Genes in breast cancer from wikipedia!
CDH1 gene
It is CD324 (cluster of differentiation 324). It is a tumor suppressor gene
The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region, and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers. Loss of function is thought to contribute to progression in cancer by increasing proliferation, invasion, and/or metastasis.
Through
Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.^[1]
This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist.<sup>[2]

Through
Ras GTPase-activating-like protein IQGAP1 (IQGAP1) also known as p195 is a ubiquitously expressed protein that in humans is encoded by the IQGAP1 gene.[1][2][3] IQGAP1 is a scaffold protein involved in regulating various cellular processes ranging from organization of the actin cytoskeleton, transcription, and cellular adhesion to regulating the cell cycle.
through</sup>

Histone deacetylase 1 is an enzyme that in humans is encoded by the HDAC1 gene.^[1]
Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family and is a component of the histone deacetylase complex. It also interacts with retinoblastoma tumor-suppressor protein and this complex is a key element in the control of cell proliferation and differentiation. Together with metastasis-associated protein-2 MTA2, it deacetylates p53 and modulates its effect on cell growth and apoptosis.^[2]

 The protein encoded by this gene 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. PTPrho has been proposed to function during development of the nervous system and as a tumor suppressor in cancer.



c-Met (MET or MNNG HOS Transforming gene) is a proto-oncogene that encodes a protein known as hepatocyte growth factor receptor (HGFR).^[1][2] The hepatocyte growth factor receptor protein possesses tyrosine-kinase activity.^[3] The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor.
MET is a membrane receptor that is essential for embryonic development and wound healing. Hepatocyte growth factor (HGF) is the only known ligand of the MET receptor. MET is normally expressed by cells of epithelial origin, while expression of HGF is restricted to cells of mesenchymal origin. Upon HGF stimulation, MET induces several biological responses that collectively give rise to a program known as invasive growth.
Abnormal MET activation in cancer correlates with poor prognosis, where aberrantly active MET triggers tumor growth, formation of new blood vessels (angiogenesis) that supply the tumor with nutrients, and cancer spread to other organs (metastasis). MET is deregulated in many types of human malignancies, including cancers of kidney, liver, stomach, breast, and brain. Normally, only stem cells and progenitor cells express MET, which allows these cells to grow invasively in order to generate new tissues in an embryo or regenerate damaged tissues in an adult. However, cancer stem cells are thought to hijack the ability of normal stem cells to express MET, and thus become the cause of cancer persistence and spread to other sites in the body.
 thrpogh HDAC1
 Sp1 has been used as a control protein to compare with when studying the increase or decrease of the aryl hydrocarbon receptor and/or the estrogen receptor, since it binds to both and generally remains at a relatively constant level.^[2] Withaferin A, a sterodial lactone from Withania Somnifera plant is known to inhibit Sp1 Transcription factor[33]. etoposide resistance
========================================================
Rhoc gene
RhoC can activate formins such as mDia1 and FMNL2 to remodel the cytoskelton.^[3]
It is prenylated at its C-terminus, and localizes to the cytoplasm and plasma membrane. It is thought to be important in cell locomotion. Overexpression of this gene is associated with tumor cell invasion and metastasis. RhoC-deficient mice can still develop tumors but these fail to metastasize, arguing that RhoC is essential for metastasis.^[4]

WNT1-inducible-signaling pathway protein 3

From Wikipedia, the free encyclopedia

Jump to: navigation, search

WNT1 inducible signaling pathway protein 3
Identifiers
Symbols	WISP3; CCN6; LIBC; PPAC; PPD
External IDs	OMIM: 603400 HomoloGene: 77038 GeneCards: WISP3 Gene
[show]Gene Ontology
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8838	327743
Ensembl	ENSG00000112761	ENSMUSG00000062074
UniProt	O95389	D3Z5L9
RefSeq (mRNA)	NM_003880	NM_001127376
RefSeq (protein)	NP_003871	NP_001120848
Location (UCSC)	Chr 6: 112.38 – 112.39 Mb	Chr 10: 39.15 – 39.16 Mb
PubMed search	[1]	[2]
This box: view talk edit

WNT1-inducible-signaling pathway protein 3^[1][2] (WISP3, also named CCN6) is a matricellular protein that in humans is encoded by the WISP3 gene.

Contents 1 Structure 2 Function 3 Clinical significance 4 References

Structure

It is a member of the CCN family (CCN intercellular signaling protein) of secreted, extracellular matrix (ECM)-associated signaling matricellular proteins. The CCN acronym is derived from the first three members of the family identified, namely CYR61 (CCN1), CTGF (connective tissue growth factor, or CCN2), and NOV. These proteins, together with WISP1 (CCN4), and WISP2 (CCN5) comprise the six-member CCN family in vertebrates. CCN proteins characteristically contain an N-terminal secretory signal peptide followed by four structurally distinct domains with homologies to insulin-like growth factor binding protein (IGFBP), von Willebrand type C repeats (vWC), thrombospondin type 1 repeat (TSR), and a cysteine knot motif within the C-terminal (CT) domain.

Loss of WISP3 expression is associated with aggressive inflammatory breast cancer and breast cancer with axillary lymph node metastasis, suggesting that WISP3/CCN6 may function as a suppressor of breast cancer growth and metastasis.^{[2]
 =================
palb2 gene}

This gene encodes a protein that functions in genome maintenance (double strand break repair). This protein binds to and colocalizes with the breast cancer 2 early onset protein (BRCA2) in nuclear foci and likely permits the stable intranuclear localization and accumulation of BRCA2.^[1] PALB2 binds the single strand DNA and directly interacts with the recombinase RAD51 to stimulates strand invasion a vital step of homologous recombination.^[4] PALB2 can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion.^[4]

Clinical significance

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]

ISSUES IN BREAST CANCER

FOR MEN
There is an increased risk
-with BRAC2 Mutation
-Klinefelter syndrome
-Obesity and Cirrhosis (E/T ratio)
-undescended testicles or testicular trauma.

*When testing in a family, the youngest woman with the disease should be the one to undergo testing!
*In Male, the risk of developing breast cancer by age 80 with BRCA2 is 7%.
*Invasive Lobular carcinoma associated with family hx of diffuse gastric cancer occur with Mutation of E-Cadherin-CDH-1 gene.
*Hormone replacement therapy has not been associated with DCIS.
*If oral contraceptive use increased your risk of Breast Cancer, you have the BRCA Mutation!
*Involution of terminal duct lobule is linked to a lower incidence of Breast cancer.
*larger waist circumfernce is linked to ER Negative breast cancer risk.

DISCUSSION OF NEW ANTI-HYPERTENSIVE APPROACHES TARGETING GENES
*Pseudo-Bartter’s syndrome has been seen in cystic fibrosis,^[12] as well as in excessive use of laxatives.^{[13] WIKIPEDIA
*IN CYSTIC FIBROSIS IT IS THE :}

"(MSD1 and MSD2) that form the chloride ion channel"WHICH PART OF THE CFTR MOLECULE,
iN CYSTIC FIBROSIS  (CFM1), a modifier gene located on chromosome 19, may determine MI susceptibility.
( U.S. Department of Energy (DOE) Human Genome Project Information Web site.) 

NEW STRATEGIES TO FIGHT HYPERTENSION AT GENETIC LEVEL

WATCH BARTER'S AND GITELMAN'S SYNDROMES! (SEE WIKIPEDIA)
IN THIS DISEASE, HYPERTENSION DOES NOT OCCUR!   THE ONLY DANGER IS OF COURSE DEAFNESS SO KEEP AWAY FROM CLCNK A and B  (CIC-kB), ALL OTHER ARE TARGETABLE, OF COURSE DO NOT REPRODUCE THE FULL DISEASE, CHALLENGES  AHEAD BUT DON'T RULE IT OUT JUST YET!

Bartter and Gitelman syndromes can be divided into different subtypes based on the genes involved:^[5]

Name	Bartter type	Associated gene mutations	Defect
neonatal Bartter's syndrome	type 1	SLC12A2 (NKCC2)	Na-K-2Cl symporter
neonatal Bartter's syndrome	type 2	ROMK/KCNJ1	thick ascending limb K+ channel
classic Bartter's syndrome	type 3	CLCNKB	Cl- channel
Bartter's syndrome with sensorineural deafness	type 4	BSND[6]	Cl- channel accessory subunit
Bartter's syndrome associated with autosomal dominant hypocalcemia	type 5	CASR[7]	activating mutation of the calcium-sensing receptor
Gitelman's syndrome	-	SLC12A3 (NCCT)	Sodium-chloride symporter

WILL JOIN THIS ACTIVITY WHILE IN DC!

INOVA FAIRFAX HOSPITAL DEPARTMENT OF MEDICINE
MEDICAL GRAND ROUNDS

"Anal Cancer and AIN: Is It Inevitable?”

Lynn Dougherty, MD, FACS, FASCRS
 Fairfax Colon and Rectal Surgery, PC
Medical Director, Division of Colon and Rectal Surgery,
Inova Fairfax Hospital
Staff Surgeon, Inova Fairfax, Fair Oaks, and Alexandria Hospitals
Part-time Assistant Professor, VCU School of Medicine

Caroline Sanchez, MD
 Fairfax Colon and Rectal Surgery, PC
Staff Surgeon, Inova Fairfax, Fair Oaks, and Alexandria Hospitals

July 2, 2013
12:30PM
Cyrus Vesuna Auditorium
(Lunch will be served at 12:00PM outside the auditorium)

GENOME AND THE FUTURE IN CANCER MEDICINE.
SOME OF THE BARRIERS TO GENOME  INTEGRATION INTO PATIENT CHARTS!
(Excerpt of our preliminary work)

As we advance in Medicine, and particularly in cancer Medicine, it is increasingly recognized that Medical patho-physiology  find its source and implications tightly linked to sets of genes.  There are genes that initiate the pathophysiology, but also pathway genes that once activated by the initiating gene(s), squarely  drive the subsequent events, or amplify them as if it release the breaks with devastating consequences.

Genes can be in all kind of states. They can be amplified or repressed, or the can be full blown expressed and participating, or they can be silenced!  Their expression can be forced or deliberate.  They are forced when in a linkage situation or in an abnormal fusion, or deliberately expressing themselves when they have something to say or do due to their intrinsic nature!  Of significant interest is the aspect that gene expression can be dependent on our age, gender, race and place !

AGE:

 Although we inherit the same from birth, if you  believe that at any given point, the genes expressed in you as an embryo, and subsequent ages, are the same, think again.  Life is in a constant flux, nothing is still in a living being! And life is purposeful.  AND SURVIVAL IS THE OBJECTIVE!  Everything our cells do is to keep surviving. and so does cancer cells to our own surprise and demise!  The first years are destined to growth and we gobble up things (unfortunately we don't know when to stop, realize you just have reached the lifetime external Carbohydrates needed!), by age 3, we stop having ability to have a fever induced seizure! in our twenties, we stop growing in height!  well age has something to say through our GENES!

GENDER:

We know that one of the X Chromosome and its genes may be silenced!
But the strongest evidence of gender influence on gene expression is on Major Histocompatibility antigens (class I antigen).  Women during their reproductive years get ready to carry a foreign body (baby)inside them without fighting it!  They have got to dampen their Class I (UNO or ONE) Antigens ability.  It is this very reason that Inflammatory bowel disease and autoimmune diseases are most fulminant (or simply more active, but I love the fulminant word) during these reproductive years.  (Lupus 15 to 45 years of age range!).  It is hypothesized that pattern of gene Methylation leads to silencing of some of the HLA-A, and B mostly!

Race

Disparity in incidence, frequency and  mortality among races are the strongest evidence of this relationship between Gene expression and the races!   class II MHC Antigen are linked to various Autoimmune and Metabolic diseases (DM).  Even high blood pressure pathophysioplogy varies among the races.
For CRBCM, it is that flagrant case of Triple Negative Breast cancer that we are struggling with (struggling to link to the  races, the class II Antigens and to PSROS-1 gene!-Go figure!)

Place!

Or better Environment!   It is incredible to realize our environmental influences affect our genes.   Cancer rates are known to increase in immigrants to match the locals over time! Immigrants share in joy but also in subsequent pains at gene levels!

BARRIERS ....STILL TO COME !

DOING OUR BEST AT CRBCM!

TH ANSWER TO THE MPIN FINALLY CAME AS WE COMPLAINED BITTERLY TO THE GOVERNMENT.  THE DEADLINE FOR SUBMISSION IS HOWEVER PAST, WE BELIEVE THEY WILL REOPEN THIS RFA BECAUSE THEY WILL MISS US (WISHFUL THINKING!)  BUT WITH A SLEW OF UNANSWERED QUESTIONS IN CANCER MEDICINE SOMEONE SOMEWHERE WILL BE INTERESTED IN WHAT WE HAVE TO SAY. AND PLEASE DON'T BE SHY, REACH OVER TO CRBCM AND TALK TO US.  OUR DOOR IS ALWAYS OPEN, OUR MIND RECEPTIVE AND ALWAYS READY TO LEARN...
CALL US AT 915-307-3354!

NIH/GOVERNMENT STRATEGY TO KEEP MINORITY AWAY FROM PARTICIPATING !
It is clear that in a so called free society, one of the fundamental principle is to allow everyone to participate, enter a competition for government services.  But to believe that free participation is true in these United States you better think again.  Especially if your name is clearly of African origin!
When you have a medical practice,  reimbursement for service rendered is a particular challenge. 8 months after starting to see Medicare patients, We are still waiting for the first penny from the Obama administration.  Every time we call them, their computer has a glitch! "wait another 60 days!".  It seems that the government that made the internet has other computer experts sleeping at the wheels or full of nerds who
can't figure out their own doing!  They have hired an Intermediary called:

[Novitas Solutions

which sounds like new solution to government no-solvency.  these guys amuse themselves with messages like "

JH Part A Provider Outreach and Education(POE) Advisory Group (AG) Meeting Minutes - May 22, 2013

https://www.novitas-solutions.com/training/poag/index.html

The JH Provider Outreach and Education (POE) Advisory Group (AG) meeting minutes from May 22, 2013 are now available for your reading pleasure.  Enjoy!"  

while we are not paid!

You just have to wonder who hired these guys and to what purpose?  what are their connections?

========================================
1 week after we had trouble with the MPIN, we still don't know who gives you a MPIN number and no government institution we spoke to knows what entity of the government gives you a MPIN, and without it we can't submit a response to an RFA.  These strategies are used stupidly to keep Minority institutions away!  It is believed that if you multiply the road blocks, folks will quit asking!

THE UNIVERSITY OF PENNSYLVANIA HAS LAUNCHED THE CD19 TRIAL
"ADOPTIVE IMMUNOTHERAPY FOR CHEMOTHERAPY RESISTANT OR REFRACTORY CD19+ LEUKEMIA AND LYMPHOMA"
THEY ARE STUDYING CTL-O19, "AN AGENT COMPRISED OF AUTOLOGOUS T CELLS ENGINEERED  TO EXPRESS AN ANTIBODY AGAINST CD19"

CALL DR NOELLE FREY AND  DAVID PORTER AT 215-662-2867 TO REFER PATIENTS!

1.ABCC1 GENE (WIKIPEDIA)
Multidrug resistance-associated protein 1 is a protein that in humans is encoded by the ABCC1 gene.^[1][2]
The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra-and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutathione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternative splicing by exon deletion results in several splice variants but maintains the original open reading frame in all forms.<sup>[3]

=====================================================ATP IS REQUIRED FOR THE FUNCTION OF ION CHANNELS BUT THE PRIMARY DYSFUNCTION APPEARS TO INVOLVE CYTOKINES AND GROWTH FACTOR.  ITS EXISTENCE SEEMS TO CONFER RESISTANCE TO DRUGS.
 ======================================================================
 ALSO READ</sup> 

1. study found a cytomegalovirus UL138-mediated loss of cell surface MRP1 and reduction of substrate export by MRP1; cytomegalovirus latency-associated loss of MRP1 and accumulation of vincristine, an MRP1 substrate, depleted virus from naturally latent progenitors all of which are in vivo sites of latency
2. This is the first study showing significant associations of a higher MRP1 protein expression with less accelerated FEV1 decline in COPD patients using long-term therapy with inhaled corticosteroids
3. Expression of ABCC1 by HRS cells in CHL patients predicts a higher risk of treatment failure and is marginally associated with poorer failure-free survival using standard frontline chemotherapy regimens.
4. A review of recent advances in understanding the role and mechanism of MRP1/ABCC1 polymorphisms in drug resistance, disease susceptibility and severity, and prognosis prediction.
5. collagen/beta1 integrin/ERK signaling up-regulates the expression and function of ABCC1
6. Substitution of two of these residues with alternative amino acids has allowed us to produce an almost cysless form of DeltaMRP1 that traffics to the plasma membrane
7. CK2alpha and MRP1 interact physically, and recombinant CK2 phosphorylates MRP1-derived peptide in vitro in a Thr249-dependent manner.
8. ABCB1 expression is limited to endothelial cells, whereas ABCC1 expression could mark a minority of tumor cells approaching a stem-like status.
9. ABCB1 and ABCC1 expression correlates with different prognostic factors in pediatric patients with acute leukemia.
10. We have demonstrated that vincristine resistance mediated by CD40 activation was induced by an increased expression of MRP1 by AKT signaling in human multiple myeloma cell lines.

²

The myeloid transcription factor GATA-2 regulates the viral UL144 gene during human cytomegalovirus latency in an isolate-specific manner.

Poole E



<sup>============================================================IS GATA 2 A VIABLE TARGET TO REDUCE DRUG RESISTANCE AND SURVIVAL OF MYELOID LEUKEMIA.
ARE LUNA AND MIEP INDICATIONS OF ROLE OF AZACITIDINE!

3.</sup>

A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency.

Liang Y, Quenelle D,

4.SPINK GENE

INVOLVED IN CELIAC DISEASE
WIKI"The structure of the Kazal repeat includes a large quantity of extended chain, 2 short alpha-helices and a 3-stranded anti-parallel beta sheet.^[2] The inhibitor makes 11 contacts with its enzyme substrate: unusually, 8 of these important residues are hypervariable.^[3] Altering the enzyme-contact residues, and especially that of the active site bond, affects the strength of inhibition and specificity of the inhibitor for particular serine proteases.^[3][4] The presence of this Pfam domain is usually indicative of serine protease inhibitors, however, Kazal-like domains are also seen in the extracellular part of agrins which are not known to be proteinase inhibitors.

Kazal_2

This domain is usually indicative of serine protease inhibitors that belong to Merops inhibitor families: I1, I2, I17 and I31. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays and have a central alpha-helix, a short two-stranded antiparallel beta-sheet and several disulphide bonds.^[5][6][7] The amino terminal segment of this domain binds to the active site of its target proteases, thus inhibiting their function."

WITH THEM A SLEW OF GENES COME TO YOUR ATTENTION:
Human genes encoding proteins containing Kazal-type domains include:

Kazal_1

• AGRIN, CPAMD8
• FST, FSTL3, FSTL4, FSTL5
• IGFBPL1
• SMOC1, SPARC, SPARCL1, SPINK1, SPINK2, SPINK4, SPINK5, SPINK5L2, SPINK5L3, SPINK6, SPINK7, SPINK9
• TMEFF1, TMEFF2

Kazal_2

• C6, CFI
• FSTL1, FSTL3
• HTRA1, HTRA3, HTRA4
• IGFBP7, KAZALD1, LST3, RECK
• SLC21A8, SLCO1A2, SLCO1B1, SLCO1B3, SLCO1C1, SLCO2A1, SLCO3A1, SLCO4A1, SLCO4C1, SLCO5A1, SLCO6A1, SMOC2, SPINK5, SPOCK1, SPOCK2, SPOCK3
• WFIKKN1, WFIKKN2
•  
• LET'S GO TO WORK!

MORE WITH MEDSCAPE
"CHICAGO, Illinois — The results of meta-analysis presented this week at the American Diabetes Association (ADA) 2013 Scientific Sessions adds new heft to earlier observations that metformin is associated with a reduction in the risk of cardiovascular events while rosiglitazone (Avandia, GlaxoSmithKline) increases the risk, including the risk of heart failure and MI."

THIS IS A BIG DEAL WITH METFORMIN!

Medscape Medical News from the:

• 2013 Annual Meeting of the American Society of Clinical Oncology®

This coverage is not sanctioned by, nor a part of, the American Society of Clinical Oncology.

Medscape Oncology

Vitamin D Deficiency in Pancreatic Cancer

An ASCO® Poster Brief

Brandon G. Smaglo, MD, Katherine Van Loon, MD, MPH

DisclosuresJun 24, 2013

 

Editors' Recommendations

• Vitamin D Gene Variations Linked to Risk for Colon Cancer
• A Cause of Cancer Disparities? Vitamin D, Say Pair

Vitamin D Deficiency Prevalent in Cancer Patients

Editor's Note: What could deficiencies in serum levels of vitamin D tell us about pancreatic cancer? Medscape spoke to Katherine Van Loon, MD, MPH, Assistant Professor, University of California, San Francisco, who presented a study at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO®) that sought to answer this question.
Medscape: You presented a study examining the levels of 25-hydroxyvitamin D and survival in patients with advanced pancreatic cancer.^[1] Obviously, we don't have a lot of good biomarkers in pancreatic cancer. Why pick vitamin D?

Information from Industry

Delivery options that allow your relapsing MS patients to spend less time on injection preparation

View product features

Dr. Van Loon: There is a growing body of literature about the role of vitamin D in various cancers.^[2] Colorectal cancer is the disease for which we have the most evidence of a possible association with vitamin D deficiency.^[3,4]
With regard to pancreatic cancer, we know that the vitamin D receptor is overexpressed in human pancreatic cancer cell lines, compared with normal pancreatic cells.^[5] Data from animal and cell-line models also suggest that vitamin D metabolism is important in pancreatic tumor maintenance and may contribute to this tumor's chemoresistance. We were interested in finding out the prevalence of vitamin D deficiency in patients with advanced pancreatic cancer and whether vitamin D levels affect survival.
Medscape: What did you find?
Dr. Van Loon: Vitamin D is a fat-soluble vitamin, and pancreatic cancer patients often present with symptoms of malabsorption. Vitamin D deficiency was highly prevalent in this patient population. Our data were similar to those from cohorts of patients with other cancers. Rates of vitamin D deficiency were particularly high among the black study participants.

 

• References

 

Section 1 of 2

Next: Would Vitamin D Supplement Improve Outcomes?

 

*Met today with DR Moreno's group as we cover their service at local hospital.  Our help is appreciated .
* Submitted SBIR grant application through local SBA Office, will recruit the help of the local Congressman!
This regarding our 2 projects on early lung cancer detection and racial disparities of triple negative Breast cancer.
* Register for participation to the FOUNDATION HOSPITAL PREVENTION DRIVE (Early detection of Hypertension, Diabetes Mellitus, Prostate cancer, etc...) in July 2013.
*will fly to Washington DC tomorrow for a short session and contacts!
*
AND YES SIRRRYYY, WE ARE INVITED!

If you are having trouble viewing this email, try viewing it in a browser.

Challenging Cases® in Hematology

Dear Dr. Mutombo Kankonde, We would like to invite you to participate as a consultant in the Challenging Cases® in Hematology research event! August 10, 2013 Loews Miami Beach Hotel Miami, FL Click Here to Register for this Event  You may only register for one meeting in this series. Our Challenging Cases®  programs utilize a case-based presentation format and an audience response system to allow for a unique peer to peer information gathering environment.  Specific market research questions are created for each program to gain an in-depth understanding of how oncology patients are diagnosed and treated across the country.  ATTENDEE REQUIREMENTS: You must be a practicing/academic medical oncologist/hematologist caring for patients on a regular basis. You must have completed your oncology fellowship. You must be able to act as a consultant for Xcenda by responding to all questions utilizing an electronic keypad. You can only attend 1 research event per series that Xcenda offers. In return for your participation as a consultant, you will be provided with the following: One round-trip coach airline ticket Hotel accommodations for Friday and Saturday evenings Meals during the event for Attendees only $100 to cover any incidental expenses; this check will be given at the conclusion of the meeting In accordance with PhRMA Guidelines, breakfast and lunch will be provided for attendees only Once you are accepted into this event you will receive a confirmation that will include program details . We look forward to your participation at this event! Sincerely, Mark Green Chief Medical Officer Xcenda, AmerisourceBergen Consulting Services

ACTIVITY AT CRBCM

After our Award winning from MDHONORS, the project was reviewed at the University of Virginia tissue bank, I am pleased to report that this University will provide tissue for the first phase of our study.  We are now in the process of acquiring PCR technology equipment, and vlam ! start working.   The challenge is on!

Our Laboratory(RGCC)

 

Aura PCR.

PCR Workstation.

• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 

123

FURTHER TARGETS

WHSC1
 histone-lysine N-methyltransferase NSD2 is an enzyme that in humans is encoded by the WHSC1 gene.^[1][2][3]
This gene encodes a protein that contains four domains present in other developmental proteins: a PWWP domain, an HMG box, a SET domain, and a PHD-type zinc finger. It is expressed ubiquitously in early development. Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4. This gene maps to the 165 kb WHS critical region and has also been involved in the chromosomal translocation t(4;14)(p16.3;q32.3) in multiple myelomas(WIKIPEDIA)
ALSO

Translocation t(4;14)(p16.3;q32) Is a Recurrent Genetic Lesion in Primary Amyloidosis

==================================

THERE WAYS TO SUPPRESS SOME OF THE CYTOKINE

 

A unique mRNA initiated within a middle intron of WHSC1/MMSET encodes a DNA binding protein that suppresses human IL-5 transcription.

Garlisi CG, Uss AS, Xiao H, Tian F, Sheridan KE, Wang L, Motasim Billah M, Egan RW, Stranick KS, Umland SP.

Source

Departments of Allergy and Immunology, and Bioinformatics, Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0539, USA. charles.garlisi@spcorp.com

Abstract

Human interleukin (IL)-5 gene transcription is regulated by several transcription factor binding sites, including CLE 0, GATA, and a region from position -123 to -92 known as response element (RE)-II. By expression cloning, a partial protein was identified that bound to concatamers of RE-II. Recombinant protein derived from this initial complementary DNA (cDNA) encoding the partial protein specifically bound to RE-II-containing oligonucleotides in electromobility shift assays."

  =============================

DTL GENE 

activates  p21

The p21(CIP1/WAF1) protein can also interact with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2, and may be instrumental in the execution of apoptosis following caspase activation. However p21 may inhibit apoptosis and does not induce cell death on its own.^[5] Two alternatively spliced variants, which encode an identical protein, have been reported.
p21(CIP1/WAF1) is a CKI that directly inhibits the activity of cyclin E/CDK2 and cyclin D/CDK4/6 complexes. p21 functions as a regulator of cell cycle progression at S phase.^[6] The expression of p21 is controlled by the tumor suppressor protein p53. Sometimes,it is expressed without being induced by p53. This kind of induction plays a big role in p53 independent differentiation which is promoted by p21. Expression of p21 is mainly dependent on two factors 1) stimulus provided 2) type of the cell. Growth arrest by p21 can promote cellular differentiation. p21 therefore prevents cell proliferation."
wikipedia
not the involvement of CASPASE, P53 

CDC45L gene
==========
an essential protein required to the initiation of DNA replication. Cdc45 is a member of the highly conserved multiprotein complex including Cdc6/Cdc18, the minichromosome maintenance proteins (MCMs) and DNA polymerase, which is important for early steps of DNA replication in eukaryotes.
this gene talks to ORC1,   a six subunits protein complex essential for the initiation of the DNA replication that serves as a template for this initiation.While other ORC subunits are stable throughout the cell cycle, the levels of this protein vary during the cell cycle, which has been shown to be controlled by ubiquitin-mediated proteolysis after initiation of DNA replication. (Mcm protein)This protein is found to be selectively phosphorylated during mitosis. It is also reported to interact with MYST histone acetyltransferase 2 (MYST2/HBO1), a protein involved in control of transcription silencing.^{[2]  wikipedia}

MYST2 has been shown to interact with Androgen receptor,^[2] ORC1L^[1] and Vimentin.<sup>[4][5]
=============================LINKING ANDROGEN HORMONE STIMULATION TO GENE SILENCING !

TOP2A</sup>

 WIKIPEDIA
This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA. Two forms of this enzyme exist as likely products of a gene duplication event. The gene encoding this form, alpha, is localized to chromosome 17 and the beta gene is localized to chromosome 3. The gene encoding this enzyme functions as the target for several anticancer agents and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced activity of this enzyme may also play a role in ataxia-telangiectasia.^[1]

 TOP2A has been shown to interact with HDAC1,^[2][3] CDC5L,^[4] Small ubiquitin-related modifier 1^[5] and P53.<sup>[6]

INHIBITORY iNTERACTION WITH BCL-2, A LIMITING FACTOR
DHFR
NCBI RESOURCE</sup>

Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids. While the functional dihydrofolate reductase gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like genes have been identified on separate chromosomes. Dihydrofolate reductase deficiency has been linked to megaloblastic anemia. [provided by RefSeq, Jul 2008]

 CIT GENE LIKENKED THROUGH SEVERAL INTERMEDIARY TO THE RHO GENE WHOSE FUNCTIONS INCLUDE:
"The Rho family of GTPases is a family of small (~21 kDa) signaling G protein (more specific, a GTPase), and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic organisms including yeasts and some plants. Three members of the family have been studied a great deal: Cdc42, Rac1, and RhoA. Rho proteins have been described as "molecular switches" and play a role in cell proliferation, apoptosis, gene expression, and multiple other common cellular functions.^[1][2]

WIKIPEDIA

CIT (gene) has been shown to interact with RHOB^[3] and RHOA.^[4][3]
 h CIT,^[4] ARHGEF3,^[5] ARHGDIG^[6] and RHPN2.^[7]
AND 

Human CNK1 Acts as a Scaffold Protein, Linking Rho and Ras Signal Transduction Pathways

 

AND  z Gene summary for CNKSR1:

This gene is a necessary element in receptor tyrosine kinase pathways, possibly as a tyrosine phosphorylation target.

It is involved in regulation of RAF in the MAPK pathway and may also play a role in a MAPK-independent pathway.

(provided by RefSeq, Jul 2008) 

 

====================================THESE ARE TARGET TO BLOCK TO AVOID SPILL OVER INTO MAJOR PATHWAYS!  IF YOU WANT TO STOP tHYROID CANCER TO FURTHER GROW!  BLOCK THE CONNECTIONS!

^"

HYPOTHESIS IN THROMBOSIS!

THE NOTION THAT INFLAMMATORY BOWEL DISEASE (IBD) CAN BE EXACERBATED BY
NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAID), opens the door to speculation that in a certain set of patients, NSAID can precipitate a catastrophic event including stroke and heart attack or sudden death syndrome.
IBD seems to include a thrombostatic state full of risk for  thrombosis formation therefore the hypothesis  does not seems far fetched.  In patients with IBD, the level of IL23 seems to be elevated.  And the disease appears to be linked to this.   IS THERE JUSTIFICATION TO RECOMMEND THAT BEFORE PUTTING PATIENT ON aSPIRIN, THAT THE LEVEL OF INTERLEUKIN-23 BE TESTED?
IT HAS BEEN ALSO SUGGESTED THAT THE EXACERBATION OF IBD IS DUE TO THE SUPPRESSION OF A COUNTER-BALANCING CYTOKINE, MAY BE INTERLEUKIN-4.  SHOULD WE BE MONITORING LEVEL OF INTERLEUKIN-4 TO PREDICT THE RISK OF FURTHER THROMBOSIS IN CORONARY ARTERY DISEASE? IS HIGH INTERLEUKIN-4 PROTECTIVE OF FURTHER THROMBOSIS?  WHAT CAUSES EXTENSION OF THROMBOSIS?

PARADIGM SHIFT NEEDED IN PREVENTION MEDICINE!

IF ONE CAN DIE BECAUSE A DYSFUNCTION IN THE NOTCH OR THE WNT PATHWAYS? WHY MONITOR CHOLESTEROL!
AN NHI RFA ASKED:" In particular, “sudden death” among dialysis patients, even in the pediatric age range, is largely unexplained and needs further study.". Well we monitor in Chronic renal failure K,Na,Ca,BUN,Creatinine,GFR,cholesterol,PTH...how come we still have these sudden death.  Nobody checked the status of amplification on the Wnt, the NOTCH, PI3K,AKT, NITRIC OXIDE, which we know to be affected in this disease. I tell you right now this will be medicine of the future!

Case in point:  The trade off Hypothesis
----------------------------------------
"When Chronic Kidney disease impairs the kidney's ability to excrete phosphate, Phosphate accumulate in the intracellular and extracellular fluid and lead to the physicochemical formation of Calcium-phospate complexes that reduce the level of ionized calcium". Low serum calcium will trigger release of PTH which suppress the reabsorption of Phosphate by the proximal tubule of the kidney and increase renal excretion of phosphate but as the process continue, the level of Phosphate drops and the relative increase of Calcium suppresses the PTH but the new steady state is achieved at a higher PTH threshold.  The recognition that a higher PTH is needed tells us that other receptor susceptible to PTH are now Hyperstimulated.  At Bone level, the bone continue to be affected and RENAL BONE DISEASE WILL PROGRESS EVEN AS CALCIUM AND PHOSPHATE ARE CORRECTED IN THE SERUM!
QUESTION FOR YOU, WHAT NEEDS TO BE MONITORED, CALCIUM OR PHOSPHATE Vs THE PTH GENE?
OVER EXPRESSION OF A GENE WILL IMPACT OTHER GENES AND UNTIL THAT OVEREXPRESSION IS CORRECTED WE HAVE NOT ACCOMPLISHED MUCH PREVENTION!
UNTIL WE START MONITORING GENE EXPRESSION, AMPLIFICATION OR SUPPRESSION, WE ARE NOWHERE IN PREVENTIVE MEDICINE FOR STROKE, CORONARY ARTERY DISEASE OR DIABETES MELITUS FOR THAT MATTER!

ANTI-TUMOR NECROSIS FACTORS

1.INFLIXIMAB
2.ADALIMUMAB (HUMIRA)
3.CERTOLIZUMAB PEGOL(CINZIA)
4.NATALIZUMAB (WATCH OUT-LEUCOENCEPHALOPATHY)

STRONG GENES ARE ASSOCIATED WITH MALFORMATIONS
================================================
Times and times again in the life of this blog, we continue to stress that the power of a gene is revealed when its deficiency, lack of function or mutation leads to a Malformation.  Another example of this is the Androgen or steroid related gene.  Women with Inflammatory bowel disease who are pregnant and given steroids have either early/premature rupture of membranes and/or their infants have a higher rates of cleft lip!

TISSUES SHARE SAME GENES !
=================================
Whenever you target a gene with target therapy treatment, always keep in mind that genes are the same in all cells!  Patterns of gene silencing in various tissues determine the expression of same genes in various tissues.  And do remember that some mechanisms of silencing are irreversible and some are reversible. It is interesting that in irreversible cases not only the cell knows that the gene is silenced it keeps memory of this, meaning de-methylation of some genes in a particular tissue has no effect into new expression of that gene, as if not only the cell Methylate a gene to silence it, it also remove proteins that helps its expression once demethylated!
It is striking that expressed genes finding themselves targeted by therapy in the white blood cells, are also active in the brain and liver, leading to liver failure and and various Central Nervous system (CNS) side effects ranging from coma to LEUCO-ENCEPHALOPATHY! IT IS UNCLEAR WHETHER STUDYING THE LEVER OF AMPLIFICATION OF TLE4, OR STATUS OF THE GROUCHO FAMILY MEMBER COULD HELP PREDICT WHO WILL MORE LIKELY DEVELOP CNS SIDE EFFCT!

KEEPING YOU IN THE LOOP!

• State Health Commissioner  
• 
  

To

• "Undisclosed recipients:"@lists.in.gov  

The Indiana State Department of Health, in collaboration with the Marion County Public Health Department, Indiana Hospital Association, Association for Professionals in Infection Control and Epidemiology (Indiana Chapter), IU Health, and The New Wishard Eskenazi Health Hospital, has convened the Indiana Antibiotic Resistance Advisory Committee. The Committee is administering this survey to health care providers and hospital administrators to assess awareness of treatment, prevention, and antibiotic stewardship for multi-drug resistant organisms (MDRO), including Clostridium difficile, methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis, and most recently, carbapenem-resistant Enterobacteriaceae (CRE).

Enterobacteriaceae, a family of bacteria that normally live in the human gut, includes organisms such as Klebsiella species and Escherichia coli. CRE have developed resistance to almost all antibiotics, including broad-spectrum agents called carbapenems. Within the past 10 years, the incidence of CRE has been increasing across the United States. CRE infections are difficult to treat and associated with a high attributable mortality.

The survey, accessible through the SurveyMonkey link below, will take about 15-20 minutes to complete. The survey includes a brief demographic section, a section specific to CRE, and a section with questions on MDRO in general. Your input is very important, as survey data will be shared in aggregate form and allow the committee to establish priorities and develop educational materials.

Please complete this survey by the close of business on Thursday, July 11, 2013.   Thank you very much for your participation!

 

https://www.surveymonkey.com/s/JB8FF3P

 

 

William C. VanNess II, MD

State Health Commissioner

A CASE IN POINT WALKED IN, GENETIC AT WORK!
==========================================RECEPTOR FAILURE LEADS TO THE CROHN'S SYNDROME.


Last night at 1:am I received a call from the Emergency Room at a local hospital, a 29 year old mother of 4, under some stress had been taking Advil 6 tablets a day for Headache for 3-4 weeks, she now presented to the emergency room with 5 days of diarrhea and fever, with Hypokalemia (K=3.0) and severe Right  lower Quadran of the Abdomen.  An appendicitis was suspected and a CT of the abdomen and pelvis was obtained suggesting changes consistent with Appendicitis but most significant is a thick swollen initial colon (CECUM) with some surrounding "fluid" and minimal surrounding Adenopathies.  A surgical consultation has been obtained, the surgeon however is advising input first from a Colonoscopy.  We are waiting for the Gastroenterologist input as we speak!  The patient is NPO and Cipro-and IV Flagyl is being given, and further laboratory results are awaited!
If this case turns out to be an inflammatory bowel disease, It will be a classic reportable case!

Indeed "Non steroidal anti-inflammatory drugs (NSAID-in this case Advil taken for Headache) appear to be associated with exacerbations of disease". (GARY LICHTEINSTEIN)

First thing to remember as we discussed failure of receptors as a cause of Triple negative Breast cancers where defect in Heparan sulfate the Glycocalyx covering receptor on breast tissue  was a cause.  Here in the terminal Ileum and early Cecum, it is the Muramyl Dipeptide, a Peptidoglycan component of  gram positive bacteria which fails to interact with a Mutated NOD2 gene product. And these failure of stimulation at cellular levels are a potential irritant to the stress related c-JUN, and to production of Heat stroke proteins (most likely HSP90) and secondary stimulation of the NF-kB which leads to Cytokines.  In Inflammatory Bowel diseases, The cytokyne of choice is IL23, its opposing cytokine (may be IL4) knocked down by the NSAID, leads to a significant exacerbation of disease!
There is susceptility conferred by class II antigen DR molecule.  And of interest is the found Hypokalemia which result from Cation related ion-channel disturbance linked to the OCTN1 GENE.  "OCTN1,LOCATED ON 5q31, codes for an ion channel".  The DLG5 is involved. It "codes for a scaffolding protein that is important for maintaining epithelial integrity in various organs".

WE WILL INFORM YOU WHEN ALL IS SAID AND DONE  IN THIS INTERESTING CASE!

YOU BE THE JUDGE OF THIS CRYPTIC COMMUNICATION:


Hi, all!
We wanted to share some really good news for consumers about health care costs so that you can also help to get out the word. 
First, health insurance premium rebates, which average nearly $100 per family, are on their way to 8.5 million Americans. That is because the Affordable Care Act now holds health insurance companies accountable to consumers and ensures that American families receive value for their premium dollars. If an insurance company spends less than 80 percent (85 percent in the large group market) of your premium on medical care and efforts to improve the quality of care and instead spends it on overhead and corporate salaries, they must rebate the portion of premium that exceeded this limit. Thanks to the law, millions of Americans will get savings from their insurers.
The law is protecting consumers from rate hikes that don’t go to care. It, along with other provision of the Affordable Care Act, has already helped consumers save a total of $3.9 billion in 2012, and $5 billion counting the 2011 rebates.
Second, Americans know health care prices for decades were skyrocketing, but the health law is changing that. This week, we learned that the official measure of health care prices, the medical price index, fell in May. The average for the last year was the lowest it has been in over four decades -- a sign that health care is getting more affordable.
And third, a new report demonstrates this good news will continue.  A new PriceWaterhouseCooper report projects that medical cost growth will be lower in 2014 than in 2013. As they say: “defying historical patterns.” The report points to how the ACA, though its policies to promote value, reduce unnecessary care, and cut waste from the system, is driving down the cost of health care for all of us.
Meanwhile, we received a number of questions in response to our last email. Here are a couple answers:
If the pre-existing limitations are no longer allowed can an insurance company still decline to cover an applicant? 
No. No new applicants may be denied coverage due to a pre-existing condition starting in 2014, and permanently thereafter. Insurance companies will also be prohibited from charging more or carving out health benefits due to a pre-existing. Charging women more will become a thing of the past. And you won’t pay more based on the type of work you do or your family’s health history.
How does the ACA help people on Medicare?
People with Medicare now have free checkups and preventive services – you don’t have to be sick to see your doctor to stay healthy. They have a new discount on their prescription medicine in the so-called “donut hole” that’s already saved over six million seniors more than $700 each. The increases in their monthly Medicare premiums, like those for private insurance, have slowed down – with the Medicare Trustees projecting that they may actually drop in 2014. And, the part of the law that prevents insurance companies from spending premium dollars on overhead not care will begin in the Medicare Advantage next year, thanks to the Affordable Care Act.
We’ll tackle more of your questions in future emails, so be sure to let us know what’s on your mind.
Thanks!
Tara
Tara McGuinness
Senior Communications Advisor
The White House
=======================================================

CRBCM DOES NOT ENDORSE ANY POLITICAL SIDE!
THIS COMMUNICATION IS PUBLISHED FOR YOUR "NEED TO KNOW" !

GENETIC ISSUES IN LYMPHOPROLIFERATIVE DISORDERS, ASPECTS OF GENETIC  BASED PATHOPHYSIOLOGY IN THIS DISEASE

Now it is established that lymphoma are due to a critical event causing Heavy chain IgH to be transposed into proximity with a promoter of PAX5 gene leading to 2 events
1. stimulation of TLE4 that force differentiation to lymphocyte proliferation. TLE4 is a tranduction enhancer which tell the cell no Brain differentiation by a negative regulation of the Groucho family members!  but it does force proliferation of lymphoblasts forward.

2.to insure survival of lymphoblasts, it consumes or de-repress the Death protein 6 leaving FAS intact and therefore NO APOPTOSIS, and favoring an intact Kinechore plate to preserve speedy cell division by preserving the Centromere  protein C.  Decrease of the Death receptor has a significant  3rd effect on a series of TNF receptors and ligand which ultimately through ETS1 and TTRAP end up affecting CD40 leading to weakening of the cell presentation of Antigen which is the underlying immunodeficeinec in lymphoma (similar to hyper IgM Syndrome)

This is the underlying pathophysiology of Lymphoma as it looks today.

OF NOTE CD40 IS ALSO INVOLVED IN ALZHEIMER!
JUST REMEMBER THE CD40 THRU TRAF GENES INTERACTS WITH CD30 TO ACTIVATE THE NF-kB AND CYCLINS!

CRITICAL TARGET IN THIS PATHWAYS

1.PROTEIN QD
2,KINETOCHORE, CENTROMERE PROTEIN C
3.FAS
4.DEATH PROTEIN 6
5.TTRAP
6.CD40
7.CD30
8.TRAF (s)
9.CASPASE 8
10.TNF

AURKA GENE/ AN INDICATION FOR TAXANES?
"Aurora A is a member of a family of mitotic serine/threonine kinases. It is implicated with important processes during mitosis and meiosis whose proper function is integral for healthy cell proliferation. Aurora A is activated by one or more phosphorylations^[4] and its activity peaks during the G2 phase to M phase transition in the cell cycle.<sup>[5]"WIKIPEDIA

"Aurora A is critical for proper formation of mitotic spindle. It is required for the recruitment of several different proteins important to the spindle formation. Among these target proteins are TACC, a microtubule-associated protein that stabilizes centrosomal microtubules and Kinesin 5, a motor protein involved in the formation of the bipolar mitotic spindle.[4] γ-tubulins, the base structure from which centrosomal microtubules polymerize, are also recruited by Aurora A. Without Aurora A the centrosome does not accumulate the quantity of γ-tubulin that normal centrosomes recruit prior to entering anaphase. Though the cell cycle continues even in the absence of deficient γ-tubulin, the centrosome never fully matures; it organizes fewer aster microtubules than normal.[5]"WIKIPEDIA

"</sup>
Aurora A dysregulation has been associated with high occurrence of cancer. For example, one study showed over-expression of Aurora A in 94 percent of the invasive tissue growth in breast cancer, while surrounding, healthy tissues had normal levels of Aurora A expression.^[4] Dysregulation of Aurora A may lead to cancer because Aurora A is required for the completion of cytokinesis. If the cell begins mitosis, duplicates its DNA, but is then not able to divide into two separate cells it becomes an aneuploid- containing more chromosomes than normal. Aneuploidy is a trait of many cancerous tumors.^[7] Ordinarily, Aurora A expression levels are kept in check by the tumor suppressor protein p53.^[4]
Mutations of the chromosome region that contains Aurora A, 20q13, are generally considered to have a poor prognosis.<sup>[4]WIKIPEDIA"

===============================================================
AGENTS THAT ACTIVATES P53 WILL HAVE A STRONGER EFFECT IN THESE CANCER AS THEY WILL SUPPRESS THE AURORA A
AND SHOULD MORE LIKELY COMBINED TO TAXANE AS IT ACTS ON MICROTUBULES?</sup>