Researchers at the University of California, Davis have developed a unique peptide that induces cell differentiation by inhibiting cellular protein CHD4, a promising approach to target dedifferentiated cancer cells and for cell therapy.

Researchers at the University of California, Davis have identified a short peptide which rapidly promotes protein degradation in cancerous enzymes and induces cell differentiation to kill lymphomas.

Researchers at the University of California, Davis have developed a virally derived homolog to increase the inflammatory response desirable in cancer immunotherapy.

Researchers at the University of California, Davis have developed a viral peptide therapeutic that targets MYC-based cancerous tumors.

Researchers at UC Irvine have identified and tested a molecular target that regulates T cell function during chronic viral infection and cancer. The molecular target is one of the high mobility group proteins (HMGB2). HMGB2 is a DNA binding protein that regulates transcriptional processes, meaning that its modulation will have profound effects on T cell differentiation and ultimate function by altering the expression of many genes.

Lipoxygenases catalyze the peroxidation of fatty acids which contain bisallylic hydrogens between two cis double bonds, such as in linoleic acid (LA) and arachidonic acid (AA). Lipoxygenases are named according to their product specificity with AA as the substrate because AA is the precursor of many active lipid metabolites that are involved in a number of significant disease states. The human genome contains six functional human lipoxygenases (LOX) genes (ALOX5, ALOX12, ALOX12B, ALOX15, ALOX15B, eLOX3) encoding for six different human LOX isoforms (h5-LOX, h12S-LOX, h12R-LOX, h15-LOX-1, h15-LOX-2, eLOX3, respectively). The biological role in health and disease for each LOX isozyme varies dramatically, ranging from asthma to diabetes or stroke. The nomenclature of the LOX isozymes is loosely based on the carbon position (e.g., 5, 12, or 15) at which they oxidize arachidonic acid to form the corresponding hydroperoxyeicosatetraenoic acid (HpETE), which is reduced to the hydroxyeicosatetraenoic acid (HETE) by intracellular glutathione peroxidases. Lipoxygenase inhibitors are difficult to formulate due to challenges with solubility and other factors, therefore new formulations are needed.

Lipoxygenases form a large family of enzymes capable of oxidizing arachidonic acid and related polyunsaturated fatty acids. One such lipoxygenase, 12/15 LOX can oxidize both the C-12 and C-15 of arachidonic acid, forming 12- or 15-hydroperosyarachidonic acid (12- or 15-HPETE). Lipoxygenases and their metabolites have been implicated in many diseases. In particular 12/15-LOX (also known as 15-LOX-1, 15-LOX, or 15-LO-1 in humans and L-12-LoX, leukocyte-type 12-LO, or L-12-LO in mice) plays a role in atherogenesis, diabetes, Alzheimer's, newborn periventricular leukomalacia, breast cancer, and stroke. Whatever the name, the protein is encoded by the gene ALOX15 in both mice and humans. Lox inhibitors are difficult to develop due to the mouse and human homologs having different substrate and inhibitor specificities - 12/15 LOX produces predominantly 15-HETE in humans and 12-HETE in mice. So existing inhibitors are not selective for 12/15 LOX with regard to other LOX isoforms. In addition, many are strong antioxidants and therefore may result in off-target effects. 

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Chimeric antigen receptor (CAR) T cells have so far shown limited efficacy on brain and solid tumors. UCSF investigators have developed a method of manufacturing recombinant immune cells by pre-treating them with a combination of small molecules to increase the number of CAR T cells in the tumor microenvironment and improve the survival of animal models bearing glioma in the brain relative to CAR T cells that have not received the pre-treatment. These results may be applicable to other solid tumors.

Researchers at UC Irvine have developed methods to facilitate the delivery of a high dose, low energy electron beam or X-ray in a compact manner.

Researchers at UC Irvine have used a computationally powered method to identify small molecule drug leads that exhibited anti-cancer activity in a human-cell-based assay. These small molecules and the approach used to find them will accelerate the research and development of anti-cancer therapeutics.

Marine sponges and microorganisms are the source of many promising bioactive products for use in the treatment of cancer. Multicompound libraries can be readily generated from these sources for comprehensive bioactivity and biosynthetic investigations. Prior studies into these organisms/communities involved examination of Zyzzya sponge metabolites and corresponding bacterial communities from this genus. One particularly potent compound was a makaluvamine extracted from a Zyzzya fulginosa sponge from Papua New Guinea was highly active on PANC-1 cells.  Additional studies show that the key structure of malakuvamine and other related compounds is a pyrrolo[4,3,2-de]quinoline motif now seen in 100 similar natural products. 

Researchers at the University of California, Davis have developed a self-assembling, fibrous photosensitizer that targets mitochondria in tumor cells for destruction via photodynamic therapy with enhanced localization and potency.

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Researchers at the University of California, Riverside (UCR) in collaboration Nationwide Children’s Hospital  have developed and characterized small peptidomimetics that act as EphA4 agonists. Given ALS is a heterogeneous disease, astrocytes reprogrammed from the fibroblasts of patients with sporadic and SOD1-linked ALS (iAstrocytes) were cultured with MNs and the UCR/Nationwide EphA4 agonists.  As seen in Fig. 1, these small agonistic peptidomimetics decrease MN death in iAstrocytes derived from sporadic ALS (sALS) cells.     

Researchers at UC Irvine have developed a novel, machine learning-assisted biochip for rapid, affordable, and practical analysis of single cell tumor heterogeneity. The technology’s low cost and ease of manufacture makes it an optimal point-of-care diagnostic in developing countries, where early cancer detection is severely lacking.

Researchers at the University of California, Davis have developed a new method for enhancing immunotherapy for solid cancer tumors by targeting multiple cancer cell elimination mechanisms simultaneously.

Positron emission tomography (PET) scanners map the metabolic or biochemical function of tissues by detecting the gamma radiation released by the decay of radioactive tracers ingested by a patient. This technology is particularly useful for mapping tumors because one can devise tracers which tumor cells uptake preferentially. Current gamma radiation detectors are expensive and inefficient, requiring large integration times and radionuclide doses for meaningful image quality. Additionally, the spatial resolution of the resulting map is limited by detector latency, which for traditional technology is 200-500 picoseconds.To address these problems, researchers at UC Berkeley have developed a novel gamma radiation detector with much greater time resolution (potentially down to 10 picoseconds), and higher efficiency (nearly all gamma rays successfully detected). Additionally, these detectors use well-established nanotechnology manufacturing methods and can be produced an order of magnitude more cheaply than existing detectors. The high efficiency of these detectors allows amounts of radioactive tracer used to be decreased by an order of magnitude and spatial resolution to be increased by an order of magnitude when compared to traditional methods.

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This invention consists of novel small molecule compounds that bind to mutant variants of p53 and induce conformational changes to restore p53 function for treatment of human cancers.