In a man, there is a 1/3 chances that if found with cancer, it will be prostate cancer. But only in 10 percent of those who are dying and who have prostate cancer is it this cancer that causes death. Meaning a number of patients with prostate cancer will die of another cause. Over 186,000 men were diagnosed with Prostate Cancer and close to 29,000 died of this disease yearly. A 6.5 to 1 ratio. This point to a heterogeneous disease, and we will fail by not stating (infamous statement) that autopsy showed that in men over 80 years of age, over 70% will be found with Prostate Cancer. As if it was part of aging. By aging, you implicate Telomeres and most likely the MTOR.
Before jumping to the MTOR which is cool lately, there is one overwhelming phenomena, that is the Prostatic cell development is significantly dependent on Testosterone for its growth. And we have in our armamentarium many agents to stop Testosterone. As we will suggest and as achieved for many hormones, Testosterone blockage can be completed at the cell level, in the testicles, in the Adrenal gland as well as by blocking it in the Pituitary stalk. It is not until one develops refractoriness to Androgen that one may die of Prostate cancer as the principal cause of death. So the physician's task is to keep coming up with new strategies to block the Androgens. There lies the key to treating Prostate Cancers.
THE REVERSAL OF FORTUNES
=========================
It is widely accepted that a small numbers of cells in the prostatic cancer mass (may be less than one percent at onset) will be mutated or spontaneously refractory to Androgen. As time goes by, more mutations related or not to treatment, will occur, while hormone sensitive cancer cells are being starved from stimulation. Over time, the refractory cells will grow in importance and drive the life of the tumor and metastasize everywhere replacing the hormone sensitive one. The disease will therefore become non responsive to Hormone and here comes patient rapid deterioration as the malignant tumor now adopts a new pattern of behavior including new locations of metastasis. Liver lesions, lung lesions and Brain invasion becomes more likely to occur. Chemotherapy with Taxane and Cabazitaxel, a derivative of natural Taxoids, become the mainstay of treatment. ( Particularly now that Sipuleucel-T is advanced to before chemotherapy) Keeping in mind that the reversal of fortune is change of proportions, there is still a portion of hormone responsive cells and Lupron needs to continue while chemotherapy is given!
PSA, Prostate Specific Antigen
======================
Prostate cancer is actually one of the rare diseases that can be screened effectively, and found early by a blood test. That is until we realize that finding a disease that may not kill early leads to unnecessary treatment and patient futile mental disturbance in many cases. We are now retracting, pulling back on our toes and people are growing reluctant to be tested. That is until we clarify what it is we should be looking for to make sure we discern who needs therapy! We needs to know who needs an early intervention. For this the tumor needs to tell us I am bad, and we need to catch the message. And most researchers believe Genetic profiling is one of the critical approaches to tell the difference. The challenge is that Adenocarcinoma seems to follow a progression in their deterioration to a full blown cancer. And some genes are present in prostatitis, Benign Prostatic hypertrophy, Low Gleason prostatic cancer and high gleason cancers. Now which one makes it a bad cancer. This is the current challenge but it will clearly open the door to Target therapy!
Molecular basis of Prostatic cancer Pathogenesis.
While dealing with Intraepithelial Atypical lesion, the presence of Alpha-Methylacyl-Coenzyme Aracemase is considered a signature of Adenocarcinoma presence! In our discussion on Choriocarcinoma, we suggested that Hypermethylation is a major Knockdown way for E2. It plays a role here too! And gene fusion is the other abnormality that is a prominent phenomenon TMPRSS2 and ETS fusion (or TMPRSS2-ERG), and things" degenerate" from there !
Also note that the Androgen receptor gene is located on Xq11-13, (note the "q")
GENES in Prostate Cancers! (TO BE DEFINITELY CONTINUED)
Showing posts with label PSA. Show all posts
Showing posts with label PSA. Show all posts
Saturday, March 23, 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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