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.
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.
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.
Diazeniumdiolates comprise a diverse class of NO-releasing compounds and materials that are known to exhibit sufficient stability to be useful as therapeutics.
Hypoxia is a characteristic of many solid tumors resulting from accelerated cellular proliferation and inadequate vascularization. HIF-1 is a transcription factor critical for maintaining cellular homeostasis in, and adaptively responding to, low oxygen environments. HIF-1 becomes activated through binding to the transcriptional co-activator protein p300. Disruption of the HIF-1/p300 interaction could potentially modulate HIF-1 activity.
Melanoma is a particularly aggressive form of cancer primarily caused by over-exposure to sunlight. Although melanoma can strike at any age, the malignancy disproportionately impacts persons of advanced age, as these individuals often have decades of repeated exposure to harmful levels of ultraviolet radiation. Scientists at NIH among others have clarified the link between advanced melanoma and other malignancies and expression of SPANX-B.
One problem with the development of immunotherapy for cancer or other diseases is the inability to stimulate a sufficient immune response in patients to tumor associated antigens. The Linker Adapted for T Cell Signaling molecule (LAT) has been shown to be an important molecule in T cell signaling. The inventions described and claimed in this patent application illustrate a new supportive role for LAT which may be harnessed to improve a patient's immune response to tumor-associated antigens.
Tissue obtained for both clinical and research purposes is routinely frozen, commonly in Optimal Cutting Temperature (OCT), an embedding media, for eventual downstream analysis, commonly including sectioning on a cryostat. Though OCT is the standard compound used for freezing, there is no standard freezing protocol. Thus, current methods of handling, labeling, and storing OCT-embedded tissue vary widely, and specimens are often damaged or degraded due to undesirable temperature fluctuations during handling and freezing.
Microduplications of the GPR101 gene (located on chromosome Xq26.3 and encodes a G-protein coupled receptor) can result in an excess of growth hormone causing gigantism, that has an onset in early childhood. It is also associated with the growth of sporadic growth hormone producing adenomas in some patients with acromegaly.
This technology consists of highly specific rabbit monoclonal antibodies reactive with phosphorylated tyrosine located at amino acid 1235 in the human MET sequence. Binding to this pYl235 residue is independent of the phosphorylation of other tyrosines in the vicinity (1230 and 1234), does not cross-react with these nearby phosphotyrosine residues, and does not occur when Y1235 is unphosphorylated.