Low Oxygen Cellular Protein Synthesis Mechanism Discovered 94
New submitter _prime writes "Until recently the mechanism by which cells make proteins in low-oxygen environments has been unknown. As published in Nature (paywall) this week, the discovery of the mechanism by an Ottawa-based team of researchers potentially means it could be 'very easy to kill cancer cells' without harming normal cells because cancer cells leverage the same low-oxygen protein synthesis mechanism even in the presence of normal oxygen levels."
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I assume this is a brand of reverse astroturfing. The goal is to make Gamemaker so hated (and reverse-google-bombed) that people will be able to find and to pay for a competitor.
filter based on user? (Score:1)
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Never.
Never.
Because of these posts.
Nope.
I don't think so.
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It would probably be pretty easy to greasemonkey them out of existence. Maybe someone has a script that does it to share.
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It's a very simple ten liner that now removes the whole tree of comments whenever a post contains whichever regular expression you want (you modify the script to your needs, and currently my regex is simply
works like a charm (for now) though it is very much optimizable I guess
If anyone is interested just let me know
Cheers...
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I flag and report them. Don't know if it will help. I click the flag in the lower right. If anyone knows a better way...
I never even knew this existed. Thanks.
What percentage of cancers leverage that? (Score:3)
Re:What percentage of cancers leverage that? (Score:5, Insightful)
Can't say definitively, but one of the major characteristics of cancer cells are that they evade apoptosis (cell 'suicide' in cases of damage, etc.), and if you go read up on apoptosis, you'll see that one of the common triggering effects is hypoxia (low oxygen). It's certainly conceivable that the cancer cells, in disregarding apoptosis commands, utilize this low-oxygen synthesis pathway to continue multiplying, and that preventing the cells from using that pathway would cause them to die normally - in other words, the cancer cell MAY receive the signal to die, and shut down its "normal oxygen" protein synthesis pathway, but start (or continue) using the low-oxygen pathway, instead of dying.
Very speculative, but it could very well be something that's fundamental to many broad categories of cancer cell. IF it turns out to be as effective as suggested (hoped), it would add a powerful new treatment to the chemotherapy, radiation, and surgical treatments already being used. If it doesn't, it still offers some potential insight into how cancer cells function, which could lead to development of other treatment protocols. It could also lead to better treatments of heart disease & stroke, since lack of oxygen to various cells & organs is one of the major components of damage in both of those conditions.
Wish Nature wasn't behind a paywall, the newspaper interview & writeup are interesting, but scant of detail.
Re:What percentage of cancers leverage that? (Score:5, Informative)
Of note in the Nature article is that none of the breathless claims in the PR bit are even alluded to. The abstract (which is typically available):
Protein synthesis involves the translation of ribonucleic acid information into proteins, the building blocks of life. The initial step of protein synthesis is the binding of the eukaryotic translation initiation factor 4E (eIF4E) to the 7-methylguanosine (m7-GpppG) 5cap of messenger RNAs1, 2. Low oxygen tension (hypoxia) represses cap-mediated translation by sequestering eIF4E through mammalian target of rapamycin (mTOR)-dependent mechanisms3, 4, 5, 6. Although the internal ribosome entry site is an alternative translation initiation mechanism, this pathway alone cannot account for the translational capacity of hypoxic cells7, 8. This raises a fundamental question in biology as to how proteins are synthesized in periods of oxygen scarcity and eIF4E inhibition9. Here we describe an oxygen-regulated translation initiation complex that mediates selective cap-dependent protein synthesis. We show that hypoxia stimulates the formation of a complex that includes the oxygen-regulated hypoxia-inducible factor 2 (HIF-2), the RNA-binding protein RBM4 and the cap-binding eIF4E2, an eIF4E homologue. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP)10 analysis identified an RNA hypoxia response element (rHRE) that recruits this complex to a wide array of mRNAs, including that encoding the epidermal growth factor receptor. Once assembled at the rHRE, the HIF-2–RBM4–eIF4E2 complex captures the 5cap and targets mRNAs to polysomes for active translation, thereby evading hypoxia-induced repression of protein synthesis. These findings demonstrate that cells have evolved a program by which oxygen tension switches the basic translation initiation machinery.
Is certainly consistent with your thoughts on apoptosis but there is scant discussion in TFA.
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Conclusions from the article:
Re:What percentage of cancers leverage that? (Score:5, Interesting)
Remarkably, not only is adaptation for low-oxygen conditions visible in the majority of malignancies (the Warburg Effect [wikipedia.org]), but it's so prevalent it's actually considered one of the hallmarks of cancer [wikipedia.org]. The reason this happens is easy to imagine: since the tumor has an extreme growth rate and abnormal vasculature, it may have trouble getting the amount of oxygen tha cells normally need in order to survive. It's likely that if they can actually safely target this pathway, they may have the next blockbuster cancer drug on their hands.
Re:What percentage of cancers leverage that? (Score:5, Informative)
Mod parent up. I just signed up for an account to say exactly the same thing.
To add to this, the major thing about Warburg metabolism is that not only does it allow cancer cells to survive in low-oxygen conditions; it actually produces the raw materials for making the protein needed to grow new cancer cells, so it allows cancer cells to grow faster than if they were using normal aerobic respiration. Here's James Watson talking about it in the NYT [nytimes.com]. So the low-oxygen conditions in a tumour are an evolutionary selection pressure for tumours to evolve towards dealing with low-oxygen conditions, but probably also for them to evolve towards growing faster and being more malignant too.
In the study in the OP they already knew the normal gubbins that engages the services of the protein-making machinery doesn't work in low-oxygen conditions, so they went looking for something that does work under these conditions and found it. It normally exists in cells so that they can make proteins when starved of oxygen. What's not clear from the Nature abstract, and what will probably need more work to study, is whether this pathway is massively boosted in cancer cells. My guess is that it will be. The Warburg effect is interesting and unique to cancer cells, but it's difficult to turn into a treatment as it's a perversion of a pathway that's essential in all cells - if you drug the pathway itself you'll likely kill the patient. This study is different as it's a pathway that's specific to oxygen-starved cells, so it may well (in about 20 years) provide some exciting new 'universal' drug targets for solid tumours, that may not kill them dead but might at least slow them down. Don't take up smoking yet though...
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Way to care about something that matters.
Re:What percentage of cancers leverage that? (Score:5, Insightful)
This kind of thinking is fantastically disconnected from reality - naive, junior-high, my-parents-don't-get-it thinking. Big pharma execs would do anything for a cancer cure; it would mean fame, money, and prestige out their eyes. And if one solitary idiot at that board meeting said something about not releasing it because of long term profits (or some other BS) he'd get laughed out of a job and be a funny story in someone's memoirs.
Now sure, they'd do what they could to milk it for profits - but they'd be damn sure it got out there before anyone else could. Hell, even if releasing it wasn't profitable at all (and it would be - obviously, obviously, obviously, obviously), they'd burn their company down if they had to.
Very, very few people would consider holding back on a cure for money; not many of those psychopaths have the personal skills to end up at the top of a big corporation, and getting a whole raft of them together would be nigh impossible. Imagining collusion across all the companies on something like this is ridiculous.
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This kind of thinking is fantastically disconnected from reality - naive, junior-high, my-parents-don't-get-it thinking. Big pharma execs would do anything for a cancer cure; it would mean fame, money, and prestige out their eyes. And if one solitary idiot at that board meeting said something about not releasing it because of long term profits (or some other BS) he'd get laughed out of a job and be a funny story in someone's memoirs.
Now sure, they'd do what they could to milk it for profits - but they'd be damn sure it got out there before anyone else could. Hell, even if releasing it wasn't profitable at all (and it would be - obviously, obviously, obviously, obviously), they'd burn their company down if they had to.
Very, very few people would consider holding back on a cure for money; not many of those psychopaths have the personal skills to end up at the top of a big corporation, and getting a whole raft of them together would be nigh impossible. Imagining collusion across all the companies on something like this is ridiculous.
What exactly is a psychopath?
"Superficially charming, psychopaths tend to make a good first impression on others and often strike observers as remarkably normal. Yet they are self-centered, dishonest and undependable, and at times they engage in irresponsible behavior for no apparent reason other than the sheer fun of it. Largely devoid of guilt, empathy and love, they have casual and callous interpersonal and romantic relationships. Psychopaths routinely offer excuses for their reckless and often outrageou
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Sorry, I wasn't perfectly clear. The ones proposing this at the board meeting would normally be execs, who could be fired.
Somebody whistle-blows this (one or more of the original scientists, some middle manager, an executive, or a board member) and gets themselves a tidy book deal and is the hero who fought back to cure cancer. But even that's unlikely to be neces
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Well, AT&T managed to invent and then bury the answering machine (and the magnetic tape) for a full 50 years before someone else re-invented it elsewhere and brought it to market. All it takes is for the board to vote to destroy all the research and evidence, and then gag everyone involved with permanent NDAs.
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A fully fleshed out cure for cancer would never be shot down in a boardroom. Something like that would be shot down on it's first steps. It would be shot down by denying funding for research that would lead to the fully fleshed out cure. Any of the millions of steps before reaching the end of the journey can be the place that the journey stops.
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Very, very few people would consider holding back on a cure for money; not many of those psychopaths have the personal skills to end up at the top of a big corporation
Hmm, what's Wikipedia say about sociopathy (Antisocial personality disorder and psychopathy are both sociopathies)
so the ideal cancer drug is continuous treatment (Score:2)
From the perspective of a pharmaceutical firm, the ideal drug is one that works well, is cheap to make, can be sold for a lot, and has to be taken for the rest of the patient's life.
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It may be that the rest of the world gets the cancer cure but it will be illegal in the US. Or only available to the few who can afford it.
They call this a patent. It's illegal to make the drug, unless the patent owner says you can (and they won't). But, for the most part, the rest of the world just ignores US patents, so everyone else will have the drug, but the US won't (except for the rich)
The only way this could be different is if the drug is somehow very difficult/expensive to make in large amounts, in which case only the rich will have it, no matter what country it is
Re:What percentage of cancers leverage that? (Score:5, Interesting)
Interestingly the Nature article doesn't make mention of this mechanism in cancer cells other than to show it exists in a particular brain cancer clone. As the saying goes, 'extraordinary claims require extraordinary data' - at this point we're at the mercy of the idiot PR summary and a single statement from one of the researchers.
The idea that you could wipe out cancer cells selectively (if this pathway is indeed common to malignant cells AND not required by normal cells) is nice but lets hold our breath, shall we.
I've lost count on how many times cancer has been cured according to various and sundry press releases. Of interest perhaps, is that there isn't an editorial note on the paper. Nature tends to do this for papers that they perceive to have a major result. The editorial typically gives some background and insight to the paper to allow people who aren't in the field to understand it's significance.
Re:What percentage of cancers leverage that? (Score:5, Informative)
One of the main problems cancer cells have is getting enough oxygen.
Their continuous unregulated reproduction outgrows their blood supply - and while a typical tumor signals for more blood vessel growth (vascularization) into itself, the vessels themselves are organized so they can't really keep up. The result is that the bulk of a solid tumor is running on very low oxygen concentration, the main limit on its growth is its ability to obtain new vascularization, and a substantial fraction of the cancer cells may be dying off due to this oxygen shortage.
So of course having essentially every low-oxygen hack available turned on is a reasonable thing to expect of dangerous tumor types. And turning them off, even through it might not completely kill the tumor, would knock it down enormously AND the remainder would be expected to be far more vulnerable to the body's immune system.
(Of course if the tumor is a type that recognizes it should die but is evading apoptosis because that works on the normal but not the low-oxygen pathway, turning off the low-oxygen pathway means the cancer cells should just commit suicide, either completely killing the tumor or knocking it back to a miniscule number of cells with further mutations.)
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http://www.youtube.com/watch?v=3xmlYr1AGx8 [youtube.com]
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There was a paper about a year or so ago that posited that cancer was actually a different strategy for multicellular life, a default state of being that more structured organisms evolved from by taming it and poking with developmental genes to direct what happens. I believe the notion came out of analysing fossils of the earliest known (and definitely unstructured) multicellular life and deciding that the organisation in it resembled a tumour. It's funny—we name so many oncogenes tumour suppressors b
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But that's a double edged sword. I was more surprised
Give this guy a Nobel (Score:3)
This has the potential to replace chemo therapies with an antibiotic. No more poisoning people to try to make them better. Not to mention the potential to treat stokes and heart disease. Well done!
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This has the potential to replace chemo therapies with an antibiotic. No more poisoning people to try to make them better. Not to mention the potential to treat stokes and heart disease. Well done!
First, they only hand out Nobels to famous people these days, not people who should be famous because of their work. Al Gore won one for giving a powerpoint about Global Warming... the hundred plus scientists who have dedicated their lives to collecting, analyzing, and releasing the data haven't gotten anything. I can provide many more examples of how much fail there is in the Nobel prize world... Winning one is no longer any great achievement... you can just buy one these days.
Second.. it's a bit early to
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This has the potential to replace chemo therapies with an antibiotic. No more poisoning people to try to make them better. Not to mention the potential to treat stokes and heart disease. Well done!
First, they only hand out Nobels to famous people these days, not people who should be famous because of their work. Al Gore won one for giving a powerpoint about Global Warming... the hundred plus scientists who have dedicated their lives to collecting, analyzing, and releasing the data haven't gotten anything. I can provide many more examples of how much fail there is in the Nobel prize world... Winning one is no longer any great achievement... you can just buy one these days.
Second.. it's a bit early to congratulate them... they've published a paper, not cured a patient.
obama and the nobel price for peace...
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They do? I thought, in Spanish, that you speak that "M" with your lips (as in English) and the "C" with your tongue (like a shortened S). Totally different sound structure.
Not that I speak Spanish, so please correct me :)
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You're right, what a fucking joke.
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Prehaps they should start on the troll gene next.
No, wait... Slashdot would collapse.
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Al Gore won one for giving a powerpoint about Global Warming... the hundred plus scientists who have dedicated their lives to collecting, analyzing, and releasing the data haven't gotten anything.
Your talking about the 'peace prize' which is has always been contraversial, even more so when people don't bother to check the facts. Gore was jointly awarded the peace prize [nobelprize.org] along with the thousands of scientists who have also DONATED their time to the IPCC reports over the last couple of decades. Gore is not a member of the IPCC but his 'slide show' put AGW into the venacular of the US public, so much so that many Americans still think it didn't exists before Gore started banging on about it in movie the
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Now, what does WP says of this treatment? "Evidence for the effectiveness of the Budwig diet is limited as most research has only been done on cell culture studies and experiments on rats and mice with inconsistent results.[...] There is no reliable evidence available for the effectiveness of the full Budwig protocol."
That doesn't really sound like Nobel material
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Nonsense. Those who nominated a peer for a Nobel can and have given publicity to their actions, particularly when they felt him or her to have been unjustly denied the award.
In contrast to the sweeping unsubstantiated WP quote you offer, there is plenty of reliable evidence for the effectiveness of the Budwig protocol: it moved out of the research stage decades ago a
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A good place to start are the words to two-time Nobel prize winner Linus Pauling: "Everyone should know that the 'war on cancer' is largely a fraud."
I was going to write a longer answer, but then you quoted Linus Pauling on cancer treatment. His view on that subject is the poster example of why you shouldn't rely on the words of a Nobel laureate on anything out of their main field, if that. Quoting him for wisdom on cancer treatment shows you don't know the first thing of the subject. Of course, even if you hadn't done that, your suggestion that testimonials is a good way to tell whether a treatment works shows that.
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Pauling won not one but two Nobel prizes and went quite kooky in his old age, he also reached his 90s with a cancer that should have killed him when he was in his 60s. He may have been lucky or he may have been on to something.
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A good place to start are the words to two-time Nobel prize winner Linus Pauling: "Everyone should know that the 'war on cancer' is largely a fraud."
Ah, the good old "appeal to authority". Always a sign that someone's talking out of the wrong orifice.
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This is a science story about cancer. It's got nothing to do with Canada except for the fact that the researchers happen to be based there.
It's a Canadian story published in Canada about Canadian researcher. What did you expect, a US flag?
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You can thank me later (or not).
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They usually have the 'Erlenmeyer flask and molecular stick-model' icon for science/research stories.
I wonder if that makes slashdot illegal in Texas?
(You need a permit to own a flask in Texas now. Apparently that's gonna slow the meth wildfire. What a joke).
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Is this statement about Texas true? I'm not in Texas, but I'm curious and concerned, lest such idiocy spreads. I have a small collection of old labware, including some flasks and Victorian-era gas valves.
Re:What's with the canadian flag? (Score:5, Informative)
There's some info on texas department of public saftey's site [state.tx.us]
You need a permit to buy/possess:
(A) a condenser
(B) a distilling apparatus
(C) a vacuum drier
(D) a three-neck or distilling flask
(E) a tableting machine
(F) an encapsulating machine
(G) a filter, Buchner, or separatory funnel
(H) an Erlenmeyer, two-neck, or single-neck flask
(I) a round-bottom, Florence, thermometer, or filtering flask
(J) a Soxhlet extractor
(K) a transformer
(L) a flask heater
(M) a heating mantel or
(N) an adaptor tube
I didn't realise it was so broad. I suppose the condenser bit bans refrigeratiors and air-conditioning. 'Transformer' bans almost all electronics. Obviously it isn't enforced like this, but that's not really the point.
Apparently glassware (and chemistry in general) is only useful for making bombs and drugs, right?
Then they wonder why there is a shortage of scientists and engineers. It would be funnier if it wasn't so sad.
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Apparently it's been like this since 1987. no wonder we have entire generations of Texans that are anti-science, they have all been brainwashed to think that chemistry has no purpose EXCEPT making meth.
Also, the condenser they are talking about is a glass coil designed to be suspended in a flask of cold water, not an A/C condenser.
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I wish Texas would just go secede already, and that the federal government would just let them. Nothing of value would be lost, and most of those silly patent trolls would go with them.
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'Transformer' bans almost all electronics.
So besides autoclaves, they are also banning autobots.
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This is a science story about cancer. It's got nothing to do with Canada except for the fact that the researchers happen to be based there.
It's a Canadian story published in Canada about Canadian researcher.
Well, that explains to me, at least, why I thought there might have been something a little funnier about it.
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Sure.
Now can you guys stop flag waving in every farking movie? We know Hollywood is in the USA you don't need to remind yourselves (and everyone else in the world) where it is located.
So what's this mechanism. (Score:2)
It's a pity that the non-paywall article doesn't say SQUAT about what the mechanism ACTUALLY IS.
(I wonder if that's deliberate, to get more people to pay up.)
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What level of detail were you hoping for? I might be able to quench your curiosity.
Probably not; to be blunt, people who post comments like GPP's are more interested in whining than they are in knowledge.
Re:So what's this mechanism. (Score:5, Insightful)
I did think about making the (extremely obvious) remark that if one is capable of handling that question, one already has access to Nature and is well-acquainted with why there's a "paywall", and why the Ottawa Citizen is not even remotely the appropriate venue for discussing hypoxia pathways or translation initiation factors—but that does look slightly worse on one's permanent record, and it burns up the opportunity for someone else to come along and have the question answered in a more serious light.
And to be honest, Slashdot doesn't need more snarkery. One of its greatest assets is its plenitude of technically intelligent and experienced comment-posters, and that's a really wonderful resource for a community to have. Cynicism can do little but poison the site's ability to attract new users—and there have been lots of times I wish I could hit someone on the head (often myself) for unnecessary posturing, taking up a position of authority obviously beyond the extent of his or her knowledge, or responding to sloppy critique with an outright attack. Being unexpectedly kind can get jerkwads to shut up, too—and it's more likely to make the impressionable newbie or lurker contribute positively in the future, rather than emulating (limp-wristedly) the venom of others.
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I admire your optimism. And that's not snark; I really do. For myself, I do my best to answer what I perceive to be honest questions, but there is just so damned much wilful ignorance on display in any science-related story that I often have a hard time keeping my baser instincts in check.
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Comment from the submitter (Score:2)
To me the Canada flag thing has become a tongue-in-cheek posting icon. The system auto-selects it depending on the keywords entered by the submitter. Given the Canadian article and research team I thought the tag was appropriate, but I have to chuckle when the flag appears (though I suppose it does help us canucks with USA inferiority complex feel a bit better - how many flags can we get up here guys!).
Bottom line: this sounded like something people need to know about. The way the article reads it seems as