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Preclinical models

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https://www.readbyqxmd.com/read/29786788/transplantable-animal-studies-and-whole-body-optical-imaging-in-prostate-carcinoma
#1
Geertje van der Horst, Maaike van der Mark, Henry Cheung, Gabri van der Pluijm
Current treatments of advanced prostate cancer only marginally increase overall survival and can be regarded as predominantly palliative. Hence, there is an urgent need for novel therapeutic strategies for the treatment of primary tumors and, more importantly perhaps, for the prevention of tumor progression and metastasis formation. Clinically relevant preclinical models are therefore urgently needed. An ideal, clinically relevant preclinical model would mimic the genetic and phenotypic changes that occur at the different stages of human prostate cancer progression and subsequent metastasis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786782/preclinical-impact-of-high-dose-intermittent-antiangiogenic-tyrosine-kinase-inhibitor-pazopanib-in-intrinsically-resistant-tumor-models
#2
Elaine Reguera-Nuñez, Shan Man, Ping Xu, Robert S Kerbel
Antiangiogenic tyrosine kinase inhibitors (TKIs) target vascular endothelial growth factor receptors and other receptor tyrosine kinases. As a result of toxicity, the clinical failures or the modest benefits associated with antiangiogenic TKI therapy may be related in some cases to suboptimal drug dosing and scheduling, thereby facilitating resistance. Most antiangiogenic TKIs, including pazopanib, are administered on a continuous daily basis. Here, instead, we evaluated the impact of increasing the dose and administering the drug intermittently...
May 21, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29786658/melatonin-as-a-therapy-for-traumatic-brain-injury-a-review-of-published-evidence
#3
REVIEW
Nicole Osier, Emily McGreevy, Lan Pham, Ava Puccio, Dianxu Ren, Yvette P Conley, Sheila Alexander, C Edward Dixon
Melatonin (MEL) is a hormone that is produced in the brain and is known to bind to MEL-specific receptors on neuronal membranes in several brain regions. MEL's documented neuroprotective properties, low toxicity, and ability to cross the blood-brain-barrier have led to its evaluation for patients with traumatic brain injury (TBI), a condition for which there are currently no Food and Drug Administration (FDA)-approved therapies. The purpose of this manuscript is to summarize the evidence surrounding the use of melatonin after TBI, as well as identify existing gaps and future directions...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786562/application-of-hepatocyte-like-cells-to-enhance-hepatic-safety-risk-assessment-in-drug-discovery
#4
REVIEW
Dominic P Williams
Hepatic stress and injury from drugs continues to be a major concern within the pharmaceutical industry, leading to preclinical and clinical attrition precautionary warnings and post-market withdrawal of drugs. There is a requirement for more predictive and mechanistically accurate models to aid risk assessment. Primary human hepatocytes, subject to isolation stress, cryopreservation, donor-to-donor variation and a relatively short period of functional capability in two-dimensional cultures, are not suitable for high-throughput screening procedures...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29786560/microfabrication-of-liver-and-heart-tissues-for-drug-development
#5
REVIEW
Grace E Brown, Salman R Khetani
Drug-induced liver- and cardiotoxicity remain among the leading causes of preclinical and clinical drug attrition, marketplace drug withdrawals and black-box warnings on marketed drugs. Unfortunately, animal testing has proven to be insufficient for accurately predicting drug-induced liver- and cardiotoxicity across many drug classes, likely due to significant differences in tissue functions across species. Thus, the field of in vitro human tissue engineering has gained increasing importance over the last 10 years...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29785833/species-differences-in-bile-acids-i-plasma-and-urine-bile-acid-composition
#6
Rhishikesh Thakare, Jawaher Abdullah Alamoudi, Nagsen Gautam, A David Rodrigues, Yazen Alnouti
Maintenance of bile acid (BA) homeostasis is essential to achieve their physiologic functions and avoid their toxic effects. The marked differences in BA composition between preclinical safety models and humans may play a major role in the poor prediction of drug-induced liver injury using preclinical models. We compared the composition of plasma and urinary BAs and their metabolites between humans and several animal species. Total BA pools and their composition varied widely among different species. Highest sulfation of BAs was observed in human and chimpanzee...
May 21, 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29785246/modulating-metabolism-to-improve-cancer-induced-muscle-wasting
#7
REVIEW
Fabio Penna, Riccardo Ballarò, Marc Beltrá, Serena De Lucia, Paola Costelli
Muscle wasting is one of the main features of cancer cachexia, a multifactorial syndrome frequently occurring in oncologic patients. The onset of cachexia is associated with reduced tolerance and response to antineoplastic treatments, eventually leading to clinical conditions that are not compatible with survival. Among the mechanisms underlying cachexia, protein and energy dysmetabolism play a major role. In this regard, several potential treatments have been proposed, mainly on the basis of promising results obtained in preclinical models...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29784598/a-novel-digital-method-to-assess-air-space-loss-associated-with-acute-lung-injury-in-experimental-acute-pancreatitis
#8
R Mukherjee, L Wen, X Zhang, P Bhattacharya, W Huang, R Sutton
BACKGROUND/OBJECTIVES: Respiratory dysfunction and/or failure from acute lung injury (ALI) are common in acute pancreatitis (AP), but assessment of ALI in experimental AP has lacked standardisation. METHODS: A range of experimental AP models induced in C57BL/6 mice with corresponding controls (n = 6/group). Full double lung or right lung specimens were taken for histopathological assessment and slides analysed by a pre-set pipeline using Aperio Scanner (Leica), ImageJ software and CellProfiler software...
May 4, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29782862/evaluation-of-cardiac-arrhythmic-risks-using-a-rabbit-model-of-left-ventricular-systolic-dysfunction
#9
Bianca Hemmeryckx, Yuanbo Feng, Liesbeth Frederix, Marleen Lox, Sander Trenson, Rob Vreeken, Hua Rong Lu, David Gallacher, Yicheng Ni, H Roger Lijnen
Patients with heart disease have a higher risk to develop cardiac arrhythmias, either spontaneously or drug-induced. In this study, we have used a rabbit model of myocardial infarction (MI) with severe left ventricular systolic dysfunction (LVSD) to study potential drug-induced cardiac risks with N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide (flecainide). Upon ligation of the left circumflex arteries, male New Zealand White rabbits developed a large MI and moderate or severe LVSD 7 weeks after surgery, in comparison to SHAM-operated animals...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782624/the-underlying-mechanisms-involved-in-the-protective-effects-of-ischemic-postconditioning
#10
Rong Xie, Jinquan Li, Heng Zhao
Cerebral ischemic postconditioning (PostC) refers to a series of brief ischemia and reperfusion (I/R) cycles applied at the onset of reperfusion following an ischemic event. PostC has been shown to have neuroprotective effects, and represents a promising clinical strategy against cerebral ischemia-reperfusion injury. Many studies have indicated that cerebral PostC can effectively reduce neural cell death, cerebral edema and infarct size, improve cerebral circulation, and relieve inflammation, apoptosis and oxidative stress...
2018: Conditioning medicine
https://www.readbyqxmd.com/read/29782011/a-preclinical-mouse-model-of-osteosarcoma-to-define-the-extracellular-vesicle-mediated-communication-between-tumor-and-mesenchymal-stem-cells
#11
Tonny Lagerweij, Maria Pérez-Lanzón, S Rubina Baglio
Within the tumor microenvironment, resident or recruited mesenchymal stem cells (MSCs) contribute to malignant progression in multiple cancer types. Under the influence of specific environmental signals, these adult stem cells can release paracrine mediators leading to accelerated tumor growth and metastasis. Defining the crosstalk between tumor and MSCs is of primary importance to understand the mechanisms underlying cancer progression and identify novel targets for therapeutic intervention. Cancer cells produce high amounts of extracellular vesicles (EVs), which can profoundly affect the behavior of target cells in the tumor microenvironment or at distant sites...
May 6, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781359/rhabdoviruses-as-vaccine-platforms-for-infectious-disease-and-cancer
#12
Franz Zemp, Jahanara Rajwani, Douglas J Mahoney
The family Rhabdoviridae (RV) comprises a large, genetically diverse collection of single-stranded, negative sense RNA viruses from the order Mononegavirales. Several RV members are being developed as live-attenuated vaccine vectors for the prevention or treatment of infectious disease and cancer. These include the prototype recombinant Vesicular Stomatitis Virus (rVSV) and the more recently developed recombinant Maraba Virus, both species within the genus Vesiculoviridae. A relatively strong safety profile in humans, robust immunogenicity and genetic malleability are key features that make the RV family attractive vaccine platforms...
May 21, 2018: Biotechnology & Genetic Engineering Reviews
https://www.readbyqxmd.com/read/29781327/the-progress-of-aav-mediated-gene-therapy-in-neuromuscular-disorders
#13
Sara Aguti, Alberto Malerba, Haiyan Zhou
The well-defined genetic causes and monogenetic nature of many neuromuscular disorders, including Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), present gene therapy as a prominent therapeutic approach. The novel variants of adeno-associated virus (AAV) can achieve satisfactory transduction efficiency of exogenous genes through the central nervous system and body-wide in skeletal muscle. Areas covered: In this review, we summarize the strategies of AAV gene therapy that are currently under preclinical and clinical evaluation for the treatment of degenerative neuromuscular disorders, with a focus on diseases such as DMD and SMA...
May 20, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29780861/the-relationship-between-recall-of-recently-versus-remotely-encoded-famous-faces-and-amyloidosis-in-clinically-normal-older-adults
#14
Irina Orlovsky, Willem Huijbers, Bernard J Hanseeuw, Elizabeth C Mormino, Trey Hedden, Rachel F Buckley, Molly LaPoint, Jennifer S Rabin, Dorene M Rentz, Keith A Johnson, Reisa A Sperling, Kathryn V Papp
Introduction: Alzheimer's disease (AD) patients exhibit temporally graded memory loss with remote memories remaining more intact than recent memories. It is unclear whether this temporal pattern is observable in clinically normal adults with amyloid pathology (i.e. preclinical AD). Methods: Participants were asked to recall the names of famous figures most prominent recently (famous after 1990) and remotely (famous from 1960-1980) and were provided with a phonemic cue to ensure that memory failure was not purely due to verbal retrieval weaknesses...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780814/targeting-chronic-myeloid-leukemia-stem-cells-can-transcriptional-program-be-a-druggable-target-for-cancers
#15
REVIEW
Yosuke Masamoto, Mineo Kurokawa
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from acquisition of constitutively active BCR-ABL protein tyrosine kinase in a hematopoietic stem cell (HSC). Though tyrosine kinase inhibitors (TKIs) have changed a fatal disease into manageable disease, most patients cannot discontinue TKI treatment due to persistence of TKI-resistant leukemia stem cells (LSCs). Much effort has been made to find out factors or pathways specifically operating in LSCs to selectively target LSCs, with some promising results at least in preclinical models...
2018: Stem Cell Investigation
https://www.readbyqxmd.com/read/29780390/dopaminergic-control-of-inflammation-and-glycemia-in-sepsis-and-diabetes
#16
Eleonora Feketeova, Zhifeng Li, Biju Joseph, Roshan Shah, Zoltan Spolarics, Luis Ulloa
Most preclinical treatments for sepsis failed in clinical trials in part because the experimental models of sepsis were performed on healthy animals that do not mimic septic patients. Here, we report that experimental diabetes worsens glycemia, inflammation, and mortality in experimental sepsis. Diabetes increases hyperglycemia, systemic inflammation, and mortality in sepsis. Diabetes exacerbates serum tumor necrosis factor (TNF) levels in sepsis by increasing splenic TNF production. Both serum from diabetic mice and glucose increase cytokine production in splenocytes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29779580/animal-models-of-endometriosis-replicating-the-aetiology-and-symptoms-of-the-human-disorder
#17
REVIEW
Ioannis Simitsidellis, Douglas A Gibson, Philippa T K Saunders
Endometriosis is a chronic incurable disorder that affects 1 in 10 women of reproductive age: associated symptoms include chronic pain and infertility. The aetiology of endometriosis remains poorly understood but patients, clinicians and researchers are all in agreement that new non-surgical therapies are urgently needed to reduce the severity of symptoms. Preclinical testing of drugs requires the development and validation of models that recapitulate the key features of the disorder. In this review we describe the best-validated animal models (primate, rodent, xenograft) and their contributions to our understanding of the factors underpinning the development of symptoms...
June 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29779406/inhalation-delivery-of-topotecan-is-superior-to-intravenous-exposure-for-suppressing-lung-cancer-in-a-preclinical-model
#18
Philip J Kuehl, Marcie J Grimes, Devon Dubose, Michael Burke, David A Revelli, Andrew P Gigliotti, Steven A Belinsky, Mathewos Tessema
Intravenous (IV) topotecan is approved for the treatment of various malignancies including lung cancer but its clinical use is greatly undermined by severe hematopoietic toxicity. We hypothesized that inhalation delivery of topotecan would increase local exposure and efficacy against lung cancer while reducing systemic exposure and toxicity. These hypotheses were tested in a preclinical setting using a novel inhalable formulation of topotecan against the standard IV dose. Respirable dry-powder of topotecan was manufactured through spray-drying technology and the pharmacokinetics of 0...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29779124/confidenht%C3%A2-system-for-diagnostic-mapping-of-renal-nerves
#19
REVIEW
Costas Tsioufis, Kyriakos Dimitriadis, Panagiotis Tsioufis, Rafael Patras, Maria Papadoliopoulou, Zoi Petropoulou, Dimitris Konstantinidis, Dimitrios Tousoulis
PURPOSE OF REVIEW: To summarize the evidence regarding the distribution of renal nerves and their patterns of anatomic variations in animal and human settings. Moreover, the methodology and results of studies regarding renal nerve stimulation (RNS) in both preclinical and clinical models are presented. RECENT FINDINGS: There are differences regarding the number and the size of renal fibers, as well as their distance from the lumen in the diverse parts of the main renal arteries and the branches...
May 19, 2018: Current Hypertension Reports
https://www.readbyqxmd.com/read/29778782/acyclovir-lipid-nanocapsules-gel-for-oromucosal-delivery-a-preclinical-evidence-of-efficacy-in-the-chicken-pouch-membrane-model
#20
Darine Abozaid, Alyaa Ramadan, Heba Barakat, Nawal Khalafallah
The study aimed to develop a patient-friendly acyclovir gel with improved efficacy in viral mouth infections, in response to patients' need for an intraoral acyclovir product. Acyclovir was loaded in lipid nanocapsules in gel form, and formulae were evaluated for oromucosal delivery. Lipid nanocapsules were prepared by the phase inversion method. Formulae were optimized to achieve maximum acyclovir entrapment and minimum acyclovir precipitation. Colloidal properties, and pharmaceutical performance indicators were assessed...
May 17, 2018: European Journal of Pharmaceutical Sciences
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