Gα12 signaling regulates transcriptional and phenotypic responses that promote glioblastoma tumor invasion.

In silico interrogation of glioblastoma (GBM) in The Cancer Genome Atlas (TCGA) revealed upregulation of GNA12 (Gα12), encoding the alpha subunit of the heterotrimeric G-protein G12, concomitant with overexpression of multiple G-protein coupled receptors (GPCRs) that signal through Gα12. Glioma stem cell lines from patient-derived xenografts also showed elevated levels of Gα12. Knockdown (KD) of Gα12 was carried out in two different human GBM stem cell (GSC) lines.

TWEAK-Fn14-RelB Signaling Cascade Promotes Stem Cell-like Features that Contribute to Post-Chemotherapy Ovarian Cancer Relapse.

Unlabelled: Disease recurrence in high-grade serous ovarian cancer may be due to cancer stem-like cells (CSC) that are resistant to chemotherapy and capable of reestablishing heterogeneous tumors. The alternative NF-κB signaling pathway is implicated in this process; however, the mechanism is unknown. Here we show that TNF-like weak inducer of apoptosis (TWEAK) and its receptor, Fn14, are strong inducers of alternative NF-κB signaling and are enriched in ovarian tumors following chemotherapy treatment.

Characterization of SOX2, OCT4 and NANOG in Ovarian Cancer Tumor-Initiating Cells.

The identification of tumor-initiating cells (TICs) has traditionally relied on surface markers including CD133, CD44, CD117, and the aldehyde dehydrogenase (ALDH) enzyme, which have diverse expression across samples. A more reliable indication of TICs may include the expression of embryonic transcription factors that support long-term self-renewal, multipotency, and quiescence. We hypothesize that SOX2, OCT4, and NANOG will be enriched in ovarian TICs and may indicate TICs with high relapse potential.

CNB-001, a pleiotropic drug is efficacious in embolized agyrencephalic New Zealand white rabbits and ischemic gyrencephalic cynomolgus monkeys.

Ischemic stroke is an acute neurodegenerative disease that is extremely devastating to patients, their families and society. Stroke is inadequately treated even with endovascular procedures and reperfusion therapy. Using an extensive translational screening process, we have developed a pleiotropic cytoprotective agent with the potential to positively impact a large population of brain ischemia patients and revolutionize the process used for the development of new drugs to treat complex brain disorders.

Cytoprotective Drug-Tissue Plasminogen Activator Protease Interaction Assays: Screening of Two Novel Cytoprotective Chromones.

Tissue plasminogen activator (tPA) is currently used in combination with endovascular procedures to enhance recanalization and cerebral reperfusion and is also currently administered as standard-of-care thrombolytic therapy to patients within 3-4.5 h of an ischemic stroke. Since tPA is not neuroprotective or cytoprotective, adjuvant therapy with a neuroprotective or an optimized cytoprotective compound is required to provide the best care to stroke victims to maximally promote clinical recovery.

4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1H-pyrazoyl-3-yl) vinyl)-2-methoxy-phenol) (CNB-001) Does Not Regulate Human Recombinant Protein-Tyrosine Phosphatase1B (PTP1B) Activity .

Protein-Tyrosine Phosphatase1B (PTP1B) is a negative regulator of the insulin signaling pathway and is a potential therapeutic target for treatment of type 2 diabetes, cardiovascular disease, metabolic syndrome and cancer. It has been postulated that CNB-001 [4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1H-pyrazoyl-3-yl) vinyl)-2-methoxy-phenol)] may regulate PTP1B activity suggested by a computer-based active site docking recognition model. This possibility was studied using a human recombinant PTP1B assay, and a phospho-peptide fragment of the insulin receptor β subunit domain (IR5).