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!
Saturday, December 29, 2012
Meet the newly approved RET/MET/VEGFR inhibitorFromExelixis
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| COMETRIQ is indicated for the treatment of patients with progressive, metastatic medullary thyroid cancer (MTC). |
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| COMETRIQ inhibits the activity of tyrosine kinases including RET, MET, and VEGFRs. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment. | ||||||||
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| COMETRIQ demonstrated significant efficacy in a phase 3 trial (N=330) in metastatic MTC patients with radiographically confirmed disease progression.* | ||||||||
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| * | Results of the international, multicenter, randomized, double-blind EXAM study in patients (N=330) with progressive, metastatic MTC. Primary endpoint: PFS; secondary endpoints: ORR and overall survival (OS). OS data are not yet mature. |
|
Friday, December 28, 2012
» About CPRIT » Purpose, Powers, and Duties
Purpose, Powers, and Duties
Purpose
The Cancer Prevention and Research Institute of Texas (CPRIT) is the state agency mandated to:- Create and expedite innovation in the area of cancer research and in enhancing the potential for a medical or scientific breakthrough in the prevention of cancer and cures for cancer;
- Attract, create, or expand research capabilities of public or private institutions of higher education and other public or private entities that will promote a substantial increase in cancer research and in the creation of high-quality new jobs in this state; and
- Develop and implement the Texas Cancer Plan.
Powers and Duties
In furtherance of its statutory mandate, CPRIT is authorized to:-
Make grants to provide funds to public or private persons to implement the Texas Cancer Plan,
and may make grants to institutions of learning and to advanced medical
research facilities and collaborations in this state for:
-
Research into the causes of and cures for all types of cancer in humans;
-
Facilities for use in research into the causes of and cures for cancer;
-
Research, including translational research, to develop therapies, protocols, medical pharmaceuticals, or procedures for the cure or substantial mitigation of all types of cancer in humans; and
-
Cancer prevention and control programs in this state to mitigate the incidence of all types of cancer in humans;
-
-
Support institutions of learning and advanced medical research
facilities and collaborations in this state in all stages in the process
of finding the causes of all types of cancer in humans and developing
cures, from laboratory research to clinical trials and including
programs to address the problem of access to advanced cancer treatment;
-
Establish the appropriate standards and oversight bodies to ensure the
proper use of funds authorized under this chapter for cancer research
and facilities development;
-
Employ an executive director as determined by the oversight committee;
-
Employ necessary staff to provide administrative support;
-
Monitor contracts and agreements; and
- Work to implement the Texas Cancer Plan and continually monitor and revise the Texas Cancer Plan as necessary.
OTHER SPECTRUM OF THE ISSUE, DON'T GO TO DEFICIENCIES
Nail changes can be a clue in diagnosing some vitamin deficiencies, as in this patient's nail beading. Beads that seem to drip down the nail like wax are associated with vitamin B deficiencies and some endocrine conditions (eg. diabetes mellitus, thyroid disorders and Addison disease). Brown-gray nails may be associated with vitamin B12 deficiency. A central nail ridge may be caused by iron deficiency, folic acid deficiency, or protein deficiency. Koilonychia (spoon nail) is associated with iron deficiency and protein deficiency (especially sulfur-containing amino acids, such as cysteine or methionine).[4]
FROM MEDSCAPE
Nail changes can be a clue in diagnosing some vitamin deficiencies, as in this patient's nail beading. Beads that seem to drip down the nail like wax are associated with vitamin B deficiencies and some endocrine conditions (eg. diabetes mellitus, thyroid disorders and Addison disease). Brown-gray nails may be associated with vitamin B12 deficiency. A central nail ridge may be caused by iron deficiency, folic acid deficiency, or protein deficiency. Koilonychia (spoon nail) is associated with iron deficiency and protein deficiency (especially sulfur-containing amino acids, such as cysteine or methionine).[4]
FROM MEDSCAPE
Mutombo --
Because of you, I'll be taking the oath of office again on January 21st.
You were part of the inauguration four years ago, and I hope you'll get involved in inaugural activities over the next few weeks -- whether that's in Washington, D.C., or wherever you call home.
As we make plans, we want to make sure the people who made this inauguration possible are the first to know what's happening -- but to do that I'll need your help.
Take a minute now to make sure your family and friends join you in being a part of this inauguration.
I'm honored each and every day to be your president, and I will never forget how I got here.
I'm so grateful for everything you've done.
Let's also remember why we're here: we've got more work to do. And we're going to begin this next chapter in the American story together.
Invite others to join us here:
http://action.2013pic.org/The-Inauguration
Thanks,
Barack
Because of you, I'll be taking the oath of office again on January 21st.
You were part of the inauguration four years ago, and I hope you'll get involved in inaugural activities over the next few weeks -- whether that's in Washington, D.C., or wherever you call home.
As we make plans, we want to make sure the people who made this inauguration possible are the first to know what's happening -- but to do that I'll need your help.
Take a minute now to make sure your family and friends join you in being a part of this inauguration.
I'm honored each and every day to be your president, and I will never forget how I got here.
I'm so grateful for everything you've done.
Let's also remember why we're here: we've got more work to do. And we're going to begin this next chapter in the American story together.
Invite others to join us here:
http://action.2013pic.org/The-Inauguration
Thanks,
Barack
ROLE OF METABOLISM IN WEIGHT CONTROL
The fact is that Metabolism of Proteins and fat are not the same as that of Carbohydrates. And every step the body has to complete to lead to energy production is good for you. Metabolism of Carbohydrates is a direct conversion of carbohydrate to energy. It is like burning fuel to have heat from a fire.
2 things here, some Carbohydrates are not easy to burn directly. So sugar you get from pure sugar is more readily burnable than sugar from a fruit. Sucrose is more burnable than Fructose. You burn Sucrose directly to energy. To burn Fructose you need to convert it. That extra step the body should make uses energy, making the energy production less efficient. Believe me, at a certain age, when you don't need to grow, a less efficient system of energy is what you need. To make up the deficiency, the body works by giving energy to produce energy. And any body work is good for you. It decreases your chance to build up obesity!
Secondly, Protein and lipid need major work to be converted to sugar prior to being burned into energy. When we eat sugar, it has to be burned by our Metabolism. If not burned, the body stores it into fat mostly, and proteins if there is a need to build and grow! BURNING YOUR STORAGE DOES NOT OCCUR IF YOU PROVIDE YOUR BODY WITH SUGARS, BECAUSE THE BODY WILL USE SUGAR FIRST FOR ENERGY PRODUCTION AND ANY EXTRA SUGAR WILL BE STORED INTO FAT FIRST (OBESITY) AND PROTEIN SECOND! (depending on our needs).
The notion that 55% of your diet need to come from Carbohydrates
15% from proteins
30% from lipids
may be good when you are trying to maintain or grow. This not true for everyone.
But it gives us a further opportunity to cut down carbohydrates from 55% to 20-30%. Such a cut will force the body to change its reserve of fat into carbohydrate. Again to do that it must WORK. Work of the body without sugar means weight stabilization or WEIGHT LOSS. SO anyone who cuts Carbohydrate intake for 6 to 8 weeks, will lose weight or at least will not grow! REMEMBER: CUTTING 10% OF YOUR WEIGHT WILL HAVE MAJOR POSITIVE IMPLICATIONS FOR YOUR HEALTH. IT'S LIKE CUTTING 10% GIVES YOU 30-40% BENEFIT IN HEALTH. 10% WEIGHT LOSS IS THE REALISTIC WORKABLE GOAL IN WEIGHT WATCHING.
LOSING 1 POUND PER WEEK IS THE GOAL!
The story does not stop here unfortunately.
By now (after 2-3 months) craving carbohydrates in our weight watcher becomes more intense, some will start adding more and more Carbohydrates in their pantry again and the program fails. The other fact is that the body always reacts to what you do to it! The body learns that "ahha! this weight watcher is not giving me the carbohydrates I need, I will need to create a more efficient way to burn the fat and therefore the weight loss is plateauing out.
And that's OK! Keeping a 10% weight loss is beneficial to your health. To further decrease the weight more after 2-3 months of low Carbohydrates, you got to increase the Metabolism. This is the step where exercise comes in strong. You will exercise easier with the 10 % initial loss of the weight anyway!
ANYONE CAN LOSE 10% WEIGHT AS LONG AS THEY CUT OUT ANYTHING THEY ADD TO VEGETABLES OR MEAT OR FISH! AND I MEAN ANYTHING FOR 6-12 WEEKS! NO CORN, NO MAIZE, NO CORNFLAKES/cereals, NO RICE, NO SUGARY INGREDIENTS TO LEAFAGE AND MEAT/FISH. AND YOU CAN DO THIS FOR 6-12 WEEKS! BEFORE SWITCHING TO INTENSIFIED REGULAR EXERCISE. YOU WILL BE MENTALLY CHALLENGED. YOU NEED A PARTNER WHO IS DOING THE SAME. YOU NEED SOMEONE TO REPORT TO, WEEKLY. CALL CRBCM AT 915-307-3354 IF YOU DO NOT HAVE A "BUDDY"! YOU CAN DO THIS!
During my home visits, I find myself with obese patients with extensive arthritis or on Oxygen who are lonely and worsening by the day. It is evident to me that they are forsaken. Primary care Doctors seem to have failed to provide individualized medicine. We are all guilty looking for money which is tied to the number of people we see (RVU) that we cannot take the time we need to confront obesity for unique patients! With this simple regimen most if not all lose the initial 10% of weight. The problem is the maintenance when you need exercise and support.
It is in the maintenance setting that medications and other interventions have a role in morbid obesity candidates!We need a STAGED INTERVENTION TO WEIGHT LOSS!
THIS IS ADDED TO THE FINITE AMOUNT OF LIFETIME HEALTH CHART WHICH IS BASED ON THE NOTION THAT THERE IS A FINITE AMOUNT OF CARBOHYDRATES PER EACH LIFE. AND ONE WOULD SPREAD IT OUT EVENLY OR EAT THE MOST EARLY IN LIFE BEFORE STARTING TO DRASTICALLY REDUCE. AND THE MORE YOU EAT OR HAVE EATEN EARLY, THE LESS YOU CAN EAT UNTIL AGE 90! THE CURVE GOES DOWN AS WE AGE!
(CHALLENGES TO THIS LOW CARB DIET TO FOLLOW)
The fact is that Metabolism of Proteins and fat are not the same as that of Carbohydrates. And every step the body has to complete to lead to energy production is good for you. Metabolism of Carbohydrates is a direct conversion of carbohydrate to energy. It is like burning fuel to have heat from a fire.
2 things here, some Carbohydrates are not easy to burn directly. So sugar you get from pure sugar is more readily burnable than sugar from a fruit. Sucrose is more burnable than Fructose. You burn Sucrose directly to energy. To burn Fructose you need to convert it. That extra step the body should make uses energy, making the energy production less efficient. Believe me, at a certain age, when you don't need to grow, a less efficient system of energy is what you need. To make up the deficiency, the body works by giving energy to produce energy. And any body work is good for you. It decreases your chance to build up obesity!
Secondly, Protein and lipid need major work to be converted to sugar prior to being burned into energy. When we eat sugar, it has to be burned by our Metabolism. If not burned, the body stores it into fat mostly, and proteins if there is a need to build and grow! BURNING YOUR STORAGE DOES NOT OCCUR IF YOU PROVIDE YOUR BODY WITH SUGARS, BECAUSE THE BODY WILL USE SUGAR FIRST FOR ENERGY PRODUCTION AND ANY EXTRA SUGAR WILL BE STORED INTO FAT FIRST (OBESITY) AND PROTEIN SECOND! (depending on our needs).
The notion that 55% of your diet need to come from Carbohydrates
15% from proteins
30% from lipids
may be good when you are trying to maintain or grow. This not true for everyone.
But it gives us a further opportunity to cut down carbohydrates from 55% to 20-30%. Such a cut will force the body to change its reserve of fat into carbohydrate. Again to do that it must WORK. Work of the body without sugar means weight stabilization or WEIGHT LOSS. SO anyone who cuts Carbohydrate intake for 6 to 8 weeks, will lose weight or at least will not grow! REMEMBER: CUTTING 10% OF YOUR WEIGHT WILL HAVE MAJOR POSITIVE IMPLICATIONS FOR YOUR HEALTH. IT'S LIKE CUTTING 10% GIVES YOU 30-40% BENEFIT IN HEALTH. 10% WEIGHT LOSS IS THE REALISTIC WORKABLE GOAL IN WEIGHT WATCHING.
LOSING 1 POUND PER WEEK IS THE GOAL!
The story does not stop here unfortunately.
By now (after 2-3 months) craving carbohydrates in our weight watcher becomes more intense, some will start adding more and more Carbohydrates in their pantry again and the program fails. The other fact is that the body always reacts to what you do to it! The body learns that "ahha! this weight watcher is not giving me the carbohydrates I need, I will need to create a more efficient way to burn the fat and therefore the weight loss is plateauing out.
And that's OK! Keeping a 10% weight loss is beneficial to your health. To further decrease the weight more after 2-3 months of low Carbohydrates, you got to increase the Metabolism. This is the step where exercise comes in strong. You will exercise easier with the 10 % initial loss of the weight anyway!
ANYONE CAN LOSE 10% WEIGHT AS LONG AS THEY CUT OUT ANYTHING THEY ADD TO VEGETABLES OR MEAT OR FISH! AND I MEAN ANYTHING FOR 6-12 WEEKS! NO CORN, NO MAIZE, NO CORNFLAKES/cereals, NO RICE, NO SUGARY INGREDIENTS TO LEAFAGE AND MEAT/FISH. AND YOU CAN DO THIS FOR 6-12 WEEKS! BEFORE SWITCHING TO INTENSIFIED REGULAR EXERCISE. YOU WILL BE MENTALLY CHALLENGED. YOU NEED A PARTNER WHO IS DOING THE SAME. YOU NEED SOMEONE TO REPORT TO, WEEKLY. CALL CRBCM AT 915-307-3354 IF YOU DO NOT HAVE A "BUDDY"! YOU CAN DO THIS!
During my home visits, I find myself with obese patients with extensive arthritis or on Oxygen who are lonely and worsening by the day. It is evident to me that they are forsaken. Primary care Doctors seem to have failed to provide individualized medicine. We are all guilty looking for money which is tied to the number of people we see (RVU) that we cannot take the time we need to confront obesity for unique patients! With this simple regimen most if not all lose the initial 10% of weight. The problem is the maintenance when you need exercise and support.
It is in the maintenance setting that medications and other interventions have a role in morbid obesity candidates!We need a STAGED INTERVENTION TO WEIGHT LOSS!
THIS IS ADDED TO THE FINITE AMOUNT OF LIFETIME HEALTH CHART WHICH IS BASED ON THE NOTION THAT THERE IS A FINITE AMOUNT OF CARBOHYDRATES PER EACH LIFE. AND ONE WOULD SPREAD IT OUT EVENLY OR EAT THE MOST EARLY IN LIFE BEFORE STARTING TO DRASTICALLY REDUCE. AND THE MORE YOU EAT OR HAVE EATEN EARLY, THE LESS YOU CAN EAT UNTIL AGE 90! THE CURVE GOES DOWN AS WE AGE!
(CHALLENGES TO THIS LOW CARB DIET TO FOLLOW)
Thursday, December 27, 2012
E-cadherin related article
To view the full text, please login as a subscribed user or purchase a subscription. Click here to
view the full text on ScienceDirect.
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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.
Banish unneeded salt and sugar from your diet!
Reducing Sugar and Salt
Discover how you can reap the benefits of cutting back on sugar and salt without sacrificing taste, flavor, or enjoyment!
Reducing Sugar and Salt
Discover how you can reap the benefits of cutting back on sugar and salt without sacrificing taste, flavor, or enjoyment!
Dear Peggy,
Your
body needs less than one gram of sodium a day. That's under half a
teaspoon of table salt. But if you are like most Americans, you consume
up to four times that amount. The result? Increased risk of high
blood pressure, heart disease, and stroke.
As
for added sugar, most of us consume more than twice the recommended
daily amount, increasing the risk of obesity, diabetes, and even
depression.
In Reducing Sugar and Salt,
the doctors at Harvard Medical School give you the know-how to
successfully monitor and effectively control the amount of sugar and
salt you and your family take in each day.
The
report exposes dozens of foods with "hidden" sodium and sugar. For
example, a tuna salad sub sandwich can have up to 1,300 milligrams of
sodium — more than the daily recommendation — while a bowl of raisin
bran delivers 19 grams of added sugar (the equivalent of five
teaspoons!)
Reducing Sugar and Salt
will give you the facts about how a high-sodium diet can lower bone
density, why "lactose-free" does not mean ''sugar-free,'' and whether
you're wasting your money on sports drinks when H2O will do. It also brings you up to date on sugar substitutes, and why you might want to cut back on diet soda.
The
report offers strategies for cutting back on sugar and salt at home or
dining out. You'll learn smart shopping and cooking tricks that make
meals delicious while limiting sodium. You'll find out which fruits are
lowest — and highest — in sugar, seven ways to spice up your meals
without salt, and satisfying ways to retrain your taste buds to
low-salt, low-sugar eating.
Reducing Sugar and Salt
also gives you a host of flavorful recipes that minimize or eliminate
sugar and salt, from delectable breakfast treats to wholesome lunches
and dinners, not to mention perfect-ending desserts and even late-night
snacks.
Be good to your body — and yourself. Order your copy of this timely Special Health Report today.
To your good health,
Anthony L. Komaroff, M.D.
Professor of Medicine, Harvard Medical School
Senior Physician, Brigham and Women's Hospital
Editor in Chief, Harvard Health Publications
Professor of Medicine, Harvard Medical School
Senior Physician, Brigham and Women's Hospital
Editor in Chief, Harvard Health Publications
Harvard Medical School offers special reports on over 50 health topics. Visit our Web site at http://www.health.harvard.edu to find reports of interest to you and your family.
Copyright © 2012 by Harvard University.
Teva Oncology is excited to announce FDA approval of SYNRIBO™ for
Injection
for the treatment of adult patients with chronic or accelerated phase chronic
myeloid leukemia (CML) with resistance and/or intolerance to two or more
tyrosine kinase inhibitors (TKIs). This indication is based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with SYNRIBO.
for the treatment of adult patients with chronic or accelerated phase chronic
myeloid leukemia (CML) with resistance and/or intolerance to two or more
tyrosine kinase inhibitors (TKIs). This indication is based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with SYNRIBO.
Indication
- SYNRIBO is indicated for the treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs). This indication is based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with SYNRIBO.
- ===========================================================
- for more info, go to the site!
Lifetime Carbohydrate Load
At the CRBCM we believe that stricter recommendations about carbohydrate reduction in diet should be instituted sooner in life. Certainly, by the time you are 20 to 25 years of age, there should be a sharp decrease in the daily sugar portion. Most adult growth has occurred by then and transition to open obesity initiates from there.
"I am gaining weight and find it difficult to lose it even with exercise". There is no weight loss without a sharp decrease in carbohydrates! We need to start believing that after a certain age: "You just have had all the carbohydrates in your life". We need to have carbohydrate charts able to tell us that we have consumed 60 percent of our lifetime carbohydrate requirement. People will understand this! They will know where they stand. We also believe that exercise, despite its important accomplishments, to be mainly a weight maintenance strategy, unless you are a top runner/bodybuilder. Other benefits of exercise are more important: they include improvement in fighting cancer progression. So keep it up!
One needs to workout for hours to lose weight significantly. And in our busy life, one finds time and impetus hard to come by. Exercise must be individualized to be successful, but communities offer less and less individualized care. People with extensive arthritis most likely end up stopping exercising altogether. We have no program adjusted for them. Those on oxygen also stop exercising; again they need some individualized program. Our disabled need adjusted programs. Diet remains an integral part to exercise for health preservation!
To expand the idea, we believe physicians should provide patients with a lifetime health chart to tell them where they stand as compared to a 90-year old person. We can debate all night long, but 90 years is pretty good. I know that those close or past this age will feel excluded. I remember the oncologists in a conference room trying to define who is an "Elderly". Every few years, as we all become older, we keep pushing that elderly-age to stay out!
LIFETIME HEALTH CHART OR STATUS: THAT'S AN IDEA! LET'S PATENT THIS QUICK!
"I am gaining weight and find it difficult to lose it even with exercise". There is no weight loss without a sharp decrease in carbohydrates! We need to start believing that after a certain age: "You just have had all the carbohydrates in your life". We need to have carbohydrate charts able to tell us that we have consumed 60 percent of our lifetime carbohydrate requirement. People will understand this! They will know where they stand. We also believe that exercise, despite its important accomplishments, to be mainly a weight maintenance strategy, unless you are a top runner/bodybuilder. Other benefits of exercise are more important: they include improvement in fighting cancer progression. So keep it up!
One needs to workout for hours to lose weight significantly. And in our busy life, one finds time and impetus hard to come by. Exercise must be individualized to be successful, but communities offer less and less individualized care. People with extensive arthritis most likely end up stopping exercising altogether. We have no program adjusted for them. Those on oxygen also stop exercising; again they need some individualized program. Our disabled need adjusted programs. Diet remains an integral part to exercise for health preservation!
To expand the idea, we believe physicians should provide patients with a lifetime health chart to tell them where they stand as compared to a 90-year old person. We can debate all night long, but 90 years is pretty good. I know that those close or past this age will feel excluded. I remember the oncologists in a conference room trying to define who is an "Elderly". Every few years, as we all become older, we keep pushing that elderly-age to stay out!
LIFETIME HEALTH CHART OR STATUS: THAT'S AN IDEA! LET'S PATENT THIS QUICK!
Is A Cure For Cancer Near?
Emily Whitehead photo via
PHILIPSBURG, Pa. — Emma Whitehead has been bounding around the house lately, practicing somersaults and rugby-style tumbles that make her parents wince.Targeted fighting of cancer at the cellular level makes a lot of sense. The problem has always been how to destroy those cancer cells without destroying everything else. This is a very promising development.
It is hard to believe, but last spring Emma, then 6, was near death from leukemia. She had relapsed twice after chemotherapy, and doctors had run out of options.
Desperate to save her, her parents sought an experimental treatment at the Children’s Hospital of Philadelphia, one that had never before been tried in a child, or in anyone with the type of leukemia Emma had. The experiment, in April, used a disabled form of the virus that causes AIDS to reprogram Emma’s immune system genetically to kill cancer cells.
The treatment very nearly killed her. But she emerged from it cancer-free, and about seven months later is still in complete remission. She is the first child and one of the first humans ever in whom new techniques have achieved a long-sought goal — giving a patient’s own immune system the lasting ability to fight cancer.
…Three adults with chronic leukemia treated at the University of Pennsylvania have also had complete remissions, with no signs of disease; two of them have been well for more than two years, said Dr. David Porter. Four adults improved but did not have full remissions, and one was treated too recently to evaluate. A child improved and then relapsed. In two adults, the treatment did not work at all. The Pennsylvania researchers were presenting their results on Sunday and Monday in Atlanta at a meeting of the American Society of Hematology.
Despite the mixed results, cancer experts not involved with the research say it has tremendous promise, because even in this early phase of testing it has worked in seemingly hopeless cases. “I think this is a major breakthrough,” said Dr. Ivan Borrello, a cancer expert and associate professor of medicine at the Johns Hopkins University School of Medicine.
=================================================================
1. CRBCM will find out what happened at the ASH regarding this reserach.
2. Despite the reported success which is impressive, could restoring one thing cure everyone (Driver Mutation)? Cancer cells are different from the normal cells in so many ways that it is hard to believe that this technique is the cure-all. Indeed, 4 patients did not achieve complete remission. These failures send the researchers back to the drawing boards.
3.Computer models are the way to go. The proper answer is to make an inventory of critical changes compared to normal, and address these changes sequentially or concurrently to improve our success.
4. The last point leads to the importance of mapping technology improvement.
5. Nice to see DR IVAN BORRELLO mentioned; I referred a few patients to him while working at Midatlantic Kaiser Permanente. I worked there for 14 years!
Wednesday, December 26, 2012
This is definitively informative for those looking who are looking for a comprehensive presentation of target of therapy. We will review the m-TOR today!
These diagrams have been assembled by Cell Signaling Technology (CST)
scientists and outside experts to provide succinct and current
overviews of selected signal transduction pathways. Knowledge about each
signaling pathway has been synthesized and integrated into
understandable paradigms of cellular communication. Please send
suggestions for developing new pathways to info@cellsignal.com.
The proteins in each pathway are linked to a search on the PhosphoSitePlus® website, which is an expert-curated knowledge base of protein phosphorylation plus other post-translational modifications in vertebrates. A matching collection of product search pathways is also online.
The proteins in each pathway are linked to a search on the PhosphoSitePlus® website, which is an expert-curated knowledge base of protein phosphorylation plus other post-translational modifications in vertebrates. A matching collection of product search pathways is also online.
Requirements: Using these pathways requires JavaScript and the free Adobe Flash Player version 10 or higher. To view the pathway PDFs, you will need the free Adobe Acrobat Reader.
Chromatin / Epigenetic Regulation
PI3 Kinase / Akt Signaling
Cellular Metabolism
Translational Control
- Protein Acetylation
- Histone Methylation
- Examples of Crosstalk Between Post-Translational Modifications
- Histone Modification Table
- Mitogen-Activated Protein Kinase Cascades
- MAPK/Erk in Growth and Differentiation
- G-Protein-Coupled Receptors Signaling to MAPK/Erk
- SAPK/JNK Signaling Cascades
- Signaling Pathways Activating p38 MAPK
- Apoptosis Overview
- Inhibition of Apoptosis
- Death Receptor Signaling
- Mitochondrial Control of Apoptosis
PI3 Kinase / Akt Signaling
Cellular Metabolism
Translational Control
Cell Cycle / DNA Damage
Immunology and Inflammation
Other
Immunology and Inflammation
- Jak/Stat Signaling: IL-6 Receptor Family
- Jak/STAT Utilization Table
- Jak and Cytokine Receptor Mutants in
Cancer Table - NF-κB Signaling
- TLR Pathway
- B Cell Receptor Signaling
- T Cell Receptor Signaling
- Amyloid Plaque and Neurofibrillary Tangle Formation in Alzheimer's Disease
- Dopamine Signaling in Parkinson's Disease
- Wnt/β-Catenin Signaling
- Notch Signaling
- Hedgehog Signaling In Vertebrates
- TGF-β Signaling
- Hippo Signaling
- ESC Pluripotency and Differentiation
Other
Feedback
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This is definitively informative for those looking who are looking for a comprehensive presentation of target of therapy. We will review the m-TOR today!
================================================================
This is definitively informative for those looking who are looking for a comprehensive presentation of target of therapy. We will review the m-TOR today!
Apoptosis. 2006 Feb;11(2):143-9.
Cathepsin-regulated apoptosis.
Source
Institute of Immunology, Otto-von-Guericke-University, Magdeburg, Germany.Abstract
Apoptosis can be mediated by different mechanisms. There is growing evidence that different proteolytic enzymes are involved in the regulation of apoptosis. Cathepsins are proteases which, under physiologic conditions, are localized intralysosomally. In response to certain signals they are released from the lysosomes into the cytoplasm where they trigger apoptotic cell death via various pathways, including the activation of caspases or the release of proapoptotic factors from the mitochondria. Here, we review different mechanisms that induce the release of lysosomal enzymes, and the functional relevance of defined cathepsins in defined models of apoptosis.- PMID:
- 16502253
- [PubMed - indexed for MEDLINE]
- ===========================================================
- Once again we remind our readers that the failure of chemotherapy to lead to a cure has led to the belief that trying to kill the cell indiscriminately has proven somewhat futile.
- Giving only less than 20% cure rates. We needed to be smart by exploiting natural path to death. Indeed the cell has a naturally programmed death called Apoptosis. Our approach to cure is to find ways to induce cancer cells into Apoptosis. It is apparent that Apoptosis whenever triggered appears to be better in achieving death of cancer cells. There are also some non Apoptotic ways to cancer cell death that we discussed in our previous posts.
- In Mitochondria, membranous events release Cytochrome C which in turn activates the Caspase family to lead to cell death. (BAX is linked to Caspase activation)
- In the Lysosmes, membranous events seems to free more Cathepsins to lead to Cell death. We also have shown that Ion Pumps maintain intralysosomal Ph gradiant to allow function of various Hydrolases which function only at Acidic Ph.
- Autophagia and Necrosis are some of the other path to cell death. Our task is to know how to harness these powerful pathways to death. Response rates are up to 75% in LUNG CANCER using current Oncogene drivers recommendation.
Not all members of the influential House Appropriations Committee were happy with who showed up to testify
FRIDAY NEWS LINKS: Amid Claims of Nonprofit Privacy, CPRIT Foundation & State Cancer Agency Come Under Scrutiny of State Legislators
Paul Webber, Associated Press
AUSTIN — A foundation that boosts executive salaries at Texas’ troubled $3 billion cancer-fighting effort defended to critical lawmakers Thursday a policy that keeps donors confidential while being lectured over appearances of pay-to-play politics.
Facing pointed and occasionally combative questions from state budget-writers, officials with the Cancer Prevention and Research Institute of Texas appeared before a public panel for the first time since prosecutors announced a criminal probe into the beleaguered agency and Gov. Rick Perry called for a moratorium on new awards.
Not all members of the influential House Appropriations Committee were happy with who showed up to testify. Absent were the three top agency executives who have resigned in the past eight months: Executive Director Bill Gimson, Chief Commercialization Officer Jerry Cobbs and Chief Scientific Officer Alfred Gilman.
All three are principal players surrounding $11 million in taxpayer funds that were awarded in 2010 to a private startup despite the project bypassing an independent review. Republican Jim Pitts, chairman of the House committee, left the door open to the agency’s former leadership being hauled in front of lawmakers as soon as January.
That left Barbara Canales, vice president of the nonprofit CPRIT Foundation and a member of the agency’s governing board, answering recurring and tough questions about the role of the nonprofit arm. One of the foundation’s chief purposes is to supplement the salaries of top institute executives, including Gimson, whose annual salary was $300,000.
The foundation has denied media requests to make its donor list public. “We have a balancing act to weigh here as board members, and to protect the privacy of our donors so they’re not unfairly solicited,” Canales said.
Rules prohibit donors from being awarded institute grants, Canales and CPRIT officials testified. But Democrat Rep. Sylvester Turner — who said, “We want an organization with integrity, not a slush fund” — and other lawmakers pressed for certainty that foundation donors were not connected to grant winners.
“What I can tell you is: To the best of my knowledge, it is not our policy to accept donors who are also grant” recipients, Canales said.
Republican Rep. Myra Crownover and other board member said the mere appearance was problematic. “The pay-to-play potential — maybe there should be more division,” Crownover said. The foundation has raised around $700,000 in each the last two years, according to Canales.
Thursday’s hearing came a day after Perry and other state leaders called for a moratorium on new grants until confidence is restored in a once-celebrated agency that has been thrown into upheaval in just three years. The institute controls the nation’s second-largest pot of cancer research dollars, behind the National Institutes of Health.
(Read more of this story at the Houston Chronicle)
RELATED COVERAGE:
Tuesday, December 25, 2012
MAPPING CANCER AND CLUSTERS OF DIFFERENTIATION
MAPPING CANCER AND CLUSTERS OF DIFFERENTIATION.
One important aspect of the fight for the cure is to obtain cancer distribution MAP in an individual. Certainly, one would not attack an enemy without knowing its size, quantity/quality, distribution and location. One of the challenges with cancer is that it comes from normal cells, therefore any attack we plan should include a component regarding how to avoid hurting the normal cell which relies on same survival strategies and components as the cancer cell! Luckily, the cancer cell wants to avoid many of the natural death processes. It wants to migrate and invade other organs, and where it has newly invaded, it wants to grow faster than the local cells and therefore creates a nutrition supply system that favors it! With each of the new needs the cancer wants to acquire, it has to develop new sets of molecules and mechanisms not necessarily expressed by the normal cell. These are globally called CLUSTERS OF DIFFERENTIATION OR CD. These include changes in membrane receptors, driver mutations, status of activation of now known targets in various pathways, and of course changes in transcription factors, DNA and even chromatin conformations.
These clusters of differentiation have been divided according to not only how we could use them, but how the cancer cell uses them. We call them Predictive as they can help us predict the existence and behavior of cancer. They are Prognostic when they determine cancer resilience to a given treatment and define or influence the outcome of the patient. They are Diagnostic when they point to the existence of cancer (these include the so called "Tumor Markers").
Mapping cancer today is limited. Staging cancer today is a crude way of mapping the extent of cancer. But in this day and age when we can visualize radiological changes in the metabolism, knowing the exact location and number of cancer cells everywhere in our body, it appears to be an achievable goal. The cure will not be secured until we can count remaining enemies. This knowledge will also help define cure. There is a perception in the treating physician community that cure is not Zero cancer cells. That we could be "cured" despite a residual amount of cancer. How much and where is not clear! Those who believe in a threshold number of cancer cells for active disease assert that, under the threshold, the immune system keeps things under control.
Molecular Therapy attacking Clusters of Differentiation have been attached to chemotherapy drugs and to radiation particles to kill exclusively cancers cells that have them. Campath, Rituxan and others follow these mechanisms. Suffice is to say we need more sophisticated ways to MAP CANCER IN OUR BODIES! THIS WILL BE THE STRONGEST DIAGNOSTIC, PREDICTOR AND DETECTOR OF CANCERS!
MERRY CHRISTMAS / JOYEUX NOEL TO ALL!
One important aspect of the fight for the cure is to obtain cancer distribution MAP in an individual. Certainly, one would not attack an enemy without knowing its size, quantity/quality, distribution and location. One of the challenges with cancer is that it comes from normal cells, therefore any attack we plan should include a component regarding how to avoid hurting the normal cell which relies on same survival strategies and components as the cancer cell! Luckily, the cancer cell wants to avoid many of the natural death processes. It wants to migrate and invade other organs, and where it has newly invaded, it wants to grow faster than the local cells and therefore creates a nutrition supply system that favors it! With each of the new needs the cancer wants to acquire, it has to develop new sets of molecules and mechanisms not necessarily expressed by the normal cell. These are globally called CLUSTERS OF DIFFERENTIATION OR CD. These include changes in membrane receptors, driver mutations, status of activation of now known targets in various pathways, and of course changes in transcription factors, DNA and even chromatin conformations.
These clusters of differentiation have been divided according to not only how we could use them, but how the cancer cell uses them. We call them Predictive as they can help us predict the existence and behavior of cancer. They are Prognostic when they determine cancer resilience to a given treatment and define or influence the outcome of the patient. They are Diagnostic when they point to the existence of cancer (these include the so called "Tumor Markers").
Mapping cancer today is limited. Staging cancer today is a crude way of mapping the extent of cancer. But in this day and age when we can visualize radiological changes in the metabolism, knowing the exact location and number of cancer cells everywhere in our body, it appears to be an achievable goal. The cure will not be secured until we can count remaining enemies. This knowledge will also help define cure. There is a perception in the treating physician community that cure is not Zero cancer cells. That we could be "cured" despite a residual amount of cancer. How much and where is not clear! Those who believe in a threshold number of cancer cells for active disease assert that, under the threshold, the immune system keeps things under control.
Molecular Therapy attacking Clusters of Differentiation have been attached to chemotherapy drugs and to radiation particles to kill exclusively cancers cells that have them. Campath, Rituxan and others follow these mechanisms. Suffice is to say we need more sophisticated ways to MAP CANCER IN OUR BODIES! THIS WILL BE THE STRONGEST DIAGNOSTIC, PREDICTOR AND DETECTOR OF CANCERS!
MERRY CHRISTMAS / JOYEUX NOEL TO ALL!
"I say to you today, my friends that in spite of the difficulties and frustrations of the moment, I still have a dream"
Christmas Reflections at CRBCM!
"I say to you today, my friends that in spite of the difficulties and frustrations of the moment, I still have a dream" and with this dream we will rise again to fight another day because we have understood that as long as we live another day, a door may be opened again, another chance may come along, we got to stay prepared and keep looking forward for an opportunity. There are in life many pits, but all have a bottom here on earth, and even in the darkness of those pits, as long as we live, our imagination will help us rise again. It is our call, the cause is too important to quit.
Those who came before us have left these words because they lived the horrors of life, went through them and came out the other side still whole. They left these words so that we do not give up, but instead keep strategizing even when faced by a wall of negative forces. We need to keep on advancing because only positive steps can generate new consequences. Not doing a thing is to lose control of the outcome. So at CRBCM we believe in new steps until life is irreversibly taken from us. So in these Christmas days, let celebrate persistence and resolve. What we fight against will not go away until we stand up to it! Merry Christmas to all.
"I say to you today, my friends that in spite of the difficulties and frustrations of the moment, I still have a dream" and with this dream we will rise again to fight another day because we have understood that as long as we live another day, a door may be opened again, another chance may come along, we got to stay prepared and keep looking forward for an opportunity. There are in life many pits, but all have a bottom here on earth, and even in the darkness of those pits, as long as we live, our imagination will help us rise again. It is our call, the cause is too important to quit.
Those who came before us have left these words because they lived the horrors of life, went through them and came out the other side still whole. They left these words so that we do not give up, but instead keep strategizing even when faced by a wall of negative forces. We need to keep on advancing because only positive steps can generate new consequences. Not doing a thing is to lose control of the outcome. So at CRBCM we believe in new steps until life is irreversibly taken from us. So in these Christmas days, let celebrate persistence and resolve. What we fight against will not go away until we stand up to it! Merry Christmas to all.
Sunday, December 23, 2012
Original Article
Inhibition of the Hedgehog Pathway in Advanced Basal-Cell Carcinoma
- Background Mutations in hedgehog pathway genes, primarily genes encoding patched homologue 1 (PTCH1) and smoothened homologue (SMO), occur in basal-cell carcinoma. In a phase 1 clinical trial, we assessed the safety and pharmacokinetics of GDC-0449, a small-molecule inhibitor of SMO, and responses of metastatic or locally advanced basal-cell carcinoma to the drug.
Methods
We selected 33 patients with metastatic or locally advanced basal-cell carcinoma to receive oral GDC-0449 at one of three doses; 17 patients received 150 mg per day, 15 patients received 270 mg per day, and 1 patient received 540 mg per day. We assessed tumor responses with the use of Response Evaluation Criteria in Solid Tumors (RECIST), physical examination, or both. Molecular aspects of the tumors were examined.
Results
The median duration of the study treatment was 9.8 months. Of the 33 patients, 18 had an objective response to GDC-0449, according to assessment on imaging (7 patients), physical examination (10 patients), or both (1 patient). Of the patients who had a response, 2 had a complete response and 16 had a partial response. The other 15 patients had either stable disease (11 patients) or progressive disease (4 patients). Eight grade 3 adverse events that were deemed to be possibly related to the study drug were reported in six patients, including four with fatigue, two with hyponatremia, one with muscle spasm, and one with atrial fibrillation. One grade 4 event, asymptomatic hyponatremia, was judged to be unrelated to GDC-0449. One patient withdrew from the study because of adverse events. We found evidence of hedgehog signaling in tumors that responded to the treatment.
Conclusions
GDC-0449, an orally active small molecule that targets the hedgehog pathway, appears to have antitumor activity in locally advanced or metastatic basal-cell carcinoma. (ClinicalTrials.gov number, NCT00607724.)
Figure 1
Mechanism of Action of GDC-0449 and Response to Treatment.Figure 2
GDC-0449 Activity in Patients with Locally Advanced Basal-Cell Carcinoma.Article Activity
238 articles have cited this article
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This article point to the importance that targets of therapy should not only focus on steps within the main pathways but also on regulator of speed of reaction. Basal Cell cancer generally do not metastasize but once the speed of reaction is increased or promoted, the disease becomes more aggressive. The Hedgehog genes promotes this disease and have been recently targeted effectively to show response to therapy.
Metabolic reaction can be promoted by a promoter gene in the main DNA, or by a variety of transcription genes which ultimately lead to a set of enzymes which ultimately accelerate the reaction.
It is also important to try to pay attention to Gradiants of Morphogens which apparently govern cellular differentiation based of cell position in the body. Controlling such determination may prove a way to impose changes within cancer cells!
It is of interest that in Breast cancer, basaloid type, the stage of disease had been reported to be "late" or advanced at diagnosis. This fact in combination with a triple negative status of this cancer lead to a poor prognosis. Is Reducing the speed of reaction a critical component of future treatment in this disease? This type of Breast cancer is genetically similar to Ovarian cancer, therefore it fair to conclude that Target therapy successes in basal cell like breast cancer could be replicated in Ovarian cancer and vice-versa?
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