Ik heb weinig tijd voor duiding, maar deze lezing door Thomas Seyfried is te belangrijk om alleen in een reactie te dumpen. Kanker een primair genetische ziekte? Het is onvoorstelbaar hoe veel mensen er anno 2016 nog rondlopen die dit denken, al het overweldigende bewijs voor een metabole, mitochondriële etiologie ten spijt.
 | Corrien op Paleo? Apenkool! |
 | Fien op Paleo? Apenkool! |
 | Faraday op Paleo? Apenkool! |
| Faraday op Crohn, AIP en de omkeerbaarhei… |
 | Jo tB op Crohn, AIP en de omkeerbaarhei… |
| Faraday op Crohn, AIP en de omkeerbaarhei… |
 | james op Crohn, AIP en de omkeerbaarhei… |
| Corrien op Crohn, AIP en de omkeerbaarhei… |
 | Alex op Crohn, AIP en de omkeerbaarhei… |
 | marcel op Crohn, AIP en de omkeerbaarhei… |
| Alex op Crohn, AIP en de omkeerbaarhei… |
| Alex op Crohn, AIP en de omkeerbaarhei… |
| Alex op Crohn, AIP en de omkeerbaarhei… |
 | Gert van der Hoek op Is er een dokter in de za… |
 | Hans op Crohn, AIP en de omkeerbaarhei… |
Het Paleo Perspectief 
Geweldige lezing Melchior. Dank voor het delen. Ik ben eigenlijk benieuwd of jij nog doet aan Freeletics? Ik wil er weer mee beginnen al is het maar om het lichaam te stimuleren meer mitochondriën te laten maken.
Ha, Freeletics! You bet, Andreas! Bijna elke dag. Vanochtend een fijne Aphrodite gedaan op mijn paradijselijke nieuwe veldje, een door de gemeente aangelegd bootcampparkje bij mij om de hoek, min of meer in de achtertuin van ziekenhuis Rijnstate in Arnhem. Ik train daar al sinds het eind dit voorjaar werd opgeleverd en verbaas me er elke keer weer over dat ik daar helemaal alleen ben 🙂 .
Seyfried begint nu echt kwaad te worden 🙂 . Hij zegt het hier en daar echt heel recht voor z’n raap.
Verrek, ‘mijn’ veldje wordt wel gebruikt! Ik ben er meestal rond 07:00 uur, das misschien een beetje vroeg 🙂 .
Op onderstaande tijden kun je deelnemen aan een obstacle Bootcamp:
Maandag: 19.30u
Dinsdag: 19.30u
Donderdag: 19.00u
Zaterdag: 10.15u
dus nog genoeg gelegenheden voor vrije training, ook na 7.00u. 🙂
Heb je ook nog naar de andere video’s gekeken? 😉
Het gekke is dat ik mij herinnerde dat jij het ooit eens ergens in een reactie had geplaatst en ik was nieuwsgierig.
Vandaag maar weer beginnen. Voor mij is het inmiddels al weer ruim 2 jaar geleden dat ik het dagelijks deed. Helaas door ziekte van mijn vrouw (kanker) is het op de lange baan beland. Het enige wat ik momenteel doe is 2x in de week ruim 10K hardlopen en soms een HIIT sprint training. Op zich ben ik wel fit maar ik weet nu al dat Freeletics in het begin weer een uitdaging gaat worden en het mij eraan gaat herinneren dat ik spieren heb op plaatsen waarvan ik het bestaan niet (meer) weet 🙂
Groot gelijk heeft hij. Er wordt tegenwoordig zo veel voor zoete koek genomen wat letterlijk en figuurlijk natuurlijk niet goed is.
De hamvraag is natuurlijk hoe zorg je voor veel en goed functionerende mitochondriën? Het zal een combinatie zijn van beweging, ‘gezond’ voedsel maar ook (zon)licht aangezien dit de elementen zijn waar we als mens groot mee zijn geworden.
O shit. Wens jullie het beste uiteraard. Smerige kutziekte.
Freeletics. De burpees zijn het ergst 🙂 . Maar ik ben er letterlijk verslaafd aan geraakt, net zo erg als aan zwemmen.
Lean, mean mitochondriën zijn alles en de vraag hoe je ze zo houdt of terugkrijgt vormt het centrale thema van het verschrikkelijke project waar ik aan werk. Het is ook de reden waarom het zo lang duurt 🙂 .
Dank en no worries. Het ziet er allemaal goed uit tot nu toe.
Ja die burpees zijn in het begin niet leuk echter wel zeer effectief tegen een zwakke onderrug en je core vaart er op de lange termijn wel bij.
Hou jij qua tijdstip van trainen ook nog rekening met ons circadiaan ritme?
Mitochondriën (b)lijken een ‘banksaldo’ te zijn voor onze gezondheid.
Dat snap ik. Take your time maar niet te lang hè 🙂
Hoi Alex,
De andere lezingen staan prominent op mijn procrastinatielijst!!!
Ik ben wel blij dat dat veldje er niet alleen voor mij ligt, ha, ha, ha. Had al plannen om een wekelijks Freeletics uurtje voor kneuzen en bejaarden te gaan organiseren 🙂 .
Arnhem rules! 😀 Zo te zien heel wat mogelijkheden voor (al dan niet gratis) outdoor sport/fitness, zo ook in Uiterwaarde http://www.uiterwaarde.nl/recreatie/Sport/outdoor-fitness-zone maar ja als je een (bijna privé) veldje naast de deur hebt zoals Melchior valt dat haast niet te toppen. 😉
Dit interview met de jonge arts Priyanka Wali door Ivor Cummins is eigenlijk ook een aparte post waard. Hopelijk lezen/kijken er een paar fossielen mee:
Die prachtige mooie jongedame is een stand-up comedian… Dat moet ze dan wel doen met wat bas in de microfoon.. overigens..
Hoe kom ik aan de tekst van de lezing Melchior Meijer?
Cobi Vink-Stephan Tel.: 0031 651 91 89 83
>
Cobi, ik heb geen tekst van mijn lezing 🙂 .
Wel een PP-presentatie die vrij duidelijk schijnt te zijn:
https://melchiormeijer.wordpress.com/2014/03/21/eerste-paleo-lezing-in-de-metropool-zuidhorn/
Wanneer je in een youtube video het ondertitel icoon kunt zien betekend dit dat google transcript de text in ieder geval automatisch uit de video heeft kunnen halen. Soms wordt deze ook nog wel eens vertaald naar andere talen.
Je kan met Google Chrome browser deze tekst in XML-formaat downloaden. Je kan hierna met wat filters de XML code verwijderen om zo uiteindelijk de ‘kale’ tekst over te houden. De kwaliteit van de tekst hangt overigens wel af van de audio kwaliteit van een video en dat er 1 persoon tegelijk spreekt.
Het is mij in ieder geval gelukt om de tekst van de eerste video in deze blog te downloaden in xml formaat.
Mocht er animo zijn dan kan ik wellicht vanavond de meest rommel er uit filteren.
Ik vond eigenlijk dat Melchior de vraag met stijl had beantwoord Andreas. 🙂 Was ook mijn eerste reactie, vandaar dat ik eerder niet reageerde…
Transcript: (tekst/layout Youtube/Epigenetix Foundation)
well thank you very much tom and angela for organizing this and inviting me here
and have this opportunity to give you guys a an update on some of the things
we’re doing in our attempt to manage cancer arm and i’ll be talking about
some fundamentals of the disease and then i’ll give you an update on some of
our unpublished work with mice and with people so let me go to the ok this is we
always have a reality check and update
what’s going on in the world of cancer we have the latest that just came out
projections for 2016 I don’t expect you to see the details of these numbers
I only want you to know they’re big and they’re getting bigger
alright so we have the 2016 we have 1632 people a day dying from cancer
we’re not really sure how many of these people are dying from the cancer from
the treatments that they used to treat the disease
this is a very difficult question and we also recognize now that brain cancer in
children pediatric brain cancer has replaced leukemia is the number one
killer cancer killer for children
so this situation is not good and something has to be done
so we have a question and this is a provocative question that needs to be
addressed in relationship to the origin of the disease i think if we better
understand the origin of the disease
we will have a better chance at managing and preventing the disease
all right so is cancer a nuclear genetic disease or is it a mitochondrial
metabolic disease
the question is weighted ok
is the disease resulting from defects in the nucleus of the cell or is it
resulting from defects in the cytoplasm and in particular the mitochondria that
we’ve heard a lot about it this meeting of the cell this is a very important
question because it will determine how we approach this disease with but with
respect to Natalie management with but with respect to prevention
all right the current dogma
cancer is a genetic disease and the hallmarks of cancer by doctors hanahan
and weinberg have solidified this over two major papers in 2000-2001 some of
the most highly cited papers in the field of cancer cancer cells carry the
oncogenic and tumor suppressor mutations that define cancer is a genetic disease
a dogma is an irrefutable truth
it’s a concept that is no longer challenged or investigated because a
dogma is solid and how do I know this is a dogma
how do we know that it’s a document when we teach general biology cell biology
and biochemistry at the college level and you look at the sections on cancer
cancer is a genetic disease
there’s no other discussion about it you go to the NCI website
cancer is a genetic disease there’s no discussion about this
this is a dogma now they
here’s the the the foundation of the dogma is the somatic mutation theory and
that it solidifies the dogma and they use these simplistic diagrams a car that
has no brakes and the accelerator is is maximally forward to replicate or to
simulate what goes on in a population of cancer cells here these cells are at a
control cell division out of control
they have no brakes and their acceleration their growth acceleration
is out of control and you have this situation
so add a control cell growth dysregulated cell growth is the
signature feature of this disease
regardless of what tissue or organ it happens to attack then we place the
hallmarks of the disease as Hannah Hannah and weinberg have done in this
the six major hallmark sustaining proliferation of aiding growth
activating invasion and metastasis enabling replicate of immortality
inducing angiogenesis and resisting cell death all the result of nuclear-driven
oncogenes and tumor suppressor genes
now in the most recent rendition of their paper we now entered into emerging
hallmarks hallmarks that have not yet reached the big six
so this concludes this regulated cellular energetics and avoiding immune
destruction
if you read their paper in in detail
it was it will say this regulated energetics is now considered an emerging
hallmark that is programmed by proliferating inducing oncogenes
preserving the dogma
ok this preserves the dogma
because we’re saying okay you can have this dysregulated energy metabolism but
the oncogenes are controlling it
everybody’s happy all right now we have here is another situation
normal chromosomes normal cell now all of a sudden cancer arises from a series
of our chance mutations in different genes in different places and they say
maybe for wii nobody really knows how many genes are responsible for the
origin of the disease some people say 12 for Michaels Stratton his group predict
that complete cancer genome sequence will eventually identify 700 million
mutations
alright several several of these driver genes and passenger jeans and all this
kind of stuff and they better calling in a Watson right the IBM computer down to
md anderson to try to figure out what’s going on with all these jeans
good luck to that all right now here we have a person staring into a screen
individuals cancer cells are genetically tested for personalized therapy
she’s going to look at these images and breast cancer cells being examined to
see if they possess extra copies of a particular gene and based on that
genetic information they’re going to either make some sort of a prognosis or
they’re going to elicit some sort of therapy and we know from President
Obama’s speech a couple of weeks ago and he emphasized in a state of the union
speech personalized therapy is the way we’re going to manage this disease and
we’re going to have the honor of job Joe Biden lead the charge
now I believe Joe Biden has a good heart and I think because the loss of his son
the glioblastoma
he has an intrinsic interest to do something about managing cancer
the question is is he going to receive the information related to the dog park
or maybe he might want to consider other
shins or other possibilities and this is what we don’t yet know
now one of the most important things about cancer is metastasis
this is what ultimately kills almost all the people that have the disease either
the DS either that process itself or the attempts to stop that process
this is a diagram here you have the cancer cells and they go through this
casting it is cascade it’s a it’s a very stereotypical cascade
regardless of where the cancer comes from it comes from along the :
the breast you know the bladder it goes through the cancer cells invade ok these
green cells of the end they break through the basement membrane and enter
into the local tissue then they in travis eight enter into the circulation
these are very sophisticated biological processes by which this happens they a
immune systems for survival ok
how come they’re surviving the immune system isn’t will come to that later on
but then they immunosuppressed the immune system and they extravasation
they leave the bloodstream and and and enter and form these Kyle distant
colonization which make it means that you can’t cut this out there spreading
all over the place so it becomes a very difficult disease but this is a very
stereotypical pattern now according to the dogma the epithelial-mesenchymal
transition is designed to explain this chance mutations happen in these cells
that shit the cells through these chants mutations enter into the bloodstream and
then many of these effects of the chance mutations become reversed in some
unknown way and then they start of replicating of the way they were before
they were actually entering into the bloodstream
now I don’t know how a bunch of chance mutations could constantly produce a
very sticky or stereo typical pattern
how to chance events caused a non chance event
I don’t know now we have a problem
how can we advance new metabolic therapies that the 800-pound gorilla who
thinks cancer is a genetic disease
who is the gorilla the National Cancer Institute academic and pharmaceutical
cancer industries
all right dogma rules if you want to come up with a new therapy
you better make sure it’s its associated with dogma
now we can say we don’t need to do that and we can putz around here with these
metabolic therapies but they will be always be on the periphery
they’re not going to be mainstream until the gorilla on NASA’s the room now how
are you going to do that
all right you can just do it by continuing to do what many people in
this room are doing or you can try to undermine the document with the evidence
that exists and this is what I’m trying to do through the scientific argument
the scientific argument and the debate
related to this disease so let’s look at the element of the evidence the
challenges the somatic mutation theory
okay i’m going to go through a series of experiments that we’re done over the
years that are inconsistent with the dogma
this work was done by dr. McDonald who I had the opportunity to talk to at the
University of Minnesota’s a professor emeritus at the University of Minnesota
and he did these studies way back in nineteen sixty-nine where he had this a
very aggressive renal tumor in the Frog
ok it’s a lethal meant a malignant tumor at front comes from the kidney and the
luck
frog what what McDonough mckinnell did is he took them to sell out of that the
tumor removed the nucleus from the tumor and put it into a nucleated fertilized
egg that had normal cytoplasm
so you take this out the nucleus that has the tumor suppressor genes of the
optimum abnormal oncogenes meet defect and you put it into a new cytoplasm and
he generated this tadpole
all right there was no dysregulated cell growth in the tent pole
you could cut the tail off the tail would grow back and this thing
the problem is the tadpole never could mature into a fully differentiated
mature fraud
so there was something in that cancer nucleus that block development but it
certainly didn’t cause the signature met that the signature defect which is this
prefer
asian findings are inconsistent with the somatic mutation theory and then I
Beatrice minutes and Carla men see leaders in the field of developmental
biology took cancer cells from a very malignant teratoma and put these whole
cells into the blastocysts and develop the mouse
that was a mixture of the tumor cell origin and and the end the other art and
the mouse was was healthy except for a few little spots but there but their
their their their conclusion was conversion to neoplasia does not involve
structural changes in the nuclear genome
ok well what happened to the tumor suppressor and the oncogenes right if
this is if this is the case the findings are inconsistent with the somatic
mutation theory
Jim Morgan’s group from st. Jude’s medical hospital in in memphis tennessee
was studying midgel blastoma to a very aggressive childhood brain tumor in the
cerebellum they had knocked out a gene patch then they made these tumors and
they took the nucleus and a of the of the modulo blastoma and they and they
put it into an embryonic stem cell and they and they said although
medulloblastoma derived embryos aborted not exhibited uncontrolled proliferation
resembling tumor Genesis what happened to the oncogenes and these tumor
suppressor genes
here’s this embryo again it aborted something is in those the cancer nucleus
that’s blocking development but it’s not causing the signature phenotype which is
up
unbridled proliferation their inconsistent
this is work done by rudy danish at MIT and his group where they took melanoma
tumors characterized genetically the mutations that were in the melanoma took
the nucleus of the melanoma put it into an embryonic stem cell and cloned mouse
from the melanoma nucleus
ok the presence of major genetic abnormalities in the mice clone from the
tumor provides unequivocal genomic evidence that the mice were cloned from
the tumor nucleus where is that this regulated
what up the mice aborted ok just like the frog and and just and just like the
modulo blastoma something in that cancer cell nucleus that’s damaged is a
boarding development but it’s not causing the signature defect
according to the document that you would have expected because the phenotype
comes from the nucleus
now this is a very important paper by many career party from baylor college of
medicine and and his group there now Benny decided to look at the train what
let’s not transfer the nucleus let’s transfer the mitochondria
so he took very aggressive breast cancer highly malignant breast cancer cells and
he replaced the mitochondria in the breast cancer self with a normal
mitochondria and non-cancer a non-cancerous mitochondria
he characterized the upregulated oncogenes and the genetic abnormalities
in the breast cancer from the malignant cells
he puts the mitochondria from the normal and the oncogenes turn off and their
energy metabolism of the cells and the cells stop growing and then when he did
the reverse experiment took the very cancerous mitochondria and put it into
extremely slow growing tumors these tumors went what went berserk and he
grew them in the mice to show this
ok the mitochondria calling the shots here now what i did just recently over
the summer I kind of bundled I’ve only given you a small snapshot of some of
these papers you have to go and read all of this for yourselves
so what I did in this paper is I throughout the data and I said let’s
interpret the data based on the the the somatic mutation theory and based on the
mitochondrial metabolic theory and you come to the conclusion of what you think
this is telling us because if it’s not if it’s telling us that this is not a
nuclear genetic disease then we have gone seriously off track and it’s takes
time to to to to look into this
so this little diagram that circulating through the web that we my students and
I put together to give us a little picture of what’s going on in a very
simplistic way this figure
normal cells to get normal cells tumor cells to get tumor cells
what is responsible for the dysregulated phenotype is that the defects in the
nucleus or is it the defects in the cytoplasm in the mitochondria remove the
nucleus to a normal cell you get normal cells sometimes normal tissues but it
aborts there’s something going on with this cancer gene you do the reverse
experiments which has been done by Israel shaper and you put a normal
nucleus into a tumor and you get debt you get either tumor cells are dead
cells you don’t get normal cells again we’re seeing evidence that challenges
the dogma that cancer is a genetic
disease so if somatic mutations are not the origin of cancer
then how do cancer cells arise big question
ok let’s throw off the dogs ok now we’re really what we’re groping now
no we’re not groping warburg had pegged a long time ago
ok a very dynamic scientists from the 20th century
he clearly stated cancer arises from damage to cellular respiration and and
we saw this from from dr. buses a presentation yesterday energy through
fermentation gradually compensates for insufficient respiration cancer cells
continue to ferment lactate in the presence of oxygen which is the Warburg
effect big field of research in cancer metabolism
what is what where does the Warburg effect come from what controls the water
if everybody’s trying to figure out how the oncology oncogenes do drive the
Warburg effect but why are the oncogenes up because they have defective
respiration warburg also clearly defined the nature of the Warburg effect that’s
not a mystery at regardless of what I people say enhance fermentation
now he is it enhanced fermentation is the signature metabolic defect malady
and all these cancer cells to some degree or another some cancer cells a
little bit of respiration some of the very few recipes but nevertheless
insufficient respiration is the common metabolic melody malady
all right every cell in that tumor is a different genetic entity they will have
different genetic mutations every cell in the tumor
you close them out they’re all different from each other why do we persist on
focusing on the unique differences of every cell in the tumor looking for the
for the therapy when the common metabolic malady is if it is sitting
right there in front of us
why we don’t we don’t do that why don’t we focus on the common defect rather
than you can meet unique defect in every single cell
ok very simplistic overview of energy metabolism
most of our energy comes from oxidative phosphorylation of mitochondria
breathing in the good air exhale exhale the bad air co2 goes out from the food
away bring in their respiring or most of the energy in our body is coming from
oxidative phosphorylation very
all energy comes from substrate level for these are primitive forms of energy
substrate level phosphorylation you get into the glycolytic pathway in in the
cytoplasm and also in the krebs cycle the citric acid cycle you can get some
energy through the sucks and Yoko a synth a step in there which can get
upregulated in cancer
I guess what happens in the tumor cells now is there is a shift away from rocks
for us to these more primitive substrate level phosphorylation this is seen that
to some degree or another
okay why is there a shift because if they don’t make the shift they’re going
to die
all right if only cells that can upregulate substrate level
phosphorylation can tolerate a loss and not in respiration
otherwise the cells die you’re never going to get cancer so a lot of people
say oh there’s nothing wrong with the mitochondrion tumors when you look at it
under the electron microscope you see often a lot of different kinds of
problems and we said we just heard from John that these are tubes
so these are tubes running through a suspicion of this organelle and this is
the barrel Orthodox shape of the CD stripes here
these are the cristae they contain the proteins of the electron transport chain
and this lipid cardiolipin of the elect these lipids and proteins work together
and they form these super complex is to generate the energy that we need to
respire ourselves and generate the energy for our body
this is a glioblastoma multiforme me that we heard about yesterday and they
have a ghost what they called crystalis leading to ghost mitochondria structure
dictates function
the very structures are missing too about to a large degree in the in the
mitochondria of the GBM and in the end a mitochondrial a lot of cancers
now they’re not all cancers don’t look exactly like this some have massive
numbers of mitochondria but they’re all dysmorphic in one way or another
most cells have very few mitochondrion the cancer cells but many of them have
this pete peterson at Johns Hopkins did a huge study never found a tumor cells
that had completely normal numbers of structures of mitochondria mitochondria
defective
if these mitochondria defective these cells are not going to be able to
respire and in order to respire effectively they’re going to have to go
to have to go back to some sort of level of fermentation
otherwise they’re going to die there’s no other way you can get energy
we looked at we we look at all this and there’s a lot of evidence to show this
now the question is how do you put all this together if you’re going to come up
with a new kind of a view of cancer
you have to be able to link all of the information that’s been done on this
disease and then reinterpret it in light of a different kind of it
view the mitochondrial metabolic theory of cancer
ok so we take the emphasis away now from the nucleus and we put it on the
mitochondria
all right and this is the oncogenic paradox that has prepared as perplexed
scientists for decades even in the book the Emperor of all maladies to do the
mortgagees book that was on the bestseller list
she was struggling you going to read this book for we don’t understand how
it’s possible that we can have all these provocative agents from the environment
causing cancer through a common path of physiological mechanism this challenge
Albert sink yogi Nobel Prize winner of this challenge on cars is a brawny
people we don’t understand how a carcinogens radiation hypoxia
inflammation rare inherited mutations p53 Oh cancer must be a genetic disease
because a person inherited the warburg said you have many secondary causes of
cancer is only one primary cause that might damage the respiration those p53
mutations that you inherit in the genome damage the respiration so distracting
one and some of these others that you hear about grass oncogenes viruses age
all of these things can produce cancer in various tissues what do they do they
produce Ross reactive oxygen species
Ross are known to be carcinogenic and mutagenic all right so they’re coming
out of the mitochondria and they’re causing the genomic mutations that you
see in the nucleus
they feed back and they cause further damage on the efficiency of the
respiration the the mitochondria signal the nucleus
if you’re going to survive we have to go to alternative energy
what’s going to drive the alternative energy the oncogenes that transcription
factors for the fermentation pathways so they’re in effect they’re not the cause
it’s very important to recognize this because it’s extremely important on how
we’re going to deal with this disease if we understand the origin so what happens
then this is a progressive situation
it’s an escalation of biological chaos
eventually leading to these ghosts mitochondria eventually shifting from
rock from from oxidative phosphorylation to substrate level phosphorylation so
the cell now becomes more and more fermentative during the progression of
the cancer genomics is all shot to hell is collecting all these mutations you
get a Warburg effect which is the shift food the fermentation
now we can begin to link this that the hallmarks of cancer
the defective respiration and this whole shift from from respiration to
fermentation
so that when you damage the cells respiration the mitochondria keeping
those cells in a differentiated state when that mitochondria becomes
dysfunctional cells begin to ferment when the cells for men they begin to
take on the characteristics that organisms had on the planet before
oxygen came in
alright so during that time when there was no oxygen in the atmosphere all the
cells were highly fermentative in a highly reduced state and proliferated
uncontrollably
all right in a in a in a unbridled proliferation
okay if that’s the case then you can account for the three major the first
three major concepts of the whole of all of this is the result of these cells
returning to their primitive state sustained angiogenesis vascularization
of the tumor that everyone massive emphasis going on this
the cells are blown out lactic acid into the micro environment creating a
specification which is telling the Sith the body to this is a wound we got it
going to and heal this the back of the blood vessels come in
it’s coming in because of the destabilized energy metabolism and those
out
they evade a potato cesis ok what controls a potato cesis cytochrome C in
the mitochondria mitochondria being blown out there for these cells are
escaping their normal program death
now this is that the big dog here
metastatic metastasis all right how do we link
how do we link the metabolic theory of the mitochondrial metabolic theory into
the most important aspect of cancer
there is growing appreciation that the metastatic cell is a fused hybrid from
our immune system with these tumor cells
this is not well appreciated because it’s not consistent with the epithelium
his ankle transition of the dogma
but there’s a growing evidence so we have normal cells we have a beginning
dysplastic carcinoma inside to the cells now begin to throw out a little lactic
acid our macro fashions of the immune cells come in as facilitators of wound
healing and the wound doesn’t heal in this chronic condition persists over
time the to facilitate wound healing the macrophages fuse with these cells so in
the fusion process these cells are now picking up this functional mitochondria
from the from these from these self that cannot and can’t do not metastasize
these cells these this condition these few hybrids now that macrophages live in
the circulation
they enter and exit extravasated travels eight there are militia in our body to
heal
bacterial infections help that help facilitate wound healing
these cells are already programmed to do all the things in the medicine
metastasis cascade
you don’t have to have new mutations as a matter of fact some of the most
metastatic cells have no mutations
I don’t know how the god with deals with that the other thing you have to realize
that as a cell of the immune system
glutamine now becomes a major fuel in addition to glucose are immune cells are
glutamine hogs
that’s because of their biology and what their program to do so it’s very
important to recognize that what we have done is unleashed a beast that is
metabolically dysregulated so if most cancers express the Warburg effect as
the result every of impaired respirate what are the therapy ok now let’s look
at the therapies
okay once we have a clear a more clear understanding of the nature and the
biology of what cancer actually is now we can begin to think about those kinds
of therapies that might be more effective or a better than what we
presently have
ok one strategy is to reduce levels of fermentable fuels while elevating levels
of non fermentable fuels a fermentation is what’s keeping those guys alive
we need to recognize that and deprive them of the fuels that are allowing them
to grow
ok so let’s look at the metabolism of glucose and glutamine are the prime
fermentable fuels for this cell
these cells are living in hypoxic environment ok glucose comes in as
glucose 6-phosphate can be metabolized through the end
meyerhoff pathway getting us nice substitute lot of substrate lot of
energy through the glycolytic pathway blowing out lactic acid into the
microenvironment also some of that some of the pyruvate can enter into the
citric acid cycle come out is situated for the synthesis of lipids using the
other part of the pathway the pentose phosphate pathway which is upregulated
glutathione keeping these cells from dying from the ross this glutathione is
upregulated in these cells that they used nadph was also a substrate for
building fatty acids
so you’re getting and of course you’re building the precursors for DNA
synthesis so these cells can proliferate using glucose is the substrate on the
other side you get glutamine coming in split by the glutaminase that am I
nitrogen is now coming in and now forming the two major Khan nitrogen
carbons are going to make the DNA and RNA and all this with the proliferation
that glutamate can be dumped back out into the out side which in the brain is
deadly because going to create excitotoxic death and not in the closest
and it’s going to facilitate rapid growth or the glutamate can be trans
amity to alpha keita glue to rate using either at the the reductive pathway or
the oxidative pathway either one to generate more substrates for the growth
of the cell so glutamine and glucose
now if you and as Angeles going to talk about if you shut down the glucose and
you starve them of this and then you give them a hyperbaric oxygen you could
potentially overwhelm their antioxidant capacity and kill them naturally by
upregulating a reactive oxygen species and the ketones from the ketogenic diets
will protect normal cells from this from this attack
so this is the thing everybody’s always you can we get a drug that’s going to
kill tumor cells and not hurt
so far that drug doesn’t exist but it can ok
calorie restriction metabolic cancer intervention we’ve heard about this
total dietary restriction differs from starvation and the fact that it
maintains minerals and nutrients enhances mitochondrial biogenesis that
some of these cancer cells that might be on the threshold could potentially be
returned to the society of cells if you could read reactivate their mitochondria
not poisoning
a
individuals to reactivate that mitochondria alright so we have reduced
now if we go into calorie restriction blood sugar goes down
insulin goes down glucagon turns on we heard about this yesterday
ok we start mobilizing fats water-soluble break down fat products by
the hydroxy butyrate acetone blows out on the breath
ok so we begin to shift the whole metabolic environment by doing calorie
restriction
now let’s look at some of the data from some of I know this is a study we did
using the Ziegler brother 0 carbohydrate ketogenic diet standard diet ketogenic
diet unrestricted like the my seat all they want and restricted calorie
restricted to reduce body weight by about fifteen percent now look at this
standard diet unrestricted tumors grow fast you restrict the count that high
carbohydrate diet the tumors grow slow you now here the ketogenic diet
unrestricted makes the tumors grow even faster
the ketogenic diet you have to know how to use a submitted it’s a tool if you
don’t know how to use it you get you can have problems you restrict the diet yes
you get this
now we saw the same effects using the trishas quito count the same same exact
findings from that from what I want to say not all these ketogenic diets are
the same
alright some some you can eat ad libitum i’ll show you data for that when you
don’t we don’t get necessarily something like this so there’s some differences
here and also some of the tumors respond differently
that’s another thing what we do each one of these mice are different under a
different diet condition and we use linear regression analysis as glucose
goes down ketones go up an evolutionarily conserved adaptation as
glucose goes down to more weight goes down and we heard that yesterday from
dr. Barth
there’s a direct correlation in the blood between how fast your tumor grows
and how much blood sugar you have and that’s we showed this in the mouse and
now it’s been shown for breast cancer and for brain cancer and from variety of
other things
now what are the mechanisms people love to know the mechanism not gonna have
time to go through all over a massive amounts of data but calorie restriction
targets multiple cancer hallmarks it down regulates the vascular endothelial
growth factor expression for angiogenesis it operates through the
nf-kappab eep pathway down regulating those signaling cascades it’s pro a
platonic it’s killing the tumor cells by a pathetic mechanism so
now what we’ve done the mechanisms in the mice and we’ve done a lot of work
like this
of course we want to look at brain cancer we’ve done a lot of work on brain
cancer we developed a very excellent model for human glioblastoma the end
this GBM model it fulfills all of the characteristics that you see in human
GBM
this is one of our first slide studies on just calorie restriction alone
here’s the brain you put the team’s dark cells here these are the tumor cells and
as dr. boss said yesterday
these cells invade right way these cells you put the sails here they’ll invade
right across the corpus callosum
they’ll go to the brainstem go to the cerebellum these cells are all out
through the brain
there’s no way you’re going to be able to surgically resected developed this
however we put some ice on calorie restriction and you can see that the
demarcation of the tumor becomes much sharper under calorie restriction and as
dr. boss said yesterday we know that if you the more you can do bolt-on a cancer
patient
the greater the longer that person is going to live if so I say why white mean
when a person has the brain tumor they going to get the brain tumor out right
away
why don’t you put them on a calorie-restricted ketogenic night
shrink the tumor and then take the tumor out and you’re going to do you’re going
to guarantee that the patient is going to live longer for some of it for some
reason soon as the poor patient gets 90 we got to take that tumor out right away
it’s just like with the poor guys even know what’s going on you know nor does
the neurosurgeon most of the time
except for the ones that at you pit Joe maroon
all right can the ketogenic diet be effective the metabolic management of of
brain cancer in people
ok the first study was done by linden Emily she took two little kids that were
failing the standard of care and they were not responding and she put them on
the ketogenic diet
loke reduced blood sugar elevated ketones and they had a remarkable
recovery
the quality of life of those kids improved significantly
now the way you’re going to see that I want I cannot emphasize more get her PhD
dissertation from the library at Case Western and read how she dealt with this
incredible challenge it when you read what would happen to those little kids
it breaks your heart what those kids went through and to see how they
recovered and the quality of life improved with this ketogenic diet
one kid lived another couple of years the other one was lost to follow-up we
think that we try to figure it out we just they couldn’t figure out maybe
maybe the child is still life that we don’t know but it was lost to follow-up
now what I don’t understand is this was shown back in 95 it it works
why are we not using this in pediatric oncology
you know we have some of the greatest minds here using the same therapy for
epilepsy children in debt with epilepsy are being treated with these ketogenic
diets but little kids with brain tumors or not
what is going on with that ok we publish the second paper as you saw yesterday in
nutrition and metabolism from this individual that was 65 years old and she
had a memory loss and you saw the data i’m not going to show you again but dr.
buss showed it yesterday
the tumor was shrunk the MRI PET scans everybody was quite excited called
radiological resolution doesn’t happen often it can happen occasionally on
standard of care but it doesn’t happen often that work we got several more
positive signs that the individual thought they were out of the woods then
went back up off the diet the tumor return
ok and rather than going back on the diet they went on avastin all right
I’ve written about avastin were staying
drug it was taken off the market for breast cancer
why are we still using it for brain cancer it causes the cells to diffuse
through the brain
you’re never gonna get this is all because of the images look a little bit
better
ok and you saw this we published this in Lancet Oncology originally and this is
the standard of care
we’re not going to make any major advances until we get rid of that
standard of care i don’t care what anybody says you create a perfect storm
of metabolic abnormalities in the brain you saw it yesterday
we’re releasing glutamine in large quantities into the brain
we’re trying to stamp it by using high-dose dexamethasone
this is increasing glucose many of these brain tumors are infected with the human
cytomegalovirus
this is like a supercharger for using glucose and blue to me
all right so we got a big problem here and as mycoplasma in those tumors
not all but some we got all this crap in there and we’re freeing up the fuels
that are going to keep those cells alive and and and save them and facilitate
their growth
now let’s look at the how it works stop this is the standard of care
radiation alone none of the people survived
they all died now his olamide was considered the breakthrough
I was at the meeting when tim is all mine was so over this is the this is
that this is the weekend work it were increasing progression-free survival by
a significant amount of we combine
tim is olamide with radiotherapy then a paper comes out 10 is all might
increases driver mutations
this is out from dr. Johnson’s group at ucsf what’s going on how are you taking
ten missoula might which is helping the patients live a little bit longer
progression-free and at the same time that they’re they’re they’re they’re
getting driver mutations
what’s going on that’s the kind of how you explain this on the dog
ok one of the adverse effects of 10 is all my diarrhea fatigue nausea and
vomiting in some patients
those are all indirect forms of calorie restriction now what would happen if we
replaced him as olamide with a calorie-restricted ketogenic diet
something like Adrian check is doing
do you think we could get a better a better
if we’re combining a radiation with a restricted ketogenic diet this evidence
to say that’s true
what happens we get ready to get rid of radiation altogether
god forbid the hospitals will lose their money
all right i’m going to give you an update on individual that we’ve been
working with for several years now
this person presented with gait disturbance at age 56
they were given her flippers to improve her swimming and you know
exit biking and all this kind of stuff didn’t go away she was dying tumor is
inoperable diffuse infiltrate of brainstem glioma and in 2012 she
initiated a restricted ketogenic diet with supplements metformin dichloro
acetate and curcumin she had to get off the dca after a while because it’s
causing some peripheral peripheral neuropathy conditions
she was up what went to cease five major medical hospitals in Europe and the
United States refused recommended chemo and radiotherapy from five major medical
centers so she’s not on any standard of care except the ketogenic diet and
supplement
I talked to her last week the tumor the tumor can MRI says the tumor is not
going away it grows very very slowly it’s still there but she still drives a
car
she’s in relatively good health but she’s depressed I told to stop getting
the MRIs every time you get the MRI you get the present
all right she’s already out that she’s six years out you know this diffusion if
you have little children have it’s devastating they die very quickly
unfortunately but if you’re in it years you can live maybe 10 or or or or or 15
years with this kind of a tumor but then it gets bad again when you get over age
55
you know in the literature we know she’s out now almost six years ago in on seven
years with this tumor and as we know of only one other person at least presented
in a deliberate literature at least that we know of that live 29 years so she’s
out the stratosphere survival without any standard of care
now we try to we learned a lot from this one case and you know we tried to open
up a
elevate ketones and reduce glucose but each one of these is that the measure
the measurements every day measuring glucose and ketones over months so we
have hundreds and hundreds of measurements of glucose and ketones in
this one person
now the problem of course is that you see a lot of scatter we’re trying to
develop a tape up a procedure that can be used in clinical trials and things
like this and my students and I are looking at the data and we’re going man
this is going to be tough to do in a clinical
how are these people and then you know she she goes out and gets into she has a
handicapped parking spot
she goes into some some guys parked in handicapped parking spot and the next
thing you know she has a big blood sugar and I think Colin champion on the web
showing how how emotional stress and all these things can do this all right so we
developed the glucose ketone index as a as a biomarker to help evaluate this you
get the ratios and weary plotted her data and now it looks much more more
much more stable and we think this is going to be an effective way to do this
I also want to say that um we’re going to try to validate in in our GBM model
and the GBM people say it doesn’t attach that’s true it doesn’t it rarely come
out of the brain but if you take those cells and humans human cells can get
outside the brain
they spread through the whole the whole mouse just like this so this is mrs. GBM
outside the brain and it’s been reported and we have a so we can bioluminescence
the tumor cells you can see the liver full of cancer spleen as well so what we
did
this is our new unpublished study look at how beautiful the body weights are
now this is a ketogenic diet kitchen that the mice to lose weight a little
after a while so it’s the one that dominic and Angela we all use we keep
the body weights really tight
standard unrestricted restricted ketogenic diet unrestricted glucose is
high and the unrestricted groups and low in the restricted groups
look how high the ketones go when you restrict the ketogenic diet if you can
get those ketones up they’ll be toxic to the tumor cells
sure they go up if you eat ketogenic diet all but they but they won’t go up
as high unless you restrict and the g ki is the lowest and here’s the results now
uh you can see that a standard diet restricted had no effect in this tumor
in this tumor because we think it’s using glue to me and now you know Jenna
diet restricted had
best effect and unrestricted replicates with dominic and Angela found yes there
is some effect but the best effect is when you restricted diet
the important thing is the blood sugar here and here is the same but the
therapeutic benefit is much greater in the restricted diet
we did a linear regression analysis as as the key glucose ketone index goes
down
survival of the mice goes up so it validates that this gk I could be
effective
we also know the 25-percent of brain cancer patients die for metastasis to
the brain
the restricted diet significantly reduces metastasis to the brain
the problem is that these tumor cells are mutated these these mutated tumor
cells will not be able to adjust the rapid shifts in dietary conditions
calorie-restricted diet and restricted raw vegan diets one or the other
putting on the press the pulse are drugs
hyperbaric oxygen procedures non toxic drug targeting for glucose including me
most of what we’re talking about so far is targeting glucose and elevating
ketones with the hope that we’re going to stop this disease
we got to hit that glutamine if we don’t take care of the glutamine we’re not
going to be completely successful and this is a problem
it’s so much more difficult to target luda me that it is the target glucose
conclusions
cancer is more of a minor chondral metabolic disease than it is a nuclear
genetic disease and until this becomes more widely known and recognized
we’re going to be we’re going to see those numbers go up the body count is
going to go up
preclinical in case report studies indicate that restricted diets can be
effective non-toxic metabolic therapy for managing malignant cancers and
children and adults the g ki index can predict the success of a metabolic
metabolic therapy for cancer
I’d like to thank all of my many collaborators that are here Angela
dominic and Joe maroon Jeff Bhasker equal replace tempted on this on the
schedule that the funding agencies my own recent my own institution
George you foundation was very interested in this travis kristofferson
single cause single cure fund foundation
so these are the small organizations that are helping us continue to do this
because i am i am convinced that we will be successful in managing cancer without
toxicity
thank you for your time
yeah
thank you
thank you very much thank you I appreciate that
any questions
Susan yes
the lesson is referred and everything she had
would you like
materials and I
the game a little simple instruction manual for you
well she just
anyway so it’s only me
just last week I’m going to have surgery
visit you were going to occur cetera and so the question is do you know if
possible can survive this
at this point down in your room tours we heard entry operator
genetic testing
I don’t need oh I’m just letting you know
well you know hope we never say there’s no hope
we know people who have gone who had advanced cancers who went on this we we
don’t cure but we give a higher quality of life
i would say that we that the metabolic therapy if done correctly can give
people a longer period of time at a higher quality of life
I don’t think it’s possible to stop this tumor at that stage with with with a
ketogenic diet alone if they’re going to do a hyperbaric oxygen
you have to have that that that that has to be in up in a high ketosis state it’s
a little risky because it but it can work at this advanced age
Andrew uh-uh Scarborough is showing it we have other people that are showing I
think Mindy LOL had some very good success with this
there’s always hope we’re not saying we can cure but we can certainly delay
until we can knock out that glutamine I don’t think we’re going to be able to
cure this disease but if we had a drug which we don’t yet have that could work
I think the op the hope and the prognosis would be much better
ok maybe I meet with that lovely
a lot of success in my view you varies community activism moving off the start
with petitions
so what are you ready
is writing letters of my popular places dinner tonight and
he wants to design
for trying to get it died at least natural
whatever the going down the problem is cancer
you think some love and the doctors are all
let him find diamonds that someone drugged you know last month maybe five
different alternatives you know Susan don’t know but that’s just the person
themselves that individual has to make this decision
okay that that person ok
and that’s the way it’s going to change yeah I know because you know sometimes
we do all we can
and if the person is not there it’s just it’s just that there’s a commitment that
it has to be an understanding these are very difficult everyone is a unique case
you know the family has to be involved because the whole family has to
participate in there why them while they’re misguided and there’s an
institutional barrier to this so this is a tough this is a very tough situation
I know I don’t know I think you have
stand top is always you have been arguing against the vagine document for
use
very good
as their response from the gorilla in the room
yeah
I mean probably
you know the have you ever been to Nico Japan the monkeys
hear no evil speak no evil see no evil that’s what you get
you’ve been noticed well this man
there’s behind the door response all right that that we we know about yeah
maybe Travis can tell you about the behind the door response on this but you
know it you’re threatening up a whole establishment here
I mean let’s be honest you know what do you think they’re going to run out the
streets and say hey let’s drop our our new up tivo on our commercial putting it
on the wall of the series trade at this year’s building in Chicago
I mean this is it is you can use this is a big problem but a table there’s ways
to get around it with with global budgeting
there’s a financial incentive to do some of this under the Obamacare or some
derivation of that that might fall in fact that the Democratic the got the
poor Democrat who doesn’t get anything from from Baltimore there
I saw him on the debate the other day I don’t know what even know what his name
is he’s always behind the other two you know but he casually he actually said
we’re using this kind of a therapy or this kind of a of a strategy and i found
that whoa it
maybe we should look at that guy a little a little more I know what’s his
name there the guy from Bolton o’malley s
maybe we should take another look at mr. O’Malley ok
so talk about water straight to my readings
you know what we need when it doesn’t
what we do
or we are drinking waters fine just fine
water and that’s how and line and and actually I’m just like you
I you know I think it’s an extremely important issue it may work orally with
the diet
I haven’t tried it i would love to try it these are some of the things that if
we had the money we could do you get what you know that’s the problem
and as adrian and i have no is it easy to get money for this Adrian
yes you know that’s the situation just a very unusual
we have been using it
and I up front and wait about that physicians are pretty years rewarded
they were not going to go a little child based on our work and patience to
mention one elbow said they were
why are obligations and is well positioned
exactly the same thing necklace
it was pushing it was the asian parents and push it
so I think that’s where the power is and everyone
community we have previously so much energy so you have any expectations in
order to push things and do things
it I agree and I want to thank you for the work that you’ve done at that that
the Barrows because you’ve been an instrumental force and and then pushing
this forward thank you
that’s Adrian check barrows but they have barriers neurological center in in
phoenix arizona
very very very
I to a free and West castro and hanging there’s a lot of
: you’re working others and discussion
about a three
operation so the information you just presented
the is there a significant difference in how you manage a two or a three girls or
more delivery
no I think we would use the same strategy
basically the those have you have a lot more to play it play around time that
the tumors grow much slower so so the issue is can you make them grow even
slower and if you can get them even to a slower growth
can we move in with a hyperbaric oxygen in certain drugs that will work
synergistically with the diet too kind of polish those those cells off so you
know that’s my strategy that’s what I would do
but as I want to say this is an exterior in a very infant stage of this procedure
we’re at the very beginning of this new phase of of managing cancer and this
things that we don’t yet know and we learned a lot from just single patients
and how they responded the data that we get back from them so but but you can we
can definitely I think I don’t want to say for sure we don’t know anything
until be to actually get the data but we can slow those tumor cells down and then
we would work through a strict strategy to keep them under control
grass spend a little time this
one of our education and respected as a preacher
and
second edition expected to continue to grow and she’s one of the two then
fine because it is
it was great so sorry just making a statement about it
I gone three standard of care and i found out about you jack
diet during the following chemo and what I went through
follow on people anxious reduction in my brain tumor size . now work
its accuracy means obviously is a grade
also discussed baston i am very good
graduate as a GM advisor survivor yet recurrences of is ready to work very
protective order to find us
he actually
production
besides it
and basically not detectable on skins
q GBM recurrence so it
it really doesn’t yeah what we want to make sure it works better
you know that that’s that’s that this is a good first step but the idea is can we
can can you come back in 25 years and so you know one time when I was a young man
I had this tumor
yeah you know that
yeah yes sir
these people act skirt and
to go it is unlikely right right well good luck to you and you and thank you
for sharing that with us
thanks to my questions about the calorie restricted the ability to be romantic
difference between here Jenny
today how do you measure
the test
that all the details but you do
yeah seventy-five percent next
ya know it we we had to struggle with that for a long time
basing it on because calorie just heard about the calories last night about
their different metabolic effects we use body weight body weight is the is the
independent variable is we restrict both groups whether regardless of what
they’re eating
we make sure that they have exactly the same body weights and that gives us a
clear indication of what’s of what’s working or not
so it’s we use because the bottom the body is the bomb calorimeter the body
tells you what you’re going to burn and then and the mice have a regulated a
body weight
so if you and that’s how we learn if your calorie restricted ketogenic diet
based on on on on calories and you give the same amount isocaloric the body
weights are very different
the reading isocaloric diets but their body weights are different
what’s going on with that we know we’ve heard all this business so you make sure
they have the same body weight and then you can vary this see which one is
working so we use body weight
here
and
musicians and we know that does these vehicles is waiting
wait you find day that we met
roughly way the that’s why we have to manage this disease quickly
all right these diets are not that they’re very hard to sustain in two
years so we we have to do this weight loss will always this is a weight loss
time we have all these guys out here telling us about all this stuff
I mean you’re losing weight it’s a therapeutic weight loss but we had but
we don’t like Trudy there she had to get off the diet to regain the weight
all right but you can shift from one kind of a diet to the other kind of a
diet to try to maintain the weight and you’re absolutely right when we did the
published paper
we didn’t know all right we were based on a powerful calorie restriction but
you’re absolutely right
you can get the same results with much less calorie restriction as long as you
can keep the ketones as high as you can get them all right you’re absolutely
right this is why we have to fine tune the system we are
he is the ad and me not you know it’s not that they’re not be at the surgeons
they’re cut they’re not trained this but they don’t get this training in their
medical education
okay you’re taking as somebody who’s been trained highly probably skilled
professional and they’ve never heard of this stuff
what what’s going on with the training program there right
why are they not getting that is a major course instead of learning about how out
tens column is going to be used for one of these other drugs
so it has to change ok who writes the curriculum for the medical schools and
who’s doing that figure out what the ok let’s change the curriculum we do it at
the University all the time
the core curriculum is always changing based on what’s going on in the world
you see is on board
it yeah well maybe that’s needed more you
you will
how to make sure where I’m going you know ok
Dank Alex. De techniek staat niet voor niets tegenwoordig 😉
Gelukkig niet Andreas. 🙂 Mocht je tijd/zin hebben om alsnog de tekst na te lopen op rommel, dan houd ik je uiteraard niet tegen, maar voor nu moet het goed zijn. 😉
Laten we eerlijk zijn, het maken van een transcript is niet gemakkelijk. 🙂
Hier is de door mij gecorrigeerde versie van de eerste 11 minuten:
“Well, thank you very much Tom and Angela for organizing this and inviting me here and have this opportunity to give you guys an update on some of the things we’re doing in our attempt to manage cancer and I’ll be talking about some fundamentals of the disease and then I’ll give you an update on some of our unpublished work with mice and with people.
We always have a reality check and update what’s going on in the world of cancer, we have the latest that just came out projections for 2016 I don’t expect you to see the details of these numbers I only want you to know they’re big and they’re getting bigger.
Alright, so we have the 2016 we have 1.632 people a day dying from cancer. We’re not really sure how many of these people are dying from the cancer or from the treatments that they used to treat the disease. This is a very difficult question. And we also recognize now that brain cancer in children pediatric brain cancer has replaced leukemia as the number one killer cancer killer for children.
So this situation is not good and something has to be done. So we have a question and this is a provocative question that needs to be addressed in relationship to the origin of the disease. I think if we better understand the origin of the disease, we will have a better chance at managing and preventing the disease.
All right, so is cancer a nuclear genetic disease or is it a mitochondrial metabolic disease?
The question is weighted. OK, is the disease resulting from defects in the nucleus of the cell or is it resulting from defects in the cytoplasm and in particular the mitochondria, that we’ve heard a lot about it this meeting, of the cell?
This is a very important question because it will determine how we approach this disease but with respect to Natalie management but with respect to prevention.
All right the current dogma: cancer is a genetic disease and the hallmarks of cancer by doctors Hanahan and Weinberg have solidified this over two major papers in 2000-2001 some of the most highly cited papers in the field of cancer. Cancer cells carry the oncogenic and tumor suppressor mutations that define cancer is a genetic disease.
A dogma is an irrefutable truth. It’s a concept that is no longer challenged or investigated because a dogma is solid and how do I know this is a dogma, how do we know that it’s a dogma when we teach general biology, cell biology and biochemistry at the college level and you look at the sections on cancer, cancer is a genetic disease.
There’s no other discussion about it. You go to the NCI website ‘cancer is a genetic disease’, there’s no discussion about this. This is a dogma.
The foundation of the dogma is the somatic mutation theory and that it solidifies the dogma and they use these simplistic diagrams, a car that has no brakes and the accelerator is maximally forward to replicate or to simulate what goes on in a population of cancer cells. Here these cells are at a control. Cell division out of control, they have no brakes and their growth acceleration is out of control and you have this situation.
So, add a control cell growth, dysregulated cell growth, is the signature feature of this disease, regardless of what tissue or organ it happens to attack.
Then we place the hallmarks of the disease, as Hanahan and Weinberg have done, in this
the six major hallmark: sustaining proliferation of aiding growth, activating invasion and metastasis, enabling replicate of immortality, inducing angiogenesis and resisting cell death, all the result of nuclear-driven oncogenes and tumor suppressor genes.
Now, in the most recent rendition of their paper, we now entered into emerging hallmarks, hallmarks that have not yet reached the big six. So this concludes this regulated cellular energetics and avoiding immune destruction. If you read their paper in detail, it will say this regulated energetics is now considered an emerging hallmark that is programmed by proliferating inducing oncogenes. Preserving the dogma, ok, this preserves the dogma
because we’re saying okay you can have this dysregulated energy metabolism but
the oncogenes are controlling it. Everybody’s happy.
All right, now we have here is another situation, normal chromosomes normal cell, now all of a sudden cancer arises from a series of our chance mutations in different genes in different places and they say maybe for nobody really knows how many genes are responsible for the origin of the disease. Some people say 1, 2, 4. Michael Stratton his group predict that complete cancer genome sequence will eventually identify 700 million
mutations. Alright, several of these driver genes and passenger genes and all this
kind of stuff and they are calling in a Watson, right, the IBM computer down to
MD Anderson (Cancer Center) to try to figure out what’s going on with all these genes. Good luck to that.
Now here we have a person staring into a screen, individuals cancer cells are genetically tested for personalized therapy. She’s going to look at these images and breast cancer cells being examined to see if they possess extra copies of a particular gene and based on that genetic information, they’re going to either make some sort of a prognosis or
they’re going to elicit some sort of therapy and we know from President Obama’s speech a couple of weeks ago and he emphasized in a State of the Union speech ‘personalized therapy is the way we’re going to manage this disease and we’re going to have the honorable Joe Biden lead the charge’. Now I believe Joe Biden has a good heart and I think because the loss of his son to glioblastoma, he has an intrinsic interest to do something about managing cancer. The question is, is he going to receive the information related to the dogma or maybe he might want to consider other options or other possibilities and this is what we don’t yet know.
Now, one of the most important things about cancer is metastasis, this is what ultimately kills almost all the people that have the disease either that process itself or in the attempts to stop that process. This is a diagram here, you have the cancer cells and they go through this cascade, it’s a very stereotypical cascade, regardless of where the cancer comes from, if it comes from the long, the colon, the breast, the bladder, it goes through the cancer cells invade. OK, these green cells they break through the basement membrane and enter into the local tissue, then they intravasate, enter into the circulation. These are very sophisticated biological processes by which this happens. Immune systems for survival, ok, how come they’re surviving the immune system? We’ll come to that later on. But then they immunosuppressed the immune system and they extravasate, they leave the bloodstream and enter and form these * distant colonization which means that you can’t cut this out there, spreading all over the place so it becomes a very difficult disease but this is a very stereotypical pattern.
Now according to the dogma, the epithelial-mesenchymal transition is designed to explain this, chance mutations happen in these cells, the cells through these chance mutations enter into the bloodstream and then many of these effects of the chance mutations become reversed in some unknown way and then they start replicating the way they were before they were actually entering into the bloodstream.
Now I don’t know how a bunch of chance mutations could constantly produce a
very sticky or stereo typical pattern, how do chance events cause a non chance event.
I don’t know.
Now we have a problem. How can we advance new metabolic therapies that the 800-pound gorilla who thinks cancer is a genetic disease and who is the gorilla, the National Cancer Institute, academic and pharmaceutical cancer industries. Dogma rules. If you want to come up with a new therapy, you better make sure it’s associated with dogma. Now we can say we don’t need to do that and we can putz around here with these
metabolic therapies, but they will be always be on the periphery, they’re not going to be mainstream until the gorilla unasses the room. Now, how are you going to do that?
All right, you can just do it by continuing to do what many people in this room are doing or you can try to undermine the dogma with the evidence that exists and this is what I’m trying to do, through the scientific argument and the debate related to this disease.
So, let’s look at the evidence that challenges the somatic mutation theory. Okay I’m going to go through a series of experiments that were done over the years that are inconsistent with the dogma. This work was done by dr. McKinnell who I had the opportunity to talk to at the University of Minnesota, a professor emeritus at the University of Minnesota
and he did these studies way back in 1969 where he had this, a very aggressive renal tumor in the frog. It’s a lethal malignant tumor, it comes from the kidney and the luck
frog, what what dr. McKinnell did, is he took the cell out of the tumor, removed the nucleus from the tumor and put it into a enucleated fertilized egg that had normal cytoplasm.
So you take the nucleus that has the tumor suppressor genes of the abnormal oncogenes with defects and you put it into a new cytoplasm and he generated this tadpole. Alright, there was no dysregulated cell growth in the tadpole. You could cut the tail off, the tail would grow back. The problem is the tadpole never could mature into a fully differentiated
mature frog. So there was something in that cancer nucleus that block development but it
certainly didn’t cause the signature defect which is this proliferation.”
De rest is voor de liefhebber, met tijd over. 😉
Grant Schofield over de briesende, Foodloggiaanse en Volkskranteske aanvallen op Paleo in Australië en Nieuw Zeeland:
http://sciblogs.co.nz/guestwork/2016/08/09/anti-paleo-attacks-miss-point/
In de “alternatieve” of “complementaire” kankerbehandelingswereld wordt al bijna tachtig jaar geaccepteerd dat kanker ontstaat daar waar cellen structureel in erbarmelijke omstandigheden verblijven. Door deze erbarmelijke omstandigheden worden via epigenetische transformaties de zgnd oncogenen aangezet en gaan de cellen in hun strijd om te overleven over op totaal ander gedrag. Cruciaal in deze oncogenesis zijn met name hypoxia, chronic inflammation en vaak ook verzuring van de extracellular matrix. Het is uiteraard een complex verhaal, maar als er 1 sleutelfactor aangewezen moet worden in het ontstaan van kanker dan is het een structureel (intermittent) gebrek aan zuurstof. En als zuurstof slecht/niet voorhanden is, waarom zou je de mitochrondien dan nog laten functioneren? De epigenetische switch naar kwaadaardigheid is inderdaad fundamenteel metabolisch van aard.
We eten met z’n allen verkeerd, omringen ons met enorme lading toxische stoffen en andere zaken (electromagnetische straling?) en ondertussen wordt gezegd dat je gewoon pech hebt als je kanker krijgt.
Een mooi paper van Gatenby en Gillies over carcinogenesis:
Klik om toegang te krijgen tot 0a85e53a172346ec26000000.pdf
Ja, dat is overigens een explosieve kwestie. Je hebt natuurlijk vette pech als je het krijgt, maar het is me zeer duidelijk wat je bedoelt. Voor mijn boek probeer ik die pech-vraag tot op de bodem uit te zoeken, omdat mensen het verwarren met schuld. Alleen al het aansnijden van de vraag – hoe genuanceerd en voorzichtig ook – lokt heftige emotionele reacties uit. Aan één van de meest vooraanstaande paleopathologen ter wereld heb ik de uitspraak ontlokt dat kanker er altijd is geweest en er altijd zal zijn, maar dat het voor de landbouwrevolutie ontzettend zeldzaam was, ook onder mensen die ouder werden. Zijn bevindingen reflecteren wat je ziet in contemporaine jager/verzamelaars.
Fermentatie is een oeroud programma om cellen door periodes van zuurstofgebrek te helpen, alleen bijt het ons in de habitat die we hebben gecreëerd in de gat. Of liever gezegd, het wordt ten onrechte getriggerd en schiet uit de bocht.
Het vermeende gelijkstellen van oorzaken en schuld is erg lastig in de communicatie. Dat ben ik helaas maar al te bekend mee. Als ik over dit soort zaken praat met mensen, dan probeer ik altijd ontzettend duidelijk te voorop te stellen dat er geen sprake is van schuld.
Kanker lijkt mij overigens absoluut een evolutionair voordeel te hebben. Als cellen in een slecht voorziene microomgeving door wat voor reden dan ook moeten kiezen tussen het vormen van een tumor of een nasty celdood, dan denk ik dat, door de lokale erbarmlijke omstandigheden, celsterfte tot acute (dodelijke) problemen zou leiden. Het creeeren van een tumor (een soort afvalvat) geeft het organisme in kwestie nog tijd om zich (verder) voort te planten
Personalized Medicine is niks anders dan een manier om de kosten per patient hoog te houden en de miljardenslurpende kankeronderzoekscentra ad nausea draaiende te houden. Als je hele werkende leven bestaat uit het zoeken van een oplossing, zit je dan ook echt te wachten op de dag dat die gevonden wordt?
Cynisch? Wellicht, maar hoe ik er ook naar kijk, dat is wat ik zie.
Helaas, zo is het. Het is de grimmige realiteit.
Je zou kunnen zeggen dat het spreekwoord “De een zijn dood is de ander zijn brood” inmiddels achterhaald is. Sterker nog we kunnen tegenwoordig stellen “De een zijn brood is de ander zijn dood” als we naar de lezingen van o.a. alessio fasano kijken.
Weinig cynisch aan overigens. Ik heb het helaas van zeer dicht bij moeten maken en je komt letterlijk in een hele andere wereld terecht.
Melchior, ik ben op zoek naar de lezing van een professor, met een poolse naam?, die de relatie legt tussen voeding en depressie. Stond op je blog. Kan je helpen?
Grapjas. 🙂
Sapolski? https://melchiormeijer.wordpress.com/2014/07/07/paleo-tussen-de-oren/#comment-25975
Thanks Alex. Dat het zo Pools was, wist ik ook niet meer 😉
Ik heb reeds eerder de interviews van Dominic en Andrew met Damian geplaatst. Goed te volgen mede dankzij transcript en show notes. Deze is ouder, maar zeker niet minder interessant.
https://thequantifiedbody.net/water-fasts-as-a-potential-tactic-to-beat-cancer/ Thomas Seyfried
Hier een evolutionaire beschouwing over kanker van een professor natuurkunde, onder het motto dat biologie (en dus ook kanker) alleen vanuit evolutionair perspectief te begrijpen valt.
Zoals ik eerder aangaf: Cancer loves hypoxia, glucose, and acid. Hypoxia is DE cruciale factor in het ontstaan en verbreiden van kanker (vooral Hypoxia-Inducible Factor 1alpha). Stuhr en collega’s (Universiteit Bergen, Noorwegen) hebben al aangetoond dat hyperbare zuurstof betere resultaten geeft dan 5-FU (een specifiek chemo). En daarnaast zou ik vooral willen wijzen op Ozon, het superzuurstof dat in het lichaam een enorm medicinaal effect kan hebben.
Schijnt een belachelijke theorie te zijn van Davies in bovenstaande video…
Totaal uit de bocht gevlogen.. Een voorbeeld van onnozele afzwaaiers van wetenschappers die op hun eigen terrein succesvol zijn (geweest). En dan vanuit grootheidswaan denken zomaar in andere gebieden even een kunstje te flikken wat grootheden op dat gebied nog niet konden.. Even Guus Hiddinkje spelen.
Bovenstaande is niet mijn kennis maar de weerslag in deze onderstaande link.
http://scienceblogs.com/pharyngula/2015/12/06/the-haeckelization-of-paul-davies/
hahahahahahaha what a load of crap, Reminiscent of the Dutch crap detectors die de natuurlijke geneesmiddelen allemaal op een hoop gooien als wishful thinking. Allemaal in de dienst van Big Pharma.