Rock Creek Pharmaceuticals Inc. (fka RCPIQ)

[Buddhahead]

NFLAMMATION, CANCER AND CANCER STEM CELLS in Entre Mediterraneen de Medecine Moleculaire, Jean Francois Peyron-Team Leader, 2013

Excerpt:
"Team4 “Inflammation, Cancer, Cancer Stem Cells“ (Head : Jean-Francois Peyron) is studying intracellular signaling pathways that transmit activation, proliferation and survival signals during inflammation and tumorigenesis. This fundamental and pre-clinical research, backed by the use of pertinent murine models, aims at the discovery of future therapeutical targets.
Our research is following two axis :
1- the molecular dissection of the role of the NF-kappaB transcription factor during the different steps of tumorigenesis.
2- The study of the self-renewal capacity of cancer stem cells.

NF-kB in carcinogenesis :
Oncogenic abnormal NF-kB activation is important for cancer initiation and progression by inducing genes that support proliferation, resistance to apoptosis and treatments, metastasis. We previously showed that pharmacological inhibition of NF-kB decrease the survival of numerous types of cancer cells and potentiates the apoptotic effect of chemotherapeutic drugs.
Our goal is to determine at a molecular level, the contribution of NF-kB to the transforming activity of the Bcr-abl oncogene in Chronic Myeloid Leukemia (CML). We previously showed that NF-kB inhibition in vitro induced apoptosis of leukemic cells and bypass imatinib resistance to to the T315I mutation of Bcr-abl. Besides, we are searching for the molecular intermediates between Bcr-abl and NF-kB, in order to identify new potential therapeutical targets.
We are studying in vivo the contribution of NF-kB to tumorigenesis in a murine model of PTEN invalidation in T cells (cre-lox) that leads to a T lymphoma. Using a transcriptomic approach, we are searching for NF-kB target genes that participates to transformation and will characterize their mode of action.

NF-kB is involved in tumor resistance to treatments. We have isolated a CPT11 topoisomerase inhibitor-resistant variant of the HT29 colon cancer cell line that displays abnormal constitutive NF-kB activation. We are searching the NF-kB target genes that mediate this resistance.
NF-kB is a molecular link between chronic inflammation and transformation. We are characterizing the biological and molecular components from the Saccharomyces boulardii (Sb) probiotic that could be responsible for the anti-inflammatory and protective effects of Sb because of their inhibition of intracellular signaling pathway including NF-kB during enterohemorrhagic E Coli infection. The participation of alterations in the integrity of the intestinal epithelial barrier is studied during irritable bowel syndrome.

Article at:
http://www.unice.fr/c3m/EN/Equipe4.html