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Cellular Oncology (Dordrecht) Aug 2022Glioblastoma (GBM) patients are notoriously difficult to treat and ultimately all succumb to disease. This unfortunate scenario motivates research into better... (Review)
Review
BACKGROUND
Glioblastoma (GBM) patients are notoriously difficult to treat and ultimately all succumb to disease. This unfortunate scenario motivates research into better characterizing and understanding this disease, and into developing novel research tools by which potential novel therapeutics and treatment options initially can be evaluated pre-clinically. Here, we provide a concise overview of glioblastoma epidemiology, disease classification, the challenges faced in the treatment of glioblastoma and current novel treatment strategies. From this, we lead into a description and assessment of advanced cell-based models that aim to narrow the gap between pre-clinical and clinical studies. Such in vitro models are required to deliver reliable and meaningful data for the development and pre-validation of novel therapeutics and treatments.
CONCLUSIONS
The toolbox for GBM cell-based models has expanded substantially, with the possibility of 3D printing tumour tissues and thereby replicating in vivo tissue architectures now looming on the horizon. A comparison of experimental cell-based model systems and techniques highlights advantages and drawbacks of the various tools available, based on which cell-based models and experimental approaches best suited to address a diversity of research questions in the glioblastoma research field can be selected.
Topics: Brain Neoplasms; Cell Line, Tumor; Glioblastoma; Humans
PubMed: 35763242
DOI: 10.1007/s13402-022-00684-7 -
Advances in Physiology Education Dec 2022Students with varying personality traits are likely to employ diverse learning and study strategies. However, this relationship has never been explored in the medical...
Students with varying personality traits are likely to employ diverse learning and study strategies. However, this relationship has never been explored in the medical education context. This study's aim was to explore the relationship between learning strategies and personality traits among medical students. This study was a cross-sectional study, and a quantitative approach was employed using two self-administered questionnaires: one to assess the personality traits from the Five-Factor Model (Conscientiousness, Neuroticism, Extraversion, Openness, and Agreeableness), and the other to assess 10 learning strategies (Anxiety, Attitude, Concentration, Information Processing, Motivation, Selecting Main Ideas, Self-Testing, Test Strategies, Time Management, and Using Academic Resources). A stratified random sampling technique was used to recruit medical students at Alfaisal University in the preclinical and clinical years ( = 309). Pearson correlation coefficient was used to measure the relationship between variables, and linear regression was used to evaluate how personality traits predicted learning strategy selection. Personality traits predicted the selection of learning strategies, especially Conscientiousness and Neuroticism. Conscientiousness showed a positive correlation with seven learning strategies and was the most important predictor of learning strategies students employ. Neuroticism correlations and predictions were negative. The other three traits showed weaker correlations. These correlations were between Extraversion and Using Academic Resources ( = 0.27), Information Processing ( = 0.23), and Attitude ( = 0.19); Openness and Information Processing ( = 0.29); and Agreeableness and Attitude ( = 0.29). All personality domains influence at least one learning strategy, especially Conscientiousness and Neuroticism. This study helps build a foundation for individualized coaching and mentorship in medical education. This study aspires to build a foundation for individualized coaching and mentorship in medical education through utilizing personality traits to empower academic success. We demonstrate that all personality domains influence students' selection of at least one learning strategy, especially Conscientiousness and Neuroticism.
Topics: Cross-Sectional Studies; Humans; Learning; Personality; Students, Medical; Universities
PubMed: 36135937
DOI: 10.1152/advan.00001.2022 -
Frontiers in Physiology 2020The purpose of this systematic review was to investigate the scientific evidence to support the use of direct renin inhibitors (DRIs) in diabetic nephropathy (DN).... (Review)
Review
The purpose of this systematic review was to investigate the scientific evidence to support the use of direct renin inhibitors (DRIs) in diabetic nephropathy (DN). MEDLINE was searched for articles reported until 2018. A standardized dataset was extracted from articles describing the effects of DRIs on plasma renin activity (PRA) in DN. A total of three clinical articles studying PRA as an outcome measure for DRIs use in DN were identified. These clinical studies were randomized controlled trials (RCTs): one double-blind crossover, one of a double-blind and placebo-controlled study, and one open-label and parallel-controlled study. Two studies reported a significant decrease of albuminuria associated with PRA reduction. One study had a DRI as monotherapy compared with placebo, and two studies had DRI as add-in to an angiotensin II (Ang II) receptor blocker (ARB). Of 10,393 patients with DN enrolled in five studies with DRI, 370 (3.6%) patients had PRA measured. Only one preclinical study was identified that determined PRA when investigating the effects of aliskiren in DN. Moreover, most of observational preclinical and clinical studies identified report on a low PRA or hyporeninemic hypoaldosteronism in DM. Renin inhibition has been suggested for DN, but proof-of-concept studies for this are scant. A small number of clinical and preclinical studies assessed the PRA effects of DRIs in DN. For a more successful translational research for DRIs, specific patient population responsive to the treatment should be identified, and PRA may remain a biomarker of choice for patient stratification.
PubMed: 32231590
DOI: 10.3389/fphys.2020.00190 -
Journal of Neurochemistry Jan 2022Therapeutic hypothermia (TH) has applications dating back millennia. In modern history, however, TH saw its importation into medical practice where investigations have... (Review)
Review
Therapeutic hypothermia (TH) has applications dating back millennia. In modern history, however, TH saw its importation into medical practice where investigations have demonstrated that TH is efficacious in ischemic insults, notably cardiac arrest and hypoxic-ischemic encephalopathy. As well, studies have been undertaken to investigate whether TH can provide benefit in focal stroke (i.e., focal ischemia and intracerebral hemorrhage). However, clinical studies have encountered various challenges with induction and maintenance of post-stroke TH. Most clinical studies have attempted to use body-wide cooling protocols, commonly hindered by side effects that can worsen post-stroke outcomes. Some of the complications and difficulties with systemic TH can be circumvented by using local hypothermia (LH) methods. Additional advantages include the potential for lower target temperatures to be achieved and faster TH induction rates with LH. This systematic review summarizes the body of clinical and preclinical LH focal stroke studies and raises key points to consider for future LH research. We conclude with an overview of LH neuroprotective mechanisms and a comparison of LH mechanisms with those observed with systemic TH. Overall, whereas many LH studies have been conducted preclinically in the context of focal ischemia, insufficient work has been done in intracerebral hemorrhage. Furthermore, key translational studies have yet to be done in either stroke subtype (e.g., varied models and time-to-treat, studies considering aged animals or animals with co-morbidities). Few clinical LH investigations have been performed and the optimal LH parameters to achieve neuroprotection are unknown.
Topics: Animals; Humans; Hypothermia, Induced; Stroke
PubMed: 34496050
DOI: 10.1111/jnc.15508 -
Neuronal Signaling Jul 2023Stress exposure is associated with psychiatric conditions, such as depression, anxiety, and post-traumatic stress disorder (PTSD). It is also a vulnerability factor to... (Review)
Review
Stress exposure is associated with psychiatric conditions, such as depression, anxiety, and post-traumatic stress disorder (PTSD). It is also a vulnerability factor to developing or reinstating substance use disorder. Stress causes several changes in the neuro-immune-endocrine axis, potentially resulting in prolonged dysfunction and diseases. Changes in several transmitters, including serotonin, dopamine, glutamate, gamma-aminobutyric acid (GABA), glucocorticoids, and cytokines, are associated with psychiatric disorders or behavioral alterations in preclinical studies. Complex and interacting mechanisms make it very difficult to understand the physiopathology of psychiatry conditions; therefore, studying regulatory mechanisms that impact these alterations is a good approach. In the last decades, the impact of stress on biology through epigenetic markers, which directly impact gene expression, is under intense investigation; these mechanisms are associated with behavioral alterations in animal models after stress or drug exposure, for example. The endocannabinoid (eCB) system modulates stress response, reward circuits, and other physiological functions, including hypothalamus-pituitary-adrenal axis activation and immune response. eCBs, for example, act retrogradely at presynaptic neurons, limiting the release of neurotransmitters, a mechanism implicated in the antidepressant and anxiolytic effects after stress. Epigenetic mechanisms can impact the expression of eCB system molecules, which in turn can regulate epigenetic mechanisms. This review will present evidence of how the eCB system and epigenetic mechanisms interact and the consequences of this interaction in modulating behavioral changes after stress exposure in preclinical studies or psychiatric conditions. Moreover, evidence that correlates the involvement of the eCB system and epigenetic mechanisms in drug abuse contexts will be discussed.
PubMed: 37520658
DOI: 10.1042/NS20220034 -
Osteoarthritis and Cartilage Jun 2022Osteoarthritis (OA) is a chronic degenerative joint disease and a leading cause of disability worldwide. Pain is the main symptom, yet no current treatment can halt... (Review)
Review
Osteoarthritis (OA) is a chronic degenerative joint disease and a leading cause of disability worldwide. Pain is the main symptom, yet no current treatment can halt disease progression or effectively provide symptomatic relief. Numerous animal models have been described for studying OA and some for the associated OA pain. This review aims to update on current models used for studying OA pain, focusing on mice and rats. These models include surgical, chemical, mechanical, and spontaneous OA models. The impact of sex and age will also be addressed in the context of OA modelling. Although no single animal model has been shown ideal for studying OA pain, increased efforts to phenotype OA will likely impact the choice of models for pre-clinical and basic research studies.
Topics: Animals; Disease Models, Animal; Mice; Osteoarthritis, Knee; Pain; Rats; Rodentia
PubMed: 35139423
DOI: 10.1016/j.joca.2022.01.010 -
Addiction Biology Sep 2016The importance of studying sex as a biological variable in biomedical research is becoming increasingly apparent. There is a particular need in preclinical studies of... (Review)
Review
The importance of studying sex as a biological variable in biomedical research is becoming increasingly apparent. There is a particular need in preclinical studies of addiction to include both sexes, as female animals are often excluded from studies, leaving large gaps in our knowledge of not only sex differences and potential prevention and treatment strategies but also with regard to the basic neurobiology of addiction. This review focuses on methodology that has been developed in preclinical studies to examine sex differences in the behavioral aspects and neurobiological mechanisms related to addiction across the full range of the addiction process, including initiation (acquisition), maintenance, escalation, withdrawal, relapse to drug seeking and treatment. This review also discusses strategic and technical issues that need to be considered when comparing females and males, including the role of ovarian hormones and how sex differences interact with other major vulnerability factors in addiction, such as impulsivity, compulsivity and age (adolescent versus adult). Novel treatments for addiction are also discussed, such as competing non-drug rewards, repurposed medications such as progesterone and treatment combinations. Practical aspects of conducting research comparing female and male animals are also considered. Making sex differences a point of examination requires additional effort and consideration; however, such studies are necessary given mounting evidence demonstrating that the addiction process occurs differently in males and females. These studies should lead to a better understanding of individual differences in the development of addiction and effective treatments for males and females.
Topics: Animals; Behavior, Addictive; Disease Models, Animal; Female; Male; Research; Sex Characteristics; Sex Factors
PubMed: 27345022
DOI: 10.1111/adb.12400 -
Cancers Feb 2020Microbeam Radiation Therapy (MRT) is an innovative approach in radiation oncology where a collimator subdivides the homogeneous radiation field into an array of... (Review)
Review
BACKGROUND
Microbeam Radiation Therapy (MRT) is an innovative approach in radiation oncology where a collimator subdivides the homogeneous radiation field into an array of co-planar, high-dose beams which are tens of micrometres wide and separated by a few hundred micrometres.
OBJECTIVE
This scoping review was conducted to map the available evidence and provide a comprehensive overview of the similarities, differences, and outcomes of all experiments that have employed animal models in MRT.
METHODS
We considered articles that employed animal models for the purpose of studying the effects of MRT. We searched in seven databases for published and unpublished literature. Two independent reviewers screened citations for inclusion. Data extraction was done by three reviewers.
RESULTS
After screening 5688 citations and 159 full-text papers, 95 articles were included, of which 72 were experimental articles. Here we present the animal models and pre-clinical radiation parameters employed in the existing MRT literature according to their use in cancer treatment, non-neoplastic diseases, or normal tissue studies.
CONCLUSIONS
The study of MRT is concentrated in brain-related diseases performed mostly in rat models. An appropriate comparison between MRT and conventional radiotherapy (instead of synchrotron broad beam) is needed. Recommendations are provided for future studies involving MRT.
PubMed: 32106397
DOI: 10.3390/cancers12030527 -
Advances in Cancer Research 2013Therapeutic vaccines represent a viable option for active immunotherapy of cancers that aim to treat late stage disease by using a patient's own immune system. The... (Review)
Review
Therapeutic vaccines represent a viable option for active immunotherapy of cancers that aim to treat late stage disease by using a patient's own immune system. The promising results from clinical trials recently led to the approval of the first therapeutic cancer vaccine by the U.S. Food and Drug Administration. This major breakthrough not only provides a new treatment modality for cancer management but also paves the way for rationally designing and optimizing future vaccines with improved anticancer efficacy. Numerous vaccine strategies are currently being evaluated both preclinically and clinically. This review discusses therapeutic cancer vaccines from diverse platforms or targets as well as the preclinical and clinical studies employing these therapeutic vaccines. We also consider tumor-induced immune suppression that hinders the potency of therapeutic vaccines, and potential strategies to counteract these mechanisms for generating more robust and durable antitumor immune responses.
Topics: Antigens, Neoplasm; Cancer Vaccines; Clinical Trials as Topic; Dendritic Cells; Humans; Immune System; Medical Oncology; Neoplasms; United States; United States Food and Drug Administration; Vaccines, DNA
PubMed: 23870514
DOI: 10.1016/B978-0-12-407190-2.00007-1 -
Endocrinology and Metabolism (Seoul,... Dec 2022The overall prognosis of thyroid cancer is excellent, but some patients have grossly invasive disease and distant metastases with limited responses to systemic... (Review)
Review
The overall prognosis of thyroid cancer is excellent, but some patients have grossly invasive disease and distant metastases with limited responses to systemic therapies. Thus, relevant preclinical models are needed to investigate thyroid cancer biology and novel treatments. Different preclinical models have recently emerged with advances in thyroid cancer genetics, mouse modeling and new cell lines. Choosing the appropriate model according to the research question is crucial to studying thyroid cancer. This review will discuss the current preclinical models frequently used in thyroid cancer research, from cell lines to mouse models, and future perspectives on patient-derived and humanized preclinical models in this field.
Topics: Animals; Mice; Adenocarcinoma, Follicular; Thyroid Neoplasms; Disease Models, Animal; Cell Line
PubMed: 36604954
DOI: 10.3803/EnM.2022.1636