AN OLD POST UPDATED TO CONTINUE THE STORY...
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?

Matrix metalloproteinases 2 and 9 increase permeability of sheep pleura in vitro

Eleni Apostolidou<sup>1*)

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! 
 
TODAY WE ADDED
12/3/2012

METASTASIS 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.  SAME WAY TUMOR NECROSIS FACTOR COULD BE USED TO INHIBIT SURROUNDING CELLS IN A INFECTION BY FOREIGN HOST.

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.</sup>
OCT 14TH WE WROTE THIS ARTICLE
TELL US WHAT YOU THINK...

Active Sunday for CRBCM!

Activities at CRBCM
good news, our representatives in Greenville, Ohio and Richmond, Indiana have elected to meet and plan strategies for approaching together their respective state representatives.  The fight is on and going wide.  We have sent them all ammunitions, the 4 projects submitted before CPRIT here in Texas and various contacts in Indiana. (I Used to work at Reid Hospital in Richmond IN after my 14 year tour at Kaiser Permanente MidAtlantic Area). We have urged them to involve Congresswoman Nina Turner and Minority leader Senator Eric H. Kearny in Ohio, all very dynamic leaders for minority populations.  Any help we can get to advance our cause will be appreciated!

Translational Research Project

Research at CRBCM

The CRBCM has determined that Breast Cancer Mortality in African American is excessive.  Of the 6000 African American women who will or have died this year, 3000 could have been saved if leaders paid more attention to this cause.
3 reasons  contribute to this excess mortality
1. Poor rates of screening mammograms in these minority population (or low income populations in general).
2. Late stage of disease at diagnosis
3. POOR HISTOLOGY, high rate of triple negative Breast cancer, which can only be managed by adjuvant and palliative chemotherapy.  Increasingly however, new target treatments are being tried. (ie.PARP and Histone De-acetylator inhibitors).

The success of chemotherapy, the only option readily available to African American women with triple negative Breast cancer is 20-40% at best.  We need further options and further investigation is required.
At CRBCM we believe that the potential contribution of Anti-Kinesin could be even more important, particularly when combined to a Taxane-Cisplatin or related Microtubule disrupting drugs.

The human Genome Project has already determined that the Genome of triple negative Breast Cancer is comparable to that of Ovarian Cancer.This fact re-enforces our choice for Taxane-platinum based combination in this disease.
Another thing we know is that cure happens when the cancer cell is killed.  The killing of cells is induced by Caspase release from cellular mitochondria.  Caspases are lytic proteins to the extent of achieving death by global disruption of sensitive pathways.  To our knowledge one of the determinant inhibitor of Caspase release is the presence of high levels of Bcl-2.  Bcl-2 seems to be more effective in mitigating the effect of drugs acting through the Topoisomerase enzyme (etoposide and Adriamycin)

In a cell such as the cancer cell which naturally intend to divide for growth of the cancer, disruption of Microtubule/microfilament, support scaffolding  for movement of chromosomes during cell division, appears a stronger argument bypassing the Bcl-2 protection for the release of caspases.  In fact, the Mitochondria nearby appear to be located there attached to close-by membranes.  Suffice is to say that significant microtubular or Microfilament  disruption  is not compatible with life.  This is why Taxanes (Erubulin and Ixabepilone) are most likely the most powerful drugs in breast cancer.  It is also why we believe that the right Anti-kinesin could add significantly to the effect of Taxane-platinum combination in triple negative Breast cancer.

Study Methology

1 We will use 50 tissue sample of 4 different cancers (Breast, Colon, lung and liver) for a total of 200 tissue samples.
2.Using Bcl-2 kits, we will detect and quantify Bcl-2 per tissue and per nature of tissue origin.  We can then identify which type of tissue has the highest Bcl-2 at cancerous status.
3.we will expose half of each group of tissue to taxal-Cisplatin ex-vivo. and, using standard kits, will detect and quantify Caspases released.
4. we will expose the other half to a triplet with Taxane-Cisplatin and Antikinesin, and detect and measure quantitatively the level of Caspases released by the tissue
5. Consideration of using Antikinesin alone has been discussed, no one would choose this option given the fact that time and again mono-target therapy have failed to achieve better than 30% because of patient genome heterogeneity.
6. We could also test these tissue response to Etoposide to verify Bcl-2 resistance and therefore appreciate the magnitude of Microtubule disruptions through the Taxane based combinations.

Our conclusions (proof of concept) will relate to:

1. Bcl-2 content by nature of the cancerous tissue.  This would predict sensitivity to tested chemotherapy drugs.
2. Verify sensitivity and specificity of Bcl-2 kits
3. Verify sensitivity and specificity of Caspase kits
4.Verify that Taxane-platinum based chemotherapy is better than Etoposide Ex-vivo.
5.Verify that adding Anti-kinesin improves response to therapy
6. By comparing to Etoposide alone by levels of Bcl-2, verify that Taxane based combination do bypass Bcl-2 protection of Mitochondria
7. If differences are corroborated, we can show that response to therapy can be predicted ex-vivo.

It is evident that such a study provide numerous commercial opportunities when it comes to kit development and Antikinesin  product selections.

Let's work with this Peggy! add any ideas and suggestions
we ask our readers to send their comments. The fight is on for the cure...

African-Americans, Economically Disadvantaged Populations More Likely to Present With Emergency Colorectal Cancer Diagnosis

http://www.aacr.org/home/public--media/aacr-press-releases.aspx?d=2896

Understanding the Laws of Biology

IMPORTANCE OF UNDERSTANDING BIOLOGIC LAWS

With every research performed around the world, scientists learn a little more.  It is important that research focuses on a particular molecule and its interactions, specificity and efficacy. Point location research should be understood within a general plan of advances in biomolecular research.  To find that, TGF Beta, when produced, will make a cancer grow and therefore make the cancer more resistant to treatment, is nice. It adds to the detailed knowledge.  TGF(s) act on membrane receptors, therefore it will harvest the signal pathways to display its might.  We know that it will reach or may emanate from some transcription genes.  The tract its actions have to follow to affect the cell is full of loopholes and pitfalls.  Going after TGF(s) should be part of a planned combination approach.  It cannot work in over 30% of the people because of genetic heterogeneity which in itself is nature's protection for host survival.

Here at CRBCM, we understand that to cross the 50% effectiveness, our current treatment strategies must include the activity of the 2nd law well described here.  And better yet the first 2 laws.  Disruption of gene, and that of Microtubule that will lead to caspase release (Cytochrome c disruption implied).  Membrane based effects are only as good as they are able to involve an increased activity of fas and Bax.  Short of that, they are 70% ineffective.  (You can't discount 30% though)

TGF could present an opportunity for treatment.  We made an early allusion to the JUDO.  Use the power of the attacker to send him to the floor "in the general direction of his attack".  TGF wants to achieve acceleration of growth and cellular multiplication.  Disruption of gene and microtubule may in fact be more effective when faster multiplication is achieved? This is risky, but not a crazy a approach.  That is also why chemotherapy works only on dividing cells!

Globally, however, TGF and Bcl-2 tend to protect cancer cell. TGF seems to give a growth advantage to cancer cells vis-a-vis surrounding cells.  Bcl-2 seems rather to be a protection mechanism from reaching the mitochondrial Caspase,  protecting therefore cancer cell from Apoptosis, the cure to cancer. 
With this background info, we can now judge any research coming along as to its importance, and see how it fits in the general strategy to achieve the cure we all want.

You Flip Flop, Changing all the time.... by Clement Albert on Ubetoo

by Clement Albert
You Flip Flop, Changing all the time...
BRINGING IT ALL TOGETHER IN A WORLD OF SOUNDS
IF YOU GUESSED WHO IS CLEMENT ALBERT, YOU ARE RIGHT!
WE WILL PROMOTE CURE AND PUBLIC HEALTH
THROUGH MUSIC MEDIA...CRBCM IS EQUIPPED WITH A MUSIC STUDIO!

3rd Law of Nature (continued) & 4th Law of Nature

3rd Law of Nature (continued)

At CRBCM we believe in the cure to cancer.
We believe that the path to cure lies in our ability to harvest natural forces and tendencies in existence in the cell, and turn these to cell death. We call these natural tendencies, laws of nature.  If nature wants you to grow, you will grow.  If nature wants you to die, you will die.  If nature wants you to resist, you will resist.  So far we have shown that nature has put in place some mechanisms to control major functions of cell life.  If there is a mistake in the genes whether caused or random, nature will stop the cycle of cell life to allow correction (1st law).   If however the Nuclear material and supporting scaffolding (the microtubule/microfilament complex) are irreparably compromised, cell destruction through the caspase is pretty much assured ( 2nd law) . The 3rd law (nature prefers what is good for it) leads to differentiation.  A cancer cell will make its own growth factors to allow its own growth and to give it unique advantage for growth compared to surrounding cells.  HOW DO YOU USE THIS GREEDY BEHAVIOR TO OUR ADVANTAGE?  IN JUDO, YOU USE THE FORCE OF THE ATTACKER TO PROJECT HIM IN THE GENERAL DIRECTION OF THE ATTACK. Meaning you could use the machinery put in place by the cancer cell to produce killer proteins.  Viruses do that in the host by incorporating their genome in the host.  Are we at the stage where we can incorporate non sense mutation, silent mutation, transversion or other silencing frame shifts into the promoter of the unique growth factor to the cancer cell?  CAN WE USE VIRUS TO SELECTIVELY INFECT CANCER CELLS AND ELECTIVELY SILENCE PROMOTER GENES OF TGF(S)? We are delving into this now...

4TH LAW: CANCER CELLS COULD BE EFFECTIVELY KILLED BY OUR IMMUNE SYSTEM IF PERCEIVED AS FOREIGN. AND WE KNOW THE ROLE OF TOLL CELL RECEPTORS IN THE INNATE IMMUNITY. WHAT CAN WE DO THERE? We will spend some time here, too...

THESE QUESTIONS WILL BE FURTHER INVESTIGATED IN THE NEXT FEW DAYS.

WE ARE LOOKING IN THE SUPEROXIDE (SOD) AND OTHER INTERVENTIONS TO FIGHT CANCER.

The 3rd Law of Nature

The 3rd LAW OF NATURE is still to come:
Harvesting the power of tissue differentiation or silencing as a way to control cancer cells.
Cancer cure is achieved by death of the cancer cell. But remission is just as powerful.  Rendering a cancer "innocuous", something you can live with, something our immune system can control, is just as critical an objective.   WHEN YOU CAN'T KILL IT, CONTROL IT AS LONG AS POSSIBLE.  FRANKLY THE MEDIAN SURVIVAL MAY NOT BE DIFFERENT, ALTHOUGH THE QUALITY OF LIFE MAY BE DIFFERENT...OR NOT! CAN WE TALK THE LANGUAGE OF THE CELL, AND ASK IT TO BE SILENT?!
WE WILL DELVE INTO THIS IN THE COMING DAYS!

Apoptosomes

Apoptosomes: engines for caspase activation.

Adams JM, Cory S.

Source

The Walter and Eliza Hall Institute of Medical Research, Melbourne, 3050, Victoria, Australia. adams@wehi.edu.au

Abstract

"Activation of the caspases that initiate apoptosis typically requires cognate scaffold proteins, including CED-4 in Caenorhabditis elegans, Apaf-1 in mammals and Dark in Drosophila. Each scaffold protein oligomerizes procaspases into a complex called the apoptosome, but the regulation and biological roles of the scaffolds differ. Whereas CED-4 is restrained by the Bcl-2 homologue CED-9, Apaf-1 is inhibited by its WD40 repeat region, until it is activated by cytochrome c, derived from damaged mitochondria. Although Dark also has a WD40 region, its activation does not seem to involve cytochrome c. CED-4 is essential for apoptosis in the worm and Dark for many apoptotic responses in the fly, but the Apaf-1/caspase-9 system probably amplifies rather than initiates the mammalian caspase cascade."
 (end of abstract)
=====================================================================

This research further confirms the path of the second law driving the forces down the cascade of events
starting with Microfilament/Microtubule disturbance or destruction.  The author clearly feels that once the
Apaf-1/Caspase-9 system is initiated, it amplifies its action leading to apoptosis.  Mention of the Bcl-2 (or other molecules comparable) is critical because it is the main barrier to full display toward apoptosis.  Last point :the Caspases are also a family of enzymes/protein based structure/meaning the potency to achieve Apoptosis varies.

Apaf-1 is Apoptotic Protease-activating Factor-1, a key factor in the cascade to Apoptosis.  I should also stress that this factor is more concentrated in liver, spleen, kidney and brain. Tissues where primary tumors are the toughest to treat.  Therefore, targeting this enzyme for activation could drive up Apoptotic cascade or cell death.

Of note, people in full inflammatory process with increased TNF have a mitigated result when it comes to Apoptosis because TNF also stimulate NF-kB which has anti-apoptotic trends.  Unless it chooses to go down the path of death-domain signaling way (Fas) or stimulate MAPK pathway which is more pro-apoptotic.   ARE PEOPLE WITH AUTOIMMUNE DISEASE POOR RESPONDERS TO TAXOL BASED CHEMOTHERAPY BECAUSE OF THIS?  SHOULD WE BE TESTING ANA AND LEVEL OF TNF (Tumor Necrosis Factor) TO GAGE RESPONSE TO THERAPY?

Great minds meet: Italy is connected

Glad to discover that Dr. Stefania Erra in a public hospital in Casale Monferrato, province of Alessandria. Casale Monferrato, Italy is also actively researching how to fight the Triple negative invasive ductal carcinoma of the breast which is, as she points out, "a particularly aggressive type of cancer with a bleak prognosis, which is resistant to traditional chemotherapy treatments and which—for the time being—is unresponsive to current molecular therapies. Additionally, this neoplasm is predominantly diagnosed in pre-menopausal women."

CRBCM today: Further evidence of 2nd law of nature

Further evidences of 2nd law of nature/CRBCM

If you compromise Cell divison, the cell will need to be destroyed
one thing is for sure.  DNA Breakage and mistakes or mismatches lead to cell cycle arrest (First law).  What is interesting is that the second law is very much linked to this. Once the repair occurs, a number of peri microtubular reactions need to occur to relieve that arrest and allow continuation of the mitosis.  This is the connection to the second law.
Also as we are further looking into this matter, we are finding further evidence that there is an intricate connection between Microtubule and Mitochondria.   Even the location of Mitochondria is not random and seems linked to the integrity of the filamentous connection.  We are learning about Nuage and Mitochondrial Cement.  The further we look, the more we can now ascertain the existence of the 2nd law.
We are also learning, that not all the antikinesin are the same.  Some are not as important, affecting peripheral molecules, but some involve the location of the "consensus sequence", and may be more important.

We also are learning that Cyclin ubiquitination and therefore destruction could be exacerbated by perimicrotubular disturbances.  Is this the mechanism of bypassing BCL-2 resistance?  More light is needed.

We will let you know what we find at CRBCM.

CRBCM is expanding

CRBCM EXPANSION

Volunteers and viewers of our blog intend to start CRBCM activities in Ohio and Indiana.
We are sending plan of activities and various suggestions of implementation.  We are holding President Obama's pledge  to help these states deal with the economic crisis and create jobs. We will dispatch our plan for expansion to our representatives Amy McCullough (Dayton, OH) and Mariane Alberts & Stephanie Hart  (Richmond, IN).  My daughter Kyle will organize in Maryland ( I still own a house in Brandywine MD).  Her help is appreciated!
Work there will be the creation of Survivorship Centers.  We have secured the attention of prominent Senators from both states to help with minority causes.  Breast cancer needs to be faced with strength of science and determination from our volunteers.
We believe success is reachable as our Clinic (Greater East Cancer Center) is getting greater footing in El Paso. Slow Progress is best for footing on solid ground.  A retiring Oncologist wants to meet to give us a look for progress.  Thank you for the call...light is clear at the end of the implementation tunnel.

OF NOTE:

1

Trastuzumab emtansine for HER2-positive advanced breast cancer.

PARP Inhibitors

PARP
Day 2 went very well in Houston
made it on time
in the meantime received positive news from El Paso
can apply for faculty time in clinic at University Medical Center
will be an honor if it gets through'
willing to cover at another Hospital over coming holidays to broaden my share of patients
while veterans physicians take it easy...will use any opportunity to shine.

Now Back to PARP inhibitor, (Poly ADP Ribose Polymerase), they are powerful drugs which follow our first law, they break DNA or cause failure to repair DNA mistakes.  Therefore cause automatic activation of intact P53 to induce automatic cell division Arrest. In other words, they act like Cisplatin and therefore will have a role in Ovarian cancer and by inference, will have a role in basal cell like Breast cancer (or triple negative Breast cancer).   Again, their limitation depend on preservation of P53 and all other molecules of that cascade.  They will also be limited by how fast the cell makes its repair.

Remember the 2nd law is the break of Microtubules/Microfilaments that leads to direct Caspase release, more powerful law.  This implies that a combination of PARP with Taxane (or Ixabepilone or Erubilin)will be the next non platinum combination of significance.

Following this logic, we predict an expanded role to Arsenic trioxyde. But fear of its use resides in its cardiac toxicity. But it acts like a Multikinase inhibitor because it interferes with so many cascades in the signal transduction.  Its limitation could also be that it may not lend itself to combination therapy because of "assumed" risk to the host.

More Field Work in Houston

I am back in Houston,
ready to embrace its heavy "Rush hour"congestion!
Never seen this much congestion in a town,
too much power concentrated in one City I guess,
somebody got to do the work,  spread it around, El Paso can take a little pressure out of this town.  Expand there, please!  We need to be put to work in El Paso.
Got to go, 8 consults planned and long trips through the "Houston congestion"awaiting!

Following-up on the 2nd Law discussed previously

Follow-up on the 2nd law discussed yesterday.
It is not by mistake that the 2 new drugs active in breast cancer, triple negative, target microtubules.
Indeed, both Erubilin and Ixabepilone target Microtubules.
I just took the test on Hope S. Rugo's presentation following the logic, passed the test without problem. So:
SHOULD WE USE CASPASE RELEASE IN LABORATORY AS PROOF OF CHEMOTHERAPY EFFECTIVENESS ON A STANDARD BASE (ROUTINELY), ON FRESHLY OBTAINED TISSUE, THAT IS!

Nature seems to tell us that when there is an error in the gene, we can repair this, but when the Microfilaments are destroyed, Mitosis is compromised and the cells' destiny is to die!  This is where the power of Vinorelbine comes from...Vinorelbine-Cisplatin is used as standard therapy for lung cancer, particularly in other parts of the world! 

DISCUSSION ON PARP INHIBITOR TO FOLLOW...

SEARCHING FOR A CANCER CURE

At CRBCM we believe that CPRIT is our necessary path to Victory over Cancer.
We also know we will not get its help this time around, not because we do not deserve the help but frankly because it is distracted.  Science is an objective thing.  It is a race.  You have the right move, the right stuff, you win, no matter where you come from.  It is the Olympics without steroids.

We at CRBCM have understood one thing, in the race for the cure, harnessing the force and laws of nature has an unparalleled advantage.  Forcing a cell to die can be done by telling and convincing it to die. Or blasting it and crossing our fingers and hoping it will die.  Chemotherapy did this mostly the second way but its success was partial.  Chemotherapy only works when it manages to finally talk the language.  Indeed, some chemotherapy manages to reach the syllables of the cellular language of death.

Sorting through the maze of messages, 2 powerful set of syllables come out:

1.  That if it fails to repair broken DNA and therefore does not perform GENE REPAIR, this fact will automatically activate your P53 leading to an automatic stop of the cell into its cycle division.  There is no loophole to this principle unless the P53 is abnormal.   Knowing this is powerful.  Now we understand why Cisplatin (and to some extent Gemcitabine)  is a powerful drug because it disrupts the DNA structure.  We also understand that cells with rapid repair of DNA, will brush it off, literally.

2.with further proof of principle, we believe that there is a second automatic message or syllables.
Destruction of Microfilaments (and therefore secondarily Microtubules in general) during cell division, leads to an automatic release of Caspase from the Mitochondria no matter what (and this is what includes the BCL-2 protection). It is in this law that resides the strength of Taxanes.  Medication that works even in resistant diseases such as Melanoma where Abraxane has a role.  Taxanes' limitations appear to be in the type of microtubules attacked. Medication that attacks Microfilament of the type involved in cell divison, where the Centromere is attached, appears to send a more determinant trigger to Caspase release.  This is where our interest comes in the Anti-kinesin.  We believe and predict that an effective anti-kinesin drug in combination with Taxane and Cisplatin/gemzar based combination, will harness best this law.  They will prove to be effective in cure because they will be effective in both treatment and maintenance settings.  This is also why the combination of Gemzar and Taxol has proven to be the strongest non platinum combination.

Following this principle, we believe now at CRBCM, that target therapy not following the laws of nature will have only 20-30% response rate, meaning effective in only the cells that lack loophole mechanisms.  (this also means because of phenotype heterogeneity, 70-85% of cells have potentially intrinsic loophole to any signal transduction target stimulation or blockage).

Lets keep our eyes on the ball, do not invest in stuff they are throwing at you!  More to come...

Googlish misadventures...

Life at CRBCM

Big money did it again,
trying to steal by corrupting search engines,
frankly it is frustrating, and Google has been bought...
This morning I woke up trying to look up Adriamycin on google
I asked for ADRIAMYCIN PACKAGE INSERT,
I got Neulasta, went to the next item on the list, I got Votrien.
I understand that people need to push new medications, but corrupting search engines is not the way.
Now I am upset against Google which must have been paid to allow such a thing
and I am upset against the drug companies which are trying to make it hard for me to use Google as a search engine.
There are in life things you don't do even if you can afford them,
one of them is to assume people are imbeciles and you can just twist their mind
and Big money has a way to try politics where it does not belong.
If you are smart, remember the word BACKFIRE when you are making your plan next time!
If Google goes this way, we need another search engine!
Did not plan to start this way my day!

Sons of the Sevenless

SONS OF THE SEVENLESS/Hypothesis for cancer Research

As we move forward here at CRBCM, we are increasingy  fond of one line of molecules;
first because of their name, and because we believe that their inhibitors could be the answer to the resistance
to some of the medications already in our armamentarium, namely Avastin,  Imatinib and Herceptin.  We believe that the Sons of The Sevenless which are regulator molecules switching on RAS would break resistance to Tyrosine Kinase resistance.  Sons of the Sevenless, what a name!  But don't you remember they say: "KILL THE SWITCH" AND DARK WILL COME.   THE SWITCH IS THE SONS OF THE SEVENLESS...BASAL CELL CANCER OF THE BREAST, THE CRBCM IS AFTER YOU...SINCE THE SUGGESTION THAT BASAL CELL CANCER OF THE BREAST IS LIKE OVARIAN CANCER BY ITS GENOME.  MARK MY WORD: KILLING THE SONS OF THE SEVENLESS OR KILLING THE SWITCH IS THE KEY TO TREATMENT.

ADDING TAXANE (or better yet an Anti-Kinesin) AFTER KILLING THE SWITCH (SONS OF THE SEVENLESS) WILL TURN ON THE MITOCHONDRIAL CASPASE BY AN INHERENT REFLEX MECHANISM WHICH WILL BYPASS BCL-2.  THAT'S HOW YOU LEAD TO CANCER CURE!

OH BY THE WAY,  ADDING STELAZINE TO AVASTIN MAY JUST DO THE TRICK FOR RECURRENT BRAIN TUMORS TOO. IT IS AN ANTI-CALMODULIN AFTER ALL!

RESEARCH IS ON AT CRBCM.  

CRBCM /Greater East Cancer Center.

Nice to stay busy with some new patients, thanks to you referring Doctors.
But time to go back to Houston to complete other contractual field work agreements,  and gather further resources which will allow us to live another day! When you are a Coalition, expect long fights and anything that allows you to go the distance needs full and careful completion.  Some, because of their circumstances, born with Silver Spoon, get an easy ride.  Some of us rise slowly and surely when circumstances are right! Some leaders get there easy, some leaders are born because life circumstances place them there...No matter how you get there, making a difference is what counts!  But you got to live another day!  Something is putting me back in Houston for 1 month, I got to go there and find it or find why!

As promised in my recent Blog, we are still looking into use of Inhibitors of Ion Pumps in membranes to kill cancer cells.  We know that in Cholera, a similar disruption kills the host.  Cells must also be susceptible.  We also spoke of using the opportunity  offered by cell cycle check points as a place for intervention.  Our work is cut out.  We will submit our comments on this while in Houston.  In the last word on Lysosome, the proton pump was discussed. PLEASE READ IT, WE WELCOME YOUR COMMENTS!

Reflections at the CRBCM

Rubric -Reflections at CRBCM,
Value of the truth...

One of the things I learned quickly in life is NOT TO LIE NO MATTER WHAT.
I grew up at my older brother's house who paid for everything in my life since my father became incapacitated from a stroke.  My brother was a lawyer. Lying to him was hard. debunking lies was a profession for him.
"Trying to lie to me is the last crime I can tolerate because it is equivalent to telling me I am an IMBECILE,"
and you did not want to be on the the bad side of that table.

On our recent blog we spoke of how important it is to stay truthful because the sanity of our conscience depends on it.  We suggested that because the truth always wins, our life needs to be wrapped in it to stand the test of time.  We went on to suggest that because the truth can be slow to surface, we need to stick to it because when it does surface, we could control the outcome of the argument being made.

Critics of our theme did not wait to point to many weaknesses of the "truth".  one of the major argument is that the TRUTH CAN BE WRONG.  It can easily be non properly used, it can be bent and easily suppressed long enough to become irrelevant. It can be obfuscated to oblivion!

But no matter the cynical argument, no matter the fact that people have gotten away with perjury, just fear the moment when people realize you are a phony.  That at the end of the day you deserve what comes to you. That you have been pulling their legs all along.  You will feel the pain of a traitor and the ire of those you deceive. You will be watching your back!

Lysosome

Hypothesis for cancer research

In the cell there is a small body covered by a membrane called Lysosome.
This body is full of enzymes capable of causing death to the cell should the enzyme (Acid hydrolase) get released in the intracellular solution.  Acid Hydrolase and related enzymes are powerfully destructive but they only act in a very acid environment.  When they come out mistakenly, the neutral state of the Cytosol (intracellular solution where all the organelles of the cell are floating)  paralyzes these enzymes.  The reason why the inside of the lysosome can stay very Acid to allow the function of these enzymes is linked to the existence in the lysosomal membranes  of proton pumps forcing hydrogen ions into the lysosome.  Scientists are looking at paralyzing these proton pumps in cancer cells in order to disturb selectively lysosomal function of targeted cancer cells.  Just changing the Ph of the cell to a more Acidic environment could kill the cell by affecting the many metabolic reactions that only occur effectively at neutral Ph.

Also in this structure (lysosome) there are other targets such the mannose Monophosphate receptors which, if successfully paralyzed, could also induce various lysosomal disturbances.  Weakening cancer cells could cure one from cancer.  The struggle continues.

Cancer Survivorship Program for El Paso

CRBCM met tonight with CIMA Hospice Administrator Michele Diaz Aboud,
discussed referral to Hospice but also looked at how some Hospice services could be integrated
in an overall Survivorship program.  We also discussed the level of government reimbursement by Medicare (and in some cases Medicaid).  We will be working with their support on future grant applications.  We concluded by discussing some of the ideas about improvement in Navigation of patient diagnosed with Cancer, and policy recommendations.  In attendance was Cynthia McWilliams of the same organization.  Great meeting!

Veterans of El Paso

Meeting Today with Chaplain Lovett of the VA in EL Paso.  The Chaplain has been in the Navy, and is currently in charge of the Home visits for Veterans in EL Paso.  We discuss strategies and opportunities in approaching veterans with a Health intervention.  We will have further contacts to sharpen our Messages.
The Meeting occurred at the CRBCM office this morning.  We are an official provider of care for the VA. Our office has engaged the VA office in El Paso for direct care to our veterans.  We have advertized aggressively in VA journal and newspaper, results are now showing slowly with interest by the VA staff.  The CRBCM and the Greater East Cancer Center will continue to push for further integration in the VA programs.

A good question: "Why Me, Why Me, Why Not Me?" by Clement Albert on Ubetoo - Listen to Clement Albert songs for free

Why Me, Why Me, Why Not Me by Clement Albert on Ubetoo - Listen to Clement Albert songs for free

CRBCM Audience as of Nov.20th, 2012

Country/Pageviews as of Nov 20,2012
United States: 1870,
Russia: 36,
United Kingdom: 21,
Sweden: 20,
Germany: 15,
France: 13,
Latvia: 10,
Ukraine: 9,
India: 4,
China: 3

Over 2000 hits, the truth is in the pudding!
we will not deceive our readers.
Will tell the truth in our position and path to progress.
We know we can't be right all the time, but we will say where we are, what our understanding is, and where we are going.  Thank you to our reviewers!

Music & Well-being, a fruitful combination!

Activities at CRBCM The CRBCM has invested heavily in Music equipment for Health Promotion songs to energize the mass into participating in health education programs. We had a 3 hours working session with J. Jarret, a member of the powerful Zion Baptist church of El Paso. Through Music, we intend to reach the youth and promote health in a vehicle sensitive to the Hispanic culture and community. Through Music, we want to send empowering health messages, energize the people to embrace health issues and recommendations, convey a way to join the action. Guitarist John Bashengezi is ready to add the last touch, an overwhelming Spanish guitar sound to conclude your excitement. Working for the masses asks us to use media loved by the locals, and Music, the world language, is ripe and right for this mission! For Samples, go to "ubetoo.com/clementalbert"  and we will be posting sample songs recorded with Jackie Jarret soon! (This Music Activity is part of a comprehensive Health plan submitted for possible funding to organizations such as CPRIT, NIH, NCI and local chapters of the NCS and the Susan G Komen)

Quantia / Brain tumors and methylated C-MET

Nice presentation on Quantia. They presented a case of a "disruptive Doctor" who was reported by staff as being "late", "not responsive to call" and "being rude to staff". Pretty much led me to agree with them. But through due process, heard the Dr's response to these accusations, I was able to give him some slack and another chance. Often we rush to condemnation without knowledge of other people's values and perspective. The key to finding the truth is due diligence! The lack of institutional due diligence led to misconstruction and mistakes!
We also attended a talk on Brain tumor, one of the resistant cancers, about importance of finding methylated C-MET as it gives a positive prognosis, responsiveness to treatment, and high pseudo-progression rate on MRI. This all is relevant to our Targeting therapy. An interesting observation to make is that, in cancers that are resistant, the response rate is consistently hovering around 15-30%. This is seen with Avastin in Brain cancers and Ipilimumab in Melanoma. This is pointing to the fact that we still have not reached the main target to apoptosis, or that we need sequential additional hits, or have not closed a loophole! We need to go back to the drawing board!

Managing the loopholes in the cell cycle

Cure to cancer is within reach and is within the management of LOOPHOLES. Cancer cells have within their pathways, redundancy that protects these pathways to maintain life of the malignant cell. You close one door, just to see another one open up to ensure that the life of the cancer cell is maintained. So, unless you hit a critical pathway with no escape routes, the treatment result will be partial and temporary. To succeed we need to hit several targets in total and and sometimes sequentially to impose on the cell to choose the path to its natural death (apoptosis). So most treatments which are limited to one or only a few targets prove partially and temporary effective. This is why building an electronic Cell and being able to put in all the pathways and observe where they lead to, what doors open and which ones are closed or closing, which are critical and which lead to apoptosis (natural cell death) is crucial. Which sequence of shut down leads to sure cell death? Right now we are at the step where we are learning about shutting or opening one door and evaluating the sequence of events that follow. But with our model in hand, we can be more comprehensive in our approach. The model will help determine effects on cancer cells by shutting several doors at once, "closing Loopholes" as Tax people would love to say. This approach with target therapy has led to breaking resistance to certain types of cancers that were notoriously resistant. Today, we are starting to have response rates in Melanoma. We have double or triple longevity in Chronic Myeloid Leukemia, GIST, Myeloma etc...Just wait to see what we will get once we manage to give Multistage Multitarget Therapies (MMT). Cure is within the management of Loopholes!

The CRBCM has completed a 3 week field work for its client. Successful completion of this work has earned the CRBCM further work in Houston. Texas. We will be back here in Houston November 26th, 2012. In the meantime, This coming week, we will continue clinic work in El Paso as Greater East Cancer Center continue to increase slowly its share of patients. This is hard work to ensure we survive the struggle and fight another day! News from Washington is positive. We just may make it with a new contract in January. We will continue to update our reader with new proposal for research as we study new opportunities offered by weakness in the Sodium-Potassion Ion pump in cancer cells and cell division check points (details to follow). Get to catch that flight to El Paso!

Targeting Triple-Negative Breast Cancer Cells With the Histone Deacetylase Inhibitor Panobinostat

Targeting Triple-Negative Breast Cancer Cells With the Histone Deacetylase Inhibitor Panobinostat Chandra R Tate, Lyndsay V Rhodes, H Chris Segar, Jennifer L Driver, F Nell Pounder Matthew E Burow, Bridgette M Collins-Burow Jul 27, 2012 Authors & Disclosures Breast Cancer Res. 2012;14(3):R79 © 2012 BioMed Central, Ltd. This article catches the Attention of the CRBCM. Thank you Medscape Alert!