FOOD FOR THOUGHT

* A trial has shown that Doxepin rinse may reduce pains from oral Radiation induced Mucositis.

*Radiation post lumpectomy does improve survival even in the elderly
*Memantine 20 mg daily did alleviate loss of cognitive functions post whole brain Radiation
* Now that Tamoxifen can be given for 10 Years, people are still suggesting that switching at 5 years to Letrozole in postmenopausal women, is better but may be we need another clinical trial?  It is reported that switching to Letrozole lead a a 48% drop of Recurrence and 24% drop in chance of death!

*Should maintenance alpha interferon be given in Esophageal and gastric cancer with Non-mutated Interferon receptors? or cancer with over expressed NF-kB.
does overexpression of FOS predict response to Interleukin or Interferon.

*It is wrong to stop inhibitor to VEGF IN CANCER TREATMENT UNTIL DISEASE PROGRESSION, AND INSTEAD OF STOPPING, REPLACE IT BY AN MTOR INHIBITOR, THIS WILL ADD AN OPTION TO COLON CANCERS!
ESMO DID SHOW THAT UPFRONT COMBINATION OF AVASTIN AND MTOR FAILED TO IMPROVE RESULTS (renal cancers) BUT GIVING MTOR AFTER AVASTIN FAILURE IS STILL BELIEVED TO BE BETTER (PROOF OF CONCEPT.  DOES THE ESCAPE MECHANISMS TO AVASTIN OFFER AN OPPORTUNITY TO MTOR INHIBITOR FOR ACTION OR ACTIVITY? WHAT ARE THE PREDICTORS TO MTOR INHIBITORS 'ACTION?  IS TISSUE HYPOXIA SECONDARY TO ENDOTHELIAL DISTURBANCES RESULTING FROM AVASTIN A PREDISPOSITION TO MTOR INHIBITOR ACTION?

*SHOULD WE GO AHEAD AND USE NAB-PACLITAXEL AND GEMZAR IN ADJUVANT SETTING NOW?(PANCREATIC CANCER)

*ADDING ERLOTINIB TO AVASTIN AS MAINTENANCE THERAPY AFTER FIRST LINE CHEMOTHERAPY OFFERED BETTER PROGRESSION FREE SURVIVAL (1 MONTH BETTER) IN A PHASE III TRIAL PRESENTED AT ASCO 2012! (COLON CANCER)

MORE APPROVED DRUGS

*Rivaroxaban  for acute treatment and long term secondary prevention of Venous thromboembolism
*Apixaban for the prevention of stroke and systemic arterial thrombosis in patients with non valvular Atrial Fibrillation.   Apixaban 5 mg PO BID
reduce dose to 2.5 mg if patient less than 60 kg weight
                        Creatinine >1.5
                         Age >80
*Rivaroxaban approved for atrial fibrillation at 20 mg daily if GFR >50
and  15 mg if GFR between 15 and 50
No use of Riva if GFR<15

*T-cell therapy, that is genetically engineered T-cells, is a valid modality of cancer treatment.  Porter et al updated their finding at the ASH describing response rate in refractory CLL and ALL.  Patients were given a lentiviral vector that expressed a chimeric antigen receptor "with specificity for the B cell Antigen CD19 paired with CD137 and CD3-zeta." (hemonc today) some of the reported results where positively dramatic.
The experience with MAGE 11 for treatment refractory melanoma did not go so well.

Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor 

What you pick to attack should not be in the brain (attack to the brain by T cell is likely), and involving a "crazy gene" the like of Androgen Receptor will have many unexpected consequences.  patient died with coma and seizures!   T-cell tissue penetration is bound to occur because it is what T cell do so your task is to pick the receptor carefully!

and don't go out there and pick p300, a potent and ubiquitous transcriptional regulator, because it is Ubiquitous!  Tissue specificity as done above in Hematologic malignancies would be more appropriate!
-----------------------------------------------------------------------------------------------

NOW A BIT OF GOOD NEWS

Infusion of Autologous dendritic cell Immunotherapy  (AGS-003) given with SUNITINIB extended survival in Metastatic Renal cell cancer!   Think Immunotherapy when the going get tough we told recently... congrats to NC researcher to have proven the point!   Follow this principle in tough Myeloma cases.  May be drendritic cell infusion will work in Myeloma!

IMPORTANT GENE FUNCTIONS WE WILL REVISIT AND CONFIRM

1. c-MYC  increases or cause progression into S-phase and DNA replication
therefore its amplification worsen proliferation and is and prognosis factor in cancer where it is involved.
But it also means you know what you get when you block this if you can.

2. Rb1 "sequester" E2F and blocks it from causing dimerization that pushes cell into S phase, the global effect of Rb1 by hiding E2F is to block the cell in G1.
amplification of E2F1 activates CPP32  and may lead to Apoptosis.
E2F5 belong to the Dream Multicomplex structure reminiscent of CBF
Rb1 is a definite member of the Crazy Genes, it interacts with many genes including the BRCA and the Androgen Receptor gene!

This stuff act directly at Histone level and its DNA.  If you want o know gene silencing here we go:


"  leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex By similarity. In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity. Ref.37"  (Uniprot.org)

"In addition to bladder cancer, somatic mutations in the RB1 gene are associated with many other types of cancer. For example, changes in the RB1 gene have been reported in some cases of lung cancer, breast cancer, a bone cancer known as osteosarcoma, and an aggressive form of skin cancer called melanoma. Somatic RB1 mutations have also been identified in some leukemias, which are cancers of blood-forming cells. Somatic RB1 mutations in cancer cells inactivate pRB so it can no longer regulate cell division effectively."(nih.gov)
question: What would happen if you target Calcineurin
Any time you act on the Histone, their remodeling, and RNA, you can affect tough cancers including Leukemias/sarcoma.

3.p16 inhibit CDK4 associated to Cyclin D1 (cell division)

 p16 has a trancript,  "this transcript contains an alternate open reading frame (ARF) that specifies a protein that is structurally unrelated to the products of the other variants. The ARF product functions as a stabilizer of the tumor suppressor protein p53, as it can interact with and sequester MDM2, a protein responsible for the degradation of p53.[4" wikipedia
This stuff Mutated in Melanoma and Pancreatic cancer....

"Concentrations of p16INK4a increase dramatically as tissue ages. Therefore p16INK4a could potentially be used as a blood test that measures how fast the body's tissues are aging at a molecular level.^{[12]"  would it explain why Pancreatic cancer is seen more in elderly?  Can we assume this mutation in elderly with pancreatic cancer?}

4. P53 acts through p21WAF1

" The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin-CDK2 or -CDK1 complexes, and thus functions as a regulator of cell cycle progression at G₁."
" p53 activates numerous microRNAs (like miR-302a, miR-302b, miR-302c, and miR-302d) that directly inhibit the p21 expression"Wikipedia
Gives us a number of targets in sarcoma where P 53 is over active

5.p14 inhibit MDM2 and free P53 to act

" p14ARF is an alternate reading frame (ARF) product of the CDKN2A locus. Both p16INK4a and p14ARF are involved in cell cycle regulation. p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G₁/S checkpoint of the cell cycle. Loss of p14ARF by a homozygous mutation in the CDKN2A (INK4A) gene will lead to elevated levels in mdm2 and, therefore, loss of p53 function and cell cycle control."

LET'S GO OUT THERE FIND SARCOMA WHERE p53 IS ACTIVATED, WE KNOW WHAT TO DO NOW!

TRIPLE NEGATIVE BREAST CANCER

At the 30th Annual Miami Breast cancer conference, this puzzling group of Breast cancer emerged one more time for discussion as it continue to be challenging to investigators.  It is a complicated topic because the disease is not unique.  Triple negative Breast Cancer is a group of diseases therefore no unique genetic Mutation was brought to light as a determinant driver.  Canadian investigators reported Mutations in P53, PTEN and PI3KCA.  There was suggestion that as a group TNBC represent 16% of Breast Cancer,  And 60% have a morphology pattern of Basal like cell cancers.  There is a reported suggestion that these basal like cell cancers had a higher P53 Mutation rate and overall higher genetic variability.  How BRCA 1, 2 Mutations fit in the group was not however discussed.

The BRCA Mutations are a challenging on their own.  Although they are interpretated to represent a familial tendency to the Breast cancer, it is good to remind ourselves they belong to a group of molecules involved in DNA repair.  We know that the neoplastic process does involve destabilizing P53 function and impairing normal control mechanisms including DNA repair and immune normal mechanisms.   There is an increased push into finding a way to discern these differences more specifically.  Whether family clustering or specific Exons will be used to make the case is still being evaluated.

Given the fact that alteration in Morphology is involved raises the issue of differentiation, status of MEK is of interest to us.  This question is of Interest to us because Globally we are talking about one pathway.
RAS/RAF/MEK/MAPK/MYC/FOS/STATs.  Disturbance at the Hormone  receptors have also been looked at since these will be also ER negative.
Given Metastatic potential of the TNBR, the Wnt pathway is also of interest.

(to be continued)

REFRESHER NEWS!

*Quizartinib,, an investigational TKI
show promises in FLT3 AML allowing time, with some effectiveness, for stem cell transplant

*A study confirm that Hct should be maintained below 45% in Polycythemia Vera as patient above this percentage had four-fold higher incidence of thrombotic events, a study confirmed.

*Once again, and repetition is good, Ibrutinib, a Bruton's TKI show appreciable activity in CLL alone or in combination with Rituxan.

* From Smita Bathia, MD
we learned that "genes involved in the metabolism of Anthracyclines include CBR1, CBR3,NQO1, MRP1,2
defense for Oxidative stress that can cause damage to heart cells, NCF4 RAC2 CYBA,SOD
Blood pressure and heart rate regulation AGT, AGTR1, ACE, ADRB1
Iron Homeostasis HFE"

This will prompt to plan a discussion of gene Nomenclature relevant to these genes!

*Adding Vorinostat to Chemotherapy during transplantation process reduces the incidence of Acute GVHD.
*Just a rminder again, Alterations in CYP2D6 affects efficacy of Tamoxifen.

CARNITINE
"In some of the studies, L-carnitine therapy was subsequently given for six months to a year, suggesting a possible role not only in acute management but also secondary prevention, according to the authors, led by Dr James J DiNicolantonio (Wegmans Pharmacy, Ithaca, NY)
The apparent survival gains from L-carnitine, which were only modestly significant, seemed to come from infarct-size limitation and cardiomyocyte membrane stabilization, with chronic improvements in cellular energy metabolism, according to their report published online today in the Mayo Clinic Proceedings."
THE ATTRACTION HERE IS ITS RELATION TO THE MTOR
THEY BOTH ACT ON GLUCOSE METABOLISM!

AVANDIA

"Rosiglitazone is a diabetes drug from the thiazolidinedione class; in September 2010, it was suspended by the European Medicines Agency (EMA) because it deemed that the product's cardiovascular risk outweighed its benefits.
At the same time, the FDA deemed there was "a signal of harm" but decided not to suspend the drug. Instead it requested readjudication of the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) study at the individual patient-data level. The agency also required that rosiglitazone-containing medicines be subject to a risk evaluation and mitigation strategy (REMS) program to ensure the safe use of the medicine in patients with no other options. (MEDSCAPE)

was avandia going to be pulled from the market? that was the 12 millions question in the article...
don't kill the messenger!

YOU WHO GOT A LAB  (THE CRBCM CAN'T, CRBCM DOES NOT HAVE  POLITICAL BACK BONE, WE ARE MUZZLED, POLITICALLY STOPPED FOR DOING RESEARCH, SO WE GIVE YOU THE CUES)
GO GET THE CURE FOR US!

USE shRNA TO SILENCE PI3K IN MELANOMA
OR RESTORE PTEN FUNCTION!

Small hairpin RNA

From Wikipedia, the free encyclopedia

Jump to: navigation, search

Lentiviral delivery of shRNA and the mechanism of RNA interference in mammalian cells.

A small hairpin RNA or short hairpin RNA (shRNA) is a sequence of RNA that makes a tight hairpin turn that can be used to silence target gene expression via RNA interference (RNAi). Expression of shRNA in cells is typically accomplished by delivery of plasmids or through viral or bacterial vectors. The promoter choice is essential to achieve robust shRNA expression. At first, polymerase III promoters such as U6 and H1 were used; however, these promoters lack spatial and temporal control.^[1] As such, there has been a shift to using polymerase II promoters to regulate expression of shRNA. shRNA is an advantageous mediator of RNAi in that it has a relatively low rate of degradation and turnover. However, shRNA is disadvantageous in that it requires use of an expression vector which can pose safety concerns.

IMPORTANT GENE INTERACTIONS II
-----------------------------------------------
2.
*In order to control Triple Negative Breast cancer, you got to control the Wnt pathway!!!
Loss of PTEN desactivates BRAFeffect by abrogating BRAF induced oncogen driven Senescence
of cancer cells.
* ACTIVATION OF BRAF INDUCES BENIGN OR GOOD PROGNOSIS LESIONS, HOWEVER MELANOMA SUPPOSE ASSOCIATED ALTERATIONS IN THE PTEN AND THEREFORE THE PI3K SIGNALING PATHWAYS OPENING THE DOOR TO A ROLE FOR THE MTOR IN MELANOMA..

*NON INHIBITION OF THE MTOR LEAD TO SUPPRESSION OF THE p15INK 48 WHICH INCREASE TELOMERE STABILITY!

IF THIS IS TRUE, PROTECTION OR RESTORATION (activation) OF PTEN SHOULD PROTECT OR PREVENT MELANOMA!

--------------------------------------------------------------
SUPPORTIVE EVIDENCES


2.1 

PTEN Loss Confers BRAF Inhibitor Resistance to Melanoma Cells through the Suppression of BIM Expression

Kim H.T. Paraiso1 et al.

"PI3K inhibitor enhanced BIM expression at both the mRNA and protein level and increased the level of apoptosis through a mechanism involving AKT3 and the activation of FOXO3a."

2.2  " Upon induction of BRaf(V600E) expression, mice developed benign melanocytic hyperplasias that failed to progress to melanoma over 15-20 months. By contrast, expression of BRaf(V600E) combined with Pten tumor suppressor gene silencing elicited development of melanoma with 100% penetrance, short latency and with metastases observed in lymph nodes and lungs. Melanoma was prevented by inhibitors of mTorc1 (rapamycin) or MEK1/2 (PD325901) but, upon cessation of drug administration, mice developed melanoma,"   Dankort et al.

3."β-catenin levels control tumor differentiation and regulate both MAPK/Erk and PI3K/Akt signaling. Highly metastatic tumors with β-catenin stabilization are very similar to a subset of human melanomas. Together these findings establish Wnt signaling as a metastasis regulator in melanoma"  Damsky et al.

• "β- catenin loss in Pten/Braf melanomas improves survival and inhibits metastasis
• β-catenin stabilization in Pten/Braf melanomas enhances metastasis
• Highly differentiated melanomas can be very metastatic in vivo
• β-catenin status in melanoma regulates PI3K/Akt and MAPK/Erk signaling"

2.4  " It has been reported that oncogenic activations of intracellular signaling pathways downstream of EGFR, including the RAS-RAF-MAPK and PI3K-PTEN-AKT signaling pathways, are important mechanisms for generating resistance to anti-EGFR MoAbs. In the RAS-RAF-MAPK pathway, active mutations of KRAS or BRAF are not uncommon"  Zhou et al
"The loss of PTEN expression, which was reported to occur in 19.0%–42.0% of Western and 30.0%–64.0% of Chinese CRC tumors, induces an increase in PIP-3 concentration and PIK3CA pathway activation"

2.5 "Beta-catenin Controls Metastasis in Braf-activated Pten-inactivated Melanomas" "beta-catenin levels control tumor differentiation and regulate both MAPK/Erk and PI3K/Akt signaling."

 

see the article.

2.6.

Abrogation of BRAF^V600E-induced senescence by PI3K pathway activation contributes to melanomagenesis PTEN depletion abrogates BRAF^V600E-induced senescence in human fibroblasts and melanocytes."

Liesbeth C.W. ET AL."

"  The PI3K pathway was often activated through either decreased PTEN or increased AKT3 expression in melanomas relative to their adjacent nevi. Pharmacologic PI3K inhibition in melanoma cells suppressed proliferation and induced the senescence-associated tumor suppressor p15^INK4B. This treatment also eliminated subpopulations resistant to targeted BRAF^V600E inhibition."

2.7

ICAM-1 Has a Critical Role in the Regulation of Metastatic Melanoma Tumor Susceptibility to CTL Lysis by Interfering with PI3K/AKT Pathway

1. Ahmed Hamaï1,
2. Franck Meslin1 ET AL.

  "More importantly, we found that the level of ICAM-1 expression by melanoma cells correlated with decreased PTEN activity. ICAM-1 knockdown in T1 cells resulted in increased phosphorylation of PTEN and the subsequent activation of AKT. We have additionally shown that inhibition of the phosphatidylinositol (3,4,5)-triphosphate kinase (PI3K)/AKT pathway by the specific inhibitor wortmannin induced a significant potentiation of susceptibility of G1 and ICAM-1 small interfering RNA–treated T1 cells to CTL-induced lysis. The present study shows that a shift in ICAM-1 expression, which was associated with an activation of the PI3K/AKT pathway, can be used by metastatic melanoma cells to escape CTL-mediated killing."

(PLEASE NOTE MART-1 AND ITS ROLE OR INTERACTION WITH PTEN!)

IMPORTANT GENE INTERACTIONS TO KEEP IN MIND!

1.  Mutation to NF1 may desensitize tumor to BRAF inhibitors:

NF1--RAS--BRAF--MEK-ERK-MAPK
Desensitization to BRAF is expected in tumor with NF1 Mutant.
Resistance to Vemurafenib (Zelboraf) should be checked for Mutation to NF1 and RAS.
Recently prostate cancer has been associated with mutation in the PKC family which interacts with RAS suggesting RAS amplification or suppression may result.  This could alter sensitivity to Cabozantinib,
"Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2." Smith et al.

REMEMBER NOW THERE ARE AT LEAST 4 MEDICATIONS DOWN THIS PATHWAYS
ANTI-EGFR/VEGF, ZELBORAF, CABOZANTINIB, MTOR INHIBITORS 
-------------------------------------------------------------------
 SUPPORTIVE EVIDENCES


1.1 "The BRAF kinase is a serine-threonine kinase that mediates signal transduction through the MEK-ERK pathway. An activating mutation of the BRAF kinase gene, located on exon 15, was recently found to result in a valine-to-glutamic acid substitution at amino acid 600 (BRAF^V600E mutation) that is an oncogene in human cancer and the most common mutation in PTC [8]. In recent years, the BRAF^V600E mutation has shown a high specificity for PTC, and its prevalence is highly variable, ranging from 30% to more than 80%, depending on the study. In the present study, the BRAF^V600E mutation was identified by multiplex real-time PCR. This method is as sensitive as dual-priming oligonucleotide-based multiplex PCR (Seegene) for detecting BRAF^V600E mutations.

The NF1 gene located on chromosome 17q11.2 encodes neurofibromin. The Ras-GAP is a potentially functional domain of neurofibromin [9]. The Ras-GAP-related domain (Ras-GRD) accelerates the conversion of active Ras-GTP to inactive Ras-GDP in various cell types and acts as a negative regulator of the p21ras signaling pathway [10]. Ras GTPases interact with multiple pathways, including the RAF-MEK-ERK mitogen-activated protein kinase pathway. Mutations in the NF1 gene result in abnormal cell growth and in the formation of benign and malignant tumors [3]. Because BRAF^V600E mutation and NF1 gene mutation are both involved in the MEK-ERK pathway, Koksal et al.[3] suggested that the development of PTC (papillary Thyroid cancer) in patients with NF1 may be associated with the ras gene but that further evidence is necessary to confirm this association."   FROM

Neurofibromatosis type 1 associated with papillary thyroid carcinoma incidentally detected by thyroid ultrasonography: a case report

Bu K Kim<sup>1et al!
------------------------------------------------------------------------------------------------------------------------------------------------

1.2</sup>  

Suppression of oncogenic Ras by mutant neurofibromatosis type1 genes with single aminoacid substitutions

NAKAfuku et al.

-------------------------------------------------------

1.3 "Once there, RAF proteins are activated and phosphorylated by different protein kinases.^24-28 Active RAF phosphorylates MEK that, in turn, phosphorylates and activates extracellular signal–regulated kinases 1 and 2 (ERK1/ 2).²⁹ Several studies have supported the importance of this effector pathway by showing the ability of Raf and MEK to transform rodent fibroblasts³⁰ as well as the ability of RAF inhibitors to revert aspects of the RAS-driven transformed phenotype, such as growth in soft agar.³¹

The second best-characterized RAS effector family is phosphoinositide 3-kinases (PI3Ks), which play important roles as mediators of RAS-mediated cell survival and proliferation.^32,33 When active, PI3K converts phosphatidylinositol (4,5)-bisphosphate (PIP₂) into phosphatidylinositol (3,4,5)-trisphosphate (PIP₃). PIP₃, in turn, binds the pleckstrin homology (PH) domain of Akt/PKB, stimulating its kinase activity, resulting in the phosphorylation of a host of other proteins that affect cell growth, cell cycle entry, and cell survival. PI3K can also activate Rac, and this activation is involved in cytoskeleton reorganization.³⁴ The functional importance of the RAS-PI3K pathway will be more extensively discussed in the next sections.

Another well-characterized RAS effector pathway involves Ral-GEF proteins. RalGEF members (RalGDS, RGL, RGL2, and RGL3) link RAS proteins to activation of the RalA and RalB small GTPases.³⁵ The biological function of these proteins is not yet fully understood, although there is evidence that they play an important role of this pathway in RAS-mediated transformation and tumorigenesis in vivo.^36,37 Expression of RalGDS cooperates with constitutively activated RAF to induce focus formation, suggesting a cooperation of RalGEF in RAS-mediated transformation in vitro.³⁸

Apart from the above-mentioned effectors, in recent years, an increasing number of molecules that specifically interact with RAS have been described, including Tiam1, p120GAP, NF1, MEKK1, Rin1, AF-6, PKC-ζ, Nore1, Canoe, and others. These proteins bind to RAS exclusively when it is in an activated state³⁹; however, the physiological role of some of these effectors has not yet been found. It has also been described that abnormal RAS signaling causes deregulation of the Rho GTPases family, including Rac1 and RhoA, but no direct association has been found yet."  (Castellano and downward)

1.4. "neurofibromatosis type I (NF1). While an association of NF1 with malignant gliomas has long been known in both adult and pediatric patients,^[32,33] this mutation was not previously known to be associated with sporadic GBM. By contrast, NF1-associated ras activation has been a hallmark of pediatric low-grade gliomas, particularly for optic pathway gliomas.^[33] These tumors lack many of the characteristic abnormalities observed in other astrocytic tumors and may help explain their excellent long-term prognosis.^[34] The rarity of low-grade glioma-development in adults with NF1 suggests a developmental period of sensitivity to this mutation in prenatal or early childhood.^[35]

Eliminate payer-denials

Find out how a team of electronic medical billing specialists can help you identify, correct, track, and challenge denials to receive maximum reimbursements.

Information from Industry

Non-NF1-associated low-grade gliomas in pediatric patients are classically associated with a truncated duplication of BRAF,^[36–40] with some variability in the breakpoint and partner rearrangement.^[41] Various researchers have shown that in these low-grade tumors, the fusion of BRAF with KIAA1549 leads to oncogene-induced senescence and improved clinical outcome."  Gilheeney et al

1.5."The most visible features of NF-1 are the neoplastic manifestations caused by the loss of Ras-GTPase-activating protein (Ras-GAP) activity mediated through the GAP-related domain (GRD) of neurofibromin (NF1), the protein encoded by NF1. However, the syndrome is also characterized by cognitive dysfunction and a number of developmental abnormalities."

 1.6"

---

Novel Tumor Suppressor Identified for Prostate Cancer
Researchers have identified the enzyme PKCζ, which acts as a tumor suppressor in prostate cancer and is part of a pathway that partly controls cell growth and metastasis…Azvolinski et al.

AT CRBCM WE ARE PROUD!

The Internal Revenue Services (IRS) after a careful review of activities at the CRBCM has bestowed upon CRBCM the status of "charity organization".   This is a milestone for CRBCM because it represents for us the successful completion of a long awaited process of careful scrutiny by United states'government.  CRBCM is a legitimate institution at its dawn.  Tomorrow is bright!  Our plans are still green and ready to unfold to help the people of El Paso and beyond.  We are strongly committed to move forward carefully but with determination...To help, please call 915-307-3354.
or send a donation to CRBCM
                                 2400 Trawood #303
                                  El Paso Tx 79938

And Help Cancer Research.
And remember the truth is not the privilege of a few,  it belongs to all of us, and anyone looking in the right place can uncover it for the benefit of all of us!  Be a part of the movement for the cure!

Finally: The IRS acknowledges the CRBCM's status of Public Charity under section 501 (c) (3) !