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Low Oxygen Cellular Protein Synthesis Mechanism Discovered

Unknown Lamer posted more than 2 years ago | from the live-forever dept.

Canada 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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94 comments

Wow! (-1, Troll)

scourningparading (2633143) | more than 2 years ago | (#39923137)

Small Boy: "Grandpa! Grandpa! Tell me the story about how a select few heroes saved the world again!"
Old Man: "All right, all right. Settle down now. I will gladly tell you the story about how much of the world used to be shrouded in darkness. The story of a select few heroes who saved the world from destruction."
Old Man: "There was once a time when much of the world was shrouded in evil and darkness. It was completely different from how the world is now. Arrogance, ignorance, and evil thrived in this land."
Old Man: "Most software in this world was extremely stable and efficient. The entire world was about to collapse under this horrible efficiency."
Old Man: "That is, until a select few Heroes rose up to save the day. No longer could they simply watch as the world was covered in ignorance. No longer could they watch as the world was threatened by efficiency. Things were simply too speedy."
Old Man: "They rose from the shadows and ushered forth a new age! No longer would the world be shrouded in darkness and uncertainty from Gamemakerlessness! They pledged to return the world to Gamemakerdom for the betterment of mankind!"
Old Man: "Wherever Gamemakerlessness lurked, they appeared. They stood in front of a stage and screeched, 'How comical! How comical! Who could possibly not return to Gamemakerdom!? Gamemaker's the best. Use Gamemaker. Use Gamemaker right now! Return to Gamemakerdom right this minuteness!'"
Old Man: "Just like this, they were finally able to realize their dream. Almost everyone was using Gamemaker. Once they finished, 99% of the population had returned to Gamemakerdom."
Old Man: "What happened to those who refused to use Gamemaker, you ask? They were constantly depressed, hated their lives, and their cheeks were made fun of by everyone else. Eventually they did the world a favor and turned to dust and died! How comical! How comical!"
Small Boy: "Wow! Such a thing! I can't believe such Gamemakerlessnesses existed once upon a time! What nothingness ultimatums they were!"
Old Man: "Yeah, it's true. I'm a big ol' buttnude. Now use Gamemaker you fuckin' pathetic piece of garbage!"

Re:Wow! (-1)

Anonymous Coward | more than 2 years ago | (#39923225)

Old Man: "What happened to those who refused to use Gamemaker, you ask? They were constantly depressed, hated their lives, ..."

... mostly because of things spam trolls posted on Slashdot.

Re:Wow! (-1)

Anonymous Coward | more than 2 years ago | (#39923417)

I still haven't figured this damn Gamemaker troll out. Is it a reference to something I missed? To another troll? To a spammer?

Re:Wow! (1)

Surt (22457) | more than 2 years ago | (#39923735)

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.

Re:Wow! (-1)

Anonymous Coward | more than 2 years ago | (#39930083)

I actually tried and subsequently bought gamemaker after seeing a bunch of these trolls. Though, I laugh at slashdot trolls and browse at -1 to read them. It's the only thing this site it good for.

Bought gamemaker because the price is right and the pirate (YYAAAAAAARRRRR!) version says "Gaymaker" in the title bar and crashes every few times you try to run your game.

Re:Wow! (-1, Troll)

Black Parrot (19622) | more than 2 years ago | (#39923803)

We, the undersigned, all agree -

Thad N. D. Knight
U. Wilby
Hope Leslie Holding
A. Little-Wiener
N. D. Hand
U. Wayne King
Wayne Kerr

Gamemakerdom! Return to it this minute! (-1, Troll)

ScrumpingAssExtreme (2633965) | more than 2 years ago | (#39923151)

Wow, Gamemaker! I love you Gamemaker! Nothing's better than Gamemaker! Wow! Wow! Wow!

I can't even stand the thought of a world without Gamemaker! Gamemaker is the greatest!

Return.
Return.
Return.
You shall return.
Without a single doubt, you shall return to Gamemakerdom!

filter based on user? (1)

rst123 (2440064) | more than 2 years ago | (#39923221)

Is there any way to filter out comments based on commenter / subject / regex / key words? If not, why not?

Re:filter based on user? (0)

Anonymous Coward | more than 2 years ago | (#39923239)

because everybody on slashdot uses ABP and this is the only way they can advertise

Re:filter based on user? (0)

Anonymous Coward | more than 2 years ago | (#39923269)

Maybe they need a new mod "-1, Spam" that will not only decrease the score of a post, but also act as an anchor to sink the post to the bottom of the display / loading order.

Re:filter based on user? (-1)

Anonymous Coward | more than 2 years ago | (#39923279)

When are you going to switch to Gamemaker, friend?

When?

Why not?

You will.

You WILL switch to Gamemaker.

Re:filter based on user? (-1)

Anonymous Coward | more than 2 years ago | (#39923367)

Indirectly, of course. After I switched to gamemaker I got infinitely more poontang; somewhere along the line I got the ol' crotch craters. Worth it, though! I had sex.

Re:filter based on user? (1)

X0563511 (793323) | more than 2 years ago | (#39928117)

Never.

Never.

Because of these posts.

Nope.

I don't think so.

Re:filter based on user? (2)

similar_name (1164087) | more than 2 years ago | (#39923363)

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...

Re:filter based on user? (1)

Surt (22457) | more than 2 years ago | (#39923777)

It would probably be pretty easy to greasemonkey them out of existence. Maybe someone has a script that does it to share.

Re:filter based on user? (1)

Guignol (159087) | more than 2 years ago | (#39925589)

I slightly modified a userscript from Brad Cable that removes (removed some time ago I suppose) bullshit posts
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 /gamemaker/ig
works like a charm (for now) though it is very much optimizable I guess
If anyone is interested just let me know :)
Cheers...

Re:filter based on user? (1)

rst123 (2440064) | more than 2 years ago | (#39937267)

I would be interested in the script.

Re:filter based on user? (1)

Guignol (159087) | more than 2 years ago | (#39938417)

do you have an email I so I can send it to you ? (or a temporary ftp server, whatever)

Re:filter based on user? (1)

rsborg (111459) | more than 2 years ago | (#39924575)

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? (2)

Elgonn (921934) | more than 2 years ago | (#39923289)

Does someone know? The summary implies all of them. But considering cancer is more of a collection of problems rather than a specific issue it just seems unlikely.

Re:What percentage of cancers leverage that? (-1)

Anonymous Coward | more than 2 years ago | (#39923307)

You're adorable. Shhh. It's okay. Shhh, baby, shhhh. I know you're miserable. I know you hate being a worthless piece of garbage.

I know. I can sense your pain. You won't be ignored.

Just use Gamemaker. Return to Gamemakerdom.

Your life will change for the better.

Re:What percentage of cancers leverage that? (5, Insightful)

Americano (920576) | more than 2 years ago | (#39923441)

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? (4, Informative)

ColdWetDog (752185) | more than 2 years ago | (#39923725)

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.

Re:What percentage of cancers leverage that? (2)

mopomi (696055) | more than 2 years ago | (#39925137)

You can usually get past a paywall by going to your local public or university library and accessing the article there. Tedious, I know.
Conclusions from the article:

Here we have identified a selective cap-dependent translation initiation mechanism that operates independently of eIF4E and that targets mRNAs for protein synthesis during hypoxia. The results suggest that the HIF-2αâ"RBM4â"eIF4E2 complex is extensively involved in coordinating the translation response to low oxygen availability and is therefore essential in cellular oxygen homeostasis. This complex probably recruits functional homologues of the canonical eIF4E-dependent pathway, as well as distinct components, to initiate hypoxic protein synthesis. This process is regulated by the oxygen-sensing machinery first identified as the main regulator of the transcriptional response to hypoxia13, 14, 15, 16. A human population that recently migrated to the Tibetan highlands contains a point mutation in the gene encoding HIF-2α (EPAS1), further emphasizing the evolutionary role of HIF-2α in the adaptation to high altitude and low oxygen tension27. The target mRNAs code for proteins such as EGFR, PDGFRA and IGF1R that are implicated in the adaptive response to hypoxia as well as a wide variety of biological processes including development and cancer. The role of these receptor tyrosine kinases in human malignancy is particularly well documented and they are at the centre of targeted therapy11, 28. EGFR is often overproduced by tumours that harbour a wild-type EGFR gene, suggesting that cancer cells hijack the eIF4E2 pathway for their proliferative advantage29, 30. The results shown here provide the foundation for further investigation of the adaptive properties of the basic protein synthesis machinery in response to environmental conditions.

Re:What percentage of cancers leverage that? (5, Interesting)

nukeade (583009) | more than 2 years ago | (#39923921)

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? (5, Informative)

Biotech_is_Godzilla (2634385) | more than 2 years ago | (#39925663)

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...

Re:What percentage of cancers leverage that? (0)

Anonymous Coward | more than 2 years ago | (#39927269)

I'd believe you, but your UID is soooo long.

Re:What percentage of cancers leverage that? (1)

X0563511 (793323) | more than 2 years ago | (#39928161)

Way to care about something that matters.

Re:What percentage of cancers leverage that? (-1, Troll)

BaldingByMicrosoft (585534) | more than 2 years ago | (#39923981)

You can't mod down the truth.

There will never be an available cure for cancer as long as the "health care" industry is making such huge profits to treat it.

If you can make an incredibly expensive vaccine, you might displace this effect with time.

This comment is US-centric. 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.

Re:What percentage of cancers leverage that? (4, Insightful)

JMZero (449047) | more than 2 years ago | (#39924417)

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.

Re:What percentage of cancers leverage that? (1)

Issarlk (1429361) | more than 2 years ago | (#39925783)

That's funny because there's an idea floating around that says that psychopaths are exactly the kind of person who climb the corporate ladder to the top.

Re:What percentage of cancers leverage that? (3, Insightful)

sir-gold (949031) | more than 2 years ago | (#39927829)

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 outrageous actions, placing blame on others instead. They rarely learn from their mistakes or benefit from negative feedback, and they have difficulty inhibiting their impulses."

Replace the word "fun" with "profit", and the word "romantic" with "economic", and you have the DEFINITION of any large publicly traded company

There has been at least one documentary showing that all corporations engage in psychopathic and sociopathic behaviors on a regular basis, especially in thier callous disregard for human life, the union carbide disaster is a great example of this.

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

What if that "one solitary idiot" is the single largest shareholder (directly representing himself)? what are they going to do, laugh at him till he sells his share of the company? You assume that board members can be fired, but the majority of board members either personally own significant stock in the company, or they represent someone who does. The CEO (and CFO, CTO, etc) are the only ones who can be fired, because they are employees of the company, not shareholder representatives.

Re:What percentage of cancers leverage that? (1)

JMZero (449047) | more than 2 years ago | (#39928789)

You assume that board members can be fired,

Sorry, I wasn't perfectly clear. The ones proposing this at the board meeting would normally be execs, who could be fired.

What if that "one solitary idiot" is the single largest shareholder (directly representing himself)?

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 necessary - again, we're imagining human behavior that's very rare, and even more rare for someone who's very successful. Even if someone privately thought this would be profitable to bury (which it almost certainly wouldn't be), they'd have to be non-functionally psychopathic to actually suggest it out loud.

Look, I fully agree corporations (and people in general) do bad things. You can get a weird group-think going where everyone does something that nobody individually would do. Humans can do all sorts of bad things when they're scared. Many times you can get a horrible result through a chain of events that are all, themselves, reasonably innocuous. People will go a long ways to rationalize their own failures. Few people respect the categorical imperative; they'll do things that contribute to problems while denying their own responsibility or moral failure.

There's lots of mechanisms that result in bad behavior - but almost all of them share some characteristics; in very few do the functional people involved feel like they're actually doing something importantly wrong. In the case of a "burying the cure for cancer", that's a very hard leap to make, and suppressing a cure over time is going to take a large number of those leaps by a lot of people (and many of these steps don't make any business sense, let alone moral sense).

Re:What percentage of cancers leverage that? (1)

sir-gold (949031) | more than 2 years ago | (#39929021)

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.

Re:What percentage of cancers leverage that? (1)

Belial6 (794905) | more than 2 years ago | (#39931893)

A journey of a thousand miles starts with the first step. If I can prevent your first step, I will have stopped the entire thousand mile journey.

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.

Re:What percentage of cancers leverage that? (0)

Anonymous Coward | more than 2 years ago | (#39932253)

I fully agree with you on how you'd best hypothetically go about burying a cancer cure. You say to yourself (and others): "it won't work out, the problem's too hard, there's other things that are more urgent, we'll get to cancer later" or even "it's shooting too high to go for a cure - we should just look for treatments to help out with specific kinds".

I'm sure there's lots of people and businesses making that kind of decision for a variety of reasons. I also think there's plenty of people honestly searching for broader "cure" type treatments.

Re:What percentage of cancers leverage that? (1)

mcgrew (92797) | more than 2 years ago | (#39928835)

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)

It is characterized by at least 3 of the following:
Callous unconcern for the feelings of others.
Gross and persistent attitude of irresponsibility and disregard for social norms, rules, and obligations.
Incapacity to maintain enduring relationships, though having no difficulty in establishing them.
Very low tolerance to frustration and a low threshold for discharge of aggression, including violence.
Incapacity to experience guilt or to profit from experience, particularly punishment.
Markedly prone to blame others or to offer plausible rationalizations for the behavior that has brought the person into conflict with society.

Sounds like Newt Gingrich to me. He rose pretty high in society. I'd say a CEO would be hindered in doing his job with a lack of sociopathy.

I was in a car wreck about fifteen years ago, and the radiologist looking at the X-Rays of my back said "well, nothing's broken, everything looks ok except you have arthritis."

I said "I know, when are you guys going to come up with a cure for that?" He replied "there's no money in cures, the money's in treatments." I'd be surprised that a "naive, junior-high, my-parents-don't-get-it thinking" person could make it through medical school and an internship.

Re:What percentage of cancers leverage that? (0)

Anonymous Coward | more than 2 years ago | (#39929795)

He replied "there's no money in cures, the money's in treatments."

For non-terminal conditions, yes. For terminal conditions, a cure is just a treatment that opens a buyer up to needing more treatments in the future.

so the ideal cancer drug is continuous treatment (1)

Chirs (87576) | more than 2 years ago | (#39931813)

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.

Re:What percentage of cancers leverage that? (0)

Anonymous Coward | more than 2 years ago | (#39924821)

talking about medication...

Re:What percentage of cancers leverage that? (1)

sir-gold (949031) | more than 2 years ago | (#39927957)

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? (5, Interesting)

ColdWetDog (752185) | more than 2 years ago | (#39923461)

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.

Post article here (0)

Anonymous Coward | more than 2 years ago | (#39923711)

Please post a text copy of the article here!

Re:What percentage of cancers leverage that? (5, Informative)

Ungrounded Lightning (62228) | more than 2 years ago | (#39923741)

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.)

Re:What percentage of cancers leverage that? (2)

dumcob (2595259) | more than 2 years ago | (#39923873)

Very well explained. Here is a nice animation (which is very similar to what you just described) of how the drug Avastin works. It essentially interferes with the "signal" for new blood vessel growth. Is already in use along with chemo for many cancer treatments.

http://www.youtube.com/watch?v=3xmlYr1AGx8 [youtube.com]

Re:What percentage of cancers leverage that? (1)

phantomfive (622387) | more than 2 years ago | (#39924695)

Wow, watching that movie, it's incredible how complex a tumor can be. The tumor releases VEGF-A to stimulate blood-vessels to grow around it, so it can get the blood flow needed to power itself. It's almost as if cancer is a parasite that has evolved to complexly interact with the human body.....

Re:What percentage of cancers leverage that? (2)

lisaparratt (752068) | more than 2 years ago | (#39925153)

Cancer *is* the human body, gone rogue and psychopathic. It's got all your superpowers, knows all your secrets, and is damned well going to use them to it's own benefit, the rest of you be damned.

Re:What percentage of cancers leverage that? (1)

Samantha Wright (1324923) | more than 2 years ago | (#39925385)

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 because that's the function they appear to provide in a medical context—and lo and behold, that's not only their function, but actually their purpose, a label that's rarely usable in genome-wide studies.

It's a bit of a downer to the idea of eliminating cancer from the genome forever, though, if you take the mindset that we're actually tamed cancer and not fundamentally structured organisms.

There is a plus side, however. The defects we experience during cancer can't actually evolve to keep pace with us—everything they do is deleterious to survival, and there's no way to place a positive selection pressure on it unless you breed for it. Once we figure out a good set of techniques to tackle cancers in a general sense, it'll probably be millions of years of evolution (or at least a few dozen horrible chemical contaminants) before the genome has drifted enough that novel mutations can arise that are sufficiently different from the ones we experience now to actually manifest.

Re:What percentage of cancers leverage that? (1)

Belial6 (794905) | more than 2 years ago | (#39931961)

I've lost count too, but what I can count are the people I have personally known who have died of cancer, and those that have been cured. The cured out number the dead at least 5 to 1.

Re:What percentage of cancers leverage that? (1)

kubernet3s (1954672) | more than 2 years ago | (#39938979)

There's probably not a list, given how many kinds of cancer there are, and the difficulty of determining biological mechanisms. Cancers are diverse, but there are certain things that most of them do, and that's where therapies are developed. A big one is overexpression of receptors or antibodies, which not all cancers do in the same way, but most do in some fashion. I'd imagine anything that kills most cancers without killing healthy cells is worth a go.

But that's a double edged sword. I was more surprised to hear that this mechanism isn't leveraged anywhere else in the body. And more importantly, now that we know this mechanism, is it really possible to selectively poison it?

Give this guy a Nobel (2)

frank249 (100528) | more than 2 years ago | (#39923309)

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!

Re:Give this guy a Nobel (0)

Anonymous Coward | more than 2 years ago | (#39923351)

"No more poisoning people to try to make them better."

Say, genius, do you know what an antibiotic is?

Re:Give this guy a Nobel (2)

Bengie (1121981) | more than 2 years ago | (#39926127)

Yeah, a poison trying to kill my-little-microbe-gut-friends(tm).

Re:Give this guy a Nobel (1)

girlintraining (1395911) | more than 2 years ago | (#39923655)

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.

Re:Give this guy a Nobel (1)

ltcdata (626981) | more than 2 years ago | (#39923703)

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...

Re:Give this guy a Nobel (1)

ltcdata (626981) | more than 2 years ago | (#39923715)

priZe... sorry... its the same as the word value "precio" in my language, spanish, i had a brainfart and wrote "price".

Re:Give this guy a Nobel (1)

phantomfive (622387) | more than 2 years ago | (#39924699)

? premio = precio?

Re:Give this guy a Nobel (1)

ltcdata (626981) | more than 2 years ago | (#39925849)

when you speak it, its has a similar phonetic signature, when i speak "prize" y think of "precio, (value, cost) so without thinking, i wrote "price".

Re:Give this guy a Nobel (1)

TapeCutter (624760) | more than 2 years ago | (#39926189)

Must be tough having a language barrier in your own head. /jk

Re:Give this guy a Nobel (1)

ltcdata (626981) | more than 2 years ago | (#39926367)

when you work and constantly switch languages, read in english, then spanish, then english.... things like this happens.

Re:Give this guy a Nobel (1)

X0563511 (793323) | more than 2 years ago | (#39928251)

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 :)

Re:Give this guy a Nobel (1)

ltcdata (626981) | more than 2 years ago | (#39929797)

What you say about pronunciation is true. "Prize" in spanish is prononunced something like "prais". The sound of the spoken word "Precio" is kind of similar to "price" and "prize" in spanish, that's why i got confused when i wrote it.

Re:Give this guy a Nobel (1)

glwtta (532858) | more than 2 years ago | (#39923823)

Last year's Nobel in Physiology and Medicine went to the discoverers of the Toll gene and Toll-like receptors (as well as dendritic cells), which play a major role in immune response activation.

You're right, what a fucking joke.

Re:Give this guy a Nobel (1)

funwithBSD (245349) | more than 2 years ago | (#39924293)

Prehaps they should start on the troll gene next.

No, wait... Slashdot would collapse.

Re:Give this guy a Nobel (1)

TapeCutter (624760) | more than 2 years ago | (#39926159)

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 theaters,

Gore, Thatcher, and Reagan were among the first political leaders who paid any attention to AGW, Reagan was probably influenced by Thatcher who was orginally trained in Chemistry at Oxford, he personally spearheaded the push for the very successfull international 'cap and trade' treaty on sulphur emmissions that effectively stopped the acid rain problem in it's tracks. Gore always has, and always will be more of a nerd than a politician, but to middle America sucking on a steady diet of Murdoch's propoganda he is just another has-been politician trying to make a buck.

Second.. it's a bit early to congratulate them... they've published a paper, not cured a patient.

If they were to win a Nobel prize for this it would be for the discovery in their paper that has stumped others for decades, not for 'curing cancer'.

Re:Give this guy a Nobel (1)

Eukariote (881204) | more than 2 years ago | (#39924503)

Too late. It has already been awarded in 1931 [hopeforcancer.com] . Yes, the import of anearobic metabolism on cancer emergence has been known of for over 80 years. Indeed, Dr. Johanna Budwig [healingcan...urally.com] has developed an effective dietary treatment based on it. She was nominated for a Nobel seven times, but never awarded one.

Re:Give this guy a Nobel (1)

sFurbo (1361249) | more than 2 years ago | (#39924985)

The lists of Nobel nominees are not publically available. Claiming someone has been nominated a certain number of times is clearly a falsehood.

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.

Re:Give this guy a Nobel (1)

Eukariote (881204) | more than 2 years ago | (#39925427)

The lists of Nobel nominees are not publically available. Claiming someone has been nominated a certain number of times is clearly a falsehood.

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 and has been used with success in practice since as evident from the many testimonials (here [budwigcenter.com] and elsewhere) of those who had their lives saved.

So how come this, or the effectiveness of several other alternative treatments, is not acknowledged? 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."

Re:Give this guy a Nobel (1)

sFurbo (1361249) | more than 2 years ago | (#39925969)

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.

Re:Give this guy a Nobel (1)

lxs (131946) | more than 2 years ago | (#39926659)

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.

Re:Give this guy a Nobel (1)

sFurbo (1361249) | more than 2 years ago | (#39926789)

No, we have tested it, he was just lucky, or at least, it doesn't seem to work for any subgroup of patients we can identify. He was not on to a universal cure for cancer.

Re:Give this guy a Nobel (1)

LeadSongDog (1120683) | more than 2 years ago | (#39926901)

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.

What's with the canadian flag? (-1)

Anonymous Coward | more than 2 years ago | (#39923335)

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.

Canadians: stop trying to prove you're a first-world country. We get it, we know you have universities and lightbulbs and don't live in igloos. You don't have wave your flag whenever you do something remotely modern.

Re:What's with the canadian flag? (2)

Kinky Bass Junk (880011) | more than 2 years ago | (#39923403)

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?

Re:What's with the canadian flag? (1)

Kinky Bass Junk (880011) | more than 2 years ago | (#39923415)

Also, what a terrible article. Shaky camera is shaky, and what is the "U of O"? Is that some kind of alien craft?

Re:What's with the canadian flag? (0)

Anonymous Coward | more than 2 years ago | (#39923609)

University of Ottawa

Re:What's with the canadian flag? (2)

Samantha Wright (1324923) | more than 2 years ago | (#39924469)

Having been there, I can say conclusively that you have not answered the grandparent's second question. :)

Re:What's with the canadian flag? (1)

Crypto Gnome (651401) | more than 2 years ago | (#39924637)

Unrelated to The Story of O [wikipedia.org] .

You can thank me later (or not).

Re:What's with the canadian flag? (0)

Anonymous Coward | more than 2 years ago | (#39923491)

Yes.

Re:What's with the canadian flag? (2)

mirix (1649853) | more than 2 years ago | (#39923955)

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).

Re:What's with the canadian flag? (1)

Rubinstien (6077) | more than 2 years ago | (#39924691)

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? (4, Informative)

mirix (1649853) | more than 2 years ago | (#39925193)

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.

Re:What's with the canadian flag? (1)

sir-gold (949031) | more than 2 years ago | (#39928151)

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.

Re:What's with the canadian flag? (1)

X0563511 (793323) | more than 2 years ago | (#39928305)

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.

Re:What's with the canadian flag? (1)

TeknoHog (164938) | more than 2 years ago | (#39929693)

'Transformer' bans almost all electronics.

So besides autoclaves, they are also banning autobots.

Re:What's with the canadian flag? (1)

catmistake (814204) | more than 2 years ago | (#39924811)

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.

Re:What's with the canadian flag? (1)

SilverJets (131916) | more than 2 years ago | (#39923631)

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. (1)

Ungrounded Lightning (62228) | more than 2 years ago | (#39923753)

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.)

Re:So what's this mechanism. (1)

Samantha Wright (1324923) | more than 2 years ago | (#39924479)

It's actually described rather well in the abstract of the journal article. What level of detail were you hoping for? I might be able to quench your curiosity.

Re:So what's this mechanism. (1)

Daniel Dvorkin (106857) | more than 2 years ago | (#39925003)

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. (4, Insightful)

Samantha Wright (1324923) | more than 2 years ago | (#39925293)

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.

Re:So what's this mechanism. (1)

Daniel Dvorkin (106857) | more than 2 years ago | (#39925333)

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.

Re:So what's this mechanism. (2)

Samantha Wright (1324923) | more than 2 years ago | (#39925423)

Well... there's the trick. That's when keeping up a strong face is the most important. I really feel like Slashdot is considered a sanitized version of 4chan these days as far as social forums go: poisonous, but not miserable enough to descend to the point that clever and ridiculous trolls are its life's blood. If the staff cared about anything long-term I have a feeling more care would've been taken. There was a time when the site was ranked higher than #1,734 by Alexa!

Comment from the submitter (2)

_prime (181525) | more than 2 years ago | (#39924499)

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 though interfering with the protein synthesis mechanism (as long as the patient is not at 10,000 feet) would result in some very good news for a lot of people. Like another commenter, I was hoping that someone in the audience who works in a related field could tell us if this would be effective for all or just some cancers. In any case, it sounds like a big step forward and I look forward to hearing more about it.

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