RRx-001, A novel dinitroazetidine radiosensitizer

Summary The ‘holy grail’ in radiation oncology is to improve the outcome of radiation therapy (RT) with a radiosensitizer—a systemic chemical/biochemical agent that additively or synergistically sensitizes tumor cells to radiation in the absence of significant toxicity. Similar to the oxygen effect, in which DNA bases modified by reactive oxygen species prevent repair of the cellular radiation damage, these compounds in general magnify free radical formation, leading to the permanent “fixation” of the resultant chemical change in the DNA structure. The purpose of this review is to present the origin story of the radiosensitizer, RRx-001, which emerged from the aerospace industry. The activity of RRx-001 as a chemosensitizer in multiple tumor types and disease states including malaria, hemorrhagic shock and sickle cell anemia, are the subject of future reviews.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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Abstract Babesia divergens is an intra-erythrocytic parasite that causes malaria-like symptoms in infected people. As the erythrocyte provides the parasite with the infra-structure to grow and multiply, any perturbation to the cell should impact parasite viability. Support for this comes from the multitude of studies that have shown that the sickle trait has in fact been selected for because of the protection in provides against a related Apicomplexan parasite, Plasmodium that causes malaria. In this paper, we examine the impact of both sickle cell anemia and sickle trait RBC environment on different aspects of th...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Funding Opportunity RFA-HL-20-009 from the NIH Guide for Grants and Contracts. This funding opportunity announcement will supportprojectsto enhance the availability and delivery of safe blood to be used for transfusion in patients from low or lower-middle income countries (LLMICs) in Sub-Saharan Africa (SSA). For example, ensuring that children with malaria or sickle cell disease and pregnant women who suffer from obstetric hemorrhage have access to safe transfusion therapies is of high programmatic interest. BLOODSAFE will support projects that develop and test feasible, effective and sustainable strategies to increase t...
Source: NIH Funding Opportunities (Notices, PA, RFA) - Category: Research Source Type: funding
Abstract Plasmodium falciparum is the etiological agent of malaria tropica, the leading cause of death due to a vector-borne infectious disease, claiming 0.5 million lives every year. The single-cell eukaryote undergoes a complex life cycle and is an obligate intracellular parasite of hepatocytes (clinically silent) and erythrocytes (disease causing). An infection can progress to a wide range of pathologies, including severe anemia and cerebral malaria, which can lead to death. P. falciparum repeatedly replicates over the course of 48h inside erythrocytes, resulting in exponential growth and rapid disease progress...
Source: Trends in Parasitology - Category: Parasitology Authors: Tags: Trends Parasitol Source Type: research
CONCLUSIONS: The effect of storage duration on clinically important outcomes has now been investigated in large, high quality RCTs, predominantly in adults. There appears to be no evidence of an effect on mortality that is related to length of storage of transfused RBCs. However, the quality of evidence in neonates and children is low. The current practice in blood banks of using the oldest available RBCs can be continued safely. Additional RCTs are not required, but research using alternative study designs, should focus on particular subgroups (e.g. those requiring multiple RBC units) and on factors affecting RBC quality....
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
Already used in Western countries, hydroxyurea eased painful episodes in African children with the condition. It also reduced the risk of malaria infection.
Source: NYT Health - Category: Consumer Health News Authors: Tags: Children and Childhood Sickle Cell Anemia Malaria Transfusions Africa New England Journal of Medicine Hydroxyurea Source Type: news
Conclusions:The most common treatment for SCD was folate therapy, followed by HU. Many patients receiving HU were formerly or currently enrolled in the clinical trials being run at UCH, which may suggest that it is not commonly prescribed by their regular providers. Most patients had faced at least one complication from SCD, and feel that their biggest deficits in treatment of SCD stem from their inability to get to a clinic or hospital in the event of a complication, and lack of information of the breadth of options that exist for management. More investigation remains to be done about the reasons for decreased usage of H...
Source: Blood - Category: Hematology Authors: Tags: 901. Health Services Research-Non-Malignant Conditions: Poster II Source Type: research
Hydroxyurea is a potent and safe disease-modifying therapy for sickle cell anemia (SCA), with available data proving laboratory and clinical efficacy for both children and adults. Although the global burden of SCA is greatest within sub-Saharan Africa, almost all studies with hydroxyurea to date have been conducted in the US and Europe. Since additional comorbidities may affect children with SCA in low-resource settings, including malnutrition, malaria, and other infections, prospective research is needed to develop locally appropriate guidelines for hydroxyurea use.To assess the feasibility, safety, and benefits of hydrox...
Source: Blood - Category: Hematology Authors: Tags: Plenary Scientific Session Source Type: research
This study evaluated the in vitro effects of heme on the adhesive properties of human neutrophils. Methods: Neutrophils were separated from the peripheral blood of healthy individuals and their adhesion in the presence/absence of heme was compared by static adhesion assays using myeloperoxidase, for quantification of cell adhesion (30 min, 37oC, 5% CO2). Results: Heme (50 µM) significantly increased the adhesion of neutrophils to fibronectin (FN) and to recombinant ICAM-1 (an endothelial ligand), when compared to non-treated neutrophils (43.7±4.6%; 10.9±21.4 %, respectively, n=5, P
Source: Blood - Category: Hematology Authors: Tags: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III Source Type: research
Heterozygosity for Hemoglobin (Hb) S, sickle cell trait (SCT), affects over 40 million people and confers resistance to severe infection by Plasmodium falciparum. Homozygosity for HbS, or compound heterozygosity with certain other alleles of Hb, affects over 4 million individuals and causes sickle cell disease (SCD). Hemolytic anaemia is a prominent feature of SCD and is mainly extravascular, mediated by hepatic and splenic macrophages. No ligands for this process have been identified. As many macrophage phagocytic receptors recognise carbohydrates, we surveyed surface glycan expression by sickle cells using a panel of 8 l...
Source: Blood - Category: Hematology Authors: Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Poster III Source Type: research
Most countries in Sub ‐Saharan Africa (SSA) are either low‐income or low‐middle income countries, that is countries whose gross national income per capita is $995 (USD) or less or $996–3895, respectively. Added to this, they have very few health care professionals specifically trained in transfusion medicine and are the countries whose populations have a high prevalence of transfusion‐transmissible agents (especially HIV, hepatitis B and malaria) and whose patients (women haemorrhaging at birth, men in motor vehicle or motorcycle accidents, children with malaria or sickle cell anaemia) are often in urgent nee...
Source: ISBT Science Series - Category: Hematology Authors: Tags: Congress Review Source Type: research
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