2 days ago a man I am following for basic medical problem and follow-up, called my clinic.
One of his daughter who is obese and diabetic was having significant leg pains. She had developed a cellulitis from an infected wound. The cellulitis/purulent wound had failed Bactrim and Mupirocin provided by a local Ambulatory clinic.
2 months prior to this incident, the same man had called me for another daughter who is also obese but was found with Breast Cancer Metastatic to the bone. The lady was on Letrozole.
I knew right away there is a genetic basis for these syndromes given the age of the patients and family congregation. As a curious mind I tried to think about this in a categorical/objective way. My current patient who is now in a local Hospital getting Infectious Disease specialist attention had a infected wound. It is clear that not all diabetics develop such a complication, but those with a Vasculitis do. So I let my self look up vasculitis...and of course I found that bio-markers of Vasculitis include ANCA, ESR, c-Reactive Protein, leucocytosis and sometime Eosinophilia.
But as I look further, I fell on the Sturge-Weber Syndrome a prominent Vasculitis. Well, this landed me on the GNAQ gene. The same gene that is incriminated in the Uveal Melanoma, mind you!
This is a Guanine nucleotide-binding protein. The same proteins that gave Alfred Gilman the Nobel Price back in the days. This same Gilman who was recently embroiled in the CPRIT debacle! Bless his soul!
-----------------------------------------------------------------------------------
"G proteins were discovered when Alfred G. Gilman and Martin Rodbell investigated stimulation of cells by adrenaline.
They found that, when adrenaline binds to a receptor, the receptor does
not stimulate enzymes directly. Instead, the receptor stimulates a G
protein, which stimulates an enzyme. An example is adenylate cyclase, which produces the second messenger cyclic AMP.[4] For this discovery, they won the 1994 Nobel Prize in Physiology or Medicine.[5]" wikipedia
G proteins are important signal transducing
molecules in cells. "Malfunction of GPCR [G Protein-Coupled Receptor]
signaling pathways are involved in many diseases, such as diabetes, blindness, allergies, depression, cardiovascular defects, and certain forms of cancer. It is estimated that about 30% of the modern drugs' cellular targets are GPCRs." [6]
The human genome encodes roughly 800 [7] G protein-coupled receptors,
which detect photons (light), hormones, growth factors, drugs, and
other endogenous ligands. Approximately 150 of the GPCRs found in the
human genome have unknown functions."wikipedia
-----------------------------------------------------------------------------
This man did great work! I am appreciating even more his work today as I am facing this family where I suspect abnormality of the G proteins must be involved in their ordeal! But with current standard I can't test this ! Nobody will pay for it! It could be that Ibrutinb or medication such as this, derivative of Pertusis or cholera toxin could help but with our current knowledge and boundaries, targeting therapy is out of bound!
Or may be minimal dose of Cytoxan and prednisone for God sake! More clinical trials are needed!
3 important gene findings though
1.As you start ramaging into the genes involved
you soon encounter the PTPN11---PLCG2----BTK (Bruton), but also Lyn, SHC1 to block Apoptosis, and GAB2 that binds Grb2 the begining of trouble ("wild gene").
2.The Breast Cancer inference comes when you bring in C1QBP---PKC zeta---YWHAC which interacts with BCAR1, and you know BRCAs are not far!
3.For 1 of the daughter to be positive for Estrogen Receptor, you must assume that her receptor stays on because of imbalance G protein. (look into the RIC8 which I assume to be decrease! leading to increase of GB gamma and of course because of the Phosducin -like Protein PHLP1). Folks I can't test any further, got to wait 10-20 years at the pace of our progress!
Or else call me to help 915-307-3354!
The CRBCM, at work always...
Monday, February 10, 2014
Sunday, February 9, 2014
more questions
Tankyrases are definitely the next gene to inhibit
is NME1 the determinant of whether or not a tumor is metastatic, what about NM23-1,2
is the NME1 always expressed in non metastatic tumors?
NME 1 the road to the Aurora? Is it prognosis or Predictive for the activity of the Aurora and their inhibitors?
is NME1 the determinant of whether or not a tumor is metastatic, what about NM23-1,2
is the NME1 always expressed in non metastatic tumors?
NME 1 the road to the Aurora? Is it prognosis or Predictive for the activity of the Aurora and their inhibitors?
Genetic work cogitations
*Should we forget DNA effect, and plunge on epigenic dysruption of etoposide and slowing of processes at the Mitochondria as mechanisms of action of this anti-topoisomerase to define it better? This may open-up a new way for use of this target therapy. Now we learn that c-MYC recruitment of Histone acetylase is highly disturbed under this drug! Acting here, the drug can affect the Histone cover of DNA?
*Is the use of the GLI as intermediate by the Hedgehog circumstantial? Is it because the Gli is more available?
*Stop the Dicer or Exporting to really be in the Belly of the beast (in liquid cancers?)
*Can work at the C-MYC decrease Cytokine production by disabling this area of the cell? How this disruption affect the Wnt (and the Notch... What Ptch1 has to do anyway?
*Is the use of the GLI as intermediate by the Hedgehog circumstantial? Is it because the Gli is more available?
*Stop the Dicer or Exporting to really be in the Belly of the beast (in liquid cancers?)
*Can work at the C-MYC decrease Cytokine production by disabling this area of the cell? How this disruption affect the Wnt (and the Notch... What Ptch1 has to do anyway?
Saturday, February 8, 2014
CRBCM is now affiliated with Vista College of El Paso
The CRBCM/Greater East Cancer Center is now affiliated with El Paso Vista College to provide
administrative and clinical ground for training of students. 3 students will start February10, 2014
the practical part of their training. We at the Cancer Center welcome them, and are ready to provide them with a great opportunity for further development of their skills in our clinical setting.
The CRBCM has provided new computers and relevant equipments that they will need for their training. We all look forward to their great work at Greater East cancer Center.
administrative and clinical ground for training of students. 3 students will start February10, 2014
the practical part of their training. We at the Cancer Center welcome them, and are ready to provide them with a great opportunity for further development of their skills in our clinical setting.
The CRBCM has provided new computers and relevant equipments that they will need for their training. We all look forward to their great work at Greater East cancer Center.
Friday, February 7, 2014
What is cancer cure anyway.
It is easy to globally point out cure for cancer patients, if the patient is staying alive after a clear diagnosis of a cancer that is remote in somebody's life. It is certainly nice to meet someone who "beat" cancer. "oh 22 years ago, I had my colon removed for cancer". You cannot imagine what it does to an Oncologist in particular. This belief that the disease we face daily is "beatable". We like to believe there is no cancer, or it is under the control of the immune "defense" or defense in general whether immune or not!
As gene goes, abnormality in terminal differentiation or genes that could be mutated and does not involve other interactions, appears to be the one we can cure. Things, Mutations and abnormal complexes of genes that is localized, peripheral (at the membrane) or in a specific pathway once correctable can lead to cure.
Gleevec will address CML and diseases bearing similar, specific, and a certain KIT Mutation. Incurrability seem to be brought in by a coexisting abnormality in gene that are "master modulators". Gens who's functions cannot be clearly limited are tougher to control.
In breast cancer for example, the involvement of Casein Kinase gene is bad since this is a gene phosphorylating diffusely other genes, and the wrong one may be taken in the course, the direct involvement of gnes placed in the epigenic area seems to suggest a poor outcome. There are gene called "master regulator or master genes" that appear critically irreversible. EP 300 Mutation appears critically bad. This is a "wild gene" interacting with all epigenetic events. Its Mutation persistent after a "cure" means that cure is fundamentally questionable since it cannot be sustained! These gene Mutation will one day be checked in every one after treatment to establish curability. At that time, cure will be genetically achievable...EP300 is a strong example of course, it is not alone in this region....(NCOA, MEF,SP1, SIN3A etc...) as compare to ie POT1 ( Telomere only)....
As gene goes, abnormality in terminal differentiation or genes that could be mutated and does not involve other interactions, appears to be the one we can cure. Things, Mutations and abnormal complexes of genes that is localized, peripheral (at the membrane) or in a specific pathway once correctable can lead to cure.
Gleevec will address CML and diseases bearing similar, specific, and a certain KIT Mutation. Incurrability seem to be brought in by a coexisting abnormality in gene that are "master modulators". Gens who's functions cannot be clearly limited are tougher to control.
In breast cancer for example, the involvement of Casein Kinase gene is bad since this is a gene phosphorylating diffusely other genes, and the wrong one may be taken in the course, the direct involvement of gnes placed in the epigenic area seems to suggest a poor outcome. There are gene called "master regulator or master genes" that appear critically irreversible. EP 300 Mutation appears critically bad. This is a "wild gene" interacting with all epigenetic events. Its Mutation persistent after a "cure" means that cure is fundamentally questionable since it cannot be sustained! These gene Mutation will one day be checked in every one after treatment to establish curability. At that time, cure will be genetically achievable...EP300 is a strong example of course, it is not alone in this region....(NCOA, MEF,SP1, SIN3A etc...) as compare to ie POT1 ( Telomere only)....
Keeping the role of MITF, RUNX3 and SIX3 in perspective (keeping notes)
something is definitely cooking here, just need to put my finger in it!
DAPK
!
!
MITF
!
!
RUNX3--------TLE---Glycoprotein 130
! !
! !
! SOX3--SIX3-----Wnt and SHH Hedge sonic
! !
! PAX3
!
Increase BIM----------Pro-Apoptosis
DAPK
!
!
MITF
!
!
RUNX3--------TLE---Glycoprotein 130
! !
! !
! SOX3--SIX3-----Wnt and SHH Hedge sonic
! !
! PAX3
!
Increase BIM----------Pro-Apoptosis
Thursday, February 6, 2014
The value of Water! (scientific speculations)
Every time it comes to mind that we need to explore further the quantity of 2-3 things in our body to prevent stroke and Myocardial infarction. And really basic things!
1.the quantity of Water in our system!
have we noticed how in a normal body, body without Diabetes or Hypertension or autoimmune disorder and infection, and mostly certain medications, the frequency of strokes and myocardial infraction is unusual....and why is it that people who use less medications may have less of these events? What this is telling us is either when these diseases are active they actually lead to these events, but potentially, that our current reaction to the existence of these disease is not appropriate and actually precipitate in certain individual and acutely these events? Does current therapy cause in certain individuals events that are catastrophic in terems of consequences for the patient?
One of the consequence of blood pressure medications is to relatively dehydrate the individual by increasing urination basically. This fact associated by unnoticed "vasculitis" or vascular adhesiveness (platelet function implied) may be the start or an irreversible closure of blood vessel in tissue that depend on low volume capillarity! We are happy that one having lost so much fluid will have low blood pressure when we commit those numbers in the chart, but are we sure the numbers are telling us the patient is really safe being so dehydrated. Do we know enough about about what are the consequence of such dehydration should a vascular adhesiveness be increased, and what are current bio-markers of such vascular adhesiveness? In general, we believe that use of Baby Aspirin could compensate our lack of knowledge and Aspirin will keep adhesiveness under-control, then we learned that this is not safe in everybody. The chronic use of Aspirin will be a chronic stimuli which at cellular genetic level may not be the thing to preconize, we learned this through the kidney response to chronic exposure to Non steroidals. Intermittent use may be better but which schedule is unknown!
2. state of "vasculitis"
3.how about the Cytokine?
4.how about cholesterol or Atheroma?
(to be continued)
1.the quantity of Water in our system!
have we noticed how in a normal body, body without Diabetes or Hypertension or autoimmune disorder and infection, and mostly certain medications, the frequency of strokes and myocardial infraction is unusual....and why is it that people who use less medications may have less of these events? What this is telling us is either when these diseases are active they actually lead to these events, but potentially, that our current reaction to the existence of these disease is not appropriate and actually precipitate in certain individual and acutely these events? Does current therapy cause in certain individuals events that are catastrophic in terems of consequences for the patient?
One of the consequence of blood pressure medications is to relatively dehydrate the individual by increasing urination basically. This fact associated by unnoticed "vasculitis" or vascular adhesiveness (platelet function implied) may be the start or an irreversible closure of blood vessel in tissue that depend on low volume capillarity! We are happy that one having lost so much fluid will have low blood pressure when we commit those numbers in the chart, but are we sure the numbers are telling us the patient is really safe being so dehydrated. Do we know enough about about what are the consequence of such dehydration should a vascular adhesiveness be increased, and what are current bio-markers of such vascular adhesiveness? In general, we believe that use of Baby Aspirin could compensate our lack of knowledge and Aspirin will keep adhesiveness under-control, then we learned that this is not safe in everybody. The chronic use of Aspirin will be a chronic stimuli which at cellular genetic level may not be the thing to preconize, we learned this through the kidney response to chronic exposure to Non steroidals. Intermittent use may be better but which schedule is unknown!
2. state of "vasculitis"
3.how about the Cytokine?
4.how about cholesterol or Atheroma?
(to be continued)
Activity at CRBCM: Preliminary results seem to concur!
Already the first phase of results from the study funded partially by the CRBCM and MDHonors are completed. This is a study on lung cancer detection completed on 50 tissues provided by a tissue bank from the University of Virginia. Preliminary results coming from the University of Texas in El Paso seem to suggest that the genes involved appear consistently in all cancers no matter the stage of disease, types and race of individual bearing the disease. This fact is strong because it attest to the early occurrence of these mutations in the neoplastic transformation. It could subsequently point to cure if indeed these mutations are no longer detected since they appear undisturbed no matter the stage of disease.
The test could therefore detect non only the disease early, but cure of the disease, an unprecedented event...But don't let CRBCM jump ahead of its conclusions which have not been finalized until the publication of our first paper. Big heads will fight these finding as skepticism is stylish , remember the CRBCM is making the research happen, we do not micro-manage the outcomes! Facts are being fed to us, and they look promising! Our purpose is to explore, find the facts, and feed them to the community at large, and in the process learn! learn! and do the deed ......CRBCM, hard at work!
The second phase is to complete the same PCR based tests in matched serum (sera) of individuals who gave the tissues and spin the same tests to confirm the presence of these mutation in the serum. We intend to show that the mutations are detectable in blood. Should we demonstrate that the serum can give us the same result, early detection could be demonstrated in blood. There are caveats however and many have to do with determining that the findings are indeed found in lung cancer. Detection through PET in positive individual (who carry these mutations without evident mass) is just another hurdle we will have to face.
Corollary detection of specific mutations that makes tumors susceptible to Avastin will be conducted as part of this series. One of the curious fact performed by the researcher at UTEP is to use Actin as the reference standard. A fact that is peculiar and call for questions when we meet next to draft the preliminary draft of the 1st article. For CRBCM actin could potentially be used as a predictive Biomarker for Taxane and or Platinum effects! or is-it? We are at the entrance of bigger things we presume!
The CRBCM...advancing deliberately without big brother breathing down our neck. Science should be free of political pressures! It makes the thruth even more powerful...We are not closed to criticism, just bringing an argument!
What is important with this exercise is learning to do scientific stuff! That is what the people watching did not understand...yes the study has been done in some form, but doing stuff open new doors to a active mind, and a new institution!
The test could therefore detect non only the disease early, but cure of the disease, an unprecedented event...But don't let CRBCM jump ahead of its conclusions which have not been finalized until the publication of our first paper. Big heads will fight these finding as skepticism is stylish , remember the CRBCM is making the research happen, we do not micro-manage the outcomes! Facts are being fed to us, and they look promising! Our purpose is to explore, find the facts, and feed them to the community at large, and in the process learn! learn! and do the deed ......CRBCM, hard at work!
The second phase is to complete the same PCR based tests in matched serum (sera) of individuals who gave the tissues and spin the same tests to confirm the presence of these mutation in the serum. We intend to show that the mutations are detectable in blood. Should we demonstrate that the serum can give us the same result, early detection could be demonstrated in blood. There are caveats however and many have to do with determining that the findings are indeed found in lung cancer. Detection through PET in positive individual (who carry these mutations without evident mass) is just another hurdle we will have to face.
Corollary detection of specific mutations that makes tumors susceptible to Avastin will be conducted as part of this series. One of the curious fact performed by the researcher at UTEP is to use Actin as the reference standard. A fact that is peculiar and call for questions when we meet next to draft the preliminary draft of the 1st article. For CRBCM actin could potentially be used as a predictive Biomarker for Taxane and or Platinum effects! or is-it? We are at the entrance of bigger things we presume!
The CRBCM...advancing deliberately without big brother breathing down our neck. Science should be free of political pressures! It makes the thruth even more powerful...We are not closed to criticism, just bringing an argument!
What is important with this exercise is learning to do scientific stuff! That is what the people watching did not understand...yes the study has been done in some form, but doing stuff open new doors to a active mind, and a new institution!
Tuesday, February 4, 2014
TRPM7 (and PLBC)
It is potentially a dangerous gene when mutated (TRPM)
Its autophosphorylation capacity makes it a potential DRIVER gene...
And it is an Ion Channel and therefore has direct implications on cellular depolarisation
Use of Calcium as a co-factor put it center to all function calcium does. It's importance in Traumatic Brain Injury cannot be undermined. It seemed to be at the center of neuronal death. It also may impact the NFAT...
1. Its implication of Alzheimer needs assessment
2. Its role in the endothelium leads to
"Defects in this gene have been associated to magnesium deficiency in human microvascular endothelial cells.[3]" wikipedia
3.It also has a significant relation with P38 or MAPK and therefore reaches ATF2, C-MYC,PAX6 and P53
And again through P38, this gene impact the epigenic event commanded by ELK1, ETS1 and MK2 by which it reach the CREB, RAR, and the NFkB/P65.
4.Through the PLBC, it reaches the Inositiol based pathway.
5. It is unclear if it participates in Micro-vascular disease seen on so many Brain MRI in elderly, raising the issue of whether this will be a biomarker for this silent disease and whether Aspirin is the best course.
6.?Disruption here is accompanied by disturbance of calcium in blood, or dysfunction of Parathyroid?
Focusing on P38!
Its autophosphorylation capacity makes it a potential DRIVER gene...
And it is an Ion Channel and therefore has direct implications on cellular depolarisation
Use of Calcium as a co-factor put it center to all function calcium does. It's importance in Traumatic Brain Injury cannot be undermined. It seemed to be at the center of neuronal death. It also may impact the NFAT...
1. Its implication of Alzheimer needs assessment
2. Its role in the endothelium leads to
"Defects in this gene have been associated to magnesium deficiency in human microvascular endothelial cells.[3]" wikipedia
3.It also has a significant relation with P38 or MAPK and therefore reaches ATF2, C-MYC,PAX6 and P53
And again through P38, this gene impact the epigenic event commanded by ELK1, ETS1 and MK2 by which it reach the CREB, RAR, and the NFkB/P65.
4.Through the PLBC, it reaches the Inositiol based pathway.
5. It is unclear if it participates in Micro-vascular disease seen on so many Brain MRI in elderly, raising the issue of whether this will be a biomarker for this silent disease and whether Aspirin is the best course.
6.?Disruption here is accompanied by disturbance of calcium in blood, or dysfunction of Parathyroid?
Focusing on P38!
Monday, February 3, 2014
Meaning of cancer recurrence
1-Meaning of recurrence
2-disease only slowed down
3-new development of new bypass pathway
4-additional escape mechanism or pathway
5-resistant disease
6-a virus act on a promoter
ie
--------------------------------------------------------------------------------------------------
YY1 and RYB are fair targets for further investigation.
note RYB gene relation with caspase 10!
2-disease only slowed down
3-new development of new bypass pathway
4-additional escape mechanism or pathway
5-resistant disease
6-a virus act on a promoter
ie
Transcriptional repression by YY1, a human GLI-Krüippel-related protein, and relief of repression by adenovirus E1A protein
Yang Shi*,et al.--------------------------------------------------------------------------------------------------
YY1 and RYB are fair targets for further investigation.
note RYB gene relation with caspase 10!
Sunday, February 2, 2014
Then it goes on to destroy the quote: another political game by excluding us! can't make up this stuff !
just a reminder and CRBCM agrees with the following quote:
"The best discoveries in science aren’t predictable,” says HHMI President Robert Tjian. “One of the things that sets HHMI apart from other organizations that support biomedical research is that we free our researchers to follow their scientific instincts—to follow things that pop up unexpectedly.”
HHMI encourages its investigators to push their research fields into new areas of inquiry. By employing scientists as HHMI investigators—rather than awarding them research grants—the Institute is guided by the principle of “people, not projects.” HHMI investigators have the freedom to explore and, if necessary, to change direction in their research. Moreover, they have support to follow their ideas through to fruition—even if that process takes many years.
“The flexibility that comes with HHMI support allows people to move into new scientific areas more easily,” said Erin K. O’Shea, vice president and chief scientific officer. “I can’t emphasize enough how difficult that kind of movement can be with traditional sources of funding.”
Candidates apply directly to HHMI. Applications must be received by June 3, 2014. Successful candidates are expected to meet the following criteria:
HHMI announced its last open competition in 2012. That competition resulted in the selection of 27 of the nation’s top biomedical scientists as HHMI investigators in 2013. Once selected, HHMI provides each investigator with his or her full salary, benefits, and a research budget over their initial five-year appointment. The Institute will also cover other expenses, including the purchase of critical equipment.
Through the HHMI Investigator Program, the Institute has joined with more than 70 distinguished U.S. universities, hospitals, institutes, and medical schools to create an environment that provides flexible, long-term support for more than 300 Hughes scientists and members of their research teams. HHMI investigators are widely recognized for their creativity and research accomplishments: 172 HHMI investigators are members of the National Academy of Sciences and there are currently 17 Nobel laureates who are HHMI investigators.'"
The Howard Hughes Medical Institute
The Howard Hughes Medical Institute plays an influential role in advancing scientific research and education in the United States. Its scientists, located across the United States, have made important discoveries that advance our fundamental understanding of biology and its relation to human disease. In a complementary program at HHMI's Janelia Farm Research Campus in Loudoun County, Virginia, leading scientists are pursuing long-term, high-risk, high-reward research in a campus designed to bring together researchers from disparate disciplines. The Institute also aims to transform science education into a creative, interdisciplinary endeavor that reflects the excitement of real research. For more information, visit www.hhmi.org.
The Institute’s endowment at the close of fiscal 2013 was about $16.9 billion. HHMI’s headquarters are located in Chevy Chase, Maryland, just outside Washington, D.C.
"The best discoveries in science aren’t predictable,” says HHMI President Robert Tjian. “One of the things that sets HHMI apart from other organizations that support biomedical research is that we free our researchers to follow their scientific instincts—to follow things that pop up unexpectedly.”
HHMI encourages its investigators to push their research fields into new areas of inquiry. By employing scientists as HHMI investigators—rather than awarding them research grants—the Institute is guided by the principle of “people, not projects.” HHMI investigators have the freedom to explore and, if necessary, to change direction in their research. Moreover, they have support to follow their ideas through to fruition—even if that process takes many years.
“The flexibility that comes with HHMI support allows people to move into new scientific areas more easily,” said Erin K. O’Shea, vice president and chief scientific officer. “I can’t emphasize enough how difficult that kind of movement can be with traditional sources of funding.”
Candidates apply directly to HHMI. Applications must be received by June 3, 2014. Successful candidates are expected to meet the following criteria:
- Hold a PhD, and/or MD or equivalent degree.
- Hold a tenured or tenure-track position as Assistant Professor or higher academic rank (or the equivalent) at an eligible U.S. institution. Federal government employees are not eligible.
- Have more than 5 but no more than 15 years of post-training, professional experience.
- Be the principal investigator on one (or more) active, national, peer-reviewed research grants with a duration of at least three years.
HHMI announced its last open competition in 2012. That competition resulted in the selection of 27 of the nation’s top biomedical scientists as HHMI investigators in 2013. Once selected, HHMI provides each investigator with his or her full salary, benefits, and a research budget over their initial five-year appointment. The Institute will also cover other expenses, including the purchase of critical equipment.
Through the HHMI Investigator Program, the Institute has joined with more than 70 distinguished U.S. universities, hospitals, institutes, and medical schools to create an environment that provides flexible, long-term support for more than 300 Hughes scientists and members of their research teams. HHMI investigators are widely recognized for their creativity and research accomplishments: 172 HHMI investigators are members of the National Academy of Sciences and there are currently 17 Nobel laureates who are HHMI investigators.'"
The Howard Hughes Medical Institute
The Howard Hughes Medical Institute plays an influential role in advancing scientific research and education in the United States. Its scientists, located across the United States, have made important discoveries that advance our fundamental understanding of biology and its relation to human disease. In a complementary program at HHMI's Janelia Farm Research Campus in Loudoun County, Virginia, leading scientists are pursuing long-term, high-risk, high-reward research in a campus designed to bring together researchers from disparate disciplines. The Institute also aims to transform science education into a creative, interdisciplinary endeavor that reflects the excitement of real research. For more information, visit www.hhmi.org.
The Institute’s endowment at the close of fiscal 2013 was about $16.9 billion. HHMI’s headquarters are located in Chevy Chase, Maryland, just outside Washington, D.C.
Related Links
For More Information
NEVER LEAVE YOUR MIND AT PEACE WHEN IT COMES TO GENES (PROGNOSIS OF SENESCENCE)
It is by now quite clear that Senescence is clearly linked to the health of your eyes (given the frequency of cataract in elderly) and intrinsic deterioration of the heart muscle and muscles in general. Elderly's muscles seem to become hypothrophic without control. Kidney deterioration seem to follow closely as if an organ shutdown is in the work. Indeed some genes seems to be at work in a very discrete way indicating to the eyes, the heart, the muscles, and peripherally the kidney that it is time to shut this thing down. The proof is that keeping exercising seems to fool this message keeping people "young".
At cellular or gene level, the genes that form the muscles must be implicated! The Myb, MyoD,Myogenein, Myf5, MEF2, GNA12 ...some of which interacts with MDFI (watch out because it is an gene inhibitor): (look at the leukemias'story when it comes to interacting with inhibitors (our eyes is square and fare in the SIX1)) six1 talks to PAX (Melanoma) (how this is liked to Breast cancer...well? did you see E2A? It's here though!)
MDFI (don't say we at CRBCM did not warned you) AND IF YOUR EYES ARE RIVETED ON THIS ONE, DON'T FORGET MDFIC AS A TARGET! OH! BY THE WAY LOOK-UP ECRG2 (esophageal cancer ) AND RBEL1 WHILE ON THIS! (Why? because it is a rebel gene! think about that!)
"UniProtKB/Swiss-Prot: MDFI_HUMAN, Q99750
At cellular or gene level, the genes that form the muscles must be implicated! The Myb, MyoD,Myogenein, Myf5, MEF2, GNA12 ...some of which interacts with MDFI (watch out because it is an gene inhibitor): (look at the leukemias'story when it comes to interacting with inhibitors (our eyes is square and fare in the SIX1)) six1 talks to PAX (Melanoma) (how this is liked to Breast cancer...well? did you see E2A? It's here though!)
MDFI (don't say we at CRBCM did not warned you) AND IF YOUR EYES ARE RIVETED ON THIS ONE, DON'T FORGET MDFIC AS A TARGET! OH! BY THE WAY LOOK-UP ECRG2 (esophageal cancer ) AND RBEL1 WHILE ON THIS! (Why? because it is a rebel gene! think about that!)
"UniProtKB/Swiss-Prot: MDFI_HUMAN, Q99750
ACTIVITIES AT CRBCM AS OF FEBRUARY 2014!
It is critical to our readers to know that CRBCM is still alive, maturing and quickly expanding its reach...
It is mind "troubling" to think where despite our struggles we have position ourselves. It point to one thing, the need for CRBCM and institution such this one is "critically" great. We are at
1. having chemotherapy patients needing us
2. patients from El Paso depending on us
3.in a week we are presenting at a local Hospital breaking news on gene studies in Breast cancers
4.Last week we were featured in "University of Texas in El Paso (UTEP) news". At least our MDHONORS/CRBCM financed work on Lung cancer work was featured.
5.We are solicited for presentation and article reviews.
6. Our work on Traumatic Brain Injury (TBI) is selected for potential publication
7.We have presented our work on TBI through the hall of the prestigious UMC (University Medical Center)
And we the reinstitution of CPRIT, we are poised to submit another research proposal (participating is key, our expectation is "zero" for CPRIT is tricky. We still don't know what this institution is trying to be...
8.We are still "medical Director" at a local Griffols/Talecris Plasma Center. And completed our work there!
9. We have taken over an over 30 year old prominent Medical Practice
10. We still have completed our mission in the snow covered Indianapolis
And yesterday when you were stretching your legs, enjoying a week-end, the CRBCM attended to more than 10 outpatient and inpatient patients who rely on this new clinic for immediate and future care!
11.On February 10, 2 Nursing students will start Rotation at CRBCM,
We will be at NIH, SBIR, and other funding institution submissions,
and most importantly we will continue our blog
now followed internationally, with more than 35,000 reviews in 1 year!
The CRBCM....the year is still young, we are going to keep moving!
It is mind "troubling" to think where despite our struggles we have position ourselves. It point to one thing, the need for CRBCM and institution such this one is "critically" great. We are at
1. having chemotherapy patients needing us
2. patients from El Paso depending on us
3.in a week we are presenting at a local Hospital breaking news on gene studies in Breast cancers
4.Last week we were featured in "University of Texas in El Paso (UTEP) news". At least our MDHONORS/CRBCM financed work on Lung cancer work was featured.
5.We are solicited for presentation and article reviews.
6. Our work on Traumatic Brain Injury (TBI) is selected for potential publication
7.We have presented our work on TBI through the hall of the prestigious UMC (University Medical Center)
And we the reinstitution of CPRIT, we are poised to submit another research proposal (participating is key, our expectation is "zero" for CPRIT is tricky. We still don't know what this institution is trying to be...
8.We are still "medical Director" at a local Griffols/Talecris Plasma Center. And completed our work there!
9. We have taken over an over 30 year old prominent Medical Practice
10. We still have completed our mission in the snow covered Indianapolis
And yesterday when you were stretching your legs, enjoying a week-end, the CRBCM attended to more than 10 outpatient and inpatient patients who rely on this new clinic for immediate and future care!
11.On February 10, 2 Nursing students will start Rotation at CRBCM,
We will be at NIH, SBIR, and other funding institution submissions,
and most importantly we will continue our blog
now followed internationally, with more than 35,000 reviews in 1 year!
The CRBCM....the year is still young, we are going to keep moving!
Friday, January 31, 2014
Many Invitations, so little time!
SENT TO CRBCM
===================================================================
===================================================================
Good morning,
The Office of Continuing Medical Education has been
in communication with the El Paso County Medical Society to submit
abstracts for consideration for publication in their journal.
Dr. Alan Tyroch, MD, the Program Director for the Rio Grande Trauma
Conference invites you to participate in the submission process. If you
would like for our office to forward the abstract you provided for the
14th Annual Rio Grande Trauma Conference
on December 5th and 6th, 2013 for consideration
for publication in the El Paso Medical Society’s next issue, please sign
the letter attached and send to
jesia.boykin@ttuhsc.edu or fax to 915-783-6220 by
Friday, February 7, 2014.
=====================================================
BUT ONE THING FOR SURE, WE WILL BE IN LAS-VEGAS FOR THE ANNUAL UPDATE IN HEMATOLOGY!
Thursday, January 30, 2014
In Lymphoproliferative disorder, particular of dangerous genes
1*Highly conserved Molecule: This means the molecule has stood the test of time and has been used under that form for years, and may have become critical in basic cellular functions. In the human cell, some genes that are now "conserved" came from or were adopted from invading Virus. For such an adoption to occur, the gene must be critical and acquired without antigenicity. It is believed that ELK-1, ETS, Myb,ERG,ETV EWS, or TEL, could be an evolutive genes that are characterized with high level of co-association and remains most of all within the epigenic zone. TEL-JAK2 has been suggested in Leukemia(Lacronique et al)
while TMPRSS-ERG has been demonstrated in Prostate cancer (clark et al).
In Breast cancer, "Elk1 also interacts with BRCA1 splice variants, namely BRCA1a and BRCA1b. This interaction enhances BRCA1-mediated growth suppression in breast cancer cells. Elk1 may be a downstream target of BRCA1 in its growth control pathway. Recent literature reveals that c-fos promoter activity is inhibited, while overexpression of BRCA1a/1b reduces MEK-induced activation of the SRE. These results show that one mechanism of growth and tumor suppression by BRCA1a/1b proteins acts through repression of the expression of Elk1 downstream target genes like Fos.[20]" wikepedia
Watson et al suggested :"
It has been over 15 years since Ets was originally identified as one of the two genes (Ets and Myb) transduced by the avian leukemia virus, E26 (Watson et al., 1990);" again suggesting these gene that control epigenetic events may be evolutive as suggested above, and keeps attractive co-association capability that may have help them escape cellular immunity ! Their location at the epigenetic location show the points to a cellular zone of weakness. But it also could point to the importance of inhibitor of de-Acetylators in human cancer and point to why we need further efforst to understand epigenetic events. The fact is that medication targeting Retinoic Acid took over by surprise the world when it comes to treatment of Promyelocytic Leukemias, re-enforces this notion...
To know more about how gene elements described above interact further with P53, histone de-acetylators, and the Telomeres, read our blog of 1 year ago on 01/31/2013.
========================================================================
I cannot pass to the next step without pointing to the fact that distant effect of Traumatic Brain injury (TBI) are not far from these region since they all depend on secondary release of Cytokines which originate from these regions!
=======================================================================================
AND SO MUCH STILL TO TALK ABOUT!
2*young selective development:
3*JAK/STAT involvement
4*The cell wants to achieve selective terminal differentiation and criss cross with gene repair and gene of variable region
5*membranous event with coexistence of Death Receptor
6*factor BSAP expression
7*Activity at TLE4, a negatve regulator of PAX5
8*relation with Ibrutinib
9*Daxx gene
10*The intervention pf the Variable region of IG
11*role of RAG1
12*emu enhancer
13*role of AML1
14*role of TATA and the Retinoblastoma genes
15*Intervention of the Telomere
16*Acetylated P53 (see blog 01/31/2013)
while TMPRSS-ERG has been demonstrated in Prostate cancer (clark et al).
In Breast cancer, "Elk1 also interacts with BRCA1 splice variants, namely BRCA1a and BRCA1b. This interaction enhances BRCA1-mediated growth suppression in breast cancer cells. Elk1 may be a downstream target of BRCA1 in its growth control pathway. Recent literature reveals that c-fos promoter activity is inhibited, while overexpression of BRCA1a/1b reduces MEK-induced activation of the SRE. These results show that one mechanism of growth and tumor suppression by BRCA1a/1b proteins acts through repression of the expression of Elk1 downstream target genes like Fos.[20]" wikepedia
Watson et al suggested :"
It has been over 15 years since Ets was originally identified as one of the two genes (Ets and Myb) transduced by the avian leukemia virus, E26 (Watson et al., 1990);" again suggesting these gene that control epigenetic events may be evolutive as suggested above, and keeps attractive co-association capability that may have help them escape cellular immunity ! Their location at the epigenetic location show the points to a cellular zone of weakness. But it also could point to the importance of inhibitor of de-Acetylators in human cancer and point to why we need further efforst to understand epigenetic events. The fact is that medication targeting Retinoic Acid took over by surprise the world when it comes to treatment of Promyelocytic Leukemias, re-enforces this notion...
To know more about how gene elements described above interact further with P53, histone de-acetylators, and the Telomeres, read our blog of 1 year ago on 01/31/2013.
========================================================================
I cannot pass to the next step without pointing to the fact that distant effect of Traumatic Brain injury (TBI) are not far from these region since they all depend on secondary release of Cytokines which originate from these regions!
=======================================================================================
AND SO MUCH STILL TO TALK ABOUT!
2*young selective development:
3*JAK/STAT involvement
4*The cell wants to achieve selective terminal differentiation and criss cross with gene repair and gene of variable region
5*membranous event with coexistence of Death Receptor
6*factor BSAP expression
7*Activity at TLE4, a negatve regulator of PAX5
8*relation with Ibrutinib
9*Daxx gene
10*The intervention pf the Variable region of IG
11*role of RAG1
12*emu enhancer
13*role of AML1
14*role of TATA and the Retinoblastoma genes
15*Intervention of the Telomere
16*Acetylated P53 (see blog 01/31/2013)
New Challenges to the human cell
In a world where new stimulants and new conditions are created, the human cell, deep in our systems, is confronted and forced to adapt and conform to new environment constantly. And doing so with the human genes that it possesses at the moment. Yes, while a chemist work hard to create new chemical product to improve our lives (I really hope this), the cell somewhere in the human body does not know it will face this new challenge once it comes to contact with it. To deal with this new product as a stimulant, the cell has to use its potentials. It has sometime to rearrange its mechanisms to deal with the new stimulant! While most of the time quick adaptation to the new product is limited in its impact on the life of the cell, certain stimulants will lead to receptor desensitization, transcription factors amplifications (particularly if gene autophosphorylation is allowed, shutdown of regulators occurs, alteration in splicing, and special miRNA are transcribed,etc.). The point is even Receptor desensitization itself may lead to shutdown of critical genes.
One of the things that makes the cell vulnerable to the effect of new stimulant, is not only its reliance to old techniques to fight new challenges (ie, activation of the NF-kB) but also proximity and interactivity of the genes particularly those in the proximity of the initial inducing events. But in a lightening fast action, distant genes are also involved. The proximity of basic cellular functions is also a player. Indeed it is common that one event could affect various cellular functions such as proliferation,growth and differentiation. In fact the ease of recruiting neighbor gene is impressive. It does not take much for a stimulant to induce de-differentiation to return cellular omnipotence to deal with the new comer, but cellular omnipotence is sitting next to shutting Apoptosis so that the new challenge does not kill the cell, But as seen in many cases, gene repair mechanisms are raised to the ready (in some cases shut down to tolerate mistakes), splicing machines are set in motion to make new RNA to create adapted novel proteins, multiplication machinery are also ready to clone resistant cells, messaging machinery is put in a "work" mode to notify surrounding cells in case they don't know already. The most sensitive function of all is the machinery to induce JAK/STAT and the variable domain of immunoglobulins. Once these are engaged, a potential neoplastic transformation is possible if attachment to the involved gene occurs!
An example of this is what happen in Hodgkin disease, if you read about PAX genes, you will find cellular de-differentiation, PAX1-engage MOX1 but surprise-surprise-BRCA1 is not far. You will argue that PAX5 is the one in 97% of some Hodgkin Lymphomas, but follow the TLE4, Daxx, AML1,TATA,and RAG1....you will find that the same story repeats itself!
The CRBCM is following the trail!
One of the things that makes the cell vulnerable to the effect of new stimulant, is not only its reliance to old techniques to fight new challenges (ie, activation of the NF-kB) but also proximity and interactivity of the genes particularly those in the proximity of the initial inducing events. But in a lightening fast action, distant genes are also involved. The proximity of basic cellular functions is also a player. Indeed it is common that one event could affect various cellular functions such as proliferation,growth and differentiation. In fact the ease of recruiting neighbor gene is impressive. It does not take much for a stimulant to induce de-differentiation to return cellular omnipotence to deal with the new comer, but cellular omnipotence is sitting next to shutting Apoptosis so that the new challenge does not kill the cell, But as seen in many cases, gene repair mechanisms are raised to the ready (in some cases shut down to tolerate mistakes), splicing machines are set in motion to make new RNA to create adapted novel proteins, multiplication machinery are also ready to clone resistant cells, messaging machinery is put in a "work" mode to notify surrounding cells in case they don't know already. The most sensitive function of all is the machinery to induce JAK/STAT and the variable domain of immunoglobulins. Once these are engaged, a potential neoplastic transformation is possible if attachment to the involved gene occurs!
An example of this is what happen in Hodgkin disease, if you read about PAX genes, you will find cellular de-differentiation, PAX1-engage MOX1 but surprise-surprise-BRCA1 is not far. You will argue that PAX5 is the one in 97% of some Hodgkin Lymphomas, but follow the TLE4, Daxx, AML1,TATA,and RAG1....you will find that the same story repeats itself!
The CRBCM is following the trail!
Wednesday, January 29, 2014
Diet is important in cancer control:(case in point, Breast cancers!)
I knew this from the Bottom of my heart but pinning the genetic reason was here before me and I just did not see it. Supply of sugar will ultimately increase Insulin which will increase the demand for Insulin receptor which in cancer is a bad actor. The increase in Insulin receptor will interact with major genes that affect cancer. First it affect the JAK /STAT pathways, which leads to Proliferation, second it affects the Gerb gene family which is a "wild" gene, meaning a gene just connected to too many others that will be influenced. But one of the aspect mostly forgotten by survivors, is the receptor connection to the PTPN11. A gene that has many links but one particular link is its relation with LAIR1, " is a protein forming a receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis. In humans, the LRP1 protein is encoded by the LRP1 gene.[wikipedia
Involvement of this LAIR1 is bad for you if it leads to consumption of Thrombospondin-1(THBS1 ) which help the cell grow its feet for walking away and metastasizing (Breast cancer has done done quite a bit! Through the interaction with PGDFR, this pathway will affect even blood clots (destruction of Caveolin) possibly inducing clot to move away and cause strokes and Myocardial infarction (science here is still growing). Drop of Thrombospondin is a major event involving CD38, and certain Integrins (be very careful which! ) and release of Metallo-proteases. It is amazing that we do not monitor THBS1 today since its drop marks Metastatic disease. (and stroke and MI presumably). And all this is induced by diet. Not changing diet in cancer helps residual disease spread.
One of the thing that is important to note, most Estrogen Receptor are covered by a sugar, and Heparan sulfate is in most case the cover. Guess what, THBS1 interact with Heparan for potentially its removal. Making thrombospondin potentially a mechanism for cessation of Receptor desensitization. What would happen in people depending on the preservation of the Receptor function (Tamoxifen)? can we also infer there is a benefit for sulfur products here?
If you follow this line of thinking, you will also find that cholesterol use by the brain will be affected. Another effect of LAIR1, opening another Pandora Box!
Eat less sugar is critical to cancer spread.....The CRBCM, work is still ahead.....
Tuesday, January 28, 2014
Questions for researchers! Melanoma as an example !
When a cancer continues to rise
-it means it is more environmental?
-It means its central mechanism continue to escape us
-It means the isoforms of the genes causing it, is more frequently found in the population
-It means that many isoforms can lead to it, again here we need to know the basics? does the frequency of cancer in society firmly linked to the frequency of the gene Isoforms?
-does the frequency means we keep missing the fundamentals?
-Or does it means the tumor has greater facility to penetrate the neoplastic transformation, or reach easily the "wild genes" or genes of importance in differentiation...
or genes capable of autoregulation?
or genes capable of suppressing other genes
or genes susceptible to Vitamin depletion
The prominence of Vitamin and hormones in society seem to suggest this last point! Or is it vitamin imbalance?
In Melanoma for example it is established that the disease seems to occur more frequently in patients who burn rather than tan. And that sunburn would more likely be the trigger! What that tells you about their MCIR gene, their FAK and induction of the Wnt (association with LEF1), and Notch, Now that we are speaking MITF, and GNAQ/GNA11, or is it a deficiency of the SOCS family gene?
-Association with moles? Dysplastic moles have up to 80% risk of Melanoma development, particularly when familial tendencies are implicated? what that tells us about what gene is involved is it MITF still?or is it PPP3CA (interferes with dephosphorylation of DNM1L, HSPB1 and SSH1)(will Etoposide helps here?with Cisplatin may be? When you say this, is it POLR2C, the culprit?
or is it PAX3,MEF2, or Calsarcin-3.
well don't forget insufficiency of p16/CDKN2A when insufficiency of inhibitor of this major pathway relieve the block on cell division...
What gets BRAF so involved Or is it the involvement of Rho/ROCK. What BRAF has to do with MITF
why inability to cope with change in skin color shuts down apoptosis? Can interfering with splicing affects
What the hell Xeroderma has to do any how?RAD2, ERCC,DDB2,POLH,XPA,XPB.
Or simply BRAF is locked in Autoregulation, being truly a driver mutation, or relieved of its blocker or ubiquitinating substrate? Is the PTEN present or not (is it more involved in internal Melanoma-lung?)
what about POU3F2 and PIAS, and miRNA-211, should we block TAF15? (sparing TATA and HSP27?)
can blocking the FGF worth while?
what about the expression of c-Kit (lentigo), where are the DNA repair genes? Should we focus on abilty of this cell to deal with hypoxia? (it seems to enjoy this path?)
There is much to be done, but where are we....
AT CRBCM, we are still at work!
-it means it is more environmental?
-It means its central mechanism continue to escape us
-It means the isoforms of the genes causing it, is more frequently found in the population
-It means that many isoforms can lead to it, again here we need to know the basics? does the frequency of cancer in society firmly linked to the frequency of the gene Isoforms?
-does the frequency means we keep missing the fundamentals?
-Or does it means the tumor has greater facility to penetrate the neoplastic transformation, or reach easily the "wild genes" or genes of importance in differentiation...
or genes capable of autoregulation?
or genes capable of suppressing other genes
or genes susceptible to Vitamin depletion
The prominence of Vitamin and hormones in society seem to suggest this last point! Or is it vitamin imbalance?
In Melanoma for example it is established that the disease seems to occur more frequently in patients who burn rather than tan. And that sunburn would more likely be the trigger! What that tells you about their MCIR gene, their FAK and induction of the Wnt (association with LEF1), and Notch, Now that we are speaking MITF, and GNAQ/GNA11, or is it a deficiency of the SOCS family gene?
-Association with moles? Dysplastic moles have up to 80% risk of Melanoma development, particularly when familial tendencies are implicated? what that tells us about what gene is involved is it MITF still?or is it PPP3CA (interferes with dephosphorylation of DNM1L, HSPB1 and SSH1)(will Etoposide helps here?with Cisplatin may be? When you say this, is it POLR2C, the culprit?
or is it PAX3,MEF2, or Calsarcin-3.
well don't forget insufficiency of p16/CDKN2A when insufficiency of inhibitor of this major pathway relieve the block on cell division...
What gets BRAF so involved Or is it the involvement of Rho/ROCK. What BRAF has to do with MITF
why inability to cope with change in skin color shuts down apoptosis? Can interfering with splicing affects
What the hell Xeroderma has to do any how?RAD2, ERCC,DDB2,POLH,XPA,XPB.
Or simply BRAF is locked in Autoregulation, being truly a driver mutation, or relieved of its blocker or ubiquitinating substrate? Is the PTEN present or not (is it more involved in internal Melanoma-lung?)
what about POU3F2 and PIAS, and miRNA-211, should we block TAF15? (sparing TATA and HSP27?)
can blocking the FGF worth while?
what about the expression of c-Kit (lentigo), where are the DNA repair genes? Should we focus on abilty of this cell to deal with hypoxia? (it seems to enjoy this path?)
There is much to be done, but where are we....
AT CRBCM, we are still at work!
Sunday, January 26, 2014
Puzzling c-KIT
C-kit presence has been used in the definition of GIST and its presence has been used for the sensitivity to TKI (Gleevec). But this is proven when C-kit is a driver Mutation (driven by localized or in-situ) autoregulation), in other disease C-kit could be present as a secondary event (mitigated response in response to upstream gene overexpression-this conditioned by normal suppressive downregulation), in those cases, TKI will have a minimal effect....
Can Monteluskast or Zafirlukast improve outcome
or does blocking IL3 receptor change outcome
or should we introduce a JAK-STAT inhibitor to affect outcome since the SOCS genes seems to be involved? SOCS1 is described as a negative inhibitor of JAK/STAT pathway! Activators of SOCS1 are being looked at in Hepatoma, How frequently is c-Kit positivity in this disease? What is the meaning of c-Kit in Adenoid Carcinoma (driver Vs secondary)? Interesting questions indeed!
Can Monteluskast or Zafirlukast improve outcome
or does blocking IL3 receptor change outcome
or should we introduce a JAK-STAT inhibitor to affect outcome since the SOCS genes seems to be involved? SOCS1 is described as a negative inhibitor of JAK/STAT pathway! Activators of SOCS1 are being looked at in Hepatoma, How frequently is c-Kit positivity in this disease? What is the meaning of c-Kit in Adenoid Carcinoma (driver Vs secondary)? Interesting questions indeed!
In Melanoma, Tribulations of the MITF gene!
The gene is a "wild" gene and can auto-regulate, 2 charateristics that make MITF a dangerous gene! Moreover, it is implicated in cellular differentiation, it regulates the BCL-2, and shows up when resistance to BRAF inhibitor come to be demonstrated. It causes a deformation and intervene in cellular ability to resist Hypoxia. Therefore VEGF amplification is a secondary event meaning it is not a driver Mutation, and Anti-VEGF will have a minimal effect in Melanoma.(This is debatable in Uveal melanoma However - Here it is the GNAQ/GNA11 thing! And PKC and MEK inhibitors may be actors). Mutations in MITF lead to Tietz syndrome[5] and Waardenburg syndrome type IIa.[6]wikipedia
Blocking Wnt 3a, and the Cyclic AMP could be meaningful and alpha MSH could be a bio-marker for BRAF resistance. Look at PAX3 role and POU3F2! Interaction with LEF-1 is under scrutiny. Briefly, we have our eyes on Melanoma and its activity. The Melanocortin Receptor is also under review...Briefly we know that the cell has predicted that MITF is an agent of differentiation and adaptation (splicing and miRNA 211), it also has planned that if the cell cannot differentiate and adapt, it should quickly die through apoptosis...let melanoma cell choose this natural pass for the cure!
?Does failure to Braf points to susceptibility to Cisplatin or Melphalan? good question to explore, again is alpha MSH a meaningful Bio-marker under these circumstances? a good question to further explore!
Blocking Wnt 3a, and the Cyclic AMP could be meaningful and alpha MSH could be a bio-marker for BRAF resistance. Look at PAX3 role and POU3F2! Interaction with LEF-1 is under scrutiny. Briefly, we have our eyes on Melanoma and its activity. The Melanocortin Receptor is also under review...Briefly we know that the cell has predicted that MITF is an agent of differentiation and adaptation (splicing and miRNA 211), it also has planned that if the cell cannot differentiate and adapt, it should quickly die through apoptosis...let melanoma cell choose this natural pass for the cure!
?Does failure to Braf points to susceptibility to Cisplatin or Melphalan? good question to explore, again is alpha MSH a meaningful Bio-marker under these circumstances? a good question to further explore!
CRBCM staying in the news!
Improving the Odds Against Lung Cancer
- Last Updated on Thursday, 23 January 2014 15:39
UTEP News Service
For many, lung cancer is diagnosed too late.
“About 85 percent of people diagnosed with lung cancer will die of that condition,” said Mutombo Kankonde, M.D., referring to the most fatal cancer in the United States.
Mutombo
Kankonde, M.D. (left), a local El Paso oncologist, and Jianying Zhang,
Ph.D., a cancer biologist at UTEP, are working together to develop a
test for the early detection of lung cancer. Photo courtesy of Dr.
Kankonde.Those striking statistics — more people die of lung cancer each year than of colon, breast and prostate cancer combined — are what compelled Kankonde to study the disease and recently assemble a team of local scientists to develop a test to detect lung cancer much earlier.
“I haven’t done much work on lung cancer myself, but I have been able to identify biomarkers of liver cancer,” said Jianying Zhang, Ph.D., a biologist at The University of Texas at El Paso who forms part of the research team. “Dr. Kankonde knows this and wants to apply the same approach that I used in my lab to detect lung cancer earlier.”
Lung cancer is currently diagnosed after a CT scan, MRI or chest X-ray — when the tumor has already become visible as a mass in the lung and is at an advanced stage.
“If we use that sort of technology for diagnosis, it’s usually too late for the patient,” Zhang said. “That’s why we want to find a way to identify the cancer before there’s a tumor.”
In an effort to develop a breakthrough kit that detects lung cancer with either blood or saliva samples, Zhang, the oncologist, and Brad Bryan, Ph.D., a biomedical scientist at Texas Tech University Health Sciences Center, are studying 50 lung cancer tissue samples and the genes that compose them for phase one of the project.
The specialists are searching for three particular cancer-related genes in the tissue that have been associated with lung cancer at an early stage.
“We want to know, ‘What is the frequency of these gene abnormalities in these known lung cancer samples?’” said Kankonde, who is interested in the genetics of cancer.
If the genes are overexpressed in the tissue samples, as the team suspects they will be, they can be used as biomarkers, or early indicators of the disease.
The next phase of the project would be to develop a test kit that can detect the specific cancer-related genes in a patient’s blood or saliva, and test the diagnostic method on frequent smokers — who are at the highest risk for lung cancer. If a smoker tests positive for the genes, he or she would undergo a PET scan to see if a tumor is present.
“This has the potential to achieve cancer intervention at an early stage,” Zhang said. “In this way, the patient can still survive and have surgery done before it’s too late.”
If the team’s research is successful, they’ll eventually be able to put their test kit on the market for doctors to use on patients who are at risk for lung cancer.
Kankonde added that another team objective is to determine which lung cancers are sensitive to Avastin, a standard drug used to reduce the size of lung tumors.
Not all patients respond to the drug, and Kankonde believes this also may be linked to a patient’s particular genetics.
“We want to identify genetically why some patients are sensitive to Avastin and why some are not,” he said.
If they can determine and validate the gene that causes a reaction, doctors could potentially determine whether Avastin will be a worthwhile treatment for a patient with lung cancer on a case-by-case basis.
Kankonde, who operates his own oncology clinic in El Paso, says he has positive expectations for the outcome of the study.
If he’s right, he may well be applying the tests in his own clinic one day.
One of the reason we have kept silence these few days is our return to Indianapolis to complete the various tasks that keeps CRBCM a float! Many contracts remain to be fulfilled, and CRBCM intends to accomplish one and every single contract to the fullest...so we are sometime on the move. Indiana was covered with snow so the mission was perilous (looking at your plane de-icing makes one critically uncomfortable, particularly when the de-icing fluid freezes on your plane window), but we are seeing the light as we progress deliberately! We still keep staying in the news though! Our research was posted in the UTEP NEWS!
Friday, January 24, 2014
DO NOT UNDERESTIMATE THE POWER OF ONE (RECEPTOR)
"IRAK1b, a Novel Alternative Splice Variant of Interleukin-1 Receptor-associated Kinase (IRAK), Mediates Interleukin-1 Signaling and Has Prolonged Stability*"
Liselotte E. Jensen‡"Please just go to article, but it is clear that TGF Beta is clearly important particularly in Breast Cancer. Anything that can autophosphorylate should make any-researcher nervous because it can set its self up and initiate something up (driver mutation). When it is a molecule that can help cancer cell elude autoimmune destruction, when it help the auto-growth, and avoid apoptosis through death receptor or otherwise, when it interfere with cellular differentiation, when its level is require at strong presence, and when it is a conserved mechanism, it is an important part of the neoplastic transformation. Through the Tollip, it can be reached by targeting the Tankyrase! CRBCM is on it!
IRAK-1 is a critical component to cancer production!
Involvement of the NFKB suggests it (through TRAF 6, PKC, and TAB)
Through the RACs and RICs, IRAK reaches Metastasis (Rho/ROCK) and the BARC1 (breast cancers). (by touching Myd...of course).
Its activity through tampering with a gene regulator (IKK) should make you double nervous and doubling with autophosphorylation means it can be a driver on its own and achieve autocrine role for the new Cancer!
Through the CHUK it acts as a multiple site hitting of the NFkB but also reaches the Wnt through CTNNB1. Hitting NCOA means the engagement of all other Hormone receptors including the "wild" gene, Andogene receptors! Once again The Tankyrases better be your Target to stop all this upstream...
And you know through the Dead Box, P53 will be spared and through mechanisms shared above, your Retinoblastoma gene will soon come into play. And I guess I should not mention the Ubiquitin C or the NOTCH!...they all are involved!
The lesson here is that it is not the gene to look at when you are trying to find a therapeutic intervention, it is its common Receptor or substrate. Don't look at IL-1, look at their receptors ...such as IRAK-1!
Thursday, January 23, 2014
BAD THINGS LOOK ALIKE, BUT TRY TO WALK WITH ME THROUGH THE MAZE OF GENES! LIGHT IS BORN!
AMBRY-GENETICS"
"Pancreatitis Panel includes concurrent full gene analysis for PRSS1, SPINK1 and CFTR. Pancreatitis Panel can detect 99% of PRSS1 and SPINK of known mutations and 97-98% of of CFTR mutations. Testing does not include CTRC gene analysis."
BUT DO YOU REMEMBER SPINK5
IN THE NETHERTON SYNDROME
WHERE THEY SPEAK OF ICHTHYOSIS AND LEKTI
AND STRATUM BASALE
AND PSORIASIS AND STRATUM BASALE, WHERE BASAL LIKE CELL COME FROM AND SEEN IN TRIPLE NEGATIVE BREAST CANCER,
REALLY LOOK IT UP, IN PSORIASIS THEY SPEAK OF CCHCRA1
WELL DOWNSTREAM THIS WE FIND POLR2C WHICH TALK TO TAF15 THEN SAFB WHICH ACTIVATES ESTROGEN RECEPTOR AND HNRPD WHICH INTERACTS WITH HSP27 AND LATER SPEAKS WITH TGFB AND PTPN12 AND BAMMMMM! IT REACHES BCAR1. AND BRCA1 BECOMES FOUND IN TRIPLE NEGATIVE BREAST CANCER WHICH IS NOT FAR FROM PANCREATIC PROCESSES. BUT IN ALL THE MAZE OF GENES OUR FOCUS REMAINS ON SP1, EP300,SIN3A,GATA1.
THE FACT REMAINS THAT TATA SPEAKS ALSO TO POLR2C, THE SAME POLR2C THAT SPEAKS TO TAF15. HMMMM....AND TATA binding protein SPEAKS TO TAF15.
PTPN12 INTERACTS WITH SHC1 BUT WATCH IT ATTACKING SHC1 (REGULATOR OF APOPTOSIS) BECAUSE IT HAS THE FAMOUS SH2 DOMAIN LIKE A GAZILLION OF OTHER MOLECULE INCLUDING THE STATS AND THE JAKs. YOU JUST DON'T KNOW WHAT YOU WILL TOUCH.
ON THE OTHER HAND UBIQUITICN C KEEPS ATTRACTING RESEARCHER FOR WHAT IT CAN DELIVER! ONE NEEDS TO STRATEGIZE THIS APPROACH!
"Pancreatitis Panel includes concurrent full gene analysis for PRSS1, SPINK1 and CFTR. Pancreatitis Panel can detect 99% of PRSS1 and SPINK of known mutations and 97-98% of of CFTR mutations. Testing does not include CTRC gene analysis."
BUT DO YOU REMEMBER SPINK5
IN THE NETHERTON SYNDROME
WHERE THEY SPEAK OF ICHTHYOSIS AND LEKTI
AND STRATUM BASALE
AND PSORIASIS AND STRATUM BASALE, WHERE BASAL LIKE CELL COME FROM AND SEEN IN TRIPLE NEGATIVE BREAST CANCER,
REALLY LOOK IT UP, IN PSORIASIS THEY SPEAK OF CCHCRA1
WELL DOWNSTREAM THIS WE FIND POLR2C WHICH TALK TO TAF15 THEN SAFB WHICH ACTIVATES ESTROGEN RECEPTOR AND HNRPD WHICH INTERACTS WITH HSP27 AND LATER SPEAKS WITH TGFB AND PTPN12 AND BAMMMMM! IT REACHES BCAR1. AND BRCA1 BECOMES FOUND IN TRIPLE NEGATIVE BREAST CANCER WHICH IS NOT FAR FROM PANCREATIC PROCESSES. BUT IN ALL THE MAZE OF GENES OUR FOCUS REMAINS ON SP1, EP300,SIN3A,GATA1.
THE FACT REMAINS THAT TATA SPEAKS ALSO TO POLR2C, THE SAME POLR2C THAT SPEAKS TO TAF15. HMMMM....AND TATA binding protein SPEAKS TO TAF15.
PTPN12 INTERACTS WITH SHC1 BUT WATCH IT ATTACKING SHC1 (REGULATOR OF APOPTOSIS) BECAUSE IT HAS THE FAMOUS SH2 DOMAIN LIKE A GAZILLION OF OTHER MOLECULE INCLUDING THE STATS AND THE JAKs. YOU JUST DON'T KNOW WHAT YOU WILL TOUCH.
ON THE OTHER HAND UBIQUITICN C KEEPS ATTRACTING RESEARCHER FOR WHAT IT CAN DELIVER! ONE NEEDS TO STRATEGIZE THIS APPROACH!
Wednesday, January 22, 2014
For fun, we also do!
Hello Clement Albert,(or DR Kankonde)
|
||
|
||
We think you'll agree that Radio Airplay is a better promotional tool than ever. More than 50,000 artists rely on Airplay to get their music out there, and here's why:
|
||
|
Cancer research questions, so many it is mind troubling!
1.Can disruption of the Nuclear CAP be used as therapeutic intervention in dividing cell?
lewis et al:
"The defects in splicing and U1 snRNP binding caused by CBC depletion can be specifically reversed by recombinant CBC. In summary, efficient recognition of the cap-proximal 5' splice site by U1 snRNP is facilitated by CBC in what may be one of the earliest steps in pre-mRNA recognition. Data in Colot et al. (this issue) indicate that this function of CBC is conserved in humans and yeast."
It is a conserved process for a reason! CAN INTERFERING WITH SPLICING BE USED IN CANCER THERAPY?
2. Could blocking Transportins (1,2) or A1 be a novel therapeutic approach in Breast cancers since levels of Molecule transfer seems of importance in this disease.
Can these molecules (transporters in general) be biomarkers of cellular activities in breast cancers. What is the role of targeting the poly tail (A) of RNA, should that limit the movement of these RNA
3. Should BH3 domains, presence of BNIP3 activation, BCL2, NOTCH activation, be surrogates for anti-apoptosis in cancer biology? what about SHC1
4. Should presence of activity at CD47 be consider a biomarker of BCL-2 activity? Anti-apoptosis?
CD47 (IAP).
wikipedia:"By blocking TSP1 from binding to its cell surface receptor (CD47) normal tissue becomes nearly immune to cancer radiation therapy and assists in tumor death."
5.GIPC 1 could turn out to be an important Target in Ovarian cancers! because of DAB2 and LRP interactions.
So many things to test, it is mind "troubling" or is it "mind buggling",they say!
lewis et al:
"The defects in splicing and U1 snRNP binding caused by CBC depletion can be specifically reversed by recombinant CBC. In summary, efficient recognition of the cap-proximal 5' splice site by U1 snRNP is facilitated by CBC in what may be one of the earliest steps in pre-mRNA recognition. Data in Colot et al. (this issue) indicate that this function of CBC is conserved in humans and yeast."
It is a conserved process for a reason! CAN INTERFERING WITH SPLICING BE USED IN CANCER THERAPY?
2. Could blocking Transportins (1,2) or A1 be a novel therapeutic approach in Breast cancers since levels of Molecule transfer seems of importance in this disease.
Can these molecules (transporters in general) be biomarkers of cellular activities in breast cancers. What is the role of targeting the poly tail (A) of RNA, should that limit the movement of these RNA
3. Should BH3 domains, presence of BNIP3 activation, BCL2, NOTCH activation, be surrogates for anti-apoptosis in cancer biology? what about SHC1
4. Should presence of activity at CD47 be consider a biomarker of BCL-2 activity? Anti-apoptosis?
CD47 (IAP).
wikipedia:"By blocking TSP1 from binding to its cell surface receptor (CD47) normal tissue becomes nearly immune to cancer radiation therapy and assists in tumor death."
5.GIPC 1 could turn out to be an important Target in Ovarian cancers! because of DAB2 and LRP interactions.
So many things to test, it is mind "troubling" or is it "mind buggling",they say!
Monday, January 20, 2014
Importance of cancer Metastasis
One thing for sure Metastasis is just not another characteristic of Cancer. It is one of the characteristics of tumoral cells that make them cancerous. Cancer will not kill anybody unless it spreads (with the exception of Brain cancer, but even in this disease, it is the tentacular infiltrations of these cells that ultimately kill. Cancer on the move kills. So it is important to focus on genes that lead to cancer spread. Prostate cancer or colon cancers will not kill if invasion and metastasis will not occur. And survivors will not be at risk if the disease stopped popping up somewhere else (in most cases, since local recurrence could be dealt with vehemently with an aggressive local treatment!). Spread has become sophisticated, from Putative genes such as MTS1, to motion evidence with non muscle Myosin (II, and sometime V)/Actin, to SNAIL and SLUG (E-Cadherin). It goes on to hiding behind P53 of which activation can increase phosphorylation of MK5 and you know what effect this will have on RAS. In Breast cancers in particular, you know about RSK dependent TGF accumulation of MK2. Increase of RSK4, decrease CXCL family member which in turn activates the Claudins...Other pathways of importance VEGF,LIMK1,P38. Putative role of RhoA/Rock. MLCK, BNIP and even LAR genes. We have so many chances to act but sit on our hands...talking to governors who have nothing to do with these markers...The Ultimate blocker to cancer research is still Human...wearing Tuxedo, unaware or innocent to science! Work with CRBCM to stop cancer, not find reasons...and you know the rest....CRBCM progressing slowly but surely ... we will continue to fight until we find a cure...and enemies become irrelevant to the fight! (So many markers, so many chances to stop cancer, but nothing substantial done to capture the moment! and politics keep going...they lost their soul! )
Sunday, January 19, 2014
?new Breast cancer Biomarker
There must be a marker in Breast cancer displaying a mutation in the fanconi like gene.
We know that disturbance in Fanconi disease affect mobilization of molecule such as Cystine.
And Fanconi gen alteration is cited a lot in Breast cancer, Is there a Beta albumin secretion when SLC gene is abnormal in Breast Cancer. take serum and Breast cancer specimen, if mutation in SLC gene is found, does the serum gives us a Beta-albumin like molecule in the serum? easy to find a biomarker...ok let's go to work.
Is SLC gene marker a surrogate of Crizotinib activity? secondary reason for investigation?
PALB2 is associated with BRCA-2, is there a secretion of protein linked to it?
We know that disturbance in Fanconi disease affect mobilization of molecule such as Cystine.
And Fanconi gen alteration is cited a lot in Breast cancer, Is there a Beta albumin secretion when SLC gene is abnormal in Breast Cancer. take serum and Breast cancer specimen, if mutation in SLC gene is found, does the serum gives us a Beta-albumin like molecule in the serum? easy to find a biomarker...ok let's go to work.
Is SLC gene marker a surrogate of Crizotinib activity? secondary reason for investigation?
PALB2 is associated with BRCA-2, is there a secretion of protein linked to it?
Saturday, January 18, 2014
CAMPTEN ! IN NEURO-ENDOCRINE TUMORS!
Somethings make you scratch your head,
and now you wonder what made them think of it...
In life revisiting stuff is not bad after all...
WHO HAD THOUGHT OF THAT
AND THEN IT MAKES YOU RUN BACK TO THE DRAWING BOARD
COMBINATION OF XELODA AND TEMODAR IN NEURO-ENDOCRINE TUMOR?
THE RESULT IS UNEXPECTEDLY GOOD!
WHAT IS THE GENETIC BASIS OF THIS, CRBCM WONDERS! LET'S GO BACK HERE....THE SEARCH SHOULD NOT BE LONG, I GUESS......to be this effective the mode of action go to be additive which in gene may mean a more total blockade of a specific gene or pathway, or blockade of 2 competing gene/pathways or may be blockade of 1 pathway and its rescue process. We have got to go deeper. And why Neuroendocrine ? Is that mean where Etoposide may work such as in the epigenetic area where Histone Deacetylase are king, or is it in the mitochondria where the CREB genes , BCL-2 are in effect. Xeloda aims a Thymidilate synthase impairing S-phase but what that have to do with silencing th MGMT gene that unleashes Temodar alkylating effect...does blocking synthase and the need in S phase give a better out look...well we need dig in further...and why neuro endocrine, why the hormone? here focus on epigenetic phenomena is warranted...
and now you wonder what made them think of it...
In life revisiting stuff is not bad after all...
WHO HAD THOUGHT OF THAT
AND THEN IT MAKES YOU RUN BACK TO THE DRAWING BOARD
COMBINATION OF XELODA AND TEMODAR IN NEURO-ENDOCRINE TUMOR?
THE RESULT IS UNEXPECTEDLY GOOD!
WHAT IS THE GENETIC BASIS OF THIS, CRBCM WONDERS! LET'S GO BACK HERE....THE SEARCH SHOULD NOT BE LONG, I GUESS......to be this effective the mode of action go to be additive which in gene may mean a more total blockade of a specific gene or pathway, or blockade of 2 competing gene/pathways or may be blockade of 1 pathway and its rescue process. We have got to go deeper. And why Neuroendocrine ? Is that mean where Etoposide may work such as in the epigenetic area where Histone Deacetylase are king, or is it in the mitochondria where the CREB genes , BCL-2 are in effect. Xeloda aims a Thymidilate synthase impairing S-phase but what that have to do with silencing th MGMT gene that unleashes Temodar alkylating effect...does blocking synthase and the need in S phase give a better out look...well we need dig in further...and why neuro endocrine, why the hormone? here focus on epigenetic phenomena is warranted...
Friday, January 17, 2014
c-MYC, a trouble maker in Breast Cancer
The expression of c-MYC suggests downregulation of BCL-2 and may open the road to use of anti-Topoisomerases.
The danger of c-MYC is through its relation with ZBTB17(Zinc Finger) which affects the Host Cell Factor 1 which in turn hits SP1 and the POU2F1. The latest activates:
"POU2F1 has been shown to interact with SNAPC4,[3][4] Ku80,[5][6] Glucocorticoid receptor,[7][8][9] Sp1 transcription factor,[10][11] NPAT,[12] POU2AF1,[4][13][14] Host cell factor C1,[15][16] TATA binding protein,[17] RELA,[18] Nuclear receptor co-repressor 2,[19] EPRS,[20] Glyceraldehyde 3-phosphate dehydrogenase,[12] MNAT1[21] and Retinoid X receptor alpha.[7][22]"wikipedia
Touching the RELA in an uncontrolled fashon is generally a mistake. It is a "wilder" gene affecting all functions and marks the Wnt/NFkB involvement, and Brings in the Casein Kinases.
The involvement of PPP1R13L further brings in the SP-1, amplifying downstream events.
Amplification of the c-MYC could always be associated with repression of Myb which impacts the mi-RNA 155, and may be associated with explosive expression of the c-FOS that needs Tamper! Of course presence of c-FOS will lead to more AP-1, should c-JUN be present! Increase of c-FOS could raise the importance of Histone de-acetylators in this disease!
So the presence of c-FOS and c-MYC could potentially raise the importance of Etoposide and Histone deacetylators! An interesting trial to suggest....
The danger of c-MYC is through its relation with ZBTB17(Zinc Finger) which affects the Host Cell Factor 1 which in turn hits SP1 and the POU2F1. The latest activates:
"POU2F1 has been shown to interact with SNAPC4,[3][4] Ku80,[5][6] Glucocorticoid receptor,[7][8][9] Sp1 transcription factor,[10][11] NPAT,[12] POU2AF1,[4][13][14] Host cell factor C1,[15][16] TATA binding protein,[17] RELA,[18] Nuclear receptor co-repressor 2,[19] EPRS,[20] Glyceraldehyde 3-phosphate dehydrogenase,[12] MNAT1[21] and Retinoid X receptor alpha.[7][22]"wikipedia
Touching the RELA in an uncontrolled fashon is generally a mistake. It is a "wilder" gene affecting all functions and marks the Wnt/NFkB involvement, and Brings in the Casein Kinases.
The involvement of PPP1R13L further brings in the SP-1, amplifying downstream events.
Amplification of the c-MYC could always be associated with repression of Myb which impacts the mi-RNA 155, and may be associated with explosive expression of the c-FOS that needs Tamper! Of course presence of c-FOS will lead to more AP-1, should c-JUN be present! Increase of c-FOS could raise the importance of Histone de-acetylators in this disease!
So the presence of c-FOS and c-MYC could potentially raise the importance of Etoposide and Histone deacetylators! An interesting trial to suggest....
Subscribe to:
Posts (Atom)