AT CPRIT,
The foundation has been deemed a NON Government body by the District Attorney.
A senator had requested that files from the CPRIT Foundation be opened under Disclosure rules and the Foundation had refused to comply, claiming it was a non government institution because of its private funding source. The district Attorney was asked to rule on the matter. Now she has ruled for the foundation.
Reportedly, the Senator has not given up and has requested the Senate make the foundation a Government institution. We at CRBCM are just watching the power play. These games will just delay the fight for the CURE (if any). Meanwhile budget discussion for new funding for CPRIT was once again by-passed, and the remaining 183 Million $ are still frozen. There is a growing concern about the future of CPRIT and Health programs are caught in this messy uncertainty!
2 major officials are still waiting to be deposed by investigators while the criminal investigation is ongoing! They reportedly were not heard by the senate because doing so would have given them automatic immunity protections.
The Audit is still ongoing and still discovering new irregularities, with over 300 more funded projects to review, they have their work cut out!
Thursday, February 28, 2013
RANDOM NEWS
1. Ibrutinib continues to impress by its performance in Refractory Mantle cell lymphoma. Ibrutinib
reportedly blocks Receptor signaling and induce Apoptosis. The Antigen is expressed in CLL also
with a 16-20% Complete response and 50-55% partial response, it is one of the highest response rate for a single Agent. Median time to progression 13.9 months.
If this drug was active on Myeloid, my article on AML would have been SHORT.
2. In second line therapy for cancer of the G-E junction, Taxotere 75mg/m2 every 3 weeks appears to be a good option increase overall survival by 2 months and controlling some of the pain.
3. Avastin failed to improve survival in early triple negative Breast Cancer.
4. A new drug called CILENGITIDE BY MERCK FAILED TO IMPROVE SURVIVAL IN GLIOBLASTOMA. The drug was an anti-angiogenetic medication. patient were screened for METHYLATION OF MGMT presence.
1. Ibrutinib continues to impress by its performance in Refractory Mantle cell lymphoma. Ibrutinib
reportedly blocks Receptor signaling and induce Apoptosis. The Antigen is expressed in CLL also
with a 16-20% Complete response and 50-55% partial response, it is one of the highest response rate for a single Agent. Median time to progression 13.9 months.
If this drug was active on Myeloid, my article on AML would have been SHORT.
2. In second line therapy for cancer of the G-E junction, Taxotere 75mg/m2 every 3 weeks appears to be a good option increase overall survival by 2 months and controlling some of the pain.
3. Avastin failed to improve survival in early triple negative Breast Cancer.
4. A new drug called CILENGITIDE BY MERCK FAILED TO IMPROVE SURVIVAL IN GLIOBLASTOMA. The drug was an anti-angiogenetic medication. patient were screened for METHYLATION OF MGMT presence.
OUR AUDIENCE IS INCREASING FAST!
AS OF TODAY
AS OF TODAY
Coalition for the Reversal of Breast Cancer Mortality in African American Women · Stats › Overview
Feb 21, 2013 2:00 PM – Feb 28, 2013 1:00 PM
 |
|
| Entry | Pageviews |
|---|---|
United States
|
8574
|
Germany
|
533
|
France
|
166
|
United Kingdom
|
155
|
Russia
|
136
|
Taiwan
|
81
|
Sweden
|
55
|
South Korea
|
48
|
Ukraine
|
40
|
India
|
39
39 WE THANK YOU FOR VISITING |
Clement Albert (Dr Mutombo Kankonde ) on Ubetoo.com!
| Gender | Male |
| City | El Paso, Texas |
| Country | United States |
PART II TARGET THERAPY IN AML (ACUTE MYELOID LEUKEMIA)
=====================================================
If you dismissed the discussion about core binding factor (CBF), or raise your eyebrows in a sign of not being impressed by the information, just you wait for a second. Because things get complicated very fast. By now you grasp the notion of the CBF, and know that overall the CBF involvement is of good prognosis.
But if you recall, the CBF seems to have at least 2 subunits. one alpha reportedly attached to a DNA or Gene substrate and one swimming and interacting with Histone and surrounding molecules. We discussed that over all the CBF act as Histone DeaCetylase Inhibitor but we also added that through this effect, CBF affects Ribosome, transcription factors and and various genes as well upstream retrograde or feedback effect on ubiquitination, signal induction pathways, and on mitochondria.
The tentacles from CBF will create an effect that depends on the nature of the surrounding molecule.
focusing on good prognosis AML, through direct interaction or through Ribosomal or gene contact effect, CBF could trigger MYCN amplification. As opposed to c-MYC, globally MYCN, a member of the MYC family that maps to the short arm of chromosome 2 at band 2p24, is considered a good prognosis in any proliferative disease. Should CBF activity lead to MYCN amplification directly or through overexpression of miR17-92 (with ribosomal location), at least 8 consequences results:
1.Overexpression of CDK4 (Cyclin dependent kinase 4) which phosphorylate RB-1 and stops the cell cycle in G-1. Remember p16ink 4a is its inhibitor (Melanoma). Therefore MYCN stops proliferation! That's why its a good prognostic factor!
2. Overexpression of RSG2 ( G protein regulator) mostly with inhibitory membrane and submembrane activity effects affecting cell division as well as angiogenesis, again good for you!
3.Overexpression of MDM2, a ubiquitination ligase of P53. In Leukemia, proliferation will be exacerbated by this action (not so good for us! but inhibitors could prove good target therapy)
(To be continued)
=====================================================
If you dismissed the discussion about core binding factor (CBF), or raise your eyebrows in a sign of not being impressed by the information, just you wait for a second. Because things get complicated very fast. By now you grasp the notion of the CBF, and know that overall the CBF involvement is of good prognosis.
But if you recall, the CBF seems to have at least 2 subunits. one alpha reportedly attached to a DNA or Gene substrate and one swimming and interacting with Histone and surrounding molecules. We discussed that over all the CBF act as Histone DeaCetylase Inhibitor but we also added that through this effect, CBF affects Ribosome, transcription factors and and various genes as well upstream retrograde or feedback effect on ubiquitination, signal induction pathways, and on mitochondria.
The tentacles from CBF will create an effect that depends on the nature of the surrounding molecule.
focusing on good prognosis AML, through direct interaction or through Ribosomal or gene contact effect, CBF could trigger MYCN amplification. As opposed to c-MYC, globally MYCN, a member of the MYC family that maps to the short arm of chromosome 2 at band 2p24
1.Overexpression of CDK4 (Cyclin dependent kinase 4) which phosphorylate RB-1 and stops the cell cycle in G-1. Remember p16ink 4a is its inhibitor (Melanoma). Therefore MYCN stops proliferation! That's why its a good prognostic factor!
2. Overexpression of RSG2 ( G protein regulator) mostly with inhibitory membrane and submembrane activity effects affecting cell division as well as angiogenesis, again good for you!
3.Overexpression of MDM2, a ubiquitination ligase of P53. In Leukemia, proliferation will be exacerbated by this action (not so good for us! but inhibitors could prove good target therapy)
(To be continued)
GENES INVOLVED IN AML
-----------------------------------
AML-1 - EAP/MDS-1 /EVI-1
CALM - FIO
AML-1 - ETO
PML- RAR
PLZF - RAR
CBF beta - MYH-11
NUP 98 -DDX 10
NUP 98 - HOXA 9
MOZ - CBP
MLL
NPM - MLF-1
DEK - CAN
SET - CAN
TLS/FUS - ERG
P53 - ARF pathway
sp 100
MRP 8
TIF 2: TRANSCRIPTION INTERMEDIATE FACTOR 2
-------------------------------------------------------------A nuclear protein complex containing a Histone deacethyl transferase and a receptor to steroids which attachs Glucocorticoid, Estrogen (BRCA-1)and facilitate DNA transcription.
Also known as Nuclear Receptor Coactivator2 NCOA-2
Overexpression of TIF or mutaion here may have an impact on one of the subunit of Cytochrome-C,
It is a ligand (other ligand SRC-1, AIB-1). It may help in tolerance of certain stressful milieu!
Is TIF 2 a biomarker for steroid response?
does TIF2 Mutation compromise effectiveness of ATRA in APL
what the role or interaction with NACA
FLIT 3
KIT
RAS
RUNX 1
EBP alpha
GATA-1
MLL-ENL FUSION
WASP
AFX
MEIS-1
HOXD-13
SMMHC, Smooth Muscle Myosin related marker of differentiation, but also imply use of multiple regulatory genes that ultimately depress P53 as a way to decrease repair of DNA and allow leukemia to proceed with proliferation. this marker is als see in Inv-16 Leukemia. Through interaction with SMAD3, it affect TGF driven migration of leukemic cells. It also interfere with ACTA 2, TGFBR-2 AND FBN-1,
THIS SUGGEST THAT BLOCKING MIGRATION AND IMMUNE BETA-2 RECEPTOR OF TGF COULD ADD TO ACUTE EOSINOPHILIC LEUKEMIA. BLOCKING NUCLEAR INTERNALIZATION OF THE BETA SUBUNIT OF THE CBF WOULD HELP IN THE CBF DRIVEN LEUKEMIA IN GENERAL
-----------------------------------
AML-1 - EAP/MDS-1 /EVI-1
CALM - FIO
AML-1 - ETO
PML- RAR
PLZF - RAR
CBF beta - MYH-11
NUP 98 -DDX 10
NUP 98 - HOXA 9
MOZ - CBP
MLL
NPM - MLF-1
DEK - CAN
SET - CAN
TLS/FUS - ERG
P53 - ARF pathway
sp 100
MRP 8
TIF 2: TRANSCRIPTION INTERMEDIATE FACTOR 2
-------------------------------------------------------------A nuclear protein complex containing a Histone deacethyl transferase and a receptor to steroids which attachs Glucocorticoid, Estrogen (BRCA-1)and facilitate DNA transcription.
Also known as Nuclear Receptor Coactivator2 NCOA-2
Overexpression of TIF or mutaion here may have an impact on one of the subunit of Cytochrome-C,
It is a ligand (other ligand SRC-1, AIB-1). It may help in tolerance of certain stressful milieu!
Is TIF 2 a biomarker for steroid response?
does TIF2 Mutation compromise effectiveness of ATRA in APL
what the role or interaction with NACA
FLIT 3
KIT
RAS
RUNX 1
EBP alpha
GATA-1
MLL-ENL FUSION
WASP
AFX
MEIS-1
HOXD-13
SMMHC, Smooth Muscle Myosin related marker of differentiation, but also imply use of multiple regulatory genes that ultimately depress P53 as a way to decrease repair of DNA and allow leukemia to proceed with proliferation. this marker is als see in Inv-16 Leukemia. Through interaction with SMAD3, it affect TGF driven migration of leukemic cells. It also interfere with ACTA 2, TGFBR-2 AND FBN-1,
THIS SUGGEST THAT BLOCKING MIGRATION AND IMMUNE BETA-2 RECEPTOR OF TGF COULD ADD TO ACUTE EOSINOPHILIC LEUKEMIA. BLOCKING NUCLEAR INTERNALIZATION OF THE BETA SUBUNIT OF THE CBF WOULD HELP IN THE CBF DRIVEN LEUKEMIA IN GENERAL
Wednesday, February 27, 2013
TARGET THERAPY FOR ACUTE MYELOID LEUKEMIA (AML)
FOR THE NEXT FEW DAYS, WE ARE GOING TO JOIN THE DISCUSSION ON DEVELOPMENT OF TARGET THERAPY FOR ACUTE MYELOID LEUKEMIA (AML)
A preliminary review announces very heated discussions and development of new hypotheses that will that may raise eyebrows, but will certainly be an exercise to go through. But until the current thinking are significantly challenged, we may remain with ARA-C and Anthracyclines as back bone of our induction treatment. We will approach this topic deliberately and systematically by first discussing in general the underlying evidences that makes an Acute Leukemia a good prognosis disease. We will then review each good prognosis AML as much as the discussion allows.
GOOD PROGNOSIS AML:
Favorable group Inv 16, (15,17), (8,21)
favorable include Inv 16,( 8,21), NPM1, CEBPA and wild type FLT-3
IN GENERAL,
These syndromes appear to result from suppression of genes at the Nuclear level. In the cell sometimes various proteins achieving similar or parallel functions sometimes refused to be isolated. so they come together in a large molecule called a complex molecule or a CORE binding Factor. Despite their association, each molecule, like a tentacle or swimming appendices continue to do its specific work. The Core binding Factor appears to have at least 2 subunits, one grabing on to the DNA and one continuing to do its job. And by attaching to an area of the gene, it can suppress its expression, while the other side is working on the cover of genes (the Histones).
In fact in those AML were t(8,21) is characteristic, the core binding factor activity act as an histone Deacytylase inhibitor sending suppression effects in the Ribosome, the Telomere, the centrosome, and transcription factors. In all the good prognosis AML, this is the center of ACTION!
NOW what happen after this irreversible suppression, please remember our discussion of the Histone Deacetylase on this blog! This suppression however is not enough to cause Leukemia, a secondary event must happen to cause Leukemia! Radiation, chemotherapy, Benzene, in AML1-ETO (8,21) AML speculation that some "Ethyl-Nitrosourea" like compound have to strike to induce finally the Leukemic process!
The Molecule attached to the Core Binding Factor determines the type of leukemia you have. If the Core binding grabs MYH11, you got yourself inversion 16. If it grabs ETO, you got M2 (8,21). The point is :
1) Giving Histone deacetylase inhibitor indiscriminately does not make sens if inhibition is there already. we will talk about why it may work sometime.
2) Notice I enumerate a number of stressor (radiation and chemicals) well in the cell stress usually goes to a member of the MAPKcalled c-JUN and the cell try to escape of fight through the NF-kB and these pathways control the Cyclins, TNF and others growth factors. What happens now ?
Suffice is to say that a group in Indonesia did bone Marrow in Lupus patients who had Cytopenia, they found among other findings, " 50 % hypercellular Marrows, 35% Plasmacytosis, 10% Aplasia, 10% dyserythropoiesis, 5% Myelofibrosis. Suggesting that Autoimmune/inflammatory process can independently produce Marrow changes suggestive or that could lead to Cutopenias and Leukemia! This rise the possibility that REGORAFENIB COULD BE CONSIDERED. (READ ABOUT IT, BEFORE RISING THE EYEBROWS!)
(TO BE CONTINUED)
A preliminary review announces very heated discussions and development of new hypotheses that will that may raise eyebrows, but will certainly be an exercise to go through. But until the current thinking are significantly challenged, we may remain with ARA-C and Anthracyclines as back bone of our induction treatment. We will approach this topic deliberately and systematically by first discussing in general the underlying evidences that makes an Acute Leukemia a good prognosis disease. We will then review each good prognosis AML as much as the discussion allows.
GOOD PROGNOSIS AML:
Favorable group Inv 16, (15,17), (8,21)
favorable include Inv 16,( 8,21), NPM1, CEBPA and wild type FLT-3
IN GENERAL,
These syndromes appear to result from suppression of genes at the Nuclear level. In the cell sometimes various proteins achieving similar or parallel functions sometimes refused to be isolated. so they come together in a large molecule called a complex molecule or a CORE binding Factor. Despite their association, each molecule, like a tentacle or swimming appendices continue to do its specific work. The Core binding Factor appears to have at least 2 subunits, one grabing on to the DNA and one continuing to do its job. And by attaching to an area of the gene, it can suppress its expression, while the other side is working on the cover of genes (the Histones).
In fact in those AML were t(8,21) is characteristic, the core binding factor activity act as an histone Deacytylase inhibitor sending suppression effects in the Ribosome, the Telomere, the centrosome, and transcription factors. In all the good prognosis AML, this is the center of ACTION!
NOW what happen after this irreversible suppression, please remember our discussion of the Histone Deacetylase on this blog! This suppression however is not enough to cause Leukemia, a secondary event must happen to cause Leukemia! Radiation, chemotherapy, Benzene, in AML1-ETO (8,21) AML speculation that some "Ethyl-Nitrosourea" like compound have to strike to induce finally the Leukemic process!
The Molecule attached to the Core Binding Factor determines the type of leukemia you have. If the Core binding grabs MYH11, you got yourself inversion 16. If it grabs ETO, you got M2 (8,21). The point is :
1) Giving Histone deacetylase inhibitor indiscriminately does not make sens if inhibition is there already. we will talk about why it may work sometime.
2) Notice I enumerate a number of stressor (radiation and chemicals) well in the cell stress usually goes to a member of the MAPKcalled c-JUN and the cell try to escape of fight through the NF-kB and these pathways control the Cyclins, TNF and others growth factors. What happens now ?
Suffice is to say that a group in Indonesia did bone Marrow in Lupus patients who had Cytopenia, they found among other findings, " 50 % hypercellular Marrows, 35% Plasmacytosis, 10% Aplasia, 10% dyserythropoiesis, 5% Myelofibrosis. Suggesting that Autoimmune/inflammatory process can independently produce Marrow changes suggestive or that could lead to Cutopenias and Leukemia! This rise the possibility that REGORAFENIB COULD BE CONSIDERED. (READ ABOUT IT, BEFORE RISING THE EYEBROWS!)
(TO BE CONTINUED)
INTERESTING ARTICLES. GO TO THEM!
1.Plastin3 is a novel marker for circulating tumor cells undergoing
the epithelial-mesenchymal transition and is associated with colorectal
cancer prognosis
Cancer Research, 02/21/2013
(APPARANTLY THIS IS NOT FOUND NATURALLY IN NORMAL BLOOD)
| 2Multicentre phase II trial of bevacizumab combined with docetaxel carboplatin for the neoadjuvant treatment of triple-negative breast cancer (KCSG BR-0905) | ||||||||||||||||||||||||||
| Annals of Oncology 02/06/2013 | STUDY COMPLETED IN KOREA |
WE WANT TO SEE YOU THERE
 |
 |
|
New and Improved for 2013
Interactive and educational, Great Debates and Updates in GI Malignancies
will focus on controversial areas in the management of gastrointestinal
malignancies as nationally-recognized thought leaders take opposing
sides on topics of clinical interest.
Located conveniently in New York City, discussions at Great Debates and Updates in GI Malignancies this year will include:
For more information, visit the conference website:
imedex.com/gi-malignancies-debate-conference/ |
|
|
| |||||||||||||||||||||||||||||||||||
PREVENTABLE CANCER DEATH, AND YOU CAN'T DO A THING! AND THIS IS TEXAS/ USA!
HOW DO YOU LOOK AT A MAN 2 YEARS BEFORE HIS PREVENTABLE CANCER DEATH, AND YOU CAN'T DO A THING! AND THIS IS TEXAS/ USA!
Just got off the phone with a wife of a man with stage IIIB Penile cancer. Their largest problem is not the cancer, but the lack of insurance and lack of money. He needs Cisplatin, a drug older than myself, but can't afford it. He has positive inguinal node but can't afford a consultation with the radiation therapy DR. What to do? As an Oncologist I am offering my service, but this is not going to save the man.
It is a time like this that challenges your soul, you just want to run from this misery of mind and hide!
It is a time like this that universal Insurance makes complete sense, but it will come too late for this one man!
If you can help, call our clinic 915-307- 3354! And it is not the only case, I also have this 38 year old woman with unresectable Angiosarcomas in the liver.... same story....call if you can help!
Just got off the phone with a wife of a man with stage IIIB Penile cancer. Their largest problem is not the cancer, but the lack of insurance and lack of money. He needs Cisplatin, a drug older than myself, but can't afford it. He has positive inguinal node but can't afford a consultation with the radiation therapy DR. What to do? As an Oncologist I am offering my service, but this is not going to save the man.
It is a time like this that challenges your soul, you just want to run from this misery of mind and hide!
It is a time like this that universal Insurance makes complete sense, but it will come too late for this one man!
If you can help, call our clinic 915-307- 3354! And it is not the only case, I also have this 38 year old woman with unresectable Angiosarcomas in the liver.... same story....call if you can help!
IT IS A CORRUPT WORLD WE LIVE IN!
IT IS A CORRUPT WORLD WE LIVE IN!
I hate it when people are right when they comment about how corrupt this world is. And this one friend has been right every time although in my deep soul I want to give credit to the the goodness of human beings. Speaking today, my friend asked me what I was doing. "writing for a new grant application for the NIH", I replied proudly. "you are wasting your time" he replied. "I was at NIH, most of the grant request are written with a beneficiary in mind". He recalled being called by his supervisor in the office, and being asked to write a grant request before the Request for Application (RFA) got released. In fact most RFA are specifically written to mach perfectly a known project. The public is let to believe that the RFA comes first. The public researcher is mislead and is used to fill the book, be included is the statistic for publicity stunt. The Public is used to show a large number of participants. The true winners are known in advance. They sometime participate to the writing of the RFA. The world is corrupt.
The NIH is not the only organization filled with politics, CPRIT was so bad they got caught.
At CPRIT, your chance of participating and winning was less then winning at the Powerball. RFA were written after consultation at MD Anderson first, and the other universities were following. In fact it was ridiculous to be far from Houston and Austin, and yet be aware of the fights between who came from what university. The fight is going to rekindle soon after the moratorium is lifted. Your chance to get a grant if you are a small independent business close to 1 percent. MD Anderson 50%, Baylor 20% followed by other Universities.
El Paso (4th city population wise) is in a hard predicament. Its leadership has been stolen by a smaller city. If you are a business from El Paso, your chance for research funding from CPRIT is 0.2%. A fictitious company from Houston got about 20 times the global funding given to El Paso as a whole. The company had even a bogus web site. Basically, you had to be blind to fund this thing! Who was behind such a fraud, I refuse to say. Suffice is to say that officials at the company were using golden furniture! No, it was bad! And of course they folded as soon as scrutiny came!
Now let's see what will come out of this bloody nose Texas tax-payers got.
What hurts is that you want to believe in the goodness of people. But the grant giving is so politically twisted that my friend is right. Why waste the time writing proposals when you know the game is tricked and skewed! But if you don't participate they win 100%, and the audits that will come will not find the normal to compare to. Yes, we agree to be vain participants because that's our role in this charade!
I hate it when people are right when they comment about how corrupt this world is. And this one friend has been right every time although in my deep soul I want to give credit to the the goodness of human beings. Speaking today, my friend asked me what I was doing. "writing for a new grant application for the NIH", I replied proudly. "you are wasting your time" he replied. "I was at NIH, most of the grant request are written with a beneficiary in mind". He recalled being called by his supervisor in the office, and being asked to write a grant request before the Request for Application (RFA) got released. In fact most RFA are specifically written to mach perfectly a known project. The public is let to believe that the RFA comes first. The public researcher is mislead and is used to fill the book, be included is the statistic for publicity stunt. The Public is used to show a large number of participants. The true winners are known in advance. They sometime participate to the writing of the RFA. The world is corrupt.
The NIH is not the only organization filled with politics, CPRIT was so bad they got caught.
At CPRIT, your chance of participating and winning was less then winning at the Powerball. RFA were written after consultation at MD Anderson first, and the other universities were following. In fact it was ridiculous to be far from Houston and Austin, and yet be aware of the fights between who came from what university. The fight is going to rekindle soon after the moratorium is lifted. Your chance to get a grant if you are a small independent business close to 1 percent. MD Anderson 50%, Baylor 20% followed by other Universities.
El Paso (4th city population wise) is in a hard predicament. Its leadership has been stolen by a smaller city. If you are a business from El Paso, your chance for research funding from CPRIT is 0.2%. A fictitious company from Houston got about 20 times the global funding given to El Paso as a whole. The company had even a bogus web site. Basically, you had to be blind to fund this thing! Who was behind such a fraud, I refuse to say. Suffice is to say that officials at the company were using golden furniture! No, it was bad! And of course they folded as soon as scrutiny came!
Now let's see what will come out of this bloody nose Texas tax-payers got.
What hurts is that you want to believe in the goodness of people. But the grant giving is so politically twisted that my friend is right. Why waste the time writing proposals when you know the game is tricked and skewed! But if you don't participate they win 100%, and the audits that will come will not find the normal to compare to. Yes, we agree to be vain participants because that's our role in this charade!
DRUGS ON THE MOVE
DRUGS ON THE MOVE
1. In Breast cancer
-Everolimus
-Pertuzumab
-T-DM-1
2. In Prostate cancer
-Abiraterone (Zytiga)
-Enzalutmide (Xtandi)
-Alpharadin (Radium 223)
3. Other
-Cabozantinib
-Orteronel
-Curtisen
-Tasquinimod
4. Melanoma
-Dabrafenib
-Trametinib
-GDC- 0973
-Vemurafenib (Zelboraf)
-Nivolumab
-Ipilimumab
-MK3754
5. Lung cancers
-Crizotinib
-Afatinib
-Dacomitinib
-Nivolumab
- Selumetinib
5. Thyroid cancer
-Pazopanib
1. In Breast cancer
-Everolimus
-Pertuzumab
-T-DM-1
2. In Prostate cancer
-Abiraterone (Zytiga)
-Enzalutmide (Xtandi)
-Alpharadin (Radium 223)
3. Other
-Cabozantinib
-Orteronel
-Curtisen
-Tasquinimod
4. Melanoma
-Dabrafenib
-Trametinib
-GDC- 0973
-Vemurafenib (Zelboraf)
-Nivolumab
-Ipilimumab
-MK3754
5. Lung cancers
-Crizotinib
-Afatinib
-Dacomitinib
-Nivolumab
- Selumetinib
5. Thyroid cancer
-Pazopanib
Tuesday, February 26, 2013
REGORAFENIB, A DEFINITIVE ADVANCEMENT IN CANCER MEDICINE!
Those of us who had treated metastatic colon cancer know that patients only dies when you have exhausted possible options. It is sobering moment to see a human being deteriorating before your eyes while you have nothing to offer!
So, when something new comes along that appears effective, we embrace it in this disease. We know our patients will be offered it at one given point. Colon cancer seems to wait until you have finished all you can do! This behavior is particular as opposed to lung cancer which appears to kill despite your doing!
The power of Regorafenib seems to reside in the number of kinases affected by this drug:VEGFR3, TIE2, PDGFR, FGFR, KIT and RET.
Through KIT, it has found its Approval for GIST.
A slew of Genes are affected by this drug (on top of those mentioned, DDR2, TrK2A, Eph2A, RAF-1,BRAF, BRAF v600E, SAPK2,PTK5, and Abl) have been included in its repertoire.
The CORRECT trial introduced us to this drug in Metastatic colon cancer. Thumbs up!
Dose approved: 160 mg orally daily!
DDR2 has been commented on plenty here in various notes!
TrK2A seems to relate to transmembranes channel allowing survival in low K+ conditions
Eph2A is downstream the MAPK and is the feedback regulator. once activated it comes back on its membrane receptor and sens inhibitory influx to shut down the MAPK. Cancer quickly desactivates this to keep the signal transduction pathway on. It kinds of remind me of the Sons of the Sevenless (my favorite).
(to be continued)
Regorafenib, the power of a good Multikinase, the next generation Multikinase!
-------------------------------------------------------------------------------
RAF-1 OR c-RAF
Remember RAS-RAF-MAPK, while c-RAF is RAF-1, people are more talking about b-RAF or BRAF.
RAF-1
"-The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'.
- Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity.
- Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1).
-Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death.
-Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation." (Reviewed, UniProtKB/Swiss-Prot)
Abnormality at RAF-1 causes the NOONAN and the LEOPARD syndromes, "short stature" from genetic stand point, gives you the largest gift in genetic finding. Again do not discriminate and round up short stature people!
SAPK-1
It is the stress induced MAPK-8 or c-JUN, block ubiquitination of P53 and therefore up-regulates it.
By involving SAPK-1, Regorafenib is indeed one of the rare drug that can impact growth factors, cyclins, TNF in a more significant way in diseases where this pathway is very amplified (from cancer to inflammatory disease and infections!)
So, when something new comes along that appears effective, we embrace it in this disease. We know our patients will be offered it at one given point. Colon cancer seems to wait until you have finished all you can do! This behavior is particular as opposed to lung cancer which appears to kill despite your doing!
The power of Regorafenib seems to reside in the number of kinases affected by this drug:VEGFR3, TIE2, PDGFR, FGFR, KIT and RET.
Through KIT, it has found its Approval for GIST.
A slew of Genes are affected by this drug (on top of those mentioned, DDR2, TrK2A, Eph2A, RAF-1,BRAF, BRAF v600E, SAPK2,PTK5, and Abl) have been included in its repertoire.
The CORRECT trial introduced us to this drug in Metastatic colon cancer. Thumbs up!
Dose approved: 160 mg orally daily!
DDR2 has been commented on plenty here in various notes!
TrK2A seems to relate to transmembranes channel allowing survival in low K+ conditions
Eph2A is downstream the MAPK and is the feedback regulator. once activated it comes back on its membrane receptor and sens inhibitory influx to shut down the MAPK. Cancer quickly desactivates this to keep the signal transduction pathway on. It kinds of remind me of the Sons of the Sevenless (my favorite).
(to be continued)
Regorafenib, the power of a good Multikinase, the next generation Multikinase!
-------------------------------------------------------------------------------
RAF-1 OR c-RAF
Remember RAS-RAF-MAPK, while c-RAF is RAF-1, people are more talking about b-RAF or BRAF.
RAF-1
"-The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'.
- Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity.
- Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1).
-Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death.
-Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation." (Reviewed, UniProtKB/Swiss-Prot)
Abnormality at RAF-1 causes the NOONAN and the LEOPARD syndromes, "short stature" from genetic stand point, gives you the largest gift in genetic finding. Again do not discriminate and round up short stature people!
SAPK-1
It is the stress induced MAPK-8 or c-JUN, block ubiquitination of P53 and therefore up-regulates it.
By involving SAPK-1, Regorafenib is indeed one of the rare drug that can impact growth factors, cyclins, TNF in a more significant way in diseases where this pathway is very amplified (from cancer to inflammatory disease and infections!)
INCIDENCE OF METASTATIC BREAST CANCER IN WOMEN 25-29 YEAR OLD IS INCREASING. THIS DEVASTATING NEWS IS THE RESULT OF A 3 DECADE OBSERVATION
WHEN ONE REVIEW THE SEER REGISTRY. THIS IS PUBLISHED IN THE NEW JAMA.
This rising incident was observed across all ethnicities and races. This news is critical because of the young age of women involved which increases family burden and loss of productive life. But also because we are not talking about a locoregional disease. It is indeed the burden of a more advanced disease that was noted to be increasing. The disease at that stage is no longer curable most of the time.
The age of the patients is critical because mammography is not yet recommended and therefore women are left to their own demise.
The finding that non Hispanic white and African American women have been more affected is of interest to researchers looking at disparities among the races. Increased scrutiny and sensitivity of diagnostic test seem to have explained the increasing. The increase was noted to be more in the ER positive breast cancer which appears to not be surprising in this young age. and Age is known to be an independent bad prognosis factor! With a 10 year survival of less that 20%, new therapeutic strategies are still needed to treat these young mothers!
WHEN ONE REVIEW THE SEER REGISTRY. THIS IS PUBLISHED IN THE NEW JAMA.
This rising incident was observed across all ethnicities and races. This news is critical because of the young age of women involved which increases family burden and loss of productive life. But also because we are not talking about a locoregional disease. It is indeed the burden of a more advanced disease that was noted to be increasing. The disease at that stage is no longer curable most of the time.
The age of the patients is critical because mammography is not yet recommended and therefore women are left to their own demise.
The finding that non Hispanic white and African American women have been more affected is of interest to researchers looking at disparities among the races. Increased scrutiny and sensitivity of diagnostic test seem to have explained the increasing. The increase was noted to be more in the ER positive breast cancer which appears to not be surprising in this young age. and Age is known to be an independent bad prognosis factor! With a 10 year survival of less that 20%, new therapeutic strategies are still needed to treat these young mothers!
Monday, February 25, 2013
NEWS FROM THE FDA!
1.PEGINESATIDE A DRUG INDICATED FOR ANEMIA OF CHRONIC RENAL FAILURE HAS BEEN PULLED FROM THE MARKET BECAUSE OF 3 DEATHS FROM ANAPHYLACTIC SHOCK REPORTEDLY.
2.REGORAFENIB, APPROVED IN METASTATIC COLON CANCER, JUST GOT APPROVED BY THE FDA FOR REFRACTORY GIST TUMOR AFTER FAILURE OF GLEEVEC AND SUTENT.
"The most common adverse effects reported with regorafenib are weakness and fatigue, hand-foot syndrome, diarrhea, loss of appetite, high blood pressure, mouth sores, infection, changes in voice volume or quality, pain, weight loss, stomach pain, rash, fever, and nausea."
FROM MEDSCAPE:
-----------------------------------------------------------------------------------------------
IN OTHER NEWS,
18 MONTHS ANDROGEN DEPRIVATION WAS COMPARBLE TO 36 MONTHS FOR SURVIVAL AFTER 77 MONTHS OF OBSERVATION WITH ABOUT 25% OF PATIENTS DYING FROM LOCALLY ADVANCED POOR PROGNOSIS PROSTATE CANCER. WITH POOR PROGNOSIS DEFINED AS PSA>20 AND GLEASON>7 ACCORDING TO CANADIAN RESEARCHERS!
1.PEGINESATIDE A DRUG INDICATED FOR ANEMIA OF CHRONIC RENAL FAILURE HAS BEEN PULLED FROM THE MARKET BECAUSE OF 3 DEATHS FROM ANAPHYLACTIC SHOCK REPORTEDLY.
2.REGORAFENIB, APPROVED IN METASTATIC COLON CANCER, JUST GOT APPROVED BY THE FDA FOR REFRACTORY GIST TUMOR AFTER FAILURE OF GLEEVEC AND SUTENT.
"The most common adverse effects reported with regorafenib are weakness and fatigue, hand-foot syndrome, diarrhea, loss of appetite, high blood pressure, mouth sores, infection, changes in voice volume or quality, pain, weight loss, stomach pain, rash, fever, and nausea."
FROM MEDSCAPE:
-----------------------------------------------------------------------------------------------
IN OTHER NEWS,
18 MONTHS ANDROGEN DEPRIVATION WAS COMPARBLE TO 36 MONTHS FOR SURVIVAL AFTER 77 MONTHS OF OBSERVATION WITH ABOUT 25% OF PATIENTS DYING FROM LOCALLY ADVANCED POOR PROGNOSIS PROSTATE CANCER. WITH POOR PROGNOSIS DEFINED AS PSA>20 AND GLEASON>7 ACCORDING TO CANADIAN RESEARCHERS!
CPRIT DID HOLD A MEETING TODAY AS PROMISED
-------------------------------------------------------------
It is our understanding that this meeting was intended to wrap up paperwork with the winners of the last
round of CPRIT deliberations. The giving of money is however still under moratorium. I refuse to comment on the winners because it was the same old dance with the MD Anderson getting 42% of all contracts!
The meeting came under a lot of tension and uncertainty. With news that there won't be an annual meeting at CPRIT this year. With exclusion from the Texas budget in 2014 and 2015, CPRIT future is more than uncertain. The dance seems to wrap up despite everybody's belief in the reason for CPRIT.
The leadership at CPRIT has been so shaken that we are still waiting to see new initiatives to depict and profile a new CPRIT. The time would have been now to start a new posture and new direction. Wrapping up old deals without showing a new organization was an opportunity missed. Particularly when a new 1 Million Dollar contract is revealed to be just as fraudulently awarded as other previously described. If you give me time and again money, I just may find my way to $100,000 furniture. We are human after all!
NEW CPRIT PLEASE COME OUT OF THE SHADOW OF THE OLD CPRIT ! THE SENATORS ARE WATCHING, PLEASE CONVINCE THEM!
-------------------------------------------------------------
It is our understanding that this meeting was intended to wrap up paperwork with the winners of the last
round of CPRIT deliberations. The giving of money is however still under moratorium. I refuse to comment on the winners because it was the same old dance with the MD Anderson getting 42% of all contracts!
The meeting came under a lot of tension and uncertainty. With news that there won't be an annual meeting at CPRIT this year. With exclusion from the Texas budget in 2014 and 2015, CPRIT future is more than uncertain. The dance seems to wrap up despite everybody's belief in the reason for CPRIT.
The leadership at CPRIT has been so shaken that we are still waiting to see new initiatives to depict and profile a new CPRIT. The time would have been now to start a new posture and new direction. Wrapping up old deals without showing a new organization was an opportunity missed. Particularly when a new 1 Million Dollar contract is revealed to be just as fraudulently awarded as other previously described. If you give me time and again money, I just may find my way to $100,000 furniture. We are human after all!
NEW CPRIT PLEASE COME OUT OF THE SHADOW OF THE OLD CPRIT ! THE SENATORS ARE WATCHING, PLEASE CONVINCE THEM!
A WELL STUDIED MOLECULE!
BUTEIN
1. It is a natural Chalconoid, derived from Toxicodendron Vernicifluum
2. It is inhibitor of EGFR and SRC Tyrosine Kinase, Please give it in all Adenocarcinoma ...(in a trial of course! and at your own expenses and risk!)
3.Inhibitor of c-AMP dependent processes
4. Induce Apoptosis in B16 Melanoma cells and in HL60 Leukemia cells.
5. Anti-inflammatory
6. An Aldolase Reductase
7. An Aromatase inhibitor, please give it in ER positive Breast Cancer
8. a chelator of Iron and Cupper, please give it in Hemosiderosis in a clinical trial
9. Inhibitor of NF-kB and TNF inhibitor, that's how it is an anti-inflammatory
(try it in Sepsis gone overboard-in clinical trial). MD Anderson claimed it does this by Inhibiting IKK, check it out!
10. Activator of Sirtuins, the stuff you give to stop Dementia! Sirtuins that you take to preserve survival through Telomere protection. Oh by the way Sirtuins are Histone Deacetylators! do the math and consequence calculation. It will add to the MTOR inhibitors!
11, Increase activity of Caspase 3, Increase activity of BAX, and decrease BCL-2 to lead to Apoptosis of cancer cells talked about above!
12. Inhibitor of Glutation reductase
Please I have to stop here, These are just too much goodies!
I will be taking this Butein myself!
I guess you can relax now!
Believe me, people take Butein to treat their Gastric Cancers even!
BUTEIN
1. It is a natural Chalconoid, derived from Toxicodendron Vernicifluum
2. It is inhibitor of EGFR and SRC Tyrosine Kinase, Please give it in all Adenocarcinoma ...(in a trial of course! and at your own expenses and risk!)
3.Inhibitor of c-AMP dependent processes
4. Induce Apoptosis in B16 Melanoma cells and in HL60 Leukemia cells.
5. Anti-inflammatory
6. An Aldolase Reductase
7. An Aromatase inhibitor, please give it in ER positive Breast Cancer
8. a chelator of Iron and Cupper, please give it in Hemosiderosis in a clinical trial
9. Inhibitor of NF-kB and TNF inhibitor, that's how it is an anti-inflammatory
(try it in Sepsis gone overboard-in clinical trial). MD Anderson claimed it does this by Inhibiting IKK, check it out!
10. Activator of Sirtuins, the stuff you give to stop Dementia! Sirtuins that you take to preserve survival through Telomere protection. Oh by the way Sirtuins are Histone Deacetylators! do the math and consequence calculation. It will add to the MTOR inhibitors!
11, Increase activity of Caspase 3, Increase activity of BAX, and decrease BCL-2 to lead to Apoptosis of cancer cells talked about above!
12. Inhibitor of Glutation reductase
Please I have to stop here, These are just too much goodies!
I will be taking this Butein myself!
I guess you can relax now!
Believe me, people take Butein to treat their Gastric Cancers even!
STILL LOOKING FOR NEW TARGETS FOR THE CURE OF CANCER?
WELL I GIVE YOU THESE TARGETS DEEP IN THE NUCLEUS
1. Esap 1
2. Esw-1
3. Esc-2 and 8
and the mighty NPT-1 gene
Here you are at the heart of cell survival
as you touch on Histone Deacetylase, gene silencing (Including Ribosomal genes or RNA) and Telomeres.
and I gave you a clue, Antibiotic from fungi can help!
The cure is at the door, open it!
WELL I GIVE YOU THESE TARGETS DEEP IN THE NUCLEUS
1. Esap 1
2. Esw-1
3. Esc-2 and 8
and the mighty NPT-1 gene
Here you are at the heart of cell survival
as you touch on Histone Deacetylase, gene silencing (Including Ribosomal genes or RNA) and Telomeres.
and I gave you a clue, Antibiotic from fungi can help!
The cure is at the door, open it!
Tips to help manage diarrhea and fatigue during advanced Renal Cell Cancer treatment
-----------------------------------------------------(From Medlinx) -----------------
Diarrhea
Diarrhea is an abnormal increase in stool liquidity
and frequency (4 to 6 stools or more per day over baseline) with or
without nocturnal bowel movements and/or moderate abdominal cramping.
Diarrhea, a common side effect of many cancer regimens, can cause
depletion of fluids and electrolytes, malnutrition, dehydration, and
hospitalization, and therefore can interfere with cancer treatment,
causing dosing delays or reductions.1
Patient education strategies
- Emphasize the importance of maximizing oral hydration strategies to avoid dehydration and electrolyte imbalances2
- Educate patients about the likelihood that diarrhea will develop3-5
Management tips for patients
- Diarrhea may be managed through diet as well as
pharmacologic treatment when necessary, based on the clinical judgment
of the treating healthcare provider (HCP).1,3,4 The first step in treatment is dietary management3,5,6:
- Yogurt containing probiotics
- Soluble fiber
- Small but frequent meals
- Fluids, such as water, diluted cranberry juice, broth, decaffeinated tea or coffee
- Over-the-counter and Rx agents may also be used, according to labeling1,3,4
Fatigue/asthenia
Fatigue/asthenia is a distressing, persistent,
subjective sense of physical, emotional, and/or cognitive tiredness or
exhaustion, related to cancer or cancer treatment, that is not
proportional to recent activity and interferes with usual functioning.7
Patient education strategies7,8
- Encourage patients to:
- Take short naps and breaks instead of long ones
- Eat well and drink plenty of fluids
- Take short walks and/or do light exercise
- Do relaxing activities as a distraction (eg, listening to music or reading)
Management tips for patients
FREE "MYLOTARG" (GEMTUZUMAB) MOVEMENT BUILDING MOMENTUM!
Prominent researchers from MD Anderson and from across the country/United States are calling for the FDA reconsideration of their decision to ban this drug which was used in Acute Myeloid Leukemia (AML). We all used this drug as a first line drug particularly in the Elderly where choices remain limited. Particularly when the performance status was poor in a patient wanting treatment. Mylotarg was dropped because lack of convincing evidence of survival benefit! Researchers who worked with the drug have since fought to bring it back in some form or shape now insisting it has a clear role in Acute Promyelocytic Leukemia (APL) where Arsenic Trioxide (Trisinox), All-Trans Retinoic Acid and Anthracyclines are kings. Mylotarg seems to have a role in both first line and relapse settings by replacing Anthracyclines in those patients who may have or are susceptible to Cardiomyopathy that could result from use of Anthracyclines.
Calling it a "Lazarus like drug", Researchers are pointing to other medications that lost luster after post marketing studies failed to keep it alive, just to be resurrected after few years because of other new indications or new convincing evidences emerged. I should stress that the death of Mylotarg was hard for those who used it! I remember sitting in a review for board examination where Mylotarg, was discussed despite the fact that it was "dead" by FDA STANDARDS! Clearly the reviewer was still emotional and could not remove this topic.
Advocates for the resurrection of MYLOTARG point to similar stories of drugs such as Omacetaxine Mepesuccinate (aka Homoharringtonine) which is back in Chronic Myeloid Leukemia (CML), Thalidomid in Multiple Myeloma, mouth ulcers and Leprosy, and Arsenic Trioxide itself in APL.
Researchers who have experience with Myelotarg, a well tolerated drug even in elderly, are calling for a "second look" by the FDA, particularly in this Era of Target therapy!
THE "FREE MYELOTARG" MOVEMENT IS SURELY GETTING MOMENTUM!
Prominent researchers from MD Anderson and from across the country/United States are calling for the FDA reconsideration of their decision to ban this drug which was used in Acute Myeloid Leukemia (AML). We all used this drug as a first line drug particularly in the Elderly where choices remain limited. Particularly when the performance status was poor in a patient wanting treatment. Mylotarg was dropped because lack of convincing evidence of survival benefit! Researchers who worked with the drug have since fought to bring it back in some form or shape now insisting it has a clear role in Acute Promyelocytic Leukemia (APL) where Arsenic Trioxide (Trisinox), All-Trans Retinoic Acid and Anthracyclines are kings. Mylotarg seems to have a role in both first line and relapse settings by replacing Anthracyclines in those patients who may have or are susceptible to Cardiomyopathy that could result from use of Anthracyclines.
Calling it a "Lazarus like drug", Researchers are pointing to other medications that lost luster after post marketing studies failed to keep it alive, just to be resurrected after few years because of other new indications or new convincing evidences emerged. I should stress that the death of Mylotarg was hard for those who used it! I remember sitting in a review for board examination where Mylotarg, was discussed despite the fact that it was "dead" by FDA STANDARDS! Clearly the reviewer was still emotional and could not remove this topic.
Advocates for the resurrection of MYLOTARG point to similar stories of drugs such as Omacetaxine Mepesuccinate (aka Homoharringtonine) which is back in Chronic Myeloid Leukemia (CML), Thalidomid in Multiple Myeloma, mouth ulcers and Leprosy, and Arsenic Trioxide itself in APL.
Researchers who have experience with Myelotarg, a well tolerated drug even in elderly, are calling for a "second look" by the FDA, particularly in this Era of Target therapy!
THE "FREE MYELOTARG" MOVEMENT IS SURELY GETTING MOMENTUM!
Sunday, February 24, 2013
Fresh from ONCOFACTS
Low Grade Serous Ovarian Cancers Respond to Selumetinib
The GOG is conducting a phase II study of low grade serous ovarian cancers, which when recurrent are usually resistant to both hormonal therapy and chemotherapy. Patients with low grade serous ovarian cancer received selumetinib, an oral small molecule inhibitor of MEK 1 and 2, part of the MAP-Kinase pathway.
Of 52 patients treated with selumetinib, all had had at least one prior systemic therapy and 15% achieved a PR while 65% maintained Stable Disease. Median PFS was 11 months and two year OS was 55%.
While 14 patients had KRAS mutations and 2 had BRAF mutations, there did not appear to be any correlation between mutation status and response. A larger phase II-III clinical trial is beginning.
The GOG is conducting a phase II study of low grade serous ovarian cancers, which when recurrent are usually resistant to both hormonal therapy and chemotherapy. Patients with low grade serous ovarian cancer received selumetinib, an oral small molecule inhibitor of MEK 1 and 2, part of the MAP-Kinase pathway.
Of 52 patients treated with selumetinib, all had had at least one prior systemic therapy and 15% achieved a PR while 65% maintained Stable Disease. Median PFS was 11 months and two year OS was 55%.
While 14 patients had KRAS mutations and 2 had BRAF mutations, there did not appear to be any correlation between mutation status and response. A larger phase II-III clinical trial is beginning.
NOMENCLATURE OF GENES TO LOOK FOR IN TRIPLE NEGATIVE BREAST CANCER
One may try to determine whether a breast cancer has bad prognosis in order to determine whether chemotherapy should be given (MammaPrint, Oncotypr DX), but more importantly, I believe, is to focus on genes of good prognosis which include driver genes against which we dispose of an answer in our Arsenal.
Currently we dispose of
1. Chemotherapy that attacks DNA and Microfilament/Microtubules, (first and second law of nature)
2. Immune Modulators such as Interferon
3. Antibody to Membrane Receptor (EGFR/VEGF) Avastin
4. Inhibitor to T-cell driven immunity (CTLA4)
5. Inhibitors to sub-membrane or first line driver Mutations KRAS, HRAS, or the RAS family
6. Inhibitors to 2nd line driver Mutations (anti MEK)
7. Inhibitor to Tertiary line driver Mutations and Mitochondrial level inhibition (MTOR, Metformin)
8. Anti-proteasome or inhibitor to cellular protein degradation (Velcade)
9. Inhibitors at Nuclear lever Include Histone Deacethylator and Acyl transferase inhibitor, check point controller inhibitors, anti-Centrosome metabolism and inhibitors of various promoters and transcription factors.
Other opportunities not included in this classification go to specific genes of proliferation, Amplification, differentiation and metastasis that have been brought forth as indicator of either response to chemotherapy or simply as "Good prognosis" genes. These will include the BRCA since a response to PARP inhibitors and Cisplatin based combinations should be anticipated.
Multikinase inhibitors such as Dasatinib (SRC+ BCR/ABL but also STAT5) and Arsenic Trioxide should be included
LBK1: could predict early disease (inhibitor controlling initiation of metastasis)
DDR2: could predict anti MEK sensitivity
MEKK-1 sensitivity to Cisplatin
TFF1-could predict sensitivity to estrogen despite negative Estrogen
DYRK2, favorable in lung cancer
c-JUN amplification and over expression of 8q23-24 could predict response to interferon/Interleukin
EGFR, VEGF, ALK, and other Driver Mutations would match those discussed By DR Kris in lung cancer.
(to be continued!)
Currently we dispose of
1. Chemotherapy that attacks DNA and Microfilament/Microtubules, (first and second law of nature)
2. Immune Modulators such as Interferon
3. Antibody to Membrane Receptor (EGFR/VEGF) Avastin
4. Inhibitor to T-cell driven immunity (CTLA4)
5. Inhibitors to sub-membrane or first line driver Mutations KRAS, HRAS, or the RAS family
6. Inhibitors to 2nd line driver Mutations (anti MEK)
7. Inhibitor to Tertiary line driver Mutations and Mitochondrial level inhibition (MTOR, Metformin)
8. Anti-proteasome or inhibitor to cellular protein degradation (Velcade)
9. Inhibitors at Nuclear lever Include Histone Deacethylator and Acyl transferase inhibitor, check point controller inhibitors, anti-Centrosome metabolism and inhibitors of various promoters and transcription factors.
Other opportunities not included in this classification go to specific genes of proliferation, Amplification, differentiation and metastasis that have been brought forth as indicator of either response to chemotherapy or simply as "Good prognosis" genes. These will include the BRCA since a response to PARP inhibitors and Cisplatin based combinations should be anticipated.
Multikinase inhibitors such as Dasatinib (SRC+ BCR/ABL but also STAT5) and Arsenic Trioxide should be included
LBK1: could predict early disease (inhibitor controlling initiation of metastasis)
DDR2: could predict anti MEK sensitivity
MEKK-1 sensitivity to Cisplatin
TFF1-could predict sensitivity to estrogen despite negative Estrogen
DYRK2, favorable in lung cancer
c-JUN amplification and over expression of 8q23-24 could predict response to interferon/Interleukin
EGFR, VEGF, ALK, and other Driver Mutations would match those discussed By DR Kris in lung cancer.
(to be continued!)
Saturday, February 23, 2013
TREATMENT OF METASTATIC MELANOMA
The reign of DTIC (Temodar) is over.
Move to Ipilimumab (Yervoy) AND
In BRAF setting, to Vemurafenib (Zelboraf)
The story of Tremolimumab is somewhat confused. It did not do better than Chemotherapy BUT WHEN IT WORKS, THE DURATION OF THE WORK IS 3 TIMES THAT OF CHEMOTHERAPY SUGGESTING THAT IN CERTAIN SUBSET, IT IS THE DRUG OF CHOICE. NOW IF YOU ASK ME WHICH SUBSET, I WILL GO INTO HIDING!
Before I run though let me remind you that Tremelimumab is cytotoxic T cell lymphocyte-associated -antigen-4 blocking monoclonal antibody. AND REMEMBER T CELL PENETRATE MUCOSA, THEREFORE SIDE EFFECTS WILL BE RASH, DIARRHEA. 7 DEATHS IN TREMELIMUMAB VS 1 DEATH IN CHEMOTHERAPY. WEIGH YOUR RISKS!
The reign of DTIC (Temodar) is over.
Move to Ipilimumab (Yervoy) AND
In BRAF setting, to Vemurafenib (Zelboraf)
The story of Tremolimumab is somewhat confused. It did not do better than Chemotherapy BUT WHEN IT WORKS, THE DURATION OF THE WORK IS 3 TIMES THAT OF CHEMOTHERAPY SUGGESTING THAT IN CERTAIN SUBSET, IT IS THE DRUG OF CHOICE. NOW IF YOU ASK ME WHICH SUBSET, I WILL GO INTO HIDING!
Before I run though let me remind you that Tremelimumab is cytotoxic T cell lymphocyte-associated -antigen-4 blocking monoclonal antibody. AND REMEMBER T CELL PENETRATE MUCOSA, THEREFORE SIDE EFFECTS WILL BE RASH, DIARRHEA. 7 DEATHS IN TREMELIMUMAB VS 1 DEATH IN CHEMOTHERAPY. WEIGH YOUR RISKS!
HER-2 Breast cancers
*First line treatment Herceptin -Taxane
improves Response rates, progression free survival, and overall survival.
A 1 year of Herceptin seems to will all other duration
*Pertuzumab seems to work best when combine to Herceptin and Taxane with Median survival of
1.5 Years (Cleopatra )--The triplet is FDA approved for first line
*Lapatinib has been reported inferior to Trastuzumab, it is an option after all is completed though.
With the arrival of Pertuzumab, it will find a role in cases where it is combined to Herceptin.
*Navelbine is the other chemotherapy drug frequently used as an alternative to Taxane.
* The standard first line in Metastatic Breast cancer is stolen from the jaw of the of the above options however by the T-DM-1 based combination. Alone or combined to Pertuzumab.
T-DM-1 is Trastuzumab emtansine. The close challenger is Herceptin -Pertuzumab and Taxane (whihc was the standard until T-DM1 got approved!
* To conquer Her-2 resistance, It appears you need to complete full circle a BOLERO DANCE.
It is either BOLERO 1 which use Herceptin-Taxol- Everolimus
or BOLERO 3 which dance to the pace of Herceptin-Vinorelbine-Everolimus
will see not only which dance is easier on our patients
but also confirm that MTOR is the answer to HER-2 resistance!
*DR HOPE S RUGO who we thank for most these comments had another take when it comes to
standard of care and therapeutic options. She suggested that
The first line / standard be : Pertuzumab - Trastuzumab - Taxol as prime line of defense in Metastatic Her-2
Second line : T-DM1as a single agent
third line: Lapatinib-Xeloda
REMEMBER THE PATIENT NEEDS TO BE HER-2 POSITIVE BEFORE YOU START READING THIS!
*First line treatment Herceptin -Taxane
improves Response rates, progression free survival, and overall survival.
A 1 year of Herceptin seems to will all other duration
*Pertuzumab seems to work best when combine to Herceptin and Taxane with Median survival of
1.5 Years (Cleopatra )--The triplet is FDA approved for first line
*Lapatinib has been reported inferior to Trastuzumab, it is an option after all is completed though.
With the arrival of Pertuzumab, it will find a role in cases where it is combined to Herceptin.
*Navelbine is the other chemotherapy drug frequently used as an alternative to Taxane.
* The standard first line in Metastatic Breast cancer is stolen from the jaw of the of the above options however by the T-DM-1 based combination. Alone or combined to Pertuzumab.
T-DM-1 is Trastuzumab emtansine. The close challenger is Herceptin -Pertuzumab and Taxane (whihc was the standard until T-DM1 got approved!
* To conquer Her-2 resistance, It appears you need to complete full circle a BOLERO DANCE.
It is either BOLERO 1 which use Herceptin-Taxol- Everolimus
or BOLERO 3 which dance to the pace of Herceptin-Vinorelbine-Everolimus
will see not only which dance is easier on our patients
but also confirm that MTOR is the answer to HER-2 resistance!
*DR HOPE S RUGO who we thank for most these comments had another take when it comes to
standard of care and therapeutic options. She suggested that
The first line / standard be : Pertuzumab - Trastuzumab - Taxol as prime line of defense in Metastatic Her-2
Second line : T-DM1as a single agent
third line: Lapatinib-Xeloda
REMEMBER THE PATIENT NEEDS TO BE HER-2 POSITIVE BEFORE YOU START READING THIS!
DISTURBANCES IN THE DIFFERENTIATION:
THE CASE OF AUTOSOMAL POLYCYSTIC KIDNEY DISEASE.
This disease is a clear example of differentiation gone rogue. In the Collecting tubule of kidney, the cells have ciliary bodies which have censors to feel reportedly general urine direction and help incidentally things along.
At Molecular level these Ciliary bodies have a skeleton and a large extracellular protein which is transmembrane, meaning it crosses the cellular membrane to impact calcium Homeostasis inside the cell. This Molecule/protein is made by the PDK-1 gene. This gene is located on Chromosome 16.
Through splicing error or mutation in this gene, This Ciliary body goes missing.
2 things happen then:
1: The cell dies and details are lost this point
we know that even at the peri-membrane level Caspases can be triggered. After all the Caspase are in the Cytosol. However at the time of the 2nd hit event, the cell is stressed and through the MAPK pathway, the c-Jun can be stimulated also. Whatever the case these cells can be destroyed.
2.The other path follows gene interactions.
We know that PDK-1 interact with RSG7 which in turn interact with SNAPAP ( a BLOC-1 component)
RSG7 is a Regulator of G-protein Signaling 7. acting somewhat as a promoter gene for SNAPAP sitting on BLOC1, And BLOC-1 is important in the formation of specialized organelles in the endosomal-lysozomal systems (Melanosome, and Platelet dense granules). This where differentiation is involved in the activity of BLOC-1. If differentiation is our Target, disabling BLOC-1 is it. This is a large molecule with many importatnt components, it is an intersection of roads in the cell!
Continuing our story, BLOC-1 will interact with Dysbindin and Pallidin, 2 very interesting Molecules in this disease. Pallidin deals with intracellular vesicle trafficking, and through its interaction with syntaxin 13, it has impact of membrane fusion and division. This bring the notion of Vacuolization which could explain also Cystic formation (speculation that needs proof of concept). But you see where I am coming from.
The Dysbindin is very important here, the skeleton of the ciliary body could come from activity in this protein but remember that the skeleton of the cell is also its nervous system. Some forms of Schizophrenia is linked to disturbances in the Dysbindin. Indeed you will find the individual suffering from this disease with a certain odd personality... mostly with obsessive and stubborn tendencies in my experience.
Individual with this diagnosis should be on ACE inhibitor, or the new TOLVAPTAN!
and should never have Caffeine which promotes the growth of cysts.
THE CASE OF AUTOSOMAL POLYCYSTIC KIDNEY DISEASE.
This disease is a clear example of differentiation gone rogue. In the Collecting tubule of kidney, the cells have ciliary bodies which have censors to feel reportedly general urine direction and help incidentally things along.
At Molecular level these Ciliary bodies have a skeleton and a large extracellular protein which is transmembrane, meaning it crosses the cellular membrane to impact calcium Homeostasis inside the cell. This Molecule/protein is made by the PDK-1 gene. This gene is located on Chromosome 16.
Through splicing error or mutation in this gene, This Ciliary body goes missing.
2 things happen then:
1: The cell dies and details are lost this point
we know that even at the peri-membrane level Caspases can be triggered. After all the Caspase are in the Cytosol. However at the time of the 2nd hit event, the cell is stressed and through the MAPK pathway, the c-Jun can be stimulated also. Whatever the case these cells can be destroyed.
2.The other path follows gene interactions.
We know that PDK-1 interact with RSG7 which in turn interact with SNAPAP ( a BLOC-1 component)
RSG7 is a Regulator of G-protein Signaling 7. acting somewhat as a promoter gene for SNAPAP sitting on BLOC1, And BLOC-1 is important in the formation of specialized organelles in the endosomal-lysozomal systems (Melanosome, and Platelet dense granules). This where differentiation is involved in the activity of BLOC-1. If differentiation is our Target, disabling BLOC-1 is it. This is a large molecule with many importatnt components, it is an intersection of roads in the cell!
Continuing our story, BLOC-1 will interact with Dysbindin and Pallidin, 2 very interesting Molecules in this disease. Pallidin deals with intracellular vesicle trafficking, and through its interaction with syntaxin 13, it has impact of membrane fusion and division. This bring the notion of Vacuolization which could explain also Cystic formation (speculation that needs proof of concept). But you see where I am coming from.
The Dysbindin is very important here, the skeleton of the ciliary body could come from activity in this protein but remember that the skeleton of the cell is also its nervous system. Some forms of Schizophrenia is linked to disturbances in the Dysbindin. Indeed you will find the individual suffering from this disease with a certain odd personality... mostly with obsessive and stubborn tendencies in my experience.
Individual with this diagnosis should be on ACE inhibitor, or the new TOLVAPTAN!
and should never have Caffeine which promotes the growth of cysts.
Friday, February 22, 2013
FDA Approves T-DM1 (Kadcyla) for HER2-Positive Breast Cancer
By Ian Ingram |
February 22, 2013
Web Editor, Cancer Network
The US Food and Drug Administration (FDA) approved ado-trastuzumab
emtansine (Kadcyla) for the treatment of patients with metastatic
HER2-positive breast cancer earlier today. HER2-positive disease
accounts for nearly 20% of all breast cancers.
The new drug, known as T-DM1 during clinical research, is intended for patients whose disease has progressed following treatment with trastuzumab (Herceptin) and a taxane.
“Kadcyla is trastuzumab connected to a
drug called DM1 that interferes with cancer cell growth,” said Richard
Pazdur, MD, director of the Office of Hematology and Oncology Products
in the FDA’s Center for Drug Evaluation and Research, in a press release.
“Kadcyla delivers the drug to the cancer site to shrink the tumor, slow
disease progression, and prolong survival. It is the fourth approved
drug that targets the HER2 protein.”
Most recently the FDA approved pertuzumab (2012) for HER2-positive breast cancer—trastuzumab (1998) and lapatinib (2007) are also FDA-approved for this indication.
The trial that led to the approval of ado-trastuzumab emtansine, the phase III EMILIA trial, was an open-label trial that included 991 patients. Patients were randomized to receive ado-trastuzumab emtansine at a dose of 3.6 mg/kg every 3 weeks or lapatinib (Tykerb) plus capecitabine. Primary endpoints of the trial were progression-free and overall survival.
Patients who received ado-trastuzumab emtansine had a median progression-free survival of 9.6 months compared with 6.4 months for patients treated with lapatinib plus capecitabine (P < .0001). The median overall survival was 30.9 months in the ado-trastuzumab emtansine arm of the trial, compared with 25.1 months for patients in the lapatinib plus capecitabine arm.
Ado-trastuzumab emtansine was well tolerated, with the most common adverse events being nausea, fatigue, pain in the muscles or joints, headache, and constipation. Common high-grade toxicities included thrombocytopenia (12.9%) and elevation in liver function test, though both were resolved when treatment was temporarily halted.
The new drug carries a boxed warning alerting patients and health care professionals that ado-trastuzumab emtansine can cause reductions in left ventricular ejection fraction, liver toxicity, and death. The drug can also cause severe birth defects, so a patient's pregnancy status should be determined prior to treatment.
The new drug, known as T-DM1 during clinical research, is intended for patients whose disease has progressed following treatment with trastuzumab (Herceptin) and a taxane.
-
<SCRIPT SRC="http://ad.adlegend.com/jscript?spacedesc=8937949_1089022_160x600_8937946_8937949&ML_NIF=Y&target=_blank&@CPSC@=http://ad.doubleclick.net/click%3Bh%3Dv8/3d91/3/0/%2a/b%3B268012614%3B0-0%3B1%3B90789172%3B2321-160/600%3B52234075/52193703/1%3B%3B%7Esscs%3D%3f"></SCRIPT> <NOSCRIPT> <A HREF="http://ad.adlegend.com/click?spacedesc=8937949_1089022_160x600_8937946_8937949&ML_NIF=Y" TARGET="_blank"> <IMG SRC="http://ad.adlegend.com/image?spacedesc=8937949_1089022_160x600_8937946_8937949&ML_NIF=Y" WIDTH=160 HEIGHT=600 ALT="Click Here" BORDER=0> </A> </NOSCRIPT>
Most recently the FDA approved pertuzumab (2012) for HER2-positive breast cancer—trastuzumab (1998) and lapatinib (2007) are also FDA-approved for this indication.
The trial that led to the approval of ado-trastuzumab emtansine, the phase III EMILIA trial, was an open-label trial that included 991 patients. Patients were randomized to receive ado-trastuzumab emtansine at a dose of 3.6 mg/kg every 3 weeks or lapatinib (Tykerb) plus capecitabine. Primary endpoints of the trial were progression-free and overall survival.
Patients who received ado-trastuzumab emtansine had a median progression-free survival of 9.6 months compared with 6.4 months for patients treated with lapatinib plus capecitabine (P < .0001). The median overall survival was 30.9 months in the ado-trastuzumab emtansine arm of the trial, compared with 25.1 months for patients in the lapatinib plus capecitabine arm.
Ado-trastuzumab emtansine was well tolerated, with the most common adverse events being nausea, fatigue, pain in the muscles or joints, headache, and constipation. Common high-grade toxicities included thrombocytopenia (12.9%) and elevation in liver function test, though both were resolved when treatment was temporarily halted.
The new drug carries a boxed warning alerting patients and health care professionals that ado-trastuzumab emtansine can cause reductions in left ventricular ejection fraction, liver toxicity, and death. The drug can also cause severe birth defects, so a patient's pregnancy status should be determined prior to treatment.
SO YOU KNOW we were warned!
"Across the medical campus we have recently detected an increase in rates of Clostridium difficile (C.diff) infection therefore we need heightened attention and
adherence to the policies and practices on hand hygiene including
routinely washing hands with soap and water especially following contact
with a C.diff patient.
Hand Hygiene must be performed:
- Upon entry to the patient’s room
-
Upon exit of the patient’s room
-
Before performing a clean or aseptic task
-
After contacting the patient’s environment
-
After exposure to blood or body fluids
-
Prior to using Work stations on Wheels (WOWs)
In addition, proper disinfection of reusable patient equipment must be performed:
Reusable Patient Equipment:
- Patients on contact or contact special isolation precautions should have dedicated patient equipment whenever possible, and all reusable patient equipment must be cleaned with bleach after each use (e.g. Stethoscopes)
- WOWs should not be moved from patient room to patient room. If the same WOW must be used in multiple patient rooms, it must be disinfected with bleach between each patient.
Thank you for your attention to this request for the safety of our patients."
ACTUAL MEMO TO MEDICAL STAFF IN VIRGINIA!
Keep CPRIT focused on research
Express-News Editorial Board
Updated 4:17 pm, Wednesday, January 30, 2013
Comments (
Printable Version
Email This
Font
For a politician who once said that government should “trust
capital markets and (the) private sector to make the decisions, and let
the consumers pick winners and losers,” Gov. Rick Perry certainly has had a change of heart.
As a candidate seeking the Republican presidential nomination, Perry was critical of the idea that government can create jobs and opposed government transfers of wealth. As governor of Texas, it's a different story.
Perry has been a staunch advocate of the Texas Enterprise Fund and the Emerging Technology Fund as tools for economic development. Taxpayer dollars bankroll both funds which, as the governor's website describes the Texas Enterprise Fund, “help attract new jobs and investment to the state.”
Perry's job creation claims, however, haven't stood up to scrutiny. His manipulation of the Texas Enterprise Fund, including circumvention of the fund's advisory panel to award $50 million to a controversial project at Texas A&M University, his alma mater, and the distribution of grants to a large number of companies whose principals are significant donors to his campaigns earned Perry charges of “crony capitalism” from his GOP competitors.
That sketchy history is enough to oppose Perry's efforts to transform the Cancer Prevention and Research Institute of Texas into another public investment vehicle from which, he told the Houston Chronicle, “wealth can be created.” What's worse, changing CPRIT's mission to commercialization and wealth creation amounts to a bait and switch with taxpayers.
Voters approved up to $3 billion for CPRIT in 2007 with the understanding that it would fund “research in Texas to find the causes of and cures for cancer.” The ballot measure, Proposition 15, said nothing about commercialization.
CPRIT's grant-making process is already a source of controversy. The institute's leaders and lawmakers should resist pressure from Perry to shift CPRIT's mission away from basic research. When it comes to commercializing cures and treatments, let the market of medical professionals and cancer patients pick winners and losers.
As a candidate seeking the Republican presidential nomination, Perry was critical of the idea that government can create jobs and opposed government transfers of wealth. As governor of Texas, it's a different story.
Perry has been a staunch advocate of the Texas Enterprise Fund and the Emerging Technology Fund as tools for economic development. Taxpayer dollars bankroll both funds which, as the governor's website describes the Texas Enterprise Fund, “help attract new jobs and investment to the state.”
Perry's job creation claims, however, haven't stood up to scrutiny. His manipulation of the Texas Enterprise Fund, including circumvention of the fund's advisory panel to award $50 million to a controversial project at Texas A&M University, his alma mater, and the distribution of grants to a large number of companies whose principals are significant donors to his campaigns earned Perry charges of “crony capitalism” from his GOP competitors.
That sketchy history is enough to oppose Perry's efforts to transform the Cancer Prevention and Research Institute of Texas into another public investment vehicle from which, he told the Houston Chronicle, “wealth can be created.” What's worse, changing CPRIT's mission to commercialization and wealth creation amounts to a bait and switch with taxpayers.
Voters approved up to $3 billion for CPRIT in 2007 with the understanding that it would fund “research in Texas to find the causes of and cures for cancer.” The ballot measure, Proposition 15, said nothing about commercialization.
CPRIT's grant-making process is already a source of controversy. The institute's leaders and lawmakers should resist pressure from Perry to shift CPRIT's mission away from basic research. When it comes to commercializing cures and treatments, let the market of medical professionals and cancer patients pick winners and losers.
NEXT TO THE MTOR,
We are getting closer to the cure every day, we are clearly at the door of the cure acquiring process,
just learning the language spoken by the cell. Already it seems we are overwhelmed by what we find.
There are things we are learning though, and fast:
1. That forces within the cell can be followed through laws of nature, as grouped here: THAT AMPLIFICATION, PROLIFERATION AND DIFFERENTIATION ARE GOVERNED BY SETS OF GENES AND HAVE VARIOUS LEVELS OF EXPRESSION.
2. That treatment strategies can be made following different steps in pathways
3. That Death traps are located at the membrane, cytoplasm, mitochondria and Nucleus
4. That downstream targets inhibition can overcome resistance to earlier target inhibition
5. That Inactivation and down-regulation of gene expression appears to be more important in Oncogenesis
6. That most of the time MAPK amplification results from the down regulation of PI3K/PTEN
7. That MTOR inhibition is deeper than EGFR/VEGF and PI3k inhibition
8. That VELCADE or antiproteasome will disturb all the pathways of which products need Ubiquitination for degradation
9. That Velcade may worsen VHL depedent syndromes
10. Then, even deeper, that MTOR, are Histone de-acyl- transferases
BUT WHAT WE HAVE NOT TALKED ABOUT ENOUGH IS THE POSSIBILITY OF CURE HIDDEN EVEN DEEPER IN THE DIFFERENTIATION.: HERE ARE HIDDEN THE SO- CALLED "PATHWAYS OF SECONDARY METABOLISM" AND SURPRISE SURPRISE THAT THE ROLE OF ANTIBIOTICS RE-EMERGES!
HERE, WE LOOK FOR DIMBOA PATHWAYS AND DNA REPLICATION
ASSOCIATION WITH STRESS (FOS, C-JUN)
ASSOCIATION WITH P450
ASSOCIATION WITH UDPG GLUCOSYL TRANSFERASES AND SOME DIOXYGENASE
WE NEED TO EXPLORE ANTIBIOTICS COMING FROM FUNGI.
LET ME COME TO THE CHASE OF BX1, BX2, AS THEY ARE TIED TO U11, U12, AND CHROMOSOME 4. THIS IS THE NEW BATTLEGROUND!
RESEARCHERS, PLEASE GO BACK TO WORK!
We are getting closer to the cure every day, we are clearly at the door of the cure acquiring process,
just learning the language spoken by the cell. Already it seems we are overwhelmed by what we find.
There are things we are learning though, and fast:
1. That forces within the cell can be followed through laws of nature, as grouped here: THAT AMPLIFICATION, PROLIFERATION AND DIFFERENTIATION ARE GOVERNED BY SETS OF GENES AND HAVE VARIOUS LEVELS OF EXPRESSION.
2. That treatment strategies can be made following different steps in pathways
3. That Death traps are located at the membrane, cytoplasm, mitochondria and Nucleus
4. That downstream targets inhibition can overcome resistance to earlier target inhibition
5. That Inactivation and down-regulation of gene expression appears to be more important in Oncogenesis
6. That most of the time MAPK amplification results from the down regulation of PI3K/PTEN
7. That MTOR inhibition is deeper than EGFR/VEGF and PI3k inhibition
8. That VELCADE or antiproteasome will disturb all the pathways of which products need Ubiquitination for degradation
9. That Velcade may worsen VHL depedent syndromes
10. Then, even deeper, that MTOR, are Histone de-acyl- transferases
BUT WHAT WE HAVE NOT TALKED ABOUT ENOUGH IS THE POSSIBILITY OF CURE HIDDEN EVEN DEEPER IN THE DIFFERENTIATION.: HERE ARE HIDDEN THE SO- CALLED "PATHWAYS OF SECONDARY METABOLISM" AND SURPRISE SURPRISE THAT THE ROLE OF ANTIBIOTICS RE-EMERGES!
HERE, WE LOOK FOR DIMBOA PATHWAYS AND DNA REPLICATION
ASSOCIATION WITH STRESS (FOS, C-JUN)
ASSOCIATION WITH P450
ASSOCIATION WITH UDPG GLUCOSYL TRANSFERASES AND SOME DIOXYGENASE
WE NEED TO EXPLORE ANTIBIOTICS COMING FROM FUNGI.
LET ME COME TO THE CHASE OF BX1, BX2, AS THEY ARE TIED TO U11, U12, AND CHROMOSOME 4. THIS IS THE NEW BATTLEGROUND!
RESEARCHERS, PLEASE GO BACK TO WORK!
ANTI-MEK ARE BETTER ANTI-VEGF
Based on what we know now, it is easy to see that in those diseases where Avastin has failed FDA approval, Anti-MEK will do better. MEK is down stream and MEK is involved in much more, including VEGF expression. MEK is part of the MEK/MAPK pathways, it is the door to Mesenchymal transformation (that is it the door to epithelial-mesenchymal transition), and therefore to angiogenesis, and to metastatic spread.
Anti-MEK also removes the negative inhibitory effect of the PTEN driven forces of the PI3K/MTOR pathways.
Metastatic Colon Cancer is the Primary target!
Only the MTOR inhibitors add to these drugs
Inability of Doxorubicin to add to DTIC in Melanoma is due to amplification of these 2 pathways.
Anti-MEK and MTOR combination will do far better in Melanoma and Pancreatic cancers, mark my words. We just need to brace ourselves to a new set of side effects.
Based on what we know now, it is easy to see that in those diseases where Avastin has failed FDA approval, Anti-MEK will do better. MEK is down stream and MEK is involved in much more, including VEGF expression. MEK is part of the MEK/MAPK pathways, it is the door to Mesenchymal transformation (that is it the door to epithelial-mesenchymal transition), and therefore to angiogenesis, and to metastatic spread.
Anti-MEK also removes the negative inhibitory effect of the PTEN driven forces of the PI3K/MTOR pathways.
PTEN inhibits insulin-stimulated MEK/MAPK activation andcell growth by blocking IRS-1 phosphorylation and IRS-1/Grb-2/Sos complex formation in a breast cancer model
- (Liang-Ping Weng1 at al.) The involvement of the Sons of the Sevenless could signify a large implication on the RAS pathway. And Anti-MEK were used as Medication to be used in lung cancer displaying amplification of the K-RAS
Metastatic Colon Cancer is the Primary target!
Only the MTOR inhibitors add to these drugs
Inability of Doxorubicin to add to DTIC in Melanoma is due to amplification of these 2 pathways.
Anti-MEK and MTOR combination will do far better in Melanoma and Pancreatic cancers, mark my words. We just need to brace ourselves to a new set of side effects.
Thursday, February 21, 2013
ACTIVITIES AT CRBCM
=====================
Invitation
==============================================================
MEETING WAS ABOUT SETTING THE POLICY TO BE FOLLOWED FOR TREATMENTS OF CRBCM PATIENTS. DR ZEINA NAHLEH, DIRECTOR OF THE INFUSION CENTER WAS PRESENT. THIS WAS A GOOD MEETING. CRBCM PATIENTS WILL BE WELL ATTENDED WITH QUALITY CARE OFFERED AT THE UNIVERSITY MEDICAL CENTER IN EL PASO! AND THANK YOU!
=====================
Invitation: To Meet with Dr. Kankonde from Greater East Cancer Center (Feb 21 10:00 AM MST in Infusion Center)
| Feb 20 (1 day ago) | | ||
| ||||
Images are not displayed. Display images below - Always display images from JCaldera@umcelpaso.org
|
Your Agenda for Thu Feb 21, 2013
|
MEETING WAS ABOUT SETTING THE POLICY TO BE FOLLOWED FOR TREATMENTS OF CRBCM PATIENTS. DR ZEINA NAHLEH, DIRECTOR OF THE INFUSION CENTER WAS PRESENT. THIS WAS A GOOD MEETING. CRBCM PATIENTS WILL BE WELL ATTENDED WITH QUALITY CARE OFFERED AT THE UNIVERSITY MEDICAL CENTER IN EL PASO! AND THANK YOU!
Subscribe to:
Posts (Atom)