Novel Biased Potent Opioid-Like Agonists as Improved Medications to Treat Chronic and Acute Pain

There are no analgesics to ameliorate chronic pain without adverse side-effects (e.g., respiratory depression, gastrointestinal effects, tolerance, dependence), thus forcing patients into a difficult choice of negative impacts on quality of life. Most of the analgesics used for chronic and acute pain are drugs such as oxycodone, morphine, oxymorphone, and codeine. All of these opioids have been subject to misuse; prescription drug abuse is a severe problem worldwide, causing high mortality and greatly increased emergency room visits.

Method for Targeted Therapeutic Delivery of Proteins into Cells

Current methods to deliver proteins into cells (e.g., using retrovirus, DNA transfection, protein transduction, microinjection, complexing the protein with lipids, etc.) have many shortcomings, such as lack of target specificity toxicity, or unwanted random integration into the host chromosome.  Protein transduction is an emerging technology for delivering proteins into cells by exploiting the ability of certain proteins to penetrate the cell membrane.  However, the majority of the proteins delivered by this means are usually trapped and subsequently degraded in the endosomes-lyso

Autophagy Modulators For Use in Treating Cancer

Cancer cells can upregulate autophagy – cell destruction – as a response to chemotherapy. Investigators in Dr. Melvin DePamphilis’ laboratory at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) have shown that compounds identified by screening a library of compounds blocks autophagy in some cancer cells (e.g., melanoma) but are not toxic to normal cells. Cancer cells with mutations in the BRAF oncogene are especially dependent on autophagy. Treatment of cancer cells with the BRAF mutation can increase the efficacy of chemotherapy.

Gene Signature for Predicting Solid Tumors Patient Prognosis

HCC is the most frequent malignant tumor in the liver and the third leading cause of cancer death worldwide.  A progressive sequence of somatic mutations and epigenetic changes of oncogenes or tumor suppressor genes are believed to cause tumor development. However, high genomic instability in tumors causes the accumulation of genomic aberrations that do not contribute to tumor progression. Therefore, it is important to distinguish between ''driver'' mutations that are functionally important and ''passenger'' mutations that do not provide a selective advantage to the tumor cells.

Methods of Producing T-cell Populations Using P38 MAPK Inhibitors

Adoptive cell therapy (ACT) uses cancer reactive T-cells to effectively treat patients. However, several obstacles inhibit the successful use of ACT for cancer treatment.  Current approaches for the expansion of T-cells may produce T-cells with a terminally differentiated phenotype that is associated with diminished anti-tumor activity and poor capacity for long-term persistence. Studies have shown that improving metabolic properties and persistence of T-cells during ex vivo expansion could improve anti-tumor efficacy of T-cells.

Assays for Measuring and Quantifying DNA Damage

Exposure to ionizing radiation or agents that induce DNA double-stranded breaks (DSBs), which is one of the most damaging types of lesions in DNA, can result in damage to cells and/or tissues.  Thiscan lead to illness (i.e., Acute Radiation Syndrome, Cancer) or death.  Identifying the amount of exposure to a DNA DSB-causing agent can be useful in determining the need for further testing, avoidance or modification of certain medical procedures, and/or types of medical treatments.

Inhibition of T Cell Differentiation and Senescence by Overexpression of Transcription Factor c-Myb

Adoptive Cell Therapy (ACT) is a promising technique that uses a patient's own T cells to treat cancer. The process requires removing and engineering a patient's T cells to express a chimeric antigen receptor (CAR) or T cell receptor (TCR) that targets a specific cancer antigen. When the modified T cells are reintroduced into the patient, the T cells attack and kill cancer cells that express the antigen, thereby treating the patient.

Novel Fixative for Improved Biomolecule Quality from Paraffin-Embedded Tissue

Tissues samples collected during medical procedures, such as biopsies, are used to diagnose a wide variety of diseases. Before diagnosis, patient samples are typically processed by fixation and paraffin embedding. This fixation/embedding process is used to preserve tissue morphology and histology for subsequent evaluation. Unfortunately, most fixative agents can damage or destroy nucleic acids (RNA and DNA) and damage proteins during the fixation process, thereby potentially impairing diagnostic assessment of tissue.

In vitro Generation of an Autologous Thymic Organoid from Human Pluripotent Stem Cells

The thymus is an integral part of the adaptive immune system as it generates T cells. Its function diminishes rapidly as the body ages, leading to a compromise of the immune system in the elderly. Reconstitution of adaptive immunity through mass production of different T cell types is therefore a therapeutic need in immunocompromised populations. Furthermore, production of T cells with specific receptors targeting cancer cells is an important cancer immunotherapy approach.

A peptide hydrogel for use in vascular anastomosis

In collaboration with surgery specialists from Johns Hopkins University, researchers at the National Cancer Institute (NCI) developed novel hydrogel compositions and methods of using them in the microsurgical suturing of blood vessels, which is particularly beneficial for surgeons in whole tissue transplant procedures. The lead candidate electropositive hydrogels, called APC1, was demonstrated in anastomosis mice models to be well tolerated, biocompatible, and non-toxic.