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CXCR1 in breast cancer
Posted on February 23rd, 2010 No commentsScientists from the University of Michigan and the INSERM (France) identified Cxcr1 gene as differentially expressed in cancer stem cells in comparison with other cancer cells in breast malignancies.
CXCR1 is the receptor for interleukin 8 and has been involved in tumour progression and metastasis in several kinds of cancers, such as prostate, glioma, ovarian and breast cancers. Furthermore, IL8 has been implicated in self renewal of stem cells in vitro. French researchers tested some small molecule inhibitors targeting CXCR1 or some antibody against this receptor in order to evaluate the effect on cellular behavior. These inhibitors directly acted versus cancer stem cells and at the same time indirectly induced cell death in bulk tumour. The promising result was that the whole cancer population was eliminated. A possible explanation for this larger effect could be the release of FAS ligand after inhibiting CXCR1 that determined apoptosis in all cancer cells. In animal model CXCR1 inhibitors reduced tumour mass and blocked metastasis, either alone or in combination with other drugs. Another possible approach to block cancer progression by acting on CXCR1 pathway is to interfere with IL8 production. Scientists from the University of Texas demonstrated that siRNA-IL8 reduced tumour weight in comparison to control in animal models. These studies seem really promising but further proof is necessary to validate CXCR1 pathway as a target for therapeutic intervention. -
Novel function for IHD1 in glioma
Posted on January 6th, 2010 No commentsGenetic mutations are usually identified in cancer. These alterations can cause loss of function, when one mutation interferes with protein functionality, or gain of function when a mutated protein over-works or is over-expressed in a wrong cellular district. In this case, a protein maintains the same function as a normal one. In some cases, mutation can generate novel functions in a protein.
This is the case of IDH1, the isocitrate dehydrogenase 1 that usually converts the isocitrate into alpha- ketoglutarate. When this protein is mutated, an overproduction of 2 hydroxyglutarate (2HG) is abundantly recovered into cells. 2HG is toxic for brain and its presence is correlated with cancer. X-ray diffraction demonstrated that the mutation at arginine 132 results in the formation of a distinct active site, different from those that catalyzes the normal reaction. So, a novel mutation has been identified and a novel function has been recognized. IDH1 could be considered a new target for therapeutic intervention. A selective and specific small molecule inhibitor could interact only with the mutated form, without interfering with the wild type protein and the glucose metabolism. This discover could hopefully help scientists to identify a treatment for glioma.
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