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Gene Therapy Ages Human Cancer Cells in Lab

mattr writes "Korean scientists are the first in the world to selectively age off and kill human cancer cells, by injecting a gene that suppresses telomerase, a cancer-specific enzyme that normally makes cancer cells immortal by protecting the telomere tips of their chromosomes. The telomere length modulation mechanism was found by two scientists from Yonsei University and colleagues at U. Central Florida, and is reported in the April 1 issue of Genes and Development magazine."

21 of 318 comments (clear)

  1. Re:Cool.. but some questions. by teh*fink · · Score: 2, Informative

    (i was just studying this)

    the /. blurb is misinformative, as telomerase is far from a "cancer-specific" enzyme. it is present in many "normal" cells, including sperm and stem cells. also, a cure would not be as simple as just injecting telomerase into a cancerous cell.

    wikipedia article

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  2. Stem cells being affected is even worse by Seoulstriker · · Score: 3, Informative

    If bone marrow stem cells are also affected by this treatment, you can have problems with production of T-cells (CD4+ and CD8+) and erythrocytes (red blood cells). I wish that they would have at least done tests on other types of human cells. The journal article becomes available April 15th, so we shall see what all the fuss is about.

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  3. Re:I wonder... by Yotsuya · · Score: 2, Informative

    You don't want immortal cells. What you want is cells that can be regenerated. Infinitely.

    --
    Claude Angers
  4. Re:Koreans by Spud+Stud · · Score: 5, Informative

    To be fair, fetal tissue research has not been blocked. Only federal funding thereof - privately funded research may proceed unabated.

  5. Re:In normal human cells... by Quirk · · Score: 2, Informative

    HeLa cells have an interesting history, they were derived from the cervical carcinoma of Henrietta Lacks. There is a theory that the loss of telomere length is at the root of aging. I recall reading that HeLa cells were sent up on Voyager, although I can't immediately recall the source.

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  6. Re:Koreans by Anonymous Coward · · Score: 1, Informative

    If cells age because child cells of a mitosified cell contain fewer telomeres, then something that prevented that telomeric loss would lead to an eternal lifetime for splitting cells.

    Yes, but if I right understood the article, it talks about supressing telomerase which prevents telomeric loss for cancer cells. Telomerase has no effect on healthy cells and can therefore not be used to prevent human cells from aging. The experiment does the opposite, it leads abnormal cells to a dying process.

  7. Re:Obvious question by Anonymous Coward · · Score: 2, Informative

    No. Making non-cancer cells immortal is not a wise idea. If you are making non-cancerous cells immortal, you are bring yourself one step closer to cancer.

    In order for a cell to become cancerous, there essentially needs to be two mutations to occur. One mutation that allows for immortality (e.g. telomerase), and one to DISregulate growth. If a cell is no longer properly inhibited (loss of a tumor repressor gene) or abnormally activated (activation of an oncogenic gene), the cell can start deviding out of control. If the cell line is not immortal, eventually, due to the inability for DNA transcription to fully replicate the DNA strands (it can't get all of the end, aka "the telomeres"). Eventually, the telemere is used up, and genes are lost, eventually leading to non-viable cells. If the cell can escape this problem, it can grow forever and for a tumor).

    I think that people are getting a little confused on the "aging" issue. Its not like they are doing something to make cancerous cells age faster, what they are doing is forcing the cells to age normally like any other cell in the body (except those that don't, e.g. your stem cells that make your blood cells).

    Another way to think about all this is to say that your body has two ways of preventing cancer. 1, it regulates when cells are allowed to devide, and 2, if mechanism one fails, cells have a built in time bomb that prevents them from deviding more than a certain number of times. If we removed this failsafe, loss of mechanism one would lead to a LOT of cancers forming in your body.

  8. Re:You've got it backwards by IdahoEv · · Score: 3, Informative

    Oops - second quote should have been:

    most cancer cells inhibit telomerase to allow survival, so you'd have to inhibit the telomerase inhibitor.

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  9. Re:Fertility is a big problem by Anonymous Coward · · Score: 5, Informative

    I think the real problem is the insertion of this gene into cells in general. Unless the technique is 100% efficient (all the cancer cells are treated), the tumor is going to just grow back again.

    Using a virus to infect cells wouldn't work because any further doses of the virus would be less effective due to immune responses. Even when just using liposomes (spherical containers made up of phospholipids) carrying the antitelomerase gene to transfect the cancer cells, the efficiency would only be about 50% max. This means that only 50% of the cells would get the gene, while the remaining will still be untreated. In this situation, the transfected cells will die off due to the effect of this new anti-telomerase gene, but the untransfected ones will have a selective advantage and take over, making the tumor continue to grow.

  10. Re:In normal human cells... by BioCS.Nerd · · Score: 2, Informative
    "What isn't clearly mentioned is that telomerase is *inactive* in normal human cells"

    Not entirely true as, "Telomerase is present in most fetal tissues, normal adult male germ cells, inflammatory cells, in proliferative cells of renewal tissues, and in most tumor cells.". This begs the question how you destroy cancerous cells without destroying normal cells that require the telomerase enzyme.

    I haven't yet accessed the full text article, but the poster mentioned that the scientists in question are selectively killing only cancerous cells via down regulation of telomerase. Can anyone verify this? If so, how are they doing it?

  11. Re:Obvious question by devastopol · · Score: 3, Informative
    If telomerase makes cancer cells immortal, is someone working on a way to make, uh, non-cancer cells immortal?

    Yes, to some degree, Geron Corporation has.

  12. Re:Fertility is a big problem by banuk · · Score: 2, Informative

    I'd say the bigger problem (other than sterility) would be affecting the telomerase inside the cells of your stomach and bone marrow (not to mention hair) which are constantly reproducing and need a certain amount of telomerase activity to replicate. Shortly after being cured of cancer you'd die of starvation. (assuming a bone marrow transplant can replace your lost marrow)

  13. Re:Who would pay money for a slashdot id? by John+Seminal · · Score: 2, Informative
    It's a style thang. You wouldn't understand.

    To impress who? Nobody is getting laid by showing a chick their slashdot id number.

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  14. Re:Cool.. but some questions. by Lennavan · · Score: 5, Informative

    I honestly hope some moderator mods this up fast. I'm a grad student working on this very thing so I'd like to hope I know something about it... When Dolly was first cloned we all thought telomeres were the key to keeping clones alive longer. So when Dolly was made as a clone the nucleus was injected into an oocyte that had telomerase activity that restored Dolly's telomeres (read: Dolly had normal telomeres). Yet Dolly displayed many diseases and phenotypes that old sheep normally would. The obvious conclusion, there are other factors that we don't know about that contribute to both aging and death. Please please please don't think telomerase is the key to immortality and the cure to cancers. Yes most cancers eventually gain telomerase activity but this isn't some magical target for immortality and cancer cures.

  15. Re:who gets credit by pio!pio! · · Score: 2, Informative

    Well my sister works in a bio research lab, and she has done all the testing herself and written the entire paper herself...and the Professor gets top billing. I think one time she didn't even get credit because she was still an undergrad..yet she did all the work and wrote the whole paper..

    Sometimes the professor acts more like a manager is just concerned w/ the progress of the schedule or research than the actual research...

  16. Re:Obvious question by blincoln · · Score: 2, Informative

    If you are making non-cancerous cells immortal, you are bring yourself one step closer to cancer.

    The latest laboratory research into enabling telomerase in normal human cells indicates that it does not result in cancer even after the cells have lived 50% longer or more than they would have otherwise.

    --
    "...always new atoms but always doing the same dance, remembering what the dance was yesterday." -Richard Feynman
  17. Re:Not always.... by penguin+king · · Score: 4, Informative

    Who was it that revolutionised the dye industry? The Americans and Germans? I'm sorry I was of the impression that an Englishman by the name (Sir) William Perkins revolutionised the dye industry. The first non-plant based die, based on coal-tar analine products was discovered by Sir William. The first such die was Mauve, this discovery of how to manipulate organic products is generally recognised as one of the discoveries that revolutionised modern chemistry, drugs etc which you credit to America and Germany. Interesting that you use American spellings, so I presume you are American yourself.

    Sure it would be true to say that other countries took the revolution and made the most of it, the revolution itself, and the start of such industrial manufacturing of dies(leading onto other related areas) started in the house of William Perkins, in London England.

    William Perkins

    Also a good read:

    Mauve

  18. Re:Koreans by Anonymous Coward · · Score: 4, Informative

    Cancer cells turn on the genes full-tilt for Telomerase, ensuring their survival. Normal, healthy cells do not and eventually die -- it is believed to be a protection AGAINST cells becoming cancerous. That is, if a cell lives long enough it will eventually accumulate enough gene damage that it stops working correctly and likely becomes cancerous.

    That is not to say that turning on telomerase in healthy cells is a bad thing -- as long as you have a way to turn it off in cancerous cells. If one could do that, then yes, the normal cells could be for all intents and purposes considered immortal.

  19. Re:Koreans by nutshell42 · · Score: 4, Informative
    The problem is that afaik it's impossible for an *institution* to get federal funding if anyone of that institution does such research.

    So you don't lose federal funding for a specific project but for everything. With very few exceptions almost any university, research institute etc. gets federal funding for something (could be the sports program, cleaning the toilets, other research projects...) so effectively it's a ban.

    Feel free to correct me if I'm wrong (and you have proof =)

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  20. Not first by a long shot by climb_no_fear · · Score: 3, Informative

    Here's a 4 year old paper about a compound that doesn't only work in cell culture but also in animals. Sorry but who's first?

    A highly selective telomerase inhibitor limiting human cancer cell proliferation

    As an aside, would you rather take a pill or inefficient, potentially mutagenic gene therapy?
    I know what I'd choose...

  21. Re:Obvious question by Anonymous Coward · · Score: 2, Informative

    Enabling telomerase itself would not result in cancer. In my earlier post, I mentioned that it is a two-hit problem. Take for instance the problem with retinoblastoma. In this pediatric cancer, the RB gene, a so called tummor suppressor gene, is mutated in one copy. The other copy functions normally. However, because it is so easy to accidently knock out the other copy via random mutation, that all of these children who have this mutation develope cancer of the retina. Not only that, they develope tumors in both eyes (from independant lines, not from spread of the original tumor). Without inherriting the original non-function gene, retinoblastoma is exceedingly rare. It would require two independant hits, knocking out each copy of the rb gene in a single cell, that it usually doesn't occur. However, if you cripple all the cells by kocking out one, the odds of the other copy begining knocked out by chance are very good.

    Back to telomerase, if you were to activate it in all of your body cells, you are just making it easier for a new cancer to occur. It still requires another mutation, but you have overcome one of cancers hurdles (namely immortality) for it.