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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."
So they can selectively age cells through gene theraphy... Can we do the inverse to stop the aging of other cells?
In Korea, only cancer gets old!
But seriously, this is very interesting. When telomeres started getting press a few years back, it was really obvious that this would eventually be the key to managing cancer. (And if Alex Chiu gets his way, the key to immortality).
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.
What has interested me about this is that babies are born with a full set of telomeres. This means that the telomeric levels of the parent (mother) is not passed to the child. All other cells in a person's body are dependent on the number of telomeres present in those first few cells clumped together in the womb.
By blocking fetal tissue research, the harvesting of these precious cells is hampered. The reasons for fetal research are many, and the study of telomeres is one big area that simply can't be replicated with non-fetal stem cells.
Telomerase is not only in cancer cells, it's in a bunch of other kind of cells - generally ones long lasting. That's what gave the idea in the first place to do research along these lines. The Wikipedia isn't totally off, would be a good thing to read for correct information: http://en.wikipedia.org/wiki/Telomerase
Inhibiting telomerase has a significant problem: it kills off the gametocytes, which need telomerase to reproduce constantly but still have constant length telomeres. The side effect has to be infertility, unless the researchers found a receptor or variation in cancer cells which allows selective target for the vector. I have a feeling that it is not what they did, since the cancer cells were grown in a tissue culture, and not in vivo. We'll have to wait for human studies to see where this is going.
This mechanism has been studied for a very long time, but this must be the first time that researchers have been successful in manufacturing the vectors.
Of course, there are still promising treatments such as angiogenesis inhibitors which has the benefit of not losing fertility.
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What isn't clearly mentioned is that telomerase is *inactive* in normal human cells. We're born with our telomeres at a certain length, and they're never renewed. That's why some cancers are unique in that they reactivate this latent gene therebye making them immortal; for example, Hela cells are used in every lab across the country. They originally were taken out of some woman's breast cancer in the 50's and they're still thriving! As a matter of fact, while she's long dead, there's still several tons of her! But even if you were to turn off a reactivated telomerase gene, it is logical to believe that they would begin to age normally; ie, if the person with the cancer is in his 50's, the cancer might not die for several decades. The important thing to remember is that *every* cancer in every person is different on a molecular level. They are all unique, and that is why we'll never have a blanket cure for cancer. What we will eventually have is effective treatment for currently untreatable types, which is a different story all together.
they don't know how the gene works, they've only killed off in vitro cells, and they haven't tested it in the context of cancer cells surrounding normal cells. how can this be selective? for all we know, the mechanism could accelerate the removal of telomeres in normal cells. really, what does "selectively" mean here, besides that they selected only cancer cells to test the gene on?
afaik, telomerase breaks down telomeres, no matter what kind of cell you have. most cancer cells inhibit telomerase to allow survival, so you'd have to inhibit the telomerase inhibitor.
Finding it and then inserting genes or drugs to kill it is hard.
Gene therapy using viruses has failed because the body attacks the modified virus . Some people have died because of this and research was stopped.
There are some new ideas on using HIV virus which is harder for the immune system to attack.
Their TVAX vaccine against cancer in a phase one at Duke caused the strongest human immune system against cancer that has ever been seen in a cancer vaccine. 19 out of 21 men with hormone refractory prostate cancer with mets, saw thier blood become free of cancer. For some there was a thousand fold reduction in the number of blood born cells. Dr's Vieweg and Bilboa are tweaking the vaccine for the phase 2 now recruiting at Duke, see Geron's web page and click on patient info, it gives you dukes number. No side effect were observed. It only targets cancer cells, which for the most part externally signal that they are making a lot of telomerase. May also be recruiting for primary kidney as well as hormone refractory prostate cancer with mets. Their other drug candidate, GRN163L is a oligo, that directly and strongly binds telomerase so it can't lengthen telomere tails. No toxicity was seen in the animal trials till they had exceeded 8 times the maximum theraputic dose. Cancer is screwed soon. Geron is using telomerase to promote the growth of stem cells in commercial scaled, (for treatments and trials). When you were in the womb, during the first trimeste of pregnancy, you produced telomerase like crazy, then it shuts off after the first trimester. If it turns on later in life, it can be real bad if the other mutations that cancer needs are also present. That's cancer. A cell gets in trouble, and doesn't die because of telomerase, but it isnt a bad thing, its the other mutations that, if present, make the cancer. Telomerase just provides the cancer cell with immortality and promotes cell division. Viral attacked cells, and warts, have telomerase turned on, but they don't have the other bad mutations too, if they get them, cancer happens. EGCG from green tea is a direct telomerase inhibitor too, need ten cups a day , try the extract capsules, each one like 4 cups of green tea per day. Put them in your coffee, it turns out that in the lab and in animals, green tea with caffiene is far more effective at killing cancer cells than the decaf green tea.
wow. I am glad to see some good news like this. I have a cousin dying of leukemia(sp?) who probably won't live through the weekend. She is 37 yrs old. she has 4 kids... the younger ones are 2 and 4.
At times like this it is hard not to get mad at the medical profession. On the other hand I have a great appreciation for what medicine has done for my family.
The cousin I mentioned got an extra year of life because of an experimental stem cell (no not the kind thats been in the news) transplant.
My father has had open heart surgery twice. He is 64 years old and still goes backpacking with my brother and I.
My mom, although a survivor has had cancer 3 seperate times: breast cancer in each breast and a melanoma in her eye.
It is from the latter that I gained a great respect for medical research, and it is why I smile reading a story like this article.
when she had her eye cancer there was a new experimental treatment at the UW hospital here in seattle. They cut her eye open and sewed a patch of radioactive material over the tumor. They then sewed the eye shut and sent her home for several days with a lead shield over her eye.
Then they took her back to the hospital and cut the eye open again and removed the patch. Over the course of the next year the tumor died back (we know because of the ultrasound and other tests they do on her). Now she has finally lost the last of the usefull sight in that eye. The sight-loss is due to the close proximity of the radiation treatment to the optic nerve.
The only other treatment at the time was to remove the eye completely. With the radiation treatment she got many years of good sight out of that eye she wouldn't have had.
It is funny to me that at the time that treatment seemed so high tech. now it just sounds barbaric. cutting the eye open twice... so invasive. Now this article highlights something that may, in our lifetime be the new exciting experimental cancer treatment, and our kids (if they can still afford health care) will wonder how we endured such brutal treatment (I would suspect no cancer treatment in our lifetime will be FUN anyway)
I guess my cousin's situation has me in an extra thoughtful mood tonight.
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That depends on what the dominent cause of aging is.
One theory is that it is just too metabolically expensive to run a really good error checking system on non-germ-line cells.* As our cells divide, errors accumulate, more of them operate with reduced efficiency or not at all, and we see the result as aging. Fixing up the telomeres wouldn't help this.
An analogy: Imagine when you buy a new car, you get 10 sets of extra tires. You can use those tires on your car, but not get any more. Once the 10th set is used, the car is useless. The telomere fix would be like having an inexhaustable supply of tires - but about the time you've used the 10 sets of tires, the car is falling apart anyhow.
* The argument goes that if you spend all that energy on error checking, you have less to spend on reproduction. Sure, you potentially get to reproduce for much longer, but for most of our evolutionary history, it was seldom age that killed our ancestors.
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telomerase is an enzyme that adds a tail to the end of the DNA strand during replication. this tail is folded over to form a primer for the lagging strand and eventually clipped. without the tail, about 100 base pairs of gene will be folded over instead every time replication occurs. the loss of this DNA during every replication is why we age.
telomerase is switched off in normal somatic cells. however, in cancer cells it is switched on (cancer cells are essentially immortal). the only place where telomerase is needed is in the germ line cells, which is why this treatment may have the side effect of infertility.
This experiment was conducted in a petri dish.
Killing cancer cells in a petri dish is one thing, locating them, isolating them and killing them in the human body is another.
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I don't that research is less of a priority in America than it used to be. Research is being funded from companies and government agencies that have fallen prey to the same thinking that caused/exacerbated the Enron-ish scandals: Only short-term rewards are important. This thinking also seems to be showing-up in our government officials (perhaps because the current crop are businessmen?).
Any research that is not expected to bear fruit within a very few years is less likely to get funding, even if the long-term rewards that might be forthcoming from that research are great.
Nod to Godwin's Law: Hitler made two large mistakes concerning scientific research. He banned any research into defensive weapons (on the theory that his uber-soldiers would never be on the defensive), and he banned any weapons research that was expected to take more than two years to deliver a weapon (probably on the theory that he would control the world in less than two years). American research is falling into this second trap.
Censorship is telling a man he can't have a steak just because a baby can't chew it. --Mark Twain
Additionally Alfred Bester alluded to this in The Computer Connection (1975!) where he referred to the fact that the immortals in his story were living just short of runaway cancer...sort of the theory "the cure for cancer is old age."
Interesting how life imitates art.
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