Renal cell cancer risk is associated to smoking and Obesity (hypertension is a corollary risk we claim). These 2 conditions lead to Hypoxia generally through sleep Apnea which in turn leads to a relative increase of Hemoglobin. The rise of Hemoglobin increases the portion of Desaturated hemoglobin. After many years of such exposure desaturated Heme enhances Phosphorylation at Tyr-530 of the SRC leading to its deactivation. In some individuals with the right MEK, suppression pf the SRC could lead to persistent amplification at the MEK which is a versatile activator of almost all signals, but particularly VEGF receptor. This in turn usually lead to papillary cancers. Amplification of signal transduction started at the MEK (which amplifies almost all major known pathways) will lead to increased ubiquitination and proteasome destruction of the HYPOXIA-inducible factor (following the Von Hippel-Lindau model. This will lead to clear cell cancer. Associated desaturated Heme and hypoxia at the mitochondria will participate in the transformation (and possibly the Atypia/clear cell transformation). The preponderance and center piece role of MEK amplification and subsequent VGEF/PDGF will justify the "bloody" nature of kidney cancers, and vessel involvement in these diseases (MEK is the driver Mutation in papillary cancers). IT ALSO EXPLAINS WHY SUTENT, NEXAVAR WORKS. AND MITOCHONDRIAL DISTURBANCES AND SECONDARY AMPLIFICATION OF AKT, THE MTOR INHIBITORS WORK IN RENAL CANCERS (MTOR participates more in clear cells) (proof of concept pending)
In Western society, obesity is increasing, and so is Sleep Apnea. Also, we live in closed homes (in some regions such as Texas and Louisiana, Mosquitoes are not helping) the level of dust participates in the increased level of allergic Rhinitis/ upper respiratory ailments. It is not unusual to sleep and wake with closed Nostrils. In obese individuals, this compounds the hypoxic episodes and worsened and prolonged hypoxia. And we are back to depression of SRC, activation of MEK---akt, MAPK and so forth.
Keeping your nostrils open at night appears to be a critical strategy in preventing renal cancer, particularly in patients with breathing issues. Lung cancer may be reduced for non smokers, but I wont touch that speculation, but do remember the role of VEGF in non-smoker lung cancers!
The involvement of PDGF which is by the way affected by Sutent seems to open a window in the frequency of strokes and heart attacks at night! That's another debate to have...!
MTOR inhibitor in combination with Anti-VGEF/ MEK could have a significant role in non smoker lung cancer.?
Velcade could have a role in VHL prevention ? and in Pheochromocytoma?
Avastin and Mtor inhibitor could treat Leiomysarcoma of the Uterus if you follow this logic!
A FREED CPRIT AND THE NIH COULD HELP!
Showing posts with label sleep apnea. Show all posts
Showing posts with label sleep apnea. Show all posts
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