Friday, February 28, 2014

In our lung study! fascinating MDM-2 Mutation? (AT UTEP WITH DRS ZHANG AND CHOI)

The MDM2 amplification/Mutation was the highest finding and remain persistently present through the various stages of lung cancers making it the strongest predictor of the tested genes.   We are now conducting studies to see its presence in nearby tissues or normal tissues of same patients in order to see if there is a baseline MDM2 amplification to be compared to levels of MDM2 in diseased tissues.   I should also stress that among the tested tissues, some were from treated patients.  Even treatment did not affect Much the MDM2 mutation/amplification expression.  A follow-up study may indicate if this affect long term recurrence.
In the ERA of testing post adjuvant therapy, corollary question will be whether a treatment that affect the MDM2 should be included to improve the cure or whether fixing the MDM2 would be crucial in achieving cure or prolonging progression free survival.   Could some of patients who achieve a cure, still display an MDM2 Mutation? what is the outcome and response rate on cancers with NO MDM-2 mutation.  To what therapy they respond to....and therefore what therapy should be included in MDM-2 positive patients.  Is there a P53 Mutation,    These are relevent questions in this era of target therapy!

and when you think LIKE WIKIPEDIA

" Mdm2 achieves this repression by binding to and blocking the N-terminal trans-activation domain of p53. Mdm2 is a p53 responsive gene—that is, its transcription can be activated by p53. Thus when p53 is stabilized, the transcription of Mdm2 is also induced, resulting in higher Mdm2 protein levels." Mdm2 is capable of auto-polyubiquitination, and in complex with p300, a cooperating E3 ubiquitin ligase, is capable of polyubiquitinating p53. In this manner, Mdm2 and p53 are the members of a negative feedback control loop that keeps the level of p53 low in the absence of p53-stabilizing signals. This loop can be interfered with by kinases and genes like p14arf when p53 activation signals, including DNA damage, are high."

IS THE MDM-2 A TRUE DRIVER MUTATION WHEN IT IS PRESENT GIVEN THE POSSIBILITY OF AUTO-UBUQUITINATION

WE THANK MDHONORS FOR THEIR SUPPORT!
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