P53 AND ITS ASSOCIATES P21, CDK2,P27 & METASTASIS OF CANCER

"If  you  want  to find out  how  genes affect  other genes, you  have to find out how proteins affect other proteins."                                       Roger Brent   "If you want to find out how proteins affect other proteins, you have to study inhibition rates by chemical toxins."                                       Robert Jones  Researcher Robert Jones' Presentation. . . As I have explored the causes of cancer it has become apparent that the real cause of cancer is genetic protein based, in other words, toxic inhibition of proteins within the cell structure allows or encourages a cell, or group of cells, to become malignant.  The International genome project flatly states that all cancers are genetic and are caused by one or more of 3 things: 1.  Radiation 2.  Chemical Toxins 3.  Spontaneity I have concentrated my efforts to uncover the cause of cancer as chemical toxins as we have no way to control or measure the rate of radiation exposure.  I started on the conquest of exploring chemical toxicity and its relationship to protein inhibition several years ago.  In the process of my research, a hugh amount of toxins have been looked at.  As we narrowed the search to a protocol of daily or chronic exposure, at the top of the list were compounds of known carcinogen and neurotoxins, these toxins being classified as thio ethers.  The most significant of these thio ethers is dimethyl-sulfide.  Although small in amounts of exposure, the average inhibition of ability to bind to the cellular membrane came to a startling conclusion of more than 90% inhibition as an average for all three proteins. To distinguish which toxins in particular, we tested 36 lanes on Affinity Labeling gels.  Specifically, as we set the protocols for this research project we used toxicity samples from over 900 extracted root canal teeth as a composite and over 4000 bone fragments obtained from biopsy samples as a separate composite.  Root canal toxins and cavitation toxins were tested separately to determine how each toxin individually inhibited the binding ability of the protein.  Establishing published cellular weights (amounts) of these proteins, we proceeded to inject Affinity Labeling gels with amounts of human protein as to the stated amount found in each individual cell.  So, therefore, using toxins extracted from human samples and human proteins, we were able to exhibit extreme or severe inhibition of these individual proteins by chronic exposure to these toxins.  We then ran additional lanes on the same Affinity Labeling gels to determine the effects of blio toxins (fungi) and also mercury from dental amalgam. As you will note during my lecture, the cavitation toxins from a composite of 100 or more cavitations was much more toxic than root canal toxins. I'd like to show you in our basic DNA, we have the chromosome ladder as illustrated in blue and protein in green with amino acids in yellow.

The inhibitions I will demonstrate will have serious effect on the protein's ability to function in the nucleus of the cell and the downstream effects of these inhibitions and how they affect the cellular functions will be noted.

This is the G1S cell structure.  We present this as published with all the proteins that make the nucleus of this oncogene cellular structure.

I'd like to talk to you about each protein individually and about how each functions which has been established by the Science of National Genome Research Project.

The 4 proteins that we are going to look at are P54, P21, CDK2 and then we are going to look at a new publication from the University of Michigan published in the Journal of the National Cancer Institute.  We ill look at how the inability to bind P27 to P21 and demonstrate how it allows the cancers to metastasis.

What is P53?  P53 is specifically a tumor suppressant protein.  It has been defined as a normal function of P53 to be antioncogenic.  While type P53 proteins introduced into cells were foound to be growth suppressand, P53 is found rarely in a tumor cell while it is very prolific in normal healthy cells.  When it is found in a malignant tumor, it is foound sparingly and in an inhibited state as we will demonstrate and therefore its ability to bind in the cellular membrane is greatly reduced.  When P53 is normal or not inhibited, tumor growth or start is depressed.

Amino acids are an important class of organic compounds that contain both the amino (_NH2) and carboxyl (_cooh) groups.  Of these acids, 20 serve as the building blocks of proteins.  These amino acids are inhibited from binding to the chromosome ladder and or just one of the examples of damage incurred by these dental toxins.

This is the nucleotide protein gel before developing.

If you will note, we have a graph that is printed out with a Hewlett Packard Phosphorescence measuring device as it measures radioactive light.  This is non-subjective analyzation of inhibition of proteins ability to bind and function.

To the left vertically is the scale of light reading.  The bottom from left to right is the amount of toxin injected into each protein extract.  They are shown in micro liters (ul).

If you will note on P53 at 5 ul injection of the cavitation extract, the inhibition is already at 58.5%, any inhibition at over 12% will render functions to be ineffective.  What's interesting about this is that at 40 ul they are inhibited at about 85%.

Then, we wanted to look at mercury amalgam vapors and what would they do to the inhibition aspects and we were surprised to find that mercury has very little effect in the binding ability to our DNA at this stage of toxicity.  In fact, photo labeling increased very slight when 10 ul was added to the cavitation toxins.  This is not to say that mercury by itself would not damage these proteins, but did not provide a synergistic effect.  So the condition was not exacerbated by the addition of the mercury.

Now we are looking at a graph of mercury from amalgams added to the Affinity Labeling gel.  As you will note, photo labeling of the protein P53 increased with increasing amounts of mercury.  So mercury is not the cause of inhibition at this stage.

This slide shows gliotoxin concentrations produced in micro molar amounts.  At 5 um this protein showed 40.7% inhibition.  This is a very severe inhibition at very low levels.

Of all three of these proteins, P53 is the top dashed line with the circles.  As you note on the chart, P53 from root canal extract inhibits at 29% at 5 ul, continuing on at 40ul at 87.5%.  The interesting thing about these toxins is, it is estimated that a molar root canal produces 45ul each 24 hours!  All root canals are infected and some do produce more toxins than others.

P53 is shown now to be almost totally inhibited.  You must remember that Druckrey (Heidelberg) found these dental toxins to be the worlds most perfect carcinogen.  Creating an appearance and function of a malignant cell until the carcinogenic dose was reached. Now we are going to jump over P21 and go to CDK2.

CDK2

Keep in mind that CDK2 is a cyclin dependent kinase.  To function properly, CDK2 has to bind P21 after P21 has bound P53.  We have already demonstrated that P53 is inhibited from binding to the cellular membrane of P21.

CDK2' main function in the GS1 phase is to control cellular mass size or cellular growth and if it is inhibited in ANY AMOUNT this function cannot occur.

This slide, expressed by the Hewlett Packard light source, showing inhibition of CDK2 of cavitation extracts of 5ul bo be huge inhibition of 57.6% and that at 40ul, a whopping 89.5%.  The lower graph shows basically the same reaction to mercury as shown on P53.

Now, we are looking at a graph of mercury from amalgams added to the Affinity Labeling gel.  As you will note photo labeling of the protein CDK2 increased with increasing amounts of mercury.  So, mercury is not the cause of inhibition at this stage.

Now, back to P23.

P21 or H-Ras is the smallest protein yet discovered, but it is the superman of proteins.  The primary function of P21 in the cellular structure is to control cell replication and apoptosis.  It is also interesting to note that the downstream function of P21 is to control the autonomic immune system. In saying this, I will return later to this function.

Protein P21 (Ras) & Protein P27 (Raf) Stereo view of the association between ras-P21, a related protein rap1a, and downstream effector RAF.  This is a small part of the cellular signal transduction pathway.  These images were obtained by docking ras-P21 and rap1a, each separately, to RAF, based on structural data obtained from x-ray crystallography, and minimizing until the RMS deviation was less than 0.1 angstroms.

So, P21, an important regulatory protein in cell growth and differentiation is a GTPase called Ras.  There are 2 cellular switches on P21 that are activated by either GTP or as  in the second switch by GDP.  When the cellular replication switch is turned on, whichis regulated by hydrolyzing GTP, and the switch is turned off by the hydrolyzing GDP as in the second switch.  When GTP is bound to the first switch and is inhibited, it cannot hydrolyze GTP.  When P21 is unable to hydrolyze GTP the switch remains constant on.  So, you have uncontrolled cell replication.  The second switch can not glycolyze GDP due to inhibition allowing the cell replication.  The second switch can not glycolyze GDP due to inhibition allowing the cell replication cycle to remain full on.  The full purpose of the second switch is to turn cell replication off and it cannot function in this capacity due to inhibition. The downstream function of P21 is to control the autonomic immune system and when neither of the switch functions can hydrolyze or glycolyze GTP, GDP, there is a free radical produced because the inability of the protein P21 to bind gamma phosphate leaves a residue identified as gamma phosphatase.  The autonomic immune system responds to the gamma phosphatase, which is a free radical, with production of an autoimmune antibodies that have been identified by Dr. D. Balomenos, of the Centro Nacional de Biotechnologia in Madrid, Spain.  Dr. Balomenos has identified this autoimmune antibody as a multi-system auto-immune disease antibody known as human Lupus.

As you note in this graph, P21 (H-Ras) is the dashed line with triangles.  In the center is root canal extract at 5ul which inhibits this protein by 24% and at 40 ul, 67.6%.  Remembering that anything over 12% renders P21 (H-Ras) to a nonfunctioning state.

At 5ul of cavitation extract, it is inhibited at 44.9% and then at 40ul this is increased to 76%.  So, cavitation extracts totally inhibit P21 (H-Ras) ability to bind and function to CDK2.  And as noted, the mercury reacts the same as shown in previous samples.

You will note that the bottom graph we also tested P21 (H-Ras) with the glio toxins.  Inhibition due to glio toxins at 5um is 32.3%.  At 20um, inhibition is at 55.7%.  This protein P53 is severely inhibited.

Now we are looking at a graph where mercury from amalgams was added to the photo labeling gel.  As you will note, photo labeling of the protein P21 increased with increasing amounts of mercury.  So, mercury is not the cause of inhibition at this stage.

Now we have noted that all 3 proteins are greatly inhibited at even 5ul from being able to function properly, and that we have produced 3 distinct markers for the start of cancer:   Inhibition of P53 due to these dental toxins is unable to suppress tumor start or growth. Inhibition of P21 causes uncontrolled cell replication. Inhibition of CDK2 creates uncontrolled cell growth. These 3 markers positively identify the diagnosis of any cancer!

Let me present one more protein.

This is not my research but it confirms my research.  This research is from a team of scientists from the University of Michigan, published in the Journal of the national Cancer Institute.  Their research into the GS1 pathway proteins, as i have explored and presented in the past 2 years, looked at the start of metastasis and prostate cancer and that P27, also known as RKIP1 or KIP1.  When P27 is bound to P21 (H-Ras), it stops the migration of malignant cells into the vascular system and when P21 is inhibited from binding P27, it allows the start of metastasis not only on prostate cancer, but on ALL malignant growths. CONCLUSION OF THE CANCER PROTEINS Inhibition of binding ability in all phases of GS1 of these three proteins expresses itself as the probable start of most, if not all, cancers.  The chronic exposures of minute amounts of these toxins, which are also proven carcinogens, inhibit the binding ability of these proteins, which take on the form of a carcinogenic or mtant cell until the carcinogenic dose is reached.  The inhibited forms of P21, P53, P27 and CDK2 cannot function in the glycolyzation, hydrolyzation and methylyzation pathways and exhibit other "downstream" effects such as production of free radicals that are introduced  into the bloodstream, which can lead to the production of antibodies exhibited in other auto-immune diseases such as lupus, Parkinson's, ALS and MS. Other toxins that could cause this same condition have not been explored.  More research is needed into inhibitions of these three proteins by chemical toxicants as a probable start of malignant growth and other downstream effects.  This research believes that the lab findings are relevant to the start of cancer.

This awesome photo is of a melanoma cell as it metastasis into the vascular system