More on the Glucose/Cancer Hypothesis

Dr. Hugh Tildesley

Status Update: Status quo, weight, appetite, blood count stable. Still await this week’s tumour marker. Another infusion of the poisons on Monday, it is frightening that I am getting used to this.

A positive meeting with Dr. Renouf, for the first time he told me not to worry about the tumour marker unless there is a large a quick upward trend. This is helpful information and reflects how long I have been on the treatment. Early on I am sure he was worried he would see a steady if not quick rise. This not being the case, I think the marker is a reflection of tumour activity and tumour mass. A downward trend is therefore where we want to go.

Skip this part if you are intimidated by bio-talk.

He also has discussed the glucose hypothesis regarding glucose levels and tumour growth. Interestingly a recent paper in Science( December 11, 2015) in part summarizes the theory we are writing up, and  importantly links the KRAS mutation (which most pancreatic patients have), with activation of the GLUT 1 transporter which facilitates glucose uptake, the hooker being that the usual on/off mechanisms are not operational therefore to “starve” the cell requires inhibiting the intracellular use of glucose. I previously have mentioned 3-Bromopyruvate as 1 agent; further research suggests some technical issues getting the compound to the tumour. (Please see post # 20 “Is Science 100 years old Important?”)

The paper focuses on how oxidized Vitamin C is transported into the cell, via GLUT 1, intracellularly it is reduced to Vitamin C, which is toxic and leads to metabolic disruption and ultimately cell death. Bottom line is that we are now discussing metabolic inhibitors rather than cellular poisons. The study in the journal Science was in mice, but provides a mechanism of action. Phase 1 and 2 studies are now underway (early clinical studies in humans)

Those in my age group will remember Linus Pauling and his claims late in his career about Vitamin C and it’s cancer-healing effects. The studies were done with oral vitamin C; this was before the recognition of cancer markers such as KRAS. It will likely turn out his intuition was right but Vit C must be high and thus delivered IV.

Here is our working hypothesis:

Pancreatic Cancer------KRAS Mutations

                                                 

                                                 

                                                 

                                    Glut 1……….up regulated

                                    

                                    Increased Glucose uptake

                                   

                                   

                                    Accelerated Tumour growth

Vitamin C Effect          KRAS Mutations

   In Cancer                                            

                                                                                             

Vitamin C is

Oxidized to DHA

(Dehydroascorbate)   Glut 1……….up regulated…..

                                                

Glut 1-DHA (DHA competes with glucose and is transported intracellularly

                                      

In the cell:

  DHA.............Vitamin C

                                                

Increased intracellular Vitamin C levels

          

Metabolic disruption

(Inhibition of glycolysis)

          

Loss of pyruvate production

        

    Cell Death

This is exciting news as intuitively infusions of Vitamin C are much more palatable than selective infusions of bromopyruvate through the arterial feeders of a tumour.

Tesla Titillations: No real cold or snowy weather, so I await to see how the car operates in true winter conditions. For now no new surprises.

One of my patients took delivery of a model S 95. A great celebration of their 35^th anniversary.

 

 

The Arts Report: 

Henry Kaplan and the Story of Hodgkin's Disease

Written by a renowned Stanford oncologist, Charlotte Jacobs, it is a story beautifully told, with personal successes of the man, his role in making Stanford Medical School world renowned, ultimate jealousy and betrayal by peers. His focus and dedication to his profession, developing Stanford, and his innate ability to solve complex medical problems is truly inspirational. It also showed little known facts about his humanitarian efforts and tireless work with Amnesty International.

Three books on the shelf ready to be devoured and of course the Christmas film season looks very rich, an expanded report next time.

Christmas Aberrations: Over the years I have reassured my kids that there is no such thing as a functional family, we are all dysfunctional at some levels, and in my ultra sensitive way reassured them to “ get over it”, the corollary was also that it would all come out in their therapy in their 40’s.

The artificial tree

A few years ago we decided that an artificial facsimile could replace the classic Christmas tree. This was satisfactory at a bunch of levels: cost, ease of decorating, cleanliness.

Then the rule of unintended consequences kicked in! Catherine and Hamish had no problem. Surprisingly the effort over 25 years of picking out a tree, loading it on the suburban, trying to get it upright, the theatre of Deborah asking why we didn’t get a smaller tree really did not seem to be missed. The other night Donovan was adamant as to how much he missed the “real tree”, the reason: there was no smell from the new tree. We never considered it. For a sighted person it would be a kin being told that the pine smell from the corner of the living room emanating from a small urn, was the tree, of course no lights or decorations would be visible. I think we would feel cheated. Fortunately we now have pine scenting, Donovan is in part placated.

Rantage:It’s been a while, but it is time. Vancouver has many with driving challenges; however there can be no excuse for not knowing or following the rules of the road. This week on my our way home from the cancer agency we witnessed 2 near accidents, both involved drivers going through stop signs from side streets onto major roads. These folks did not even look! More galling when lights are flashed, or a horn honked, there is indigninty, anger and single finger salutes. Stop with the roadside suspensions, police get out there and censor these idiots!!

Until next time…….