Link http://www.youtube.com/watch?v=JXt5Ga2WqZI&NR=1 to very
interesting video by Prof Trevor Marshall, one of the Helicobacter
pylori microbiologists.
It is described as being the reply to the Australian ABC film about
"catching Cancer" http://www.youtube.com/watch?v=8bpijebze6A - trailer,
whole film was shown last October and download facility now expired, but
Canadians can watch it for a short while on
http://www.cbc.ca/documentaries/passionateeyeshowcase/2009/catchingcancer/ )
Additional reference:
http://blogs.abc.net.au/abc_tv/2009/10/catching-cancer-abc-documentary-asks-is-cancer-contagious.html
"Approximately 20 per cent of all cancers worldwide are caused by infections. Some
scientists say it could be as high as 50-95 per cent . Across the planet, startling new
evidence is emerging that links viruses and bacteria to an increasing number of cancers.
And two Nobel prizes in the last five years mean the story of infections causing cancer
cannot be ignored."
Here on the viewer replies list, a woman tells of her experience with lymphoma,
which she believes she caught from a friend she used to lunch with every day.
Also:
http://www.youtube.com/watch?v=YRBvYcckoWE&NR=1
VDR Receptor Competence Induces Recovery from Autoimmune Disease
(VDR - Vitamin D Receptor)
Here are some on-the-spot notes I made on the Cancer video; they might be of
interest or use in deciding whether you want to watch it.
(Look out for the question of why a patient having a hip operation had germs in
that capsule that previously had only been identified at under-ocean vents).
"Everybody knows Inflammation Induces Cancer" - how? and can this
pragma help us find drug targets.
Co-morbidities. Depression a key problem in China, anxiety, allergies,
thyroiditis, IBD, - chart took studies out of PubMed and showed
co-morbidities - inflammation not unique - not jut one problem. Chart
of Co-morbidities. (ie you don't just get inflammation for one reason, you
likely have a whole host of other germs causing your problem - RE)
Why?
Human Microbiome project NIH - is body really sterile compartment as
previously assumed.
Expect there will be about a million bacterial genes found active in
the human body compared with 250,000 human.
Yersinia, klebsiella, over 100 species identified from saliva of
healthy human subjects.
Hip joint composition - different mix of bacteria - Lysobacter
predominant, Hydrothermal vent eubacterium - previously identified
under ocean - found during arthroplasty. How would this turn up as
contamination in surgery?
JRA Lymphocyte - able to image cells exploding in patients who were
seriously ill after blood allowed to age six hours.
Long extruded polymers visualised.
VDR Nuclear Receptor. What could be allowing persistent pathogens in
what was thought to be sterile compartment. In humans only, the VDR
transcribes genes for TR2 and others.
Knocking out the VDR causes human chronic disease.
Mycobacterium tuberculosis - VDR downregulated x 3.3 times.
Borrelia burgdorfii using bead assay found 50 fold downregulation and 8 fold.
.....
EBV - omnipresent pathogen? VDR downregulated particularly in
lymphoblastoid cell lines. After a while downregulated by 15 times.
Strong effect on VDR.
Believed to transcribe or express VDR
HIV totally takes the VDR, binds and steals so it can transcribe its
own genome.
Part of the survival mechanism of HIV.
Transcribes for about 17 proteins. Yet they are documented to have over
3000 interactions with human metabolome.
Why?
Human CBLP/P300 with disordered loops - depending on what the loops
bind to it will determine where they work along the DNA strand. They
can really go into many confirmations.
Depending what they bind to.
Salivary metagenome: 50,000 proteins rather than 17 of HIV.
Potential imponderable complexity of interactions with human metabolome.
Genomes accumulate gradually during life, shutting down immune system.
Catastrophic failure metabolism in chronic inflammatory disease due to
common underlying mechanism due to ubiquitous microbiota ...
Get a VDR agonist? - Omesartan quite adequate.
When you do that, can reverse autoimmune disease. Recovery as chronic
and slow as the disease process, 3-6 years. Study for 7 years in
variety autoimmune diagnoses, between 18 and 53 months, 81% experienced
reduced disease and symptoms.
Many had total disease reversal.
Carcinomas - 750 subjects 3-7 years, all disabling disease, only two
carcinomas and neither were metastatic.
Breast and bladder carcinoma subjects studied. 30 months just getting
to stage where it's interesting.
Why did study cohort not succumb to cancer?.
More direct relationship. Chronic Inflammation is the result of a
diverse intraphagocytic metagenomic microbiota. When this metagenome
reduces expression of the host VDR in order to protect the microbiota
against the endogenous antimicrobials, it also knocks out
transcription of a key gene - MTSSI - the Metastasis Suppressor #1,
expresses the protein MIM (Missing in Metastasis).
The immune system of VDR or vitamin D-deficient mice is grossly normal
but shows increased sensitivity to autoimmune diseases such as
inflammatory bowel disease or type 1 diabetes. VDR deficient mice do
not have a spontaneous increase in cancer but are more prone to
oncogene or chemocarcinogen-induced tumors.
Vitamin D and human health lessons from Vit D receptor nul mice (2008)
Wang et al did study in 2003 of 913 genes confirmed with array No 1 is
CYP24 and No. 2 is MTSS1 met suppressor.
MTSS1 identified as drug target but hard to make drug to suit. MIM is large
molecule, the protein is missing in metastasis. Implicated in breast,
ovarian, fallopian tube, gastric, colon, bladder and lung cancers. Exact
mode of action uncertain, but it is essential for actin polymerization
and phagocytoses, for cytoskeletal reorganisation, and for control of
cell growth.
Dr M proposes that VDR expression and activation is an entirely more
suitable target, a proxy target, and there is both human and murine
data to indicate the likelihood of success.
Meanwhile we are collaborating with West China Hospital in Chengdu to
institute large scale Phase 3 trials of the Olmesartan VDR agonist in
Autoimmune inflammatory diagnoses. Those trials should confirm that
meteastasis andinflammation can indeed be addressed with a singular
therapy.
Large Phase III trials. Ankylosing spondilitis.
There has been work on MIM in cancers including knock out mouse murine
work. VDR receptor unique to humans. Murine VDR does not express ... so
hard to get animal models.
--
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