Yes, don't forget the TELOMERES!

• October 2013
• > Vannier et al., 342 (6155): 239-242

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 WATCH THIS ONE!

RTEL1 Is a Replisome-Associated Helicase That Promotes Telomere and Genome-Wide Replication

1. Jean-Baptiste Vannier¹,*,
2. Sumit Sandhu²,*,
3. Mark IR. Petalcorin¹,
4. Xiaoli Wu²,
5. Zinnatun Nabi²,
6. Hao Ding²,³,^†,
7. Simon J. Boulton¹,^†

+ Author Affiliations

1. ¹DNA Damage Response laboratory, London Research Institute, Cancer Research UK, Clare Hall, South Mimms EN6 3LD, UK.
2. ²Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3E 3J7, Canada.
3. ³Manitoba Institute of Child Health, Winnipeg, Manitoba, R3E 3P4, Canada.

1. ↵†Corresponding author. E-mail: dingh@cc.umanitoba.ca (H.D.); simon.boulton@cancer.org.uk (S.J.B.)

1. ↵* These authors contributed equally to this work.

• Abstract
• Editor's Summary

Regulator of telomere length 1 (RTEL1) is an essential DNA helicase that disassembles telomere loops (T loops) and suppresses telomere fragility to maintain the integrity of chromosome ends. We established that RTEL1 also associates with the replisome through binding to proliferating cell nuclear antigen (PCNA). Mouse cells disrupted for the RTEL1-PCNA interaction (PIP mutant) exhibited accelerated senescence, replication fork instability, reduced replication fork extension rates, and increased origin usage. Although T-loop disassembly at telomeres was unaffected in the mutant cells, telomere replication was compromised, leading to fragile sites at telomeres. RTEL1-PIP mutant mice were viable, but loss of the RTEL1-PCNA interaction accelerated the onset of tumorigenesis in p53-deficient mice. We propose that RTEL1 plays a critical role in both telomere and genome-wide replication, which is crucial for genetic stability and tumor avoidance.
================================================
PLEASE GO TO THE FULL ARTICLE,
GOOD JOB FOR THESE SCIENTISTS!

Until we can talk to the CBX, the piccolo, and the IKAROS, Brain tumors and certain Leukemia will remain elusive!

It is striking what similarities exist between brain tissue function and white blood cell function at the molecular level.  When it comes to Neoplasia, Medulloblastoma is linked to hematologic neoplasm!
And any therapeutic intervention against blood cell proliferative disorders may have Neurologic side effects, and it is important that Phase 1 studies be conducted in centers that can handle seizures and accurately evaluate mental status changes (Leucodystrophic Encephalopathy)!  The similarities are not only found at the membrane where the frizzled and the Lck, and Merlin (Neurofibromatosis) are located, but deep inside the cells at the Nuclear/Chromatin level where the Ikoros and CBX5 are plenty at play!
It is evident that the CBXs and the Ikoros are epigenetic and this is where Leukemia and most malignant Brain tumors come to hide their source and powers.  And guess who is following them, the triple negative breast cancers!  It is actually amazing that this last disease may be more likely Cytokine driven given its selective appearance in certain groups of our population (HLADRs implicated).
The CRBCM continues its unfettered progress, not distracted by belligerent political forces, but tracking down this disease from the Wnt, Notch, Wisp3, non expressed Hormone Receptors, to the STAT5, SMADs, and now to the SUV39H1-CBX, Ikoros, Piccolo,Tousled, a Ku70, and to chromatin modulation.
Progress is slow but deliberate.  It is surprising that even deep here, through the FADD-MBD4, the Caspases can help achieve Apoptosis...there is hope for the cure!

Controversial but reportable (marginal benefit)-Ramucirumab

ONLINE FIRST: FDA Grants Priority Review of Ramucirumab for Gastric Cancer, Phase III REGARD Findings Now Online in Lancet; Concerns, Though, from a Lead Recruiter to the Trial(from Oncology Times)
what we know about the drug
"

Ramucirumab

From Wikipedia, the free encyclopedia

Jump to: navigation, search

Ramucirumab ^?

Monoclonal antibody
Type	Whole antibody
Source	Human
Target	VEGFR2 (KDR)
Clinical data
Pregnancy cat.	?
Legal status	Investigational
Identifiers
CAS number	947687-13-0
ATC code	None
UNII	D99YVK4L0X
Chemical data
Formula	C6374H9864N1692O1996S46
Mol. mass	143.6 kDa
(what is this?)  (verify)

Ramucirumab (IMC-1121B)^[1] is a fully human monoclonal antibody (IgG1) being developed for the treatment of solid tumors. It is directed against the vascular endothelial growth factor receptor 2 (VEGFR2). By binding to VEGFR2 it works as a receptor antagonist blocking the binding of vascular endothelial growth factor (VEGF) to VEGFR2. VEGFR2 is known to mediate the majority of the downstream effects of VEGF in angiogenesis.
Ramucirumab is being tested in several phase III clinical trials for the treatment of metastatic gastric adenocarcinoma,^[2] non-small cell lung cancer,^[3] among other types of cancer. On September 26, 2013 Eli Lilly announced that its Phase III study for ramucirumab failed to hit its primary endpoint on progression-free survival among women with metastatic breast cancer.^[4][5]
This drug was developed by ImClone Systems Inc. It was isolated from a native phage display library from Dyax. " wikipedia

Real clinical questions

1. Identifying best chemotherapy drugs in patients with Mutation in the NOTCH pathway?
Taxotere?
association with Her-2 overexpression and use of Herceptin
NF-kB blocker
or AKT blocker.
Histone de-acetylator

2. Understanding the patterns of Metastasis between epithelial (squamous) (more local recurrence)  Vs AdenoCA (more distant recurrence in Esophageal cancer? Genes at play.
Does mesenchymalization dictate or drive long distance metastasis?

3. Mitomycin in NFKB amplification/Mutations

distraction for the Public

NCI SBIR at the 2014 Personalized Medicine World Conference January 27-28 The National Cancer Institute (NCI) invites you to attend the Personalized Medicine World Conference (PMWC) on January 27-28 in Silicon Valley, CA. Dr. Andrew Kurtz from the NCI Small Business Innovation Research (SBIR) Development Center will present details on NIH SBIR funding opportunities and other initiatives that support small businesses developing innovative biomedical technologies. Dr. Kurtz will give a presentation in Track 3 on January 27, 2014. To view the full program, please click here.     PMWC 2014 January 27-28, 2014 Computer History Museum 1401 N Shoreline Blvd Mountain View, CA PMWC is the only fully integrated conference to examine the advances and challenges of Personalized Medicine through a practical lens. PMWC brings together the thought-leaders of business, government, healthcare-delivery, research, and technology into one information-rich, two-day conference. For Emerging Companies: The PMWC 2014 Most Promising Company Competition is officially launched! Track 3 offers pre-selected, emerging companies defining the next generation of personalized medicine platforms and technologies the chance to compete towards the PMWC 2014 Most Promising Company Award. The deadline to nominate and submit is December 23. Please click here for additional information. NCI SBIR promo rate (until Nov. 12): 10%-off registration Register here: http://pmwc2014.eventbrite.com/ Enter promo code: NCISBIR_Nov12  Opportunities to exhibit and present are also currently available. Please click here to add this event to your calendar. For more information, visit the PMWC 2014 website or contact Magali Cohen at: magalic@pmwcintl.com. To learn more about other NCI SBIR upcoming events, please click here.     If you are interested in discussing your organization's project with NCI Development Center staff to explore how it aligns with NCI's priorities, please contact a Program Director at ncisbir@mail.nih.gov. To learn more about the NCI SBIR Development Center, please visit: http://sbir.cancer.gov/index.asp. To read about the benefits of NCI SBIR & STTR funding and how to apply please click here.  The SBIR & STTR Programs are NCI's engine of innovation for developing and commercializing novel technologies and products to prevent, diagnose, and treat cancer. The SBIR & STTR Programs are government set-aside programs for domestic small businesses to engage in research and development that has the potential for commercialization and public benefit. Sign up to receive updates about SBIR & STTR funding opportunities at sbir.cancer.gov   Follow us on Twitter   Connect with us on LinkedIn

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!

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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