CELL IN CANCER MODE

In a normal cell, things are operating normally.  The cell feeds itself and uses energy to allow its normal functions to unfold, and knowing that hard times will come to it, it even puts some energy aside for reserve. When one looks at Mitochondrial activity, one will find Gluconeogensis in full display.  This Normal Metabolism that some have called NORMAL CELLULAR MODE tends to show anabolism and normal oxygen.  In clear Hypoxic conditions which are read by the cell as a stress, there is the reversal of the chemical reactions as catabolism ensue and Fatty Acid become the source of energy and Glycolysis enters into play.   Under these circumstances, which can occur in normal life, catabolism is accompanied with Glycolysis.

In 1920, Walburg described the Walburg effect which characterizes the CANCER CELL MODE.
Indeed in cancer there is a dissociation of Glycolysis and with Catabolism.  In Cancer mode, the cell adopts Glycolysis and Anabolism.  Glycolysis is to escape the normal requirements of constant feeding, be in a stress like while Making new proteins (Anabolism) to allow cell division and proliferation.  One hundred years after the Walburg effect was described, it is now molecularly explained by Researchers.  Indeed, to do this the cell induces a genetic controlled hypoxia  by suppressing SIRT3 which overexpresses HIF.  This induces Hypoxic conditions in the Mitochondria.

http://onlinedigeditions.com/publication/?i=104782&p=12

The Cancer mode can now be measured
but quantifying:
1 Pyruvate Dehydrogenase kinase
2. Over-expression of GLUT1
3. level of vascular endothelial growth factor
4. level of suppression of SIRT3 and related  Increase in ROS1
5. level of HK2, IDH, and SOD3

and if you are very smart, start by including c-JUN, HIF, Myc and TCA (fatty acid)

And as you progress with the clues given you will understand why overexpression of ROS1 could predict resistance to MTOR Inhibitors.   And I believe it predicts of low participation of MAPK as a driver of pathogenesis therefore decreasing the value of MTOR inhibitors.  more detail to come.

ANOTHER WAY OF INDUCING HIF:
"Description

Dimethyloxaloylglycine (DMOG) is an inhibitor of PHF (prolyl hydroxylase, PHD) and asparaginyl hydroxylase FIH-1 (Factor inhibiting HIF, FIH). DMOG has been observed to upregulate HIF (hypoxia stabilize) HIF-1α at specific concentrations. In HMEC-1 cells DMOG attenuated REF-1 (redox factor 1) through activation of HIF. PHT cells exposed to DMOG were observed to upregulate the FSTL3 (follistatin-like 3) transcript. Attenuation of myocardial injury by DMOG was demonstrated in the rabbit ischemia reperfusion model. In NGF deprived neurons DMOG increased cell survival through inhibition of cytochrome c release." SOURCE

 santa cruz biotechnology, inc.

PLEASE DON'T TAKE DMOG WITHOUT BEING IN A CLINICAL TRIAL!  (CRBCM OPINION PROTECTED BY THE FIRST AMENDMENT!)

NEXT TO THE MTOR,

We are getting closer to the cure every day, we are clearly at the door of the cure acquiring process,
just learning the language spoken by the cell. Already it seems we are overwhelmed by what we find.
There are things we are learning though, and fast:
1. That forces within the cell can be followed through laws of nature, as grouped here:  THAT AMPLIFICATION, PROLIFERATION AND DIFFERENTIATION ARE GOVERNED BY SETS OF GENES AND HAVE VARIOUS LEVELS OF EXPRESSION.
2. That treatment strategies can be made following different steps in pathways
3. That Death traps are located at the membrane, cytoplasm, mitochondria and Nucleus
4. That downstream targets inhibition can overcome resistance to earlier target inhibition
5. That Inactivation and down-regulation of gene expression appears to be more important in Oncogenesis
6. That most of the time MAPK amplification results from the down regulation of PI3K/PTEN
7. That MTOR inhibition is deeper than EGFR/VEGF and PI3k inhibition
8. That VELCADE or antiproteasome will disturb all the pathways of which products need Ubiquitination for degradation
9. That Velcade may worsen VHL depedent syndromes
10. Then, even deeper, that MTOR, are Histone de-acyl- transferases

BUT WHAT WE HAVE NOT TALKED ABOUT ENOUGH IS THE POSSIBILITY OF CURE HIDDEN EVEN DEEPER IN THE DIFFERENTIATION.: HERE ARE HIDDEN THE SO- CALLED "PATHWAYS OF SECONDARY METABOLISM"  AND SURPRISE SURPRISE THAT THE ROLE OF ANTIBIOTICS RE-EMERGES!
HERE, WE LOOK FOR DIMBOA PATHWAYS AND DNA REPLICATION
ASSOCIATION WITH STRESS (FOS, C-JUN)
ASSOCIATION WITH P450
ASSOCIATION WITH UDPG GLUCOSYL TRANSFERASES AND SOME DIOXYGENASE

WE NEED TO EXPLORE ANTIBIOTICS COMING FROM FUNGI.

LET ME COME TO THE CHASE OF BX1, BX2, AS THEY ARE TIED TO U11, U12, AND CHROMOSOME 4.  THIS IS THE NEW BATTLEGROUND!

RESEARCHERS, PLEASE GO BACK TO WORK!

HURTHLE CELLS:  Thyroid MALIGNANCY SHOULD BE A PART OF THE VON HIPPEL LINDAU SYNDROME.
It all makes basic sense.  There are significant disturbances in the Mitochondria of cells of patients with VHL syndrome.  These disturbances involve Mitochondrial DNA and Cytochrome Oxidase.  Multiplication of Mitochondria results, with the abnormal content giving the appearance of "Hurthle" cells!  This just hit me as I was looking into a new case of Hurthle cells, the patient had a History of VHL!

Curcio-Morelli et al. (Harvard institute) also described how VHL protein affects Thyroid hormone activation through de-Ubiquitination of regulating enzymes.

ARSENIC TRIOXIDE COULD SIGNIFICANTLY EXPAND ITS ROLE IN CANCER TREATMENT. AND VITAMIN C AND MICROHYDRIN COULD COME TO THE RESCUE

Cancer cure is through death of the cancer cell.  To date, the main way of death for the cancer cell
is through Caspase activation cascade.  In most cells, we know how the main way the activation of Caspase occurs.  That is Cytochrome C is naturally anchored at the membrane inside the Mitochondria. The Anchor is in fact a chemical bonding or attachment through electrons, like molecules do attach to each other.  We believe there, Cytochrome C is attached to a Cardiolipin which is part of the lipids of the membrane.  Just imagine another molecule showing up with a free electron, the free electron could attract and pull the one involved in the attachment and break free the Cytochrome C.  That Cytochrome C electron no longer attached comes out and activates the Caspase (mostly Caspase 9 which eventually activates members of its family) and there starts the Caspase its work to coagulate DNA and genes start breaking,  thus leading to cancer cell death.  One of the molecules that produce such disturbing free electrons is Arsenic Trioxide.  This delivery of free electrons by arsenic trioxide is not limited to the mitochondria.   It occurs through the cytosol (liquid milieu of the cell) disrupting many cellular pathways, delivering global intracellular disruption.  ( for those savvy people, do remember that the " breaking" of the anchor could be induced from outside the Mitochondrial membrane through the AKT or Bax effect- this is where Bcl-2 negative effect is the strongest ) arsenic trioxide

This global disruption has been established to treat Acute Promyelocytic Leukemia (APL)  (by the way, Chinese researchers lead the way on this one).  Frankly speaking, this "Global disruption"can be used in any cancer.  The problem is that it can occur in any cell, including our normal cells.  Giving caution to the amount you use because of a narrow safety index. 

Vitamin C and Microhydrin have also free electron, that is why they can cool down free radicals and therefore are called Anti-Oxydants . The free electrons of these compounds seem to add to those of Arsenic Trioxide to Increase toxicity to the cancer cell.   It is worth mentioning that, at the DNA level, these free electron break the strand, triggering our first law (activation of P53 and stoppage of cell cycle).

3 main problems

1. Good and bad pathways are stopped, mitigating the effects of global destruction.
2. (non selectivity) Good and bad cells are killed. This effect is worse in patients with poor reserve of free electron clearing molecules (Gluthatione based, Superoxide based and others).  (CAUTION TO EVERYONE)
3. Arsenic is hard to get rid of, and chronic exposure signs will result.

But frankly speaking, you can use this to kill any Cancer.  Research will continue at CRBCM no matter what!

Of Note: Use of this information outside of the topic discussed herein, is not endorsed by the CRBCM

CRBCM today: Further evidence of 2nd law of nature

Further evidences of 2nd law of nature/CRBCM

If you compromise Cell divison, the cell will need to be destroyed
one thing is for sure.  DNA Breakage and mistakes or mismatches lead to cell cycle arrest (First law).  What is interesting is that the second law is very much linked to this. Once the repair occurs, a number of peri microtubular reactions need to occur to relieve that arrest and allow continuation of the mitosis.  This is the connection to the second law.
Also as we are further looking into this matter, we are finding further evidence that there is an intricate connection between Microtubule and Mitochondria.   Even the location of Mitochondria is not random and seems linked to the integrity of the filamentous connection.  We are learning about Nuage and Mitochondrial Cement.  The further we look, the more we can now ascertain the existence of the 2nd law.
We are also learning, that not all the antikinesin are the same.  Some are not as important, affecting peripheral molecules, but some involve the location of the "consensus sequence", and may be more important.

We also are learning that Cyclin ubiquitination and therefore destruction could be exacerbated by perimicrotubular disturbances.  Is this the mechanism of bypassing BCL-2 resistance?  More light is needed.

We will let you know what we find at CRBCM.