One of the main activities of cancer cells to complete their "criminal enterprise" is to escape proliferation control, and cancer cells have known this and have mastered the way to achieve this very efficiently through the Cadherins. Though it is emphasized that the cancer cells reduce E-cadherin expression to free themselves from their neighbors by reducing Adhesion molecules, the truth is that there is a more ominous enterprise going on. Degradation of E-cadherin through Ubiquitilation consumes or distracts E3 from its main job which is to remove some of the Inhibitors to CDK, LEAVING THE CELL WITH UNCHECKED CELL DIVISION.
Occupying the HAKAI (ASSASSIN) would be helpful in achieving control of the process.
The E3 ubiquitin-protein ligase Hakai (HAKAI) also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1 (CBLL1) is an enzyme that in humans is encoded by the CBLL1 gene.[1] This gene encodes an E3 ubiquitin ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation.
Showing posts with label e-cadherin. Show all posts
Showing posts with label e-cadherin. Show all posts
Sunday, November 3, 2013
Tuesday, April 23, 2013
THE Wnt PATHWAY
THE Wnt PATHWAY
It is one of the most complex and versatile pathways. It is a powerful pathway because Mutations here have direct impact on cell totipotentiality, metastasis and cell differentiation and survival. It involves the most genes .
1.The Wnt interacts with E-Cadherin and therefore intervenes in the Cell Adhesion and Metastatic spread of cancers.
2. The Wnt influences Calcium concentration in the cell.
Remenber Calcium have influence on Calmodulin function and in Alzheimer dementia, microtubule entanglement is worsened by influx of Calcium
3. Interaction with the Frizzled assure membrane polarity
?control of the flippase or calcium channels?
4. It has nuclear effect through activation of beta-Catenin (through activation OCT4) which is normally degraded by Ubiquitination, therefore opening the door to Velcade
5. Totipotentiality of cells comes back through the Wnt (through Nanog derepression by removing TCF3 influence)
6. Activate the MTOR to ensure cell survival (through GSK)
8. It controls Mesodermal differentiation (through FLK1)
9. It attenuates the Sonic HedgeHog (through GSK)
10. It has full control of the Neurologic sytem of the cell, and through is wingless system, determines where the function will be displayed
11. It is a stimulator of the c-JUN through RAC-1
12. It confers the status of Neuroendocrine differentiation, control where nerves go or do not go!
It is why Cisplatin has a role in in Neuroendocrine differentiated tumor
13. It is the master of Embryonal Gastrulation
Watch out: attacking Wnt can activate the cancer because of its c-JUN connection which leads to Tumor Growth factor!
14. Viral penetration involves the Wnt
15. It controls cell morphology, migration, endocytosis and cell cycle progression (through Cdc42)
I have to stop to spare you! Look, I have not started to talk about how it leads to Metastasis...I just have to stop. The Wnt, a powerful pathway!
It is one of the most complex and versatile pathways. It is a powerful pathway because Mutations here have direct impact on cell totipotentiality, metastasis and cell differentiation and survival. It involves the most genes .
1.The Wnt interacts with E-Cadherin and therefore intervenes in the Cell Adhesion and Metastatic spread of cancers.
2. The Wnt influences Calcium concentration in the cell.
Remenber Calcium have influence on Calmodulin function and in Alzheimer dementia, microtubule entanglement is worsened by influx of Calcium
3. Interaction with the Frizzled assure membrane polarity
?control of the flippase or calcium channels?
4. It has nuclear effect through activation of beta-Catenin (through activation OCT4) which is normally degraded by Ubiquitination, therefore opening the door to Velcade
5. Totipotentiality of cells comes back through the Wnt (through Nanog derepression by removing TCF3 influence)
6. Activate the MTOR to ensure cell survival (through GSK)
8. It controls Mesodermal differentiation (through FLK1)
9. It attenuates the Sonic HedgeHog (through GSK)
10. It has full control of the Neurologic sytem of the cell, and through is wingless system, determines where the function will be displayed
11. It is a stimulator of the c-JUN through RAC-1
12. It confers the status of Neuroendocrine differentiation, control where nerves go or do not go!
It is why Cisplatin has a role in in Neuroendocrine differentiated tumor
13. It is the master of Embryonal Gastrulation
Watch out: attacking Wnt can activate the cancer because of its c-JUN connection which leads to Tumor Growth factor!
14. Viral penetration involves the Wnt
15. It controls cell morphology, migration, endocytosis and cell cycle progression (through Cdc42)
I have to stop to spare you! Look, I have not started to talk about how it leads to Metastasis...I just have to stop. The Wnt, a powerful pathway!
Saturday, December 29, 2012
AS WE SEARCH FOR THE CURE, IT IS IMPORTANT TO REMEMBER THAT:
Molecular Biology offers tremendous opportunities to fight cancer. In fact, it is surprising that we seem so early (or late, depending on how you understand this) in the game. The cell can be affected in so many ways that we are late reacting. Using integrated methods and our computer abilities, we should by now be involved in developing patterns of attacks by cancer cell type.
We should define clearly the major drivers by type of cancer, and pick the counter attacks specifically per type of cancer. We should be at the stage where each patient who presents to us has his genotype defined, changes in his membrane receptors described, driver mutations enunciated, status of P53, level of major Cyclins and various cell protections (P-gp, Bcl-2), status and quantitative expression of transcription factors, expression of Metastatic potential (E-Cadherin, Metallo-protease, TGF), histone conformation, level of Endonuclases, status of mitotic speed, types of protein Anchor at cell membranes, and Kinesins (Kif2a,b,c) and so on so forth, all spelled out on his file!
IT IS ONLY WITH THIS LEVEL OF DEFINITION, THAT WE CAN PICK AND CHOOSE AN APPROPRIATE TREATMENT, OR UNDERSTAND THE SHORTCOMINGS OF OUR CURRENT STANDARD TREATMENTS. Computers should also be used to tell us if combination treatments should be used sequentially or concurrently, and at which sequences, order and time our therapeutics should be given.
Molecular Biology, so many "distractions" and stuff that some scientists are spending days on, and may lead to something some day, but as we work in a race against death situation, and people are dying every day, it is time to pause and regroup, look at how to create this panel per patient, and develop computer supported patterns of therapy. And every 2-5 years make a stop, update our computer and reload for the Cure!
Molecular Biology offers tremendous opportunities to fight cancer. In fact, it is surprising that we seem so early (or late, depending on how you understand this) in the game. The cell can be affected in so many ways that we are late reacting. Using integrated methods and our computer abilities, we should by now be involved in developing patterns of attacks by cancer cell type.
We should define clearly the major drivers by type of cancer, and pick the counter attacks specifically per type of cancer. We should be at the stage where each patient who presents to us has his genotype defined, changes in his membrane receptors described, driver mutations enunciated, status of P53, level of major Cyclins and various cell protections (P-gp, Bcl-2), status and quantitative expression of transcription factors, expression of Metastatic potential (E-Cadherin, Metallo-protease, TGF), histone conformation, level of Endonuclases, status of mitotic speed, types of protein Anchor at cell membranes, and Kinesins (Kif2a,b,c) and so on so forth, all spelled out on his file!
IT IS ONLY WITH THIS LEVEL OF DEFINITION, THAT WE CAN PICK AND CHOOSE AN APPROPRIATE TREATMENT, OR UNDERSTAND THE SHORTCOMINGS OF OUR CURRENT STANDARD TREATMENTS. Computers should also be used to tell us if combination treatments should be used sequentially or concurrently, and at which sequences, order and time our therapeutics should be given.
Molecular Biology, so many "distractions" and stuff that some scientists are spending days on, and may lead to something some day, but as we work in a race against death situation, and people are dying every day, it is time to pause and regroup, look at how to create this panel per patient, and develop computer supported patterns of therapy. And every 2-5 years make a stop, update our computer and reload for the Cure!
Thursday, December 27, 2012
E-cadherin related article
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Molecular Cell, Volume 48, Issue 6, 914-925, 15 November 2012
Copyright © 2012 Elsevier Inc. All rights reserved.
10.1016/j.molcel.2012.10.011
Copyright © 2012 Elsevier Inc. All rights reserved.
10.1016/j.molcel.2012.10.011
Authors
Yulia A. Komarova
, Fei Huang, Melissa Geyer, Nazila Daneshjou, Alexander Garcia,
Luiza Idalino, Barry Kreutz, Dolly Mehta, Asrar B. MalikSee Affiliations
CLINICAL HYPOTHESIS IN CANCER RESEARCH AND COMMERCIALIZATION:
PUBLISHED 10/14/12
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.
, Fei Huang, Melissa Geyer, Nazila Daneshjou, Alexander Garcia,Luiza Idalino, Barry Kreutz, Dolly Mehta, Asrar B. MalikSee Affiliations
Molecular Cell, Volume 48, Issue 6, 914-925, 15 November
2012
Copyright © 2012 Elsevier Inc. All rights reserved.
10.1016/j.molcel.2012.10.011
Authors
Yulia A. Komarovasend email, Fei Huang, Melissa Geyer,
Nazila Daneshjou, Alexander Garcia,
Luiza Idalino, Barry Kreutz, Dolly Mehta, Asrar B. MalikSee Affiliations
Luiza Idalino, Barry Kreutz, Dolly Mehta, Asrar B. MalikSee Affiliations
Hint: Rollover
Authors and Affiliations
Department of Pharmacology, University of Illinois College
of Medicine, Chicago, IL 60612,
USA The Center for Lung and Vascular Biology, University of Illinois College of Medicine,
Chicago, IL 60612, USA Corresponding author These authors contributed equally to this work
USA The Center for Lung and Vascular Biology, University of Illinois College of Medicine,
Chicago, IL 60612, USA Corresponding author These authors contributed equally to this work
Highlights
VE-cadherin
homophilic adhesion maintains Ca2+ homeostasis
VE-cadherin-mediated adhesion suppresses MT growth
VE-cadherin-mediated adhesion inhibits CaN-dependent dephosphorylation
of EB3
EB3
phosphorylation is required for suppression of MT growth and formation of AJs
Summary
Vascular endothelial (VE)-cadherin homophilic adhesion
controls endothelial barrier permeability
through assembly of adherens junctions (AJs). We observed that loss of VE-cadherin-mediated
adhesion
induced the activation of Src and phospholipase C (PLC)γ2, which mediated Ca2+ release from
endoplasmic reticulum (ER) stores, resulting in activation of calcineurin (CaN), a Ca2+-dependent
phosphatase.
Downregulation of CaN activity induced phosphorylation of serine 162 in end binding (EB) protein 3.
This phospho-switch was required to destabilize the EB3 dimer, suppress microtubule (MT) growth,
and assemble AJs. The phospho-defective S162A EB3 mutant, in contrast, induced MT growth in
confluent endothelial monolayers and disassembled AJs. Thus, VE-cadherin outside-in
signaling regulates
cytosolic Ca2+ homeostasis and EB3 phosphorylation, which are required for assembly of AJs.
These results identify a pivotal function of VE-cadherin homophilic interaction in modulating endothelial
barrier through the tuning of MT dynamics.
=====================================================================through assembly of adherens junctions (AJs). We observed that loss of VE-cadherin-mediated
adhesion
induced the activation of Src and phospholipase C (PLC)γ2, which mediated Ca2+ release from
endoplasmic reticulum (ER) stores, resulting in activation of calcineurin (CaN), a Ca2+-dependent
phosphatase.
Downregulation of CaN activity induced phosphorylation of serine 162 in end binding (EB) protein 3.
This phospho-switch was required to destabilize the EB3 dimer, suppress microtubule (MT) growth,
and assemble AJs. The phospho-defective S162A EB3 mutant, in contrast, induced MT growth in
confluent endothelial monolayers and disassembled AJs. Thus, VE-cadherin outside-in
signaling regulates
cytosolic Ca2+ homeostasis and EB3 phosphorylation, which are required for assembly of AJs.
These results identify a pivotal function of VE-cadherin homophilic interaction in modulating endothelial
barrier through the tuning of MT dynamics.
CLINICAL HYPOTHESIS IN CANCER RESEARCH AND COMMERCIALIZATION:
PUBLISHED 10/14/12
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.
Tuesday, December 4, 2012
Early detection of Lung Cancer
LUNG CANCER EARLY DETECTION:
CRBCM IS SEEKING FUNDING FOR A STUDY TO SEE WHETHER CURRENT MOLECULAR TESTING COULD DETECT EARLY LUNG CANCER IN SELECTED GROUPS OF HEAVY SMOKERS. WE PLAN TO SELECT 150 HEAVY SMOKERS (HISTORY OF 60 PACK A YEAR).
OBTAIN SEQUENCIAL SERUM LEVELS OF E-CADHERIN, METALLOPROTEINASE, AND TUMOR GROWTH FACTOR BETA (EVERY 3 MONTHS FOR 1 YEAR). A PET SCAN WILL BE OBTAINED AT DAY 1 AND DAY 365. SELECTED INDIVIDUALS WILL BE OBSERVED FOR 3-5 YEARS THERE AFTER WITH YEARLY CHECK OF MARKERS AFTER THE FIRST YEAR.
ALTHOUGH PET FINDINGS ARE CRITICAL FOR OUR EVALUATION, WHAT WE ARE CONCENTRATING ON IS TO SEE WHETHER THESE "TUMOR MARKERS" FOLLOWED SEQUENTIALLY COULD PREDICT LUNG CANCER IN HEAVY SMOKERS.
IT WOULD BE INTERESTING TO SEE THE LEVELS OF THESE MARKERS ON PATIENTS WITH INCIDENTAL POSITIVE PET FINDINGS. ANOTHER COROLLARY MEASUREMENT WILL SCREEN FOR ANA AND RHEUMATOID FACTOR TO SEE WHETHER COEXISTING AUTOIMMUNE DISEASES AFFECT THE PATTERN OF THESE MARKERS, PARTICULARLY THE TGF.
SHOULD THESE FINDINGS BE SIGNIFICANT, A TRIPLE KIT COULD BE DEVELOPED FOR EARLY DETECTION OF LUNG CANCER.
CRBCM IS SEEKING FUNDING FOR A STUDY TO SEE WHETHER CURRENT MOLECULAR TESTING COULD DETECT EARLY LUNG CANCER IN SELECTED GROUPS OF HEAVY SMOKERS. WE PLAN TO SELECT 150 HEAVY SMOKERS (HISTORY OF 60 PACK A YEAR).
OBTAIN SEQUENCIAL SERUM LEVELS OF E-CADHERIN, METALLOPROTEINASE, AND TUMOR GROWTH FACTOR BETA (EVERY 3 MONTHS FOR 1 YEAR). A PET SCAN WILL BE OBTAINED AT DAY 1 AND DAY 365. SELECTED INDIVIDUALS WILL BE OBSERVED FOR 3-5 YEARS THERE AFTER WITH YEARLY CHECK OF MARKERS AFTER THE FIRST YEAR.
ALTHOUGH PET FINDINGS ARE CRITICAL FOR OUR EVALUATION, WHAT WE ARE CONCENTRATING ON IS TO SEE WHETHER THESE "TUMOR MARKERS" FOLLOWED SEQUENTIALLY COULD PREDICT LUNG CANCER IN HEAVY SMOKERS.
IT WOULD BE INTERESTING TO SEE THE LEVELS OF THESE MARKERS ON PATIENTS WITH INCIDENTAL POSITIVE PET FINDINGS. ANOTHER COROLLARY MEASUREMENT WILL SCREEN FOR ANA AND RHEUMATOID FACTOR TO SEE WHETHER COEXISTING AUTOIMMUNE DISEASES AFFECT THE PATTERN OF THESE MARKERS, PARTICULARLY THE TGF.
SHOULD THESE FINDINGS BE SIGNIFICANT, A TRIPLE KIT COULD BE DEVELOPED FOR EARLY DETECTION OF LUNG CANCER.
Wednesday, November 14, 2012
CLINICAL RESEARCH AND COMMERCIALIZATION FOR OUR CPRIT SUBMISSION.
Our suggestion of a CPRIT submission formulated on Oct 14th (see our posts) has excited our readers
we felt compelled to dig deeper in this story. We basically suggested that in Prostate Cancer, the incidence was much higher as opposed to a relative low mortality. We went on to say that this paradox begs scientists to find ways of discriminating which Prostate Cancer should be considered dangerous for our patient to compel us to aggressively treat the patient. We suggested that a cancer that is spreading needs to be treated because only metastasis ( spread of the cancer) can kill the patient. How to tell which cancer will spread? We submitted that cancer cells before they spread, needed to lose their attachments to other cells by decreasing their Membrane Adhesion Molecules. One of the Adhesion Molecule of interest was E-Cadherin. We therefore suggested that in all cancers of the prostate, dosing the amount of Adhesion molecule was a way to predict its potential for spreading. If we make it simple to quantify E-Cadherin, a kit can be commercialized to determine quickly the spread of disease. We also suggested that cancer cells to penetrate tissues and leading to organ failure and killing the host, must create its road through cellular tissues. It needs to secrete enzymes called Metalloproteases (2,9) to break through. We suggested that a high level of these Metalloproteases in the biopsy tissue could predict a moving cancer. A Kit to detect Metalloproteases could be commercialized to help Doctors take medical decisions for the benefit of patients. All this, if proven in our intended research could advance medical practice.
There is further discussion to have about this:
1. Could Blocking Metalloprotease gene stop the spread of disease?
2. Could restoring E-Cadherin level or function stop the spread of disease?
Scientist from California believe that activating P120 could restore E-Cadherin function efficiently enough to restore or correct deficiency of E-cadherin function. Should we use this approach to slow down cancer.
The story of E-Cadherin is just beginning. We know that cancer in fact spread very early. In small cell lung cancers, Doctors perform a bone marrow biopsy to see that even in early stage, the cancer has already invaded away from the lung. This is true also in Breast cancer where even in stage I (the first stage of Breast cancer) the Bone marrow could already be invaded. The meaning of this distant invasion has been interpreted with controversy. But even in these cases, it portend a bad prognosis. Worse prognosis then that of patient with negative Bone Marrow finding. DOES E-CADHERIN REDUCTION CORRELATES WITH POSITIVE INVASION OF THE BONE MARROW? COULD WE SPARE PATIENTS A BONE MARROW PROCEDURE IF THE E-CADHERIN IS LOW. These are some of the question that have a bearing on clinical matter and would impact today practice as we move forward.
The level of E-Cadherin has broad implications. In Colon cancers, particularly in the Familial Adenomatous Polyposis (FAP), The E-cadherin level could predict not only evolution to cancer state of the Polyposis but also and again predict metastasis. He even beg to suggest that it could have prognosis implication. The decrease of E-cadherin has profound consequence on the amount the Beta-catenin that E-cadherin can not longer "sequester". Whether this will lead to increase the Cyclin D level down the line could be assumed and therefore sustain life of cancer cell. It is also worth mentioning that in the sequence of gene Mutation leading to Colorectal cancer, the loss of 5q (ADENOMA PHASE)which seems to correspond to the phase where Beta- Catenin is important is the earliest stage in the sequence of transformation. This fact correspond to the "good Prognosis" of these cancer....COULD E-CADHERIN REDUCTION BE AN EARLY SIGN OF COLORECTAL CANCER METASTASIS? OR SHOULD THIS MODEL BE CHALLENGED?
Assuming we find a Molecule A which, when it is incorporated by the cell, it opens up and adopt a conformational change increasing phosphorylation of Beta-Catenin leading it to proteasomic destruction, could that decrease Cyclin D formation and induce Apoptosis? What would be the impact if that incorporation was selective to cancer cells? These are the challenges we face!
Through genetic intervention, could we restore the wnt-signalling pathways to prevent FAP and prevent removal of the Colon in FAP? Remember this, 80-85% of sporadic colorectal cancers have disturbance in the wnt pathways, what we are talking about could impact the majority of Colorectal cncers (second leading cause of cancer death in the United States)
Does the wide spread use of Calcium based product for Osteoporosis prevention correspond to decrease of Colorectal cancer in the terminal colon. Calcium is critical in the function of membrane receptors.
The cure is achievable, let get it!
Our suggestion of a CPRIT submission formulated on Oct 14th (see our posts) has excited our readers
we felt compelled to dig deeper in this story. We basically suggested that in Prostate Cancer, the incidence was much higher as opposed to a relative low mortality. We went on to say that this paradox begs scientists to find ways of discriminating which Prostate Cancer should be considered dangerous for our patient to compel us to aggressively treat the patient. We suggested that a cancer that is spreading needs to be treated because only metastasis ( spread of the cancer) can kill the patient. How to tell which cancer will spread? We submitted that cancer cells before they spread, needed to lose their attachments to other cells by decreasing their Membrane Adhesion Molecules. One of the Adhesion Molecule of interest was E-Cadherin. We therefore suggested that in all cancers of the prostate, dosing the amount of Adhesion molecule was a way to predict its potential for spreading. If we make it simple to quantify E-Cadherin, a kit can be commercialized to determine quickly the spread of disease. We also suggested that cancer cells to penetrate tissues and leading to organ failure and killing the host, must create its road through cellular tissues. It needs to secrete enzymes called Metalloproteases (2,9) to break through. We suggested that a high level of these Metalloproteases in the biopsy tissue could predict a moving cancer. A Kit to detect Metalloproteases could be commercialized to help Doctors take medical decisions for the benefit of patients. All this, if proven in our intended research could advance medical practice.
There is further discussion to have about this:
1. Could Blocking Metalloprotease gene stop the spread of disease?
2. Could restoring E-Cadherin level or function stop the spread of disease?
Scientist from California believe that activating P120 could restore E-Cadherin function efficiently enough to restore or correct deficiency of E-cadherin function. Should we use this approach to slow down cancer.
The story of E-Cadherin is just beginning. We know that cancer in fact spread very early. In small cell lung cancers, Doctors perform a bone marrow biopsy to see that even in early stage, the cancer has already invaded away from the lung. This is true also in Breast cancer where even in stage I (the first stage of Breast cancer) the Bone marrow could already be invaded. The meaning of this distant invasion has been interpreted with controversy. But even in these cases, it portend a bad prognosis. Worse prognosis then that of patient with negative Bone Marrow finding. DOES E-CADHERIN REDUCTION CORRELATES WITH POSITIVE INVASION OF THE BONE MARROW? COULD WE SPARE PATIENTS A BONE MARROW PROCEDURE IF THE E-CADHERIN IS LOW. These are some of the question that have a bearing on clinical matter and would impact today practice as we move forward.
The level of E-Cadherin has broad implications. In Colon cancers, particularly in the Familial Adenomatous Polyposis (FAP), The E-cadherin level could predict not only evolution to cancer state of the Polyposis but also and again predict metastasis. He even beg to suggest that it could have prognosis implication. The decrease of E-cadherin has profound consequence on the amount the Beta-catenin that E-cadherin can not longer "sequester". Whether this will lead to increase the Cyclin D level down the line could be assumed and therefore sustain life of cancer cell. It is also worth mentioning that in the sequence of gene Mutation leading to Colorectal cancer, the loss of 5q (ADENOMA PHASE)which seems to correspond to the phase where Beta- Catenin is important is the earliest stage in the sequence of transformation. This fact correspond to the "good Prognosis" of these cancer....COULD E-CADHERIN REDUCTION BE AN EARLY SIGN OF COLORECTAL CANCER METASTASIS? OR SHOULD THIS MODEL BE CHALLENGED?
Assuming we find a Molecule A which, when it is incorporated by the cell, it opens up and adopt a conformational change increasing phosphorylation of Beta-Catenin leading it to proteasomic destruction, could that decrease Cyclin D formation and induce Apoptosis? What would be the impact if that incorporation was selective to cancer cells? These are the challenges we face!
Through genetic intervention, could we restore the wnt-signalling pathways to prevent FAP and prevent removal of the Colon in FAP? Remember this, 80-85% of sporadic colorectal cancers have disturbance in the wnt pathways, what we are talking about could impact the majority of Colorectal cncers (second leading cause of cancer death in the United States)
Does the wide spread use of Calcium based product for Osteoporosis prevention correspond to decrease of Colorectal cancer in the terminal colon. Calcium is critical in the function of membrane receptors.
The cure is achievable, let get it!
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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