Proviral Integration for the Moloney murine leukemia virus (PIM) kinases are overexpressed in many solid cancers – including prostate, breast, colon, endometrial, gastric and pancreatic. High of PIM1 expression is predictive of poor survival in multiple cancer types. While several selective pan-PIM inhibitors were developed and tested in clinical trials, all ultimately increased PIM1-3 protein levels and developed intrinsic resistance.
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.
The high mortality rate from ovarian cancers can be attributed to late-stage diagnosis and lack of effective treatment. Despite enormous effort to develop better targeted therapies, platinum-based chemotherapy still remains the standard of care for ovarian cancer patients, and resistance occurs at a high rate. One of the rate limiting factors for translation of new drug discoveries into clinical treatments has been the lack of suitable preclinical cancer models with high predictive value.
The National Cancer Institute's Molecular Targets Development Program is seeking parties interested in collaborative research to further develop, evaluate, or commercialize cancer inhibitors isolated from the African plant Phyllanthus englerii. The technology is also available for exclusive or non-exclusive licensing.
Crimean-Congo hemorrhagic fever (CCHF) is a deadly hemorrhagic fever having a high mortality rate. The disease results from infection of an individual by Crimean-Congo hemorrhagic fever virus (CCHFV), which is a tick-borne bunyavirus endemic in Southern and Eastern Europe, Africa, the Middle East, and Asia. Geographically, case distribution is consistent with the range of Hyalomma genus ticks, the main reservoir of CCHFV, and is likely to expand due to climate change. Humans may be infected from tick bites, through contact with infected animals or animal tissue.
Programed Death-Ligand 1 (PD-L1, also known as B7-H1 or CD274) is a cell surface protein that binds to Programmed Cell Death Protein 1 (PD-1, also known as CD279). An imbalance in PD-1/PD-L1 activity contributes to cancer immune escape. PD-1 is expressed on the surface of antigen-stimulated T cells. The interaction between PD-L1 and PD-1 negatively regulates T cell-mediated immune responses. It has been suggested that disrupting the PD-L1/PD-1 signaling pathway can be used to treat cancers. The aberrant expression of PD-L1 on multiple tumor types supports this suggestion.
Protein translation is a central cellular function attracting increasing attention from cell biologists as they integrate gene product specific information into a systems view of cellular function. Scientists at NIAID developed the puromycin-specific antibodies that allow for the specific detection of puromycin-containing nascent polypeptides via standard immunofluorescence or flow cytometry.
Spatial proteomics and transcriptomics are fast-emerging fields with the potential to revolutionize various branches of biology. In the last five years, various multiplex immunofluorescence and immunohistochemistry imaging methods have been developed to stain 5-60 different protein markers in a given tissue. Nonetheless, most of these techniques are iterative and can image a maximum of 3-8 markers in a single cycle, resulting in processing time of several hours to days.
This technology includes a novel method to train deep learning convolution neural network model to improve the signal-noise-ratio for the magnetic resonance (MR) imaging. The novelty lies on the fact that actual MR imaging physics information is used in the deep learning training. The resulting model achieves significant signal-to-noise ratio (SNR) improved for different acceleration factors in MR imaging. The resulting model can be used for many body anatomies (e.g., brain, heart, liver, spine, etc.) to significantly improve the SNR.
Disorders of adult beta-globin synthesis, which include sickle cell disease (SCD) and beta-thalassemia, are the most common monogenic disorders in the world. While the curative potential of bone marrow transplantation has been demonstrated, this approach is limited to a small fraction of affected patients due to the requirement for an HLA-matched donor, the highly specialized approach that requires critical infrastructure, and the high cost.