Showing posts with label MEK. Show all posts
Showing posts with label MEK. Show all posts

Friday, September 20, 2013

Profiling through at the CRBCM!

At the CRBCM something is coming through:

1. Deterioration at membrane receptor by lack of stimulation or "false or abnormal stimulation" could not only alter the nature of the "glycan" covering the protein portion of the receptor, but also induce stress like molecules.(HSP)
2. As a result of receptor failure new cytokines and TGFs are secreted which unfortunately fail at the initial receptor, but induce other receptors, amplifying standard pathways like RAS or PIK
3. Certains TGFs have an intrinsic power to maintain life of cells no matter what and induce metastasis.
4. Certain genes have an auto-phosphorylation or self-limiting mechanism that can easily go wrong  (RAS, FAK) driving to neoplastic process
5. FAK plays a larger role in aggressive prostate cancer than it has been recognized!
6. FAK has a closer relation to Androgen than recognized
7. NOTCH has closer relation with MEK and "stem cell potential" than recognized.
8. FAK disturbance prominence in cancer explains its sensitivity to Taxanes!  That is on top of Microtubule disturbances induced by the drug!
9. Metalloproteases are the ultimate Biomarkers of membrane events !
10.  Epigenetic methylation and its patterns are one of the largest mystery still to be elucidated!

Tuesday, March 19, 2013

Ovarian Cancer

*Researchers who conducted the study who conducted the use of Selumetinib in low grade serous Ovarian cancer were still puzzled because its activity did not follow presence of KRAS or BRAF. They have been wondering if it used another pathway.  But remember MEK is the revolving door to de-differentiation and to the reversal of mesengialization and as such increase tor susceptibility not only to chemotherapy drugs, but also to the secondary angiogenic potentiation of MEK.  That is, with anti-MEK, there is a down regulation of MAPK (as suggested) and therefore  the C-JUN and TGF and cyclins, but also down regulation of the VEGF!

They say " Our results suggest that selumetinib is an active agent, but not necessarily because of BRAF or KRAS mutational activation per se,” the authors concluded.
In an interview, Gershenson said that one reason for the lack of correlation could be biomarker instability. Among the 52 patients, specimens were available for only 40, mutational analysis was done in 34, and in 28 of those the tissue was from the primary therapy and not from the recurrent tumor. “The question arises, are these biomarkers stable over time or do they change, so that what you find in the primary tumor may not be what you find in the recurrent tumor,” he said."   They suggesting here that the lack of correlation could be due to a changing nature of Biomarker.  But the existence of other factors and pathways could not be be excluded!

Gene-Expression Profiling May Help Select Best Drugs for Pancreatic Cancer

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Caroline Helwick 
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In this study patient with pancreatic cancer had reportedly circulating cell and their genes could predict response to therapy but unfortunately they did not spell out which genes were reviewed.  We will investigate further this article...

Tuesday, February 5, 2013

NOMENCLATURE OF GENES AND PATHWAYS INVOLVED IN BUTEIN INHIBITIONS: IKK and Sirtuin

IKK:
The subunit to be inhibited for the activation of the Nuclear factor and pathway NF-kB which has versatile transforming capacity to combat, escape and resist various attackers including infection and chemotherapy.  Inhibition here reduces the cell capacity to adapt.  It appears that the Transcription factor NFkB is sitting there in the Cytosol totally inactive, touch the IKK through phosphorylation, wakes the NFkB which spring into motion and unleashes its power.  One of the best described pathway flow is TNF posphorylation of IKK which detaches and goes on to  being ubiquitinated and degraded through the Proteasome.  detachment of the IKK lead to a free NFkB kinase which enter the nucleus to unleash all kinds of genes of defense.  DO REMEMBER that upstream NFkB go through MEK (also involved in Angiogenesis) to reach MAP3K and you can see how through networking of these pathways the phenomena gets global.

Sirtuin:
This compound is SIRT1, it is  activated by BUTEIN
Butein actually activate SIRT1 and may induce aging in the cell.  Remember Butein by activating Sirtuin will have a role in Diabetes, Gout, Alzheimer dementia, and Amyloid related disease.  Butein, a versatile anti-inflammatory drug with effect on NAD (Nicotinamid), and may be a Histone De-acetylase inhibitor. This stuff has potential!