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Tuesday, November 5, 2013
distraction for the Public
THE FBI HAS GIVEN UP ON FOLKS!
THE NEXT FBI INVESTIGATION SHOULD BE AT THE SMALL BUSINESS ADMINISTRATION WHERE ORGANIZED CRIME HAS TAKEN OVER GOVERNMENT GRANT PROCESS. APPLYING FOR GRANTS HAS BECOME A NIGHTMARE AT NIH AND SBIR. THE MAFIA SYSTEM HAS BEEN EASY TO INSTALL. REQUIRE LETTER OF INTENT, DETERMINE WHERE THE DANGER OF POTENTIAL APPLICATION WILL COME FROM. AND DETERMINE WHO TO STALL BY MULTIPLYING REQUIREMENTS FOR APPLICATION, MAKE THE MOST CUMBERSOME COMPUTER SYSTEM FORCING PEOPLE TO CALL, AND FURTHER IDENTIFYING THREAT OF APPLICATIONS AND CREATING MULTIPLE LAYERS OF REQUIRED GOVERNMENT NUMBERS TO WEED OUT NEW COMERS. THE END RESULT IS TO END UP WITH THE SAME FOLKS WHO ARE NOW "FRIENDS" AS APPLICANTS. THE COMPUTER SYSTEMS IS SO RIGGED THAT WALKING IN THE ICY TERRAIN IN SIBERIA OR LIFE IN THE RUSSIAN GOULAG ARE "PIECE OF CAKE". TO DISCOURAGE NEW APPLICANTS, FIRST IDENTIFY THEM. YOU ARE ENCOURAGED TO TALK TO THE OFFICE. THIS WAY THEY KNOW YOUR INTENTION TO APPLY. THEY WON'T TELL YOU MUCH IN FACT OTHER THAN " YES PLEASE APPLY". THEY WILL NOT TELL YOU THE NUMBER OF GOVERNMENT NUMBERS REQUIRED BUT EACH STEP OF THE APPLICATION PROCESS REQUIRED ONE, THEY ALSO PUT IN PLACE THE MOST ARCHAIC COMPUTER SYSTEM, THE MAFIA HAS PROVIDED THEM THE EXPERTS. YOU LITERALLY HAVE TO SAVE EVERY LETTER YOU ENTER AND EVERY TIME YOU SAVE, THE SYSTEM MAKES YOU WAIT BECAUSE YOU ARE SAVING 20 PAGES OF INFO! AND IF YOU DON'T SAVE THAT OFTEN, ALL DISAPPEARS ON YOU! YOUR OWN LOGIN INFORMATION DOES NOT WORK. YOU NEED TO CONTACT THE WATCH DOGS. BRIEFLY, TAKE ANTI-ACID BEFORE YOU START THE APPLICATION PROCESS BEFORE YOU END UP WITH A PERFORATED ULCER! BUT BELIEVE ME, LIKE ANY OTHER RIGGED SYSTEM, IT WILL END -UP BEING DISCOVERED AND HEADS WILL ROLL. THEN AGAIN, THESE GUYS HAVE BEEN IN AND OUT OF PRISON, THAT IS JUST ANOTHER DAY AT THE OFFICE...THE ONLY CHANCE LEFT, A CONGRESSIONAL INVESTIGATION...AT CRBCM WE DON'T REALLY CARE ANYMORE , IN THERE, DISCRIMINATION IS SO RAMPANT, IT IS A WAY OF LIFE AND JUST PART OF THE EQUATION!
Monday, November 4, 2013
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CPRIT’s Oversight Committee met November 1 for the first time since
February beginning a new era for the agency – one with a higher level
of transparency, improved processes and strengthened accountability to
the taxpayers of Texas. As I reported to the Oversight Committee, in
addition to provisions in SB 149 which modified CPRIT’s enabling
legislation, the agency has taken action to implement all 41 of the
State Auditor’s January 2013 recommendations.
We accomplished a number of important items at the meeting that will allow CPRIT’s work to move forward. We also began our commitment to transparency by holding the meeting at the State Capitol and streaming the meeting live over the web – a first for CPRIT. Within days, we’ll post a video of the proceedings to our website as well. Major actions of the Oversight Committee include:
It’s nice to be back at work! Regards, Wayne R. Roberts Interim Executive Director Cancer Prevention & Research Institute of Texas P.O. Box 12097 Austin, Texas 78711 |
Digging deeper ! Chromatin remodeling
As we are progressing deeper into our understanding of disease pathophysiology, we are discovering that some of the cancers are caused or exacerbated by abnormalities of cyclin pathways (Triple negative breast cancers). There are disturbances at Cyclins and Hormone Receptors at the membranes. But deeper into the cells, there is disturbance at the Histones (epigenetic zone) where modulation is needed for transcriptions factors to be formed and unleashed. Here, the dance is governed by the PRBM1, BAFs, PBAF, BRDs, RSC, ARIDs and SWI/SNF (Chromatin remodeling). This is where BRAC-1 also plays its main function. Indeed some of the Adaptors or cofactor fail the BRCA-1 to continue to repair DNAs! And some cytokines fail here! we are working deeper!
Marching on toward future therapies in Cancer Medicine
Most cancers result from a disturbance of our genes. The disturbance could be functional or simply a change in the nature of genes called Mutations. Mutations that are deleterious are those that stop or otherwise alter the fundamental function of the gene. Genes can initiate, regulate, facilitate or simply hook to other genes. Hooking (Adapter) to other genes has a strong impact because it can change the direction of the pathways, or give a gene the powers of the gene it is now hooked onto! There are those who simply allow hooking to membranes as in Anchor genes that sometimes allow trans-membrane transport, sometime just providing a substrate from other reactions to occur.
Hooks can also connect several molecules (Homeobox).
Suffice is to say that if a gene is broken, let's introduce a new gene.
The challenge is: how do we get a new gene in there?
Here we are looking at Nanotechnology to achieve this challenge!
Hooks can also connect several molecules (Homeobox).
Suffice is to say that if a gene is broken, let's introduce a new gene.
The challenge is: how do we get a new gene in there?
Here we are looking at Nanotechnology to achieve this challenge!
Sunday, November 3, 2013
4 Posters at 1st BIOMED Symposium, El Paso 10/26/2013
Dr.Zhang and Dr.Kankonde, Early Detection of Lung Cancer
Dr. Kankonde, Immunotherapy in Ovarian Cancer
Dr.Kankonde, Decrease of TBI by early use of Butein, a Sirtuin Activator
Dr.Kankonde at 1st BIOMED Symposium El Paso, 10/26/2013
Dr.Zhang, UTEP, and Peggy Kankonde, Greater East Cancer Center
The true role of E-Cadherin Vs the ASSASSIN (destructors)
One of the main activities of cancer cells to complete their "criminal enterprise" is to escape proliferation control, and cancer cells have known this and have mastered the way to achieve this very efficiently through the Cadherins. Though it is emphasized that the cancer cells reduce E-cadherin expression to free themselves from their neighbors by reducing Adhesion molecules, the truth is that there is a more ominous enterprise going on. Degradation of E-cadherin through Ubiquitilation consumes or distracts E3 from its main job which is to remove some of the Inhibitors to CDK, LEAVING THE CELL WITH UNCHECKED CELL DIVISION.
Occupying the HAKAI (ASSASSIN) would be helpful in achieving control of the process.
The E3 ubiquitin-protein ligase Hakai (HAKAI) also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1 (CBLL1) is an enzyme that in humans is encoded by the CBLL1 gene.[1] This gene encodes an E3 ubiquitin ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation.
Occupying the HAKAI (ASSASSIN) would be helpful in achieving control of the process.
The E3 ubiquitin-protein ligase Hakai (HAKAI) also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1 (CBLL1) is an enzyme that in humans is encoded by the CBLL1 gene.[1] This gene encodes an E3 ubiquitin ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation.
Saturday, November 2, 2013
BASIC SCIENCE QUESTIONS
Should patients with lymphoproliferative disorders avoid Alcohol since LMRP positivity suggests COOH involvement?
Can pain at lymph nodes in Hodgkin disease after ingestion OF ALCOHOL or pruritus predict the presence of LMRP mutation?
Is the pruritus in Hodgkin disease linked to the presence of COOH at the nerve terminal?
Should we treat lymphoproliferative disorders with LRMP expression with Cisplatin etoposide based therapy?
Interleukin-4 is the best protective Interleukin of all, I wonder if we should be measuring it as a prognosis factor in Lymphoproliferative disorders? Is overexpression of HGAL or GCET2 a corollary indication of IL-4 activity?
Can pain at lymph nodes in Hodgkin disease after ingestion OF ALCOHOL or pruritus predict the presence of LMRP mutation?
Is the pruritus in Hodgkin disease linked to the presence of COOH at the nerve terminal?
Should we treat lymphoproliferative disorders with LRMP expression with Cisplatin etoposide based therapy?
Interleukin-4 is the best protective Interleukin of all, I wonder if we should be measuring it as a prognosis factor in Lymphoproliferative disorders? Is overexpression of HGAL or GCET2 a corollary indication of IL-4 activity?
Critical importance of the Notch1
TSG1, HGS, and STAM2 appear critical in the importance of the NOTCH1.
We have stressed the importance of the NOTCH in cancer and wanted to provide some of the proof for the supportive evidence found in the literature. The Notch through its interaction with MAML1, easily affects EP300 leading to activation of TSG, a critical gene in the action of P53. Indeed P53 acts by activating TSG which leads to an increasing inhibitory activity of p21 on CDKs, blocking as a result cell division and therefore proliferation.
Inhibition at the NOTCH will therefore remove breaks to cell division and will mark a significant tendency to cancer incurability!
And I wish things stop there, but they don't:
The Activation of TSG will disturb the resting HSG which bothers the Merlin and blocks NF2 leading to the loss of growth control by contact of surrounding cells, the cell losing control of its growth...Hyperplasia can easily ensue!
The HSG now excited, engages the STAM2 and 3 things:
1. Interaction with JAK1 leading to metastasis
" Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body (wikipedia)"
the involvement of JAK-1 multiply the worsening of the situation because it will excite: PTPN11
" PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation."
and with the ELP gene, the process will affect the SMAD3 leading to loss of control of proliferation and normal ubiquitylation of inhibitory proteins.
2.S TAM2 will engage Cytokin Receptors (Cullins)
3. STAM2 will engage the tract to E3.
But the engagement of the Notch does still not stop there...
the GSK3B comes into play! and ....
We have stressed the importance of the NOTCH in cancer and wanted to provide some of the proof for the supportive evidence found in the literature. The Notch through its interaction with MAML1, easily affects EP300 leading to activation of TSG, a critical gene in the action of P53. Indeed P53 acts by activating TSG which leads to an increasing inhibitory activity of p21 on CDKs, blocking as a result cell division and therefore proliferation.
Inhibition at the NOTCH will therefore remove breaks to cell division and will mark a significant tendency to cancer incurability!
And I wish things stop there, but they don't:
The Activation of TSG will disturb the resting HSG which bothers the Merlin and blocks NF2 leading to the loss of growth control by contact of surrounding cells, the cell losing control of its growth...Hyperplasia can easily ensue!
The HSG now excited, engages the STAM2 and 3 things:
1. Interaction with JAK1 leading to metastasis
" Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body (wikipedia)"
the involvement of JAK-1 multiply the worsening of the situation because it will excite: PTPN11
" PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation."
and with the ELP gene, the process will affect the SMAD3 leading to loss of control of proliferation and normal ubiquitylation of inhibitory proteins.
2.S TAM2 will engage Cytokin Receptors (Cullins)
3. STAM2 will engage the tract to E3.
But the engagement of the Notch does still not stop there...
the GSK3B comes into play! and ....
Friday, November 1, 2013
PONATINIB: ARIAD ASKED TO STOP PRODUCTION !
THROMBOTIC EVENTS AND POSSIBLE VASCULOPATHY MAY HAVE LED TO THE FDA ORDER TO SUSPEND REPORTEDLY THE PRODUCTION OF PONATINIB A DRUG JUST RECENTLY APPROVED IN THE TREATMENT OF CHRONIC MYELOID LEUKEMIA
Ponatinib (Iclusig, previously AP24534) is an Food and Drug Administration approved oral drug candidate developed by ARIAD Pharmaceuticals for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). It is a multi-targeted tyrosine-kinase inhibitor.[1] Some forms of CML, those that have the T315I mutation, are resistant to current therapies such as imatinib. Ponatinib has been designed to be effective against these types of tumors.[2]
Oncologists have complained, however, that many patients can not afford the "astronomical" cost of $138,000 a year, which makes it one of the most expensive drugs in medicine, and far more expensive than what is needed to pay the development costs.[3][4] WIKIPIDIA
THE THROMBOTIC COMPLICATION WAS NOT NEW HOWEVER, IT IS UNCLEAR WHY THE FDA MOVED TO ORDER ARIAD TO STOP THE PRODUCTION.
"The United States Food and Drug Administration issued a partial clinical hold on new trial enrollment for Iclusig on 9 October 2013 due to an increased number of blood clots observed in patients taking the drug.[6] The EPIC trial was later cancelled on 18 October.[7]"WIKIPEDIA
Ponatinib (Iclusig, previously AP24534) is an Food and Drug Administration approved oral drug candidate developed by ARIAD Pharmaceuticals for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). It is a multi-targeted tyrosine-kinase inhibitor.[1] Some forms of CML, those that have the T315I mutation, are resistant to current therapies such as imatinib. Ponatinib has been designed to be effective against these types of tumors.[2]
Oncologists have complained, however, that many patients can not afford the "astronomical" cost of $138,000 a year, which makes it one of the most expensive drugs in medicine, and far more expensive than what is needed to pay the development costs.[3][4] WIKIPIDIA
THE THROMBOTIC COMPLICATION WAS NOT NEW HOWEVER, IT IS UNCLEAR WHY THE FDA MOVED TO ORDER ARIAD TO STOP THE PRODUCTION.
"The United States Food and Drug Administration issued a partial clinical hold on new trial enrollment for Iclusig on 9 October 2013 due to an increased number of blood clots observed in patients taking the drug.[6] The EPIC trial was later cancelled on 18 October.[7]"WIKIPEDIA
NOW THE STOP ORDER IS IN EFFECT REPORTEDLY!
Thursday, October 31, 2013
CPRIT: GET INVOLVED ! IT'S TOMORROW! Be there...
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The CPRIT Oversight Committee meeting this Friday, November 1, 2013 will be broadcast live online. To access the livestream of the meeting, please click here.
Please note, to view the broadcast, you will need to have the basic RealPlayer installed, which can be downloaded for free from: http://www.real.com/
The meeting agenda and supporting materials are available on the CPRIT website.
Please note, to view the broadcast, you will need to have the basic RealPlayer installed, which can be downloaded for free from: http://www.real.com/
The meeting agenda and supporting materials are available on the CPRIT website.
CPRIT Oversight Committee Meeting
Texas State Capitol Extension
1400 N. Congress Avenue, Austin, Texas 78701
Room: E1.012
November 1, 2013
9:00 A.M.
Texas State Capitol Extension
1400 N. Congress Avenue, Austin, Texas 78701
Room: E1.012
November 1, 2013
9:00 A.M.
ADAPTER GENES
Nothing is simple but yet as determinant as an Adapter gene.
The cell continues to amaze scientists.
When a stimulant attaches to a receptor, the 2, stimulant and receptor, enter the cell in some cases, detaching from the membrane and enter the cell. Most of the time there is a triggering of main pathways such as the RAS, but sometimes, at the site of attachment, the raw edges of the membrane are not healing and wage their own war...here it is the focal Adhesion kinases that are going to war. Now, that war is not necessarily random. Depending on the nature of the stimulant and receptor involved, the FAK can turn to a Gerb2, Lyn or Flyn with a totally new orientation in the metabolism of the cell. Sometimes the adapter is simply a b-cell linker or it is a T-cell linker and the cell will follow that path or attract these different cells. It may use RUS1 to block the excited RAS that we spoke about or orient the cell to Rho in order to exacerbate metastasis.
These linkers are a way to control differentiation, but when erratic, they could compromise the host! Certain genes are destined to help many proteins such as a portion of an Antibody, imagine them wrongly linked to some other gene leading to unwarranted multiplication! Things are set for hematologic malignancies!
Preliminary impression:
- Attachment to Lyn- B cell differentiation (some) and if Gerb2 involved, T cell differentiation definitely if the stimulant is TGF alpha!
Flyn- well may be muscle dystrophy, of some form.
Attachment to TBS - mental retardation
Lck-depression such as seen with chronic autoimmune disease (locus Coereleus)
Watch your Adaptor genes carefully! Otherwise things are going in a direction you may not wish!
The cell continues to amaze scientists.
When a stimulant attaches to a receptor, the 2, stimulant and receptor, enter the cell in some cases, detaching from the membrane and enter the cell. Most of the time there is a triggering of main pathways such as the RAS, but sometimes, at the site of attachment, the raw edges of the membrane are not healing and wage their own war...here it is the focal Adhesion kinases that are going to war. Now, that war is not necessarily random. Depending on the nature of the stimulant and receptor involved, the FAK can turn to a Gerb2, Lyn or Flyn with a totally new orientation in the metabolism of the cell. Sometimes the adapter is simply a b-cell linker or it is a T-cell linker and the cell will follow that path or attract these different cells. It may use RUS1 to block the excited RAS that we spoke about or orient the cell to Rho in order to exacerbate metastasis.
These linkers are a way to control differentiation, but when erratic, they could compromise the host! Certain genes are destined to help many proteins such as a portion of an Antibody, imagine them wrongly linked to some other gene leading to unwarranted multiplication! Things are set for hematologic malignancies!
Preliminary impression:
- Attachment to Lyn- B cell differentiation (some) and if Gerb2 involved, T cell differentiation definitely if the stimulant is TGF alpha!
Flyn- well may be muscle dystrophy, of some form.
Attachment to TBS - mental retardation
Lck-depression such as seen with chronic autoimmune disease (locus Coereleus)
Watch your Adaptor genes carefully! Otherwise things are going in a direction you may not wish!
Wednesday, October 30, 2013
IN A BIG ANNOUNCEMENT TODAY: CPRIT IS FREE AGAIN! CONGRATULATIONS!
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Genetic basis of Autism
The notion that an inflammatory process such as the one induced by an immunization may contribute to children's mental retardation or Autism has fundamental truth when it comes to gene pathways. Indeed, during an acute inflammatory insult, Macrophages that are called to the theater will liberate several cytokines which include TGF alpha. This cytokine will bind to EGFR receptors while other cytokines induced by the inflammatory process will bind their relevant receptors. Internalization of these receptors will leave deep edges at the membrane, activating the Focal adhesion molecules of Kinase (FAK ). The first known gene to react with the FAK gene is the Tuberous sclerosis gene which is known to lead to Autism. In a forming or developing brain, certain isoforms of this gene may predispose some children to develop autism. The crux of the problem is to determine which inflammatory process (immunization or other processes) is at the source of the problem!
PTK2 protein tyrosine kinase 2 (PTK2), also known as Focal Adhesion Kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene.[2] PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to each other and their surroundings) and spreading processes (how cells move around).[3] It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility.[4]
PTK2 has been shown to interact with TSC2, (22 wikipedia)
Tuberin also known as tuberous sclerosis 2 is a protein that in humans is encoded by the TSC2 gene.
About 50% of people with TSC have learning difficulties ranging from mild to significant,[2] and studies have reported that between 25% and 61% of affected individuals meet the diagnostic criteria for autism, with an even higher proportion showing features of a broader pervasive developmental disorder.[3] A 2008 study reported self-injurious behavior in 10% of people with TSC.[4] Other conditions, such as ADHD, aggression, behavioral outbursts and OCD (obsessive compulsive disorder) can also occur. Lower IQ is associated with more brain involvement on MRI.(wikipedia)
====================================================
THERE YOU HAVE IT THE FULL STORY!
PTK2 protein tyrosine kinase 2 (PTK2), also known as Focal Adhesion Kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene.[2] PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to each other and their surroundings) and spreading processes (how cells move around).[3] It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility.[4]
PTK2 has been shown to interact with TSC2, (22 wikipedia)
Tuberin also known as tuberous sclerosis 2 is a protein that in humans is encoded by the TSC2 gene.
About 50% of people with TSC have learning difficulties ranging from mild to significant,[2] and studies have reported that between 25% and 61% of affected individuals meet the diagnostic criteria for autism, with an even higher proportion showing features of a broader pervasive developmental disorder.[3] A 2008 study reported self-injurious behavior in 10% of people with TSC.[4] Other conditions, such as ADHD, aggression, behavioral outbursts and OCD (obsessive compulsive disorder) can also occur. Lower IQ is associated with more brain involvement on MRI.(wikipedia)
====================================================
THERE YOU HAVE IT THE FULL STORY!
Tuesday, October 29, 2013
Progress in Genome studies: case in point the DIGITAL PCR.
If what they promise is real, we are entering an important phase where not only we can count mutations, but can also try to determine levels of gene amplifications that are secondary, versus those that are in response or a consequence of upstream genes normally amplified or amplified because they are mutated!
" Next-generation sequencing technology has transformed cancer genomics, but faces the challenge of genome and transcriptome heterogeneity inherent to any tumor sample. One strategy for capturing the complex landscape of mutational processes, clonal evolution/amplification and tissue invasion is the application of digital PCR, which enables the identification and precise quantitation of individual mutations - including those present at a very low frequency."(Biomedcentral)
This new technology will open new evaluations of gene quantities as to their meaning and trigger! It will allow also to detect levels of suppression of a normal gene when it is found in an unexpected amount. We know for example that in many lung cancers PTEN is suppressed. Whether this is a primary happening or secondary can be further debated. In Ovarian cancer DAB2 is suppressed. ("The down-regulation of DAB2 may play an important role in ovarian carcinogenesis. This gene was initially named DOC2 (for Differentially expressed in Ovarian Cancer) and is distinct from the DOC2A and DOC2B genes (for double C2-like domains, alpha and beta).[3]
Most of these suppressions are the result of an amplification of an upstream gene or an overexpression of an inhibitory protein. When it comes to DAB2, it is important to report that this gives the cancerous process some teeth and bad prognosis. Indeed, the suppression of DOC2 gives the tumor ways of escaping proliferation control by the cancerous cell by activating E3 (removing by unbiquitilation of the inhibitor of the inhibitor of E3). This new technology will allow direct quantification of the 2 inhibitors or the E3 for that matter. It may also clarify how Velcade works in relation to the 3 compounds!
" Next-generation sequencing technology has transformed cancer genomics, but faces the challenge of genome and transcriptome heterogeneity inherent to any tumor sample. One strategy for capturing the complex landscape of mutational processes, clonal evolution/amplification and tissue invasion is the application of digital PCR, which enables the identification and precise quantitation of individual mutations - including those present at a very low frequency."(Biomedcentral)
This new technology will open new evaluations of gene quantities as to their meaning and trigger! It will allow also to detect levels of suppression of a normal gene when it is found in an unexpected amount. We know for example that in many lung cancers PTEN is suppressed. Whether this is a primary happening or secondary can be further debated. In Ovarian cancer DAB2 is suppressed. ("The down-regulation of DAB2 may play an important role in ovarian carcinogenesis. This gene was initially named DOC2 (for Differentially expressed in Ovarian Cancer) and is distinct from the DOC2A and DOC2B genes (for double C2-like domains, alpha and beta).[3]
Most of these suppressions are the result of an amplification of an upstream gene or an overexpression of an inhibitory protein. When it comes to DAB2, it is important to report that this gives the cancerous process some teeth and bad prognosis. Indeed, the suppression of DOC2 gives the tumor ways of escaping proliferation control by the cancerous cell by activating E3 (removing by unbiquitilation of the inhibitor of the inhibitor of E3). This new technology will allow direct quantification of the 2 inhibitors or the E3 for that matter. It may also clarify how Velcade works in relation to the 3 compounds!
Monday, October 28, 2013
COLLABORATION AT CRBCM
A STRONG COLLABORATION BEING BUILT AT CRBCM
KEY MEETING THIS FRIDAY AT UTEP AND TEXAS TECH!
KEY MEETING THIS FRIDAY AT UTEP AND TEXAS TECH!
That is great!
I
can reserve a small conference room (Bioscience Building Room 3.118) at
UTEP. Would you like to give a brief presentation for your current
project? If so,
I can also prepare a laptop computer and projector.
The core of Autoimmune diseases?
TGF alpha WITH ITS CONNECTION TO HLA-DR1 Vs. MIF,
the alpha 4 Beta Integrin WITH THE VASCULITIS!
E3 AND ITS INHIBITORS and the CXCR4 GENES
THAT IS IN THE CORE OF THE BELLY OF THE BEAST!
DO YOU NEED A FULL TEXT, CALL ME,
WANT MORE, HOW ABOUT NCK1? POWERFUL TARGET IN LEUKEMIA!
GO FIGURE!
STILL DON'T BELIEVE
THIS IS THE SUPPORTIVE EVIDENCE
the alpha 4 Beta Integrin WITH THE VASCULITIS!
E3 AND ITS INHIBITORS and the CXCR4 GENES
THAT IS IN THE CORE OF THE BELLY OF THE BEAST!
DO YOU NEED A FULL TEXT, CALL ME,
WANT MORE, HOW ABOUT NCK1? POWERFUL TARGET IN LEUKEMIA!
GO FIGURE!
STILL DON'T BELIEVE
THIS IS THE SUPPORTIVE EVIDENCE
Lupus. 2007;16(8):587-92.
Macrophage activation syndrome in juvenile systemic lupus erythematosus: an under-recognized complication?
Source
Istituto di Ricovero e Cura a Carattere Scientifico Giannina Gaslini, Genova, Italy, Hospital Pedro de Elizalde, Buenos Aires, Argentina.Abstract
Macrophage
activation syndrome (MAS) is a life-threatening complication of
rheumatic diseases that is thought to be caused by the activation and
uncontrolled proliferation of T lymphocytes and macrophages, leading to
widespread haemophagocytosis and cytokine overproduction. It is seen
most commonly in systemic juvenile idiopathic arthritis, but is
increasingly recognized also in juvenile systemic lupus erythematosus
(J-SLE). Recognition of MAS in patients with J-SLE is often challenging
because it may mimic the clinical features of the underlying disease or
be confused with an infectious complication. This review summarizes the
characteristics of patients with J-SLE-associated MAS reported in the
literature or seen by the authors and analyses the distinctive clinical,
diagnostic and therapeutic issues that the occurrence of MAS may raise
in patients with J-SLE.
Sunday, October 27, 2013
WE WENT AND SAW IT!
IT IS THE SAME GAME OVER
WE PLAYED OUR ROLE WHICH IS TO MAKE US PART OF STATISTICS
BUT ONE THING FOR SURE WE HAVE MADE CONTACTS
BUT WE GOT TO BE MOVING FORWARD DESPITE THEM!
FOR THE FIGHT AGAINST THE CURE IS ABOVE POLITICAL GAMES
WILL LOOK TO FOREIGN COUNTRIES FOR HELP IF NEEDED
BECAUSE THERE, LOCAL POLITICS WILL NOT WEIGH IN
ALL WE CARE ABOUT IS KEEPING THE ENGINES WORKING,
THE FIRST SYMPOSIUM LOOKED LIKE OLD DANCE
'CAUSE WE HAVE SEEN IT BEFORE!
WE PLAYED OUR ROLE WHICH IS TO MAKE US PART OF STATISTICS
BUT ONE THING FOR SURE WE HAVE MADE CONTACTS
BUT WE GOT TO BE MOVING FORWARD DESPITE THEM!
FOR THE FIGHT AGAINST THE CURE IS ABOVE POLITICAL GAMES
WILL LOOK TO FOREIGN COUNTRIES FOR HELP IF NEEDED
BECAUSE THERE, LOCAL POLITICS WILL NOT WEIGH IN
ALL WE CARE ABOUT IS KEEPING THE ENGINES WORKING,
THE FIRST SYMPOSIUM LOOKED LIKE OLD DANCE
'CAUSE WE HAVE SEEN IT BEFORE!
Saturday, October 26, 2013
A NEW PLAYER IN TOWN: THE MEDICAL CENTER OF THE AMERICAS.
We are pleased that El Paso can now claim a chance to shine in the area of Biomedical research with the Medical Center of the Americas (MCA). We don't need to deal only with the stress of ignorance by CPRIT and the lack of interest by the Texan central government. By the same token, the new shining star (Medical Center of the Americas, with 60 Millions dollars in its war chest ( less than 3 billions being squandered by CPRIT) is in danger of experiencing the same fate as CPRIT- a global takeover by local Universities!
In this town, the drama will unfold just the same unless the leadership shin up and brace from the onslaught which will come from Lubbock the small town that engineered years ago El Paso takeover through Texas Tech University! Already we are seeing the take over unfold by the prominence of Texas Tech into the activities of the CMAs. It is surprising that to this day the University of of Texas in El Paso (UTEP) the true local El Paso school has not rise up, as if accepting this dedicated secondary role, as if already prepared to let the takeover unfold! There is no representative for the private corporations on the MCAs' Board as far as I can tell. And very soon by the 3rd year of life of the MCAs, the CPRIT story will be lived at El Paso scale! Unless of course the leardership wakes up early and strategizes a response for prevention! I met the President of the fundation Ms. Shwartz, she was first to mention the CPRIT story but I am not sure she did realize where the threat to CPRIT came from, Universities' takeover! Universities in Texas have shown to have the brightest minds but also by being the most expensive and wasteful organizations. Record suggest that only 15-20 percent of money given to them goes to actual research. The only thing that can change this, the MCA dictates during contract negotiations and follow-ups...
Believe me, when you are the donor, you can stand your ground in defining the rules of engagement. WILL MCAs STAND ITS GROUND? WE HAVE YET TO SEE IT!
THE CRBCM CAN HELP, WE WILL CONTINUE THE FIGHT FOR THE CURE UNTIL OUR ENEMIES BECOME IRRELEVANT!
In this town, the drama will unfold just the same unless the leadership shin up and brace from the onslaught which will come from Lubbock the small town that engineered years ago El Paso takeover through Texas Tech University! Already we are seeing the take over unfold by the prominence of Texas Tech into the activities of the CMAs. It is surprising that to this day the University of of Texas in El Paso (UTEP) the true local El Paso school has not rise up, as if accepting this dedicated secondary role, as if already prepared to let the takeover unfold! There is no representative for the private corporations on the MCAs' Board as far as I can tell. And very soon by the 3rd year of life of the MCAs, the CPRIT story will be lived at El Paso scale! Unless of course the leardership wakes up early and strategizes a response for prevention! I met the President of the fundation Ms. Shwartz, she was first to mention the CPRIT story but I am not sure she did realize where the threat to CPRIT came from, Universities' takeover! Universities in Texas have shown to have the brightest minds but also by being the most expensive and wasteful organizations. Record suggest that only 15-20 percent of money given to them goes to actual research. The only thing that can change this, the MCA dictates during contract negotiations and follow-ups...
Believe me, when you are the donor, you can stand your ground in defining the rules of engagement. WILL MCAs STAND ITS GROUND? WE HAVE YET TO SEE IT!
THE CRBCM CAN HELP, WE WILL CONTINUE THE FIGHT FOR THE CURE UNTIL OUR ENEMIES BECOME IRRELEVANT!
Thursday, October 24, 2013
BY COMMUNITY ONCOLOGIST, THE CRBCM IS CLEARLY NOT INCLUDED! THEY KNOW WHO THEY MEAN!
Community Oncologist Education and Support Systems ‐
Renal Cell Carcinoma and Hematologic Malignancies
Request for Proposals
National Comprehensive Cancer Network and
Pfizer Independent Grants for Learning & Change
Pfizer
and National Comprehensive Cancer Network (NCCN) are collaborating
to offer a new grant opportunity focused on improving care for patients with rare types of cancer such as renal cell carcinoma (RCC) and certain hematologic malignancies, where treatment options are complex and rapidly advancing.
The
mission of Pfizer Independent Grants for Learning & Change
(IGL&C) is
to accelerate the adoption of evidence‐based innovations that align the mutual interests of patients, healthcare professionals, and Pfizer, through support of independent professional education activities. The term “independent” means the initiatives funded by Pfizer are the full responsibility of the recipient organization. Pfizer has no influence over any aspect of the initiatives, and only asks for reports about the results and impact of the initiatives, which it may share publicly.
NCCN,
a not‐for‐profit alliance of twenty‐three (23) of the world’s leading
cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. NCCN has access, through its member institutions, to the world’s leading thought leaders in all areas and aspects of oncology who are integral to the execution of this program.
This
Request for Proposals (RFP) is being issued by both organizations. NCCN
is
the lead organization for review and evaluation of applications. A review committee, led by NCCN, will make decisions on which proposals will receive funding. Grant funding will be provided by Pfizer. Collectively, up to $2 million is available for the program.
Once announced through this distribution list, the RFP
will also be
posted on our website at www.pfizer.com/ refer to the full text of the RFP for various key dates and submission instructions.
Please send an email to
IGLC@pfizer.com to unsubscribe from this distribution.
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Bubbling with excitements!
A Message from Medical Center of the Americas:
Dear BIOMED Registrants:
We look forward to seeing you at the region’s upcoming BIOMED Symposium on October 26, 2013
at the Camino Real Hotel located at 101 South El Paso Street in
Downtown El Paso. And, we are excited to announce that we have surpassed
our original registration expectation of 150 participants; we are now
expecting approximately 350 participants! Thank you for already helping
to make this event a success through great participation! We do want to
note, however, that this unexpected level of participation may result in
a few logistical problems at the events. Furthermore, we will be
experimenting with different types of sessions and events to determine
what works best. We request that you be patient with us as we work hard
to make this first year event successful. We will have evaluation forms
available and hope that you provide honest feedback to so that we can
improve the
event in future years.
Below
are a few reminders and updates regarding the Symposium that should
help to make things run smoothly over the next couple of days.
OCTOBER 25, 2013: PRE-SYMPOSIUM NETWORKING MIXER INFORMATION
OCTOBER 25, 2013: PRE-SYMPOSIUM NETWORKING MIXER INFORMATION
We hope you will consider attending BIOMED’s Pre-Symposium Networking Mixer on October 25, 2013 from 5:30pm-7:30pm at the El Paso Club, 18th floor, Chase Building, 201 East Main Drive, Downtown El Paso.
Network with over 200 of the region’s researchers, clinicians and
nurses, future leaders and other healthcare professionals. Valet parking
is available in the Chase Building garage, accessible via Mesa Street.
Simply bring your parking ticket to the El Paso Club for validation. Please RSVP to nsehgal@bmiamericas.org by 5 pm on Thursday, October 24, 2013.
OCTOBER 26: 2013: BIOMED SYMPOSIUM INFORMATION
Symposium Registration
Check-In Table
If you have pre-registered, please come to the Check-In Table on the Mezzanine (2nd Floor). Do not forget to bring your ticket and a form of identification. We will be providing a complimentary drink ticket to the first 180 people for the Collaboration Grant and Networking Reception from 3:30pm-4:30pm in the Ballroom.
Check-In Table
If you have pre-registered, please come to the Check-In Table on the Mezzanine (2nd Floor). Do not forget to bring your ticket and a form of identification. We will be providing a complimentary drink ticket to the first 180 people for the Collaboration Grant and Networking Reception from 3:30pm-4:30pm in the Ballroom.
Media & VIP Table
If you are affiliated with the Press, please collect your “Press Pass” from the Media & VIP Table on the Mezzanine (2nd Floor).
If you are affiliated with the Press, please collect your “Press Pass” from the Media & VIP Table on the Mezzanine (2nd Floor).
If you are a VIP
(speakers, exhibitors, moderators, judges, elected officials, head of
institutions, volunteers, and BMIA or MCA board members), please
check-in at the Media & VIP Table on the Mezzanine (2nd Floor).
**Please remember that this is a networking event, so bring lots of your business cards to trade with new contacts you make.
Hotel AccommodationsWe have reserved a block of rooms at the Camino Real Hotel located at 101 South El Paso Street and DoubleTree Hotel located at 600 North El Paso Street in Downtown El Paso at a discounted rate. Please make hotel reservations as soon as possible, as we anticipate the hotels will up fast. When you call to make a reservation, please indicate to the hotel clerk that you are making a reservation for the “BIOMED Symposium” so that you receive the discounted rate.
Symposium Parking & Directions
Parking
JUST GO AHEAD AND HELP OUT FOLKS (PHYSICIANS)!
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October 16, 2013
Dear Indiana Licensed Controlled Substance Prescribers and Dispensers,
On
behalf of the Indiana Professional Licensing Agency, the Indiana State
Department of Health, and the Attorney General’s Prescription Drug Abuse
Prevention Task Force, we request your assistance in achieving our
mutual goals to address the increasing problem of prescription drug
addiction in Indiana.
The
survey is completely anonymous, and we will have no ability to track
participants’ identities. The instrument will take approximately 10-15
minutes to complete.
The
survey was created in collaboration with the Indiana Professional
Licensing Agency, the Center for Health Policy, the Indiana State
Department of Health, and the Attorney General’s Prescription Drug Abuse
Prevention Task Force.
The
survey is being administered through the Center for Health Policy at
the IU Richard M. Fairbanks School of Public Health at IUPUI.
The
Center for Health Policy will be solely responsible for analyzing the
data and preparing a public report that summarizes the findings from
this research. The final report will be distributed electronically and
be available on the Center’s website: www.healthpolicy.iupui.edu in early 2014. Their report will be used to improve the INSPECT program and provide better support to healthcare providers.
Please click on the link below for additional details and to begin the survey.
Thank you in advance for your vital assistance with this endeavor!
Sincerely,
Greg Pachmayr
INSPECT Director Indiana Professional Licensing Agency 402 W Washington St RM W072 Indianapolis, IN 46204 |
A very important read!
Arkadia Activates Smad3/Smad4-Dependent Transcription by Triggering Signal-Induced SnoN Degradation▿†
- Laurence Levy1,
- Michael Howell1,
- Debipriya Das1,
- Sean Harkin1,
- Vasso Episkopou2 and
- Caroline S. Hill1,*
+ Author Affiliations
ABSTRACT
E3 ubiquitin ligases play important roles
in regulating transforming growth factor β (TGF-β)/Smad signaling.
Screening of
an E3 ubiquitin ligase small interfering RNA
library, using TGF-β induction of a Smad3/Smad4-dependent luciferase
reporter
as a readout, revealed that Arkadia is an E3
ubiquitin ligase that is absolutely required for this TGF-β response.
Knockdown
of Arkadia or overexpression of a dominant-negative
mutant completely abolishes transcription from Smad3/Smad4-dependent
reporters,
but not from Smad1/Smad4-dependent reporters or
from reporters driven by Smad2/Smad4/FoxH1 complexes. We show that
Arkadia
specifically activates transcription via
Smad3/Smad4 binding sites by inducing degradation of the transcriptional
repressor
SnoN. Arkadia is essential for TGF-β-induced SnoN
degradation, but it has little effect on SnoN levels in the absence of
signal.
Arkadia interacts with SnoN and induces its
ubiquitination irrespective of TGF-β/Activin signaling, but SnoN is
efficiently
degraded only when it forms a complex with both
Arkadia and phosphorylated Smad2 or Smad3. Finally, we describe an
esophageal
cancer cell line (SEG-1) that we show has lost
Arkadia expression and is deficient for SnoN degradation. Reintroduction
of
wild-type Arkadia restores TGF-β-induced
Smad3/Smad4-dependent transcription and SnoN degradation in these cells,
raising
the possibility that loss of Arkadia function may
be relevant in cancer.
=================================================================
This is very important because,
1. we are not very good at activating genes, so this is one important way. (all we do is inhibit genes and their protein derivative-that we know!)
2. cancer decreases SMAD to induce lack of proliferation control (through CDK1 for SMAD3 suppression) and disturbance of Ubiquitilation (E3 for SMAD3). Increasing SMAD is taking away cancer "aggressiveness" a new modality of treatment!! very closely followed at CRBCM- This is to be proposed in Metastatic prone diseases such as triple negative breast cancer, pancreatic cancer and few others!
Disruption (suppression) at SMADs is a major biomarker of bad Prostate cancers!!!
=================================================================
This is very important because,
1. we are not very good at activating genes, so this is one important way. (all we do is inhibit genes and their protein derivative-that we know!)
2. cancer decreases SMAD to induce lack of proliferation control (through CDK1 for SMAD3 suppression) and disturbance of Ubiquitilation (E3 for SMAD3). Increasing SMAD is taking away cancer "aggressiveness" a new modality of treatment!! very closely followed at CRBCM- This is to be proposed in Metastatic prone diseases such as triple negative breast cancer, pancreatic cancer and few others!
Disruption (suppression) at SMADs is a major biomarker of bad Prostate cancers!!!
A dangerous gene PTPRT (PTPrho)
If you follow our blogs, you will be aware of 3 things about why a gene could be dangerous,
1. Its ability to induce malformation once absent
2. Its interaction with either multiple other genes but particularly its involvement with a "wild gene", genes that are cofactors to anything happening in the cell (Gerb2,FYN) or globally a gene that have just too many interactions with other genes (Androgen related gene).
3.In terms of cancer metastasis and non-curability, the gene involvement with the Wnt (cathenin) and the Notch. Involvement with the Rho increases the rate of multiplication.
Based on these criteria, PTPRT (PTPrho) wins the cake!
It is stimulated by Actinin alpha 1
which itself interacts with:
Actinin, alpha 1 has been shown to interact with:
Receptor-type tyrosine-protein phosphatase T is an enzyme that in humans is encoded by the PTPRT gene.[1][2][3]
PTPRT is also known as PTPrho, PTPρ and human accelerated region 9. The human accelerated regions are 49 regions of the human genome that are conserved among vertebrates, but in humans show significant distinction from other vertebrates. This region may, therefore, have played a key role in differentiating humans from apes.[4]
PTPrho is phosphorylated on tyrosine 912 in the wedge region of its first catalytic domain by Fyn tyrosine kinase. Phosphorylation at this site attenuates synapse formation in cultured neurons. When PTPrho is phosphorylated by Fyn, PTPrho appears to form homophilic multimerizations, likely in cis, which appear to decrease PTPrho association with neuroligins and neurexins. The reduction of cis interactions with neuroligins and neurexons is hypothesized to ultimately lead to the reduction in synapse formation.[12]
Evaluation of the 5’untranslated regions of PTPrho (PTPRT) cDNA indicate a number of transcription factor binding site consensus sequences, including those for AP-2, c-Myb, NF-1, sox-5, and Sp-1, Oct-1, CdxA, C/EBP, En-1, GATA-1, GATA-2, GKLF, HoxA3, Ik-2, Msx-1, Pax-4 and SRY.[5]
(RE1-silencing transcription factor) (REST) is a transcription repressor that binds to REST DNA recognition element (RE-1) in 5’UTRs. A screen of single nucleotide polymorphic genetic changes within the REST binding regions of DNA sequences revealed a polymorphism in the RE-1 of PTPrho (PTPRT). This SNP would result in less REST repressor activity, which could lead to increased expression of PTPrho (PTPRT) in cells that harbored this SNP.[15]
PTPrho is also upregulated in estrogen receptor alpha positive breast tumor samples versus estrogen receptor alpha negative tumor samples.[18] The authors evaluated 560 selected genes by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) in estrogen receptor alpha positive tissue and compared it to estrogen receptor alpha negative tissue, and found that PTPrho(PTPRT) was upregulated in the estrogen receptor alpha tissue, suggesting a non-tumor suppressor role for PTPrho. [18]"
1. Its ability to induce malformation once absent
2. Its interaction with either multiple other genes but particularly its involvement with a "wild gene", genes that are cofactors to anything happening in the cell (Gerb2,FYN) or globally a gene that have just too many interactions with other genes (Androgen related gene).
3.In terms of cancer metastasis and non-curability, the gene involvement with the Wnt (cathenin) and the Notch. Involvement with the Rho increases the rate of multiplication.
Based on these criteria, PTPRT (PTPrho) wins the cake!
It is stimulated by Actinin alpha 1
which itself interacts with:
Actinin, alpha 1 has been shown to interact with:
- CDK5R1,[3]
- CDK5R2,[3]
- Collagen, type XVII, alpha 1,[4]
- GIPC1,[5]
- PDLIM1,[6][7]
- Protein kinase N1,[8]
- SSX2IP,[9] and
- Zyxin.[10][11]
- PTPRT(PTPrho)[12] wikipedia
- The involvement with GIPC1 needs to be noted! because it provide the link to DAB2, a gene suppressed in Ovarian cancers! GIPC1 reaches DAB2 through MYO-6.
- well Actinin
Receptor-type tyrosine-protein phosphatase T is an enzyme that in humans is encoded by the PTPRT gene.[1][2][3]
PTPRT is also known as PTPrho, PTPρ and human accelerated region 9. The human accelerated regions are 49 regions of the human genome that are conserved among vertebrates, but in humans show significant distinction from other vertebrates. This region may, therefore, have played a key role in differentiating humans from apes.[4]
PTPrho is phosphorylated on tyrosine 912 in the wedge region of its first catalytic domain by Fyn tyrosine kinase. Phosphorylation at this site attenuates synapse formation in cultured neurons. When PTPrho is phosphorylated by Fyn, PTPrho appears to form homophilic multimerizations, likely in cis, which appear to decrease PTPrho association with neuroligins and neurexins. The reduction of cis interactions with neuroligins and neurexons is hypothesized to ultimately lead to the reduction in synapse formation.[12]
Evaluation of the 5’untranslated regions of PTPrho (PTPRT) cDNA indicate a number of transcription factor binding site consensus sequences, including those for AP-2, c-Myb, NF-1, sox-5, and Sp-1, Oct-1, CdxA, C/EBP, En-1, GATA-1, GATA-2, GKLF, HoxA3, Ik-2, Msx-1, Pax-4 and SRY.[5]
(RE1-silencing transcription factor) (REST) is a transcription repressor that binds to REST DNA recognition element (RE-1) in 5’UTRs. A screen of single nucleotide polymorphic genetic changes within the REST binding regions of DNA sequences revealed a polymorphism in the RE-1 of PTPrho (PTPRT). This SNP would result in less REST repressor activity, which could lead to increased expression of PTPrho (PTPRT) in cells that harbored this SNP.[15]
PTPrho is also upregulated in estrogen receptor alpha positive breast tumor samples versus estrogen receptor alpha negative tumor samples.[18] The authors evaluated 560 selected genes by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) in estrogen receptor alpha positive tissue and compared it to estrogen receptor alpha negative tissue, and found that PTPrho(PTPRT) was upregulated in the estrogen receptor alpha tissue, suggesting a non-tumor suppressor role for PTPrho. [18]"
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