Saturday, March 30, 2013

ESOPHAGEAL CANCER
Whether you consider Adenocarcinoma or squamous cell cancer of the Esophagus, you will have to come to the realization that you are looking at the result of a chronic irritation on Esophageal mucosa.  The irritation in chemical when it comes to Gastric Acid for the Adenocarcinoma of the Gastro-esophageal (G-E) junction, or it could be traumatic as rough  stuffs are swallowed, this include chemicals and alcohols (these days you cannot imagine what people put in their mouth-live scorpions even!)   So chemical and rough stuff induce a squamous cell cancer in the upper Esophagus while Gastric reflux lead to an An Adenocarcinoma.   However you get their the insult will be register at cell level through our membrane receptors which are trans-membrane structures.  In some of these receptors, there is portion facing the cytoplasm called RTK (receptor Tyrosine Kinase) which dimerize on stimulation and/or autophosphorylate, , and   This commotion attracts the Sons of the Sevenless which lights up the RAS by bringing in the Erb2 to attach to he RTK. My sons of the Sevenless gives off a Guanine that activates RAS.    And here we go with Ras and related molecule amplifications.  RAS is known to amplify 3 pathways
1. the MAP Kinase pathways which will go on to stimulate formation of transcription factors that will make proteins structures to deal with the situation, or tell the cell what directions things will go or manage the challenge globally!
2. the RAL/CDC42 pathways that send message to the Cytoskeleton (the nervous system at cell level)
we are talking about stand up and fight Vs flight management.  This system by following the Actininic cytoskeleton through the mambrane and the Reticulum endothelium (RE) reaches in a flash the Nucleus (that's where RE goes )  We are talking in a flash the cell is informed at Histone level and is ready to process the info and react!
3. The PI3K pathways which readies the cellular response which include needed protein response but also include initiating programmed death if that is an appropriate response!  (The FOX (o) is hidden behind the MTOR down this pathway!  FOXO hold the key to survival of the cell!

REMEMBER RAS CAN NOT GO WILD EXCITING THESE PATHWAYS, IT IS TEMPERED BY NF1 WHICH BELONG TO THE FAMILY OF GAP, GIVING A GAP (BREAK) OF FUNCTION TO RAS .  IF THERE IS NO GAP, AND RAS GOES WILD, YOU GOT YOURSELF A NEUROFIBROMATOSIS ON YOUR HAND TO DEAL WITH!  IT IS WORTH NOTING THAT GAP CAN BE DECREASED RELATIVELY TO GEF.  THAT IS TO MUCH GEF IS TRANSLATED AS A DECREASED GAP AS GEF TAKES CONTROL.  SO ONE WAY TO AFFECT RAS IS TO INCREASE GEF (THE BALANCE WILL BE BROKEN TO THE DISADVANTAGE OF GAP) AND RAS WILL BE HYPERSTIMULATED! (TARGET THERAPY)

AFTER THIS VERIFICATION OF THE NOTION THAT THINGS START SIMPLY BUT GET OUT OF HAND QUICKLY IN CELLULAR METABOLISM, LETS GO BACK TO ESOPHAGEAL CANCER AND PATHWAYS STIMULATION.

(WILL CONTINUE)
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