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https://www.readbyqxmd.com/read/28821631/6-methoxyethylamino-numonafide-inhibits-hepatocellular-carcinoma-xenograft-growth-as-a-single-agent-and-in-combination-with-sorafenib
#1
Yanning Liu, Guohua Lou, John T Norton, Chen Wang, Irawati Kandela, Shuai Tang, Nathaniel I Shank, Pankaj Gupta, Min Huang, Michael J Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang
Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28819441/vsv-based-virotherapy-in-ovarian-cancer-the-past-the-present-and-%C3%A2-future
#2
REVIEW
Beata Urszula Orzechowska, Marcin Jędryka, Katarzyna Zwolińska, Rafał Matkowski
The standard approach to treating patients with advanced epithelial ovarian cancer (EOC) after primary debulking surgery remains taxane and platinum-based chemotherapy. Despite treatment with this strategy, the vast majority of patients relapse and develop drug-resistant metastatic disease that may be driven by cancer stem cells (CSCs) or cancer initiating cells (CICs). Oncolytic viruses circumvent typical drug-resistance mechanisms, therefore they may provide a safe and effective alternative treatment for chemotherapy-resistant CSCs/CICs...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819363/combined-analysis-of-endothelial-hematopoietic-and-mesenchymal-stem-cell-compartments-shows-simultaneous-but-independent-effects-of-age-and-heart-disease
#3
Carine Ghem, Lucinara Dadda Dias, Roberto Tofani Sant'Anna, Renato A K Kalil, Melissa Markoski, Nance Beyer Nardi
Clinical trials using stem cell therapy for heart diseases have not reproduced the initial positive results obtained with animal models. This might be explained by a decreased regenerative capacity of stem cells collected from the patients. This work aimed at the simultaneous investigation of endothelial stem/progenitor cells (EPCs), mesenchymal stem/progenitor cells (MSCs), and hematopoietic stem/progenitor cells (HSCs) in sternal bone marrow samples of patients with ischemic or valvular heart disease, using flow cytometry and colony assays...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28819122/anti-inflammatory-drugs-suppress-ultrasound-mediated-mesenchymal-stromal-cell-tropism-to-kidneys
#4
Scott R Burks, Ben A Nguyen, Michele N Bresler, Matthew E Nagle, Saejeong J Kim, Joseph A Frank
Mesenchymal stromal cells (MSC) are potential renal therapeutics. Clinically, results are mixed partly because MSC tropism to kidneys is minimal following infusion. Ultrasound augmentation of the renal microenvironment is becoming increasingly-important in renal MSC therapies. We demonstrated pulsed-focused-ultrasound (pFUS) increases enhanced homing permeability and retention of MSC in mouse kidneys. Here, we characterized the temporal proteomic response to pFUS in mouse kidneys and its association with MSC tropism...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819075/-advances-in-neurological-therapeutics-for-friedreich-ataxia-and-machado-joseph-disease
#5
Ichiro Yabe, Hidenao Sasaki
We reviewed advances in therapeutics for both Friedreich ataxia and Machado-Joseph disease. Various clinical trials have been carried out, mainly for Friedreich ataxia; however, the therapeutic reports from these trials have not provided much evidence for success. Some interesting clinical trials have been reported, and further developments are expected. Regenerative therapy using umbilical cord mesenchymal stem cells and a therapeutic study investigating a new pathomechanism in animal and/or cell culture studies were reported...
August 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28819064/the-tumor-microenvironment-regulates-sensitivity-of-murine-lung-tumors-to-pd-1-pdl1-antibody-blockade
#6
Howard Y Li, Maria V McSharry, Bonnie Bullock, Teresa T Nguyen, Jeff Kwak, Joanna M Poczobutt, Trisha R Sippel, Lynn E Heasley, Mary C Weiser-Evans, Eric T Clambey, Raphael A Nemenoff
Immune checkpoint inhibitors targeting the interaction between programmed cell death-1 (PD-1) and its ligand PD-L1 induce tumor regression in a subset of non-small cell lung cancer patients. However, clinical response rates are less than 25%. Evaluation of combinations of immunotherapy with existing therapies requires appropriate pre-clinical animal models. In this study, murine lung cancer cells (CMT167 and LLC) were implanted either orthotopically in the lung or subcutaneously in--- syngeneic mice, and response to anti-PD-1/PD-L1 therapy was determined...
August 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28819004/acute-oxygen-sensing-by-the-carotid-body-from-mitochondria-to-plasma-membrane
#7
Andy J Chang
Maintaining oxygen homeostasis is crucial to the survival of animals. Mammals respond acutely to changes in blood oxygen levels by modulating cardiopulmonary function. The major sensor of blood oxygen that regulates breathing is the carotid body (CB), a small chemosensory organ located at the carotid bifurcation. When arterial blood oxygen levels drop in hypoxia, neuroendocrine cells in the CB called glomus cells are activated to signal to afferent nerves that project to the brainstem. The mechanism by which hypoxia stimulates CB sensory activity has been the subject of many studies over the last 90 years...
August 17, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28818494/gts-21-reduces-microvascular-permeability-during-experimental-endotoxemia
#8
Karsten Schmidt, Sukanya Bhakdisongkhram, Florian Uhle, Christoph Philipsenburg, Aleksandar R Zivkovic, Thorsten Brenner, Johann Motsch, Markus A Weigand, Stefan Hofer
INTRODUCTION: No effective pharmacological therapy is currently available to attenuate tissue edema formation due to increased microvascular permeability in sepsis. Cholinergic mediators have been demonstrated to exert anti-inflammatory effects via the α7 nicotinic acetylcholine receptor (α7nAChR) during inflammation. GTS-21, a partial α7nAChR agonist, is an appealing therapeutic substance for sepsis-induced microvascular inflammation due to its demonstrated cholinergic anti-inflammatory properties and its favorable safety profile in clinical trials...
August 14, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28818104/neuroprotective-properties-of-curcumin-in-toxin-base-animal-models-of-parkinson-s-disease-a-systematic-experiment-literatures-review
#9
Xin-Shi Wang, Zeng-Rui Zhang, Man-Man Zhang, Miao-Xuan Sun, Wen-Wen Wang, Cheng-Long Xie
BACKGROUND: Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Meanwhile, the neuroprotective actions of curcumin have been documented for experimental therapy in Parkinson's disease (PD). METHODS: In this study, we used a systematic review to comprehensively assess the efficacy of curcumin in experimental PD. Using electronic and manual search for the literatures, we identified studies describing the efficacy of curcumin in animal models of PD...
August 17, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28817983/the-use-of-soft-robotics-in-cardiovascular-therapy
#10
Isaac Wamala, Ellen T Roche, Frank A Pigula
Robots have been employed in cardiovascular therapy as surgical tools and for automation of hospital systems. Soft robots are a new kind of robot made of soft deformable materials. They are uniquely suited for biomedical applications because they are inherently less likely to injure body tissues and more likely to adapt to biological environments. Awareness of the soft robotic systems under development will help promote clinician involvement in their successful translation for therapeutic use. Areas Covered: The soft robotic systems, across the size scale from nano to macro, that have shown the most promise for clinical application in cardiovascular therapy because they represent the most mature technology and also they offer solutions where a clear therapeutic need still exists...
August 18, 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28817977/a-short-and-efficient-transduction-protocol-of-mouse-hematopoietic-stem-cells-with-lentiviral-vectors
#11
Maria Fernandez-Garcia, Cristina Mesa-Nuñez, Elena Almarza, Juan Bueren, Rosa Yañez
Transduction of hematopoietic stem and progenitor cells (HSPC) with therapeutic lentiviral vectors (LVs) constitutes a new therapeutic option for the treatment of different monogenic diseases affecting the lympho-hematopoietic system. The development of detailed preclinical studies of gene therapy in animal disease models constitutes an essential step in expanding the application of gene therapy in a wide variety of inherited and acquired diseases. Here we describe an efficient protocol to transduce HSPCs from wild-type and Fanconi anemia mice with either gene marking or therapeutic LVs...
August 17, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28817740/influence-of-microtextured-implant-surfaces-on-peri-implantitis-and-its-treatment-a-preclinical-trial
#12
Juan C Rodriguez, Tapan Koticha, Diana L Eubanks, Ivan Rudek, Fred J Molz, Ludovica Chiavaccini, Andrew Claude, Steven Elder, Hom-Lay Wang
PURPOSE: The prevalence of peri-implantitis has increased significantly, forcing clinicians to search for ways to prevent it. Laser-microtextured surfaces promote soft tissue attachment and provide a tight seal around implants. Hence, the aim of this study was to examine the clinical, radiographic, and histologic features of ligature-induced peri-implantitis, as well as the effect of surgical treatment of these induced peri-implantitis lesions on laser-microtextured implants in a controlled animal model...
August 17, 2017: International Journal of Oral & Maxillofacial Implants
https://www.readbyqxmd.com/read/28816544/animal-inflammation-based-models-of-depression-and-their-application-to-drug-discovery
#13
Li Ma, Konstantin A Demin, Tatyana O Kolesnikova, Sergey L Kharsko, Xiaokang Zhu, Xiaodong Yuan, Cai Song, Darya A Meshalkina, Brian E Leonard, Li Tian, Allan V Kalueff
Depression, anxiety and other affective disorders are globally widespread and severely debilitating human brain diseases. Despite their high prevalence and mental health impact, affective pathogenesis is poorly understood, and often remains recurrent and resistant to treatment. The lack of efficient antidepressants and presently limited conceptual innovation necessitate novel approaches and new drug targets in the field of antidepressant therapy. Areas covered: Herein, the authors discuss the emerging role of neuro-immune interactions in affective pathogenesis, which can become useful targets for CNS drug discovery, including modulating neuroinflammatory pathways to alleviate affective pathogenesis...
August 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28815847/mastitis-treatment-reduction-in-antibiotic-usage-in-dairy-cows
#14
REVIEW
V Krömker, S Leimbach
Animal-friendly, economical, resource-saving milk production provides the basis for sustained consumer acceptance. Bovine mastitis plays a decisive role in the dairy industry-disturbing animal health and welfare and causing considerable economic losses on the other hand. Currently, antimicrobial treatment is indispensable to keep bovine udder health, animal welfare and economic aspects in balance. On the contrary, emergence and spread of antimicrobial resistance (AMR) is an urgent matter of particular public interest, and as a consequence, antimicrobial usage (AMU) in production livestock is a critically discussed subject...
August 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28815604/chronic-morphine-reduces-the-readily-releasable-pool-of-gaba-a-presynaptic-mechanism-of-opioid-tolerance
#15
Adrianne R Wilson-Poe, Hyo-Jin Jeong, Christopher W Vaughan
The midbrain periaqueductal grey (PAG) plays a critical role in tolerance to the analgesic actions of opioids such as morphine. While numerous studies have identified the postsynaptic adaptations induced by chronic morphine treatment in this and other brain regions, the presence of presynaptic adaptations remains uncertain. We examined GABAergic synaptic transmission within rat PAG brain slices from animals which underwent a low dose morphine treatment protocol which produces tolerance, but not withdrawal. Evoked GABAergic IPSCs (inhibitory postsynaptic currents) were less in morphine compared to control saline treated animals...
August 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28815315/emerging-gene-therapies-for-genetic-hearing-loss
#16
REVIEW
Hena Ahmed, Olga Shubina-Oleinik, Jeffrey R Holt
Gene therapy, or the treatment of human disease using genetic material, for inner ear dysfunction is coming of age. Recent progress in developing gene therapy treatments for genetic hearing loss has demonstrated tantalizing proof-of-principle in animal models. While successful translation of this progress into treatments for humans awaits, there is growing interest from patients, scientists, clinicians, and industry. Nonetheless, it is clear that a number of hurdles remain, and expectations for total restoration of auditory function should remain tempered until these challenges have been overcome...
August 16, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28814738/identification-of-novel-non-secosteroidal-vitamin-d-receptor-agonists-with-potent-cardioprotective-effects-and%C3%A2-%C3%AF-%C3%AF-devoid-of-hypercalcemia
#17
Santosh A Khedkar, Mohammed A Samad, Sangita Choudhury, Ji Yoo Lee, Dongsheng Zhang, Ravi I Thadhani, S Ananth Karumanchi, Alan C Rigby, Peter M Kang
Vitamin D regulates many biological processes, but its clinical utility is limited by its hypercalcemic effect. Using a virtual screening platform to search novel chemical probes that activate the vitamin D signaling, we report discovery of novel non-steroidal small-molecule compounds that activate the vitamin D receptor (VDR), but are devoid of hypercalcemia. A lead compound (known as VDR 4-1) demonstrated potent transcriptional activities in a VDR reporter gene assay, and significantly ameliorated cardiac hypertrophy in cell culture studies and in animal models...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814374/from-bench-laboratory-to-bed-hospital-home-how-to-explore-effective-natural-and-synthetic-pak1-blockers-longevity-promoters-for-cancer-therapy
#18
REVIEW
Hiroshi Maruta, Mok-Ryeon Ahn
PAK family kinases are RAC/CDC42-activated kinases that were first found in a soil amoeba 4 decades ago, and 2 decades later, were discovered in mammals as well. Since then at least 6 members of this family have been identified in mammals. One of them called PAK1 has been best studied so far, mainly because it is essential not only for malignant cell growth and metastasis, but also for many other diseases/disorders such as diabetes (type 2), AD (Alzheimer's disease), hypertension, and a variety of inflammatory or infectious diseases, which definitely shorten our lifespan...
August 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28814329/severe-persistent-pulmonary-hypertension-of-the-newborn-and-dysmorphic-features-in-neonate-with-a-deletion-involving-twist1-and-phf14-a-case-report
#19
Carina Schinagl, Guro Reinholt Melum, Olaug Kristin Rødningen, Kathrine Bjørgo, Jannicke Hanne Andresen
BACKGROUND: Persistent pulmonary hypertension is a well-known disease of the newborn that in most cases responds well to treatment with nitric oxide and treatment of any underlying causes. Genetic causes of persistent pulmonary hypertension of the newborn are rare. The TWIST1 gene is involved in morphogenetics, and deletions are known to cause Saethre-Chotzen syndrome. Deletions of PHF14 have never been reported in neonates, but animal studies have shown a link between severe defects in lung development and deletions of this gene...
August 17, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28814237/statins-in-aortic-stenosis
#20
Karl Norrington, Emmanuel Androulakis, Evangelos Oikonomou, Georgia Vogiatzi, Dimitris Tousoulis
Calcific aortic stenosis (AS) is the most common form of valvular heart disease in Europe and North America. It is a progressive disease with a prolonged period of asymptomatic latency which eventually leads to critical left ventricular outflow tract obstruction necessitating surgical replacement of the valve. Statins are lipid-lowering drugs with a robust evidence base demonstrating clinical benefit in atherosclerotic coronary artery disease. There has therefore been significant interest in the potential benefit of statins in AS...
August 15, 2017: Current Pharmaceutical Design
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