-
Medecine Sciences : M/S Dec 2020One of the major challenges of the 21 century is the fight against aging, defined as a set of physiological mechanisms altering the physical and intellectual capacities... (Review)
Review
One of the major challenges of the 21 century is the fight against aging, defined as a set of physiological mechanisms altering the physical and intellectual capacities of human beings. Aging of the skin is only one visible part of this process. It is associated with major healing defects linked in part to the alteration of the biomechanical properties of skin cells, mainly dermal fibroblasts. The immune system, another key component in maintaining skin homeostasis and the efficient healing of wounds, also suffers the effects of time: the consequent skin immunosenescence would limit the anti-infectious and vaccine response, while promoting a pro-tumor environment. The main skin damages due to aging, whether intrinsic or extrinsic, will be detailed before listing the effective anti-aging strategies to combat age-related dermal and epidermal stigmas.
Topics: Aging; Animals; Cellular Senescence; Drugs, Investigational; Epidermis; Humans; Skin; Skin Aging; Therapies, Investigational; Wound Healing
PubMed: 33296633
DOI: 10.1051/medsci/2020232 -
Frontiers in Endocrinology 2020Thyroid cancer is the most common endocrine cancer. The discovery of new biomarkers for thyroid cancer has significantly improved the understanding of the molecular... (Review)
Review
Thyroid cancer is the most common endocrine cancer. The discovery of new biomarkers for thyroid cancer has significantly improved the understanding of the molecular pathogenesis of thyroid cancer, thus allowing more personalized treatments for patients with thyroid cancer. Most of the recently discovered targeted therapies inhibit the known oncogenic mechanisms in thyroid cancer initiation and progression such as MAPK pathway, PI3K/Akt-mTOR pathways, or VEGF. Despite the significant advances in molecular testing and the discoveries of new and promising therapeutics, effective treatments for advanced and metastatic, iodine-refractory thyroid cancer are still lacking. Here, we aim to summarize the current understanding of the genetic alterations and the dysregulated pathways in thyroid cancer and to discuss the most recent targeted therapies and immunotherapy for advanced thyroid cancer with a promising anti-tumor activity and clinical benefit.
Topics: History, 21st Century; Humans; Immunotherapy; Molecular Targeted Therapy; Mutation; Signal Transduction; Therapies, Investigational; Thyroid Neoplasms
PubMed: 32528402
DOI: 10.3389/fendo.2020.00082 -
Microbiology Spectrum Mar 2019is capable of becoming resistant to all classes of antibiotics clinically available and resistance can develop through mutations in chromosomal genes or through... (Review)
Review
is capable of becoming resistant to all classes of antibiotics clinically available and resistance can develop through mutations in chromosomal genes or through acquisition of horizontally transferred resistance determinants. This review covers the most important antibiotics available for treatment of infections and a special emphasis is dedicated to the current knowledge of the wide variety of resistance mechanisms that employ to withstand antibiotics. Since resistance development has been inevitable for all currently available antibiotics, new therapies are continuously under development. Besides development of new small molecules affecting cell viability, alternative approaches including anti-virulence and bacteriophage therapeutics are being investigated and may become important tools to combat staphylococcal infections in the future.
Topics: Anti-Bacterial Agents; DNA Replication; Drug Resistance, Multiple, Bacterial; Drugs, Investigational; Genes, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Viability; Mutation; Protein Synthesis Inhibitors; Staphylococcal Infections; Staphylococcus aureus; Virulence
PubMed: 30900543
DOI: 10.1128/microbiolspec.GPP3-0057-2018 -
British Journal of Clinical Pharmacology Mar 2015Safety and efficacy data on many medicines used in children are surprisingly scarce. As a result children are sometimes given ineffective medicines or medicines with... (Review)
Review
Safety and efficacy data on many medicines used in children are surprisingly scarce. As a result children are sometimes given ineffective medicines or medicines with unknown harmful side effects. Better and more relevant clinical trials in children are needed to increase our knowledge of the effects of medicines and to prevent the delayed or non-use of beneficial therapies. Clinical trials provide reliable evidence of treatment effects by rigorous controlled testing of interventions on human subjects. Paediatric trials are more challenging to conduct than trials in adults because of the paucity of funding, uniqueness of children and particular ethical concerns. Although current regulations and initiatives are improving the scope, quantity and quality of trials in children, there are still deficiencies that need to be addressed to accelerate radically equitable access to evidence-based therapies in children.
Topics: Child; Clinical Trials as Topic; Drug Evaluation; Drugs, Investigational; Ethics, Medical; Humans; Pediatrics; Research Design
PubMed: 24325152
DOI: 10.1111/bcp.12305 -
Medecine Sciences : M/S 2020The prognosis for phenylketonuria (PKU) has been improved by neonatal screening and dietary management via a low-phenylalanine diet. This treatment must be followed... (Review)
Review
The prognosis for phenylketonuria (PKU) has been improved by neonatal screening and dietary management via a low-phenylalanine diet. This treatment must be followed throughout life, which induces severe compliance problems. Drug treatment with sapropterin (or BH4) has come to help a reduced percentage of patients who respond to this drug. A subcutaneous enzyme therapy is available in the USA and has obtained European marketing authorization, but generates significant side effects, which limits its effectiveness. New therapeutic options for PKU are currently being developed, in particular gene therapy. The purpose of this article is to take stock of the pathophysiology and the various new therapeutic modalities currently in development.
Topics: Biopterins; Diet; Genetic Therapy; Humans; Infant, Newborn; Neonatal Screening; Phenylketonurias; Prognosis; Therapies, Investigational
PubMed: 32821049
DOI: 10.1051/medsci/2020127 -
The Journal of Clinical Endocrinology... Nov 2018To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010.
OBJECTIVE
To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010.
CONCLUSIONS
The writing committee presents updated best practice guidelines for the clinical management of congenital adrenal hyperplasia based on published evidence and expert opinion with added considerations for patient safety, quality of life, cost, and utilization.
Topics: Adrenal Hyperplasia, Congenital; Cost-Benefit Analysis; Endocrinology; Female; Fetal Therapies; Genetic Counseling; Glucocorticoids; Humans; Infant, Newborn; Long-Term Care; Neonatal Screening; Patient Safety; Quality of Life; Societies, Medical; Therapies, Investigational
PubMed: 30272171
DOI: 10.1210/jc.2018-01865 -
Annals of Oncology : Official Journal... Oct 2018
Topics: Anemia, Iron-Deficiency; Antineoplastic Combined Chemotherapy Protocols; Biosimilar Pharmaceuticals; Erythrocyte Transfusion; Europe; Hematinics; Hematopoietic Stem Cell Transplantation; Humans; Iron; Medical Oncology; Neoplasms; Societies, Medical; Therapies, Investigational; Treatment Outcome
PubMed: 29471514
DOI: 10.1093/annonc/mdx758 -
Brazilian Journal of Medical and... Dec 2016The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which... (Review)
Review
Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.
The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.
Topics: Animals; Biomedical Research; Clinical Trials, Phase I as Topic; Drug Evaluation, Preclinical; Drugs, Investigational; Humans; Laboratories; Mutagenicity Tests; Pharmacology, Clinical
PubMed: 27982281
DOI: 10.1590/1414-431X20165646 -
Epilepsia Aug 2013A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of... (Review)
Review
A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. Such biomarkers could be used to create animal models for more cost-effective screening of potential antiepileptogenic and antiseizure drugs and devices, and to reduce the cost of clinical trials by enriching the trial population, and acting as surrogate markers to shorten trial duration. The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.
Topics: Animals; Anticonvulsants; Biomarkers; Brain; Clinical Trials as Topic; Cost-Benefit Analysis; Disease Models, Animal; Disease Progression; Drug Discovery; Drug Evaluation, Preclinical; Drug Resistance; Drugs, Investigational; Electroencephalography; Epilepsy; Humans; Precipitating Factors
PubMed: 23909854
DOI: 10.1111/epi.12299 -
Frontiers in Endocrinology 2021
Topics: Aging; Animals; Cancer Survivors; Congresses as Topic; Endocrinology; Female; History, 21st Century; Humans; Male; Neoplasms; Pregnancy; Risk Factors; Therapies, Investigational
PubMed: 34335482
DOI: 10.3389/fendo.2021.722929