Oct 01 2012
Mouse “avatars”: New predictors of response to chemotherapy?
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The story of 9-year-old Michael Feeney made me very sad, especially after I read this in the NYT article:
“The results came back in July. A combination of four drugs — gemcitabine, docetaxel, Avastin and Afinitor — was “astonishingly active” in shrinking the tumor in the mice, said Michael’s oncologist, Dr. Leonard H. Wexler of the Memorial Sloan-Kettering Cancer Center. Dr. Wexler said that the combination was not something oncologists would typically choose.
Michael has not tried the combination yet because he is participating in a clinical trial of an experimental drug. But if that drug does not work, his mother said, “we have the home run in the back pocket.”
The mother thinks her child is cured no matter what. It makes me sick that Champions Oncology thinks it’s alright to sell this level of what could be false hope to a child and their family. If avatars were touted as the experimental procedure they are, patients would probably keep a reasonable expectation of treatment outcome. Also, no one should have to pay for experimental therapy.
Hi Dr. Gorski –
I saw this @ RI and meant to comment how much I appreciated this post. Very interesting stuff. Thank you.
- pD
I think I’ve listed other companies where they offer to test cell lines but am having a hard time finding that today. Then there are companies that just sequence your tumor.
None of these people are proposing trials though, which seems terribly wrong. Try just one tumor type, and perhaps just one targeted therapy, and see if you can predict who will be helped by that more than conventional treatment – that’s the way we usually do research. It’s slow, but you end up with knowledge that is instrumental.
Aside: I am starting to have a problem with the word “predict” and “predictive” out there in the wild. Always say what you mean – predictive of what. I’m not saying that wasn’t done here, just grabbing my teachable moment. A marker can be associated with outcome (be prognostic), and we might say it predicts outcome. Statisticians often mean something much stronger though when they say a marker is predictive: they mean that high marker means more difference (or less) between two treatments than for low marker – it’s an interaction between a marker and the treatment effects. When true, it can be useful for saying what treatment you should get. Note that if a marker is prognostic, that doesn’t mean it is predictive in the strong sense – you don’t have data to demonstrate that usually, and need to do a study. (For example, should “bad” folks be treated more, or “good” folks less, or even good folks more – we don’t know. We can guess, but that’s not evidence, and the docs will often disagree about what we should try.) Conversely, if a marker is not prognostic, that doesn’t mean it is not predictive in the strong sense (useless to assign treatment). I see seasoned researchers make mistakes about this all the time, and discredit themselves (to perhaps 10-30% of the people who know better). There’s also often an assumption that a marker (or set of markers) that is prognostic is a good bet to be predictive in two particular arms of a trial – even if it was not designed to be useful in the particular case of those two treatments. That’s just trying to get lucky. Yet people ask me to do exactly that rather often (I forgive them somewhat – we want a function of the markers that is pre-specified before we do the study if possible, so we can randomize based on that function, as opposed to hunting for associations among perhaps hundreds of markers post-hoc.)
Anyway, watch it when people say “predict” and you aren’t sure what they mean.
This is so cool! Thanks for adding a bit of moderation, Dr. G.
I wish I had the money to run some of these experiments…
Best,
-David
Why is it getting more expensive to maintain a pool of lab animals?
Redox Signaling Molecules and ASEA
ASEA
Let’s start at the beginning.The human body is made up of somewhere in the range of 100 trillion cells. Within each cell are mitochondria, which are responsible for the creation of energy by way of what is called the Krebs Cycle. This process entails the conversion of glucose to ATP. The byproducts of the Krebs Cycle along the Electron Transport Chain are what are known as redox signaling molecules (“RSM”). Originally, scientists perceived these byproducts as metabolic waste – oxidants and reductants that must be purged from the cell in order to remain healthy. However, current research suggests otherwise. That in fact a proper homeostatic balance of oxidants and reductants is absolutely necessary for maintaining cellular health, including virtually all of the functions of the immune system and tissue regeneration response.
In the most simplistic terms, they provide a means by which cells
participate in intra- and inter-cellular damage-control
communications, activation of antioxidants, cellular protection and
defense against toxins and free radicals, and in the healing
response. The human body is constantly working to maintain cellular health by balancing these redox signaling molecules to rid the body of harmful components and to clean up the oxidative stress and free radical damage that occurs at the cellular level, while simultaneously ensuring the cell’s ability to maintain proper
communication with its environment. When these reactive molecules are in the proper balance, the immune system and healing process function at their optimal level.
Virtually all disease and bodily challenges are caused by what is
called oxidative stress – a increasingly salient reality of living
in modern times attributable to a wide variety of factors, including
sun damage, excessive exercise, electromagnetic radiation, food
additives and preservatives, x-ray radiation, prescription drugs,
heavy metals, stress, anxiety, air & water pollution, lack of
sleep, and toxic industrialized chemicals to name a few. These
factors cause our cells to produce an excess of oxidants in
comparison to reductants – thus throwing off the cell’s
homeostatic balance of RSMs and promoting the proliferation of
harmful free radicals. But this imbalance is how the cell detects
damage and is signaled to repair itself. The immune system is
summoned, prompting repair, or replacement of the cell via mitosis (cell division) of a neighboring healthy cell. Without this excess of oxidants indicating oxidative stress, the cell wouldn’t know to reach out for restorative help. Too many oxidants leads to a proliferation of damaged cells. But too few oxidants impairs the cell’s ability to signal an immune response and to repair damage. Therefore, balance – homeostasis – is key.
However, chronic oxidative stress leads to a
proliferation of free radicals that unless neutralized, lead to cell
damage that will continue to worsen – damaging the cell walls,
vessel walls, proteins, fats and even the DNA nucleus of our cells
until the cell can no longer properly function. The result advances
the aging of tissues, leading to poor health and the potentiality for
degenerative disease.
It is for this reason that we are constantly inundated with the
health benefits of anti-oxidants. The idea is that these molecules
combat the proliferation of free radicals in an effort to bring the
cell back to healthy homeostasis. But herein lies the rub. First,
most antioxidant supplements are molecules far too large to pass
through the cell wall, averaging about 200 atoms in diameter.
Therefore, most (some scientists estimate about 90%) are denied entry to the place where they are needed most – inside the cell where the free radicals are found. Second, one anti-oxidant molecule is empowered to combat one free radical molecule before becoming essentially inert. It is thus a 1:1 ratio. However, the body generally harbors about 100 sextillion free radicals a day. That’s a heck of a lot! Due to this restrictive 1:1 ratio, scientific studies show that your body can’t possibly ingest enough antioxidants to eliminate the number of free radicals your body makes every day. For example, you would have to eat 32 pounds of strawberries, 31 pounds of raspberries, AND 15 pounds of dark chocolate per day to achieve the antioxidant power that it would take to eliminate the free radicals that are created naturally in the body.
ASEA
This is where ASEA comes in – as the first and only RSM
supplement. As stated above, stable RSMs are central to the body’s healing mechanisms, mediating multiple cellular defense, repair & replacement signaling pathways. ASEA purports to have determined a completely stable, balanced, bio-available and entirely non-toxic formula of RSMs native to the body that can effectively penetrate the cell wall (unlike most anti-oxidant supplements), efficiently combat free radicals, stimulate the body’s production of its own anti-oxidant defenses, and stabilize the proper homeostasis of oxidants to reductants to optimize cellular communication, repair, and replacement, thus enhancing the body’s ability to properly function, recover, and simply work as designed.
Moreover, independent studies show that ASEA when in contact with living cells increased the efficiency of some of our body’s most important native antioxidants inside living cells – such as
glutathione peroxidase and superoxide dismutase (SOD) — more than 500%. In other words, ASEA is purported to significantly stimulate the cell’s own production of the master antioxidants inside the cells without causing an inflammatory immune system response.
What does this mean?
It means that the body becomes empowered to
neutralize approximately 70,000,000 free radicals per second — the rate at which native Glutathione Peroxidase is able to process
oxidative free radicals. Quite an improvement over the results that can be achieved by a diet rich in anti-oxidants.
“Asea merely enhances the body’s innate ability to repair itself”
Article obtain from http://pure-healing.info/redox_signaling_molecules_and_asea/
@aeolis,
You posted this on the magnesium thread also. Please take your commercials elsewhere. If you have any actual evidence that ASEA is anything more than salt water or that it has actual clinical benefits to patients, please post your comments on the ASEA thread.
I think that ASEA has about as much science behind it as Radithor did.