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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: Adopting new bylaws for how the Oversight Committee will operate as a governing body, including an updated code of conduct. These bylaws indicate the Oversight Committee commitment to operating with the highest level of integrity; Posting revised administrative rules to the Texas Register for public comment. The rules expanded from 40 to over 120 pages, and implement many of the State Auditor’s recommendations as well as other process and accountability improvements; Restarting our grantmaking process, including the approval of Scientific Review Council appointees. This action allows CPRIT to resume review of grants and enable healthcare and medical professionals to apply for new grants. We expect additional steps at the next Oversight Committee meeting scheduled for November 22, 2013. At that session, I anticipate discussion about research and prevention program priorities, and a number of other actions important to our continuing operations. I want to express my gratitude to the members of the 83rd Legislature and their staffs, state leadership offices and CPRIT staff for getting us to November 1. The new Oversight Committee came to the meeting well-prepared and eager to resume the important responsibilities assigned to CPRIT by the citizens of Texas. 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!

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.

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?

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 ....

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.<sup>[3][4] WIKIPIDIA

THE THROMBOTIC COMPLICATION WAS NOT NEW HOWEVER, IT IS UNCLEAR WHY THE FDA MOVED TO ORDER ARIAD TO STOP THE PRODUCTION.</sup>  


"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!

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/realplayer/player-plus

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.

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!

IN A BIG ANNOUNCEMENT TODAY: CPRIT IS FREE AGAIN! CONGRATULATIONS!

Cancer Prevention and Research Institute of Texas via mail185.atl21.rsgsv.net	2:24 PM (16 hours ago)
to me

Email not displaying correctly? View it in your browser. CPRIT has been notified by Governor Perry, Lt. Governor Dewhurst and Speaker Straus that the moratorium   on CPRIT’s grant award processes has been lifted. Over the last ten months CPRIT has taken purposeful strides to strengthen agency governance and restore trust in its commitment to the fight against  cancer in Texas. CPRIT appreciates the confidence state leadership has in the agency’s efforts – this action marks a critical milestone for CPRIT. We have been working hard in preparation  for this moment and are ready to move forward with deliberate purpose, accountability and transparency to  serve all Texans. Staff will contact CPRIT grantees affected by the moratorium to provide additional information and next steps  per this announcement. On November 1,  2013, the CPRIT Oversight Committee  will discuss restarting all of CPRIT’s review processes including resuming review of applications that have been submitted and the release of new requests for applications.

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!

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!

COLLABORATION AT CRBCM

A STRONG COLLABORATION BEING BUILT AT CRBCM
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

Lupus. 2007;16(8):587-92.

Macrophage activation syndrome in juvenile systemic lupus erythematosus: an under-recognized complication?

Pringe A, Trail L, Ruperto N, Buoncompagni A, Loy A, Breda L, Martini A, Ravelli A.

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.

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!

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!

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/independentgrants  Please  refer to the full text of the RFP for various key dates and submission  instructions. Clinical Areas: Category 1: Oncology Communities – RCC Category 2: Oncology Communities –  Hematologic Malignancies LOI Due Date: December 5, 2013 Please send an email to IGLC@pfizer.com to unsubscribe from this distribution.

RFP Community Oncologist Education and Support Systems.pdf 205K   View   Download

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

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, 18^th 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 (2^nd 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 (2^nd 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 (2^nd Floor).

**Please remember that this is a networking event, so bring lots of your business cards to trade with new contacts you make.

Hotel Accommodations
We 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)!

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. http://www.healthpolicy.iupui.edu/checkbox/INSPECT.aspx  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▿†

1. Laurence Levy1,
2. Michael Howell1,
3. Debipriya Das1,
4. Sean Harkin1,
5. Vasso Episkopou2 and
6. Caroline S. Hill1,*

+ Author Affiliations

1. ¹Laboratory of Developmental Signalling, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom
2. ²Mammalian Neurogenesis, MRC Clinical Sciences Centre, Imperial School of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom

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!!!

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:

• 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}

 ===================================================FROM WIKIPEDIA, THIS FOLLOW:"
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]"

SOME MOVEMENTS FROM CPRIT

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CPRIT OVERSIGHT COMMITTEE MEETING   Notice of Open Meeting Texas State Capitol Extension 1400 N. Congress Avenue, Austin, Texas 78701 Room: E1.012 November 1, 2013 9:00 A.M. Agenda   For more information, please call: (512) 463-3190   Please forward this announcement to your networks.

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our movie project moving forward!

Hi kanko1,

The project you are following "A WHITE WOMAN TO THE CONGO" has reached level 4! Click on the following link to view the latest update of the project now!
http://juntoboxfilms.com/projects/a-white-woman-to-the-congo

join us at the BIOMED RESEARCH CONFERENCE /MEDICAL CENTER OF THE AMERICAS/CRBCM WILL BE PRESENT!

A Message from Medical Center of the Americas:

Dear BIOMED Registrants:

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, 18^th 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. 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.

Sincerely,

Neyha Sehgal
BIOMED Organizer

Imperfection of current tools for genetic evaluations

It is quite evident that despite major advances in genetic studies through the PCR and other sequencing measures, the evaluation of genes and their effects still require highly qualified technicians using sophisticated equipments. One of the implications of this fact is that when one wants to try to look into any scientific fact, a battery of scientists need to be mobilized!

For example, we know that when patients are exposed to a new medication (ie. chemotherapy drug), some patient will have inherent resistance to the drug.  That is they are promptly rejecting the drug, while other will respond first and then develop mechanisms of resistance.  To date, they are no ways of determining which patient is doing what when exposed to the drug!  And this despite our advances in technology.

Our current practice is to give the drug, and wait 3-6 months and check through radiologic and biomarker means  if the tumor grow despite the drug.  During the 3 to 6 months, refractory tumors have time to build in new genetic mutations giving them new mechanisms of escape, defense and otherwise eluding future attacks, and most importantly metastasize to new sites in the host, complicating our battle and making full eradication impossible and dooming our chance for a cure!  Indeed with tumors of "aggressive" tendencies, 6 months is a lifetime of opportunities to settle in and impose a toll of reversible and irreversible disruptions into the host!
This strategy is not good for us.

This is happening despite our knowledge of many facts that could help us avoid this current practice. we know already many pathways and mechanisms of resistance (ie. the MDR gene) but we don't use them for our relevant patients.   We try it on dogs however!
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"Get Your Dog Tested*

Blood sample or cheek swab?

DNA obtained from a dog’s blood is the same DNA that would be obtained from that dog’s cheek cells using a swab. We allow submission of either sample because blood is often the sample preferred by veterinary hospitals while cheek swabs are generally preferred by dog owners."

College of Veterinary Medicine

Veterinary Clinical Pharmacology Lab

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We know that pathways get underway through consumption of measurable co-factors and obligatory steps that we can promptly measure and determine that the drug is being used or allowed to act at cellular level.   Is it the lack of will, or the sense of desperation because of limitations in our available options that make us afraid to know the truth early.  The point is we cannot go on avoiding to know what is in store for the patients!
Many drugs act through Adenyl Cyclase, many drugs use the Gerb-2, Gab1, etc....why can't we use these available biomarkers of drug actions.   DNMT1 AT EPIGENETIC LEVEL (OR SIMILAR MOLECULES)

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DNA (cytosine-5)-methyltransferase 1 is an enzyme that in humans is encoded by the DNMT1 gene.^[1]
DNA (cytosine-5-)-methyltransferase 1 has a role in the establishment and regulation of tissue-specific patterns of methylated cytosine residues. Aberrant methylation patterns are associated with certain human tumors and developmental abnormalities.<sup>[2][3]" wikipedia

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has been proposed as a way to gauge imprinted information
can we try this as a biomarker of drug effect?

SUFFICE IS TO SAY WE CAN'T GO ON FOOLING OUR PATIENTS INTO INEFFECTIVE DRUG TRIALS! THE TIME TO KNOW IS NOW! AND HERE WE GO AGAIN, A TEAM OF INVESTIGATORS WITH SOPHISTICATED MACHINES NEED TO GO BACK TO WORK AGAIN ON THIS NEW LEAD!  THE ANSWER IN 5 YEARS!</sup>

EVEN HYPERTENSION IS CYTOKINE INDUCED

e-MED:

"Due to investigations into the pathophysiology of hypertension, both in animals and humans, growing evidence suggests that hypertension may have an immunological basis. Studies have revealed that hypertension is associated with renal infiltration of immune cells and that pharmacologic immunosuppression (such as with the drug mycophenolate mofetil) or pathologic immunosuppression (such as occurs with HIV) results in reduced blood pressure in animals and humans. Evidence suggests that T lymphocytes and T-cell derived cytokines (eg, interleukin 17, tumor necrosis factor alpha) play an important role in hypertension. One hypotehesis is that prehypertension results in oxidation and altered mechanical forces that lead to the formation of neoantigens, which are then presented to T cells, leading to T-cell activation and infiltration of critical organs (eg, kidney, vasculature). This results in persistent or severe hypertension and end organ damage. promote T-lymphocyte activation and infiltration and contribute to the pathophysiology of hypertension."

Protease inhibitors could play a role in 2nd line ER positive breast cancer by blocking cytokine formation

"
Researchers are investigating whether protease inhibitors could possibly be used to treat cancer. For example, nelfinavir and atazanavir are able to kill tumor cells in culture (in a Petri dish).^[10][11] This effect has not yet been examined in humans; but studies in laboratory mice have shown that nelfinavir is able to suppress the growth of tumors in these animals, which represents a promising lead towards testing this drug in humans as well.^[11]
Inhibitors of the proteasome, such as Velcade/Bortezomib are now front-line drugs for the treatment of various cancers, notably Multiple Myeloma." wikipedia

could you imagine blocking formation of undesirable cytokines, you could prevent resistance to to AIs., you could delay resistance to hormone based treatment modalities!

other puzzling roles of cytokines!

It is not hard to believe that reactivation of TB under Infliximab therapy would be linked to some cytokine or that pain and increased risk of Achille's tendon rupture following chronic use of Ciprofloxacin would be under the doing by cytokines.  And that any disease state associated with the so called "constitutional symptoms would be also a manifestation of Cytokines'effect.  What surprise the most is how little we do ot care to determine exactly which one.  We instead jump to give NSAID and related compound (steroids or Interferons) without further characterization of these cytokine. No wonder why we meet several side effcts that are unforseen such as increase of strokes and cardiovascular disorders or even bleeding!  Cytokines are notorious in inducing vascular disturbances!  Just ask Wegener or Paget for that matter!

Role of Cyclins in ER positive Breast cancers resistance

Now it is increasingly apparent that cyclins may have an increased presumptive role in the resistance to Aromatase inhibitors and hormone driven therapy for ER positive breast cancer. Yes as you apply pressure on the cancer cell by Blocking Receptor ultimately the cell will desensitize  itself from this deadly lack of stimulation. Cancer cells want to survive, Increasing evidences suggest that cell desensitization is by way of   the cytokines.  It is not by mistake that disruption of epigenetic events by Entinostat which ultimately change significantly the profile of cyclins produced by the cell will lead to breaking of cancerous cell resistance to Hormone receptor  driven target therapy.   The cancerous cell uses the NF-kB and c-jun (stress related PI3K/AKT/MTOR) for survival and we know what happens when these pathways reach the epigenetic zone, new cyclins are metabolized to induce resistance.  The proof is in the pudding, only MTOR inhibitors, and anti-CDK break the resistance to AI or SERMs.
Which Cytokines affects induce desensitization is a hot question, and the mechanism trggering the need for desensitization need to be aggressively pursued.  Assumption is that dying cells may through the Wnt and Notch give information that eventually leads to resistance in surviving cells.  How ? when?  remember cell since they are born have the instinctive reflex to survive.  It is their mission, it is their commitment!  Dying cancer cells will have to tell somehow the living cells how and why they are dying for those uninvolved to be prepared and possibly a global cellular desensitization of growth inducing receptor is a reflex.  Indeed it has been shown that cancer cells significantly reduce dependency on growth factor stimulation for an internal "stress" like metabolism.  What trigger this alternative "mode de vie" is in itself a pathway to global resistance to outside stimulation and death inducing external compounds!
On epigenetic level, a switch in transcription, would be enough to alter the cytokines with a resulting resistant change in effects at the receptors!
Here at the CRBCM, work is increasing daily as leads multiply.

The main question is should we incrementally add these agents in a sequential way, or should we give these agents together or all 3 for greater good.   will concurrent use actually disrupt the effect of the other, in other words, should we wait for the resistance to develop in order to add the other mode of of targeting agents when the cancer is counting on it the most?  Adding the MTOR after Avastin failure has proven to be supportive of the sequential  intervention by some reports whereas giving them concurrently may not be additive!  Why? by now receptor site of Avastin is "desensitize" while the surviving cell use the PI3K/MTOR to survive, hit it now with MTOR inhibitor, and Histone deacetylator inhibitor like we are doing now with ER positive breast cancers!