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Yahoo message board is down or else I've been banned, LOL!!! EOM
Good Job Bob, There's a hell of a difference between having two telomerase cancer therapies in human trials , and a telomerase activator about ready to supernova in China, and a damn animal trial. Please post their reply. The reporter was obviously pretty lazy in researching the story.
Gene Found to Switch Off Stem Cells During Aging
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By NICHOLAS WADE
Published: September 6, 2006
Biologists have uncovered a deep link between lifespan and cancer in the form of a gene that switches off stem cells as a person ages.
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p16INK4a Induces an Age-dependent Decline in Islet Regenerative Potential (Nature)
Increasing p16INK4a Expression Decreases Forebrain Progenitors and Neurogenesis During Ageing (Nature)
Stem-Cell Ageing Modified by the Cyclin-Dependent Kinase Inhibitor p16INK4a (Nature)The critical gene, already well known for its role in suppressing tumors, seems to mediate a profound balance between life and death. It weighs the generation of new replacement cells, required for continued life, against the risk of death from cancer, which is the inevitable outcome of letting cells divide. To offset the increasing risk of cancer as a person ages, the gene gradually reduces the ability of stem cells to proliferate.
The new finding, reported by three groups of researchers online Wednesday in Nature, was made in a special breed of mice that lack the pivotal gene, but is thought likely to apply to people as well.
The finding indicates that many of the degenerative diseases of aging are caused by an active shutting down of the stem cells that renew the body’s various tissues, and are not just a passive disintegration of tissues under life’s daily wear and tear, as is often assumed.
“I don’t think aging is a random process – it’s a program, an anti-cancer program,” said Dr. Norman E. Sharpless of the University of North Carolina, senior author of one of the three reports. The two other senior authors are Dr. Sean J. Morrison of the University of Michigan and Dr. David T. Scadden of the Harvard Medical School.
The finding’s implications for cell therapy based on using a patient’s own adult stem cells are not yet clear, but news that the cells get switched off with age does not seem particularly encouraging. The result may undercut opponents of research with human embryonic stem cells who argue that adult stem cells are sufficient for cell therapy. Dr. Sharpless said his finding emphasized the need to pursue both types of research.
The gene involved in the new finding has the unmemorable name of p16-Ink4a but plays a central role in the body’s defenses against cancer. It produces two quite different proteins that interact with the two principal systems for deciding whether a cell will be allowed to divide.
One of these proteins had also been noted to increase substantially with age. The cells of a 70-year-old person produce 10 times as much of the Ink-4 protein as do those of a 20 year-old, Dr. Sharpless said. To help understand why this was so, Dr. Sharpless genetically engineered a strain of mouse in which the gene was knocked out.
He set out to see if loss of the gene would have any effect on the mice’s blood-making stem cells. Learning that Dr. Morrison was interested in the same question with brain cells, and Dr. Scadden with the insulin-making cells of the pancreas, he shared his mice with them and the three teams agreed to publish their findings together, a departure from the usual competitiveness between researchers.
All three teams report essentially the same result, that in each type of tissue the cells have extra ability to proliferate when the Ink-4 protein can no longer be made. At the same time the Ink-less mice are highly prone to cancer, which they start to develop as early as one year of age.
The researchers assume, but have not yet proved, that the increasing amounts of Ink-4 made as a person ages will thrust the stem cells into senescence, meaning they can never divide again. The evolutionary purpose is evidently to avert the risk that a damaged stem cell might evade controls and proliferate into a tumor.
One implication is that therapists hoping to increase longevity must tackle a system that may be hard to cheat. Any intervention that reduces production of the Ink-4 protein in order to prevent the age-related decline of stem cells will also increase the risk of cancer.
“There is no free lunch — we are all doomed,” Dr. Sharpless said. But he quickly modified his comment by noting that a calorically restricted diet is one intervention that is known to increase lifespan and reduce cancer, at least in laboratory mice. The reason, he said, is probably because these diets reduce cell division, the prime source of cancer risk. For cell therapists, the dual activity of Ink4 may be “a hard box to get out of,” he said, unless they use cells that are somehow much younger than the patient. Dr. Scadden, however, said he hoped there would turn out to be some sloppiness in the Ink-4 gene’s balancing trick, allowing it to be switched off temporarily with yet to be invented drugs in a way that would promote stem cell proliferation without greatly increasing the risk of cancer.
“There is clearly a dark side to the finding, but whether or not we can exploit it, that’s the challenge,” he said.
Some proposals for stem cell therapy with adult stem cells envisage taking a patient’s stem cells, making them divide in the laboratory, and putting them back in the patient to build new tissue. “The notion that adult stem cells are infinite in proliferative capacity is seriously undermined by this work,” Dr. Sharpless said.
Dr. Morrison said it had long been known that older patients don’t do as well in bone marrow transplants as younger ones, and the new finding might explain why. “I don’t think any of these findings dims the promise of stem cell research at all,” he said, because the greater robustness of younger people’s cells was already well known.
The researchers say they do not yet know what stimulus makes cells increase their production of the Ink-4 protein as a person grows older. Their suspicion is that the usual factors implicated in aging, such as mutation and oxidative damage to tissues, would turn out to play a role in making cells produce more Ink-4.
Dr. Ronald A. DePinho, an expert on cellular aging and a co-author of Dr. Scadden’s report, said the new finding, in showing how the renewal capacity of stem cells was governed, might enable drugs to be made that would improve cell transplants.
Dr. Scott Lowe, a cancer gene expert at the Cold Spring Harbor Laboratory who was not involved in the three papers, said the new results were very interesting because they linked to aging a gene of central importance in cancer.
More Articles in Science »
Switching off Aging in Stem Cells, Howard Hughes Medical:::
September 06, 2006
Switching off Aging in Stem Cells
A single molecular switch plays a central role in inducing stem cells in the brain, pancreas, and blood to lose function as they age, researchers have found. Mice lacking that switch show considerably reduced aging-related decline in stem cell function and tissue regeneration.
“People tend to think that old tissues have less regenerative capacity because they are wearing out,” said Sean J. Morrison, a Howard Hughes Medical Institute investigator at the University of Michigan who led the study of the switch's role in the brain. “This work shows that they are not just wearing out; they are actively shutting themselves down.”
“People tend to think that old tissues have less regenerative capacity because they are wearing out. This work shows that they are not just wearing out; they are actively shutting themselves down.”
Sean J. Morrison
While the finding could ultimately lead to drugs to slow or reverse degeneration in the brain and other tissues, the researchers cautioned such treatments would have to be balanced against the chance of increasing cancer risk in patients. Stem cells are the immature progenitor cells that are the continuing self-renewing source of mature, differentiated cells in the body.
Morrison's study was published online September 6, 2006, in Nature, ahead of publication in the journal's print version, along with two other studies from independent research teams that studied how a protein called inhibitor of cyclin-dependent kinase 4A, or p16INK4a, contributes to stem cell decline. The other papers reported studies of the gene's role in stem cell decline in insulin-producing pancreatic islet cells and hematopoietic stem cells, which generate blood cells. Those studies were headed, respectively, by Norman Sharpless of the University of North Carolina at Chapel Hill and David Scadden of Harvard University.
“Before this work, p16INK4a was thought of only as a gene that inhibited cancer formation by inducing senescence in the cell,” said Morrison. “The idea was that it wasn't expressed in normal tissues, and therefore probably didn't have a physiological role but only came on when something went wrong in the cell.”
However, said Morrison, studies in Sharpless's laboratory found that the gene becomes increasingly active as tissues age. “That started us thinking that maybe this gene is part of why old tissues have less stem cell activity and less regenerative capacity, for example taking longer to heal,” said Morrison. “In our lab, for example, we've found that the brain makes fewer neurons with age, but the molecular mechanism for that effect was not known.”
Morrison and his colleagues followed stem cell activity in the brains of normal mice as they aged. The researchers analyzed a particular area of the forebrain, the subventricular zone, known to be an important center of neuronal production, called neurogenesis, in adults. The other two research teams studied pancreatic islet cells and hematopoietic stem cells for the same reason - that they are a constant source of new cells in the adult.
Morrison and his colleagues found that stem cell number and self-renewal function, as well as neurogenesis, declined with age in the mice. But they found that during aging, p16INK4a gene activity increased.
However, in genetically engineered mice that were deficient in p16INK4a, stem cell function and neuronal production were enhanced in old but not young mice as compared to normal mice. “We didn't turn an old brain into a young brain by deleting p16INK4a, but the deficient mice did show significantly increased progenitor cell function and neurogenesis with age, compared to normal mice,” said Morrison. “This tells us that p16INK4a is not the whole story, although it's an important part, and that other genes also regulate the aging process.”
Morrison and his colleagues also found evidence that the gene does not play the same role in other neural tissues. “There are different kinds of stem cells in different regions of the brain, and some of those stem cells are more sensitive to factors like p16INK4a than others,” said Morrison. p16INK4a deficiency did not prevent the atrophy of the cortex that normally occurs with aging, they found. Nor did the deficiency prevent loss of function in another brain region, the hippocampus, that is also a center for neurogenesis in adults. The researchers also analyzed peripheral nerve cells in the gut and found that p16INK4a did not prevent loss of stem cell function there. “There are probably other factors that are important for aging of the hippocampus and the peripheral nervous system,” Morrison noted.
Nevertheless, he said, the discovery of the central role of p16INK4a is highly significant. “I think if you asked before these studies whether you could delete a single gene and rescue stem cell function in multiple tissues, and neurogenesis in an old brain, many people would have said that aging is such a complex phenomenon that you would not get a significant effect,” he said.
Morrison theorized that p16INK4a is a suppressor of stem cell function that evolved as part of the regulatory machinery that also includes proto-oncogenes that encourage cell proliferation. “We are all evolutionarily selected to, on the one hand, maintain regenerative capacity of our tissues through adult life so that we can repair our cells and survive injuries — while on the other hand, limit proliferation in our tissues with age, so cells don't divide out of control, causing cancers,” he said. “And the way that we achieve that balance is by having proto-oncogenes that promote proliferation come into balance with tumor suppressor genes that inhibit proliferation. This work shows one way that this balance changes with age.
“While these tumor suppressor mechanisms don't even exist during fetal development, where cells must divide rapidly, it makes sense that they become stronger in old age, when we are more at risk of getting a cancer,” said Morrison. “So, the benefit is that genes like p16 allow us to get older before we get cancer, but the bad news is that they make us lose function with age.”
Thanks Dude! Just tellin it like it is. This thing is going critical IMHO.
I agree Jimcw, the stone is rolling and its a big one. Better to be the stone than the bug,, right about now ,, in my humble opinion. siRNA in nanotubes is just amazing stuff. Read Kurtzweil's book or see his website for a good background. The science of it is moving fast. That the nanotubes used in the studies were non toxic was amazing. Now they want to make them respond to a surface antigen target, telomerase perhaps.
Do note that Johns Hopkins is where Geron used GRN163L to kill cancer stem cells. This seems important. Discussion?
In the meantime, an international research team has shown that carbon nanotubes can also deliver siRNA agents into malignant cells and suppress tumor growth. Yongsheng Chen, Ph.D., from Nankai University, in Tianjin, China, and Richard Roden, Ph.D., from Johns Hopkins University School of Medicine, led the effort to deliver an siRNA that targets the protein telomerase reverse transcriptase using positively charged single-walled carbon nanotubes. The researchers chose this type of carbon nanotube because negatively charged siRNA molecules would bind tightly to the surface of the nanotubes and because previous research had shown that these types of nanotubes easily cross the cell membrane without associated toxicities.
Initial experiments with tumor cells growing in culture showed that siRNA-nanotube complexes did enter the malignant cells easily. More importantly, once inside the cells the siRNA was able to stop production of telomerase reverse transcriptase and suppress proliferation of the treated cells. In followup experiments, the investigators injected the siRNA-nanotube conjugates directly into tumors, which had the effect of markedly reducing the size and weight of the tumors. The researchers note that while the direct injection technique might be useful with some types of cancer, a more efficient approach would be to add a tumor-targeting agent to the surface of the carbon nanotubes
The work targeting ovarian tumors, which was supported in part by the National Cancer Institute, is detailed in a paper titled, “Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy.” Investigators from University of California at Los Angeles also participated in this study. An abstract of this paper is available through PubMed. View abstract.
The work using carbon nanotubes as a delivery vehicle, which was supported in part by the National Cancer Institute, is detailed in a paper titled, “Delivery of telomerase reverse transcriptase small interfering RNA in complex with positively charged single-walled carbon nanotubes suppresses tumor growth.” An abstract of this paper is available through PubMed. View abstract.
http://nano.cancer.gov
Posted 29th August 2006
Nanotechnology News Archive
Nanoparticles Successfully Deliver Protein-Suppressing RNA-Based Therapies
Small pieces of nucleic acid, known as siRNAs (short interfering RNAs), can turn off the production of specific proteins, a property that makes them one of the more promising new classes of anticancer drugs in development. Two reports in the journal Clinical Cancer Research now show that nanoparticles may be the vehicle of choice for delivering these agents into tumor cells.
"Short interfering RNA is a great technology we can use to silence genes, shutting down production of harmful proteins," said Anil Sood, M.D., of the University of Texas M. D. Anderson Cancer, who together with colleague Gabriel Lopez-Berestein, M.D., led one of the two studies. "It works well in the lab, but the question has been how to get it into tumors." Short pieces of RNA don't make it to a tumor without being injected directly, and injection methods used in the lab are not practical for clinical use.
As their therapeutic agent, the investigators used an siRNA that targets a protein known as focal adhesion kinase (FAK) that helps ovarian cancer cells survive and spread. They packaged this siRNA inside a nanoscale liposome. Getting the siRNA inside tumor cells is important, Sood said, because the targeted protein, FAK, is inside the cell, rather than on the cell surface where most proteins targeted by cancer drugs are found. "Targets like FAK, which are difficult to target with a drug, can be attacked with this liposomal siRNA approach, which penetrates deeply into the tumor," Sood said.
TMice implanted with three human ovarian cancer cell lines derived from women with advanced cancer were treated for 3 to 5 weeks. They received liposomes that contained either the FAK siRNA, a control siRNA, or were empty. Some mice received siRNA liposomes plus the chemotherapy docetaxel. Mice receiving the FAK-silencing liposome had reductions in mean tumor weight ranging from 44 to 72 percent compared with mice in the control groups. Combining the FAK-silencing liposome with docetaxel boosted tumor weight reduction to the 94 to 98 percent range. These results also held up in experiments with ovarian cancer cell lines resistant to docetaxel and the chemotherapy drug cisplatin.
In addition to its anti-tumor effect, the researchers found that the therapeutic liposome attacked the tumor's blood supply, especially when combined with chemotherapy. By inducing programmed cell death, or apoptosis, by angiogenic blood vessel cells, the treatment steeply reduced the number of small blood vessels feeding the tumor, cut the percentage of proliferating tumor cells and increased apoptosis among cancer cells. Based on these results, the M. D. Anderson research team plans to begin safety testing as the next step toward human clinical trials.
In the meantime, an international research team has shown that carbon nanotubes can also deliver siRNA agents into malignant cells and suppress tumor growth. Yongsheng Chen, Ph.D., from Nankai University, in Tianjin, China, and Richard Roden, Ph.D., from Johns Hopkins University School of Medicine, led the effort to deliver an siRNA that targets the protein telomerase reverse transcriptase using positively charged single-walled carbon nanotubes. The researchers chose this type of carbon nanotube because negatively charged siRNA molecules would bind tightly to the surface of the nanotubes and because previous research had shown that these types of nanotubes easily cross the cell membrane without associated toxicities.
Initial experiments with tumor cells growing in culture showed that siRNA-nanotube complexes did enter the malignant cells easily. More importantly, once inside the cells the siRNA was able to stop production of telomerase reverse transcriptase and suppress proliferation of the treated cells. In followup experiments, the investigators injected the siRNA-nanotube conjugates directly into tumors, which had the effect of markedly reducing the size and weight of the tumors. The researchers note that while the direct injection technique might be useful with some types of cancer, a more efficient approach would be to add a tumor-targeting agent to the surface of the carbon nanotubes
The work targeting ovarian tumors, which was supported in part by the National Cancer Institute, is detailed in a paper titled, “Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy.” Investigators from University of California at Los Angeles also participated in this study. An abstract of this paper is available through PubMed. View abstract.
The work using carbon nanotubes as a delivery vehicle, which was supported in part by the National Cancer Institute, is detailed in a paper titled, “Delivery of telomerase reverse transcriptase small interfering RNA in complex with positively charged single-walled carbon nanotubes suppresses tumor growth.” An abstract of this paper is available through PubMed. View abstract.
http://nano.cancer.gov
Posted 29th August 2006
Nanotechnology News Archive
Public Employees for Environmental Responsibility News Release (www.peer.org)
For Immediate Release: February 10, 2006
Contact: Carol Goldberg (202) 265-7337
BUSH AXING LIBRARIES WHILE PUSHING FOR MORE RESEARCH — EPA Set to Close Library Network and Electronic Catalog
Washington, DC — Under President Bush’s proposed budget, the U.S. Environmental Protection Agency is slated to shut down its network of libraries that serve its own scientists as well as the public, according to internal agency documents released today by Public Employees for Environmental Responsibility (PEER). In addition to the libraries, the agency will pull the plug on its electronic catalog which tracks tens of thousands of unique documents and research studies that are available nowhere else.
Under Bush’s plan, $2 million of a total agency library budget of $2.5 million will be lost, including the entire $500,000 budget for the EPA Headquarters library and its electronic catalog that makes it possible to search for documents through the entire EPA library network. These reductions are just a small portion of the $300 million in cuts the administration has proposed for EPA operations.
At the same time, President Bush is proposing to significantly increase EPA research funding for topics such as nanotechnology, air pollution and drinking water system security as part of his “American Competitive Initiative.”
“How are EPA scientists supposed to engage in cutting edge research when they cannot find what the agency has already done?” asked PEER Executive Director Jeff Ruch, noting that EPA Administrator Stephen Johnson is moving to implement the proposed cuts as soon as possible. “The President’s plan will not make us more competitive if we have to spend half our time re-inventing the wheel.”
EPA’s own scientists and enforcement staff are the principal library users. EPA’s scientists use the libraries to research questions such as the safety of chemicals and the environmental effects of new technologies. EPA enforcement staff use the libraries to obtain technical information to support pollution prosecutions and to track the business histories of regulated industries.
EPA currently operates a network of 27 libraries operating out of its Washington, D.C. Headquarters and ten regional offices across the country. The size of the cuts will force the Headquarters library and most of the regional libraries to shut their doors and cease operations. Each year, the EPA libraries –
Handle more than 134,000 research requests from its own scientific and enforcement staff;
House and catalog an estimated 50,000 “unique” documents that are available nowhere else; and
Operate public reading rooms and provide the public with access to EPA databases.
“Access to information is one of the best tools we have for protecting the environment,” added Ruch, calling the cuts the “epitome of penny wise and pound foolish.” “By contrast, closing the Environmental Protection Agency libraries actually threatens to subtract from the sum total of human knowledge.”
###
Read about the impacts of the EPA library system cuts
Look at the number of library services on the chopping block
View the staff and budget cuts, library-by-library
Dr. Eliz Blacburn speaks about telomerase and Bush ethics panel.
Click on the link, under the photo of Blackburn and some guy, is a link to which audio player you want to use. Its audio only, but is interesting...
http://www.abc.net.au/queensland/conversations/stories/s1710712.htm?queensland
New vaccine antigen found in both cancer and fetus !!!
This isn't Geron but its more excellent news on vaccines and cancer!!!!!!!!!!
Cancer hope as vaccine trials start
Doctors aim to save thousands of lives by forcing the body's immune system to destroy tumours
Jo Revill, health editor
Sunday August 27, 2006
The Observer
A new vaccine which targets some of the most serious forms of cancer may prevent patients from suffering a relapse once they have had initial surgery or drugs treatment.
A trial involving 700 patients with kidney cancer will start this year across Britain and other European countries. Half will be given injections of TroVax as well as their normal chemotherapy drugs. The others will have the drugs plus a placebo injection. The survival rates of the two groups will then be compared.
Although it is still early days, the work already done suggests the therapy is safe and that it does trigger the body's own immune system to attack the tumour. Other clinical trials looking at the vaccine's impact on patients with colorectal cancer is also planned, as are further studies for breast cancer sufferers. There is even a veterinary product which has been made in order to treat cancer in dogs and cats.
One of the most exciting areas for cancer treatment now lies in the development of vaccines, 40 years after the idea was first mooted. There are two types of immunisation: those that are therapeutic and used to treat existing cancers, such as TroVax, or those which are prophylactic to prevent the development of cancer in the first place.
The NHS is likely to see the introduction within the next year of a vaccine to prevent women developing cervical cancer. The vaccine Gardasil has been designed to fight four strains of the human papilloma virus (HPV) which are responsible for around the great majority of cases. If teenagers could be vaccinated at school before they become sexually active, they could drastically reduce the incidence of the cancer, which kills around 1,000 British women a year.
Therapeutic vaccines are able to take advantage of the fact that some molecules which live on the surface of cancer cells are either unique to that cancer, or more abundant than they would be in healthy cells. But there are no such treatments yet licensed - all are in varying degrees of development.
The idea for TroVax initially came from scientists at the Paterson Institute for Cancer Research in Manchester, who were interested to know why the immune system doesn't 'see' cancer cells as dangerous or foreign and therefore does not mount an attack on them.
The same applies to the growing foetus, which for some reason is not rejected by the pregnant mother although it contains foreign cells, so scientists hunted for proteins that might be found in both cancer patients and pregnant women.
What they found was 5T4, a protein which lies on the surface of a cancer cell but is also found in the placenta and in the foetus, and which appears to be key to helping cells move around the body. Scientists took a modified form of a virus and genetically engineered it so that it would enable the body to produce antibodies to fight 5T4.
Oxford Biomedica, a biotech company spun off from Oxford University which manufactures the therapy, is now about to embark on a Phase III trial which will look at the long-term survival rates of patients with the main form of kidney cancer, known as renal cell carcinoma.
More than 6,000 patients are diagnosed with kidney cancer each year, and if caught early, it has a good prognosis, but many are diagnosed when it has spread to other parts of the body. The company is planning further studies involving patients with colorectal and prostate cancer.
Mike McDonald, its chief medical officer, said : 'Unlike vaccinations for measles or mumps, patients having this treatment would need to have injections every one or two months because once the effect starts to diminish, you need to do it again. But we are hopeful that it can help people who may already have undergone surgery but where there is a danger of relapse.
'We know in colorectal cancer there is this danger because you get these deposits of small and isolated cells which have escaped, and are suitable for attack by the immune system.'
Gus Dalgleish, professor of oncology at St George's Hospital in south London, has helped to develop a vaccine which may prove effective against prostate cancer, and is now embarking on a large-scale randomised trial carried out across many centres.
He said: 'There have been problems with some of these therapies such as resistance building up as the cancers themselves change, but I think overall it's positive, and that we are close to having active cancer vaccines for many people.'
Agree with your read , Yahoo boards are junk,
By the time they get their stuff together, someone will have duplicated their old format, and will take over their space in stock message boards. This board is close but needs rec's and a proper subject line. The moderator here is tops, Paula won't tolerate short lies and I appreciate that. Honest debate is great and we all learn from it, but the micro types and huge idiots are meant to make learning about the companies technology, an excercise in wading through garbage.
I'd love to see cancerfoe in here. He seemed to leave almost completely with the new yahoo format. Has he been here yet?
Prime3
Yahoo board has turned into a dung heap.
I keep looking at it hoping they will go back to the old format or at least make the new one readable. No dice. Its a real pile of junk. The shorts seem to be the most prolific posters and of course the ever doubt spreading micro is there. Did anyone notice that Yahoo, with the new format, is insisting on an even greater level of privacy invasion?? I had to give it more ability to spy in my firewall,,, then decided it wasn't worth it. My spam increased 3 fold after I let it in. I'm sure glad for spam filters. I would still love to see a subject line here, but that can be done by using the first line in your post as the subject line. Something we should try to do. I still think rec's are important, they help to cut through the clutter, but the boards maker doesn't agree. This board would be more readable if we all learned to use the first line of our posts as a subject line. Still much better than the idiocy of the Yahoo board.
Article Preview
Telomerase inhibition impairs tumor growth in glioblastoma xenografts
Gene Therapy Weekly - Aug. 24, 2006
2006 AUG 24 - (NewsRx.com) -- According to recently published research from Italy, telomerase inhibition impairs tumor growth in glioblastoma xenografts.
"Telomerase is a specialized DNA polymerase that is required to replicate the ends of linear chromosomes, the telomeres. The majority of human cancers express high levels of telomerase activity that is permissive for tumor growth because it provides cells with an extended proliferative potential," wrote M.L. Falchetti and colleagues, CNR.
"Additionally, telomerase exerts cell growth promoting functions and favors cell survival. Human glioblastoma multiforme (GBM) cells express high level of telomerase activity owing to the overexpression of human ...
Another telomerase based study::
Original Article
Oncogene (2006) 25, 5037–5045. doi:10.1038/sj.onc.1209513; published online 17 April 2006
Expression of hTERT immortalises normal human urothelial cells without inactivation of the p16/Rb pathway
E J Chapman1, C D Hurst1, E Pitt1, P Chambers2, J S Aveyard1 and M A Knowles1
1Cancer Research UK Clinical Centre, St James's University Hospital, Leeds, UK
2Cancer Research UK Mutation Detection Facility, St James's University Hospital, Leeds, UK
Correspondence: Dr MA Knowles, Cancer Research UK Clinical Centre, St James's University Hospital, Beckett Street, Leeds LS97TF, UK. E-mail: margaret.knowles@cancer.org.uk
Received 23 June 2005; Revised 7 February 2006; Accepted 15 February 2006; Published online 17 April 2006.
Top of pageAbstract
The CDKN2A locus is frequently inactivated in urothelial cell carcinoma (UCC), yet how this alteration contributes to bladder tumorigenesis is not known. Although most UCC express telomerase, inactivation of the p16/Rb pathway is generally required for in vitro immortalisation. This and the involvement of p16 in senescence of normal human urothelial cells (NHUC) suggest that CDKN2A deletion may aid bypass of senescence and allow immortalisation. CDKN2A encodes p16 and p14ARF and therefore inactivation of this locus can disrupt both the Rb and p53 tumour suppressor pathways. Retrovirus-mediated transduction was used to specifically modulate the p16/Rb and/or p53 tumour suppressor pathways in NHUC and to express human telomerase reverse transcriptase (hTERT). Expression of hTERT bypassed Rb and p53 pathway-dependent barriers to proliferation and immortalised NHUC. TERT-NHUC had normal karyotypes, were non-tumorigenic and unexpectedly retained CDKN2A. Thus, the phenotypic significance of inactivation of CDKN2A in UCC may not be solely related to bypass of senescence. Phenotypic assays in human urothelial cells have relied on cell strains derived from invasive tumours or NHUC immortalised by expression of SV40-large T. The production of genetically normal but immortal NHUC lines now provides a valuable platform for experiments to examine the timing and combination of events necessary for UCC tumorigenesis.
FROM THE METHUSELA PRIZE BOARD::
As I've noted in the past, it seems a number of strategies under development to repair or offset damage done by AIDS to the immune system may also - at some point in the future - be usefully applied to declines in the aging immune system. At least some of the underlying damage is similar in both cases. A recent release from Geron has this to say:
The new studies demonstrate that our orally available telomerase activator drug broadly reactivates anti-HIV immunity in AIDS patients' lymphocytes. The lymphocytes are the primary mechanism for containing HIV infection early in the course of the disease. Over time, telomere loss in these cells results in the gradual decline of their anti-HIV function, leading to clinical disease progression. Our hope is to use TAT0002 to prevent this immune decline and thereby prevent HIV progression.
Telomeres shorten with age; AIDS research would suggest that this shortening is occuring due to overuse. If your immune system is constantly set on high, the level of wear and tear leads this portion of your biochemistry to look and act like that of someone many decades your senior. If you can fix the first case, why not try the same methodologies for the second?
The more is known of human biochemistry, the more we'll see overlapping science between various fields. Research into manipulating telomeres to treat specific age-related conditions is increasingly active, for example.
Technorati tags: medical research, science
Nature aritcle, longevity
Published online: 17 August 2006; | doi:10.1038/news060814-12
Longevity genes fight back at cancer
Long-lived worms hint at new ways to tackle tumours.
Helen Pilcher
C elegans worms with long-life genes do well even with cancer.
SPL
Genetic mutations that increase lifespan also seem to be particularly good at fighting tumours, a worm study suggests. The finding could shed light on why cancer risk increases as we get older, and may also suggest new targets for cancer therapeutics.
You might expect that genes that promote long life and fight cancer would go hand-in-hand: a gene that protects against tumours would help to stop cancer from killing you, after all, so you would probably live longer. But it seems that the relationship is more complicated than that. Genes that make some animals live longer through non-cancer-related mechanisms also seem to have a particular skill for suppressing tumours.
Cynthia Kenyon and colleagues from the University of California, San Francisco, studied the link in the tiny transparent worm Caenorhabditis elegans, a species that doesn't usually get cancer.
Some genetic mutations in these worms are known to boost lifespan by affecting processes such as hormone signalling, food intake and respiration. Inactivating a gene called daf-2, for example, which is involved in regulating insulin, more than doubles the animals' lifespan from around 17 to 35 days.
When the researchers genetically altered the worms so that they were susceptible to cancer, inactivating daf-2 still let the worms live to 35 days and restricted tumour growth to half the expected size. "These animals still live twice as long as normal even though they've got a tumour," says Kenyon. "It's really amazing."
Knockout round
To perform the study, the team first had to knock out a tumour suppressor gene called gld-1 in the worms, causing cells in the animals' gonads to divide rapidly and form germ-line tumours. Left alone, these cancer cells break out of the gonad and fill the body, killing the worm at around 9 days old.
They then investigated the effects of a handful of different 'longevity' genes in the tumour-ridden animals, to assess the effects on lifespan and tumour growth. All of the longevity mutations tested increased the worms' lifespans even though they had cancer, the team reports in Science1.
In the daf-2 example, the link isn't too mysterious. Researchers have long known that insulin boosts tumour growth in rats. And when tumour-bearing rats are made diabetic, decreasing insulin levels, tumour growth slows. "The study is another example of the intimate tie-in between insulin and tumorigenesis," says David Kritchevsky from the Wistar Institute in Philadelphia, Pennsylvania, who studies the effects of diet on cancer.
In the worms, lowering insulin levels seems to slow cell division and increase apoptosis - the process by which some cells are able to commit suicide — with a particular impact on tumour cells.
The results suggest that tumour cells are generally more susceptible to the effects of longevity-causing mutations than normal cells. So investigating these long-life mechanisms might provide better ways to target cancer. Drugs created this way might even have the side effect of prolonging life, beyond the usual limit for someone without cancer.
Of mice and worms
The authors also hope that their work will help researchers to fathom exactly why aged animals are so much more prone to cancer than young ones.
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The worm study makes for a great start in this direction: the short lifespan of the worms makes for a quick study of old age. But other experts add that other, more human-like models will need to be studied to unpick what's really going on.
Biologist Siegfried Hekimi from McGill University in Montreal, Canada, who studies C. elegans, cautions that the laboratory-engineered worm tumours are very different to naturally occurring mammalian ones: they aren't created by the same mechanism, nor do they spread the same way. So this one study is hard to generalize from. "It tells us that these pathways should be studied in vertebrates," he says. "Only then might we be able to explain how ageing relates to cancer," he says.
Powerpoint presentation for TAT by Harley
Go to this site: http://www.aids2006.org/PAG/PSession.aspx?SessionID=262
Go down to the 5th presentation, which is by Harley. To the left, click your right mouse button on the word,,, Powerpoint, select "save target" , and you can save the power point presentation to your desktop and run it if you have Microsoft Power Point.
TAT is based on a root or herbal extract used in Chinese traditional medicine someone said. Does anyone know which Chinese medicine it's based on? Ginseng?
The story you posted is absolutely amazing. Contagious cancer, inherent stability,, must be shedding a ton of cancer stem cells. DNA stored inherently stable fashion, plenty of telomerase for glycolysis activation, immortality, and upregulating 65 other cancer genes. I read some work a year or so ago where cancer stem cells were very implantable, while regular cancer cells were not. You could use far far fewer cancer stem cells to accomplish cancer starts in animals, compared to plain ol cancer cells. Discussion?
Others believe that the transient activation of telomerase might work to extend lifespan, how much? who knows. Then, with improved cancer detection methods, inhibit telomerase, and turn off its genes. There are some variants of the telomerase gene, and some make more telomerase than others, in cancer cells. This could be a part of the genetic programming she speaks of. But there are a lot of other genes that can help determine lifespan. They are working on technology that can switch genes on and off like a wall switch.
Blackburn Speaks:::
Last Update: Wednesday, August 9, 2006. 2:41pm AEST
Australian-born Dr Elizabeth Blackburn is a Professor of Biology and Physiology at the University of California, San Francisco. Now a US citizen and one of the world's leading bio-medical researchers, Elizabeth's area of research is telomeres and the telomerase enzyme, which has led her into looking at cancer, and also the ageing process.
Elizabeth says that a telomere occurs at the end of a chromosome. "The chromosome contains our whole genetic blueprint, and the telomeres protect the ends of the genetic material from fraying away," she explains. "But they're always at the risk of wearing down, so the telomerase tops them up.
"The analogy that's made is that if you think of the chromosome as a shoelace, the ends need to be protected because they're always fraying away. It's a really interesting race in which the wearing down is happening, but it's being counteracted by the telomerase. So it's the race between the wearing down and the counteracting... and the question is, who's going to win?"
Telomerase is connected to cancer. "Cancer cells are the hardened criminals of your body. They just multiply and multiply and they won't listen to anybody. But it's not good having all these bad properties if you can't keep multiplying, so by hook or crook, they've made their telomerase very active. It gives the cancer cell permission - it doesn't give it it's property - but permission to keep on going and being the bad guys."
Telomerase is also ties in with ageing; in fact, research in this area could potentially be used to extend out lifespan. "What seemed to be fantasy land, the methods have opened up so much that you've got to say, 'well is it plausible'?" asks Elizabeth. "And so the scenarios vary.
There are two kinds of aging that vary. One is the wear and tear, and there's evidence that telomerase is related to that. Telomerase and the maintenance of telomeres, and that looks like it's tied into diseases like cancer and diabetes and heart disease. We die of things that telomerase seems to play helpful roles in counteracting. Then you ask, "Why do people NOT live beyond 120 years?' There really seems to be something that is programmed that way, in the genes...
"Back to the question of ramifications, so we're looking at the part of ageing... that makes old age a misery.. the things that make you frail and infirm, so if you could take care of the wear and tear, then you'd get into the part of natural aging, because people DON'T live beyond 120, but if you could be healthy up to then, that would be a good way to go. So I think our research in the immediate future relates more to living healthily [than developing a] greater age span."
*****************
Big thing is selecting cancer types for each trial that are easiest to determine the drugs effectiveness. For other drugs that have a cancer specific target that other cancers don't have, or express to a varying degree, you have to spend a lot of money on imaging etc ,, to see how well the drug is doing. So as far as expensing, for the most part Geron is able to keep the costs low by selecting cancers that are easy to get good indications on, like prostate in the phase 1/2 vaccine trial, and like CLL for the GRN163 phase 1/2. The all comers, all tumore types trial at U of Chicago might be different, I don't know but its possible that the hospital or patients insurance is going to pay for some of the imaging? , etc, anyway. I'd like to know that and like to be reminded how many will be in the trial.
Its not a gamble, she simply laid down a winning hand.
I keep returning to the Yahoo Geron board, hoping that I will see something interesting in all the short poison that is posted there in the jungle of the new and horrible format. Yahoo is hopeless. They should fire the people who pushed the new format. Their "vision" is blind.
Now, a spice did this,, imagine what a dedicated telomerase inhibitor will do:
1. STOP the expression of 70 cancer genes.
2. REVOKE cancers replicative immortality.
3. DENY cancer cells and cancer stem cells, the glycolysis that is required for their desired rate of growth.
Curcumin inhibits telomerase a bit and slams colon polyps:::;
The newspaper of The Johns Hopkins University August 7, 2006 | Vol. 35 No. 41
Chemicals in Curry and Onions May Help Stop Colon Cancer
By Eric Vohr
Johns Hopkins Medicine
A small but informative clinical trial by Johns Hopkins investigators shows that a pill combining chemicals found in turmeric, a spice used in curries, and onions reduces both the size and number of precancerous lesions in the human intestinal tract.
In the study, published in the August issue of Clinical Gastroenterology and Hepatology, five patients with an inherited form of precancerous polyps in the lower bowel known as familial adenomatous polyposis, of FAP, were treated over an average of six months with regular doses of curcumin, the chemical found in turmeric, and quercetin, an antioxidant in onions. The average number of polyps dropped 60.4 percent, and the average size dropped by 50.9 percent, according to a team led by gastroenterologist Francis M. Giardiello, a professor at the School of Medicine, and Marcia Cruz-Correa, a visiting professor from the University of Puerto Rico School of Medicine.
"We believe this is the first proof of principle that these substances have significant effects in patients with FAP," Giardiello said.
Familial adenomatous polyposis is a disorder that runs in families and is characterized by the development of hundreds of colorectal adenomas (polyps) and eventual colon cancer. Recently, nonsteroidal anti-inflammatory drugs, known as NSAIDs, have been used to treat some patients with this condition, but these compounds often produce significant side effects, including gastrointestinal ulcerations and bleeding.
Previous observational studies in populations that consume large amounts of curry, as well as laboratory research on rodents, have strongly suggested that curcumin — a relatively innocuous yellow pigment extracted from turmeric, the powdered root of the herb curcuma longa and one of the main ingredients in Asian curries — might be effective in preventing and/or treating cancer in the lower intestine, according to Cruz-Correa. Curcumin has been given to cancer patients, she said, and previous studies have demonstrated that it is well tolerated at high doses.
Similarly, quercetin — a member of a group of plant-derived polyphenolic anti-oxidant substances known as flavanoids (found in a variety of foods including onions, green tea and red wine) — has been shown to inhibit growth of colon cancer cell lines in humans and abnormal colorectal cells in rodents.
Although these substances were administered together, Giardiello said that due to their relative dose levels, he believes that curcumin is the key agent.
"The amount of quercetin we administered was similar to what many people consume daily; however, the amount of curcumin is many times what a person might ingest in a typical diet, since turmeric only contains on average 3 percent to 5 percent curcumin by weight," Giardiello said. Because of this, he cautions that simply consuming curry and onions may not have the same effect as was produced in this study.
In the trial, five patients were selected from the Cleveland Clinic Florida. All had previously had their colons surgically removed; four of the five retained the rectums, whereas the remaining patient had had both colon and rectum removed and part of the small intestine adapted to serve as colon and rectum. All patients had five or more adenomas in their lower intestinal tract. None of the patients had taken NSAIDS for more than one week during the three months leading up to the study.
Participants were examined using a flexible sigmoidoscope before treatment was initiated and at three-month intervals (range three to nine months) during treatment. Number and size of polyps were examined at each visit.
Each patient received 480 milligrams of curcumin and 20 milligrams of quercetin orally three times a day for six months and was told not to use NSAIDs for the duration of the study. Three patients followed treatment as prescribed. One patient did not follow the scheduled treatment doses between months three and six and was continued on therapy until the ninth month. Another patient dropped out of the study after the third month.
A decrease in polyp number was observed in four of the five patients at three months and four of the four patients at six months.
Side effects were minimal. One patient reported slight nausea and a sour taste within a couple of hours of taking the pill, an effect that went away within three days, and a second patient had mild diarrhea for five days.
"This study showed for the first time that curcumin treatment was efficacious in decreasing the number of polyps in patients with FAP, similar to what has been seen with the use of synthetic NSAID agents but with minimal side effects. Furthermore, we saw that adenomas found in the small intestine of our patients also responded to curcumin," Cruz-Correa said.
A randomized clinical trial involving more patients will be conducted at Johns Hopkins and the University of Puerto Rico Comprehensive Cancer Center, she said. No date has been set for this trial.
This study was supported by a grant from the National Institutes of Health. Additional researchers who contributed to this study are Daniel A. Shoskes, Patricia Sanchez, Rhongua Zhao and Steven D. Wexner, all of the Cleveland Clinic Florida; and Linda M. Hylind, of the Johns Hopkins School of Medicine.
GO TO AUGUST 7, 2006 TABLE OF CONTENTS.
GO TO THE GAZETTE FRONT PAGE.
--------------------------------------------------------------------------------
The Gazette | The Johns Hopkins University | Suite 540 | 901 S. Bond St. | Baltimore, MD 21231 | 443-287-9900 | gazette@jhu.edu
pancreatic cancer vaccine :::
Pancreatic Cancer VaccineAugust 5 - More than 30,000 Americans are diagnosed with pancreatic cancer each year, and about the same number die. Chances of surviving more than five years with this disease are low. But researchers hope to reverse that trend with a new vaccine.
When Ron Windle was diagnosed with pancreatic cancer, he never imagined he'd be alive and still walking hand-in-hand with his wife three years later. "I was afraid," Windle says. "I still have many things to do in life."
He had surgery, chemo and radiation. Still, he only had a 20-percent chance of surviving five years based on statistics. That was until he enrolled in a clinical trial testing a new vaccine.
During the study, doctors at Johns Hopkins University in Baltimore give patients the vaccine after surgery and again after chemo and radiation.
"I think we're very encouraged. What makes it exciting is the science behind the vaccine," says Daniel Laheru, M.D., an oncologist at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.
The vaccine uses genetically altered cells to create a molecule. The molecule lures immune cells and retrains them to recognize the tumor as cancer and fight it.
Dr. Laheru tells Ivanhoe, "Essentially, it teaches the immune system to recognize those pancreas cancer cells as being foreign and attack them specifically."
So far, he says the results have been encouraging. With the vaccine, 76 percent of patients are alive after two years, compared to 42 percent of patients who only received chemo and radiation.
Windle is one of the lucky ones. Today, he's cancer-free! "I'm sure it's why I'm here today. I've had many MRIs and cat scans, and there's no sign of cancer. None," he says, and he hopes to continue beating the odds.
The vaccine is injected about eight weeks after surgery and again after chemo and radiation treatment. Researchers at Johns Hopkins will conduct another study to refine the vaccine's targets. That study will start next year. If results come back as expected, they will apply for FDA approval.
If you would like more information, please contact:
Vanessa Wasta
Assistant Director, Media and Web Projects
Johns Hopkins Kimmel Cancer Center
901 S. Bond Street, Suite 573
Baltimore, MD 21231
(410) 955-1287
http://www.hopkinskimmelcancercenter.org
Inhibiting hTERT 2
Our data suggest that inhibition of hTERT expression by siRNA may constitute a valid strategy of chemosensitization. Future investigation will reveal whether hTERT-specific siRNAs with improved in vivo pharmacokinetics may enter the clinics. Intriguingly, there are a number of drugs used in experimental chemotherapy that are able to downmodulate hTERT expression at the mRNA or protein levels. This applies to rapamycin (Zhou et al., 2003), histone deacetylase inhibitors (Wu et al., 2005), imatinib mesylate (Gleevec) (Uziel et al., 2005), the Bcl-2/Bcl-XL-specific antisense oligonucleotide 4625 (Del Bufalo et al., 2005), as well as vitamin D3 (Jiang et al., 2004). It remains to be determined, however, to which extent hTERT downmodulation may explain the cytotoxic and chemosensitizing effects of such drugs.
Irrespective of these incognita, it appears that hTERT may constitute an ideal target for a double-hit anticancer strategy. Whereas inhibition of the catalytic telomerase activity should limit the lifespan of tumor cells and hence exert a long-term effect obtained by chronic therapy, acute inhibition of the second antiapoptotic function can yield an immediate chemosensitizing effect, including in tumors in which the p53 pathway is subverted. However, tumors in which the Bax-dependent mitochondrial pathway of apoptosis induction has been invalidated by loss of expression of Bax or overexpression of Bcl-2 are refractory to chemosensitization by hTERT inhibition.
Top of pageMaterials and methods
Inhibiting hTERT
http://www.nature.com/onc/journal/v25/n3...
Concluding remarks
It has been suspected for long that hTERT may contribute to tumorigenesis by a telomere length-independent mechanism because mutant hTERT, incapable of maintaining telomere length, can transform cell lines in vitro (Stewart et al., 2002). As shown, here, hTERT functions as an endogenous inhibitor of the mitochondrial pathway of apoptosis, in addition to its cardinal importance in tumor cell immortalization. This contention is based on the observation that downmodulation of hTERT by siRNAs has no toxic effects by itself (Figure 1), yet sensitizes cancer cells to apoptosis induction by DNA-damaging agents as well as by reactive oxygen species (Figure 2). Although suppression of hTERT sensitizes to the mitochondrial pathway of apoptosis, it has no such effect on CD95-induced cell death. The chemosensitizing effect is obtained immediately, as soon as the hTERT protein expression level is reduced (within 48–72 h). This time frame excludes the possibility that telomere erosion participates in the chemosensitizing effect.
As to the mechanisms that are involved in the sensitization to cell death induction by hTERT downmodulation, our data clearly show that p53 is not required for this effect (Figures 7 and 8). In contrast, our results point to increased activation of the Bax protein, which triggers the mitochondrial pathway of apoptosis, and Bax is required for apoptosis facilitated by hTERT inhibition (Figures 9 and 10). We did not find any effect of hTERT depletion on the expression level of Bax itself or on that of Bax-regulatory proteins such as Bak, Bcl-2, Bcl-XL, Puma/Bbc3, Noxa, Bim, Bid or Bad (not shown), suggesting that post-translational (rather than transcriptional or translational) modifications in the Bax interactome account for the enhanced activation of Bax in hTERT-depleted cells. Thus, the mechanism through which Bax is activated in this pathway remains an open question for future investigation. Santos et al. (2004) have shown that hTERT is targeted to the mitochondria and could sensitize cells to oxidative stress. Moreover, Haendeler et al. (2003, 2004) have published evidence suggesting that oxidative stress favors the nuclear export of hTERT, which in turn might contribute to the antiapoptotic activity of hTERT. Thus, a direct effect of hTERT on cytoplasmic, presumably mitochondrial, targets appears plausible, and a possible overlap between the hTERT and the Bax interactomes should be
Blackburn's 70 cancer genes, that are upregulated when the telomerase RNA template are intact, will turn out to be one of the FIRSTS of GRN163L. Several of those genes activate glycoysis, the rocket fuel of cancer and its spread through the body. So when telomerase is inhibited in such a manner:::
70 CANCER genes are downregulated (Blackburn)
cancer cell immortality is revoked (many works)
cancer stem cells DIE (Geron at Johns Hopkins)
Stopping glycolysis, and the downregulation of these 70 genes are the immediate effect of GRN163L that Okarma spoke of during one of his recent presentations. The longer term (one week) effect of GRN163L is the revocation of replicative immortality, which quickly affects the already short telomeres of rapidly dividing cancer cells. (my guess)
Corinna Kaarlela, News Director
Source: Nancy Chan
nchan@pubaff.ucsf.edu
415-476-2557
10 July 2006
Mohammed Kashani-Sabet, M.D.
UCSF study shows suppression of telomerase enzyme can inhibit spread of melanoma
UCSF researchers have found that the spread of melanoma can be inhibited by suppressing telomerase, the enzyme active in cancer cell growth.
Findings reported in the July 5 Proceedings of the National Academy of Sciences show for the first time a link between telomerase and glycolysis, the metabolic pathway used to consume glucose and produce lactic acid within the body.
"Identification of this relationship has great significance in understanding the role of telomerase and glycolysis together," said Mohammed Kashani-Sabet, MD, UCSF associate professor of dermatology and lead author of the study. "These results support the rationale for blocking telomerase in cancer therapy."
In the study, researchers found through gene expression profiling in mice that eight genes involved in glucose metabolism were lowered when telomerase was suppressed in skin cancer cells. The result was a return of pigmentation, frequently absent in advanced melanomas, and of cancer cells losing their metastatic potential.
"We introduced a telomerase inhibitor into melanoma cells and found that by suppressing telomerase, melanoma cells start to change," said Kashani-Sabet. "In some melanomas, pigmentation is lost. We found that when we are able to shut down telomerase, the cells regain functions previously lost, such as the ability to make pigment."
"As the cells become too acidic from the buildup of lactic acid, the proteins that control pigment production can be turned off, suggesting that glucose metabolism plays a key role when combined with telomerase in metastasis."
The ribonucleoprotein enzyme, telomerase, was discovered by study co-investigator Elizabeth Blackburn, PhD, Morris Herzstein Professor of Biology and Physiology in the UCSF Department of Biochemistry and Biophysics. Telomerase is well-documented as an instigator of cancer cell proliferation, but according to the researchers, its impact on tumor invasion and metastasis has been less studied.
In normal cells, the telomere is a strand of DNA that exists at the end of each chromosome and shortens with each cell division until it stops dividing, signaling the end of the cell life. Telomerase is activated in abnormal cells such as cancer cells, restoring the telomeres, and allowing them to divide and grow. As such, telomerase has been found to be over-expressed in 90 percent of human cancers.
Researchers were also able to ascertain for the first time how the use of a glucose compound injected into the body for positron emission topography (PET) scans was effective in diagnosing cancer. Use of the PET scan is now a regularly used method to diagnose and effectively pinpoint the source of cancer in an individual by utilizing radiation emitted from a patient to develop images. A radioactive substance is made up of glucose, a naturally occurring sugar, combined with a radioactive fluoride atom. The metabolism of glucose can be seen through gamma radiation produced from the positron-emitting fluoride that is detected by the PET scanner.
"Now for the first time, we understand why melanomas have high glucose uptake," Kashani-Sabet said. "We knew that use of PET scanning was effective in detecting melanoma metastasis, but we really didn't know why. Through this study, we found that telomerase is responsible for activation of glycolysis in melanoma cells."
Connecting telomerase and glucose metabolism together has implications for further therapeutic study. "By manipulating telomerase in cancer cells and suppressing glycolysis, it is possible to inhibit both melanoma invasion and metastasis." The study was funded by the Zackheim Endowment Fund, American Cancer Society, Damon Runyon Postdoctoral Fellowship program, Steven and Michelle Kirsch Foundation and the U.S. Public Health Service grants.
Co-authors from UCSF were Sepideh Bagheri and Mehdi Nosrati, Comprehensive Cancer Center and Department of Dermatology; Shang Li and Elizabeth H. Blackburn, Department of Biochemistry and Biophysics; Sima Torabian, Javier Rangel, and Dan H. Moore, Department of Epidemiology and Biostatistics; Scot Federman, Rebecca R. LaPosa, Frederick L. Baehner, Richard W. Sagebiel, James E. Cleaver, and Christopher Haqq, Department of Medicine and Comprehensive Cancer Center. Co-authors from California Pacific Medical Research Institute, San Francisco, were Sylvia Fong and Robert J. Debs.
UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.
###
Top
I did also, but I'm not really convinced, I don't agree with the answer which was that "to the moon" posts would get lots of recs, and I should pay to post to enjoy better features. With this boards current moderator I'm sure that recs would be meaningful. Especially after people catch on that the first sentence of their post is the subject line.
Good to have the moderated boards at investorshub.com , I am a refugee from the yahoo boards, driven out by the idiotic format and the lack of a real moderator. One thing that made it easy for me to catch up on good posts, was the feature that the old yahoo boards had, where you could endorse a post, each endorsement or 'rec' would tag up the tally for that post , visible to the right of the subject line. Is this something that can be added to this board?
Thanks
Prime3end
By the way, I absolutely hate the yahoo board format. I would tell the programmer and whole team that they have 3 days to put the old system in place or walk out the door. But the board has NO moderator. Nothing to keep the scum of the earth from posting absolute lies. However, this board could use a way to rate posts. Is there a benefit of not having rec's on this board?
Survival, a function of how much telomerase is produced?
From my archives
http://www.cancerwise.org/June_2005/print.cfm?id=532D2B2B-3832-43A2-BFD0AD197E4AAF24&method=Disp...
June 2005 MD Anderson:
Gene Variant Predicts Brain Tumor Survival
Enzyme Related to Chromosome Length Holds the Key
A large study of patients with glioblastoma multiforme, a deadly form of brain cancer, has found that a genetic variation appears to double the survival rate.
The study of 301 patients, presented recently by M. D. Anderson scientists at the annual meeting of the American Association for Cancer Research, establishes the strongest link to date between genetic variation and clinical outcome. Researchers found that the 36 patients (about 11%) who had the “SS” variant of the hTERT gene survived an average of 25 months, compared to about 14 months for those who had either the “SL” or “LL” genotypes.
hTERT produces human telomerase, an enzyme that helps regulate the length of telomeres, the structures that cap the end of chromosomes. In cancer, it is believed that telomerase is activated and intervenes to keep telomeres from shortening, allowing for unlimited division of cancer cells.
Positive results pave way for future research
Lead investigator Melissa Bondy, Ph.D., a professor in M. D. Anderson’s Department of Epidemiology, says the findings are exciting because they suggest new treatment directions for a brain tumor that is common, but offers little hope of survival for patients.
“It is a real advance because we have never seen any genotype that can stratify glioblastoma multiforme patients into different treatment outcome groups like this,” Bondy says. “Now we need to verify the finding, study the mechanism, and see if there is a way that these results can be used either as a biomarker or to individualize treatment.”
For example, if the SS variant of hTERT is confirmed to have better response to chemotherapy and radiation treatment, then it is possible that these therapies will extend survival for patients with glioblastoma multiforme, she says.
hTERT genetic variation is mysterious and promising
The research group looked at genetic variation of hTERT because an abnormal production of the gene contributes to unregulated cell growth, and production of the gene has been evaluated as one of the most common tumor markers in most primary tumors, says the study’s first author, Luo Wang, M.D., Ph.D., a research scientist in the Department of Epidemiology.
Exactly why patients with the SS variant of hTERT showed better survival remains unknown. But some forms of hTERT may be less destructive to cancer cells than others because they may be produced at a lower level, Wang says.
The association between the SS variant genotype and improved outcome held up, even when differences in age, sex and the extent of surgery, chemotherapy and radiation were taken into account. “We have looked at a lot of different genes associated with cancer, such as DNA repair genes and p53, but this is the first time we have found a genotype that has such a large effect on clinical outcome,” Wang says.
Not funding ESC research is killing more than hitler. If you look at the several years of delay , and future delay caused by the veto, this policy will have killed more people than adolph hitler.
Even todays court recently ruled against the intent of congress , most recently on the clean water act.
In the "fetal farming" bill, the definition of pregnancy in the administrative rules (which determine how the law is enforced) could be a yes/no to Geron's scalable manufacture of ESCs. These administrative rules will be written by Karl Rove and the church ladies from hell. They could define pregnancy as the time between conception and bith, which would be bad, or they could define pregnancy as having to occur in a woman, which would be good. Don't expect them to let it happen. They are trying to outlaw ESC research with the fetal farming bill? Comments please.
Cancerfoe , should you visit this board, as we all hope, I hope you will give your opinion on this article. It seems so much more important than most of us understand. There are natural compounds and perhaps approved drugs which inhibit glycolysis. When combined with Geron's inhibitor or natural telomerase inhibitors, there could be some good results.
Public release date: 10-Jul-2006
[ Print Article | E-mail Article | Close Window ]
Contact: Nancy Chan
nchan@pubaff.ucsf.edu
415-885-7277
University of California - San Francisco
UCSF study shows suppression of telomerase enzyme can inhibit spread of melanoma
UCSF researchers have found that the spread of melanoma can be inhibited by suppressing telomerase, the enzyme active in cancer cell growth.
Findings reported in the July 5 Proceedings of the National Academy of Sciences show for the first time a link between telomerase and glycolysis, the metabolic pathway used to consume glucose and produce lactic acid within the body.
"Identification of this relationship has great significance in understanding the role of telomerase and glycolysis together," said Mohammed Kashani-Sabet, MD, UCSF associate professor of dermatology and lead author of the study. "These results support the rationale for blocking telomerase in cancer therapy."
In the study, researchers found through gene expression profiling in mice that eight genes involved in glucose metabolism were lowered when telomerase was suppressed in skin cancer cells. The result was a return of pigmentation, frequently absent in advanced melanomas, and of cancer cells losing their metastatic potential.
"We introduced a telomerase inhibitor into melanoma cells and found that by suppressing telomerase, melanoma cells start to change," said Kashani-Sabet. "In some melanomas, pigmentation is lost. We found that when we are able to shut down telomerase, the cells regain functions previously lost, such as the ability to make pigment."
"As the cells become too acidic from the buildup of lactic acid, the proteins that control pigment production can be turned off, suggesting that glucose metabolism plays a key role when combined with telomerase in metastasis."
The ribonucleoprotein enzyme, telomerase, was discovered by study co-investigator Elizabeth Blackburn, PhD, Morris Herzstein Professor of Biology and Physiology in the UCSF Department of Biochemistry and Biophysics. Telomerase is well-documented as an instigator of cancer cell proliferation, but according to the researchers, its impact on tumor invasion and metastasis has been less studied.
In normal cells, the telomere is a strand of DNA that exists at the end of each chromosome and shortens with each cell division until it stops dividing, signaling the end of the cell life. Telomerase is activated in abnormal cells such as cancer cells, restoring the telomeres, and allowing them to divide and grow. As such, telomerase has been found to be over-expressed in 90 percent of human cancers.
Researchers were also able to ascertain for the first time how the use of a glucose compound injected into the body for positron emission topography (PET) scans was effective in diagnosing cancer. Use of the PET scan is now a regularly used method to diagnose and effectively pinpoint the source of cancer in an individual by utilizing radiation emitted from a patient to develop images. A radioactive substance is made up of glucose, a naturally occurring sugar, combined with a radioactive fluoride atom. The metabolism of glucose can be seen through gamma radiation produced from the positron-emitting fluoride that is detected by the PET scanner.
"Now for the first time, we understand why melanomas have high glucose uptake," Kashani-Sabet said. "We knew that use of PET scanning was effective in detecting melanoma metastasis, but we really didn't know why. Through this study, we found that telomerase is responsible for activation of glycolysis in melanoma cells."
Connecting telomerase and glucose metabolism together has implications for further therapeutic study. "By manipulating telomerase in cancer cells and suppressing glycolysis, it is possible to inhibit both melanoma invasion and metastasis."
###
The study was funded by the Zackheim Endowment Fund, American Cancer Society, Damon Runyon Postdoctoral Fellowship program, Steven and Michelle Kirsch Foundation and the U.S. Public Health Service grants.
Co-authors from UCSF were Sepideh Bagheri and Mehdi Nosrati, Comprehensive Cancer Center and Department of Dermatology; Shang Li and Elizabeth H. Blackburn, Department of Biochemistry and Biophysics; Sima Torabian, Javier Rangel, and Dan H. Moore, Department of Epidemiology and Biostatistics; Scot Federman, Rebecca R. LaPosa, Frederick L. Baehner, Richard W. Sagebiel, James E. Cleaver, and Christopher Haqq, Department of Medicine and Comprehensive Cancer Center. Co-authors from California Pacific Medical Research Institute, San Francisco, were Sylvia Fong and Robert J. Debs.
UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.
So how does this board suit everyone. No post recs. but at lesast you don't have to chekc 20,000 different threads to get to the discussions. I agree that I very much like Paula as the moderator!