keyword
MENU ▼
Read by QxMD icon Read
search

Proof of concept clinical trial

keyword
https://www.readbyqxmd.com/read/28201851/the-design-of-clinical-trials-in-portal-hypertension
#1
Juan G Abraldes, Guadalupe Garcia-Tsao
Portal hypertension (PH) is the main consequence of cirrhosis and is responsible for the majority of its complications. Gastroesophageal varices and variceal hemorrhage are direct consequences of PH; therefore, most clinical trials in PH have been directed toward treating or preventing variceal hemorrhage. However, varices and variceal hemorrhage are not isolated events; they must be considered in the context of the presence (or absence) of other complications of cirrhosis/PH. Cirrhosis progresses across different stages, each with a different prognosis and pathophysiology and hence different therapeutic targets...
February 2017: Seminars in Liver Disease
https://www.readbyqxmd.com/read/28193778/ag-221-a-first-in-class-therapy-targeting-acute-myeloid-leukemia-harboring-oncogenic-idh2-mutations
#2
Katharine Yen, Jeremy Travins, Fang Wang, Muriel D David, Erin Artin, Kim Straley, Anil Padyana, Stefan Gross, Byron DeLaBarre, Erica Tobin, Yue Chen, Raj Nagaraja, Sung Choe, Lei Jin, Zenon Konteatis, Giovanni Cianchetta, Jeffrey O Saunders, Francesco G Salituro, Cyril Quivoron, Paule Opolon, Olivia Bawa, Véronique Saada, Angelo Paci, Sophie Broutin, Olivier A Bernard, Stéphane de Botton, Benoît S Marteyn, Monika Pilichowska, YingXia Xu, Cheng Fang, Fan Jiang, Wentao Wei, Shengfang Jin, Lee Silverman, Wei Liu, Hua Yang, Lenny Dang, Marion Dorsch, Virginie Penard-Lacronique, Scott A Biller, Shin-San Michael Su
Somatic gain-of-function mutations in isocitrate dehydrogenase (IDH) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite, (R)-2-hydroxyglutarate (2HG). 2HG competitively inhibits α-ketoglutarate-dependent dioxygenases, including histone demethylases and methylcytosine dioxygenases of the Tet family, causing epigenetic dysregulation and a block in cellular differentiation. In vitro studies have provided proof of concept for mutant IDH inhibition as a therapeutic approach...
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193216/a-high-throughput-expression-screening-platform-to-optimize-the-production-of-antimicrobial-peptides
#3
Christine Schreiber, Hagen Müller, Oliver Birrenbach, Moritz Klein, Doreen Heerd, Tobias Weidner, Denise Salzig, Peter Czermak
BACKGROUND: Antimicrobial peptides (AMPs) are promising candidates for the development of novel antibiotics, but it is difficult to produce sufficient quantities for preclinical and clinical studies due to their toxicity towards microbial expression hosts. To avoid laborious trial-and-error testing for the identification of suitable expression constructs, we have developed a small-scale expression screening platform based on a combinatorial plasmid library. RESULTS: The combinatorial library is based on the Golden Gate cloning system...
February 13, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28191757/cartilage-regeneration-in-osteoarthritic-patients-by-a-composite-of-allogeneic-umbilical-cord-blood-derived-mesenchymal-stem-cells-and-hyaluronate-hydrogel-results-from-a-clinical-trial-for-safety-and-proof-of-concept-with-7-years-of-extended-follow-up
#4
Yong-Beom Park, Chul-Won Ha, Choong-Hee Lee, Young Cheol Yoon, Yong-Geun Park
Few methods are available to regenerate articular cartilage defects in patients with osteoarthritis. We aimed to assess the safety and efficacy of articular cartilage regeneration by a novel medicinal product composed of allogeneic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Patients with Kellgren-Lawrence grade 3 osteoarthritis and International Cartilage Repair Society (ICRS) grade 4 cartilage defects were enrolled in this clinical trial. The stem cell-based medicinal product (a composite of culture-expanded allogeneic hUCB-MSCs and hyaluronic acid hydrogel [Cartistem]) was applied to the lesion site...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28186705/current-and-future-perspectives-on-alginate-encapsulated-pancreatic-islet
#5
Berit L Strand, Abba E Coron, Gudmund Skjak-Braek
Transplantation of pancreatic islets in immune protective capsules holds the promise as a functional cure for type 1 diabetes, also about 40 years after the first proof of principal study. The concept is simple in using semipermeable capsules that allow the ingress of oxygen and nutrients, but limit the access of the immune system. Encapsulated human islets have been evaluated in four small clinical trials where the procedure has been evaluated as safe, but lacking long-term efficacy. Host reactions toward the biomaterials used in the capsules may be one parameter limiting the long-term function of the graft in humans...
February 2, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28174390/-surgical-regeneration-therapy-using-myoblast-sheets-for-severe-heart-failure
#6
Yoshiki Sawa
Heart failure is a life-threatening disorder worldwide, and the current end-stage therapies for severe heart failure are replacement therapies such as ventricular-assist devices and heart transplantation. Although these therapies have been reported to be useful, there are many issues in terms of the durability, complications, limited donors, adverse effect of continuous administration of immunosuppressive agents, and high costs involved. Recently, regenerative therapy based on genetic, cellular, or tissue engineering techniques has gained attention as a new therapy to overcome the challenges encountered in transplantation medicine...
January 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28174194/safety-and-efficacy-of-remote-ischemic-preconditioning-in-patients-with-severe-carotid-artery-stenosis-prior-to-carotid-artery-stenting-a-proof-of-concept-randomized-controlled-trial
#7
Wenbo Zhao, Ran Meng, Chun Ma, Baojun Hou, Liqun Jiao, Fengshui Zhu, Weijuan Wu, Jingfei Shi, Yunxia Duan, Renling Zhang, Jing Zhang, Yongxin Sun, Hongqi Zhang, Feng Ling, Yuping Wang, Wuwei Feng, Yuchuan Ding, Bruce Ovbiagele, Xunming Ji
BACKGROUND: -Remote ischemic preconditioning (RIPC) can inhibit recurrent ischemic events effectively in patients with acute or chronic cerebral ischemia. However, it is still unclear that whether RIPC can impede ischemic injury after carotid artery stenting (CAS) in patients with severe carotid artery stenosis. METHODS: -Subjects with severe carotid artery stenosis were recruited in this randomized controlled study, and assigned to RIPC, sham and no intervention (control) groups...
February 7, 2017: Circulation
https://www.readbyqxmd.com/read/28174191/augmentation-of-muscle-blood-flow-by-ultrasound-cavitation-is-mediated-by-atp-and-purinergic-signaling
#8
J Todd Belcik, Brian P Davidson, Aris Xie, Melinda D Wu, Mrinal Yadava, Yue Qi, Sherry Liang, Chae Ryung Chon, Azzdine Y Ammi, Joshua Field, Leanne Harmann, William M Chilian, Joel Linden, Jonathan R Lindner
BACKGROUND: - Augmentation of tissue blood flow by therapeutic ultrasound is thought to rely on convective shear. Microbubble contrast agents that undergo ultrasound-mediated cavitation markedly amplify these effects. We hypothesized that purinergic signalling is responsible for shear-dependent increases in muscle perfusion during therapeutic cavitation. METHODS: -Unilateral exposure of the proximal hindlimb of mice (with or without ischemia produced by iliac ligation) to therapeutic ultrasound (1...
February 7, 2017: Circulation
https://www.readbyqxmd.com/read/28161513/the-burden-of-proof-the-current-state-of-atrial-fibrillation-prevention-and-treatment-trials
#9
Rosita Zakeri, David R Van Wagoner, Hugh Calkins, Tom Wong, Heather M Ross, E Kevin Heist, Timothy E Meyer, Peter R Kowey, Robert J Mentz, John G Cleland, Bertram Pitt, Faiez Zannad, Cecilia Linde
Atrial fibrillation (AF) is an age-related arrhythmia of enormous socio-economic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalised care. However considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management in high-risk patients with multiple comorbidities...
February 1, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28158239/let-them-eat-fruit-the-effect-of-fruit-and-vegetable-consumption-on-psychological-well-being-in-young-adults-a-randomized-controlled-trial
#10
Tamlin S Conner, Kate L Brookie, Anitra C Carr, Louise A Mainvil, Margreet C M Vissers
: This study tested the psychological benefits of a 14-day preregistered clinical intervention to increase fruit and vegetable (FV) consumption in 171 low-FV-consuming young adults (67% female, aged 18-25). Participants were randomly assigned into a diet-as-usual control condition, an ecological momentary intervention (EMI) condition involving text message reminders to increase their FV consumption plus a voucher to purchase FV, or a fruit and vegetable intervention (FVI) condition in which participants were given two additional daily servings of fresh FV to consume on top of their normal diet...
2017: PloS One
https://www.readbyqxmd.com/read/28153778/accelerating-the-clinical-development-of-protein-based-vaccines-for-malaria-by-efficient-purification-using-a-four-amino-acid-c-terminal-c-tag
#11
Jing Jin, Kathryn A Hjerrild, Sarah E Silk, Rebecca E Brown, Geneviève M Labbé, Jennifer M Marshall, Katherine E Wright, Sandra Bezemer, Stine B Clemmensen, Sumi Biswas, Yuanyuan Li, Aadil El-Turabi, Alexander D Douglas, Pim Hermans, Frank J Detmers, Willem A de Jongh, Matthew K Higgins, Rebecca Ashfield, Simon J Draper
Development of bespoke biomanufacturing processes remains a critical bottleneck for translational studies, in particular when modest quantities of a novel product are required for proof-of-concept Phase I/II clinical trials. In these instances the ability to develop a biomanufacturing process quickly and relatively cheaply, without risk to product quality or safety, provides a great advantage by allowing new antigens or concepts in immunogen design to more rapidly enter human testing. These challenges with production and purification are particularly apparent when developing recombinant protein-based vaccines for difficult parasitic diseases, with Plasmodium falciparum malaria being a prime example...
January 30, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28142257/transcranial-direct-current-stimulation-targeting-primary-motor-versus-dorsolateral-prefrontal-cortices-proof-of-concept-study-investigating-functional-connectivity-of-thalamo-cortical-networks-specific-to-sensory-affective-information-processing
#12
Vishwanath Sankarasubramanian, David Cunningham, Kelsey Potter, Erik Beall, Sarah Roelle, Nicole Varnerin, Andre Machado, Stephen Jones, Mark Lowe, Ela Plow
Pain matrix is subtended by an extensive cortical network spanning across sensory and affective domains. Transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC) represent popular methods to modulate such networks. However, differences between their mechanisms remain unknown. Here, in a proof-of-concept study, resting-state functional MRI was used to investigate the effects of stimulating M1 versus DLPFC on functional connectivity (FC) of networks within a healthy pain matrix...
January 31, 2017: Brain Connectivity
https://www.readbyqxmd.com/read/28137534/is-there-a-place-for-human-fetal-derived-stem-cells-for-cell-replacement-therapy-in-huntington-s-disease
#13
REVIEW
Sophie V Precious, Rike Zietlow, Stephen B Dunnett, Claire M Kelly, Anne E Rosser
Huntington's disease (HD) is a neurodegenerative disease that offers an excellent paradigm for cell replacement therapy because of the associated relatively focal cell loss in the striatum. The predominant cells lost in this condition are striatal medium spiny neurons (MSNs). Transplantation of developing MSNs taken from the fetal brain has provided proof of concept that donor MSNs can survive, integrate and bring about a degree of functional recovery in both pre-clinical studies and in a limited number of clinical trials...
January 27, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28137460/the-pharmacological-treatment-of-aggression-in-children-and-adolescents-with-conduct-disorder-do-callous-unemotional-traits-modulate-the-efficacy-of-medication
#14
REVIEW
Carla Balia, Sara Carucci, David Coghill, Alessandro Zuddas
BACKGROUND: Children and adolescents with conduct disorder (CD) show repetitive and persistent patterns of aggressive behaviour and the more severe forms are often associated with callous-unemotional (CU) traits. OBJECTIVES: To systematically review and, where data are adequate, conduct meta-analyses on the efficacy of medication on aggression in children and adolescent with CD considering the impact of CU traits. RESULTS: Few studies have investigated patients with CD as primary diagnosis, and few of these have discriminated between different types of aggression or reported measures of CU traits...
January 27, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28130586/gene-therapy-approaches-in-the-non-human-primate-model-of-parkinson-s-disease
#15
REVIEW
D Pignataro, D Sucunza, A J Rico, I G Dopeso-Reyes, E Roda, A I Rodríguez-Perez, J L Labandeira-Garcia, V Broccoli, S Kato, K Kobayashi, José L Lanciego
The field of gene therapy has recently witnessed a number of major conceptual changes. Besides the traditional thinking that comprises the use of viral vectors for the delivery of a given therapeutic gene, a number of original approaches have been recently envisaged, focused on using vectors carrying genes to further modify basal ganglia circuits of interest. It is expected that these approaches will ultimately induce a therapeutic potential being sustained by gene-induced changes in brain circuits. Among others, at present, it is technically feasible to use viral vectors to (1) achieve a controlled release of neurotrophic factors, (2) conduct either a transient or permanent silencing of any given basal ganglia circuit of interest, (3) perform an in vivo cellular reprogramming by promoting the conversion of resident cells into dopaminergic-like neurons, and (4) improving levodopa efficacy over time by targeting aromatic L-amino acid decarboxylase...
January 27, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28130432/azithromycin-in-labor-lowers-clinical-infections-in-mothers-and-newborns-a-double-blind-trial
#16
Claire Oluwalana, Bully Camara, Christian Bottomley, Sean Goodier, Abdoulie Bojang, Beate Kampmann, Samba Ceesay, Umberto D'Alessandro, Anna Roca
BACKGROUND AND OBJECTIVES: We have recently completed a proof-of-concept trial showing that bacterial colonization decreased in women and newborns after the administration of azithromycin during labor. Here, we aim to assess the effect of the intervention on maternal and neonatal clinical infections. METHODS: This was a double-blind, placebo-controlled randomized trial. Gambian women in labor were given either an oral dose of azithromycin (2 g) or placebo. Follow-up was conducted for 8 weeks after delivery...
February 2017: Pediatrics
https://www.readbyqxmd.com/read/28122742/ex-vivo-drug-response-profiling-detects-recurrent-sensitivity-patterns-in-drug-resistant-all
#17
Viktoras Frismantas, Maria Pamela Dobay, Anna Rinaldi, Joelle Tchinda, Samuel H Dunn, Joachim Kunz, Paulina Richter-Pechanska, Blerim Marovca, Orrin Pail, Silvia Jenni, Ernesto Diaz-Flores, Bill H Chang, Timothy J Brown, Robert H Collins, Sebastian Uhrig, Gnana P Balasubramanian, Obul R Bandapalli, Salome Higi, Sabrina Eugster, Pamela Voegeli, Mauro Delorenzi, Gunnar Cario, Mignon L Loh, Martin Schrappe, Martin Stanulla, Andreas E Kulozik, Martina U Muckenthaler, Vaskar Saha, Julie A Irving, Roland Meisel, Thomas Radimerski, Arend Von Stackelberg, Cornelia Eckert, Jeffrey W Tyner, Peter Horvath, Beat C Bornhauser, Jean-Pierre Bourquin
Drug sensitivity and resistance testing on diagnostic leukemia samples should provide important functional information to guide actionable target and biomarker discovery. We provide proof of concept data by profiling 60 drugs on 68 acute lymphoblastic leukemia (ALL) samples mostly from resistant disease in co-cultures on bone marrow stromal cells. Patient-derived xenografts retained the original pattern of mutations found in the matched patient material. Stromal co-culture did not prevent leukemia cell cycle activity, while a specific sensitivity profile to cell cycle related drugs identified samples with higher cell proliferation both in vitro and in vivo as leukemia xenografts...
January 25, 2017: Blood
https://www.readbyqxmd.com/read/28117875/antipruritic-effect-of-pretreatment-with-8-topical-capsaicin-on-histamine-and-cowhage-evoked-itch-in-healthy-volunteers-a-randomized-placebo-blinded-proof-of-concept-trial
#18
H H Andersen, J B Marker, E A Hoeck, J Elberling, L Arendt-Nielsen
BACKGROUND: Chronic itch is difficult to treat and associated with significantly decreased life quality. Topical low-concentration capsaicin (0.006-0.05%) has previously been investigated and applied in therapy of itch but contradictory evidence exits regarding its efficacy. OBJECTIVES: This placebo-controlled, double-blinded study investigated the effect of 8% topical capsaicin applied for 1 and 24 hours on evoked itch, neurogenic inflammation and itch-associated dysesthesia...
January 24, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28111276/recapitulation-of-clinical-individual-susceptibility-to-drug-induced-qt-prolongation-in-healthy-subjects-using-ipsc-derived-cardiomyocytes
#19
Tadahiro Shinozawa, Koki Nakamura, Masanobu Shoji, Maya Morita, Maya Kimura, Hatsue Furukawa, Hiroki Ueda, Masanari Shiramoto, Kyoko Matsuguma, Yoshikazu Kaji, Ippei Ikushima, Makoto Yono, Shyh-Yuh Liou, Hirofumi Nagai, Atsushi Nakanishi, Keiji Yamamoto, Seigo Izumo
To predict drug-induced serious adverse events (SAE) in clinical trials, a model using a panel of cells derived from human induced pluripotent stem cells (hiPSCs) of individuals with different susceptibilities could facilitate major advancements in translational research in terms of safety and pharmaco-economics. However, it is unclear whether hiPSC-derived cells can recapitulate interindividual differences in drug-induced SAE susceptibility in populations not having genetic disorders such as healthy subjects...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28110445/non-invasive-photodynamic-therapy-in-brain-cancer-by-use-of-tb-3-doped-laf3-nanoparticles-in-combination-with-photosensitizer-through-x-ray-irradiation-a-proof-of-concept-study
#20
Min-Hua Chen, Yi-Jhen Jenh, Sheng-Kai Wu, Yo-Shen Chen, Nobutaka Hanagata, Feng-Huei Lin
The use of photodynamic therapy (PDT) in the treatment of brain cancer has produced exciting results in clinical trials over the past decade. PDT is based on the concept that a photosensitizer exposed to a specific light wavelength produces the predominant cytotoxic agent, to destroy tumor cells. However, delivering an efficient light source to the brain tumor site is still a challenge. The light source should be delivered by placing external optical fibers into the brain at the time of surgical debulking of the tumor...
December 2017: Nanoscale Research Letters
keyword
keyword
85926
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"