1.CDH 17
The change in expression of this gene in advance pancreatic cancer does not come as a surprise
because by now we have become familiar with the fact that advance cancer is on the move and should metastasize, CDH belong to the Cadherin family, the family of adhesion molecule, cells need to detach and go. Takamura M et al. have shown that the Liver-intestine Cadherins reduction correlated with Colon cancer metastatic to lymph nodes.
CDH17 appears to be a gene of differentiation and could help determine the origin of of tissue in those ambivalent cases where we are dealing with an cancer of unknown primary. It is a proton pump dependent cellular membrane structure. What is fascinating is the fact that how quickly these structures are internalized or their stimulation effect is transmitted to the Nucleus at splicing center to be expressed as differentiation agents.
Zhu at al. have suggested that the hepatic Nuclear factor 1 and CDX2 participate in the regulation of CDH17 expression. (larger speculation Where is the p molecule counterpart? since this cadherin is on 8q)
2. PSCA: PROSTATE stem cell Antigen
When the prostate lends a hand to the pancreas you know this is bad news. This antigen does not exist in the normal pancreas. But when it appears in the Pancreas you know the disease is advanced. Even in the Prostate the amplification of this antigen marks very high Gleason at presentation or bone Metastatasis. It is not PSA we should be looking for, but PCR overexpression of PSCA. By its name it says it all "Stem cell" meaning the cancer is now OMNIPOTENT and Incredibly resistant. The presence of this antigen is not only predictive but also prognosis. The makers of SIPULEUCEL-T should be incubating patient dendritic cells with with this antigen rather than PAP to be active in pancreatic cancers.
One interesting observation was made by Moore et al. while they were knocking down rats to further study this gene, they noted an over-expression of the AURORA kinases, these genes that regulate mitosis by controlling events at the Centrosomes. It is interesting because it raises the possibility of using the PSCA as an indicator for use of Aurora inhibitors (Hesperadin, ZM447439,Tozasertib,VX680). Also recent evidence of activity of Abraxane in Pancreatic cancer would open up the opportunity to use Abraxane in combination with Aurora kinase inhibitor in this disease. Clearly if P53 is dysregulated, we can safely assume the Aurora kinase may have a role since they are more likely over-expressed.
SO: new target Therapy in Pancreatic cancer ABRAXANE with an Aurora MutiKinase Inhibitor would be the next step if we want to introduce target therapy in Pancreatic cancers.
A recent TV documentary showed that a chemical compound that the EPA is investigating because it has contaminated the drinking waters in the USA caused cells to have Multiple Centrosomes in exposed cells, clearly is it affecting the AURORA and most likely AURORA A. It raised the possibility that Metallic based chemical compound toxicity may have a larger weight on this pathways. I wonder what Arsenic Trioxyde would add to this! remember the anti-Aurora have a secondary anti-Histone (3) activity contributing to their effect in CML.
3. MYC:
*a GLOBAL AMPLIFIER OF ALL GENES INCLUDING PROLIFERATIVE GENES.
*RECRUITER OF HISTONES DEACETYLASE PROTEIN
*OVERACTION OF CBF LIKE MOLECULES
*IT HAS IRES THE INTERNAL RIBOSOME ENTRY SITES WHICH IS THE KEY TO THE DOOR TO RIBOSOME FOR PROTEIN FORMATION (REGULATOR FOR MATION) AND HAS A THE ZIPPER TO ATTACH AND OPEN WIDE DNA FOR TRANSLATION. OVER-EXPRESSION OF MYC DRIVES PROLIFERATION AT HIGH PACE!
WIKIPEDIA SAYS IT ALL
Myc protein is a transcription factor that activates expression of many genes through binding on consensus sequences (Enhancer Box sequences (E-boxes)) and recruiting histone acetyltransferases (HATs). It can also act as a transcriptional repressor. By binding Miz-1 transcription factor and displacing the p300 co-activator, it inhibits expression of Miz-1 target genes. In addition, myc has a direct role in the control of DNA replication.[4]
Myc is activated upon various mitogenic signals such as Wnt, Shh and EGF (via the MAPK/ERK pathway).
By modifying the expression of its target genes, Myc activation results
in numerous biological effects. The first to be discovered was its
capability to drive cell proliferation (upregulates cyclins, downregulates p21), but it also plays a very important role in regulating cell growth (upregulates ribosomal RNA and proteins), apoptosis (downregulates Bcl-2), differentiation and stem cell self-renewal. Myc is a very strong proto-oncogene and it is very often found to be upregulated in many types of cancers. Myc overexpression stimulates gene amplification,[5] presumably through DNA over-replication."
"
Showing posts with label cadherin. Show all posts
Showing posts with label cadherin. Show all posts
Saturday, March 16, 2013
Sunday, October 14, 2012
CLINICAL HYPOTHESIS IN CANCER RESEARCH AND COMMERCIALIZATION:
CLINICAL HYPOTHESIS IN CANCER RESEARCH AND COMMERCIALIZATION:
Of 186,000 Prostate cancers diagnosed each year, only 29,000 patients will die of this disease. In fact 70% of men over 80 years of age may be found with Prostate Cancer. Most will not die of this cancer. This fact has made almost futile the testing for prostate cancer in elderly patients. How does one chose who should be followed closely or treated? In other words how do you know what prostate cancer to observe versus which one to actually treat? In more scientific terms, which are the predictive factors that would prompt us to act versus observe the cancer? To make the matter more confusing, the success of PSA (prostate Specific Antigen) testing has complicated the issue. It has led to over-diagnosis, and experts are now recommending to use PSA findings with caution.
One thing is for sure: the difference between a benign and malignant tumor is that the malignant ones spread and invade our body. This is called "ability to metastasize". It is by invading other organs that cancer causes these organs to fail and finally causing death of the patient. Researchers have now started to look at cancer cells to try to predict which ones will spread and therefore kill the individual.
The Hypothesis:
For a cancer to spread, it has to detach itself from its surroundings and create a way to where it wants to go. Scientists have suggested that wherever a cell is located, it is maintained in place by ADHESION MOLECULES which tie them to the location. To make its move, the cancer cell has to lose these molecules.
This is why E-Cadherin has to be reduced by the cell, so that it can free itself from this environment. The question now is: Is a REDUCTION OF E-CADHERIN A PREDICTOR OF BAD CANCER? IN OTHER WORDS, SHOULD WE BE TESTING FOR THE REDUCTION OF E-CADHERIN IN PROSTATE CANCER TO PREDICT WHICH ONES NEEDS INTERVENTION? This is thought provoking.
P120 and beta- catenins are 2 molecules which could potentially be surrogates of cancer metastasis...who knows for sure!
After it has freed itself, the cancer cell has to move through tissues, it uses enzymes to break through the fibers. Some of these enzymes are called METALLOPROTEINASE. The current question is: SHOULD WE BE MEASURING LEVELS OF METALLOPROTEINASES TO DETECT CANCER CELLS ON THE MOVE?
These questions have been raised, it is time to work.
We could actually improve current means of screening for cancer by checking for reduction of E-Cadherin and increase of metalloproteinase in the tumor or blood if this is possible. Potential for commercialization is high if we can conquer this detection technology. "lets go to work!
12/3/2012
METASTATASIS AND SEEDING INTO NEW OR INVADED TISSUE
When the cancer cell reaches the new location, it uses the TGF beta to help its growth and to create exceptional advantage for its growth versus surrounding tissue. This Lead scientists to conclude that TGF beta presence is a sign of resistant disease. When in facts, it is first a late sign of metastasis already COMPLETED, TGF beta seems to be a sign of SEEDING INTO A NEW LOCATION. TGF BETA NOT ONLY STIMULATE GROWTH BUT COULD BE AN INHIBITORY PROTEIN FOR THE HOST DEFENSE AND REJECTION.
QUESTION:
SHOULD TGF BETA INCREASE BE THE THE SIGN OF SEEDING VS LATE STEP OF METASTASIS. WE BELIEVE THAT BY THE TIME TGF BETA IS BEING ELEVATED, SEEDING HAS ALREADY OCCURRED.
Of 186,000 Prostate cancers diagnosed each year, only 29,000 patients will die of this disease. In fact 70% of men over 80 years of age may be found with Prostate Cancer. Most will not die of this cancer. This fact has made almost futile the testing for prostate cancer in elderly patients. How does one chose who should be followed closely or treated? In other words how do you know what prostate cancer to observe versus which one to actually treat? In more scientific terms, which are the predictive factors that would prompt us to act versus observe the cancer? To make the matter more confusing, the success of PSA (prostate Specific Antigen) testing has complicated the issue. It has led to over-diagnosis, and experts are now recommending to use PSA findings with caution.
One thing is for sure: the difference between a benign and malignant tumor is that the malignant ones spread and invade our body. This is called "ability to metastasize". It is by invading other organs that cancer causes these organs to fail and finally causing death of the patient. Researchers have now started to look at cancer cells to try to predict which ones will spread and therefore kill the individual.
The Hypothesis:
For a cancer to spread, it has to detach itself from its surroundings and create a way to where it wants to go. Scientists have suggested that wherever a cell is located, it is maintained in place by ADHESION MOLECULES which tie them to the location. To make its move, the cancer cell has to lose these molecules.
This is why E-Cadherin has to be reduced by the cell, so that it can free itself from this environment. The question now is: Is a REDUCTION OF E-CADHERIN A PREDICTOR OF BAD CANCER? IN OTHER WORDS, SHOULD WE BE TESTING FOR THE REDUCTION OF E-CADHERIN IN PROSTATE CANCER TO PREDICT WHICH ONES NEEDS INTERVENTION? This is thought provoking.
P120 and beta- catenins are 2 molecules which could potentially be surrogates of cancer metastasis...who knows for sure!
After it has freed itself, the cancer cell has to move through tissues, it uses enzymes to break through the fibers. Some of these enzymes are called METALLOPROTEINASE. The current question is: SHOULD WE BE MEASURING LEVELS OF METALLOPROTEINASES TO DETECT CANCER CELLS ON THE MOVE?
Matrix metalloproteinases 2 and 9 increase permeability of sheep pleura in vitro
Eleni Apostolidou1*)These questions have been raised, it is time to work.
We could actually improve current means of screening for cancer by checking for reduction of E-Cadherin and increase of metalloproteinase in the tumor or blood if this is possible. Potential for commercialization is high if we can conquer this detection technology. "lets go to work!
12/3/2012
METASTATASIS AND SEEDING INTO NEW OR INVADED TISSUE
When the cancer cell reaches the new location, it uses the TGF beta to help its growth and to create exceptional advantage for its growth versus surrounding tissue. This Lead scientists to conclude that TGF beta presence is a sign of resistant disease. When in facts, it is first a late sign of metastasis already COMPLETED, TGF beta seems to be a sign of SEEDING INTO A NEW LOCATION. TGF BETA NOT ONLY STIMULATE GROWTH BUT COULD BE AN INHIBITORY PROTEIN FOR THE HOST DEFENSE AND REJECTION.
QUESTION:
SHOULD TGF BETA INCREASE BE THE THE SIGN OF SEEDING VS LATE STEP OF METASTASIS. WE BELIEVE THAT BY THE TIME TGF BETA IS BEING ELEVATED, SEEDING HAS ALREADY OCCURRED.
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