To target NF-kB, BCL2
, P53; increase apoptosis; inhibit angiogenesis.
This dysregulation, which is manifested in the excess production of BCL2
protein, is believed to provide certain cancer cells with the ability to resist naturally occurring programmed cell death, a process referred to as apoptosis, which is a primary mechanism for the removal of aged, damaged or unnecessary cells.
Effects of EGCG and L-theanine on TNF-[alpha]-induced BCL2
, BAX and CASP9 gene expression in cultured endothelial cells
Note multiple interphase nuclei with 2 fusions of red and green fluorescent signals (yellow color) and separated red (BCL2
) and/or green (IGH) signal representing cells harboring fusion of IGH and BCL2
NF-kB helps protect the cell from apoptosis by stimulating mitochondrial transmembrane molecules of the BCL2
family, which inhibit apoptosis.
Additionally, pre-clinical data on RGB-286638 in solid tumor cell lines are being presented by GPC Biotech researchers in a poster entitled, "RGB-286638, a multi-targeted protein kinase inhibitor, induces apoptosis involving the inhibition of RNA polymerase II carboxyl-terminal domain phosphorylation and the loss of the anti-apoptotic BCL2
family member Mcl-1" (Abstract #3265).
ProNAi's lead DNAi drug PNT2258 is specifically designed to treat cancers that overexpress BCL2
The typical immunophenotype of LPL demonstrates expression of CD19, CD20, CD22, FMC7, BCL2
, CD38, and CD79a with monotypic surface light chain.
Other positive characteristics include reduction of exosomes, which are particles that inhibit both NK cells and gamma interferon, and increasing BAX gene 500% that kills cancer cells via allowing apoptosis and decreasing BCL2
gene by 200%.
6] Human genes: KLK3, kallikrein-related peptidase 3; AR, androgen receptor; CYP17A1, cytochrome P450, family 17, subfamily A, polypeptide 1; CDKN2A, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4); CDH1, cadherin 1, type 1, E-cadherin (epithelial); CD44, CD44 molecule (Indian blood group); MGMT, O-6-methylguanine-DNA methyltransferase; RASSF1A, Ras association (RalGDS/AF-6) domain family member 1; ABCB1, ATP-binding cassette, sub-family B (MDR/TAP), member 1; APC, adenomatous polyposis coli; GSTP1, glutathione S-transferase pi 1; BCL2
, B-cell CLL/lymphoma 2; PTEN, phosphatase and tensin homolog.
Investigators used immunohistochemistry to score seven protein markers (ER, PR, Her2, EGFR, BCL2
, p27/Kip1, and p53) and fluorescence in situ hybridization to score one genomic marker (MYC/8q24) in tumor cells in tissue sections.
First Patient Dosed in the "Wolverine" Phase II Trial Evaluating ProNAi's BCL2