Today we have concluded a meeting with DR Zhang and (UTEP) and DR Bryan (Texas Tech) on future projects. We have discussed our collaborative efforts on several projects, and discussed to use "gene interference" techniques to affect several genes and see whether we can affect several pathways for the cure of cancer.
Several critical areas:
ie. Could blocking PMS2 (MLH-1 or MLH1 protein ) increase the efficiency of 5-FU in Colon cancer?
ie. Could activation of ARF amplify MDM2 with increased proteosomal degration of P53 in certain Sarcoma?
ie. Could a genetically engineered AATCC Nucleotide set keep Telomeres busy to increase Apoptosis?
ie. Could genetic instability induced by inactivation of telomerase increase radiation sensitivity and response to certain chemotherapy agents?
ie. Examining the role of RPTPs in Alzheimer dementia
ie. Blocking the Farnesyl to delocalize RAS in lung cancers
ie. Blocking Phospholipase C in PIK3 driven cancers?
The meeting was concluded with a tour of the Laboratory.
Our work is cut out, CRBCM, is still working hard for the cure, no stone will stay unturned!
Showing posts with label MDM2. Show all posts
Showing posts with label MDM2. Show all posts
Tuesday, November 12, 2013
Saturday, January 26, 2013
PRELIMINARY DISCUSSION ON THE 4TH LAW. THE 4TH LAW IS BEST UNDERSTOOD AS THE SET OF FORCES THAT DRIVE THE CELL FUNCTIONS IN A PARTICULAR ELECTED DIRECTION.
THE 4TH LAW IS BEST UNDERSTOOD AS THE SET OF FORCES THAT DRIVE THE CELL FUNCTIONS IN A PARTICULAR ELECTED DIRECTION.
At molecular level, this is enforced by GENE AMPLIFICATION. That is if the cell is going toward differentiation, the cell will make cellular processes to direct all the cellular function to that aim. for specific cancer this equivalent to the notion of DRIVER Mutation. Cellular functions are not totally random and living things do not stay still! life is always on the go, and on the go for survival. And once it has chosen a direction, it direct its functions toward an overall goal which at cellular level is to ensure survival. The drive, the stamina, the direction is battery powered and purposeful!
In the cell that drive is powered and to ensure that it has direction, AMPLIFICATION GENES go to work.
One good example of this is what happens with some Viruses. A number of viruses when the enter the host cell, will incorporate their viral genome into the genome of the host to manage to use the host survival machinery to their advantage. Insertion in the genome of the host sometimes is not enough to trigger the use of the Viral genome in the host machinery, the Virus has to recruit a "growth factor" most of the time called FACTOR-1 to ensure amplification of its genetic material. (this is known for HIV infection)
In cancer cells, there are amplification genes toward the completion and survival of the cancerous process.
In lung and thyroid cancers, TTF-1 represent such a gene. found amplified in about 10 % of tumors. Scientist have had trouble defining its role. But they know its AMPLIFICATION is bad news for the host. It is a driver gene for the cancerous process. In the cell, there are several levels of GENE AMPLIFICATIONS.
The first level is mission driven. If the mission is to differentiate, this 4th law push to achieve the mission.
if the mission is to grow a cancer, the cell uses all its resources to make a "perfect cancer." This means, tolerate error in the DNA multiplication, down-regulate the repair mechanism, down-regulate or mutate the regulator of P53, MDM2. Amplify VGEF so that the tumor has plenty of good blood vessels.
The second level of amplification is actually originating from the stimulus, the cause of the transformation. the cause could be a change in Oxygen level, a break of shorten Telomerase tail, Tumor growth factor (FGF-1), Cyclins, or an oncogenic mutation or break of DNA strands. This will ultimately stimulate receptors with subsequent signal transduction pathways flow that could be amplified by way of intensity of the signals, but also enzymatic up-regulation and nuclear transcription amplification. Amplification can be then cancerous based, but also stimuli caused.
the 3rd amplification is what occurs at the DRIVER Mutation due to growth factors or increased catalytic rate from related enzymes.
It is hard to measure cancer driven gene Amplification. Most of the study keeps taking Metothrexate and its mechanism of Resistance because amplification of Dehydrofolate Reductase is the mechanism of resistance. every body focus on this enzyme to measure resistance. But when you look at amplification at this various levels, it is not hard to see that these measurements are missing the point or are just misleading.
We will discuss the relevant Genes under the section or Rubric "NOMENCLATURE". Frankly speaking, we have not finished yet the genes for the 3rd law.
We are working hard at CRBCM!
At molecular level, this is enforced by GENE AMPLIFICATION. That is if the cell is going toward differentiation, the cell will make cellular processes to direct all the cellular function to that aim. for specific cancer this equivalent to the notion of DRIVER Mutation. Cellular functions are not totally random and living things do not stay still! life is always on the go, and on the go for survival. And once it has chosen a direction, it direct its functions toward an overall goal which at cellular level is to ensure survival. The drive, the stamina, the direction is battery powered and purposeful!
In the cell that drive is powered and to ensure that it has direction, AMPLIFICATION GENES go to work.
One good example of this is what happens with some Viruses. A number of viruses when the enter the host cell, will incorporate their viral genome into the genome of the host to manage to use the host survival machinery to their advantage. Insertion in the genome of the host sometimes is not enough to trigger the use of the Viral genome in the host machinery, the Virus has to recruit a "growth factor" most of the time called FACTOR-1 to ensure amplification of its genetic material. (this is known for HIV infection)
In cancer cells, there are amplification genes toward the completion and survival of the cancerous process.
In lung and thyroid cancers, TTF-1 represent such a gene. found amplified in about 10 % of tumors. Scientist have had trouble defining its role. But they know its AMPLIFICATION is bad news for the host. It is a driver gene for the cancerous process. In the cell, there are several levels of GENE AMPLIFICATIONS.
The first level is mission driven. If the mission is to differentiate, this 4th law push to achieve the mission.
if the mission is to grow a cancer, the cell uses all its resources to make a "perfect cancer." This means, tolerate error in the DNA multiplication, down-regulate the repair mechanism, down-regulate or mutate the regulator of P53, MDM2. Amplify VGEF so that the tumor has plenty of good blood vessels.
The second level of amplification is actually originating from the stimulus, the cause of the transformation. the cause could be a change in Oxygen level, a break of shorten Telomerase tail, Tumor growth factor (FGF-1), Cyclins, or an oncogenic mutation or break of DNA strands. This will ultimately stimulate receptors with subsequent signal transduction pathways flow that could be amplified by way of intensity of the signals, but also enzymatic up-regulation and nuclear transcription amplification. Amplification can be then cancerous based, but also stimuli caused.
the 3rd amplification is what occurs at the DRIVER Mutation due to growth factors or increased catalytic rate from related enzymes.
It is hard to measure cancer driven gene Amplification. Most of the study keeps taking Metothrexate and its mechanism of Resistance because amplification of Dehydrofolate Reductase is the mechanism of resistance. every body focus on this enzyme to measure resistance. But when you look at amplification at this various levels, it is not hard to see that these measurements are missing the point or are just misleading.
We will discuss the relevant Genes under the section or Rubric "NOMENCLATURE". Frankly speaking, we have not finished yet the genes for the 3rd law.
We are working hard at CRBCM!
Friday, November 2, 2012
The secret for Cure of cancer is located in the selective apoptosis, or cancer cell death
We know there are several ways that lead to cell death. The main 2 ways are through the Extrinsic pathway which uses Receptors located at the skin of the cell called cellular membrane (receptors such as TNF-R1 and FAS) and Intrinsic pathways that use internal proteins (i.e. Caspases) that may destroy or paralyze the breathing and energy producing organs of the cell called mitochondria. The challenge is to control these processes in the cell, know how to trigger them, and to do this only in the cancer cells without affecting the normal cells. We need to know how to tag cancer cells, give that tag to a killing molecule that can attach to the apoptosis receptor. This is just one way to be looking for a cure. The complexity and multitude of metabolic pathways presents a problem, but also opportunities to kill the cancer cell.We are in the wee hours of learning them.Target therapy is in its early hour.
When there is a mistake in the gene during replication, there is a repair mechanism. To allow that repair,
the cell needs to be slowed down in its life cycle. This slowing seems to be the main action of P53. If repair does not occur, P53 leads the cell to cell destruction/apoptosis. That's why most cancers remove or change the P53 to stay alive. Like most Molecules in the cell, the P53 has its own path to destruction. MDM2 seems to be that path to the loss of this so important P53. Scientists are looking at knocking down MDM2 to see if this may restore the P53 function in those conditions where the P53 is not fundamentally altered. We will follow this for you and give an update!
The Cure is achievable we know that for sure, we need just need to become better "cell mechanics"....stay tuned...
When there is a mistake in the gene during replication, there is a repair mechanism. To allow that repair,
the cell needs to be slowed down in its life cycle. This slowing seems to be the main action of P53. If repair does not occur, P53 leads the cell to cell destruction/apoptosis. That's why most cancers remove or change the P53 to stay alive. Like most Molecules in the cell, the P53 has its own path to destruction. MDM2 seems to be that path to the loss of this so important P53. Scientists are looking at knocking down MDM2 to see if this may restore the P53 function in those conditions where the P53 is not fundamentally altered. We will follow this for you and give an update!
The Cure is achievable we know that for sure, we need just need to become better "cell mechanics"....stay tuned...
Subscribe to:
Posts (Atom)