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yep igf is leuk spul, maar hier is dan toch de negatieve kant ervan:
Please do not cut and past the below workings, you will find my information to be the best out there. But I do like to reserve the right to distribute it to the boards I see fit. Thanks
TheGAME
In response to high demand, here is the truth about cancer that half the Dr's out there don't even grasp at times.
The big misconception about cancer is its something you get. This is not true, we all live with cancer type cells all the time, but our body has its own control over these cells, and kills them off via apoptosis. The things that cause cancer,don't neccissarily make more cancerous cells all the time, some of the time they damage the cells ability to detect, and kill itself if it becomes cancerous. And because of the way DNA is replicated and the flaws in it, this is what happens with age.
The breif summary:
Your body has specific genes, and receptors that regulate programmed cell death through a method called apoptosis. Apoptosis basically results in the destruction of the mitochondrial membrane, destruction of the cellular DNA and eventually your body digest the dead cell with special enzymes, etc. and the cell is gone comepletely without a trace.
This is what your body does when it detects a faulty cell. In the case of cancer these cells have their fault in that they have lost their ability to control their growth cycle. They just keep dividing, over and over. In a healthy individual these cells are detected either by themselves or the body, and it is signaled to under apoptosis. If this doesnt happen and the cells can keep dividing, eventually this leads to a tumor. When they refer to metastisizing in cancer, they are refering to the point at which the cells that were duplicating, at least some of them have broken off and spread throughout the body so that they can now reattach anywhere and start making more tumors.
How do Growth factors and Selegiline fit into the picture. First of all, neither of these cause cells to become cancerous. One could argue that b/c growth factors cause cell growth and progression though the cycle, the more times a cell duplicates the more chances there is for a mistake and a cancer cell made. However you are duplicating cells all the time eveyr day. So really the increased risk there is extremely low. In addition to that, muscle specific growth factors, have even less of a risk, b/c adult muscle cells can not divide. You will never have bicep cancer unforunantly, although it might be nice to have your muscles grow on there own for a while by mistake, it will never happen.
The risk with IGF and selegiline exist primarily on their ability to preserve cell life by upregulating proteins that actually block your bodies apoptotic factors. This is why selegiline and IGF are neuroprotective drugs. They can protect cells from undergoing apoptosis, which in the case of many neurological diseases, is the cause. For unknown reasons these brain cells start undergoing programmed cell death. They are not cancerous. So these drugs are used to treat the condition.
However if a cell in the body was cancerous, it is conceivable that enough singaling via IGF or selegiline could prevent the body from killing it off. Thus it would be allowed to grow in duplicate. This is why I am going to suggest cycling any type of compound that effects tumor surpressors in the body. Because IGF and Selegiline do not permanently effect the ability of the cell to undergo apoptosis, one would assume that discontinued stimulation would then result in the body being able to successfully kill the cells.
So you may ask then, why do people get cancer/tumors if we have such a great mechanism for defense. The flaw is in our gene replication. When DNA replicates often times it leaves off little peices on the ends. So there is a loss of DNA. But the cell has a special enzyme called telomerase that can actually use an imbeded sequence in the enzyme to fix these ends. But this doesnt happen 100% of the time. So as you get older you are actually losing your DNA due to the clipping off or incomplete ends during replication. The biggest downside here, is that two very important genes are close to the ends of the DNA, one codes for telomerase itself, the very thing trying to reduce DNA loss, and the other codes for the p53 gene which is considered the primary tumor surpressor gene. This is the gene most responsible for a cell to be able to program its own death if it becomes cancerous. Loss of this gene= a major loss in cancer defense for this cell and every cell it makes from there on.
So while IGF/and Selegiline due effect tumor supressor action, I beleive cancer if it is going to occur, will happen with or without them present. However long term use if either of these without cycling, could speed up the process considerably. So, what I recommend is the same for any drug. Take as directed.
The BIG scientific version. (you knew it was coming) Sorry about picture size I know some of them are hard to read, but it was the only way I could get them in here. You can save them and zoom if you like.
Programmed cell death (PCD), or apoptosis, can be triggered by a wide range of stimuli, including cell surface receptors like Fas and FasL. It constitutes a system for the removal of unnecessary, aged, or damaged cells that is regulated by the interplay of proapoptotic and antiapoptotic proteins of the Bcl-2 family. The proapoptotic proteins Bax, Bad, Bid, Bik, and Bim contain an a-helical BH3 death domain that fits the hydrophobic BH3 binding pocket on the antiapoptotic proteins Bcl-2 and Bcl-XL, forming heterodimers that block the survival-promoting activity of Bcl-2 and Bcl-XL. Thus, the relative abundance of proapoptotic and antiapoptotic proteins determines the susceptibility of the cell to programmed death. The proapoptotic proteins act at the surface of the mitochondrial membrane to decrease the mitochondrial trans-membrane potential and promote leakage of cytochrome c. In the presence of dATP cytochrome c complexes with and activates Apaf-1. Activated Apaf-1 binds to downstream caspases, such as procaspase-9, and processes them into proteolytically active forms. This begins a caspase cascade resulting in apoptosis.
[Afbeelding niet meer beschikbaar]
Activation and Inhibition of Apoptosis
Several mechanisms have been identified in mammalian cells for the induction of apoptosis. These mechanisms include factors that lead to perturbation of the mitochondria leading to leakage of cytochrome c or factors that directly activate members of the death receptor family. Fas is a member of the tumor necrosis factor (TNF) receptor superfamily, a family of transmembrane receptors that include neurotrophin receptor (p75NTR), TNF-R1, and a variety of other cell surface receptors. Fas Ligand (Fas L) transmits signals to Fas on a target cell by inducing trimerization of Fas. Activation of Fas causes the recruitment of Fas-associated protein with death domain (FADD) via interactions between the death domain of Fas and FADD and is followed by pro-caspase-8 binding to FADD via interactions between the death effector domains (DED) of FADD and pro-caspase-8 leading to the activation of caspase-8. Activation of caspase-8 leads to the activation of other caspases, in effect beginning a caspase cascade that ultimately leads to apoptosis. Caspase-8 activation can also activate Bid, leading to activation of the apoptotic program. Fas-induced apoptosis can be effectively blocked at several stages by either FLICE-inhibitory protein (FLIP), by Bcl-2, or by the cytokine response modifier A (CrmA). In addition, activation of caspase-3 by caspase-9 can be blocked by inhibitor of apoptosis proteins (IAPs). Moreover, the protein kinase, Akt, can be activated by various growth factors and its activity can be blocked by PTEN. Akt functions to promote cell survival through two distinct pathways. Akt inhibits apoptosis by phosphorylating the Bcl-2 family member Bad, which then interacts with 14-3-3 and dissociates from Bcl-xL allowing for cell survival. Alternatively, Akt activates IKKα that ultimately leads to NFκB activation and cell survival. Proapoptotic Bcl-2 family members, such as Bax and Bak can promote mitochondrial permeability, while Bcl-2 can inhibit their effects. Upon mitochondrial permeability, apoptogenic factors are released from the mitochondrial inter-membrane space and leak into the cytosol. One factor is cytochrome c, which induces the liberation of protease activators (caspases) that ultimately lead to apoptosis through nuclear damage (DNA fragmentation, DNA mutations). In addition, Smac/Diablo is released and can block IAP inhibition of capsase activity. Mitochondrial permeability is also related to the increased generation of reactive oxygen species (ROS), which plays a role in the degradation phase of apoptosis (i.e. plasma membrane alterations).
[Afbeelding niet meer beschikbaar]
You should recognize a few things in this image. PI3K is one of the two pathways in which IGF is known to act, and AKT is the downstreamindirect signaling pathway of IGF as well .
Mitochondria in Apoptosis
Increases in cytosolic Ca2+ levels due to activation of ion channel-linked receptors, such as that for the excitatory amino acid neurotransmitter glutamic acid, can induce permeability transition (PT) of the mitochondrial membrane. PT constitutes the first rate-limiting event of the common pathway of apoptosis. Upon PT, apoptogenic factors leak into the cytoplasm from the mitochondrial intermembrane space. Two such factors, cytochrome c and apoptosis inducing factor (AIF), begin a cascade of proteolytic activity that ultimately leads to nuclear damage (DNA fragmentation, DNA mutations) and cell death. Cytochrome C, a key protein in electron transport, appears to act by forming a multimeric complex with Apaf-1, a protease, which in turn activates procaspase 9, and begins a cascade of activation of downstream caspases. Smac/Diablo is released from the mitochondria and inhibits IAP (inhibitor of apoptosis) from interacting with caspase 9 leading to apoptosis. Bcl-2 and Bcl-X can prevent pore formation and block the release of cytochrome c from the mitochondria and prevent activation of the caspase cascade and apoptosis. PT is also related to the mitochondrial generation of reactive oxygen species which plays a role in the degradation phase of apoptosis (i.e. plasma membrane alterations).
Mitochondrial induced apoptosis is the specific pathway that Selegiline is used to protect against. Selegiline prevents the mitochondrial from releaseing Cytochrome c from the membrane by upregulating Bcl-2 and increasing membrain stability.
[Afbeelding niet meer beschikbaar]
IGF Regulation of Apoptosis
Model of IGF-I Receptor regulation of apoptosis. Ligand binding to IGF-IR activates the tyrosine kinase domain which initiates a set of signaling cascades. This leads to a higher concentration of the anti-apoptotic proteins bcl-2 and bcl-xL a lower level of the apoptotic proteins bax and bcl-xs. IGF-IR signaling also activates phosphatidylinositol 3-kinase (P13-K), which in turn activates protein kinase B (PKB/Akt) that also prevent apoptosis. These pathways converge on the inhibition of caspases, especially caspase-3, which is then blocked from performing an apoptosis-initiating cleavage of poly(adenosine diphosphate ribose) polymerase (PARP) and blocked from degrading β-catenin, part of the cadherin cell-adhesion system. Thus, IGF stimulates IGF-IR
TNF is resposnible for inducing apoptosis via signaling at the Fas Ligand, which you can see in the above pathways.
Involvement of the TNF-alpha autocrine-paracrine loop, via NF-kappaB and YY1, in the regulation of tumor cell resistance to Fas-induced apoptosis.
Huerta-Yepez S, Vega M, Garban H, Bonavida B.
Department of Microbiology, Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer Center, University of California, 10833 Le Conte Ave., Los Angeles, CA 90095-1747, USA; Unidad de Investigacion Medica en Inmunologia e Infectologia, Hospital de Infectologia, CMN "La Raza", IMSS, Mexico.
Many tumors are resistant to Fas ligand (FasL)-induced apoptosis. This study examined the role of tumor-derived TNF-alpha, via an autocrine/paracrine loop, in the regulation of tumor-cell resistance to FasL-induced apoptosis. We have reported that Fas expression and sensitivity to FasL is negatively regulated by the transcription repressor factor Yin Yang 1 (YY1). Thus, we hypothesized that tumor-derived TNF-alpha induces the activation of NF-kappaB and the transcription repressor YY1, both of which negatively regulate Fas expression and sensitivity to FasL-induced apoptosis. This hypothesis was tested in PC-3 prostate cancer cells which synthesize and secrete TNF-alpha and express constitutively active NF-kappaB and YY1. Treatment of PC-3 cells with TNF-alpha (10 units) resulted in increased NF-kappaB and YY1 DNA-binding activity, upregulation of YY1 expression, downregulation of surface and total Fas expression and enhanced resistance of PC-3 to apoptosis induced by the FasL agonist antibody CH-11. In contrast, blocking the binding of secreted TNF-alpha on PC-3 cells with soluble recombinant sTNF-RI resulted in significant inhibition of constitutive NF-kappaB and YY1 DNA-binding activity, downregulation of YY1 expression, upregulation of Fas expression and sensitization of tumor cells to CH-11-induced apoptosis. The regulation of YY1 expression and activity by NF-kappaB was demonstrated by the use of the NF-kappaB inhibitor Bay 11-7085 and by the use of a GFP reporter system whereby deletion of the YY1-tandem binding site in the promoter significantly enhanced GFP expression. The direct role of YY1 expression in the regulation of PC-3 resistance to CH-11-induced apoptosis was shown in cells transfected with siRNA YY1 whereby such cells exhibited upregulation of Fas expression and were sensitized to CH-11-induced apoptosis. These findings demonstrate that the TNF-alpha autocrine-paracrine loop is involved in the constitutive activation of the transcription factors NF-kappaB and YY1 in the tumor cells and this loop leads to inhibition of Fas expression and resistance to FasL-induced apoptosis. Further, these findings identify new targets such as TNF-alpha, NF-kappaB and YY1, whose inhibition can reverse tumor cell resistance to FasL-mediated apoptosis.
Please do not cut and past the below workings, you will find my information to be the best out there. But I do like to reserve the right to distribute it to the boards I see fit. Thanks
TheGAME
In response to high demand, here is the truth about cancer that half the Dr's out there don't even grasp at times.
The big misconception about cancer is its something you get. This is not true, we all live with cancer type cells all the time, but our body has its own control over these cells, and kills them off via apoptosis. The things that cause cancer,don't neccissarily make more cancerous cells all the time, some of the time they damage the cells ability to detect, and kill itself if it becomes cancerous. And because of the way DNA is replicated and the flaws in it, this is what happens with age.
The breif summary:
Your body has specific genes, and receptors that regulate programmed cell death through a method called apoptosis. Apoptosis basically results in the destruction of the mitochondrial membrane, destruction of the cellular DNA and eventually your body digest the dead cell with special enzymes, etc. and the cell is gone comepletely without a trace.
This is what your body does when it detects a faulty cell. In the case of cancer these cells have their fault in that they have lost their ability to control their growth cycle. They just keep dividing, over and over. In a healthy individual these cells are detected either by themselves or the body, and it is signaled to under apoptosis. If this doesnt happen and the cells can keep dividing, eventually this leads to a tumor. When they refer to metastisizing in cancer, they are refering to the point at which the cells that were duplicating, at least some of them have broken off and spread throughout the body so that they can now reattach anywhere and start making more tumors.
How do Growth factors and Selegiline fit into the picture. First of all, neither of these cause cells to become cancerous. One could argue that b/c growth factors cause cell growth and progression though the cycle, the more times a cell duplicates the more chances there is for a mistake and a cancer cell made. However you are duplicating cells all the time eveyr day. So really the increased risk there is extremely low. In addition to that, muscle specific growth factors, have even less of a risk, b/c adult muscle cells can not divide. You will never have bicep cancer unforunantly, although it might be nice to have your muscles grow on there own for a while by mistake, it will never happen.
The risk with IGF and selegiline exist primarily on their ability to preserve cell life by upregulating proteins that actually block your bodies apoptotic factors. This is why selegiline and IGF are neuroprotective drugs. They can protect cells from undergoing apoptosis, which in the case of many neurological diseases, is the cause. For unknown reasons these brain cells start undergoing programmed cell death. They are not cancerous. So these drugs are used to treat the condition.
However if a cell in the body was cancerous, it is conceivable that enough singaling via IGF or selegiline could prevent the body from killing it off. Thus it would be allowed to grow in duplicate. This is why I am going to suggest cycling any type of compound that effects tumor surpressors in the body. Because IGF and Selegiline do not permanently effect the ability of the cell to undergo apoptosis, one would assume that discontinued stimulation would then result in the body being able to successfully kill the cells.
So you may ask then, why do people get cancer/tumors if we have such a great mechanism for defense. The flaw is in our gene replication. When DNA replicates often times it leaves off little peices on the ends. So there is a loss of DNA. But the cell has a special enzyme called telomerase that can actually use an imbeded sequence in the enzyme to fix these ends. But this doesnt happen 100% of the time. So as you get older you are actually losing your DNA due to the clipping off or incomplete ends during replication. The biggest downside here, is that two very important genes are close to the ends of the DNA, one codes for telomerase itself, the very thing trying to reduce DNA loss, and the other codes for the p53 gene which is considered the primary tumor surpressor gene. This is the gene most responsible for a cell to be able to program its own death if it becomes cancerous. Loss of this gene= a major loss in cancer defense for this cell and every cell it makes from there on.
So while IGF/and Selegiline due effect tumor supressor action, I beleive cancer if it is going to occur, will happen with or without them present. However long term use if either of these without cycling, could speed up the process considerably. So, what I recommend is the same for any drug. Take as directed.
The BIG scientific version. (you knew it was coming) Sorry about picture size I know some of them are hard to read, but it was the only way I could get them in here. You can save them and zoom if you like.
Programmed cell death (PCD), or apoptosis, can be triggered by a wide range of stimuli, including cell surface receptors like Fas and FasL. It constitutes a system for the removal of unnecessary, aged, or damaged cells that is regulated by the interplay of proapoptotic and antiapoptotic proteins of the Bcl-2 family. The proapoptotic proteins Bax, Bad, Bid, Bik, and Bim contain an a-helical BH3 death domain that fits the hydrophobic BH3 binding pocket on the antiapoptotic proteins Bcl-2 and Bcl-XL, forming heterodimers that block the survival-promoting activity of Bcl-2 and Bcl-XL. Thus, the relative abundance of proapoptotic and antiapoptotic proteins determines the susceptibility of the cell to programmed death. The proapoptotic proteins act at the surface of the mitochondrial membrane to decrease the mitochondrial trans-membrane potential and promote leakage of cytochrome c. In the presence of dATP cytochrome c complexes with and activates Apaf-1. Activated Apaf-1 binds to downstream caspases, such as procaspase-9, and processes them into proteolytically active forms. This begins a caspase cascade resulting in apoptosis.
[Afbeelding niet meer beschikbaar]
Activation and Inhibition of Apoptosis
Several mechanisms have been identified in mammalian cells for the induction of apoptosis. These mechanisms include factors that lead to perturbation of the mitochondria leading to leakage of cytochrome c or factors that directly activate members of the death receptor family. Fas is a member of the tumor necrosis factor (TNF) receptor superfamily, a family of transmembrane receptors that include neurotrophin receptor (p75NTR), TNF-R1, and a variety of other cell surface receptors. Fas Ligand (Fas L) transmits signals to Fas on a target cell by inducing trimerization of Fas. Activation of Fas causes the recruitment of Fas-associated protein with death domain (FADD) via interactions between the death domain of Fas and FADD and is followed by pro-caspase-8 binding to FADD via interactions between the death effector domains (DED) of FADD and pro-caspase-8 leading to the activation of caspase-8. Activation of caspase-8 leads to the activation of other caspases, in effect beginning a caspase cascade that ultimately leads to apoptosis. Caspase-8 activation can also activate Bid, leading to activation of the apoptotic program. Fas-induced apoptosis can be effectively blocked at several stages by either FLICE-inhibitory protein (FLIP), by Bcl-2, or by the cytokine response modifier A (CrmA). In addition, activation of caspase-3 by caspase-9 can be blocked by inhibitor of apoptosis proteins (IAPs). Moreover, the protein kinase, Akt, can be activated by various growth factors and its activity can be blocked by PTEN. Akt functions to promote cell survival through two distinct pathways. Akt inhibits apoptosis by phosphorylating the Bcl-2 family member Bad, which then interacts with 14-3-3 and dissociates from Bcl-xL allowing for cell survival. Alternatively, Akt activates IKKα that ultimately leads to NFκB activation and cell survival. Proapoptotic Bcl-2 family members, such as Bax and Bak can promote mitochondrial permeability, while Bcl-2 can inhibit their effects. Upon mitochondrial permeability, apoptogenic factors are released from the mitochondrial inter-membrane space and leak into the cytosol. One factor is cytochrome c, which induces the liberation of protease activators (caspases) that ultimately lead to apoptosis through nuclear damage (DNA fragmentation, DNA mutations). In addition, Smac/Diablo is released and can block IAP inhibition of capsase activity. Mitochondrial permeability is also related to the increased generation of reactive oxygen species (ROS), which plays a role in the degradation phase of apoptosis (i.e. plasma membrane alterations).
[Afbeelding niet meer beschikbaar]
You should recognize a few things in this image. PI3K is one of the two pathways in which IGF is known to act, and AKT is the downstreamindirect signaling pathway of IGF as well .
Mitochondria in Apoptosis
Increases in cytosolic Ca2+ levels due to activation of ion channel-linked receptors, such as that for the excitatory amino acid neurotransmitter glutamic acid, can induce permeability transition (PT) of the mitochondrial membrane. PT constitutes the first rate-limiting event of the common pathway of apoptosis. Upon PT, apoptogenic factors leak into the cytoplasm from the mitochondrial intermembrane space. Two such factors, cytochrome c and apoptosis inducing factor (AIF), begin a cascade of proteolytic activity that ultimately leads to nuclear damage (DNA fragmentation, DNA mutations) and cell death. Cytochrome C, a key protein in electron transport, appears to act by forming a multimeric complex with Apaf-1, a protease, which in turn activates procaspase 9, and begins a cascade of activation of downstream caspases. Smac/Diablo is released from the mitochondria and inhibits IAP (inhibitor of apoptosis) from interacting with caspase 9 leading to apoptosis. Bcl-2 and Bcl-X can prevent pore formation and block the release of cytochrome c from the mitochondria and prevent activation of the caspase cascade and apoptosis. PT is also related to the mitochondrial generation of reactive oxygen species which plays a role in the degradation phase of apoptosis (i.e. plasma membrane alterations).
Mitochondrial induced apoptosis is the specific pathway that Selegiline is used to protect against. Selegiline prevents the mitochondrial from releaseing Cytochrome c from the membrane by upregulating Bcl-2 and increasing membrain stability.
[Afbeelding niet meer beschikbaar]
IGF Regulation of Apoptosis
Model of IGF-I Receptor regulation of apoptosis. Ligand binding to IGF-IR activates the tyrosine kinase domain which initiates a set of signaling cascades. This leads to a higher concentration of the anti-apoptotic proteins bcl-2 and bcl-xL a lower level of the apoptotic proteins bax and bcl-xs. IGF-IR signaling also activates phosphatidylinositol 3-kinase (P13-K), which in turn activates protein kinase B (PKB/Akt) that also prevent apoptosis. These pathways converge on the inhibition of caspases, especially caspase-3, which is then blocked from performing an apoptosis-initiating cleavage of poly(adenosine diphosphate ribose) polymerase (PARP) and blocked from degrading β-catenin, part of the cadherin cell-adhesion system. Thus, IGF stimulates IGF-IR
TNF is resposnible for inducing apoptosis via signaling at the Fas Ligand, which you can see in the above pathways.
Involvement of the TNF-alpha autocrine-paracrine loop, via NF-kappaB and YY1, in the regulation of tumor cell resistance to Fas-induced apoptosis.
Huerta-Yepez S, Vega M, Garban H, Bonavida B.
Department of Microbiology, Immunology, and Molecular Genetics, Jonsson Comprehensive Cancer Center, University of California, 10833 Le Conte Ave., Los Angeles, CA 90095-1747, USA; Unidad de Investigacion Medica en Inmunologia e Infectologia, Hospital de Infectologia, CMN "La Raza", IMSS, Mexico.
Many tumors are resistant to Fas ligand (FasL)-induced apoptosis. This study examined the role of tumor-derived TNF-alpha, via an autocrine/paracrine loop, in the regulation of tumor-cell resistance to FasL-induced apoptosis. We have reported that Fas expression and sensitivity to FasL is negatively regulated by the transcription repressor factor Yin Yang 1 (YY1). Thus, we hypothesized that tumor-derived TNF-alpha induces the activation of NF-kappaB and the transcription repressor YY1, both of which negatively regulate Fas expression and sensitivity to FasL-induced apoptosis. This hypothesis was tested in PC-3 prostate cancer cells which synthesize and secrete TNF-alpha and express constitutively active NF-kappaB and YY1. Treatment of PC-3 cells with TNF-alpha (10 units) resulted in increased NF-kappaB and YY1 DNA-binding activity, upregulation of YY1 expression, downregulation of surface and total Fas expression and enhanced resistance of PC-3 to apoptosis induced by the FasL agonist antibody CH-11. In contrast, blocking the binding of secreted TNF-alpha on PC-3 cells with soluble recombinant sTNF-RI resulted in significant inhibition of constitutive NF-kappaB and YY1 DNA-binding activity, downregulation of YY1 expression, upregulation of Fas expression and sensitization of tumor cells to CH-11-induced apoptosis. The regulation of YY1 expression and activity by NF-kappaB was demonstrated by the use of the NF-kappaB inhibitor Bay 11-7085 and by the use of a GFP reporter system whereby deletion of the YY1-tandem binding site in the promoter significantly enhanced GFP expression. The direct role of YY1 expression in the regulation of PC-3 resistance to CH-11-induced apoptosis was shown in cells transfected with siRNA YY1 whereby such cells exhibited upregulation of Fas expression and were sensitized to CH-11-induced apoptosis. These findings demonstrate that the TNF-alpha autocrine-paracrine loop is involved in the constitutive activation of the transcription factors NF-kappaB and YY1 in the tumor cells and this loop leads to inhibition of Fas expression and resistance to FasL-induced apoptosis. Further, these findings identify new targets such as TNF-alpha, NF-kappaB and YY1, whose inhibition can reverse tumor cell resistance to FasL-mediated apoptosis.
idd
