I have to agree with your assertion that Cancer is a result of long lived organisms, but I disagree with your conclusion. I do believe that cancer, or at least some cancers are curable. Cancer plain and simple is the manifistation of genetic mutations that occur over many years. Necrosis is a outcome that is a direct result of an accute injury so it should not be looked at with regard to cancer. With that said, Cancer comes in two flavors. The first is the don't die, don't die type. Cancers involving this mechnism, evade the death signals (apoptosis) and continue to live. Leukemias are a good example. The other flavor is the grow, grow type. These cancers are due to mutations that regulate cell growth and differentiation. What is common to all cancers is that they are a result of many genetic hits. If if a cell becomes disregulated in its growth genes does not mean that you will have a cancer that will kill. Primary cancers rarely if ever kill the organism(exception to the leukemias). In order for the cancer to kill, it must learn to go elsewhere in the body and it must learn to survive in the blood. These are all controlled and all must be genetically hit to have metastasis.
Good post but I would like to add a few points. TNF-alpha is one mediator and the other major mediator is IL-1 (with regard to flus and inflamation). Downregulation of the immune system is a "slipery" statement. If the cd8+ T cells could recognize the HIV then they would kill the cell and the infection would be over. It seems that HIV is better recognized by the CD4+ T cells. Furthermore, HIV can remain dormant in cells for quite a while and while dormant, the immune system respnse is not triggered. This explains the data that peaple being treated with AZT and protease inhibitors show a marked reduction of viral load but later develop AIDs none the less. In order for AZT to work well, the virus must be in the replication phase. With this in mind, new studies are being done that stimulate the living crap out of the immune system (massive IL-2 injections) that cause all the resting immune cells to become activated. The early data seems to show that this method with "cocktail drugs" can reduce the viral load to undetectable levels.
Get real. The entire genome of the HIV virus has been elucidated. Would you not crack up laughing if someone told you the it is just an urban legend that computers really exist????
I think you do not quite understand HIV. Yes HIV does mutate and yes it does mutate quickly but the immune system has no problem seeing it. The blood of peaple that are infected with AIDS has plenty and I mean plenty of antiobodies that recognize HIV particles. The problem is that all that the antobodies do is tag the virus particle to be picked up by a macrophage which then gets infected. AIDS is so hard to fight because the cells that it goes after are the cells that are supposed to do the fighting. Some evidence exists that seems to imply that posssilbly CD8 T cells are needed to wage the war in the body. There are a few reported cases of prosstitutes in Africa that have been repeatly exposed to HIV yet have never been infected. Further more, there is a resivior of AIDs particles that lie inside cells that are not replicating, these guys completely escape immune survelence
c'mon. You are kidding right? Go and look at drugs and where they come from. What you will find is that probably 90+ percent of all drugs have been derived from nature. Most notably antibiotics and asprin
Viruses can only be used once maybe two times before the immune system gets wise to its presence. As a Liver researcher, I can say that viral vecters are not good for cancer therapy but may be useful in correcting genetic defects such as hemophilia. Cancer cells have many defects that allow them to increase in number in an uncontrolled manner. Trying to find a magic bullet may be impossible.
What makes HIV particularly nasty is that it attacks the cells that are supposed to fight it as well as HIV has the ability to "hide" in dorment immune cells. It is the specific mechanism of recognition of the CD4+ cells and macrophages that make HIV a very interesting virus and what makes it so leathal.
Interesting statement but slightly off base. "Of course, since dying itself is simply an evolved cellular-level defence against cancer, let's hope cancer is solved along the way.... (and before anyone answers the obvious point raised here, remember that evolution favours individual genes, not individual animals.)"
I like to think of cancer as god's way of telling us that we have lived too long. Cancer is actually a fairly well understood process but the players are not. Let me explain. Cancer is the result of a disregulation of genes involved in cell growth and differentiation and can be broken down into two groups. The first group are cancers such as breast cancer which have genes screwed up that regulate growth of an individual cell which allows that cell to grow outside of the normal regulation. The second type of cancer are cancers such as non Hodgins lymphoma which prevent a cell from comiting suicide (apoptosis) when they are supposed to. I am sure that some could be a mixture of both. With this said, for a cell to become malignant and result in the death of the organism, many genes must get genetically hit or mutated. The mutation can be in the coding region of the protein or in the promoter or both. So cancer that kills is actually an accumulation of mutations rather then just one mutation. The genes that must be mutated are termed oncogenes and thier normal couterparts are call proto oncogenes. Here in lies the problem. Who are the oncogenes? We know of many but not all. Also, what mutation is important? Does the promoter region need to be hit or does the protein need to be hit? Our current understanding of promoter regions is very primative to say the least and it may be decades before we understand them more fully. Short range enhancer regions(on switches) are relatively easy to find but enhacers located far away are dificult to identify and enhancers within introns(non coding region of genes) go virtually unexplored. Over time, we all get mutations in our genes and that is unavoidable. If you use that DNA for cloning then the mutations will accumulate even more till cancer is unavoidable. A good example of this is pediatric cancers. These individuals are ussually born with only one good copy of a key gene and if mutations occur in the only good copy then cancer is sure to occur. This is how the Retenoblastoma gene was found and Wilms tumor antigen as well. So in a nut shell, Cancer is solvable only if you know what genes are screwed up but to determine that the genome needs to looked at. And that is no small task
What is happening to Dolly's clones is a predictable event and one which did not surprise me at all. It simply proves a point. Eucaryotes(aka multicellular life forms) have linear Chromosomes as opposed to prokaryotes(bacteria) which have circular chromosomes. Each time a linear chromasome replicates thru cell division, it losses some of its ends. This is called degenerate replication. An enzyme with an RNA core (used as a template) is used by the cell to replace the bases that can not be replicated and it is called Telomerase. The strech of DNA that is shortening is called the Telemere. Normally, telomerase is NOT active in cells other than in very early life(before the 2nd trimester). Although it has been found in some cells in the adult. Those cells are believed to be the pluripotent stem cells(capable of forming just about any cell in the body) and CANCER cells. If a cell wants to live forever, telomerase will have to reawaken and repair its ends if it does not, the belief in the scientific community is that the cell will undergo "Programmed death" (aka apoptosis) when the telemeres on the ends of the chromosome gets to short. An example of this principle can be seen in the disease ATAXIA TELANGIESIA (AT). These poor souls are born with abherently short telomeres and by the age of 18, the individuals resemble a 70 year old. With that said, the DNA that was used for Dolly's clones was obtained from the breast of Dolly and the cells were fully differentiated and thus had already undergone significant shortening of the chromosome before the DNA was harvested. One would expect several things to happen. 1) DNA will age faster due to telemeric shortening and 2) DNA will have acumulated mutations from Dolly's life as well as from its own life and thus will have a higher disposition for cancer. I define cancer as the acuumulation of mutations that allows for genes to be disregulated and thus cells live when they should die. We have cells in our lab that were harvested from a lady named Helen ~30 years ago(Hela cells) and they are still alive and kicking while Helen is not. This cells are very screwed up(>90 chromasomes) and they have active telmerase.
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I have to agree with your assertion that Cancer is a result of long lived organisms, but I disagree with your conclusion. I do believe that cancer, or at least some cancers are curable. Cancer plain and simple is the manifistation of genetic mutations that occur over many years. Necrosis is a outcome that is a direct result of an accute injury so it should not be looked at with regard to cancer. With that said, Cancer comes in two flavors. The first is the don't die, don't die type. Cancers involving this mechnism, evade the death signals (apoptosis) and continue to live. Leukemias are a good example. The other flavor is the grow, grow type. These cancers are due to mutations that regulate cell growth and differentiation. What is common to all cancers is that they are a result of many genetic hits. If if a cell becomes disregulated in its growth genes does not mean that you will have a cancer that will kill. Primary cancers rarely if ever kill the organism(exception to the leukemias). In order for the cancer to kill, it must learn to go elsewhere in the body and it must learn to survive in the blood. These are all controlled and all must be genetically hit to have metastasis.
Good post but I would like to add a few points.
TNF-alpha is one mediator and the other major mediator is IL-1 (with regard to flus and inflamation).
Downregulation of the immune system is a "slipery" statement. If the cd8+ T cells could recognize the HIV then they would kill the cell and the infection would be over. It seems that HIV is better recognized by the CD4+ T cells. Furthermore, HIV can remain dormant in cells for quite a while and while dormant, the immune system respnse is not triggered. This explains the data that peaple being treated with AZT and protease inhibitors show a marked reduction of viral load but later develop AIDs none the less. In order for AZT to work well, the virus must be in the replication phase. With this in mind, new studies are being done that stimulate the living crap out of the immune system (massive IL-2 injections) that cause all the resting immune cells to become activated. The early data seems to show that this method with "cocktail drugs" can reduce the viral load to undetectable levels.
Get real.
The entire genome of the HIV virus has been elucidated.
Would you not crack up laughing if someone told you the it is just an urban legend that computers really exist????
I think you do not quite understand HIV. Yes HIV does mutate and yes it does mutate quickly but the immune system has no problem seeing it. The blood of peaple that are infected with AIDS has plenty and I mean plenty of antiobodies that recognize HIV particles. The problem is that all that the antobodies do is tag the virus particle to be picked up by a macrophage which then gets infected. AIDS is so hard to fight because the cells that it goes after are the cells that are supposed to do the fighting. Some evidence exists that seems to imply that posssilbly CD8 T cells are needed to wage the war in the body. There are a few reported cases of prosstitutes in Africa that have been repeatly exposed to HIV yet have never been infected. Further more, there is a resivior of AIDs particles that lie inside cells that are not replicating, these guys completely escape immune survelence
c'mon. You are kidding right?
Go and look at drugs and where they come from. What you will find is that probably 90+ percent of all drugs have been derived from nature. Most notably antibiotics and asprin
Viruses can only be used once maybe two times before the immune system gets wise to its presence. As a Liver researcher, I can say that viral vecters are not good for cancer therapy but may be useful in correcting genetic defects such as hemophilia.
Cancer cells have many defects that allow them to increase in number in an uncontrolled manner. Trying to find a magic bullet may be impossible.
What makes HIV particularly nasty is that it attacks the cells that are supposed to fight it as well as HIV has the ability to "hide" in dorment immune cells. It is the specific mechanism of recognition of the CD4+ cells and macrophages that make HIV a very interesting virus and what makes it so leathal.
Interesting statement but slightly off base.
"Of course, since dying itself is simply an evolved cellular-level defence against cancer, let's hope cancer is solved along the
way.... (and before anyone answers the obvious point raised here, remember that evolution favours individual genes, not
individual animals.)"
I like to think of cancer as god's way of telling us that we have lived too long. Cancer is actually a fairly well understood process but the players are not. Let me explain. Cancer is the result of a disregulation of genes involved in cell growth and differentiation and can be broken down into two groups. The first group are cancers such as breast cancer which have genes screwed up that regulate growth of an individual cell which allows that cell to grow outside of the normal regulation. The second type of cancer are cancers such as non Hodgins lymphoma which prevent a cell from comiting suicide (apoptosis) when they are supposed to. I am sure that some could be a mixture of both.
With this said, for a cell to become malignant and result in the death of the organism, many genes must get genetically hit or mutated. The mutation can be in the coding region of the protein or in the promoter or both. So cancer that kills is actually an accumulation of mutations rather then just one mutation. The genes that must be mutated are termed oncogenes and thier normal couterparts are call proto oncogenes. Here in lies the problem. Who are the oncogenes? We know of many but not all. Also, what mutation is important? Does the promoter region need to be hit or does the protein need to be hit? Our current understanding of promoter regions is very primative to say the least and it may be decades before we understand them more fully. Short range enhancer regions(on switches) are relatively easy to find but enhacers located far away are dificult to identify and enhancers within introns(non coding region of genes) go virtually unexplored.
Over time, we all get mutations in our genes and that is unavoidable. If you use that DNA for cloning then the mutations will accumulate even more till cancer is unavoidable. A good example of this is pediatric cancers. These individuals are ussually born with only one good copy of a key gene and if mutations occur in the only good copy then cancer is sure to occur. This is how the Retenoblastoma gene was found and Wilms tumor antigen as well.
So in a nut shell, Cancer is solvable only if you know what genes are screwed up but to determine that the genome needs to looked at. And that is no small task
Regards
Peter
....a rubber biscquit, of course
What is happening to Dolly's clones is a predictable event and one which did not surprise me at all. It simply proves a point.
Eucaryotes(aka multicellular life forms) have linear Chromosomes as opposed to prokaryotes(bacteria) which have circular chromosomes. Each time a linear chromasome replicates thru cell division, it losses some of its ends. This is called degenerate replication. An enzyme with an RNA core (used as a template) is used by the cell to replace the bases that can not be replicated and it is called Telomerase. The strech of DNA that is shortening is called the Telemere. Normally, telomerase is NOT active in cells other than in very early life(before the 2nd trimester). Although it has been found in some cells in the adult. Those cells are believed to be the pluripotent stem cells(capable of forming just about any cell in the body) and CANCER cells. If a cell wants to live forever, telomerase will have to reawaken and repair its ends if it does not, the belief in the scientific community is that the cell will undergo "Programmed death" (aka apoptosis) when the telemeres on the ends of the chromosome gets to short. An example of this principle can be seen in the disease ATAXIA TELANGIESIA (AT). These poor souls are born with abherently short telomeres and by the age of 18, the individuals resemble a 70 year old.
With that said, the DNA that was used for Dolly's clones was obtained from the breast of Dolly and the cells were fully differentiated and thus had already undergone significant shortening of the chromosome before the DNA was harvested. One would expect several things to happen. 1) DNA will age faster due to telemeric shortening and 2) DNA will have acumulated mutations from Dolly's life as well as from its own life and thus will have a higher disposition for cancer. I define cancer as the acuumulation of mutations that allows for genes to be disregulated and thus cells live when they should die. We have cells in our lab that were harvested from a lady named Helen ~30 years ago(Hela cells) and they are still alive and kicking while Helen is not. This cells are very screwed up(>90 chromasomes) and they have active telmerase.