A5019594240- Cancer-related gene regulation
- Genital Health and Disease
- Acute Myeloid Leukemia Research
- RNA Interference and Gene Delivery
- Carbohydrate Chemistry and Synthesis
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Urological Disorders and Treatments
- Epigenetics and DNA Methylation
- Ethics and Legal Issues in Pediatric Healthcare
- Nuclear Receptors and Signaling
- Urologic and reproductive health conditions
- Bone Metabolism and Diseases
- Retinoids in leukemia and cellular processes
- Bone and Joint Diseases
- Hematopoietic Stem Cell Transplantation
- Female Genital Mutilation/Cutting Issues
- Genetics and Neurodevelopmental Disorders
- Histone Deacetylase Inhibitors Research
- T-cell and B-cell Immunology
- Mesenchymal stem cell research
- Science, Research, and Medicine
- Neonatal Respiratory Health Research
- Phytochemistry and Bioactivity Studies
- Adenosine and Purinergic Signaling
Louis Stokes Cleveland VA Medical Center
2018-2020
Case Western Reserve University
2014-2019
The University of Sydney
2019
Warrington Hospital
2018
University School
2016
Io Therapeutics (United States)
2016
Case Comprehensive Cancer Center
2014
Ineos (United Kingdom)
2002
Natural killer cells harnessed from healthy individuals can be expanded ex vivo using various platforms to produce large doses for adoptive transfer into cancer patients. During such expansion, NK are increasingly activated and more efficient at killing cells. Adoptive however introduces these a highly immunosuppressive tumor microenvironment mediated in part by excessive transforming growth factor beta (TGF-beta) both their surrounding stroma. This ultimately limits the clinical efficacy of...
Abstract Natural killer cells from acute myeloid leukaemia patients (AML-NK) show a dramatic impairment in cytotoxic activity. The exact reasons for this dysfunction are not fully understood. Here we that the glycogen synthase kinase beta (GSK3β) expression is elevated AML-NK cells. Interestingly, GSK3 overexpression normal NK impairs their ability to kill AML cells, while genetic or pharmacological inactivation enhances Mechanistic studies reveal increased activity correlates with an...
Abstract NK cell adoptive therapy is a promising cancer therapeutic approach, but there are significant challenges that limiting its feasibility and clinical efficacy. One difficulty the paucity of grade manufacturing platforms to support large scale expansion highly active cells. We created an feeder line termed ‘NKF’ through overexpressing membrane bound IL-21 capable inducing robust sustained proliferation (>10,000-fold at 5 weeks) cytotoxic The expanded cells exhibit increased...
Abstract More than half of T-cell acute lymphoblastic leukemia (T-ALL) patients harbor gain-of-function mutations in the intracellular domain Notch1. Diffuse infiltration bone marrow commonly occurs T-ALL and relapsed B-cell patients, is associated with worse prognosis. However, mechanism outgrowth resulting biologic impact on hematopoiesis are poorly understood. Here, we investigated targetable cellular molecular abnormalities stroma responsible for suppression normal using a mouse model...
1,25-dihydroxyvitamin D3 (1,25D), the biologically active form of vitamin D, is widely considered a promising therapy for acute myeloid leukemia (AML) based on its ability to drive differentiation leukemic cells. However, clinical trials have been disappointing in part dose-limiting hypercalcemia. Here we show how inhibiting glycogen synthase kinase 3 (GSK3) can improve response AML cells 1,25D-mediated differentiation. GSK3 inhibition enhanced differentiating effects low concentrations...
Standard therapies used for the treatment of acute myeloid leukemia (AML) are cytotoxic agents that target rapidly proliferating cells. Unfortunately, this therapeutic approach has limited efficacy and significant toxicity majority AML patients still die their disease. In contrast to poor prognosis most patients, individuals with a rare subtype AML, promyelocytic leukemia, can be cured by differentiation therapy using regimens containing all-trans retinoic acid. GSK3 been previously...
Abstract Inactivation of the p53 tumor suppressor by mutation or overexpression negative regulators occurs frequently in cancer. As plays a key role regulating proliferation apoptosis response to DNA-damaging chemotherapies, strategies aimed at reactivating are increasingly being sought. Strategies reactivate wild-type include use small molecules capable releasing from key, cellular regulators, such as Hdm2 and HdmX. Derivatives antagonist Nutlin-3 clinical trials. However, specifically...
Meatal stenosis: getting the diagnosis right Brian J Morris,1,2 Stephen Moreton,3 John N Krieger4 1School of Medical Sciences, University Sydney, NSW, Australia; 2Bosch Institute, 3CircFacts.org, Warrington, UK; 4Department Urology, Washington School Medicine, Seattle, WA, USA
<h3>Key Messages</h3> Population-based studies in high-income countries have generally failed to find protection of male circumcision (MC) against sexually transmitted infections (STIs). This stems from the overrepresentation men who sex with (MSM) national STI statistics, inability MC protect STIs during receptive anal intercourse. Studies settings where is performed early life showed lower prevalence circumcised men. However, a Danish database study reported an association increased risk...
Silica gel impregnated with iron(III) salts functions as a humidity indicator, turning from deep amber color when dry, to nearly colorless humidified. The mechanism is proposed being the result of formation species Fe-OH-Si bridges. These are thought be highly colored dry buy dissociate into pale monomeric exposed moisture.
We critically evaluate an online “Global survey of circumcision harm” that gauged beliefs men who thought their neonatal had harmed them. Sequential evaluation the data and claims reveal numerous serious flaws are at odds with strong scientific evidence. Moreover, one-sided study design “loaded” title meant findings were not representative general population circumcised males. None participants’ claimed physical problems confirmed by a health practitioner. Belief in this seriously flawed has...
Medical male circumcision has been adopted by the WHO, and other professional public health medical bodies, as a vital weapon in fight against HIV. This prompted large body of research into acceptability procedure, attitudes to it, barriers it. A systematic review these studies found that satisfaction with is strongly associated having accurate knowledge about survey-based paper Earp, Sardi Jellison entitled “False beliefs predict increased sample US American men” only one find opposite. It...
Abstract Acute myeloid leukemia (AML) is characterized by a differentiation block in progenitors resulting aberrant proliferation of immature cells. Therapeutics that induce leukemic cells would overcome the high toxicity and low potency conventional chemotherapy. Securinine, plant-derived alkaloid from Securinega suffruticosa, has been shown to be promising AML agent through an unclear mechanism, but limited its (~20μM) toxicity. We performed lead optimization chemistry on securinine led...