It is increasingly recognized that Cyclins are the ultimate effectors of health. Yes the fascination with the DNA, its replication in cell division, its activities with RNA transcription which translate in protein formation, its very nature of keeping the the code of cellular destiny, all that is nice and dandy. But beyond the genes, what will determine the state of your health, what makes live long, healthy or sick, what makes it happen, ARE THE STATE OF YOUR CYCLINS!
1.It is the cyclins that make you grow (growth factors)
2.It is the cyclins that control passage of stage to stage during cell division (the name CYCLIN-dependent Kinase-Cdk comes to mind..
3.It is the cyclins that makes obesity a disease
4.It is the that kick the kinase gene into motion
5.It is the cyclin that inhibit and promote...makes feminine or masculine...
6.It is the cyclins that kill post synaptic cell in Traumatic Brain Injury or strokes
7.It is the cyclins that call specific inflammatory cells to the theater of infection
8. It is the cyclins that determine the virulence or resistance (persitence of a cancer) of a cancer
9. It is through cyclin control that the NF-kB operates to insure survival and adaptation
10. It is through cyclins that some mutations occur, some genes are amplified or repressed and therefore entire pathways are affected, and more importantly it is through the cyclins that some Receptors are desensitized!
It is through cyclins that Stem cells are stem cells!
It is through cyclins that old people look frail, their muscle hypotrophic!
when a cancer is uncontrollable such as melanoma and kidney cancer, give a cytokine ! (Interleukin-2 or Interferon!)
FOR MOST DEMENTIA TO DEVELOP! LOOK INTO THE CYTOKINS!
So with all this, it is surprising that we don't hear more about the Cyclins!
some are inhibitory, some are promoters, although they can belong to the same family
you die old or from infection because of the cytokines!
so it is a surprise that these no CYTOKINE UNIVERSITY!
HEAD IN THE SAND AGAIN, OR LOSS OF WHAT IS ESSENTIAL!
Saturday, October 12, 2013
Thursday, October 10, 2013
IT IS ALL ABOUT THE CYTOKINES!
The discovery of DNA and nuclear material has led to the emphasis on the alteration of Nuclear functions to fight cancer, indeed most of the original chemotherapy drugs had mechanisms of action centered on breaking or somehow impairing DNA. This focus to a certain extent affected our judgement in the evaluation of certain drugs. We are now finding out that the strength of certain drug (and weakness /susceptibility to resistance) is not really due to their main effect on DNA (ie. epigenetic disturbances induced by Etoposide). The discovery that BCL-2 has a mechanism of resistance to certain drugs is point in case that nuclear material induced disturbances have significant limitations that occur away from the nucleus (at the Mitochondria). Anti-proliferative chemotherapies have now shown their limits and scientists have kept this in our panoply of options against cancer.
Scientists have long been fascinated by the laws of nature, these driving forces that drive in certain ways or directions the chains of chemical reactions within the cells. From Glycogenolysis to the Krebs' cycle, to the cellular pathways, role of enzymes these catalysts of chemical reaction and gene regulators, our focus has been progressively shifting. The maximal effect of standard chemotherapy having been realized, the shift now has gone to driver Mutations, blocking pathways and modulating reactions etc. But beyond the mutation, gene alterations and so forth, one thing that make a cancer spread like a wild fire is its stimulation by a growth factor, or its self dependence in achieving survival most of the time at very different levels of energy expenditure! This role squarely falls into the area of epigenetics which is the critical area of Cytokine production determination. Now, once produced, Cytokines, to be effective, must connect to their receptors! This is where the wheels rub the asphalt to speed up the chemical reactions!
One of the mechanisms of increased cytokine production, aside from their gene amplification, is failure at the receptor. Indeed, when a receptor fails, the normal reaction (law of nature) is to concur the resistance by sending more of the same cytokine. While this increase could be partially succesful in restoring homeostasis depending on the level of abnormality at the receptor, the relative increase has other side effects due to the non specificity of receptors. Co-receptors or other receptors susceptible to the same cytokine find themselves super excited and are driving downstream reactions at higher rates. A SIGNIFICANT PHENOMENON NEEDS TO OCCUR AT THIS POINT, THAT IS THE DESENSITIZATION OF SECONDARY RECEPTORS, A TRAUMATIC PHENOMENON WITH POTENTIALLY NEOPLASTIC CONSEQUENCES (TO BE CONTINUED)
Scientists have long been fascinated by the laws of nature, these driving forces that drive in certain ways or directions the chains of chemical reactions within the cells. From Glycogenolysis to the Krebs' cycle, to the cellular pathways, role of enzymes these catalysts of chemical reaction and gene regulators, our focus has been progressively shifting. The maximal effect of standard chemotherapy having been realized, the shift now has gone to driver Mutations, blocking pathways and modulating reactions etc. But beyond the mutation, gene alterations and so forth, one thing that make a cancer spread like a wild fire is its stimulation by a growth factor, or its self dependence in achieving survival most of the time at very different levels of energy expenditure! This role squarely falls into the area of epigenetics which is the critical area of Cytokine production determination. Now, once produced, Cytokines, to be effective, must connect to their receptors! This is where the wheels rub the asphalt to speed up the chemical reactions!
One of the mechanisms of increased cytokine production, aside from their gene amplification, is failure at the receptor. Indeed, when a receptor fails, the normal reaction (law of nature) is to concur the resistance by sending more of the same cytokine. While this increase could be partially succesful in restoring homeostasis depending on the level of abnormality at the receptor, the relative increase has other side effects due to the non specificity of receptors. Co-receptors or other receptors susceptible to the same cytokine find themselves super excited and are driving downstream reactions at higher rates. A SIGNIFICANT PHENOMENON NEEDS TO OCCUR AT THIS POINT, THAT IS THE DESENSITIZATION OF SECONDARY RECEPTORS, A TRAUMATIC PHENOMENON WITH POTENTIALLY NEOPLASTIC CONSEQUENCES (TO BE CONTINUED)
Monday, October 7, 2013
WE BELIEVE IN THE CURE FOR BREAST CANCER
In this month of re-commitment to fighting Breast cancer, it is imperative to stop a while in a moment of reflection for those who have lost the fight, remind ourselves of who they were, what lives they touched as they made us who we are today in many ways. I remember my mother who was afflicted by this disease, a kind loving soul, who despite our number (family of 15) had managed to make all of us feel special. I grew up truly believing that of all her kids, I was the one. But talking to my other siblings, each one of us felt that special feeling! In 1974, 3 years before she was diagnosed and treated in Belgium, she added to my name a secret portion, "Muendela yenda" (the one who will walk alone) and here I am today, far from the country of origin, in El Paso, Texas, the sole American Citizen of my family! Preaching to a silent choir on this blog. Breast cancer victims are our mothers, sisters, daughters and friends who have affected our lives in many ways. Survivors continue their paths and work touching our lives everyday, reminding us that our fight is needed and is just because there is a price to fight for. Reminding us that until the cure happens, there is no stone that should remain unturned, no places we should not go, no politician we should not talk to, no genes,proteins, and other molecules that could make a difference we should not explore, poke and tease. We could wander to other matters of our lives, but this month of October, we should renew our commitment to the fight for the cure of breast cancer.
Efforts made so far have made a meaningful difference, our eyes have opened to new dimensions of cancer research, and the belief in the cure has hardened because through advances in targeting therapy and genetic works, THE CURE IS MORE POSSIBLE, REACHABLE AND REAL!
All we need is cast off the doubt, stop infighting, keep the eyes open, and bring the cure to the shores of our daily reality! We have the means, we have the science, we are full of justified hope, let's keep on marching until the victory rings, making the CURE REAL, PALPABLE AND ALIVE!
Efforts made so far have made a meaningful difference, our eyes have opened to new dimensions of cancer research, and the belief in the cure has hardened because through advances in targeting therapy and genetic works, THE CURE IS MORE POSSIBLE, REACHABLE AND REAL!
All we need is cast off the doubt, stop infighting, keep the eyes open, and bring the cure to the shores of our daily reality! We have the means, we have the science, we are full of justified hope, let's keep on marching until the victory rings, making the CURE REAL, PALPABLE AND ALIVE!
Sunday, October 6, 2013
Another misunderstanding? the TGF story
One of the misunderstanding of common practitioner is related to the lack of appreciation of the extent of the impact of TGF or the extent of its actions! The Tumor Growth factor effects are not limited to growth of cancer cells. Their mission is not what their name means, remember the cells' aim is not to "grow" it is to survive. Globally survival means expansion of life but it also means shutting down by inhibition any or most doors to Apoptosis. In cancer Medicine, Growth factors are probably one of the biggest challenge to therapy because they are the impetus or one of the many driver for cancer resistance! TGFs block for the cancer as many roads to programmed cell death as possible, They also function as desensitizers by not only altering Receptors working against their mission, but epigenetically suppress all mechanisms working against them. And they do this do this effectively by using the c-JUN and the NF-kB. and through their interactions with the Wnt, the Notch and the FAK.
The power and versatility of TGFs action lay in the fact in there no one TGF, but a family of TGFs with numbers attached to them (TGF1,2,3 etc). And each member having a different effect, some being completely opposed to each other but circumstances (including location) in the life of the cell will determine which family member will be at work at a given time.
ie.
=============================================
IE.WATCH "ACTIVIN" BECAUSE
"
The power and versatility of TGFs action lay in the fact in there no one TGF, but a family of TGFs with numbers attached to them (TGF1,2,3 etc). And each member having a different effect, some being completely opposed to each other but circumstances (including location) in the life of the cell will determine which family member will be at work at a given time.
ie.
Identification of Novel TGF-β/Smad Gene Targets in Dermal Fibroblasts using a Combined cDNA Microarray/Promoter Transactivation Approach*
Franck Verrecchia‡et al!"Members of the TGF-β1superfamily (activin, bone morphogenic proteins, TGF-βs, and decapentaplegic) are multifunctional cytokines that control various aspects of cell growth and differentiation and play an essential role in embryonic development, tissue repair, or immune homeostasis (1, 2). In addition, TGF-β is the prototypic fibrogenic cytokine, enhancing extracellular matrix (ECM) gene expression and down-regulating that of matrix-degrading enzymes. Increased expression of TGF-β is often associated with fibrotic states and abnormal accumulation of ECM proteins in affected tissues (3-6). The TGF-βs signal via serine/threonine kinase transmembrane receptors, which phosphorylate cytoplasmic mediators of the Smad family (7-9). The ligand-specific Smad1, Smad2, Smad3, and Smad5 interact directly with, and are phosphorylated by, activated TGF-β receptors type I. Smad1 and Smad5 are specific for bone morphogenic proteins, whereas Smad2 and Smad3 can be activated by both TGF-β and activin receptors. Receptor-activated Smads are kept in the cytoplasm in the basal state bound to the protein SARA (Smad anchor forreceptor activation) (10). Upon phosphorylation at their SSXS carboxyl-terminal motif, they are released from SARA and form heteromeric complexes with Smad4, a common mediator for all Smad pathways. The resulting Smad heterocomplexes are then translocated into the nucleus where they activate target genes, binding DNA either directly or in association with other transcription factors. Members of the third group of Smads, the inhibitory Smads, Smad6 and Smad7, prevent phosphorylation and/or nuclear translocation of receptor-associated Smads (7-9)."=============================================
IE.WATCH "ACTIVIN" BECAUSE
"
The ACVRL1 gene provides instructions
for making a protein called activin receptor-like kinase 1. This
protein is found on the surface of cells, especially in the lining of
developing arteries.
The ACVRL1 protein is a receptor. It acts as a "lock" waiting for a specific protein, called its ligand, to serve as the "key." In the case of the ACVRL1 protein, the ligand is called transforming growth factor beta. The interaction between these proteins plays a role in the development of blood vessels. In particular, this protein interaction is involved in the specialization of new blood vessels into arteries or veins."
ACVR2A has been shown to interact with INHBA,[4][5] SYNJ2BP[6][7] and ACVR1B.[8][9]
=================================================THROUGH IN SYNJ2BP,
SYNJ2BP has been shown to interact with LRP2,[3] ACVR2B,[1] ACVR2A[1][4] and LRP1.[3]
=========================================================THROUGH LRP1
LRP1 has been shown to interact with Apolipoprotein E,[11][12] Lipoprotein lipase,[13][14][15] Urokinase receptor,[16] MAPK8IP2,[17] Tissue plasminogen activator,[18][19] Thrombospondin 1,[20][21][22] SYNJ2BP,[17] DLG4,[17] NOS1AP,[17] calreticulin,[23] APBB1,[24] ITGB1BP1,[17] MAPK8IP1,[17] GIPC1[17] and SHC1.[25][26]
SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene.[1] SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells.
==============================================================
THAT'S HOW YOU FIND OUT HOW TGF WORKS TO BLOCK APOPTOSIS!
ACTIVIN IS A MALFORMATION INDUCING GENE
IT IS BOUND TO INHIBIN A BAD PROGNOSIS BIOMARKER IN GERM CELL CANCER
IT HAS A LINK TO ANGIOGENESIS (DOES AVASTIN WORKS HERE?)
WANT TO GO AFTER SHC1, BE MY GUEST!
IF WE ARE TREATING CANCER PATIENTS LIKE WE DO TODAY WITHOUT LOOKING AT THE CANCER CYTOKINES, WE ARE MISSING THE BIG PICTURE!
WE THANK THE NIH, MDHONORS, AND WIKIPEDIA FOR THEIR CONTRIBUTION TO SCIENCE AND PROGRESS TOWARD THE CURE (WE HOLD OFF ON OTHER FUNDING SOURCES )
The ACVRL1 protein is a receptor. It acts as a "lock" waiting for a specific protein, called its ligand, to serve as the "key." In the case of the ACVRL1 protein, the ligand is called transforming growth factor beta. The interaction between these proteins plays a role in the development of blood vessels. In particular, this protein interaction is involved in the specialization of new blood vessels into arteries or veins."
ACVR2A has been shown to interact with INHBA,[4][5] SYNJ2BP[6][7] and ACVR1B.[8][9]
=================================================THROUGH IN SYNJ2BP,
SYNJ2BP has been shown to interact with LRP2,[3] ACVR2B,[1] ACVR2A[1][4] and LRP1.[3]
=========================================================THROUGH LRP1
LRP1 has been shown to interact with Apolipoprotein E,[11][12] Lipoprotein lipase,[13][14][15] Urokinase receptor,[16] MAPK8IP2,[17] Tissue plasminogen activator,[18][19] Thrombospondin 1,[20][21][22] SYNJ2BP,[17] DLG4,[17] NOS1AP,[17] calreticulin,[23] APBB1,[24] ITGB1BP1,[17] MAPK8IP1,[17] GIPC1[17] and SHC1.[25][26]
SHC-transforming protein 1 is a protein that in humans is encoded by the SHC1 gene.[1] SHC has been found to be important in the regulation of apoptosis and drug resistance in mammalian cells.
==============================================================
THAT'S HOW YOU FIND OUT HOW TGF WORKS TO BLOCK APOPTOSIS!
ACTIVIN IS A MALFORMATION INDUCING GENE
IT IS BOUND TO INHIBIN A BAD PROGNOSIS BIOMARKER IN GERM CELL CANCER
IT HAS A LINK TO ANGIOGENESIS (DOES AVASTIN WORKS HERE?)
WANT TO GO AFTER SHC1, BE MY GUEST!
IF WE ARE TREATING CANCER PATIENTS LIKE WE DO TODAY WITHOUT LOOKING AT THE CANCER CYTOKINES, WE ARE MISSING THE BIG PICTURE!
WE THANK THE NIH, MDHONORS, AND WIKIPEDIA FOR THEIR CONTRIBUTION TO SCIENCE AND PROGRESS TOWARD THE CURE (WE HOLD OFF ON OTHER FUNDING SOURCES )
Saturday, October 5, 2013
DUPLICITE ROLE OF BMPs (BONE MORPHOGENIC PROTEINS)
While one will see their role in bone formation (BMP3) as evidently suggested by their name, in cancer medicine, the BMPs are more important in their potential to direct metastatic disease to the bones, to affect response to Androgen in metastatic Prostate cancers (BMP2)
---------------------------------------------------------------------------
===================================================
BUT ALSO TO AFFECT THE METABOLISM OF IRON
ie.." BMP6 Plays a role in joint integrity in adults. Controls iron homeostasis via regulation of hepcidin."WIKIPEDIA.
THIS IS AN EXAMPLE OF CYTOKINES THAT ARE MADE IN FAMILY WITH EACH OF THE MEMBERS AFFECTING VARIOUS TARGET CELLS, TO ACHIEVE A PANOPLY OF EFFECTS.
Hepcidin is one of the major modulator (regulatory hormone)of Iron metabolism. It decreases significantly in Hemochromatosis while increase in Iron deficiency as if increasing liver ability to store Iron!
----------------------------------------------------------------------------
removal of cellular Iron is "toxic" to certain bacterial and lack of Iron leads to Increase of transferrins (Iron carriers) increasing their chance to interact with class I MHC decreasing innate immunologic defense A BIG WAY FOR CANCER CELLS TO ESCAPE IMMUNOLOGIC SURVEILLANCE. SURPRISE SURPRISE IRON DEFICIENCY IS NOT GOOD FOR YOU IF YOU HAVE CANCER!
---------------------------------------------------------------------------
Alteration of gene expression in response to bone morphogenetic protein-2 in androgen-dependent human prostate cancer LNCaP cells.
Source
Department of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.Abstract
Bone morphogenetic protein (BMP)-2, a multifunctional member of the transforming growth factor (TGF)-beta superfamily with powerful osteoinductive effects, has various biological activities in a variety of cells. We observed that BMP-2 inhibits cell proliferation in the androgen-dependent human prostate cancer cell line, LNCaP. To investigate the mechanism of inhibition of androgen-dependent growth by BMP-2, we compared the gene expression in LNCaP cells treated with dihydrotestosterone (DHT) to that of LNCaP cells treated with DHT and BMP-2, using DNA microarray analysis......"===================================================
BUT ALSO TO AFFECT THE METABOLISM OF IRON
ie.." BMP6 Plays a role in joint integrity in adults. Controls iron homeostasis via regulation of hepcidin."WIKIPEDIA.
THIS IS AN EXAMPLE OF CYTOKINES THAT ARE MADE IN FAMILY WITH EACH OF THE MEMBERS AFFECTING VARIOUS TARGET CELLS, TO ACHIEVE A PANOPLY OF EFFECTS.
Hepcidin is one of the major modulator (regulatory hormone)of Iron metabolism. It decreases significantly in Hemochromatosis while increase in Iron deficiency as if increasing liver ability to store Iron!
The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation
Gaël Nicolas,1et al.----------------------------------------------------------------------------
removal of cellular Iron is "toxic" to certain bacterial and lack of Iron leads to Increase of transferrins (Iron carriers) increasing their chance to interact with class I MHC decreasing innate immunologic defense A BIG WAY FOR CANCER CELLS TO ESCAPE IMMUNOLOGIC SURVEILLANCE. SURPRISE SURPRISE IRON DEFICIENCY IS NOT GOOD FOR YOU IF YOU HAVE CANCER!
speculations in errors of metabolism!
*How a single nucleotide polymorphism affect
-gene regulator
-messenger RNA
-proteins
-metabolomic effects
Post-transcriptional modification affect the destiny of the resulting proteins
variations in splicing to protein isoform
prediction of protein plasticity variation based on electronic raprochement and disposition throughout the molecule
patient with nanism
and their susceptibility or not to vascular disease
or metabolic disease,
variation of metabolic flow in nanism
genetic variations that may induce early cancers (through genomic microarrays)
while looking at Butein, select observational SNPs, and P-450,CYP, electrolytes (Mg,Zn,Fe) to see in whom positive effect is observed
what variation in flow is a consequence of the mutation
is there a different metabolite produced (Galactitol-cataract, G-1-phosphatase-liver and Ovarian failure)
what enzyme is exacerbated as a result of the mutation
does this mutation affect an autophosphorylating gene
Are some forms of dementia linked to galactose-1-phosphate levels? can we slow down the disease through inhibition of G1P.
Is GLI-1 a flippase
and GLI-2 a floppase? located at 2 different pole of the cell
-gene regulator
-messenger RNA
-proteins
-metabolomic effects
Post-transcriptional modification affect the destiny of the resulting proteins
variations in splicing to protein isoform
prediction of protein plasticity variation based on electronic raprochement and disposition throughout the molecule
patient with nanism
and their susceptibility or not to vascular disease
or metabolic disease,
variation of metabolic flow in nanism
genetic variations that may induce early cancers (through genomic microarrays)
while looking at Butein, select observational SNPs, and P-450,CYP, electrolytes (Mg,Zn,Fe) to see in whom positive effect is observed
what variation in flow is a consequence of the mutation
is there a different metabolite produced (Galactitol-cataract, G-1-phosphatase-liver and Ovarian failure)
what enzyme is exacerbated as a result of the mutation
does this mutation affect an autophosphorylating gene
Are some forms of dementia linked to galactose-1-phosphate levels? can we slow down the disease through inhibition of G1P.
Is GLI-1 a flippase
and GLI-2 a floppase? located at 2 different pole of the cell
Friday, October 4, 2013
NOT ONE BUT 4 CRBCM ABSTRACTS SELECTED, WE ARE INDEED IN THE KNOW! WORK AHEAD AWAIT!
BIOMED Symposium - Abstracts Accepted
Inbox
x
Inbox
|  4:48 PM (7 minutes ago) | | ||
| ||||
Dear Dr. Kankonde:
Congratulations! On Behalf of the Selection
Committee, I am pleased to inform you that your three abstracts have
been selected for presentation at the
1st Annual BIOMED Symposium on October 26, 2013 at the
Camino Real in Downtown El Paso. Your posters will be displayed in the
Mezzanine (Level 2) and published in the 1st BIOMED
Poster Sessions Abstract Book. Poster awards will be announced during
the Collaboration Grant Reception and Networking session from 3:30 p.m. to 4:30 p.m.
Registration Information
Pre-registration is required for all poster presenters. Please register online for the event at
www.mcabiomed.com. Registration is $25 before October 18, and includes breakfast and lunch. After October 18, registration is $45 online and $65
at the door. Funding opportunities will be available only to presenters who are registered.
Guidelines for Poster Presentations
To assist you in preparing for your presentation, additional information is attached.
Should you have any questions or need additional assistance, please contact me at
(915) 773-5804 or by email at nsehgal@bmiamericas.org.
Again, let me congratulate you on being selected to present at the Symposium. We look forward to seeing you.
Enclosure:
1.
Guidelines for Poster Presentations
Sincerely,
Neyha Sehgal | Assistant Director of Market Analysis
BioMedical Institute of the Americas
201 East Main Street, Suite 401
El Paso, Texas 79901
(P): (915) 773-5804
(F): (915) 231-1949
Medical Center of the Americas Foundation
The Medical Center of
the Americas (MCA) Foundation is a 501(c)3 organization that advances
the development of the MCA campus and the region’s biomedical innovation
pipeline. The vision is to position the Paso
del Norte region as the leader of health services delivery, medical
education and research concentrating on issues unique to Hispanic,
border and military populations. Go to MCAmericas.org.
BioMedical Institute of the Americas
The BioMedical
Institute of the Americas (BMIA) is a 501(c)3 created by the MCA
Foundation to accelerate growth of biomedical innovations taking place
in the Paso del Norte. The BMIA does this through translational
research programs, incubation and economic cluster development. Go to
MCAmericas.org/bmia.
---------------------------------------------
THE 4TH IS THE LUNG CANCER PROJECT ACCEPTED BY MDHONORS AND BEING IN FULL SWING OF PROGRESS WITH UTEP! TISSUES WERE PROVIDED BY THE UNIVERSITY OF VIRGINIA TISSUE BANK!
THE 4TH IS THE LUNG CANCER PROJECT ACCEPTED BY MDHONORS AND BEING IN FULL SWING OF PROGRESS WITH UTEP! TISSUES WERE PROVIDED BY THE UNIVERSITY OF VIRGINIA TISSUE BANK!
WHAT GOT MY ATTENTION
*THE COMBINATION OF ERIBULIN WITH XEALODA IN TRIPLE NEGATIVE BREAST CANCER.
*WHAT REMAINS A QUESTION IS THE ROLE OF INTERFERON AS AN ADJUVANT (OR MAINTENANCE )THERAPY IN TRIPLE NEGATIVE BREAST CANCER
*I COULD SEE HOW THE ANDROGEN RECEPTOR WOULD BE OF IMPORTANCE IN LUMINAL A BREAST CANCER GIVEN ITS RICH HORMONE RECEPTOR PRESENCE (WHEN LOW Ki-67 IS PRESENT)
*WHAT REMAINS A QUESTION IS THE ROLE OF INTERFERON AS AN ADJUVANT (OR MAINTENANCE )THERAPY IN TRIPLE NEGATIVE BREAST CANCER
*I COULD SEE HOW THE ANDROGEN RECEPTOR WOULD BE OF IMPORTANCE IN LUMINAL A BREAST CANCER GIVEN ITS RICH HORMONE RECEPTOR PRESENCE (WHEN LOW Ki-67 IS PRESENT)
REPORTS FROM VARIOUS SOURCES
*Breast cancer remains the most frequent cancer in women
the 5 year survival has improved however from 75% to the 90% over the last 30 Years
mostly for early disease because of early detection and better adjuvant therapies!
Metastatic breast cancers remains however incurable (Jennifer Klem et al)
4 types:
Luminal A mostly ER and PR positive (Hormone rich) with low Ki-67
Luminal B (Her-2 negative by ER/PR positive with high Ki-67
Luminal B (Her-2 positive and ER/PR positive with random Ki-67
Basal like which is triple negative
HER-2 positive
Hormone positive treated with Endocrine therapy
Hormone negative treated with Chemotherapy
Combination therapy in patient losing performance status, and Visceral involvement and heavy tumor burden.
For Her-2 positive - Taxol-Herceptin would be an option (Her positive means 3+ on IHC or Fish >2.2 amplification(ASCO), T-DM1 and perjeta could add to the Herceptin option while,
for ER/PR positive-addition of everolimus could add to hormone therapy"
the 5 year survival has improved however from 75% to the 90% over the last 30 Years
mostly for early disease because of early detection and better adjuvant therapies!
Metastatic breast cancers remains however incurable (Jennifer Klem et al)
4 types:
Luminal A mostly ER and PR positive (Hormone rich) with low Ki-67
Luminal B (Her-2 negative by ER/PR positive with high Ki-67
Luminal B (Her-2 positive and ER/PR positive with random Ki-67
Basal like which is triple negative
HER-2 positive
Hormone positive treated with Endocrine therapy
Hormone negative treated with Chemotherapy
Combination therapy in patient losing performance status, and Visceral involvement and heavy tumor burden.
For Her-2 positive - Taxol-Herceptin would be an option (Her positive means 3+ on IHC or Fish >2.2 amplification(ASCO), T-DM1 and perjeta could add to the Herceptin option while,
for ER/PR positive-addition of everolimus could add to hormone therapy"
"Everolimus Gains FDA Approval for Metastatic Breast Cancer"
Afinitor may be given with exemestane for hormone receptor-positive, HER2 negative disease
August 1, 2012
Written By Nicole Katze, MA, Writer and Editorial Coordinator
Reviewed By Robert A. Somer, MD"
Reviewed By Robert A. Somer, MD"
Research Underway at CRBCM! thanks to MDHONORS'FUNDING
INTERNAL COMMUNICATION
|
Oct 1 (3 days ago)
| | ||
| ||||
Good Afternoon,
the five first tissues have been shipped and will arrive at your laboratory tomorrow morning.--
We have moved to a new location on Sept.6th, 2013:
Dr. Mutombo KANKONDE M.D., M.Ph.
Greater East Cancer Center & CRBCM
Coalition for the Reversal of Breast Cancer Mortality in African American Women
Thursday, October 3, 2013
Interesting aspects of Herpetic Infections
No infection is as intriguing as the Herpetic infection. Its interest lays in several facts
1. The mere fact that a Third of the US population may be involved makes this disease one of the most prevalent ones, but it is also feared. Whether the fear is justified or not remains a question.
2. Certainly it has something to do with horrific stories of potential recurrence of horrific burning neuropathic pains that we have heard about. Science does not know for sure whether only specific viral serotypes lead to this or whether certain hosts genes isoforms or inflammatory reactions may be contributing to this presentation.
3. The outbreak is accompanied with guilt and sense of guiltiness that is mostly unjustified...many questions arise after the realization that those painful skin or otherwise lesions could be herpetic...that a partner you have gave this to you and that you may give this to a new partner? Those questions are valid but with the prominence of the prevalence of this disease in the US, who and when one got exposed to Herpes is one of the great mysteries in herpetic disease. Herpes 1 has been linked to Over crowding, and Herpes 2 is the one with a sexual connotation. But one should remember that the Herpetic Virus will invade teguments (particularly abrasions) when contact happens, sexual or not! And very often this happens in our tender ages of infancy. Remember the infection can be symptomatic, but most of the time completely without any clinical manifestations. And enters quietly a dormancy.
4. The dormancy itself is quite a puzzling event! All we know is that the capsule to this double stranded DNA viral particule is from the host! This may help it to be "tolerated " by the host. We can speculate that class I MHC will not be bothered. Only the class II may note the invader most likely and provide the Antibody that we can measure!
5. The exacerbation of the herpetic infection is also puzzling in many ways
-It happens when we are under stress (menstruation and exposure to UV light), pregnancy state and post chemotherapy, the so called state of "when the immune system" is down!
-To the writer this is a state of activity of the c-JUN and Fos, the NF-kB and full epigenetic phenomena as if cyclines and TNF, TGFs are in full swing! Epigenetic events seem to free or unleash genes (regulators or not) that will reactivate the Virus.
-How and where these events occur (Golgi, Nucleus, or cytosolic) remains to be clarified.
(Let raise the eyelid of this dormant disease and look at it through its eyes/pupils without awakening it!)
6. The bad exacerbation could be virally induced or it could be in fact a reaction of the Host (Neutrophilic Grazymes) or Cyclin effects. ie. In post Brain trauma injury (TBI) we know that post synaptic nerve death is due to Cytokins that kill post synaptic nerve, is it the same in this herpetic disease?And if it is, what would be the therapeutic implications?!
1. The mere fact that a Third of the US population may be involved makes this disease one of the most prevalent ones, but it is also feared. Whether the fear is justified or not remains a question.
2. Certainly it has something to do with horrific stories of potential recurrence of horrific burning neuropathic pains that we have heard about. Science does not know for sure whether only specific viral serotypes lead to this or whether certain hosts genes isoforms or inflammatory reactions may be contributing to this presentation.
3. The outbreak is accompanied with guilt and sense of guiltiness that is mostly unjustified...many questions arise after the realization that those painful skin or otherwise lesions could be herpetic...that a partner you have gave this to you and that you may give this to a new partner? Those questions are valid but with the prominence of the prevalence of this disease in the US, who and when one got exposed to Herpes is one of the great mysteries in herpetic disease. Herpes 1 has been linked to Over crowding, and Herpes 2 is the one with a sexual connotation. But one should remember that the Herpetic Virus will invade teguments (particularly abrasions) when contact happens, sexual or not! And very often this happens in our tender ages of infancy. Remember the infection can be symptomatic, but most of the time completely without any clinical manifestations. And enters quietly a dormancy.
4. The dormancy itself is quite a puzzling event! All we know is that the capsule to this double stranded DNA viral particule is from the host! This may help it to be "tolerated " by the host. We can speculate that class I MHC will not be bothered. Only the class II may note the invader most likely and provide the Antibody that we can measure!
5. The exacerbation of the herpetic infection is also puzzling in many ways
-It happens when we are under stress (menstruation and exposure to UV light), pregnancy state and post chemotherapy, the so called state of "when the immune system" is down!
-To the writer this is a state of activity of the c-JUN and Fos, the NF-kB and full epigenetic phenomena as if cyclines and TNF, TGFs are in full swing! Epigenetic events seem to free or unleash genes (regulators or not) that will reactivate the Virus.
-How and where these events occur (Golgi, Nucleus, or cytosolic) remains to be clarified.
(Let raise the eyelid of this dormant disease and look at it through its eyes/pupils without awakening it!)
6. The bad exacerbation could be virally induced or it could be in fact a reaction of the Host (Neutrophilic Grazymes) or Cyclin effects. ie. In post Brain trauma injury (TBI) we know that post synaptic nerve death is due to Cytokins that kill post synaptic nerve, is it the same in this herpetic disease?And if it is, what would be the therapeutic implications?!
Wednesday, October 2, 2013
Reports from various sources
*In Metastatic Renal cell cancer : Sutent Response rate was 38%
with median response duration 53 weeks
most of the responses were observed in 12 weeks (European Journal)
*In Metastatic HER-2 positive Breast cancers, Adding chemotherapy to Herceptin increases the response Rate from 15-26% to 60-70%, weekly Taxol +/- Carboplatin is one of the option aside from Vinorelbie and Taxotere with improvement of both the one year and overall survival!
*Lapatinib, a dual EGFR-1 and Her-2 Tyrosine Kinase inhibitor, when combined to Capecitabine only increase (more likely double) for sure progression free survival. The overall survival could not be proven because of cross-over! (ASCO)
with median response duration 53 weeks
most of the responses were observed in 12 weeks (European Journal)
*In Metastatic HER-2 positive Breast cancers, Adding chemotherapy to Herceptin increases the response Rate from 15-26% to 60-70%, weekly Taxol +/- Carboplatin is one of the option aside from Vinorelbie and Taxotere with improvement of both the one year and overall survival!
*Lapatinib, a dual EGFR-1 and Her-2 Tyrosine Kinase inhibitor, when combined to Capecitabine only increase (more likely double) for sure progression free survival. The overall survival could not be proven because of cross-over! (ASCO)
Tuesday, October 1, 2013
And the questions dance continua
1.Can infusion of purified IL-17 boost the anti-cancer property of IL-2?
2.Can infusion of IL4 (IL-10, TGF-beta) helps in treatment of autoimmune diseases
3.can elimination of Treg cells boost the effect of IL-2
4.Can TCR editing or "molecular mimicry" be used in cancer therapeutics.
5 What the associated biomarkers that could be in conjunction with HLA typing to predict response to therapy or cancer responsiveness to autoimmune therapeutic intervention?
6.Can inhibitors of the NOTCH pathways or the Wnt treat Pemphigus
7. what is the role of human opsonins in cancer therapy (surfactant A and D, Fibronectin, Vitronectin in lung cancer)
2.Can infusion of IL4 (IL-10, TGF-beta) helps in treatment of autoimmune diseases
3.can elimination of Treg cells boost the effect of IL-2
4.Can TCR editing or "molecular mimicry" be used in cancer therapeutics.
5 What the associated biomarkers that could be in conjunction with HLA typing to predict response to therapy or cancer responsiveness to autoimmune therapeutic intervention?
6.Can inhibitors of the NOTCH pathways or the Wnt treat Pemphigus
7. what is the role of human opsonins in cancer therapy (surfactant A and D, Fibronectin, Vitronectin in lung cancer)
Sunday, September 29, 2013
potential questions in biomedical science
questions in basic medical sciences
1. Can new heat shock Proteins made to be recognized by the the endosomal immune system?
2. Can cancer cells express DNA motifs recognizable by the TLR9
3. Can cytokines (IL11, IL 17, GCSF,Interferon-beta, be used as reliable predictor markers of pulmonary fibrosis in patient treated with Bleomycin)
4. Can we electively silence MHC class I on cancer cell enough to trigger the "missing self Hypothesis".
(CD159,CD 158, CD 85)
5.Review the full role of Immunoglobulin-like transcription receptors
6.Harvesting Metastatic potential of cancer cell in their tagging with IgG susceptible to trigger FcyR NK cell-antibody dependent cell mediated cytotoxicity. (survey of cancer cell receptors).
7Quantifying heat shock proteins in normal Vs cancer cells as a way to detect cancer cells, targeting them for increased scusceptibilty to be detected by dendritic cells?
8. Silencing MHC class I gene in cancer cells could be a significant way to trigger NK cells
9. Can perturbation at the FAK, decrease of E-Cadherin be associated with antigenic triggering changes of memebrane phospholipids?
10. developement of small peptide susceptible to change MHC class I in cancer cells
11. pertubations of endonuclease in cancer cell as a way to induce changes in TCR
12. Is TAP (transporter in Antigen Processing) a valid target in cancer therapy?
1. Can new heat shock Proteins made to be recognized by the the endosomal immune system?
2. Can cancer cells express DNA motifs recognizable by the TLR9
3. Can cytokines (IL11, IL 17, GCSF,Interferon-beta, be used as reliable predictor markers of pulmonary fibrosis in patient treated with Bleomycin)
4. Can we electively silence MHC class I on cancer cell enough to trigger the "missing self Hypothesis".
(CD159,CD 158, CD 85)
5.Review the full role of Immunoglobulin-like transcription receptors
6.Harvesting Metastatic potential of cancer cell in their tagging with IgG susceptible to trigger FcyR NK cell-antibody dependent cell mediated cytotoxicity. (survey of cancer cell receptors).
7Quantifying heat shock proteins in normal Vs cancer cells as a way to detect cancer cells, targeting them for increased scusceptibilty to be detected by dendritic cells?
8. Silencing MHC class I gene in cancer cells could be a significant way to trigger NK cells
9. Can perturbation at the FAK, decrease of E-Cadherin be associated with antigenic triggering changes of memebrane phospholipids?
10. developement of small peptide susceptible to change MHC class I in cancer cells
11. pertubations of endonuclease in cancer cell as a way to induce changes in TCR
12. Is TAP (transporter in Antigen Processing) a valid target in cancer therapy?
Saturday, September 28, 2013
OVEREXPRESSION OF TRIB3 AMD SUPPRESSION OF TIAF1,NEW TARGETS IN THERAPY!
Based on our current understanding most receptor failure will go on to induce the stress related pathways which ultimately will go on to produce epigenetic events which will include not only transcription factors production but also significant cytokines production. Some of these Cytokines includes growth factors which not only have the role of inducing growth of the cell, but also blocking Apoptosis.
The activation of NF-kB, one of our stress coping pathway, happens to induce TRIB3 but this elevation has a negative regulator effect on the NF-kB therefore decreasing the intensity of one of the most significant trigger (in chronic exposure to irritant stimuli) or amplifier of specific cancers, and driver of cytokine production. Activating this TRIB3 could have significant effect in autoimmune diseases and have a significant effect in supportive cancer treatment and maintenance settings.
TIAF1, however, needs to be suppressed because it is the mechanism by the TGF to block death of cells.
In diseases where growth factors are the drivers , block the hell out of this TIAF1 please. At CRBCM we are trying to see if these 2 interventions may help IL-2 effect in melanoma and Renal cancers. FUNDS are missing so please help if you can!
What we keep as a secret is the work on anti-granulin (because here Cyclin T is involved, and with it TRIB3)!(HIV is not far a target!)
"The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB, and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1.[3]
The activation of NF-kB, one of our stress coping pathway, happens to induce TRIB3 but this elevation has a negative regulator effect on the NF-kB therefore decreasing the intensity of one of the most significant trigger (in chronic exposure to irritant stimuli) or amplifier of specific cancers, and driver of cytokine production. Activating this TRIB3 could have significant effect in autoimmune diseases and have a significant effect in supportive cancer treatment and maintenance settings.
TIAF1, however, needs to be suppressed because it is the mechanism by the TGF to block death of cells.
In diseases where growth factors are the drivers , block the hell out of this TIAF1 please. At CRBCM we are trying to see if these 2 interventions may help IL-2 effect in melanoma and Renal cancers. FUNDS are missing so please help if you can!
What we keep as a secret is the work on anti-granulin (because here Cyclin T is involved, and with it TRIB3)!(HIV is not far a target!)
"The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB, and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1.[3]
Interactions
TRIB3 has been shown to interact with:- AKT1,[1]
- CSNK2B,[4]
- Fibronectin[4]
- MCM3AP,[5]
- RELA,[6]
- SIAH1,[4] and
- TIAF1.[4]"
- wikipedia
- ==================================================================
-
TGFB1-induced anti-apoptotic factor 1 is a protein that in humans is encoded by the TIAF1 gene.[1][2]
Interactions
TIAF1 has been shown to interact with Janus kinase 3[3] and TRIB3.[4]wikipedia
(watch this in Promyelocytic leukemia)
CRBCM is coming!
Friday, September 27, 2013
CPRIT NEW BOARD MEMBERS APPOINTED
THINGS ARE GETTING IN SHAPE AT CPRIT AS GOVERNOR RICK PERRY HAS NOMINATED NEW MEMBERS TO THE BOARD. THESE NOMINATIONS REPORTEDLY WERE MANDATED BY STATE LAW.
CPRIT IS STILL RESHAPING ITSELF AND WILL BE SOON BACK INTO OPERATION BEFORE THE END OF THE YEAR ACCORDING TO SEVERAL SOURCES... MANY STILL ARE HOPEFUL THIS TIME AROUND WILL BE LESS POLITICAL AND BIASED!
-----------------------------------------------------------------
CRBCM MEANWHILE HAS COMPLETED A MOVE AIMED AT HAVING A DIRECT FRONTAGE TO THE STREET. OUR PELLICANO LOCATION GIVES US DIRECT STREET EXPOSURE AS WE WELCOME WALK-INS.
-----------------------------------------------------------------------------
THE BEGINNING OF OCTOBER WILL MARK THE START OF THE FULL COLLABORATION WITH UTEP ON THE LUNG CANCER DETECTION EVALUATION. PER CONTRACTUAL AGREEMENT, THE PI WILL BE PROFESSOR JIANYING ZHANG and the University of Virginia is still providing the tissue SAMPLES. CRBCM is providing additional funding for the project !
CPRIT IS STILL RESHAPING ITSELF AND WILL BE SOON BACK INTO OPERATION BEFORE THE END OF THE YEAR ACCORDING TO SEVERAL SOURCES... MANY STILL ARE HOPEFUL THIS TIME AROUND WILL BE LESS POLITICAL AND BIASED!
-----------------------------------------------------------------
CRBCM MEANWHILE HAS COMPLETED A MOVE AIMED AT HAVING A DIRECT FRONTAGE TO THE STREET. OUR PELLICANO LOCATION GIVES US DIRECT STREET EXPOSURE AS WE WELCOME WALK-INS.
-----------------------------------------------------------------------------
THE BEGINNING OF OCTOBER WILL MARK THE START OF THE FULL COLLABORATION WITH UTEP ON THE LUNG CANCER DETECTION EVALUATION. PER CONTRACTUAL AGREEMENT, THE PI WILL BE PROFESSOR JIANYING ZHANG and the University of Virginia is still providing the tissue SAMPLES. CRBCM is providing additional funding for the project !
FOR POWER, WATCH THE COMPANY YOU KEEP! IBRUTINIB, A WONDER DRUG.
IBRUTINIB, A WONDER DRUG.
=========================
If there is a wonder drug, nothing comes close to Ibrutinib! This drug could be a wonder drug for sure because it affect not only powerful genes that cause malformations when they are mutated (a clear power of the gene) but also involve all mighty "wild genes" (those having multiple interactions).
Malformations involved by the Bruton (BTK) gene are particularly wide going from Agammaglobulinemia which kill children with multiple infections, to the Sturge-Weber syndrome which lead to mental Retardation and seizures, to the Albright syndrome! Even bone dysmorphy is in the wing.
wild genes involved include the Gerb2 through the GAB1, the LYN, PTPN1 etc...
The mere involvement of the Adenyl Cyclase remind us of some of the undesirable effect of powerful infection such as E.coli, Mycobacterium, and the Whooping cough! All these various pathways are affected broadening the impact of Ibrutinib to all white blood cell neoplastic process!
By affecting the GNAQ, Bruton's Inhibitor could work in Uveal Melanoma theoritically
And through inhibition of the GPCR family (S1PR1) Bruton inhibitor could act in Angiosarcoma and harmartomatous syndromes. Remember RIC8A and the Gs -ALPHA are affected!
Investors, if you have not jump on the wagon, it is not too late! Ibrutinib is a wild one with unlimited potential! IBRUTINIB IS POWERFUL BECAUSE OF THE GENE COMPANY IT KEEPS!
===========================================
the CRBCM has not invested in any drug to this point! But the science is behind this drug!
===========================================
WIKIPEDIA comes to the Rescue with scientific comments!
In preclinical studies on chronic lymphocytic leukemia (CLL) cells, ibrutinib has been reported to promote apoptosis, inhibit proliferation, and also prevent CLL cells from responding to survival stimuli provided by the microenvironment.[11] In this study, treatment of activated CLL cells with ibrutinib resulted in inhibition of Btk tyrosine phosphorylation and also effectively abrogated downstream survival pathways activated by this kinase including ERK1/2, PI3K, and NF-κB. Additionally, ibrutinib inhibited proliferation of CLL cells in vitro, effectively blocking survival signals provided externally to CLL cells from the microenvironment including soluble factors (CD40L, BAFF, IL-6, IL-4, and TNF-α), fibronectin engagement and stromal cell contact.
In early clinical studies, the activity of ibrutinib has been described to include a rapid reduction in lymphadenopathy accompanied by a transient lymphocytosis, suggesting that the drug might have direct effects on cell homing or migration to factors in tissue microenvironments.[12]
Ibrutinib has been reported to reduce CLL cell chemotaxis towards the chemokines CXCL12 and CXCL13, and inhibit cellular adhesion following stimulation at the B cell receptor.[13][14] Together, these data are consistent with a mechanistic model whereby ibrutinib blocks BCR signaling, which drives cells into apoptosis and/or disrupts cell migration and adherence to protective tumor microenvironments.
1.S1PR1 is one of the main responsible of vascular growth and development, at least during embryogenesis.[9] In vascular endothelial cells the binding of S1P to S1PR1 induces migration, proliferation, cell survival and morphogenesis into capillary-like structures.[10] Moreover, the binding of S1P to S1PR1 is implicated in the formation of cell-cell adherens junctions, therefore inhibiting paracellular permeability of solutes and macromolecules.[11][12] It was also shown in vivo that S1P synergizes with angiogenic factors such as FGF-2 and VEGF in inducing angiogenesis and vascular maturation through S1PR1.[12][13] showed that S1PR1-KO mice died during development due to a defect in vascular stabilization, suggesting that this receptor is essential for vascular development. In conclusion, several evidences confirm that S1P via S1PR1 is a potent regulator of vascular growth and development, at least during embryogenesis.[9]
2.RGS16. It inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits.
3.GNAQ1 activity is terminated by:
Activation of GNAQ1 is terminated by a GTPase intrinsic to the G-alpha subunit. G-alpha-q is the alpha subunit of one of the heterotrimeric GTP-binding proteins that mediates stimulation of phospholipase C-beta (MIM 600230).[supplied by OMIM][2]
4. Bruton's tyrosine kinase (abbreviated Btk or BTK) is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). Its exact mechanism of action remains unknown, but it plays a crucial role in B cell maturation as well as mast cell activation through the high-affinity IgE receptor. Patients with XLA have normal pre-B cell populations in their bone marrow but these cells fail to mature and enter the circulation. The Btk gene is located on the X chromosome.[1] At least 400 mutations of the Btk gene have been identified.WIKIPEDIA
=========================
If there is a wonder drug, nothing comes close to Ibrutinib! This drug could be a wonder drug for sure because it affect not only powerful genes that cause malformations when they are mutated (a clear power of the gene) but also involve all mighty "wild genes" (those having multiple interactions).
Malformations involved by the Bruton (BTK) gene are particularly wide going from Agammaglobulinemia which kill children with multiple infections, to the Sturge-Weber syndrome which lead to mental Retardation and seizures, to the Albright syndrome! Even bone dysmorphy is in the wing.
wild genes involved include the Gerb2 through the GAB1, the LYN, PTPN1 etc...
The mere involvement of the Adenyl Cyclase remind us of some of the undesirable effect of powerful infection such as E.coli, Mycobacterium, and the Whooping cough! All these various pathways are affected broadening the impact of Ibrutinib to all white blood cell neoplastic process!
By affecting the GNAQ, Bruton's Inhibitor could work in Uveal Melanoma theoritically
And through inhibition of the GPCR family (S1PR1) Bruton inhibitor could act in Angiosarcoma and harmartomatous syndromes. Remember RIC8A and the Gs -ALPHA are affected!
Investors, if you have not jump on the wagon, it is not too late! Ibrutinib is a wild one with unlimited potential! IBRUTINIB IS POWERFUL BECAUSE OF THE GENE COMPANY IT KEEPS!
===========================================
the CRBCM has not invested in any drug to this point! But the science is behind this drug!
===========================================
WIKIPEDIA comes to the Rescue with scientific comments!
In preclinical studies on chronic lymphocytic leukemia (CLL) cells, ibrutinib has been reported to promote apoptosis, inhibit proliferation, and also prevent CLL cells from responding to survival stimuli provided by the microenvironment.[11] In this study, treatment of activated CLL cells with ibrutinib resulted in inhibition of Btk tyrosine phosphorylation and also effectively abrogated downstream survival pathways activated by this kinase including ERK1/2, PI3K, and NF-κB. Additionally, ibrutinib inhibited proliferation of CLL cells in vitro, effectively blocking survival signals provided externally to CLL cells from the microenvironment including soluble factors (CD40L, BAFF, IL-6, IL-4, and TNF-α), fibronectin engagement and stromal cell contact.
In early clinical studies, the activity of ibrutinib has been described to include a rapid reduction in lymphadenopathy accompanied by a transient lymphocytosis, suggesting that the drug might have direct effects on cell homing or migration to factors in tissue microenvironments.[12]
Ibrutinib has been reported to reduce CLL cell chemotaxis towards the chemokines CXCL12 and CXCL13, and inhibit cellular adhesion following stimulation at the B cell receptor.[13][14] Together, these data are consistent with a mechanistic model whereby ibrutinib blocks BCR signaling, which drives cells into apoptosis and/or disrupts cell migration and adherence to protective tumor microenvironments.
1.S1PR1 is one of the main responsible of vascular growth and development, at least during embryogenesis.[9] In vascular endothelial cells the binding of S1P to S1PR1 induces migration, proliferation, cell survival and morphogenesis into capillary-like structures.[10] Moreover, the binding of S1P to S1PR1 is implicated in the formation of cell-cell adherens junctions, therefore inhibiting paracellular permeability of solutes and macromolecules.[11][12] It was also shown in vivo that S1P synergizes with angiogenic factors such as FGF-2 and VEGF in inducing angiogenesis and vascular maturation through S1PR1.[12][13] showed that S1PR1-KO mice died during development due to a defect in vascular stabilization, suggesting that this receptor is essential for vascular development. In conclusion, several evidences confirm that S1P via S1PR1 is a potent regulator of vascular growth and development, at least during embryogenesis.[9]
2.RGS16. It inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits.
3.GNAQ1 activity is terminated by:
Activation of GNAQ1 is terminated by a GTPase intrinsic to the G-alpha subunit. G-alpha-q is the alpha subunit of one of the heterotrimeric GTP-binding proteins that mediates stimulation of phospholipase C-beta (MIM 600230).[supplied by OMIM][2]
4. Bruton's tyrosine kinase (abbreviated Btk or BTK) is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). Its exact mechanism of action remains unknown, but it plays a crucial role in B cell maturation as well as mast cell activation through the high-affinity IgE receptor. Patients with XLA have normal pre-B cell populations in their bone marrow but these cells fail to mature and enter the circulation. The Btk gene is located on the X chromosome.[1] At least 400 mutations of the Btk gene have been identified.WIKIPEDIA
ROLE OF GLYCOPEPTIDE (receptor) ALTERATION IN THE MALIGNANT TRANSFORMATION
One of the function of the Glycan coverage of protein receptor is not only to be a an integral part of the Glycopeptide nature of the receptor as it is recognized, but to also induce Antigenic like recognition by the immune system when the cell is altered as it occurs during a neoplastic transformation of the cell. During such a transformation, it is believed that cyclines and altered FAK abnormally produced may cause membrane alterations which include alterations at cellular receptors that will dampen cellular induction of chemokines that could be naturally induced. This effect will reduce normal recognition of cellular abnormality, and dampen caspase 3 stimulation as well as allowing the changed cell to escape immune recognition. There is indeed a cascade of maneuvers that allow the cell to survive a neoplastic transformation. Aside for an uncontrolled DNA duplication and cellular proliferation, gene alterations and mistakes must be tolerated through suppression of control genetic mechanisms, gen repair must fail, BRCA genes and the like of them must be "mutated" and Breaks such as P53 must be 'MUTATED" to let the neoplastic process advance. Suppressor gene such as Rb1 must be silenced! Receptors under the attack of cytokines, will have their Glycan portion altered. the Receptor consequently become resistant to its stimulant growth factor, a fact which under normal considition will stimulate further growth factor to try to conquer the resistance, this increase will stimulate intact secondary factor and dampen some pathway genes (PTEN) an break to the PI3K pathway. further stressful action will start the HSP family of Heat stroke Protein and cause the c-JUN/c-fos, increasing further epigenetic events....Again glycopeptide alteration is a critical step in cellular tolerance of malignant transformed cell (IT IS BELIEVED)
Thursday, September 26, 2013
NEW! Market Research
Clinical Trial Detail
◄ Back to SearchStudies on Tumors of the Thyroid
See this on ClinicalTrials.gov
| Trial Phase N/A |
Enrollment Quota 99999999 |
Specialty: Endocrinology,Internal Medicine,Oncology Subspecialty: Endocrine Oncology,Thyroid/Parathyroid,Endocrinology,Hematology/Oncology,Endocrine Oncology Sponsor: National Institutes of Health Clinical Center (CC) |
Estimated Completion Date: Not specified
Interventions
No interventions citedInclusion criteria
- Adults and children with known or suspected thyroid neoplasm will be considered for participation. Enrollment will be capped accordingly:
- Patients with thyroid nodules requiring evaluation and possible biopsy (no more than 30 per year)
- Patients with recent diagnosis of thyroid cancer requiring consultation and counseling about therapeutic options (no more than 10 per year)
- Patients with established thyroid cancer requiring specialized studies such as (131)I dosimetry (no more than 5 per year)
- Enrollment of high risk, non-iodine avid, inoperable thyroid cancer only for purposes of screening for eligibility for other specific thyroid cancer protocols
Exclusion criteria
- Serious underlying medical conditions that restrict diagnostic testing or therapy such as renal failure, congestive cardiac failure or active coexisting non-thyroid carcinoma
- Patients unable or unwilling to give informed consent
Study Locations And Contact Information
-
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda Maryland
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 prpl@mail.cc.nih.gov
Description:
Participants in this study will be patients diagnosed with or suspected to have a thyroid nodule or thyroid cancer. The main purpose of this study is to further understand the methods for the diagnosis and treatment of thyroid nodules and thyroid cancer. Many of the test performed are in the context of standard medical care that is offered to all patients with thyroid nodules or thyroid cancer. Other tests are performed for research purposes. In addition, blood and tissue samples will be taken for research and genetic studies.See this on ClinicalTrials.gov
1
General practitioner involvement in follow-up of childhood cancer survivors: A systematic review
Pediatric Blood & Cancer, July 8, 2013
Evidence Based Medicine
Review Article
2
Cancer incidence and survival among adolescents in Israel during the years 1998 to 2009
Pediatric Blood & Cancer, July 8, 2013
Clinical Article
3
PAX8 is expressed in Anaplastic Thyroid Carcinoma diagnosed by
fine needle aspiration. A study of three cases with histological
correlates
European Journal of Endocrinology, July 1, 2013
4
Targeting mTOR in RET mutant medullary and differentiated thyroid cancer cells
Endocrine-Related Cancer, July 8, 2013
Review Article
5
Thyroid carcinoma in children and adolescents: diagnostic implications of analysis of the tumor genome
Current Opinion in Pediatrics, July 19, 2013
Review Article
Sponsor
Just an annoucement from the "District"
"Evaluation
of the recent cases of perinatal HIV infection and/or exposure shows
that some of our HIV-infected District residents need more support,
ranging from medication adherence and medical appointment compliance to
more social issues such as inadequate housing and food insecurity. As
such, the HIV/AIDS, Hepatitis, STD and TB Administration has made
pregnancy in HIV-infected women a reportable condition. This change was
made so that we can ensure the health of pregnant women, prevent the
transmission of a communicable disease and offer medical and/or social
services they may require.
The report form is available at the DOH website (http://doh.dc.gov/page/doh-applications-and-forms).
It is also attached to this announcement. For additional details there
is an attached “Dear Colleague” letter that was agreed to by our local
American Academy of Pediatrics and local American College of
Obstetricians and Gynecologists chapters. There is also a Frequently
Asked Questions document.
New, expanded library hours start
Oct. 1. More hours for story time. More hours for
community meetings. More hours to use free computers. Check out the
library's new hours at dclibrary.org/newhours."
Be aware of PAX8
What is the normal function of the PAX8 gene?
The PAX8 gene belongs to a family of
genes that plays a critical role in the formation of tissues and organs
during embryonic development. The PAX gene family is also important for
maintaining the normal function of certain cells after birth. To carry
out these roles, the PAX genes provide instructions for making proteins
that attach to specific areas of DNA. By attaching to critical DNA
regions, these proteins help control the activity of particular genes
(gene expression). On the basis of this action, PAX proteins are called
transcription factors.
During embryonic development, the PAX8 protein is thought to activate genes involved in the formation of the kidney and the thyroid gland. The thyroid gland is a butterfly-shaped tissue in the lower neck. It releases hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). Following birth, the PAX8 protein regulates several genes involved in the production of thyroid hormones.(fromGenetics home reference)
=======================================
It is now used a biomarker:
"PAX8 is expressed in Anaplastic Thyroid Carcinoma diagnosed by
fine needle aspiration. A study of three cases with histological
correlates
"
===========================
"
During embryonic development, the PAX8 protein is thought to activate genes involved in the formation of the kidney and the thyroid gland. The thyroid gland is a butterfly-shaped tissue in the lower neck. It releases hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). Following birth, the PAX8 protein regulates several genes involved in the production of thyroid hormones.(fromGenetics home reference)
=======================================
It is now used a biomarker:
"PAX8 is expressed in Anaplastic Thyroid Carcinoma diagnosed by
fine needle aspiration. A study of three cases with histological
correlates
"
European Journal of Endocrinology, 07/01/2013
Bellevicine C et al. – The aim of this study was to evaluate
whether PAX8 could identify anaplastic thyroid carcinoma (ATC) also on
cytology. PAX8 immunocytochemistry can help the cytopathologist to
diagnose ATC.
"
Wednesday, September 25, 2013
just in now!
 |
Developed under the direction and sponsorship of Bristol-Myers Squibb. |
|
||||||||||||||
|
||||||||||||||||
|
| |||||||||||||||
Genetic going deeper in the Obesity research!
Going deep into Obesity issues and tumor induced cachexia, we stumble upon RIP 140, Sp1, and believe or not E2F1(a wild gene).
"RIP140 is part of the chain by which tumors can cause cachexia.[15][16]
Levels of RIP140 expression in various tissues varies during aging in mice, suggesting changes in metabolic function.[17] RIP140 is implicated in certain human disease processes. In morbid obesity, RIP140 levels are down-regulated in visceral adipose tissue.[18] In breast cancer, RIP140 is involved in regulation of E2F1, an oncogene which discriminates between luminal and basal types of tumours. RIP140 has an influence upon cancer phenotype and prognosis.[19] In addition, RIP140 has a role in inflammation, since it acts as a coactivator for NFkappaB/RelA-dependent cytokine gene expression. Lack of RIP140 leads to an inhibition of proinflammatory pathways in macrophages."
wikipedia
It seems that this is where Obesity becomes a disease by its state of high inflammatory state. The diease process in Obesity is defined or determined by a relatively high level of Growth factor and Cytokines inducing major deleterious consequences on the muscle skeletal system through the activated NF-KB. The RIP 140 (also known as NRIP1) is hard at work. Remember it interacts with DAX1 which involves the COPS2 (nothing to do with the police!),SREBF1 (the bone modulator) and SF1 ("feminization" of the obese individual).
It is clearly important that the understanding and measurement of the obese by clear new biomarkers allow us to establish new guidelines for monitoring. Following BMI, lipid profile and pushing diet is clearly insufficient. Blocking the central Nervous system to force mental rejection of food is not the only answer ...remember RIP-140 modulation is part of cachexia induced by Tumors.
(remember the rule, if it can induce a malformation, it is an important gene (check out DAX1 and SREBF1)
Othre gene in the link TRERF1, CREB-binding protein,EP 300.
Get to work! At CRBCM...the race is on!
"RIP140 is part of the chain by which tumors can cause cachexia.[15][16]
Levels of RIP140 expression in various tissues varies during aging in mice, suggesting changes in metabolic function.[17] RIP140 is implicated in certain human disease processes. In morbid obesity, RIP140 levels are down-regulated in visceral adipose tissue.[18] In breast cancer, RIP140 is involved in regulation of E2F1, an oncogene which discriminates between luminal and basal types of tumours. RIP140 has an influence upon cancer phenotype and prognosis.[19] In addition, RIP140 has a role in inflammation, since it acts as a coactivator for NFkappaB/RelA-dependent cytokine gene expression. Lack of RIP140 leads to an inhibition of proinflammatory pathways in macrophages."
wikipedia
It seems that this is where Obesity becomes a disease by its state of high inflammatory state. The diease process in Obesity is defined or determined by a relatively high level of Growth factor and Cytokines inducing major deleterious consequences on the muscle skeletal system through the activated NF-KB. The RIP 140 (also known as NRIP1) is hard at work. Remember it interacts with DAX1 which involves the COPS2 (nothing to do with the police!),SREBF1 (the bone modulator) and SF1 ("feminization" of the obese individual).
It is clearly important that the understanding and measurement of the obese by clear new biomarkers allow us to establish new guidelines for monitoring. Following BMI, lipid profile and pushing diet is clearly insufficient. Blocking the central Nervous system to force mental rejection of food is not the only answer ...remember RIP-140 modulation is part of cachexia induced by Tumors.
(remember the rule, if it can induce a malformation, it is an important gene (check out DAX1 and SREBF1)
Othre gene in the link TRERF1, CREB-binding protein,EP 300.
Get to work! At CRBCM...the race is on!
Tuesday, September 24, 2013
Breakthrough!
"The U.S. Food and Drug
Administration has granted breakthrough therapy designation to
volasertib for the treatment of patients with previously untreated acute
myeloid leukemia who are ineligible for intensive remission induction
therapy, and who are 65 or older. Volasertib is an investigational
inhibitor of polo-like kinase (Plk)." from Oncology time. go to full article
*Kathy Miller from Indiana University suggests that the best adjuvant chemotherapy in relevent Breast cancer patient is AC Q3weeks followed by weekly Paclitaxel as it has comparative efficacy and better tolerance of the weekly Taxol part!
*Kathy Miller from Indiana University suggests that the best adjuvant chemotherapy in relevent Breast cancer patient is AC Q3weeks followed by weekly Paclitaxel as it has comparative efficacy and better tolerance of the weekly Taxol part!
Subscribe to:
Posts (Atom)