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The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
Genetic information is stored and transferred in the form of the nucleic acids deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). These molecules provide the necessary information for protein production. Like many biological molecules, nucleic acids are multimers of smaller units; which in this case are known as nucleotides. A set of four nucleotide components is used to generate DNA or RNA. Adenine (A), guanine (G) and cytosine (C) are common to both DNA and RNA. Thymine (T) is found in DNA but absent from RNA, with uracil (U) present in its place.
Characteristics, Events, and Stages in Tumorigenesis
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
Extracellular vesicles (EVs) comprise a heterogeneous population of vesicles differing in size, composition, morphology, or biogenic mechanisms. EVs secreted by cells were initially assumed to simply involve the selective elimination of proteins, lipids, and RNA from cells [828]. However, they now are considered to be a novel way of conducting intercellular communication [828–831]. Wolf is attributed as the first to observe mammalian vesicle-like structures in platelet-free plasma after ultracentrifugation in 1967 [832]. Multiple machineries exist that play a role in the generation of extracellular vesicles, but components of the endocytic sorting system seem to predominate over others [828]. EVs are thought to be an early evolutionary adaptation of the first language of cell–cell communication [833]. These structures encapsulated biological molecules and sequestered encoding nucleic acids and their replication machinery from the hazardous external surroundings [834]. Nonclassical secretory vesicles, EVs, are ubiquitous in nature and found both in bacteria and multicellular organisms [834, 835]. Among the cell biology, biotechnology, and pharmaceutical fields, EVs are steadily garnering attention due to their promising uses as new clinical diagnostic markers and therapeutic vehicles [832, 835].
Methods in molecular exercise physiology
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Adam P. Sharples, Daniel C. Turner, Stephen Roth, Robert A. Seaborne, Brendan Egan, Mark Viggars, Jonathan C. Jarvis, Daniel J. Owens, Jatin G. Burniston, Piotr P. Gorski, Claire E. Stewart
While genomic (gDNA) and mitochondrial DNA (mtDNA) are present in nearly all the body’s cells (an important exception being red blood cells), DNA collection for the purposes of research is typically limited to buccal epithelial cells (cheek cells) or leukocytes (white blood cells). For studies in which blood drawing is a typical procedure, white cells (or the ‘buffy coat’) from a typical non-coagulated blood sample may be used for DNA isolation. If blood sampling is not required for a research study, then collection of buccal cells from the inside of the cheek using a cotton-type swab is a less invasive way to collect DNA. These cells are then processed to burst (‘lyse’) the cells and release the DNA from the cell nuclei, most often using commercially available DNA isolation kits (e.g. DNeasy Blood and Tissue Kit, Qiagen, Manchester, UK), which contain the chemicals needed for cell lysis, protein denaturation (to remove histone and other proteins from the DNA) and purify the remaining DNA. DNA isolation typically requires a couple of hours using the reagents provided in the kits across multiple steps involving centrifugation at high speeds, but many samples can be processed at the same time for efficiency. Once DNA is collected and purified, it can be stored in a sealed tube in a typical refrigerator or freezer for many years; it is one of the most stable biological molecules known. This DNA can then be assessed across a variety of DNA analysis methods typically employed in the field of molecular exercise physiology.
Nanocarrier functionalization strategies for targeted drug delivery in skin cancer therapy: current progress and upcoming challenges
Published in Expert Opinion on Drug Delivery, 2023
Leonardo Delello Di Filippo, Mariana Carlomagno de Paula, Jonatas Lobato Duarte, Geanne Aparecida de Paula, Isadora Frigieri, Marlus Chorilli
Polymeric micelles and polymeric nanoparticles are two promising drug delivery systems for the treatment of skin cancer. Both have advantages and limitations, which must be considered for adequate formulation. Both nanosystems have been shown to improve drug stability, reduce toxicity, and increase drug uptake by skin cancer cells, besides presenting controlled release. However, due to their small size, polymeric micelles can easily penetrate in the skin layers, while polymeric nanoparticles – with higher size – not. Still, both polymeric micelles and polymeric nanoparticles can present low stability under physiological conditions and can be destabilized in the presence of proteins and other biological molecules, which can reduce their efficacy and stability, while polymeric nanoparticles are more stable in this sense. This limitation can be overcome by modifying the surface of polymeric nanosystems with PEG and its derivatives to improve circulation time and stability. Additionally, polymeric nanocarriers have limitations regarding their compatibility with certain drugs, which can lead to low loading efficiency and shelf-life stability. According to the current literature, polymeric nanoparticles, particularly PLGA nanoparticles, are the most promising nanoparticles for skin cancer treatment. They have shown improved drug efficacy, reduced toxicity, and increased drug uptake by skin cancer cells, and their biocompatibility and biodegradability make them suitable for clinical use. However, further research is needed to optimize their properties and evaluate their long-term safety and efficacy [28,30,31].
Venetoclax in acute myeloid leukemia
Published in Expert Opinion on Investigational Drugs, 2023
Antonella Bruzzese, Enrica Antonia Martino, Francesco Mendicino, Eugenio Lucia, Virginia Olivito, Antonino Neri, Fortunato Morabito, Ernesto Vigna, Massimo Gentile
Albeit a noteworthy improvement in outcome, AML patients disappointingly relapse or become resistant frequently, especially in the elderly age. Thus, new approaches are needed, as standard treatment has yet to be available for those patients. The landscape of AML treatment is constantly changing with the growing development of targeted therapy in frontline and relapsed refractory patients. In recent years, there has been an increasing shift toward combination strategies involving biological and targeted therapies. During the last years, preclinical studies have made it possible to better understand the biology of acute myeloid leukemia cells, thus allowing the development of targeted biological therapies that act on the altered intracellular signal pathways. Combination strategies involving biological molecules with different targets may have benefits compared to monotherapies, suggesting a synergism between different molecules and greater possibility of overcoming drug resistance. In this complex scenery, venetoclax-based combination strategies play a crucial role in R/R and treatment-naïve AML. Combined with 5-azacitidine, venetoclax doubled the 5-azacitidine response rate and significantly improved clinical outcomes in older adults with newly diagnosed AML. A similar scenario was seen with the combination of venetoclax/LDAC. The success of venetoclax combination strategies in unfit patients suggests that this drug’s potential role must be further explored in combination strategies for young and fit patients.
Discovery and design of G protein-coupled receptor targeting antibodies
Published in Expert Opinion on Drug Discovery, 2023
Sean M. Peterson, Catherine J. Hutchings, Cameron F. Hu, Melina Mathur, Janelle W. Salameh, Fumiko Axelrod, Aaron K. Sato
Biological molecules (biologics) are a class of drugs that are produced by living cells [4], for the purpose of this review, the biologics we will refer to most commonly are antibodies and their related fragments and bioactive peptides. Biologics have many unique properties that are not possible with small-molecule drugs. Many biologics take advantage of the properties of antibodies, in particular, the Fc (crystallizable fragment) region can be engineered to enhance drug half-life and induce antibody-dependent cellular cytotoxicity (or avoid cytotoxicity altogether) [5]. Typically, antibodies diffuse through the blood stream, interstitial space, and lymphatic system and are excluded from the central nervous system. Unlike small molecules, antibodies are not cleared by the kidneys, but instead are degraded through Fc-receptor mediated endocytosis [6]. Another advantage of biologics, as we will detail in this review, is that antibodies can be fused together to create bispecific molecules that target two different receptors, or biparatopic molecules that target two epitopes on the same receptor. Finally, because of their biological nature, it is possible to apply synthetic biology methods, such as directed evolution, to engineer antibodies, antibody fragments and peptides with desired drug-like properties [7].