Non-steroidal anti-inflammatory drugs (NSAIDs) have long been used to treat a variety of inflammatory conditions. Many of these conditions, such as cancer or arthritis, require long term use of the NSAIDs due to the chronic nature of the disease. However, the NSAIDs in current use have toxicities associated with their long-term use that hinder their use for these chronic conditions.
Researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) developed an MRI-method that is based on the acquisition of multiple pulsed field gradient (m-PFG) rather than single-pulsed field gradient (s-PFG) MRI sequences. In particular, double PFG (dPFG) MRI sequences offer higher sensitivity and greater robustness, as they are more sensitive to the effects of “restriction;” i.e., to water trapped within the axon’s intracellular space, and thus to the diameter of the axons.
Neurites of the central nervous system can be conceptualized as cylindrical pores with finite lengths and radii. In response to physical trauma, axons may assume a “beaded” morphology which alters their ability to conduct electrical impulses, impairing brain function. These microstructural changes are thought to underlie some of the cognitive defects observed in patients with traumatic brain injury (TBI). Current methods for characterizing traumatic brain injury (TBI) cannot provide microstructural detail on the 3-dimensional shape of axonal segments.
The pattern or latency connectome was hypothesized to change in physiological development and disease. For example, in amyotrophic lateral sclerosis (ALS), large diameter axons are damaged selectively – while in autism, small-diameter axons may be over-expressed. These anatomical changes are expected to alter the latency connectome or pattern of delays of information transmission between different gray matter areas involved in salient brain networks.
Fms-like tyrosine kinase 3 (FLT3) is a cytokine receptor which belongs in the receptor tyrosine kinase class III. FLT3 is expressed on the surface of many hematopoietic progenitor cells and plays an important role in hematopoietic stem/progenitor cell survival and proliferation. It is often overexpressed in acute lymphoblastic leukemia (ALL) and is frequently mutated in acute myeloid leukemia (AML). The standard therapies for ALL and AML are still suboptimal for many patients, especially pediatric. In certain types of ALL or AML, the survival rate is less than 40 and
Heptamethine cyanines are among the most widely used near-IR fluorophores. The near-IR range (between about 650 nm and 900 nm) is very useful for imaging applications due to the absence of background autofluorescence. Despite extensive use, many of these fluorophores suffer from chemical instability. Specifically, most of the current and commonly used fluorophores undergo a phenoxy to thiol exchange reaction in the presence of primary thiols. This exchange reaction is problematic during conjugation reactions of cysteine containing macromolecules.
The proto-oncogene c-Myc is deregulated and overexpressed in ~70% of all cancers. Thus, c-Myc is an attractive therapeutic target since disrupting c-Myc activity could be used as pan-chemotherapy. Beyond cancer, Myc is also a positive effector of tissue inflammation, and its function has been implicated in the pathophysiology of heart failure. Because c-Myc is a transcription factor, a rationally designed small molecule targeting c-Myc would be required to exhibit significant specificity.
The clinical promise of cancer immunotherapy relies on the premise that the immune system can recognize and eliminate tumor cells identified as non-self. The success of cancer immunotherapy is limited by tumor immune evasion, preventing long-lasting tumor control. Recent evidence suggests that certain anticancer therapies can alter the biology of the surviving cell population to restore their sensitivity to T-cell-mediated lysis and help treat patients.
RNA interference (RNAi) is a naturally occurring post-transcriptional gene regulation process that represses the expression of specific genes. Exploiting endogenous RNAi by externally-delivered small-interfering RNA (siRNA) is a promising therapeutic for the treatment of various diseases representing several major unmet medical needs.
Tyrosyl-DNA phosphodiesterase 2 (TDP2) is an enzyme that playings a critical role in repairing nucleic acid lesions, namely by repairing trapped DNA cleavage complexes. TDP2 repairs topoisomerase (TOP2)-mediated DNA damage induced by chemotherapeutic agents and removes endogenous TOP2-DNA cleavage complexes. Further, TDP2 deficiency potentiates the antiproliferative activity of TOP2 inhibitors. This suggest that combination therapies consisting of TDP2 and TOP2 inhibitors have a synergistic effect on tumor tissues.