Friday, November 8, 2013

Genes in Breast CANCERS

1.Variants in the PALB2 gene are associated with an increased risk of developing breast cancer [5] and PALB2-deficient cells are sensitive to PARP inhibitors. [4]
PALB2 was recently identified as a susceptibility gene for familial pancreatic cancer by scientists at the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins. This has paved for the way for developing a new gene test for families where pancreatic cancer occurs in multiple family members.[6] Tests for PALB2 have been developed by Ambry Genetics [7]and Myriad Genetics[8] that are now available through a genetic counselor.
Biallelic mutations in PALB2 (also known as FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia.[3]wikipedia


2 xia et al: described superbly the role of PALB2
" the identification of PALB2, a BRCA2 binding protein. PALB2 colocalizes with BRCA2 in nuclear foci, promotes its localization and stability in key nuclear structures (e.g., chromatin and nuclear matrix), and enables its recombinational repair and checkpoint functions. In addition, multiple, germline BRCA2 missense mutations identified in breast cancer patients but of heretofore unknown biological/clinical consequence appear to disrupt PALB2 binding and disable BRCA2 HR/DSBR function. Thus, PALB2 licenses key cellular biochemical properties of BRCA2 and ensures its tumor suppression function."

3. And has mentioned hematologic complication is not very far!

" Fanconi anemia is a rare, recessive, chromosomal instability disorder characterized by growth retardation, congenital malformations, progressive bone marrow failure, cancer predisposition and cellular hypersensitivity to DNA cross-linking agents1. The syndrome is genetically heterogeneous with 12 complementation groups currently recognized, 11 of which have been attributed to distinct genes: FANCA (FA-A), FANCB (FA-B), FANCC (FA-C), BRCA2 (FA-D1), FANCD2 (FA-D2), FANCE (FA-E), FANCF (FA-F), FANCG (FA-G), BRIP1 (FA-J), FANCL (FA-L) and FANCM (FA-M)2, 3." Sarah Reid et al....

4. And the devastation does not stop to Fanconi and Breast cancer!

ERKKO et al:

"These results indicate that PALB2 is a breast cancer susceptibility gene that, in a suitably mutant form, may also contribute to familial prostate cancer development." in a Finnish population

SIAN JONES ET AL

"the role of PALB2 as a susceptibility gene for pancreatic cancer. PALB2 mutations have been previously reported in patients with familial breast cancer, and the PALB2 protein is a binding partner for BRCA2. "

SOME AUTHORS ADD GALLBLADDER,MELANOMA AND GASTRIC CANCERS TO THIS SAD LITANY.
====================================================================

6.RAD51

"In humans, RAD51 is a 339-amino acid protein that plays a major role in homologous recombination of DNA during double strand break repair. In this process, an ATP dependent DNA strand exchange takes place in which a template strand invades base-paired strands of homologous DNA molecules. RAD51 is involved in the search for homology and strand pairing stages of the process.
Unlike other proteins involved in DNA metabolism, the RecA/Rad51 family forms a helical nucleoprotein filament on DNA.[2]
This protein can interact with the ssDNA-binding protein RPA, BRCA2, PALB2[3] and RAD52."WIKIPEDIA

RAD 51 KEEPS BAD ASSOCIATIONS, BROADENING THE DANGER!

" RAD51 has been shown to interact with BRE,[12] RAD54B,[13] Ataxia telangiectasia mutated,[14] BRCC3,[12] BARD1,[12] BRCA2,[12][15][16][17][18][19][20][21][6][22][23][24][25] UBE2I,[26][27] Abl gene,[14] BRCA1,[12][24][28][29] ATRX,[13][30] RAD52,[14] DMC1,[31] P53[12][32][33] and Bloom syndrome protein.[34]"WIKIPEDIA

====================================
ON TOP OF ALL THIS 
YOU STILL HAVE 
- CDH1
- p53 MUTATIONS
- PTEN

OUR WORK IS CUT OUT TO TRAVEL THIS MAZE!

Thursday, November 7, 2013

SOME LITTLE GENES WITH A BIG IDEA: SHP GENE

IF YOU KNOW HOW IMPORTANT ESTROGEN RECEPTORS ARE IN BREAST CANCERS,
IF YOU KNOW HOW IMPORTANT ANDROGEN RECEPTORS ARE IN PROSTATE CANCER
IF YOU REALIZE HOW IMPORTANT THE THYROID FUNCTION IS DRIVING THE RATE OF METABOLISM
IF YOU REALIZE THE DIFFICULTY THAT POSES HEPATOMA IN TERMS OF TREATMENT,
IF YOU KNOW THAT SARCOMA IS TOUGH TO TREAT,

THEN YOU SHOULD DIG DEEPER IN UNDERSTANDING THAT ALL THESE RECEPTORS HAVE ONLY ONE INHIBITOR, THE "SMALL HETERODIMER PARTNER"  GENE!

WHAT IS IT AND HOW AND WHEN SHOULD IT COME IN?

Small heterodimer partner has been shown to interact with:

I refuse to comment on the PPARgamma for now, did you know that this is the staff that interacts with Rb1?  watch it as it is coming to a Diabetic control and evaluation near you!

At CRBCM we are working hard!

A WILD GENE! THE EP 300

Every time we talk about a "wild gene", we get a reaction from our readers.  This is a good sign.  Basically, what we call wild gene is one full of interactions.  We talked about adapter genes which basically direct in one or the other direction of global Metabolism, but we also make sure that readers understand that these adapters can allow a gene to acquire proliferative potential by hooking it to another gene that routinely drives proliferation (such as the gene that pushes Antibody formation).  By all definitions, EP300 is a wild gene.

Another power to this gene is the fact that it leads to Malformation when it is missing:
"Rubinstein-Taybi syndrome.", THROUGH THE MAML1 GENE, THIS GENE IS IN COMPLICITY WITH THE NOTCH1.  And you know how we hold dearly the Notch as an important gene/pathway...

EP300 is involved in all major cancers including Acute Leukemia.  You remember that Acute AML cells have not fully completed differentiation.  EP300 is the master of differentiation and of course will be mutated or altered in bad AML.  So, in a way, it is prognostic!

" Somatic mutations in the EP300 gene have been found in a small number of solid tumors, including cancers of the colon and rectum, stomach, breast, and pancreas. Studies suggest that EP300 mutations may also play a role in the development of some prostate cancers, and could help predict whether these tumors will increase in size or spread to other parts of the body. In cancer cells, EP300 mutations prevent the gene from producing any functional protein. Without p300, cells cannot effectively restrain growth and division, which can allow cancerous tumors to form."

HOW MANY GENES INTERACT WITH EP300? YOU BE THE JUDGE!

"Interactions"

EP300 has been shown to interact with Mothers against decapentaplegic homolog 7,[6] MAF,[7] TSG101,[8] Peroxisome proliferator-activated receptor alpha,[9][10] NPAS2,[11] PAX6,[12] DDX5,[13] MYBL2,[14] Mothers against decapentaplegic homolog 1,[15][16] Mothers against decapentaplegic homolog 2,[17][18] Lymphoid enhancer-binding factor 1,[19] SNIP1,[20] TRERF1,[21] STAT3,[16] EID1,[22][23] RAR-related orphan receptor alpha,[24] ELK1,[25] HIF1A,[26][27] ING5,[28] Peroxisome proliferator-activated receptor gamma,[29][30] SS18,[31] TCF3,[32] Zif268,[33] Estrogen receptor alpha,[29][34][35] GPS2,[36] MyoD,[24][37] YY1,[38][39] ING4,[28] PROX1,[7] CITED1,[40] HNF1A,[41] MEF2C,[37] MEF2D,[42][43] MAML1,[44][45] Twist transcription factor,[46] PTMA,[47] IRF2,[48] DTX1,[49] Flap structure-specific endonuclease 1,[50] Myocyte-specific enhancer factor 2A,[51] CDX2,[12] BRCA1,[34][52] HNRPU,[53] STAT6,[54] CITED2,[55][56][57][58] RELA,[59][60] TGS1,[61] CEBPB,[62] Mdm2,[63] NCOA6,[64] NFATC2,[65] Thyroid hormone receptor alpha,[51] BCL3,[66] TFAP2A,[56] PCNA,[67] P53[68][63][69][70][71] and TAL1.[72]wikipedia"

Wednesday, November 6, 2013

TANTALIZING PRESENTATION OF NEW TECHNOLOGIES!

Presentations from GSK, Broad Institute, Indiana University on RNA-Seq


Izzy Scott-Moncrieff
6:05 AM (6 hours ago)

to me
  Dear Mutombo,



Sick of my emails? Bear with me. Because this week I have something very exciting for you.
 Not one, or even two, but THREE PRESENTATIONS from the inaugural RNA-Seq 2013 meeting
 that took place in Boston earlier this year.

Have a read through the summaries below. Which gets your number 1 vote? We’re running
 a poll on our Linkedin page (search Linkedin groups for RNA-Seq Forum) to establish which,
 of groups from GSK, Broad Institute or Indiana University School of Medicine are engrossed
 in the most exciting work at the moment. 

Numéro un (1). Ganesh Sathe, DNA Sequencing Manager, GSK.
“Applications of RNA-Seq within Research & Development at GSK”
Ganesh spoke about using RNA-Seq for cancer target identification using very small

amount of starting material. How GSK are going about sequencing blood samples

for biomarker identification. Which new technologies are they using for cell line validation?

Numero due (2). Brian Haas, Senior Computational Biologist, Broad Institute
“Trinity de novo RNA-Seq Assembly for Analysis of Model and Non-Model Organisms”
Brain gave a fascinating comparison of Trinity software when used with model and

non-model organisms. An overview of how, in the absence of a reference genome

, this software coupled with companion utilities enables de novo transcript

reconstruction. And subsequently how this yields insights into gene content

and transcriptional regulation. 

Nummer drei (3). Yunlong Liu, Assistant Professor, Medical and Molecular Genetics,
 Indiana University 
“Statistical Modelling in Non-Coding RNA Mediated Regulatory Networks”
Yunlong presents a bioinformatics strategy to construct the microRNA mediated

regulatory network using genome-wide binding patterns of transcription factors.

As well as this, brand new findings on long noncoding RNA in determining alcohol

dependence in rat brains, using RNA-seq derived transcriptome mapping data. 
You know the drill by now. Click here to download the presentation

And if you thought that was all, not at all! These three presentations are brought you in
 the run up to RNA-Seq Europe (3-5 December, Basel), where we’ll be bringing you
even more top rate presentations on everything RNA-Seq. Make sure you check out the brochure.

Remember, visit the Linkedin group to cast your vote on which is your number 1
 presentation.

As per, drop me a reply if you want more info on how to register. You can also send
 me your vote directly. Maybe your company will hit the top spot next year…

Bye for now!

Izzy 

Genomics Programme Director
Hanson Wade

P.S If you like the free presentations then check out the RNA-Seq website. You can peruse
 the other exciting bits of RNA-Seq themed content there.

Yes, don't forget the TELOMERES!

Prev | Table of Contents | Next

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

  1. 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.
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!

Tuesday, November 5, 2013

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 Yes
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

National Cancer Institute
SBIR and STTR
 
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!

Monday, November 4, 2013

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State of Texas Seal
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!

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.

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?

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 ....



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

NOW THE STOP ORDER IS IN EFFECT REPORTEDLY!