Therapeutic targeting of non-coding RNAs in cancer

2017 ◽  
Vol 474 (24) ◽  
pp. 4219-4251 ◽  
Author(s):  
Ondrej Slaby ◽  
Richard Laga ◽  
Ondrej Sedlacek
Keyword(s):  
Clinical Trials ◽  
Targeted Therapeutics ◽  
Phase I Clinical Trials ◽  
Comprehensive Overview ◽  
Future Directions ◽  
New Class ◽  
Novel Treatment ◽  
Normal Expression ◽  
Non Coding Rnas

The majority of the human genome encodes RNAs that do not code for proteins. These non-coding RNAs (ncRNAs) affect normal expression of the genes, including oncogenes and tumour suppressive genes, which make them a new class of targets for drug development in cancer. Although microRNAs (miRNAs) are the most studied regulatory ncRNAs to date, and miRNA-targeted therapeutics have already reached clinical development, including the mimics of the tumour suppressive miRNAs miR-34 and miR-16, which reached phase I clinical trials for the treatment of liver cancer and mesothelioma, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognised. Here, we describe obstacles and advances in the development of ncRNA therapeutics and provide the comprehensive overview of the ncRNA chemistry and delivery technologies. Furthermore, we summarise recent knowledge on the biological functions of miRNAs and their involvement in carcinogenesis, and discuss the strategies of their therapeutic manipulation in cancer. We review also the emerging insights into the role of lncRNAs and their potential as targets for novel treatment paradigms. Finally, we provide the up-to-date summary of clinical trials involving miRNAs and future directions in the development of ncRNA therapeutics.

The Oxford Handbook of Hope

2017 ◽  
Keyword(s):  
Current Knowledge ◽  
Physical And Mental Health ◽  
Comprehensive Overview ◽  
Future Directions ◽  
Theoretical Perspectives ◽  
The Many ◽  
The Impact ◽  
Made In

The Oxford Handbook of Hope provides a comprehensive overview of current knowledge regarding the science and practice of hope. Hope has long been a topic of interest to philosophers and the general public, but it was only in recent decades that hope became a focus of psychological science. Rick Snyder defined hope as a cognitive trait that helps individuals to identify and pursue goals and consists of two components: pathways, the perceived capacity to identify strategies necessary to achieve goals, and agency, the willpower or motivation to pursue those pathways to achieve goals. Hope has become one of most robust and promising topics in the burgeoning field of positive psychology. This book reviews the progress that has been made in the past 25 years regarding the origins and influence of hope. Topics covered include current theoretical perspectives on how best to define hope and how it is distinct from related constructs, current best practices for measuring and quantifying hope, interventions and strategies for promoting hope across different settings and the lifespan, the impact that hope has on many dimensions and domains of physical and mental health, and the many ways and contexts in which hope promotes resilience and positive functioning. Experts in the field both review what is currently known about the role of hope in different domains and identify topics and questions that can help to guide the next decade of research. The handbook concludes with a collaborative vision on the future directions of the science of hope.

scholarly journals A Review of Registered Clinical Trials on Dietary (Poly)Phenols: Past Efforts and Possible Future Directions

Foods ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1606
Author(s):  
Mirko Marino ◽  
Cristian Del Bo’ ◽  
Daniela Martini ◽  
Marisa Porrini ◽  
Patrizia Riso
Keyword(s):  
Clinical Trials ◽  
Intervention Studies ◽  
Controlled Trial ◽  
Individual Variability ◽  
Future Directions ◽  
Main Research ◽  
Research Areas ◽  
Pure Compounds ◽  
Randomised Controlled

In recent years, the increasing number of studies on polyphenol demonstrates the efforts in elucidating the potential role of these bioactives on human health. This study reviews the main topics and characteristics of clinical trials on polyphenols registered over the last 20 years, in order to track past and current efforts as well as to highlight the main research gaps in this field. The review was conducted by collecting trials registered in ClinicalTrials.gov and International Standard Randomised Controlled Trial Number (ISRCTN) registry. Overall, 750 clinical trials were selected and included in the final evaluation. Most of the trials were performed on extracts or pure compounds followed by studies conducted on polyphenol-rich foods, in particular berries. A total of 520 clinical trials focused on health effects, 55 on bioavailability, and 175 on both. Regarding outcomes, 139 registered intervention studies had the lipid profile and blood pressure as primary outcomes. The overview provided by this analysis also emphasizes the emerging interest in new outcomes related to polyphenols intervention such as microbiota composition and the evaluation of inter-individual variability in response to the intake of polyphenols. Our review underlines the need of further trials covering unexplored or debated research aspects and provides insights for the design and development of future intervention studies and related research areas.

The role of an initial single-blind placebo period in phase I clinical trials

1994 ◽  
Vol 8 (2) ◽  
pp. 185-187 ◽  
Author(s):  
P. Nony ◽  
JP Boissel ◽  
P. Girard ◽  
L. Lion ◽  
MC Haugh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Phase I Clinical Trials ◽  
Placebo Period ◽  
Single Blind

scholarly journals A STUDY OF THE ROLE OF MICRORNA IN PITUITARY ADENOMA

2018 ◽  
Vol 5 (2) ◽  
pp. 8-15
Author(s):  
I. F. Gareev ◽  
O. A. Beylerli
Keyword(s):  
Pituitary Adenoma ◽  
Target Genes ◽  
Decisive Role ◽  
Cellular Processes ◽  
New Class ◽  
Number Of Genes ◽  
Non Coding Rnas ◽  
New Biomarkers ◽  
New Evidence

MicroRNAs are a new class of small non-coding RNAs, a length of 18–22 nucleotides that play a decisive role as posttranscriptional regulators of gene expression. Due to the large number of genes, regulated microRNAs, microRNAs are involved in many cellular processes. The study of the impairment of the expression of the target genes of microRNA, often associated with changes in important biological characteristics, provides a significant understanding of the role of microRNAs in oncogenesis. New evidence suggests that aberrant microRNA expression or dysregulation of endogenous microRNAs affects the onset and development of tumors, including adenomas of the pituitary gland. In this review, the significance of some microRNAs in the pathology of the pituitary adenoma will be assessed, as well as data on the study of microRNAs as therapeutic targets and new biomarkers.

scholarly journals A Breath of Fresh Air in the Fog of Antimicrobial Resistance: Inhaled Polymyxins for Gram-Negative Pneumonia

Antibiotics ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 27 ◽  
Author(s):  
Mark Biagi ◽  
David Butler ◽  
Xing Tan ◽  
Samah Qasmieh ◽  
Eric Wenzler
Keyword(s):  
Potential Role ◽  
Treatment Strategies ◽  
Comprehensive Overview ◽  
Gram Negative ◽  
Novel Treatment ◽  
Pharmacodynamic Profile ◽  
Inhaled Antibiotics ◽  
Novel Treatment Strategies ◽  
Significant Attention

Despite advancements in therapy, pneumonia remains the leading cause of death due to infectious diseases. Novel treatment strategies are desperately needed to optimize the antimicrobial therapy of patients suffering from this disease. One such strategy that has recently garnered significant attention is the use of inhaled antibiotics to rapidly achieve therapeutic concentrations directly at the site of infection. In particular, there is significant interest in the role of inhaled polymyxins for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia, due to their retained activity against multi-drug resistant Gram-negative pathogens, including Acinetobacter baumannii and Pseudomonas aeruginosa. This review will provide a comprehensive overview of the pharmacokinetic/pharmacodynamic profile, clinical outcomes, safety, and potential role of inhaled polymyxins in clinical practice.

scholarly journals The Role of Galcanezumab in Migraine Prevention: Existing Data and Future Directions

2021 ◽  
Vol 14 (3) ◽  
pp. 245
Author(s):  
Panagiotis Gklinos ◽  
Dimos D. Mitsikostas
Keyword(s):  
Clinical Trials ◽  
Real World Data ◽  
Future Directions ◽  
Migraine Headaches ◽  
Humanized Monoclonal Antibody ◽  
Potential Association ◽  
Calcitonin Gene

Galcanezumab is a humanized monoclonal antibody blocking the calcitonin gene-related peptide (CGRP) pathway by targeting the CGRP. Data from four phase-3 randomized placebo-controlled clinical trials showed that galcanezumab is superior to placebo in reducing migraine headaches, migraine-specific quality of life, and headache-related disability. Most of the adverse events (AEs) were mild to moderate and did not affect trial completion rates significantly. Along with erenumab, fremanezumab, and eptinezumab, galcanezumab forms a novel class of anti-migraine preventative treatments that is disease-specific and mechanism-based, unlike the standard ones. In addition, galcanezumab has also been shown to be effective in cluster headache, though more clinical trials are required. Overall, galcanezumab is a promising emerging treatment in migraine prophylaxis. However, it needs to be tested in larger clinical trials focused on treatment-resistant migraine. Furthermore, its safety profile, especially its potential association with an increased cardiovascular risk, needs to be established through long-term, real-world data. This review aims to give an overview of its pharmacological properties as well as to report and discuss data from clinical trials and its potential place in headache therapeutics.

scholarly journals Role of Tumor-Associated Macrophages in Sarcomas

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1086
Author(s):  
Tomohiro Fujiwara ◽  
John Healey ◽  
Koichi Ogura ◽  
Aki Yoshida ◽  
Hiroya Kondo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Tumor Microenvironment ◽  
Dominant Role ◽  
Tumor Associated Macrophages ◽  
Novel Treatment ◽  
Promote Tumor Growth ◽  
Elevated Expression ◽  
Tumor Growth And Metastasis ◽  
Sarcoma Cells

Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRPα, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas.

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