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Annals of Eye Science Mar 2022Animal models are crucial for the study of tumorigenesis and therapies in oncology research. Though rare, uveal melanoma (UM) is the most common intraocular tumor and...
Animal models are crucial for the study of tumorigenesis and therapies in oncology research. Though rare, uveal melanoma (UM) is the most common intraocular tumor and remains one of the most lethal cancers. Given the limitations of studying human UM cells in vitro, animal models have emerged as excellent platforms to investigate disease onset, progression, and metastasis. Since Greene's initial studies on hamster UM, researchers have dramatically improved the array of animal models. Animals with spontaneous tumors have largely been replaced by engrafted and genetically engineered models. Inoculation techniques continue to be refined and expanded. Newer methods for directed mutagenesis have formed transgenic models to reliably study primary tumorigenesis. Human UM cell lines have been used to generate rapidly growing xenografts. Most recently, patient-derived xenografts have emerged as models that closely mimic the behavior of human UM. Separate animal models to study metastatic UM have also been established. Despite the advancements, the prognosis has only recently improved for UM patients, especially in patients with metastases. There is a need to identify and evaluate new preclinical models. To accomplish this goal, it is important to understand the origin, methods, advantages, and disadvantages of current animal models. In this review, the authors present current and historic animal models for the experimental study of UM. The strengths and shortcomings of each model are discussed and potential future directions are explored.
PubMed: 35350473
DOI: 10.21037/aes-21-30 -
Frontiers in Oncology 2017The limited effectiveness of conventional therapy for malignant pleural mesothelioma demands innovative approaches to this difficult disease. Even with aggressive... (Review)
Review
The limited effectiveness of conventional therapy for malignant pleural mesothelioma demands innovative approaches to this difficult disease. Even with aggressive multimodality treatment of surgery, radiation, and/or chemotherapy, the median survival is only 1-2 years depending on stage and histology. Oncolytic viral therapy has emerged in the last several decades as a rapidly advancing field of immunotherapy studied in a wide spectrum of malignancies. Mesothelioma makes an ideal candidate for studying oncolysis given the frequently localized pattern of growth and pleural location providing access to direct intratumoral injection of virus. Therefore, despite being a relatively uncommon disease, the multitude of viral studies for mesothelioma can provide insight for applying such therapy to other malignancies. This article will begin with a review of the general principles of oncolytic therapy focusing on antitumor efficacy, tumor selectivity, and immune system activation. The second half of this review will detail results of preclinical models and human studies for oncolytic virotherapy in mesothelioma.
PubMed: 28884088
DOI: 10.3389/fonc.2017.00179 -
Revista de Investigacion Clinica;... 2023Since the dawn of civilization, ancient cultures have utilized hallucinogens from plants and fungi in the context of religious and healing practices. Recently, their use... (Review)
Review
Since the dawn of civilization, ancient cultures have utilized hallucinogens from plants and fungi in the context of religious and healing practices. Recently, their use has expanded to other cultures. Hallucinogens are natural or synthetic substances that alter the perception of reality at nontoxic doses, producing intense psychological and physiological effects. The initial research on hallucinogens began in the 1950s. However, their non-medical use, studies without proper controls, and negative social opinion resulted in legal restrictions that limited their use for clinical and preclinical research for more than two decades. A renewed interest in studying hallucinogens as potential therapeutic agents for treating different psychiatric conditions has recently re-emerged. This review summarizes the effects of main hallucinogen drugs and their therapeutic potential. Classic hallucinogens such as LSD, dimethyltryptamine, psilocin, and mescaline have chemical structures similar to serotonin and directly activate 5-hydroxy-tryptamine (5-HT) receptors. Ketamine is a dissociative anesthetic with antagonist effects at the glutamatergic N-methyl-D-aspartate receptor, indirectly activating 5-HT receptors. Ketamine has rapid antidepressant effects and reduces suicidal ideation, but its effects are short-lasting. Other hallucinogens are under study. It is necessary to continue this research with a more rigorous methodology and include studying the long-term effects of psychedelics use.
Topics: Humans; Hallucinogens; Ketamine; Serotonin; Mescaline; N,N-Dimethyltryptamine
PubMed: 37441761
DOI: 10.24875/RIC.23000108 -
Journal of Translational Science Feb 2021Aging is a complex multidimensional process of progressive decline affecting multiple organ systems by a number of processes that are still not well understood. While...
Aging is a complex multidimensional process of progressive decline affecting multiple organ systems by a number of processes that are still not well understood. While many studies have focused on the approach of studying aging across multiple organs, assessment of the contribution of individual organs to overall aging processes is under appreciated. The ability to study and compare organs in the context of organismal aging has been documented recently using a geropathology grading platform in laboratory mice. This concept consists of identifying and grading age-related histologic lesions within organs to generate a quantitative lesion score for each organ, which is representative of the presence and degree of organ-related pathology, and can be compared to scores from other organs examined. This geropathology approach provides a powerful tool to elucidate the basic mechanisms of aging in multiple organs, as well as the response of organs to therapeutic interventions. Furthermore, ongoing work with the concept has expanded and adapted the geropathology grading system to other preclinical animal model species that are commonly used to understand disease associated phenotypes in aging humans, ultimately adding to the utility of the concept.
PubMed: 34504718
DOI: 10.15761/jts.1000458 -
Experimental & Molecular Medicine Jun 2023Sphingolipids, which are components of cellular membranes and organ tissues, can be synthesized or degraded to modulate cellular responses according to environmental... (Review)
Review
Sphingolipids, which are components of cellular membranes and organ tissues, can be synthesized or degraded to modulate cellular responses according to environmental cues, and the balance among the different sphingolipids is important for directing immune responses, regardless of whether they originate, as intra- or extracellular immune events. Recent progress in multiomics-based analyses and methodological approaches has revealed that human health and diseases are closely related to the homeostasis of sphingolipid metabolism, and disease-specific alterations in sphingolipids and related enzymes can be prognostic markers of human disease progression. Accumulating human clinical data from genome-wide association studies and preclinical data from disease models provide support for the notion that sphingolipids are the missing pieces that supplement our understanding of immune responses and diseases in which the functions of the involved proteins and nucleotides have been established. In this review, we analyze sphingolipid-related enzymes and reported human diseases to understand the important roles of sphingolipid metabolism. We discuss the defects and alterations in sphingolipid metabolism in human disease, along with functional roles in immune cells. We also introduce several methodological approaches and provide summaries of research on sphingolipid modulators in this review that should be helpful in studying the roles of sphingolipids in preclinical studies for the investigation of experimental and molecular medicines.
Topics: Humans; Sphingolipids; Genome-Wide Association Study; Cell Membrane; Homeostasis
PubMed: 37258585
DOI: 10.1038/s12276-023-01018-9 -
International Journal of Molecular... Nov 2023Neuromuscular diseases (NMDs) are a genetically or clinically heterogeneous group of diseases that involve injury or dysfunction of neuromuscular tissue components,... (Review)
Review
Neuromuscular diseases (NMDs) are a genetically or clinically heterogeneous group of diseases that involve injury or dysfunction of neuromuscular tissue components, including peripheral motor neurons, skeletal muscles, and neuromuscular junctions. To study NMDs and develop potential therapies, remarkable progress has been made in generating in vitro neuromuscular models using engineering approaches to recapitulate the complex physical and biochemical microenvironments of 3D human neuromuscular tissues. In this review, we discuss recent studies focusing on the development of in vitro co-culture models of human motor neurons and skeletal muscles, with the pros and cons of each approach. Furthermore, we explain how neuromuscular in vitro models recapitulate certain aspects of specific NMDs, including amyotrophic lateral sclerosis and muscular dystrophy. Research on neuromuscular organoids (NMO) will continue to co-develop to better mimic tissues in vivo and will provide a better understanding of the development of the neuromuscular tissue, mechanisms of NMD action, and tools applicable to preclinical studies, including drug screening and toxicity tests.
Topics: Humans; Neuromuscular Diseases; Muscle, Skeletal; Neuromuscular Junction; Motor Neurons; Organoids
PubMed: 38069329
DOI: 10.3390/ijms242317006 -
British Journal of Pharmacology May 2019The endocannabinoid system has emerged as an important target for the treatment of many diverse diseases. In addition to the well-established palliative effects of... (Review)
Review
The endocannabinoid system has emerged as an important target for the treatment of many diverse diseases. In addition to the well-established palliative effects of cannabinoids in cancer therapy, phytocannabinoids, synthetic cannabinoid compounds and inhibitors of endocannabinoid degradation have attracted attention as possible systemic anticancer drugs. Results emerging from preclinical studies suggest cannabinoids elicit effects at different levels of cancer progression, including inhibition of proliferation, neovascularization, invasion and chemoresistance, induction of apoptosis and autophagy as well as enhancement of tumour immune surveillance. Although the clinical use of cannabinoid receptor ligands is limited by their psychoactivity, non-psychoactive compounds, such as cannabidiol, have gained attention due to preclinically established anticancer properties and a favourable risk-to-benefit profile. Thus, cannabinoids may complement the currently used collection of chemotherapeutic agents, as a broadly diversified option for cancer treatment, while counteracting some of their severe side effects. LINKED ARTICLES: This article is part of a themed section on 8 European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.
Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Phytogenic; Cannabinoid Receptor Agonists; Cannabinoids; Cell Line, Tumor; Cell Survival; Clinical Trials as Topic; Endocannabinoids; Humans; Neoplasms; Receptors, Cannabinoid
PubMed: 30019449
DOI: 10.1111/bph.14426 -
Journal of Cerebral Blood Flow and... Dec 2016Obesity is a risk factor for stroke and is consequently one of the most common co-morbidities found in patients. There is therefore an identified need to model... (Review)
Review
Obesity is a risk factor for stroke and is consequently one of the most common co-morbidities found in patients. There is therefore an identified need to model co-morbidities preclinically to allow better translation from bench to bedside. In preclinical studies, both diet-induced and genetically obese rodents have worse stroke outcome, characterised by increased ischaemic damage and an altered inflammatory response. However, clinical studies have reported an 'obesity paradox' in stroke, characterised by reduced mortality and morbidity in obese patients. We discuss the potential reasons why the preclinical and clinical studies may not agree, and review the mechanisms identified in preclinical studies through which obesity may affects stroke outcome. We suggest inflammation plays a central role in this relationship, as obesity features increases in inflammatory mediators such as C-reactive protein and interleukin-6, and chronic inflammation has been linked to worse stroke risk and outcome.
Topics: Animals; Humans; Inflammation; Obesity; Rodentia; Stroke; Translational Research, Biomedical
PubMed: 27655337
DOI: 10.1177/0271678X16670411 -
Nanotheranostics 2022Novel targeted therapies are rapidly emerging for the treatment of cancer. With the advent of new immune targeting agents, understanding the changes in the tumor... (Review)
Review
Novel targeted therapies are rapidly emerging for the treatment of cancer. With the advent of new immune targeting agents, understanding the changes in the tumor microenvironment (TME) is critical. Given the complexity and several cellular mechanisms and factors that play a role in the TME, novel imaging methods to assess and evaluate the dynamic changes in the TME during treatment are needed. Several techniques are being developed for imaging TME including optical, fluorescence and photoacoustic methods. Positron emission tomography (PET) imaging can be used to track the dynamics of different molecular targets in the TME in live animals and in humans. Several novel PET imaging probes including radiolabeled antibodies, antibody fragments, and small molecules have been developed with many more that are under development preclinically and in early human studies. This review is a brief overview of some of the PET agents that are either in the preclinical developmental phase or undergoing early clinical studies.
Topics: Animals; Neoplasms; Positron-Emission Tomography; Tumor Microenvironment
PubMed: 35223381
DOI: 10.7150/ntno.66556 -
World Journal of Oncology Apr 2024Pigs are playing an increasingly vital role as translational biomedical models for studying human pathophysiology. The annotation of the pig genome was a huge step... (Review)
Review
Pigs are playing an increasingly vital role as translational biomedical models for studying human pathophysiology. The annotation of the pig genome was a huge step forward in translatability of pigs as a biomedical model for various human diseases. Similarities between humans and pigs in terms of anatomy, physiology, genetics, and immunology have allowed pigs to become a comprehensive preclinical model for human diseases. With a diverse range, from craniofacial and ophthalmology to reproduction, wound healing, musculoskeletal, and cancer, pigs have provided a seminal understanding of human pathophysiology. This review focuses on the current research using pigs as preclinical models for cancer research and highlights the strengths and opportunities for studying various human cancers.
PubMed: 38545477
DOI: 10.14740/wjon1763