidosis, Familial; Animals; Gene Knockdown Techniques; Humans; Prealbumin
PubMed: 33155274
DOI: 10.1111/jnc.15233 -
Biomedicine & Pharmacotherapy =... Dec 2020Aptamers are single-stranded nucleic acid sequences that can bind to target molecules with high selectivity and affinity. Most aptamers are screened in vitro by a...
Aptamers are single-stranded nucleic acid sequences that can bind to target molecules with high selectivity and affinity. Most aptamers are screened in vitro by a combinatorial biology technique called systematic evolution of ligands by exponential enrichment (SELEX). Since aptamers were discovered in the 1990s, they have attracted considerable attention and have been widely used in many fields owing to their unique advantages. In this review, we present an overview of the advancements made in aptamers used for biosensors and targeted therapy. For the former, we will discuss multiple aptamer-based biosensors with different principles detected by various signaling methods. For the latter, we will focus on aptamer-based targeted therapy using aptamers as both biotechnological tools for targeted drug delivery and as targeted therapeutic agents. Finally, challenges and new perspectives associated with these two regions were further discussed. We hope that this review will help researchers interested in aptamer-related biosensing and targeted therapy research.
Topics: Animals; Antineoplastic Agents; Aptamers, Nucleotide; Biomarkers, Tumor; Biosensing Techniques; Drug Carriers; Drug Delivery Systems; Gene Transfer Techniques; Humans; Nanoparticles; Neoplasms; Predictive Value of Tests; RNA, Small Interfering; RNAi Therapeutics; SELEX Aptamer Technique
PubMed: 33096353
DOI: 10.1016/j.biopha.2020.110902 -
The Science of the Total Environment Feb 2021Fish environmental DNA (eDNA) studies have made substantial progress during the past decade, and significant advances in monitoring fishes have been gained by taking... (Review)
Review
Fish environmental DNA (eDNA) studies have made substantial progress during the past decade, and significant advances in monitoring fishes have been gained by taking advantage of this technology. Although a number of reviews concerning eDNA are available and some recent fish eDNA reviews focused on fisheries or standard method have been published, a systematic review of methodology of fish eDNA and its applications in ecology and environment has not yet been published. To our knowledge, this is the first review of fish eDNA for solving ecological and environmental issues. First, the most comprehensive literature analysis of fish eDNA was presented and analyzed. Then, we systematically discuss the relevant experiments and analyses of fish eDNA, and infers that standard workflow is on the way to consensus. We additionally provide reference sequence databases and the primers used to amplify the reference sequences or detecting fish eDNA. The abiotic and biotic conditions affecting fish eDNA persistence are also summarized in a schematic diagram. Subsequently, we focus on the major achievements of fish eDNA in ecology and environment. We additionally highlight the exciting new tools, including in situ autonomous monitoring devices, CRISPR nucleic acid detection technology, and meta-omics technology for fish eDNA detection in future. Ultimately, methodology of fish eDNA will provide a wholly new paradigm for conservation actions of fishes, ecological and environmental management at a global scale.
Topics: Animals; Biodiversity; DNA Primers; Environmental Monitoring; Fisheries; Fishes
PubMed: 33059148
DOI: 10.1016/j.scitotenv.2020.142622 -
Current Pharmaceutical Biotechnology 2021Cancer is the most devastating disease in the present scenario, killing millions of people every year. Early detection, accurate diagnosis, and timely treatment are...
Cancer is the most devastating disease in the present scenario, killing millions of people every year. Early detection, accurate diagnosis, and timely treatment are considered to be the most effective ways to control this disease. Rapid and efficient detection of cancer at their earliest stage is one of the most significant challenges in cancer detection and cure. Numerous diagnostic modules have been developed to detect cancer cells early. As nucleic acid equivalent to antibodies, aptamers emerge as a new class of molecular probes that can identify cancer-related biomarkers or circulating rare cancer/ tumor cells with very high specificity and sensitivity. The amalgamation of aptamers with the biosensing platforms gave birth to "Aptasensors." The advent of highly sensitive aptasensors has opened up many new promising point-of-care diagnostics for cancer. This comprehensive review focuses on the newly developed aptasensors for cancer diagnostics.
Topics: Aptamers, Nucleotide; Biomarkers, Tumor; Biosensing Techniques; Early Detection of Cancer; Humans; Nanostructures; Neoplasms
PubMed: 32957883
DOI: 10.2174/1389201021999200918152721