Like other stimulant-receptor, the notch is stimulated by an external stimulator (delta) which is sensed by O-glycose derivative before the signal is processed by the protein part of the receptor, here that processing end up by clivage of the internal portion of the protein receptor which is internalized and moved directly the nucleus stimulate mostly genes of proliferation such as c-MYC
But it is not the portion internalized only that is important, the portion left at the membrane is vibrating with effects, electronic polarization, release of TNF and Metalloprotease 2, activation of endocytosis in neighboring , cells and in the cell itself, offering itself to death,
but most interesting NOTCH at the membrane is sending to other cell a consensus and reminder message "this is what we all should be doing" if it "cease" and "desist" or "we keep on going", and that message is cease...you are dead.
if resuscitation is started and the notch says its ok, you are alive again!
The TNF is in charge when infection is the aggressor, so don't go out there upsetting your notch, remember the electric current in your brain and heart is notch driven, don't you go out there to upset it! for some people just the sight of blood is enough to pass out!
NOTCH is the "consensus" gene about what a group of cells should be doing "or cellular fate gene". if the notch is not ready and you are in coma, vegetative life is allowed!
Notch controls immunization by the memory of exposure, it controls resistance to drug by giving the consensus "we ought to resist" and provide the machinery to back up the decision. well wake-up to the fact that certain cancer cells are just darn resistant, and wherever they are, they get the message!
Monday, May 13, 2013
Sunday, May 12, 2013
More from the "NOTCH"
DESPITE THE FACT THAT THE NOTCH PATHWAY IS CRITICAL IN THE NORMAL FUNCTION OF THE PANCREAS, A FEW TREATMENTS AIMING AT PARALYZING THE NOTCH DID NOT WORK EITHER BECAUSE THEY DID NOT EFFECTIVELY DISABLE IT, OR BECAUSE THEY COULD ONLY OPEN UP THE DOOR TO SUSCEPTIBILITY OR REFRACTORINESS TO DRUGS THAT SUBSEQUENTLY WERE NOT GIVEN.
NOW WE KNOW WHY ANTI-VEGF BY THEMSELVES DO NOT WORK (TUMOR OVER EXPRESSION OF VEGFR2 ?DECOY).
WE SHOULD REMEMBER THAT MAIN THE PATHWAYS THERE ARE NOT HEDGEHOG, NOTCH OR ANGIOGENESIS, BUT CLEARLY RECEPTOR FAILURE AND SUBSEQUENT UPSET OF THE NF-kB...(IN PANCREATIC CANCERS) . THE NOTCH, HOWEVER, INTERVENES IN THE PAIN THIS CANCER GIVES!
NOW WE KNOW WHY ANTI-VEGF BY THEMSELVES DO NOT WORK (TUMOR OVER EXPRESSION OF VEGFR2 ?DECOY).
WE SHOULD REMEMBER THAT MAIN THE PATHWAYS THERE ARE NOT HEDGEHOG, NOTCH OR ANGIOGENESIS, BUT CLEARLY RECEPTOR FAILURE AND SUBSEQUENT UPSET OF THE NF-kB...(IN PANCREATIC CANCERS) . THE NOTCH, HOWEVER, INTERVENES IN THE PAIN THIS CANCER GIVES!
PHENOMENA AT THE "NOTCH"
THE NOTCH PROVIDES MANY OPPORTUNITIES FOR CURE OR INTERVENTIONS FOR THE CURE IN THOSE CANCERS:
1. WE KNOW THE Numb INHIBITS IT
2. IT IS REGULATED BY DELTEX
3. IT REGULATES BMP10, NRG1, Ephrin-B2
(CHECK OUT Rex-1)
INFLUENCED BY DII4
LIGAND DELTA STIMULATE IT
DLL1, DLL3, JAG-1,2
INDUCE PROLIFERATION BY ACTING ON c-MYC, p21, HES FAMILY
REDUCES AVASTIN EFFECT BY OVER-EXPRESSION OF VEGFR2
INTERACT WITH HEY GENE AND Cbf-1
PRESENILINS 1,2
THE BEAUTY IS THAT BEING A RECEPTOR, IT'S GLYCOSYLATION IS CRUCIAL TO ITS FUNCTION, DESTROY POFUT-1 AND SOMETHING WILL HAPPEN OR IMPAIR O-GLYCOSYLATION AND THE RECEPTOR FUNCTION IS KAPUTT!
FIBROBLAST GROWTH FACTOR 10,
WE ARE LOOKING AT ALL THIS AT CRBCM,
BUT KNOW THIS: YOU ARE DANCING WITH DEATH WHILE AT THE "NOTCH"
1. WE KNOW THE Numb INHIBITS IT
2. IT IS REGULATED BY DELTEX
3. IT REGULATES BMP10, NRG1, Ephrin-B2
(CHECK OUT Rex-1)
INFLUENCED BY DII4
LIGAND DELTA STIMULATE IT
DLL1, DLL3, JAG-1,2
INDUCE PROLIFERATION BY ACTING ON c-MYC, p21, HES FAMILY
REDUCES AVASTIN EFFECT BY OVER-EXPRESSION OF VEGFR2
INTERACT WITH HEY GENE AND Cbf-1
PRESENILINS 1,2
THE BEAUTY IS THAT BEING A RECEPTOR, IT'S GLYCOSYLATION IS CRUCIAL TO ITS FUNCTION, DESTROY POFUT-1 AND SOMETHING WILL HAPPEN OR IMPAIR O-GLYCOSYLATION AND THE RECEPTOR FUNCTION IS KAPUTT!
FIBROBLAST GROWTH FACTOR 10,
WE ARE LOOKING AT ALL THIS AT CRBCM,
BUT KNOW THIS: YOU ARE DANCING WITH DEATH WHILE AT THE "NOTCH"
THE SECRET OF LIFE IS LOCKED IN THE NOTCH PATHWAY
1. DO YOU KNOW WHY YOU DIE AFTER A LARGE STROKE? IT IS BECAUSE OF THE NOTCH PATHWAY. (The notch commend the electrical impulse that can tell the brain to quit all together, it can send the message that this is too much ABORT!)
2. DO YOU KNOW WHY YOU DIE AFTER A HEART ATTACK? IT IS BECAUSE OF THE NOTCH PATHWAY (send message ABORT to cardiac electricity)
3. DO YOU KNOW WHY YOU HAVE A GOOD MEMORY? IT IS BECAUSE OF THE NOTCH PATHWAY. (Notch allow memory to form on thing it is able to transmit to other cell)
4. DO YOU KNOW WHY YOU GET DEMENTIA (ALZHEIMER OR NOT) ? BECAUSE OF THE NOTCH PATHWAY (memory of old things already made "accepted" (consensus) are the last to disappear )
5. DO YOU SEE SOMEONE (EVEN A PRESIDENT) PASS OUT AND WONDER WHY? BECAUSE OF THE NOTCH PATHWAY (Notch "abort" message was triggered may be through vaso-vagal nerve!)
6. DO YOU KNOW WHY AN INFECTION CAN KILL YOU, AND WHY? BECAUSE OF THE NOTCH (proximity of the notch with TNF which in excess kills you even in the best hospitals in the world, there no defense against massive liberation of TNF)
7. SOMEONE WALKING AND SMILING DROPS DEAD, THE NOTCH DID IT! ALL OTHER ORGANS CAN BE GOOD, IN FACT WE TAKE THEM FOR TRANSPLANT, BUT THE NOTCH DID IT (ABORT! message was sent)
8. CAR ACCIDENT DEATH, THE NOTCH....JUST FINISH THE PHRASE FOR ME (Abort!)
9. MACROPHAGE DESTROY OTHER CELLS BY EATING THEM, THE NOTCH TELL THEM TO DO SO (Notch is involved with endophage, and vacuole formation)
10. WHY IMMUNIZATION WORKS, THE NOTCH DID IT (memory of the biologic agent-aggressor is kept because of ....)
WHY WE AGREE ON BASIC THINGS , THE NOTCH DID THAT (we remember what make sense to all)
WHY WE STAND AND BELIEVE IN FUNDAMENTAL HUMAN RIGHTS, SOMEWHERE IN US WE REMEMBER WHAT IS RIGHT, WELL THE NOTCH DID THAT!
WHY AN ORGAN STOP AND ANOTHER START, THE NOTCH PLAYS HERE (Notch is at the transition of proliferation and differentiation this is where Numb comes in!)
WHY CERTAIN TYPES OF CANCER ARE REFRACTORY TO CANCER KILLING DRUGS NO MATTER WHAT, THE NOTCH DOES THAT TOO. IT'S AS IF THEY "REMEMBER" TO BE REFRACTORY
WHY CERTAIN TISSUES HAVE A FUNCTION AND NOT ANOTHER, THE NOTCH DID IT
WHY HORMONES ARE SECRETED BY SOME ORGAN NO MATTER WHERE THEY ARE, THE NOTCH (keep remember what they are about!)
WHY AVASTIN STOPS WORKING AND ALL THE CANCERS KNOW HOW TO RESIST (BY VEGFR2)
LADIES AND GENTLEMEN, THIS IS NOTCH PATHWAY IS THE SECRET OF LIFE!
PLAY WITH THE NOTCH, YOU WILL STOP BREATHING, AND YOUR HEART WILL STOP, YOUR EYES WILL STOP SEEING, AND YOU CAN'T READ ME......
VEGETATIVE LIFE IS DUE TO THE NOTCH!
why basket ball player drops dead, drug overdose- it's all in the notch!
Resuscitation and resurrection, the NOTCH again!
BY DETERMINING CELLULAR FATE, IT IS THE CONDUCTOR OF THE ORCHESTRA .
2. DO YOU KNOW WHY YOU DIE AFTER A HEART ATTACK? IT IS BECAUSE OF THE NOTCH PATHWAY (send message ABORT to cardiac electricity)
3. DO YOU KNOW WHY YOU HAVE A GOOD MEMORY? IT IS BECAUSE OF THE NOTCH PATHWAY. (Notch allow memory to form on thing it is able to transmit to other cell)
4. DO YOU KNOW WHY YOU GET DEMENTIA (ALZHEIMER OR NOT) ? BECAUSE OF THE NOTCH PATHWAY (memory of old things already made "accepted" (consensus) are the last to disappear )
5. DO YOU SEE SOMEONE (EVEN A PRESIDENT) PASS OUT AND WONDER WHY? BECAUSE OF THE NOTCH PATHWAY (Notch "abort" message was triggered may be through vaso-vagal nerve!)
6. DO YOU KNOW WHY AN INFECTION CAN KILL YOU, AND WHY? BECAUSE OF THE NOTCH (proximity of the notch with TNF which in excess kills you even in the best hospitals in the world, there no defense against massive liberation of TNF)
7. SOMEONE WALKING AND SMILING DROPS DEAD, THE NOTCH DID IT! ALL OTHER ORGANS CAN BE GOOD, IN FACT WE TAKE THEM FOR TRANSPLANT, BUT THE NOTCH DID IT (ABORT! message was sent)
8. CAR ACCIDENT DEATH, THE NOTCH....JUST FINISH THE PHRASE FOR ME (Abort!)
9. MACROPHAGE DESTROY OTHER CELLS BY EATING THEM, THE NOTCH TELL THEM TO DO SO (Notch is involved with endophage, and vacuole formation)
10. WHY IMMUNIZATION WORKS, THE NOTCH DID IT (memory of the biologic agent-aggressor is kept because of ....)
WHY WE AGREE ON BASIC THINGS , THE NOTCH DID THAT (we remember what make sense to all)
WHY WE STAND AND BELIEVE IN FUNDAMENTAL HUMAN RIGHTS, SOMEWHERE IN US WE REMEMBER WHAT IS RIGHT, WELL THE NOTCH DID THAT!
WHY AN ORGAN STOP AND ANOTHER START, THE NOTCH PLAYS HERE (Notch is at the transition of proliferation and differentiation this is where Numb comes in!)
WHY CERTAIN TYPES OF CANCER ARE REFRACTORY TO CANCER KILLING DRUGS NO MATTER WHAT, THE NOTCH DOES THAT TOO. IT'S AS IF THEY "REMEMBER" TO BE REFRACTORY
WHY CERTAIN TISSUES HAVE A FUNCTION AND NOT ANOTHER, THE NOTCH DID IT
WHY HORMONES ARE SECRETED BY SOME ORGAN NO MATTER WHERE THEY ARE, THE NOTCH (keep remember what they are about!)
WHY AVASTIN STOPS WORKING AND ALL THE CANCERS KNOW HOW TO RESIST (BY VEGFR2)
LADIES AND GENTLEMEN, THIS IS NOTCH PATHWAY IS THE SECRET OF LIFE!
PLAY WITH THE NOTCH, YOU WILL STOP BREATHING, AND YOUR HEART WILL STOP, YOUR EYES WILL STOP SEEING, AND YOU CAN'T READ ME......
VEGETATIVE LIFE IS DUE TO THE NOTCH!
why basket ball player drops dead, drug overdose- it's all in the notch!
Resuscitation and resurrection, the NOTCH again!
BY DETERMINING CELLULAR FATE, IT IS THE CONDUCTOR OF THE ORCHESTRA .
FDA Warns Against Products From The Compounding Shop
Healthcare providers should not administer any
products produced by The Compounding Shop of St. Petersburg, Florida,
the US Food and Drug Administration (FDA) advised today.
During a recent inspection of the facility, FDA inspectors observed "poor sterile production practices that raise concerns about a lack of sterility assurance of The Compounding Shop's sterile drug products. Therefore, these products should not be administered to patients," according to the agency.
"If an injectable drug product that is intended to be sterile is contaminated, it could result in a life-threatening infection in patients," Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, said in a statement.
"We do not have reports of patient infections. However, due to concerns about a lack of sterility assurance at the facility and out of an abundance of caution, we have advised the firm to remove its sterile products from the market to protect patients," she added.
The Compounding Shop has informed the FDA that it is recalling sterile products and is in the process of notifying customers, the agency said.
The FDA advises healthcare providers and hospital staff to immediately check their medical supplies, quarantine any sterile products from The Compounding Shop, not administer them to patients, and await further instructions from the company regarding the recalled products.
Patients who have received any product produced by The Compounding Shop and have concerns are being advised to contact their healthcare provider.
The problems and product recall involving The Compounding Shop in St.
Petersburg, Florida, comes on the heels of recalls last month at other
compounding pharmacies because of similar problems and concerns about
sterility of products after FDA inspections.
As reported by Medscape Medical News, those companies include ApothéCure Inc and NuVision, Green Valley Drugs, and Balanced Solutions Compounding Pharmacy.
Healthcare professionals and patients are encouraged to report adverse events potentially related to the use of these or other products to MedWatch, the FDA's safety information and adverse event reporting program, by telephone at 1-800-FDA-1088; by fax at 1-800-FDA-0178; online at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm; with postage-paid FDA form 3500, available at http://www.fda.gov/MedWatch/getforms.htm; or by mail to MedWatch, 5600 Fishers Lane, Rockville, Maryland 20852-9787.
During a recent inspection of the facility, FDA inspectors observed "poor sterile production practices that raise concerns about a lack of sterility assurance of The Compounding Shop's sterile drug products. Therefore, these products should not be administered to patients," according to the agency.
"If an injectable drug product that is intended to be sterile is contaminated, it could result in a life-threatening infection in patients," Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, said in a statement.
"We do not have reports of patient infections. However, due to concerns about a lack of sterility assurance at the facility and out of an abundance of caution, we have advised the firm to remove its sterile products from the market to protect patients," she added.
The Compounding Shop has informed the FDA that it is recalling sterile products and is in the process of notifying customers, the agency said.
The FDA advises healthcare providers and hospital staff to immediately check their medical supplies, quarantine any sterile products from The Compounding Shop, not administer them to patients, and await further instructions from the company regarding the recalled products.
Patients who have received any product produced by The Compounding Shop and have concerns are being advised to contact their healthcare provider.
As reported by Medscape Medical News, those companies include ApothéCure Inc and NuVision, Green Valley Drugs, and Balanced Solutions Compounding Pharmacy.
Healthcare professionals and patients are encouraged to report adverse events potentially related to the use of these or other products to MedWatch, the FDA's safety information and adverse event reporting program, by telephone at 1-800-FDA-1088; by fax at 1-800-FDA-0178; online at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm; with postage-paid FDA form 3500, available at http://www.fda.gov/MedWatch/getforms.htm; or by mail to MedWatch, 5600 Fishers Lane, Rockville, Maryland 20852-9787.
Saturday, May 11, 2013
MTOR Inhibitor ....
THE NOTION THAT MTOR INHIBITOR SHOULD FOLLOW VEGF INHIBITOR FAILURE HAS BEEN ADOPTED BY THE MSKCC PHASE 3 STUDY OF Anti-PD1 ANTIBODY (BMS) vs EVEROLIMUS "FOLLOWING VEGF-TARGETED THERAPY FOR RENAL CANCER.
In this study, patients with Renal cell cancer who have progressed after 1 or 2 anti-VEGF systemic treatments are randomized to Anti-PD1 Antibody or Everolimus.
The primary endpoint is survival whereas secondary endpoints include progression free survival, safety of drugs and quality of life!
Please access the trial through clinicaltrials.gov
----------------------------------------------------------------------------------------------
TREATMENT RECOMMENDATION FOR CLEAR CELL RENAL CELL CANCER
SETTING PATIENT LEVEL 1 HIGHER LEVEL
---------------------------------------------------------------------------------------------------
Good or Sunitinib
Intermediate risk Bevaczumab +INF-alpha high dose IL2
1st line Pazopanib Sorafenib
---------------------------------------------------------------------------
Poor risk Temsirolimus
(Sunitinib)
==================================================================
Sorafenib Sunitinib
Prior Cytokine Pazopanib Bevacizumab
2nd and 3rd line ----------------------------------------------------------------------------
Prior VEGF-TKI Everolimus or Axitinib Sorafenib
Prior MTOR Inhib. Axitinib
=================================================================
from Molina et al....
In this study, patients with Renal cell cancer who have progressed after 1 or 2 anti-VEGF systemic treatments are randomized to Anti-PD1 Antibody or Everolimus.
The primary endpoint is survival whereas secondary endpoints include progression free survival, safety of drugs and quality of life!
Please access the trial through clinicaltrials.gov
----------------------------------------------------------------------------------------------
TREATMENT RECOMMENDATION FOR CLEAR CELL RENAL CELL CANCER
SETTING PATIENT LEVEL 1 HIGHER LEVEL
---------------------------------------------------------------------------------------------------
Good or Sunitinib
Intermediate risk Bevaczumab +INF-alpha high dose IL2
1st line Pazopanib Sorafenib
---------------------------------------------------------------------------
Poor risk Temsirolimus
(Sunitinib)
==================================================================
Sorafenib Sunitinib
Prior Cytokine Pazopanib Bevacizumab
2nd and 3rd line ----------------------------------------------------------------------------
Prior VEGF-TKI Everolimus or Axitinib Sorafenib
Prior MTOR Inhib. Axitinib
=================================================================
from Molina et al....
Nul n'est prophete chez soi!
No one is prophet at Home! (The French know best!)
In these United States, politics will block us from obtaining a grant, we understood that! Our cause, however, is just, and we will pursue it by all means found anywhere in the world! Cancer is a common cause for the fight, let those who are distracted by local conditions they live in go by the wayside while we stick to the mission to cure cancer!
We cannot thank MDHonors enough for providing much needed funding for our research!
In these United States, politics will block us from obtaining a grant, we understood that! Our cause, however, is just, and we will pursue it by all means found anywhere in the world! Cancer is a common cause for the fight, let those who are distracted by local conditions they live in go by the wayside while we stick to the mission to cure cancer!
We cannot thank MDHonors enough for providing much needed funding for our research!
Friday, May 10, 2013
ONCE AGAIN FAILURE OF RECEPTORS PROVE TO BE THE REASON CANCER DEVELOPS.
WHILE IN TRIPLE NEGATIVE HEPARAN SULFATE ALTERATION OR LACK OF, SEEMS TO BE THE CULPRIT THAT WILL LEAD TO SECONDARY OVER-EXPRESSION OF TUMOR GROWTH FACTORS FOR BREAST CANCER, IN OVARIAN CANCER IT IS THE BETAGLYCAN WHICH APPEARS TO BE DEFICIENT AND TRIGGER A SECONDARY INCREASE OF ACTIVIN. THE PROOF IS IN THE PUDDING,
IF YOU FIGHT ACTIVIN, YOU GO NOWHERE BUT IF YOU FIGHT BETAGLYCAN BY RESTORING ITS FUNCTION, THE RECEPTOR WORKS RELATIVELY AND YOU KIND OF STOP THE METASTASIS AND SPREAD OF THE DISEASE
NOBODY HAS SHOWN THIS YET BUT YOU WILL FIND A DROP OF ACTIVIN (HOW DIFFERENT IT IS FROM SURVIVIN? HELL DON'T LET ME CONFUSE YOU BY JUMPING FROM CAMELS TO RABBITS!)
THE GLYCAN ARE MORE IMPORTANT THAN YOU THINK
IT IS AN INTERESTING SPECULATION THAT HISTONE DEACETYLASE INHIBITOR WORK BECAUSE IN RESTORING THE GLYCAN OR IS IT CAUSATIVE OF THE ABNORMALITY.
ONE THING THAT IS WORRISOME IS THAT A SINGLE FRAME SHIFT AT THE m-ARNA COULD TRIGGER THESE EPIGENETIC EVENTS.
ALL IN ALL THIS AT THE RECEPTOR IS READ AS A CRISIS OR STRESS THE AKT IS OVEREXPRESSED AND CAUSE PTEN DEPRESSION, OR GSK DEPRESSION, AND AFFECT THE Wnt THROUGH CROSS TALK AND OVARIAN CANCER IS WELL ON ITS WAY EXACERBATED AT THIS POINT BY SECONDARY INCREASE OF TGF CALLED ACTIVIN!
WHILE IN TRIPLE NEGATIVE HEPARAN SULFATE ALTERATION OR LACK OF, SEEMS TO BE THE CULPRIT THAT WILL LEAD TO SECONDARY OVER-EXPRESSION OF TUMOR GROWTH FACTORS FOR BREAST CANCER, IN OVARIAN CANCER IT IS THE BETAGLYCAN WHICH APPEARS TO BE DEFICIENT AND TRIGGER A SECONDARY INCREASE OF ACTIVIN. THE PROOF IS IN THE PUDDING,
IF YOU FIGHT ACTIVIN, YOU GO NOWHERE BUT IF YOU FIGHT BETAGLYCAN BY RESTORING ITS FUNCTION, THE RECEPTOR WORKS RELATIVELY AND YOU KIND OF STOP THE METASTASIS AND SPREAD OF THE DISEASE
NOBODY HAS SHOWN THIS YET BUT YOU WILL FIND A DROP OF ACTIVIN (HOW DIFFERENT IT IS FROM SURVIVIN? HELL DON'T LET ME CONFUSE YOU BY JUMPING FROM CAMELS TO RABBITS!)
THE GLYCAN ARE MORE IMPORTANT THAN YOU THINK
IT IS AN INTERESTING SPECULATION THAT HISTONE DEACETYLASE INHIBITOR WORK BECAUSE IN RESTORING THE GLYCAN OR IS IT CAUSATIVE OF THE ABNORMALITY.
ONE THING THAT IS WORRISOME IS THAT A SINGLE FRAME SHIFT AT THE m-ARNA COULD TRIGGER THESE EPIGENETIC EVENTS.
ALL IN ALL THIS AT THE RECEPTOR IS READ AS A CRISIS OR STRESS THE AKT IS OVEREXPRESSED AND CAUSE PTEN DEPRESSION, OR GSK DEPRESSION, AND AFFECT THE Wnt THROUGH CROSS TALK AND OVARIAN CANCER IS WELL ON ITS WAY EXACERBATED AT THIS POINT BY SECONDARY INCREASE OF TGF CALLED ACTIVIN!
GENETIC DISTURBANCES IN OVARIAN CANCERS! ANOTHER CASE OF RECEPTOR FAILURE
In many triple negative Breast Cancers, we have submitted that a failure of the receptor for either HER-2 or ER are the origin. Defective Heparan surface may be one example leading to Receptor ineffective performance. There is a secondary over production of Tumor Growth factor which impact other Receptors which are naturally susceptible leading to hyperplasia and eventually to a neoplastic process.
In ovarian cancer, the findings that the DAB2 gene is suppressed appears to be central to the pathophysiology of this cancer.
==================================================================
Disabled homolog 2 is a protein that in humans is encoded by the DAB2 gene.[1][2]
DAB2 mRNA is expressed in normal ovarian epithelial cells but is down-regulated or absent from ovarian carcinoma cell lines. The 770-amino acid predicted protein has an overall 83% identity with the mouse p96 protein, a putative mitogen-responsive phosphoprotein;=============================================================
IF YOU FOLLOW THE MONEY FOR A WHILE YOU WILL COME TO THE NATURAL CONCLUSION. OVARIAN CANCERS HAPPEN IN MOTHERS! AND GUESS WHO DAB2 GENE WILL PICK ON, OF COURSE A GENE CALLED "MOTHER".
Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.[1][2] SMAD3 is a member of the SMAD family of proteins.
The human SMAD3 gene is located on chromosome 15. It is one of several human homologues of a gene that was originally discovered in the fruit fly Drosophila melanogaster.
Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual cycle. Many other functions have been found to be exerted by activin, including roles in cell proliferation, differentiation, apoptosis,[1] metabolism, homeostasis, immune response, wound repair,[2] and endocrine function. Conversely inhibin downregulates FSH synthesis and inhibits FSH secretion.[3]
Activin is a dimer composed of two identical or very similar beta subunits. Inhibin is also a dimer wherein the first component is a beta subunit similar or identical to the beta subunit in activin. However, in contrast to activin, the second component of the inhibin dimer is a more distantly-related alpha subunit.[4][5] Activin, inhibin and a number of other structurally related proteins such as anti-Müllerian hormone, bone morphogenetic protein, and growth differentiation factor belong to the TGF-β protein superfamily.[6]
==============================================================================
SO CLEARLY DEPRESSION AT DAB2 WILL INDUCE DE-SENSITIZATION AT THE TGF-BETA RECEPTOR LEADING TO CHANGES OR MODULATION THAT FAVOR ACTIVIN'S ACTIVITY AND PROLIFERATION
BUT DEPRESSION OF DAB2 DOES NOT STOP THERE, THROUGH ITS GIPC1 CONNECTION IT WILL AFFECT VERY BAD ACTORS INCLUDING MYO6 (WHICH DISTURBS ORGANELLE MOVEMENT AND VACUOLE CONTROL TRAFFIC IN THE CELL) AND LPR1,2 A DISFIGURING GENE ASSOCIATED WITH A BAD SYNDROME AND THE "DEVIL" DVL3. AND REMEMBER A GENE THAT INDUCES MORPHOLOGIC DISTURBANCE SUCH AS THE LRP2 IS DANGEROUS TO DANCE WITH! ALWAYS REMEMBER THALIDOMIDE WITH ITS SHORT LIMB SYNDROME!
==================================================================================
Mutations in the LRP2 gene are associated with Donnai-Barrow syndrome.[6]
This disorder is characterized by unusual facial features, including prominent, wide-set eyes with outer corners that point downward; a short bulbous nose with a flat nasal bridge; ears that are rotated backward; and a widow's peak hairline.
Individuals with Donnai-Barrow syndrome have severe hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). In addition, they often experience vision problems, including extreme nearsightedness (high myopia), detachment or deterioration of the light-sensitive tissue in the back of the eye (the retina), and progressive vision loss. Some have a gap or split in the colored part of the eye (iris coloboma).[2][3]
In almost all people with Donnai-Barrow syndrome, the tissue connecting the left and right halves of the brain (corpus callosum) is underdeveloped or absent. Affected individuals may also have other structural abnormalities of the brain. They generally have mild to moderate intellectual disability and developmental delay.
People with Donnai-Barrow syndrome may also have a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a diaphragmatic hernia. This potentially serious birth defect allows the stomach and intestines to move into the chest and possibly crowd the developing heart and lungs. An opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel may also occur in affected individuals. Occasionally people with Donnai-Barrow syndrome have abnormalities of the intestine, heart, or other organs and scoliosis.[2][3]
Myosin VI, also known as MYO6, is a protein. It has been found in humans, mice, fruit flies (Drosophila melanogaster), and nematodes (Caenorhabditis elegans).
Myosin VI is a molecular motor involved in intracellular vesicle and organelle transport. It is one of the so-called unconventional myosins.[supplied by OMIM][1]
=============================================================================
CAN THIS ENTIRE MACHINERY BE SHUT DOWN BY AN ANTI-CD81
I BET YOU!
THE CENTRAL GENE TO GO AFTER IS GIPC1 FROM MY VOTE, THERE IS THE CROSS-ROAD! BUT IT INVOLVES THE ADRENAL RECEPTORS AND BETA RECEPTOR OF THE HEART SO CARDIAC MONITOR WOULD BE ADVISED DURING PHASE 1 STUDIES!
If LPR2 is amplified, will that predict activity of Avastin and other immunomodulation? we know that when morphology is involved, these agents are active!
In many triple negative Breast Cancers, we have submitted that a failure of the receptor for either HER-2 or ER are the origin. Defective Heparan surface may be one example leading to Receptor ineffective performance. There is a secondary over production of Tumor Growth factor which impact other Receptors which are naturally susceptible leading to hyperplasia and eventually to a neoplastic process.
In ovarian cancer, the findings that the DAB2 gene is suppressed appears to be central to the pathophysiology of this cancer.
==================================================================
DAB2
From Wikipedia, the free encyclopedia
| Dab, mitogen-responsive phosphoprotein, homolog 2 (Drosophila) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 PDB rendering based on 1m7e. |
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| Identifiers | |||||||||||
| Symbols | DAB2; DOC-2; DOC2 | ||||||||||
| External IDs | OMIM: 601236 MGI: 109175 HomoloGene: 1026 GeneCards: DAB2 Gene | ||||||||||
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| RNA expression pattern | |||||||||||
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| More reference expression data | |||||||||||
| Orthologs | |||||||||||
| Species | Human | Mouse | |||||||||
| Entrez | 1601 | 13132 | |||||||||
| Ensembl | ENSG00000153071 | ENSMUSG00000022150 | |||||||||
| UniProt | P98082 | P98078 | |||||||||
| RefSeq (mRNA) | NM_001244871 | NM_001008702 | |||||||||
| RefSeq (protein) | NP_001231800 | NP_001008702 | |||||||||
| Location (UCSC) | Chr 5: 39.37 – 39.46 Mb |
Chr 15: 6.3 – 6.44 Mb |
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| PubMed search | [1] | [2] | |||||||||
DAB2 mRNA is expressed in normal ovarian epithelial cells but is down-regulated or absent from ovarian carcinoma cell lines. The 770-amino acid predicted protein has an overall 83% identity with the mouse p96 protein, a putative mitogen-responsive phosphoprotein;=============================================================
IF YOU FOLLOW THE MONEY FOR A WHILE YOU WILL COME TO THE NATURAL CONCLUSION. OVARIAN CANCERS HAPPEN IN MOTHERS! AND GUESS WHO DAB2 GENE WILL PICK ON, OF COURSE A GENE CALLED "MOTHER".
Mothers against decapentaplegic homolog 3
From Wikipedia, the free encyclopedia
.The human SMAD3 gene is located on chromosome 15. It is one of several human homologues of a gene that was originally discovered in the fruit fly Drosophila melanogaster.
Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual cycle. Many other functions have been found to be exerted by activin, including roles in cell proliferation, differentiation, apoptosis,[1] metabolism, homeostasis, immune response, wound repair,[2] and endocrine function. Conversely inhibin downregulates FSH synthesis and inhibits FSH secretion.[3]
Activin is a dimer composed of two identical or very similar beta subunits. Inhibin is also a dimer wherein the first component is a beta subunit similar or identical to the beta subunit in activin. However, in contrast to activin, the second component of the inhibin dimer is a more distantly-related alpha subunit.[4][5] Activin, inhibin and a number of other structurally related proteins such as anti-Müllerian hormone, bone morphogenetic protein, and growth differentiation factor belong to the TGF-β protein superfamily.[6]
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SO CLEARLY DEPRESSION AT DAB2 WILL INDUCE DE-SENSITIZATION AT THE TGF-BETA RECEPTOR LEADING TO CHANGES OR MODULATION THAT FAVOR ACTIVIN'S ACTIVITY AND PROLIFERATION
BUT DEPRESSION OF DAB2 DOES NOT STOP THERE, THROUGH ITS GIPC1 CONNECTION IT WILL AFFECT VERY BAD ACTORS INCLUDING MYO6 (WHICH DISTURBS ORGANELLE MOVEMENT AND VACUOLE CONTROL TRAFFIC IN THE CELL) AND LPR1,2 A DISFIGURING GENE ASSOCIATED WITH A BAD SYNDROME AND THE "DEVIL" DVL3. AND REMEMBER A GENE THAT INDUCES MORPHOLOGIC DISTURBANCE SUCH AS THE LRP2 IS DANGEROUS TO DANCE WITH! ALWAYS REMEMBER THALIDOMIDE WITH ITS SHORT LIMB SYNDROME!
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Mutations in the LRP2 gene are associated with Donnai-Barrow syndrome.[6]
This disorder is characterized by unusual facial features, including prominent, wide-set eyes with outer corners that point downward; a short bulbous nose with a flat nasal bridge; ears that are rotated backward; and a widow's peak hairline.
Individuals with Donnai-Barrow syndrome have severe hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). In addition, they often experience vision problems, including extreme nearsightedness (high myopia), detachment or deterioration of the light-sensitive tissue in the back of the eye (the retina), and progressive vision loss. Some have a gap or split in the colored part of the eye (iris coloboma).[2][3]
In almost all people with Donnai-Barrow syndrome, the tissue connecting the left and right halves of the brain (corpus callosum) is underdeveloped or absent. Affected individuals may also have other structural abnormalities of the brain. They generally have mild to moderate intellectual disability and developmental delay.
People with Donnai-Barrow syndrome may also have a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a diaphragmatic hernia. This potentially serious birth defect allows the stomach and intestines to move into the chest and possibly crowd the developing heart and lungs. An opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel may also occur in affected individuals. Occasionally people with Donnai-Barrow syndrome have abnormalities of the intestine, heart, or other organs and scoliosis.[2][3]
MYO6
From Wikipedia, the free encyclopedia
.Myosin VI is a molecular motor involved in intracellular vesicle and organelle transport. It is one of the so-called unconventional myosins.[supplied by OMIM][1]
Interactions
MYO6 has been shown to interact with GIPC1[2][3] and DAB2.[4][5]=============================================================================
CAN THIS ENTIRE MACHINERY BE SHUT DOWN BY AN ANTI-CD81
I BET YOU!
THE CENTRAL GENE TO GO AFTER IS GIPC1 FROM MY VOTE, THERE IS THE CROSS-ROAD! BUT IT INVOLVES THE ADRENAL RECEPTORS AND BETA RECEPTOR OF THE HEART SO CARDIAC MONITOR WOULD BE ADVISED DURING PHASE 1 STUDIES!
If LPR2 is amplified, will that predict activity of Avastin and other immunomodulation? we know that when morphology is involved, these agents are active!
A WILD WILD TARGET!
While investigating why Gaucher disease would be linked to Lymphoproliferative disorders (Multiple Myeloma,CLL,AML LYMPHOMA INCLUDING THE HODGKIN , AND RARELY ALL.) and following downstream of CD 19, one stumble upon Grb2. just by the extent of its interactions, you know you cannot come-up empty targeting this wild gene. The crux of the endeavor will be how to electively hit the cancer cell exclusively.
"
Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap. Gads and Grap are expressed specifically in hematopoietic cells and function in the coordination of tyrosine kinase mediated signal transduction."wikipedia
You just look at the variety of interaction and you know this is an important step to anything in the cellular sun! WOW!
Gerb2 a lifetime project!
While investigating why Gaucher disease would be linked to Lymphoproliferative disorders (Multiple Myeloma,CLL,AML LYMPHOMA INCLUDING THE HODGKIN , AND RARELY ALL.) and following downstream of CD 19, one stumble upon Grb2. just by the extent of its interactions, you know you cannot come-up empty targeting this wild gene. The crux of the endeavor will be how to electively hit the cancer cell exclusively.
"
Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap. Gads and Grap are expressed specifically in hematopoietic cells and function in the coordination of tyrosine kinase mediated signal transduction."wikipedia
Interactions
Grb2 has been shown to interact with Arachidonate 5-lipoxygenase,[5][6] Lymphocyte cytosolic protein 2,[7][8][9][10][11] GAB2,[12][13][14] B-cell linker,[15][16][17][18] Abl gene,[19][20] CD28,[21][22] FRS2,[23][24][25][26] Mitogen-activated protein kinase 9,[27][28] CD22,[29][30] NEU3,[31] ETV6,[12] MAP2,[32][33] Dock180,[34][35] PIK3R1,[36][37] SH2B1,[38][39] CRK,[40][41][42] GAB1,[7][43][44] MST1R,[45][46] DNM1,[47][48] Huntingtin,[49] Src,[50][51] Beta-2 adrenergic receptor,[52] VAV2,[53][54] ADAM15,[55] RAPGEF1,[56][57] VAV1,[58][59][60][61] HER2/neu,[54][62][63] Epidermal growth factor receptor,[2][43][53][62][64][65][66][67][68][69] PDGFRB,[69][70][71] PTK2,[72][73][74][75][76] Erythropoietin receptor,[77][78] Linker of activated T cells,[79][80][81] Dystroglycan,[82] SH3KBP1,[83][84] Granulocyte colony-stimulating factor receptor,[85] DCTN1,[86] CDKN1B,[87] Colony stimulating factor 1 receptor,[88] EPH receptor A2,[89] KHDRBS1,[43][90][91] RET proto-oncogene,[92][93] PLCG1,[94][95][96] TrkA,[97][98] PRKAR1A,[66] Janus kinase 2,[99][100] MUC1,[101] CD117,[78][102][103] Fas ligand,[104][105] Janus kinase 1,[100][106] VAV3,[53][107] BCAR1,[73][108] PTPN1,[109][110] INPP5D,[111] ITK,[112][113] SHC1,[51][53][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132] PTPN12,[133] C-Met,[134][135] PTPN11,[71][85][127][136][137][138][139][140][141] Glycoprotein 130,[61] PTPN6,[51][136][142] Syk,[51][136] MAP4K1,[143][144][145][146] Wiskott-Aldrich syndrome protein,[147][148] NCKIPSD,[149][150] PTPRA,[151][152][153] BCR gene,[12][115][154][155][156][157] CBLB,[158][159][160] Cbl gene,[9][24][51][90][124][158][161][162][163][164][165][166][167] SOS1,[8][24][42][43][48][51][53][60][68][90][95][101][115][122][124][131][168][169][170][171][172] IRS1,[100][114][173] TNK2,[116][174] MED28,[175] MAP3K1[176] and HNRNPC.[177]You just look at the variety of interaction and you know this is an important step to anything in the cellular sun! WOW!
Gerb2 a lifetime project!
AQUA TECHNOLOGY-AUTOMATED QUANTITATIVE ANALYSIS
IT IS A QUANTITATIVE IMMUNOPHENOTYPING TECHNIQUE
DISCUSSED BY EXPERTS (ASCO/CAP GUIDELINES AND NCCN TASKFORCE) MOST APPROPRIATE FOR SAMPLE WITH 'LOW NUCLEAR STAINING". it has proven itself for measurement of ER and PR positivity in breast cancers!
The Cutt-off is 5.2 for determining receptor status
AQUA combines immunofluorescence and automated image technology.
NCCN
- ER and PR negative tumor status should be retested if tumor histology is lobular,tubular or mucinous because these types of tumors are rarely negative
-Also retest if tumors are GRADE1 since these are rarely negative
-Retesting is indicated at Diagnosis and at Relapse
-The option of endocrine therapy for ER&PR negative tumors does not depend on level of hormone Receptor Expression.
With this technique,
the cut off point for positive HER-2 is 572
less than 572, no HER-2 expression
more than 572, positive HER-2
(Material provided by Genoptix )
IT IS A QUANTITATIVE IMMUNOPHENOTYPING TECHNIQUE
DISCUSSED BY EXPERTS (ASCO/CAP GUIDELINES AND NCCN TASKFORCE) MOST APPROPRIATE FOR SAMPLE WITH 'LOW NUCLEAR STAINING". it has proven itself for measurement of ER and PR positivity in breast cancers!
The Cutt-off is 5.2 for determining receptor status
AQUA combines immunofluorescence and automated image technology.
NCCN
- ER and PR negative tumor status should be retested if tumor histology is lobular,tubular or mucinous because these types of tumors are rarely negative
-Also retest if tumors are GRADE1 since these are rarely negative
-Retesting is indicated at Diagnosis and at Relapse
-The option of endocrine therapy for ER&PR negative tumors does not depend on level of hormone Receptor Expression.
With this technique,
the cut off point for positive HER-2 is 572
less than 572, no HER-2 expression
more than 572, positive HER-2
(Material provided by Genoptix )
Thursday, May 9, 2013
News
Special Announcement About Tolvaptan
A major announcement was made by Otsuka Pharmaceutical Co. on Saturday, Nov. 3, 2012 at the American Society of Nephrology (ASN) meeting regarding the results of the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease Outcomes (TEMPO) Trial.This is the first time that a drug specifically targeted to alter ADPKD progression in humans has been shown to be of benefit. This is an exciting milestone for PKD patients and the Foundation. (It is important to know that though tolvaptan is already approved for treatment of other medical conditions, the doses of tolvaptan used in the TEMPO trial were significantly higher than used in previous studies of other diseases. In addition, ADPKD patients are a unique patient population. Because of this, until the data are reviewed in detail by Otsuka and the FDA, it could be dangerous to take tolvaptan for treatment of PKD.)
The concept of using vasopressin blockade as a way of slowing ADPKD progression was originally developed by Dr. Vincent Gattone, whose research has been in part supported by the PKD Foundation. The Foundation is proud to have been a part of this critical work, and our hope is that this is just the first step toward finding other treatments that will improve the quality of people's lives who suffer from PKD.
Click on the links below to read the full announcement and learn more about the study.
FROM THE PKD FOUNDATION!
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