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Cancer Cured in Mice


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#1 MichaelAnissimov

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Posted 09 May 2006 - 01:02 PM


See this link:

http://www.wesh.com/...673/detail.html

#2 rahein

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Posted 09 May 2006 - 02:51 PM

Michael do you have a link to the study or anything else. This story is by a local news station and gives no referances.

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#3 rahein

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Posted 09 May 2006 - 02:53 PM

I found it on the BBC

http://news.bbc.co.u...lth/2982525.stm

#4 FunkOdyssey

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Posted 09 May 2006 - 03:20 PM

Why isn't this all over the news?

#5 Live Forever

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Posted 09 May 2006 - 04:03 PM

Why isn't this all over the news?


Probably cause of this statement from the BBC article: "There are no immediate practical benefits to humans"
They (apparently) just bred a new strain of mice that was resistant to the disease, which, although impressive, isn't the same as being able to cure mice who have cancer, or prevent cancer in regular mice. We already know of species (sharks for example) that can not get cancer, it is the ability to cure or prevent cancer in species that can get it that would be a major breakthrough. (imo)

#6 John Schloendorn

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Posted 09 May 2006 - 04:20 PM

The BBC article (cancer-resistant strain) is from 2003. There does not seem to be a publication out yet on the new result (immune therapy using the resistant strain's cells). I would imagine that a super-blood stem cell transplant conferring resistance to cancer, atherosclerosis, HIV and others, based only on naturally occuring, rare alleles might make a rather glorious biotech product in the mid-to-late 21st century...

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#7 FunkOdyssey

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Posted 09 May 2006 - 04:54 PM

Why isn't this all over the news?


Probably cause of this statement from the BBC article: "There are no immediate practical benefits to humans"
They (apparently) just bred a new strain of mice that was resistant to the disease, which, although impressive, isn't the same as being able to cure mice who have cancer, or prevent cancer in regular mice. We already know of species (sharks for example) that can not get cancer, it is the ability to cure or prevent cancer in species that can get it that would be a major breakthrough. (imo)


You must have only read the 2003 BBC article. Here is the relevant text from today's news story that Michael linked to in the first post:

Now, they said white blood cells from that mouse's descendants were injected into ordinary mice with cancer and their disease was completely wiped out.

The treatment worked with a variety of cancers, including those similar to end-stage human cancers.

“This is a really remarkable recovery from a very aggressive tumor,” Wake Forest cancer researcher Dr. Zheng Cui said.

The mice did not suffer any side effects from the treatment. They had no problems with rejection.

The goal now is to find a human treatment that could avoid the rejection problem by using a patient's own cells.

White cells from a cancer patient would be combined in a test tube with the specific anti-cancer gene and then given back to the same patient.

“The hope would be that those activated white blood cells would be able to treat that person's cancer successfully,” Wake Forest Pathologist Dr. Mark Willingham said.

In mice, the white blood cells were able to find the cancers no matter where they were located in the body, suggesting that the cancer cells produce some kind of signal that the killer cells can detect.

The treatment also worked with naturally occurring cancers.

Next steps include trying to determine exactly how the cancer-fighting mechanism works, and Wake Forest researchers are working on a specific test that can indicate cancer resistance in humans.

A cure is still a long way off, but they believe that, like mice, there are humans out there with genes to fight cancer.

For example, out of all people who smoke, only a small percentage get cancer. What keeps them safe is still unknown.


That seems like big news to me.

#8 Live Forever

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Posted 09 May 2006 - 04:57 PM

Aaah, you are right, I just read the BBC one. Thanks for the correction guys. (and sorry!) [wis]

This is indeed tremendously big news!

Looks like the story has been Dugg. [thumb]

#9 RighteousReason

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Posted 09 May 2006 - 06:25 PM

That's right, put away the steel toed boots

[sfty]

#10 Mind

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Posted 09 May 2006 - 06:30 PM

John:....might make a rather glorious biotech product in the mid-to-late 21st century


I tend to think it would be developed sooner than mid-century, more like a couple decades or less.

#11 John Schloendorn

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Posted 09 May 2006 - 06:43 PM

Well, there are a number of key issues that will require unforeseeable creative breakthroughs (e.g. sustainable large-scale sources of stem cells and immune cells, safe bone-marrow transplants, reproducible tolerance induction, regulation of not-so-medical "enhancement" biotech products). So we cannot make very precise predictions there. In the case of cancer prevention (rather than destruction of existing ones) you'd also need to extremely long and large trials to assess the effect.

#12 RighteousReason

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Posted 09 May 2006 - 11:33 PM

Sean Hannity gave a lot of airtime to this tonight news article tonight.

#13

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Posted 10 May 2006 - 12:17 AM

This is the most significant discovery for a complete cancer cure that I have ever come across.

If there was the equivalent of a Methuselah Prize for a cancer cure this team would have won in it in 2003 when they first disocvered this mutant.

If it can be made to work in humans, and there is nothing to suggest that it cannot, it will mean that even the most advanced forms of cancer will be completely treatable by an injection of modified immune cells. Unfortunately, they don't know how it works yet and are only reporting on which components of immune cells transplanted induced the complete recovery.

They report more than one combination of immune cells will work whether they are derived from the spleen, bone marrow or peritoneal cavity so I suspect that the cancerless mutants carry a mesenchymal stem cell that is able to recognise cancer cells and rapidly program the host immune system to attack the cancer either by innate or adaptive immunity.

http://www.pnas.org/...ourcetype=HWCIT

I first read about the cancer resistant mouse in 2003 and I am very surprised that it has taken this research team 3 years to merely establish a simple fact (that a transplant of a component of its immune cells will mediate complete cancer recovery in a non mutant-mouse). The mutant mice should be distributed in research centres all around the world and millions of dollars of government funding be available to rapidly investigate the mechanism by which this effect is mediated and how it can be reproduced in humans. Since the mechanism remains to be discovered, pharma companies can also participate.

These mice are the most valuable experimental animals in the world.

#14 John Schloendorn

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Posted 10 May 2006 - 04:56 AM

Thanks Prometheus for the paper, this is exciting!

To dampen your optimism a little bit, bear in mind that there are considerable differences between mouse and human tumors. The most important ones of them derive from the fact that human tumors have more time and more cells, so they have greater potential to evolve against any type of treatment.
For example, a major histological difference between tumors in resistant mice and normal mice is that in resistant mice tumors were fraught with immune cells that killed them, while in normal mice there were litte immune cells in the tumor. Now in humans, it's actually normal to have tumors fraught with immune cells, but they are doing nothing, because the tumor has figured out some way to defuse them with various signaling molecules.
I think if one wants reliably target human tumors with an extrinsic therapy, one has to do it very early, before they have enough cells, time and genetic instability to effectively evolve against the treatment. The problem with that is that you don't know what the very early stages of a tumor look like, because you can't predict which cell is going to turn into one.

Still, I think immune therapy is the most promising anti-cancer approach we have. This is mainly because by nature, our immune system does not do much at all against cancer, as can be seen by the fact that people with severe immune dysfunctions have only very slightly increased cancer rates. So, unlike for example with augmenting cell-intrinsic molecular defenses, there is simply plenty of room for improvement in immune therapy.
Another question that rises is of course, why on earth did evolution not install even modest immune-based defenses in us, but did install extremely elaborate cell-intrinsic defenses? I really have no clue there. Ideas, anyone?

The fact that the trait is part of innate, rather than adaptive immunity is neat, because this really minimizes potential side-effects of transplantation (ie GVHD).

The claim of a normal life-span of the treated mice seems surprising, when it is so effective against naturally occurring tumors. How can life-span possibly remain "normal" when cancer is the major cause of death in inbred strains? The data is luckily not reported in the paper, because if it were convincing, it would in fact suggest severe side-effects to bring the life-span down to normal.

In sum, I tend to agree that these findings are highly promising and should be explored at full force.

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Posted 10 May 2006 - 12:13 PM

To dampen your optimism a little bit, bear in mind that there are considerable differences between mouse and human tumors. The most important ones of them derive from the fact that human tumors have more time and more cells, so they have greater potential to evolve against any type of treatment.


I'ts not dampened in the slightest. ;) My view is that it does not matter how much a cancer evolves, if it is expressing innapropriate genes then it will stand out immunologically and be a target for this type immune system reprogramming. Also MDR expression is not a problem since the treatment is non-chemotherapeutic. As for the size of the tumor, as you can see histologically, the reprogrammed leukocytes appear to penetrate deep into the tumor mass to mediate destruction of cancer cells indicating that the size of the tumor mass does not inhibit the anti-cancer effect. In fact as the authors state: "Another observation in this study was that large established solid s.c. tumors in WT mice completely regressed after transfer of SRCR leukocytes. This finding is remarkable given that reversal of this type of malignancy has, to our knowledge, never before been reported"

#16 kent23

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Posted 10 May 2006 - 12:53 PM

liveforever22 wrote:

We already know of species (sharks for example) that can not get cancer, ...


Sharks do get cancer. Here is the abstract from "Shark cartilage, cancer and the growing threat of pseudoscience."
Ostrander et. al. (2004) (italics mine)

The promotion of crude shark cartilage extracts as a cure for cancer has contributed to at least two significant negative outcomes: a dramatic decline in shark populations and a diversion of patients from effective cancer treatments. An alleged lack of cancer in sharks constitutes a key justification for its use. Herein, both malignant and benign neoplasms of sharks and their relatives are described, including previously unreported cases from the Registry of Tumors in Lower Animals, and two sharks with two cancers each. Additional justifications for using shark cartilage are illogical extensions of the finding of antiangiogenic and anti-invasive substances in cartilage. Scientific evidence to date supports neither the efficacy of crude cartilage extracts nor the ability of effective components to reach and eradicate cancer cells. The fact that people think shark cartilage consumption can cure cancer illustrates the serious potential impacts of pseudoscience. Although components of shark cartilage may work as a cancer retardant, crude extracts are ineffective. Efficiencies of technology (e.g., fish harvesting), the power of mass media to reach the lay public, and the susceptibility of the public to pseudoscience amplifies the negative impacts of shark cartilage use. To facilitate the use of reason as the basis of public and private decision-making, the evidence-based mechanisms of evaluation used daily by the scientific community should be added to the training of media and governmental professionals. Increased use of logical, collaborative discussion will be necessary to ensure a sustainable future for man and the biosphere.

John Schloendorn wrote:

Another question that rises is of course, why on earth did evolution not install even modest immune-based defenses in us, but did install extremely elaborate cell-intrinsic defenses? I really have no clue there. Ideas, anyone?


It hasn't had enough time to do so? It's had much more time (and a much larger population) with which to evolve single-cell quality control mechanisms (checkpoints, DNA repair, etc.)? Yeast don't get cancer. Maybe we should take yeast cartilage extracts...? Maybe cancer is smarter than evolution? What kind of mutations are there in the cancer-resistant mice? What kind of mutations give them such good tumor surveillance (if that's what they have?) Are there life span issues (antagonistic pleiotropy)?

(later...)

No life span issues, and the trait is supposed to be conferred by something dominant in a single autosomal locus. We need some trillionaire overlord to step in and have them sequence the entirety of whatever autosome they've got it down to...

Edited by kent23, 10 May 2006 - 01:15 PM.


#17 rahein

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Posted 10 May 2006 - 03:06 PM

I was watching CNN last night and this story came across the ticker at the bottom of the screen while they where discussing mine safety. I thought great they are putting more time and energy into saving a few people in a very risky (and polluting) job then saving everyone who has or will ever get caner.

We live in an F*ed up socity(USA). People fight aginst saving people in mass, but will spend billions on saving a few.

Last month there was a study that put the cure for cancer worth $50t for the US alone. You would think they would *AT LEAST* give a few labs $1b a piece to work on this breakthough.

http://www.eurekaler...p-cfc042606.php

#18 theone

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Posted 10 May 2006 - 04:11 PM

I have also been following this for the past three years and was wondering what ever happened. The fact that they can transfer this immunity to ordinary mice is breath taking. Like the previous post above I also believe billions should be put into researching this ability immediately. Finding the specific genes responsible for this immunity should not take long with proper funding.
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#19 John Schloendorn

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Posted 10 May 2006 - 04:28 PM

why on earth did evolution not install even modest immune-based defenses in us, but did install extremely elaborate cell-intrinsic defenses?
- It hasn't had enough time to do so? It's had much more time (and a much larger population) with which to evolve single-cell quality control mechanisms (checkpoints, DNA repair, etc.)? Yeast don't get cancer. Maybe we should take yeast cartilage extracts...? Maybe cancer is smarter than evolution?

Kent? What are you talking about? For unicellulars, "cancer" (i.e. uncontrolled replication) is "desirable"... That's why they all replicate without constraints. DNA maintenance in yeast prevents dysfunction, not uncontrolled replication. Also, why would immune systems have had enough time to evolve their exceptional sophistication against exogenous infection, but not at all against endogenous infection (cancer)?

#20 rahein

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Posted 10 May 2006 - 04:34 PM

Also, why would immune systems have had enough time to evolve their exceptional sophistication against exogenous infection, but not at all against endogenous infection (cancer)?


Because you have equal change at getting an exogenous infection at all points in your life. Anything that affects you before reproductive/child rearing age will selected against (negative or positive). Where as cancer is almost unique to post child bearing ages. Some childhood cancer happens, but I think most is due to environmental factors.

#21 John Schloendorn

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Posted 10 May 2006 - 04:37 PM

it is expressing innapropriate genes then it will stand out immunologically and be a target for this type immune system reprogramming

True, but you need not only some foreign epitope to get an immune response going, but also a danger signal (cytokines and things). Otherwise you'd for example die in puberty, when many new antigens first appear. But, because the danger signal is missing, you get tolerized, rather than immunized. Unfortunately, the danger signal is something the tumor has near complete control over. The innate tumor immunity described here might provide a way out by generating the danger signal from leukocytes with invariant tumor pattern recognition receptors (similar to e.g. bacterial LPS recognition by macrophage scavenger receptors), but we don't know if this is so yet, nor can we really imagine why there should be anything like an invariant pattern in advancing human tumors.

Edited by John Schloendorn, 10 May 2006 - 05:06 PM.


#22 John Schloendorn

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Posted 10 May 2006 - 04:43 PM

Some childhood cancer happens, but I think most is due to environmental factors

No, it's because our cell-intrinsic cancer defenses are so good (compare with other species -- mice are almost guaranteed to have tumors after two years). So the selective pressure to evolve tumor defenses is clearly there, because sophisticated defenses did evolve. The question remains, why did they only evolve on the cell-intrinsic side?

#23

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Posted 10 May 2006 - 07:12 PM

The claim of a normal life-span of the treated mice seems surprising, when it is so effective against naturally occurring tumors. How can life-span possibly remain "normal" when cancer is the major cause of death in inbred strains? The data is luckily not reported in the paper, because if it were convincing, it would in fact suggest severe side-effects to bring the life-span down to normal.


There is nothing to suggest that such a treatment would accelerate aging, unless it also targetted stem cells, which unlike existing and some proposed treatments (SENS/WILT), it evidently doesn't. We cannot (and should not) expect a cure for cancer to extend lifespan beyond the limits imposed by other fundamental degenerative and pathological processes.

Worth mentioning is that this mechanism may already exist in some humans who do not die from nor have ever had cancer, therefore once the murine SR/CR leukocytes are sufficiently characterised a hunt for the human analogues could begin, perhaps by devising a test to screen all the public blood banks. This would bypass the requirement to genetically engineer leukocytes which would add years of delays before usage in humans would be permittted.

#24

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Posted 10 May 2006 - 07:54 PM

why there should be anything like an invariant pattern in advancing human tumors


Just because we have not discovered it in the lab does not mean it does not exist. It would make sense that an invariant marker should exist for atypical growth. I suspect it is evolutionarily disadvantageous to have such a tight system of immune regulation as it could inhibit certain types of proliferative responses to injury. If we consider the shark, which was mentioned before, aside from its recognised ability to withstand cancer what else it is known for? The fossil record of shark teeth and studies using mtDNA suggest that their rate of evolution is slow - 8 times slower than humans - and there is no evidence of punctuated equilibrium. A slow rate of evolution could lead to extinction in other more rapidly changing environments. Another effect of a rapidly responsive system for atypical growth would be a decrease in scarring and an increase in the rate of wound healing (note the remarkable rate of healing of the lesion in the PNAS study). Once again, the shark demonstrates an unusually fast rate of wound healing and reduced scar formation. Of course, these are loose associations but interesting to note nevertheless.

#25 kent23

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Posted 10 May 2006 - 08:59 PM

Quoting John Schloendorn:

Kent? What are you talking about? For unicellulars, "cancer" (i.e. uncontrolled replication) is "desirable"... That's why they all replicate without constraints. DNA maintenance in yeast prevents dysfunction, not uncontrolled replication.


But aren't those DNA maintenance pathways conserved in us? And don't they get screwed up in cancer? So, as multicellular creatures, we have another level of control above that, that tries to keep our cells sociable, whereas unicellulars don't have social constraints on replication.

Also, why would immune systems have had enough time to evolve their exceptional sophistication against exogenous infection, but not at all against endogenous infection (cancer)?


Because it's a more complex problem- a betrayal rather than an invasion? And because it's more complex, evolution would have to search a larger solution space? And cancer usually happens after we've made kids?...

Okay, so this is dumb... I guess I would try to read a review on tumor surveillance (etc.) if I really wanted to contribute something here...

Quoting Prometheus:

Worth mentioning is that this mechanism may already exist in some humans who do not die from nor have ever had cancer, therefore once the murine SR/CR leukocytes are sufficiently characterised a hunt for the human analogues could begin, perhaps by devising a test to screen all the public blood banks. This would bypass the requirement to genetically engineer leukocytes which would add years of delays before usage in humans would be permittted.


Great observation. It's interesting also to note that the strain founder apparently acquired the trait sporadically, not as part of a forward genetics screen (I don't even know if anyone does forward genetics in mice)... So maybe it's a condition that arises sporadically with relative ease... Anyway, the first thing to do, I'm guessing, is track down a bunch of people with a family history of not getting cancer, and see if their leukocytes can kill tumors in vitro!

#26

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Posted 10 May 2006 - 10:40 PM

track down a bunch of people with a family history of not getting cancer, and see if their leukocytes can kill tumors in vitro!


I think you're right on the money Kent23. I'm flabbergasted that this hasn't been attempted before in light of all the brutal alternatives..

#27 RighteousReason

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Posted 11 May 2006 - 01:25 AM

Do it!

[lol]

#28 kent23

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Posted 11 May 2006 - 03:05 AM

Do it!


Sure. Here I go.

After googling "immunosurveillance" and poking around for twenty minutes, it seems to me that it's not going to be easy to just go out and "find a bunch of people who are cancer-resistant". Like everything, it's going to be buttloads more complex than that. Luckily there seem to be labs headed in that direction.

I'm going to call a few people tomorrow and ask some completely naive questions. Probably, questions I could answer myself if I spent all night reading, but I don't have time for that. If anyone can add any to this list, let me know. I'll report back.

A. So, has anyone looked at human leukocytes killing tumors in vitro?

B. Are there people we can safely say are "cancer-resistant", and has anyone looked at their leukocytes?

C. What about the leukocytes of centenarians and their progeny?

D. Regression of moles in young people has been proposed as possible visible evidence of immunosurveillance. Has anyone tried to culture proliferating melanocytes from moles?

E. In the rare cases of spontaneous remission of advanced tumors, did anyone collect blood from these people? Where is it?

F. Quoting J.Schloendorn: "...why would immune systems have had enough time to evolve their exceptional sophistication against exogenous infection, but not at all against endogenous infection (cancer)?" (I suspect that the guy I'm gonna call is gonna say "who says they haven't?")

G...?

#29 John Schloendorn

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Posted 11 May 2006 - 04:06 PM

Good questions, I can't think of anything else. You can formulate F in a more PC way that might avoid to provoke the not-so productive defense of ingrained evolutionary models: "Why don't people on immune suppression or HIV get much more cancer?" and then get to the point more slowly...

C: Interesting, the plan over at the supercentenarian research foundation seems to be to completely ignore innate immunity, which may be a mistake.

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#30 kent23

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Posted 11 May 2006 - 10:47 PM

Talked to Researcher #1 today. Very friendly guy. He could tell I was an undergrad, but he considered the questions to be sophisticated and thought-provoking.

A. So, has anyone looked at human leukocytes killing tumors in vitro?


R #1 says such an assay would face the serious technical difficulty of the need for autologous tumors. I think the point being, that if it's not an autologous tumor, of course the leukocytes will attack it, and the other point being, if it is an autologous tumor, then apparently the leukocytes aren't working anyway. (Didn't get around to my question D.) So as far as he knows, this hasn't been done.

B. Are there people we can safely say are "cancer-resistant", and has anyone looked at their leukocytes?

C. What about the leukocytes of centenarians and their progeny?


Grouping these together, he thought that C was intriguing. He referred me to papers by Donin et. al. (1995). It's all very confusing.

No answers for D-F... He hadn't read the Hicks paper and told me I could call him next week after he looks at it (he's in the field, so he was going to get around to it anyway.)

As for the evolutionary stuff: this guy has written a review in which he makes the case that the immune response actually stimulates tumor progression in a lot of cases. Oy vey.




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