Lunch with Dr. Padilla and Dr. Kankonde
WE ARE WORKING HARD AT CRBCM
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Tuesday, February 5, 2013
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THE CLEAN-UP AT CPRIT SHOULD BE EASY NOW!
I read again the good independent audit of CPRIT's operation and organization. In a way, this is good, what happened to CPRIT.
The experiment/trial at CPRIT is over. An evaluation is in. The powers will look at it and frame it better. From the bad will come the good. CPRIT will sharpen its image and work. This, however, will not occur until a clean-up is completed. Once again, I believe the task at the end should be easier than one would think. The new leaders at CPRIT will have a clear map for their work thanks to this audit. Act on each recommendation, with honesty and leadership, and a solid dose of vision for the cure, and you put CPRIT back to work in no time, and elevate it to how grand it should be.
There is a key to success: A CLEAN-UP!
THOSE WHO SLEPT, SHRINK THE VISION, THE POLITICIZED CPRIT NEED TO BE REMOVED. NO NEW "BIDON (FALSE)" FOUNDATIONS OR NETWORK OR INCUBATED COMPANIES. NO NEW INFORMATION GATHERING OR REFERRAL SERVICES CLOGGING THE SYSTEM WITH NON PRODUCING ENTITIES (WE HAVE THE GOOD OLD YELLOW PAGES FOR THAT).
4 REGIONAL OFFICES with power to approve grants for a greater Texas, and dilute the fight among the universities. I can't say this enough: 42% of funds to one single university is the worst thing done by CPRIT! You and I agree on this very point. CPRIT funds are coming from all Texans, not just Houstonians. These funds need to be redistributed accordingly to serve the cancer needs of all Texans.
Nobody knows how the cure will come, but an early attempt of a formulation must be made to
guide the research. Prevention must be centered around Regional Survivorship centers, and all companies moving to Texas should not end up in only one town. (Gridlock of Houston is not what you want anymore, I was there for 1 month doing home visits, I swear...!) ALL IN ALL REMEMBER EL PASO, 4TH CITY OF TEXAS, with a meager 0.2% INVESTMENT FROM CPRIT DESPITE A LOCAL UNIVERSITY PRESENT (UTEP). CRBCM spoke to university professors there at the Border Biomedical Research Center. They have no clout, political muscle in CPRIT stalling all communication, they say. But here is where CPRIT would have easily picked up the people's support...El Paso is an underserved city, and with a large low income population, prevention programs would and will have a huge impact. Richer cities like Houston will not exerience similar per capita benefits. Prevention programs have higher impact in low income areas where people are hungry for new directions and opportunities. Its like feeding a rich man Vs a poor one. The rich will send you a list of complaints on he quality of your offer, the poor will be mesmerized by a good looking loaf of bread! Send a meaningful cancer prevention program our way (EL Paso), and you will see how the people will embrace it!
7 years left, lets get back to work, FREE CPRIT, cut our losses, and give the people another chance to find the cure!
I read again the good independent audit of CPRIT's operation and organization. In a way, this is good, what happened to CPRIT.
The experiment/trial at CPRIT is over. An evaluation is in. The powers will look at it and frame it better. From the bad will come the good. CPRIT will sharpen its image and work. This, however, will not occur until a clean-up is completed. Once again, I believe the task at the end should be easier than one would think. The new leaders at CPRIT will have a clear map for their work thanks to this audit. Act on each recommendation, with honesty and leadership, and a solid dose of vision for the cure, and you put CPRIT back to work in no time, and elevate it to how grand it should be.
There is a key to success: A CLEAN-UP!
THOSE WHO SLEPT, SHRINK THE VISION, THE POLITICIZED CPRIT NEED TO BE REMOVED. NO NEW "BIDON (FALSE)" FOUNDATIONS OR NETWORK OR INCUBATED COMPANIES. NO NEW INFORMATION GATHERING OR REFERRAL SERVICES CLOGGING THE SYSTEM WITH NON PRODUCING ENTITIES (WE HAVE THE GOOD OLD YELLOW PAGES FOR THAT).
4 REGIONAL OFFICES with power to approve grants for a greater Texas, and dilute the fight among the universities. I can't say this enough: 42% of funds to one single university is the worst thing done by CPRIT! You and I agree on this very point. CPRIT funds are coming from all Texans, not just Houstonians. These funds need to be redistributed accordingly to serve the cancer needs of all Texans.
Nobody knows how the cure will come, but an early attempt of a formulation must be made to
guide the research. Prevention must be centered around Regional Survivorship centers, and all companies moving to Texas should not end up in only one town. (Gridlock of Houston is not what you want anymore, I was there for 1 month doing home visits, I swear...!) ALL IN ALL REMEMBER EL PASO, 4TH CITY OF TEXAS, with a meager 0.2% INVESTMENT FROM CPRIT DESPITE A LOCAL UNIVERSITY PRESENT (UTEP). CRBCM spoke to university professors there at the Border Biomedical Research Center. They have no clout, political muscle in CPRIT stalling all communication, they say. But here is where CPRIT would have easily picked up the people's support...El Paso is an underserved city, and with a large low income population, prevention programs would and will have a huge impact. Richer cities like Houston will not exerience similar per capita benefits. Prevention programs have higher impact in low income areas where people are hungry for new directions and opportunities. Its like feeding a rich man Vs a poor one. The rich will send you a list of complaints on he quality of your offer, the poor will be mesmerized by a good looking loaf of bread! Send a meaningful cancer prevention program our way (EL Paso), and you will see how the people will embrace it!
7 years left, lets get back to work, FREE CPRIT, cut our losses, and give the people another chance to find the cure!
BETTER IMAGING FOR BREAST CANCER: TOMOSYNTHESIS
*Tomosynthesis gives "200 one-millimeter-thick images for an average sized breast, compared to 4 images in a regular 2-D digital mammogram" leading to 41 to 61% increase of cancer detection compared to standard 2-D digital mammography. It also reduces the return for additional imaging, according to a report by Donna Plecha, MD, Director of the Dept. of Radiology at UH, Case Western School of Medicine.
*Thomas Bachelot et al. submitted results of a phase II study related to use of Capecitabine and Lepatinib as first line therapy for patients with Brain metastasis from HER-2 positive Breast cancer. 45 patients enrolled, Median follow-up 21 months. 65.9% of patients had a partial response noted.
*Another Disparity: Although white Americans have twice as high an incidence of Bladder cancers, at similar grade and stage of disease, Black Americans do have a higher mortality!". There is a 5 fold relative risk for those who smoked 20cigarettes/day for over 40 years, compared, of course, to non smokers.
*Marginal Zone Lymphoma.includes:
-MALT
-Nodal type
-Primary splenic type which can have villious cells that can be confused with Hairy cell morphologically on peripheral blood.
has CD20+, CD5-, CD10-, CD23-
In extranodal cases, 60% have Trisomy 3 and t(11;18) which produce fusion API2and MLT, and will mark resistance to Antibiotics
API2 is an inhibitor of Apoptosis
MALT1 (procaspase) bind to Bcl-10 leading to activation of NF-bK which ultimately impair Apoptosis
Associated to Sjogren disease in some cases, in the stomach, associated with H.Pylori
Rituxan as a single agent, local RT,
*Thomas Bachelot et al. submitted results of a phase II study related to use of Capecitabine and Lepatinib as first line therapy for patients with Brain metastasis from HER-2 positive Breast cancer. 45 patients enrolled, Median follow-up 21 months. 65.9% of patients had a partial response noted.
*Another Disparity: Although white Americans have twice as high an incidence of Bladder cancers, at similar grade and stage of disease, Black Americans do have a higher mortality!". There is a 5 fold relative risk for those who smoked 20cigarettes/day for over 40 years, compared, of course, to non smokers.
*Marginal Zone Lymphoma.includes:
-MALT
-Nodal type
-Primary splenic type which can have villious cells that can be confused with Hairy cell morphologically on peripheral blood.
has CD20+, CD5-, CD10-, CD23-
In extranodal cases, 60% have Trisomy 3 and t(11;18) which produce fusion API2and MLT, and will mark resistance to Antibiotics
API2 is an inhibitor of Apoptosis
MALT1 (procaspase) bind to Bcl-10 leading to activation of NF-bK which ultimately impair Apoptosis
Associated to Sjogren disease in some cases, in the stomach, associated with H.Pylori
Rituxan as a single agent, local RT,
NOMENCLATURE OF GENES AND PATHWAYS INVOLVED IN BUTEIN INHIBITIONS: IKK and Sirtuin
IKK:
The subunit to be inhibited for the activation of the Nuclear factor and pathway NF-kB which has versatile transforming capacity to combat, escape and resist various attackers including infection and chemotherapy. Inhibition here reduces the cell capacity to adapt. It appears that the Transcription factor NFkB is sitting there in the Cytosol totally inactive, touch the IKK through phosphorylation, wakes the NFkB which spring into motion and unleashes its power. One of the best described pathway flow is TNF posphorylation of IKK which detaches and goes on to being ubiquitinated and degraded through the Proteasome. detachment of the IKK lead to a free NFkB kinase which enter the nucleus to unleash all kinds of genes of defense. DO REMEMBER that upstream NFkB go through MEK (also involved in Angiogenesis) to reach MAP3K and you can see how through networking of these pathways the phenomena gets global.
Sirtuin:
This compound is SIRT1, it is activated by BUTEIN
Butein actually activate SIRT1 and may induce aging in the cell. Remember Butein by activating Sirtuin will have a role in Diabetes, Gout, Alzheimer dementia, and Amyloid related disease. Butein, a versatile anti-inflammatory drug with effect on NAD (Nicotinamid), and may be a Histone De-acetylase inhibitor. This stuff has potential!
The subunit to be inhibited for the activation of the Nuclear factor and pathway NF-kB which has versatile transforming capacity to combat, escape and resist various attackers including infection and chemotherapy. Inhibition here reduces the cell capacity to adapt. It appears that the Transcription factor NFkB is sitting there in the Cytosol totally inactive, touch the IKK through phosphorylation, wakes the NFkB which spring into motion and unleashes its power. One of the best described pathway flow is TNF posphorylation of IKK which detaches and goes on to being ubiquitinated and degraded through the Proteasome. detachment of the IKK lead to a free NFkB kinase which enter the nucleus to unleash all kinds of genes of defense. DO REMEMBER that upstream NFkB go through MEK (also involved in Angiogenesis) to reach MAP3K and you can see how through networking of these pathways the phenomena gets global.
Sirtuin:
This compound is SIRT1, it is activated by BUTEIN
Butein actually activate SIRT1 and may induce aging in the cell. Remember Butein by activating Sirtuin will have a role in Diabetes, Gout, Alzheimer dementia, and Amyloid related disease. Butein, a versatile anti-inflammatory drug with effect on NAD (Nicotinamid), and may be a Histone De-acetylase inhibitor. This stuff has potential!
BUTEIN, A POWERFUL INHIBITOR
As we speak with the University of Texas in El Paso, the CRBCM would like to look further into the clinical use of a potent Inhibitor in a phase I study. We believe this compound will have a significant role in Triple Negative Breast Cancer. Butein, a derivative of Charcone, a powerful anti-Oxidant and known anti-inflammatory used in ASIA, seems to have a global inhibitory effect. It is one of the 3 inhibitors of the SRC, it is a Glutathione inhibitor, Blocker of EGF, inhibitor of IKK, and of the NF-kB signal transduction pathway, cause phosphorylation of the AKT, reduction of Cyclin D1 and D2, activation of WAF1/p21 and KIP1/p27, Iron induced inhibitor of Xanthine Oxidase (love that enzyme since I first learned about Asthma).
This Butein stuff is a global inhibitor. If you add this to MTOR inhibitors, you may end up with too toxic a combination for any cancer! This would be an overwhelming attack on cells!
It has demonstrated powerful Ex-vivo activity against breast and prostate cancer cell lines, and is empirically used against Gastric cancer.
This global and versatile inhibitor, Butein, should have activity in Sarcoma since it inhibits SRC and potentially the fibroblast. Other Inhibitors of SRC, heme supported phosphorylation and CYIKYYF. (of note CDK1, PTRC and PTK2)
Gave you so many letters, lets move to gene Nomenclature please! we are still working hard at the CRBCM!
This Butein stuff is a global inhibitor. If you add this to MTOR inhibitors, you may end up with too toxic a combination for any cancer! This would be an overwhelming attack on cells!
It has demonstrated powerful Ex-vivo activity against breast and prostate cancer cell lines, and is empirically used against Gastric cancer.
This global and versatile inhibitor, Butein, should have activity in Sarcoma since it inhibits SRC and potentially the fibroblast. Other Inhibitors of SRC, heme supported phosphorylation and CYIKYYF. (of note CDK1, PTRC and PTK2)
Gave you so many letters, lets move to gene Nomenclature please! we are still working hard at the CRBCM!
Monday, February 4, 2013
CRBCM MET DR RENATO AGUILARE of the University of Texas in El Paso.
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The Meeting was centered on potential scientific collaboration between the BBRC and the CRBCM & Greater East Cancer Center. The collaboration is called for by most grant funding source for both entities. The Biomedical research (BBRC) needs cooperation with cancer centers, and the CRBCM needs ties with the local University.
We discussed the careful handling of exchanged study tissue or fluid samples which should follow NCI protocols related to studies on human subjecst (Dr Kankonde attended appropriate NCI training and is a certified investigator like most American Oncologists) and proper handling of patient information should follow HIPPA guidleines. Under the term of the understanding, no patient name will be released to the University staff.
CRBCM also met DR GIULIO FRANCIA, PHD, Assistant professor in the Dept. of Biological Sciences at UTEP. The line of discussion was similar. Collaboration on future investigations and publications was the bulk of the discussion.
The CRBCM has 2 grant request application letters pending before the BBRC.
Details of the plans are still waiting to be finalized. The meeting was informative about the spectrum of clinical research projects at this Dept. at UTEP.
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| Feb 1 (3 days ago) | | ||
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Shown
below is the parking pass –it needs to be displayed so please print it
and follow the instructions below to avoid a ticket. A campus map is
also enclosed. My office is located in the new Biosciences Research
Bldg and I am in room 4.144
Renato J. Aguilera, Ph.D.
Professor of Biology
Deputy Director and
Director of the Cell Culture and HTS Core Facility
Border Biomedical Research Center
University of Texas at El Paso
500 W. University Dr.
El Paso, TX 79968-0519
Ph:(915)747-6852======================================================================
The Meeting was centered on potential scientific collaboration between the BBRC and the CRBCM & Greater East Cancer Center. The collaboration is called for by most grant funding source for both entities. The Biomedical research (BBRC) needs cooperation with cancer centers, and the CRBCM needs ties with the local University.
We discussed the careful handling of exchanged study tissue or fluid samples which should follow NCI protocols related to studies on human subjecst (Dr Kankonde attended appropriate NCI training and is a certified investigator like most American Oncologists) and proper handling of patient information should follow HIPPA guidleines. Under the term of the understanding, no patient name will be released to the University staff.
CRBCM also met DR GIULIO FRANCIA, PHD, Assistant professor in the Dept. of Biological Sciences at UTEP. The line of discussion was similar. Collaboration on future investigations and publications was the bulk of the discussion.
The CRBCM has 2 grant request application letters pending before the BBRC.
Details of the plans are still waiting to be finalized. The meeting was informative about the spectrum of clinical research projects at this Dept. at UTEP.
CELLULAR LANGUAGE (II)
In Cellular Language I published recently that we tried to emphasize that big functions of the cell start up with an on-and-off switch. The Tic and The Tan like in MORSE language, the 1and 0 of the computer. While this is true, there are many other simple things at the molecular level that are just as simple, but full of physiologic and scientific implications.
1.ON and OFF switch:
--------------------------
Events that lead to cancer are sometimes an exaggeration of a signal. The K-RAS (there exist many RAS (es) as we discussed in differentiation) has a switch called the Sons of the Sevenless which can stay on, sending signals down the cell continuously. Activated RAS will light on 3 signal pathways:
-MAP kinase (through RAF)--->FOS, JUN (stress), MYC (the dangerous leading to Burkitt)-TF
-RAL/CDC42 (important in the movement of the membrane, Metastasis)
-PI3K (leading to affect on AKT/MTOR) FOXO downstream hiding the PUMA-remember)
Mutations at the RAS itself can also cause it to stay on, as opposed to knocking it out.
Remember, Mutations of RAS occur in 80% of Pancreatic cancers and 50% of colon cancer.
Therefore, a simple switch can kill you with one of the most devastating diseases.
2. Change of shape:
---------------------
To confuse and look smart, your scientist calls this post-translational conformation to emphasize that this change has occurred later because of the nteraction with another molecule (in general).
At the surface of the membrane, there are here and there some Molecules called INTEGRINS; these are of various types and increasing molecular diversity and are best known as Receptors. They are large complexes of molecules gathered in chunks called 'subunits'. They basically cross the thickness of the cellular membrane and, outside the cell, they sense what is going on. Integrins serve many great purposes including cell division, proliferation, migration, adhesion to each either, differentiation, sensing etc. You name it, they do it! Only division of DNA, this, they don't do. But the membrane has to be divided also to make 2 cells in cell divison. Even anti-coagulation happens here. The versatility of the integrins is linked to the variety of subunits it is composed with. Some are nature of cell specific and some are contact specific. By contact specific, I mean what molecule outside the cell it will attach to (ie fibronectin Vs GPIIb).
Suffice is to say that kinking of the Integrins causes exposure of some parts of the Integrin molecule not naturally exposed. If one looks at the skin of the joint at the back of the finger, one will see folded skin. if you forcefully bend your finger, the fold you were looking at will unfold and the bottom of the fold will come out. This is what happen to the integrin when it meets outside the cell another molecule such as TALIN.
That bending triggers the attachment of other molecules or ions (phosphorylation) to the now exposed skin, lighting up the Integrins for the cascade of events which will unfold, including the activation of SRC in Sarcoma.
The shape imposed by the bending is also Molecule specific. Despite the resemblance of SRC with the c-ABL (leukemia), their bending does not offer the same shape, and therefore, different parts of the molecule are exposed and 2 different diseases result.
CELL ADHESION- "join at the hip"
----------------------------------------
At many points the cells are joined to each other at the hips of the Talins. Say, at the hip of the Talin which linked to one Integrin, there is a PLUS SIGN at Cell A, and at the next TALIN attached to the Integrin of cell B, there is a NEGATIVE sign. These 2 integrins will be attached, and cell adhesion is achieved. Simple as that!
Wheels of cellular migration,
-----------------------------,
Cells can roll over other cells by progressively attaching Talin to Talins and breaking the talin-talins (integrin-integrin) behind, engulfing the integrins and using them again in the forthcoming attachment like a wheel touching the ground. The cell is that smart at the membrane.
More simple things to come...
Hiding the PUMA behind the FOXO to have a death TRAP (Apoptsosis) in case the FOXO is compromised!
Just simple, but effective tricks ...
1.ON and OFF switch:
--------------------------
Events that lead to cancer are sometimes an exaggeration of a signal. The K-RAS (there exist many RAS (es) as we discussed in differentiation) has a switch called the Sons of the Sevenless which can stay on, sending signals down the cell continuously. Activated RAS will light on 3 signal pathways:
-MAP kinase (through RAF)--->FOS, JUN (stress), MYC (the dangerous leading to Burkitt)-TF
-RAL/CDC42 (important in the movement of the membrane, Metastasis)
-PI3K (leading to affect on AKT/MTOR) FOXO downstream hiding the PUMA-remember)
Mutations at the RAS itself can also cause it to stay on, as opposed to knocking it out.
Remember, Mutations of RAS occur in 80% of Pancreatic cancers and 50% of colon cancer.
Therefore, a simple switch can kill you with one of the most devastating diseases.
2. Change of shape:
---------------------
To confuse and look smart, your scientist calls this post-translational conformation to emphasize that this change has occurred later because of the nteraction with another molecule (in general).
At the surface of the membrane, there are here and there some Molecules called INTEGRINS; these are of various types and increasing molecular diversity and are best known as Receptors. They are large complexes of molecules gathered in chunks called 'subunits'. They basically cross the thickness of the cellular membrane and, outside the cell, they sense what is going on. Integrins serve many great purposes including cell division, proliferation, migration, adhesion to each either, differentiation, sensing etc. You name it, they do it! Only division of DNA, this, they don't do. But the membrane has to be divided also to make 2 cells in cell divison. Even anti-coagulation happens here. The versatility of the integrins is linked to the variety of subunits it is composed with. Some are nature of cell specific and some are contact specific. By contact specific, I mean what molecule outside the cell it will attach to (ie fibronectin Vs GPIIb).
Suffice is to say that kinking of the Integrins causes exposure of some parts of the Integrin molecule not naturally exposed. If one looks at the skin of the joint at the back of the finger, one will see folded skin. if you forcefully bend your finger, the fold you were looking at will unfold and the bottom of the fold will come out. This is what happen to the integrin when it meets outside the cell another molecule such as TALIN.
That bending triggers the attachment of other molecules or ions (phosphorylation) to the now exposed skin, lighting up the Integrins for the cascade of events which will unfold, including the activation of SRC in Sarcoma.
The shape imposed by the bending is also Molecule specific. Despite the resemblance of SRC with the c-ABL (leukemia), their bending does not offer the same shape, and therefore, different parts of the molecule are exposed and 2 different diseases result.
CELL ADHESION- "join at the hip"
----------------------------------------
At many points the cells are joined to each other at the hips of the Talins. Say, at the hip of the Talin which linked to one Integrin, there is a PLUS SIGN at Cell A, and at the next TALIN attached to the Integrin of cell B, there is a NEGATIVE sign. These 2 integrins will be attached, and cell adhesion is achieved. Simple as that!
Wheels of cellular migration,
-----------------------------,
Cells can roll over other cells by progressively attaching Talin to Talins and breaking the talin-talins (integrin-integrin) behind, engulfing the integrins and using them again in the forthcoming attachment like a wheel touching the ground. The cell is that smart at the membrane.
More simple things to come...
Hiding the PUMA behind the FOXO to have a death TRAP (Apoptsosis) in case the FOXO is compromised!
Just simple, but effective tricks ...
Sunday, February 3, 2013
-
Anonymous
Posted January 28, 2013Heard all sorts of things about Simba Beer mentioned in the stor
Heard all sorts of things about Simba Beer mentioned in the story. Does it still exist? How does it taste?Was this review helpful? Yes No Report this review
Wish I could try the traditional chicken and the peanut paste snack! -
KONGOKONGAPosted January 28, 2013
Just wish to go on such a river journey, for days on end, seeing
Just wish to go on such a river journey, for days on end, seeing the lush forest pass by... vivid descriptions, the characters of the novel are well sketched and quickly feel like friends...Was this review helpful? Yes No Report this review
FEW FACTS/10 news by HEMOnc today
1. BMI (body mass index) did not influence survival in early breast cancer women who received adhuvant therapy. This the work by EWERTZ et al. like any thing these day there was a trend toward benefit for those with BMI less than 30.
2. Reinfusion of Autologous T-cell containing a chimeric protein combining CD19 Antigen (CART 19 cells)
showed effective therapeutic effect in CLL.
3.Xarelto, a new anti-Xa was approved by the FDA in November 2012.
4. Adding Aspirin after discontinuation of Coumadin reduced recurrence rate of Thrombotic events.
5. BRAF inhibition and anti-CTLA4 Tremelimumab (+/- Interferon ) are the new kids on the Melanoma block! On the other spectrum, Taxol Carboplatin and Sorafenib failed to improve survival.
Trametinib may have activity in BRAF mutated Melanoma.
6. Zaltrap /Regorafenib has been approved in Metastatic Colorectal cancer. it is It is an anti-Angiogenesis agent by trapping VEGF A, B prior to its link to their respective receptors
7. Fibulin-3 an early biomarker for Mesothelioma? read the article...
8. Adding Avastin to Standard Taxane or Adriamycin based chemotherapy failed to improve survival in triple negative breast cancer as reported by Researcher in Scotland.
9. ZOLINZA (histone Deacetylase inhibitor ) may have a role in modulating Graft Vs Host (GVHD) in patients
10. Only a third of ITP patients who stopped Thrombopoietin Receptor Agonist (ELtrombopag) maintained a Platelet count 20-30,000 above the initial PLT count after 6 months of stopping the drug.
1. BMI (body mass index) did not influence survival in early breast cancer women who received adhuvant therapy. This the work by EWERTZ et al. like any thing these day there was a trend toward benefit for those with BMI less than 30.
2. Reinfusion of Autologous T-cell containing a chimeric protein combining CD19 Antigen (CART 19 cells)
showed effective therapeutic effect in CLL.
3.Xarelto, a new anti-Xa was approved by the FDA in November 2012.
4. Adding Aspirin after discontinuation of Coumadin reduced recurrence rate of Thrombotic events.
5. BRAF inhibition and anti-CTLA4 Tremelimumab (+/- Interferon ) are the new kids on the Melanoma block! On the other spectrum, Taxol Carboplatin and Sorafenib failed to improve survival.
Trametinib may have activity in BRAF mutated Melanoma.
6. Zaltrap /Regorafenib has been approved in Metastatic Colorectal cancer. it is It is an anti-Angiogenesis agent by trapping VEGF A, B prior to its link to their respective receptors
7. Fibulin-3 an early biomarker for Mesothelioma? read the article...
8. Adding Avastin to Standard Taxane or Adriamycin based chemotherapy failed to improve survival in triple negative breast cancer as reported by Researcher in Scotland.
9. ZOLINZA (histone Deacetylase inhibitor ) may have a role in modulating Graft Vs Host (GVHD) in patients
10. Only a third of ITP patients who stopped Thrombopoietin Receptor Agonist (ELtrombopag) maintained a Platelet count 20-30,000 above the initial PLT count after 6 months of stopping the drug.
Biotech firm credits CPRIT funds for experimental cancer-fighting drug
A 100-page report by the state auditor made public Monday slams the Cancer Research Institute of Texas, or CPRIT, with details of internal rule violations, misappropriated funds and grant applications not receiving proper scientific review.For now, all CPRIT grants have been put on hold at the direction of the governor's office. Following news of the State Audit report, a $25 Million CPRIT grant recipient shut down operations, causing 30 people to lose their job.
The audit is critical of how Statewide Clinical Trials Network of Texas was spending large portions of the grant.
The report is evidence of an ongoing statewide investigation of the five-year-old state agency. Widely celebrated upon being approved by Texas voters in 2007, CPRIT is now under criminal investigation after spending much of the past year in turmoil over questions surrounding several lucrative awards.
But scientists at local biotech research company Mirna Therapeutics says the CPRIT multimillion dollar grant it received is helping its battle against cancer.
The state’s Emerging Technology Fund gave $5 million to what scientists at the Mirna Therapeutics research lab call ‘pioneering research.’
The embattled CPRIT added another $10.3 million.
Mirna Therapeutics CEO Dr. Paul Lammers says the $15 million worth of public dollars has done its part inside his lab.
"Oh, absolutely vital, because it is very difficult time right now for funding in biotech," he said."Developing a new medicine, a new drug, doesn't matter if it's for cancer or for hypertension or diabetes, it is a long exercise.”
Scientists at Mirna have successfully created an experimental cocktail called the MRX34, which contains the mimic of a tumor suppressor called the miR-34. The miR-34 mimic can inhibit the growth of tumors related to lymphoma, liver, lung and prostate cancer. The drug is currently on its way to the U.S. Food Drug and Administration for clinical testing.
Lammers says the tumor suppressor wouldn’t have been created if it wasn’t for help from CPRIT funds.
“Beginning in 2008 was the first time we use that on animals where we saw tumors go away," Mirna Therapeutics Director of Research David Brown said.
Human clinical studies on MRX34 could begin in as early as two months.
The Associated Press contributed to this report.
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SHARE
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Comment:
We had warned CPRIT that some of these Biotech companies being bought or started-up will run off after the money dries out! What a waste! the ink is not even dried out...The FDA may not approve the so called advancement. And then?
A little more about HUMAN PAPILLOMA VIRUS AND CANCER:
--------------------------------------------------------------------------
HPV, the most sexually transmitted disease, has been implicated in:
- Cervical cancer
- Head and neck cancer
- Anal and most vaginal Cancers, penile cancers
- the role in lung and Esophageal cancers is not clear.
With over 130 types, only few have been implicated with cancer . (HPV16, 18 being the most cited since the work by Durst and Boshart)
90 % of infected people will see their infection cleared.
10 % will develop chronic infection. and by year 30 after original infection, 50% of the 10% will develop eventually a malignancy. It is widely believed that in those who developed the disease, the HPV gene E6 and E7 and their proteins products have managed to inactivate suppressor genes such as P53 and RB1 as part of the mechanism to cancerous transformation with loss of regulation of cellular proliferation, and control of chromosome instability. This process led to immortalization of Keratinocytes in the laboratory.
In the Oropharyngeal cancers, the verrucous squamous subtype is the most associated with HPV. HPV positive tumor however has a higher response rate with a better 2 year progression free disease.
Most of these cancers can be avoided by HPV immunization. The HPV presence can be confirmed by in-situ Hybridization. Expression of the P16 type appear to correlate with less P53 and RB1 inactivation and therefore leads to best prognosis whereas EGFR over expression tends to suggest a poorer outcome.
--------------------------------------------------------------------------
HPV, the most sexually transmitted disease, has been implicated in:
- Cervical cancer
- Head and neck cancer
- Anal and most vaginal Cancers, penile cancers
- the role in lung and Esophageal cancers is not clear.
With over 130 types, only few have been implicated with cancer . (HPV16, 18 being the most cited since the work by Durst and Boshart)
90 % of infected people will see their infection cleared.
10 % will develop chronic infection. and by year 30 after original infection, 50% of the 10% will develop eventually a malignancy. It is widely believed that in those who developed the disease, the HPV gene E6 and E7 and their proteins products have managed to inactivate suppressor genes such as P53 and RB1 as part of the mechanism to cancerous transformation with loss of regulation of cellular proliferation, and control of chromosome instability. This process led to immortalization of Keratinocytes in the laboratory.
In the Oropharyngeal cancers, the verrucous squamous subtype is the most associated with HPV. HPV positive tumor however has a higher response rate with a better 2 year progression free disease.
Most of these cancers can be avoided by HPV immunization. The HPV presence can be confirmed by in-situ Hybridization. Expression of the P16 type appear to correlate with less P53 and RB1 inactivation and therefore leads to best prognosis whereas EGFR over expression tends to suggest a poorer outcome.
HERBIMYCIN AND AVASTIN
Based of the evidence presented on the Myristoylation story, we predict that the combination of dasatinib or Herbimycin with Avastin will have a larger response rate on Angiosarcoma and papillary cancers because of a combined suppression of VGEF and SRC/MEK.
Dasatinib, previously known as BMS-354825, is a cancer drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel. Dasatinib is an oral multi- BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML) after imatinib treatment and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It is being evaluated for use in numerous other cancers, including advanced prostate cancer.
The drug is named after one of the inventor chemists, Jagabandhu Das, who was a member of the large discovery and development team at Bristol Myers Squibb.[1]
Herbimycin is a benzoquinone ansamycin antibiotic that binds to Hsp90
(Heat Shock Protein 90) and alters its function. HSP90 client proteins
play important roles in the regulation of the cell cycle, cell growth,
cell survival, apoptosis, angiogenesis and oncogenesis.
It was originally found by its herbicidal activity, and thus named.
-----------------------------------------------------------------------------------------------------------
Interferon will have a reasonable role, and studies have certainly reported cases of response of Angiosarcoma to Interferon. At CRBCM and the GREATER East cancer Center we are following a case of a young 38 year old female who has been referred to us after receiving Gemzar and Taxotere followed by MAID x 3 cycles for a 12 cm Angiosarcoma in the liver. She had an extensive skin reaction with desquamative feature to the Taxane. We plan to start her on Avastin alone at this point. We understand Navelbine could have a role.
Her case will be presented at Tumor Board to completely exhaust salvage surgical resection option. We are still awaiting a gene profiling which was not obtained at onset. An update will be forthcoming.
We are still working hard at CRBCM.
Role of Nexavar has also been discussed in Angiosarcoma...
Based of the evidence presented on the Myristoylation story, we predict that the combination of dasatinib or Herbimycin with Avastin will have a larger response rate on Angiosarcoma and papillary cancers because of a combined suppression of VGEF and SRC/MEK.
Dasatinib
From Wikipedia, the free encyclopedia
 |
|
|---|---|
| Systematic (IUPAC) name | |
| N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)- 1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide monohydrate |
|
| Clinical data | |
| Trade names | Sprycel |
| Pharmacokinetic data | |
| Protein binding | 96% |
| Metabolism | Hepatic |
| Half-life | 1.3 to 5 hours |
| Excretion | Fecal (85%), renal (4%) |
 |
|
| Chemical data | |
| Formula | C22H26ClN7O2S |
The drug is named after one of the inventor chemists, Jagabandhu Das, who was a member of the large discovery and development team at Bristol Myers Squibb.[1]
Herbimycin
From Wikipedia, the free encyclopedia
| Herbimycin | ||
|---|---|---|
 | ||
| ||
| Properties | ||
| Molecular formula | C30H42N2O9 | |
| Molar mass | 574.66 g/mol | |
| Hazards | ||
It was originally found by its herbicidal activity, and thus named.
Synonyms
- Antibiotic Tan 420F
- Herbimycin A
Biological activity
Herbimycin induces the degradation of proteins that are mutated in tumor cells such as v-Src, Bcr-Abl and p53 preferentially over their normal cellular counterparts. This effect is mediated via HSP90.-----------------------------------------------------------------------------------------------------------
Interferon will have a reasonable role, and studies have certainly reported cases of response of Angiosarcoma to Interferon. At CRBCM and the GREATER East cancer Center we are following a case of a young 38 year old female who has been referred to us after receiving Gemzar and Taxotere followed by MAID x 3 cycles for a 12 cm Angiosarcoma in the liver. She had an extensive skin reaction with desquamative feature to the Taxane. We plan to start her on Avastin alone at this point. We understand Navelbine could have a role.
Her case will be presented at Tumor Board to completely exhaust salvage surgical resection option. We are still awaiting a gene profiling which was not obtained at onset. An update will be forthcoming.
We are still working hard at CRBCM.
Role of Nexavar has also been discussed in Angiosarcoma...
- Fiona Godlee, editor, BMJ
Drug
treatment for age related macular degeneration is one of medicine’s
success stories. As Ning Cheung and colleagues explain (doi:10.1136/bmj.e2970),
anti-vascular endothelial growth factors are preserving and restoring
vision to millions around the world. But a related and less edifying
story is stealing the limelight: ranibuzimab (Lucentis) versus
bevacizumab (Avastin). It casts a shadow over this great medical advance
and puts the world’s drug development and licensing systems under the
spotlight.
In its anti-cancer drug, bevacizumab, drug
developer Genentech has created what may be the world’s first “not me”
(as opposed to “me too”) drug, say Robert Campbell and colleagues (doi:10.1136/bmj.e2941).
Despite evidence that it works in macular degeneration, the
manufacturers and marketers (Roche in the US, Novartis in the UK and
elsewhere) are actively discouraging its use for this condition, even
going so far as taking legal action to prevent such off-label use. Why?
Because they want people to use their other drug, ranibuzimab, which is
licensed for treating macular degeneration.
The bottom
line is that ranibuzimab is about 12 times more expensive: Cheung and
colleagues report that the UK could save close to £300m (€368m; $485m) a
year if it were standard treatment. So are Roche and Novartis simply
fighting to protect their profits? They say no, that they are also
protecting patients from the cheaper drug’s higher risk profile.
Although data from the publicly funded CATT trial in the US found
similar effectiveness and safety for the two drugs in treating macular
degeneration, the safety of bevacizumab remains a worry. Concerns relate
to its greater systemic absorption and the fact that it has to be
decanted into smaller quantities for intraocular injection, which
introduces the risk of infection.
Whatever the
motivation, the company has done all it can to limit the use of
bevacizumab outside cancer, most notably by not applying for regulatory
approval for use in patients with macular degeneration. Some health
systems are finding ways round this, as Campbell and colleagues explain.
But the combination of legal threats, safety concerns, and financial
incentives to use ranibuzimab has maintained the more expensive drug’s
lucrative market. Sales in the US in 2010 topped $1.8bn.
In the UK, as Ingrid Torjesen reports (doi:10.1136/bmj.e3012),
efforts are under way to get bevacizumab approved for use in macular
degeneration despite resistance from Novartis. The National Institute
for Health and Clinical Excellence has said it could appraise the drug
if asked to by the Department of Health. Campbell and colleagues report
that the department is waiting for the results of the IVAN trial in the
UK, due to be published this month. But it is unlikely to resolve the
safety concerns. Neither this nor the CATT trial was big enough to
detect small but clinically relevant differences in adverse outcomes
such as stroke, they say. Long term postmarketing surveillance is needed
for that.
So what’s to be done in the best interests of
patients and the public purse? Campbell and colleagues call for clear
guidance to use bevacizumab from professional organisations, a review of
policies that discourage off-label use if there is good evidence for a
drug’s use, and better communication among health technology assessors
in different parts of the world.
Notes
Cite this as: BMJ 2012;344:e3162
Footnotes
- Follow BMJ Editor Fiona Godlee on Twitter @fgodlee and the BMJ @bmj_latest
Saturday, February 2, 2013
MYRISTOYLATION, A TRUE COMMITMENT AT THE CELLULAR MEMBRANE!
Proliferation, growth and spread of cancers is mainly driven by phenomena occurring at the membrane. A Molecular structure called SRC or sarc (for sarcoma) is anchored there, and Myristoylation is the process that keep it there. SARC or SRC
Wikipedia suggests:
Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.[1]
Src (pronounced "sarc" as it is short for sarcoma) is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they were awarded the 1989 Nobel Prize in Physiology or Medicine.[2] It belongs to a family of non-receptor tyrosine kinases called Src family kinases. The discovery of Src family proteins has been instrumental to the modern understanding of cancer as a disease where normally healthy cellular signalling has gone awry.
This gene is similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene.[3]
==============================================================
In fact, SRC gene is at the center of Metastatic process through interaction with cell adhesion molecules, growth factors and many signal transduction pathways:
Wikipedia:
Interactions
Src (gene) has been shown to interact with
MET ACTIVITY INDUCED BY SRC ACTIVATION BY PHOSPHORYLATION SEEMS TO BE DETERMINED BY THE TYPE OF GROWTH FACTOR INDUCED. THROUGH HGFR, IT LEADS TO EMBRYONIC DEVELOPMENT IN THE EARLY CELL, AND TO WOUND HEALING IN RELEVANT TISSUE (SKIN), AND THROUGH HGF, IT LEADS TO MESENCHYMAL DIFFERENTIATION.
THROUGH MET, SRC LEADS TO RAS, PI3K/MAP K AND STAT EFFECTS
PHENOMENA AT THE MEMBRANE, A TRUE HISTORY, STILL UNFOLDING.
PLEASE ALSO NOTE CONFORMATION RAPPROCHEMENT BETWEEN SRC AND THE C-ABL WHERE IMITIMAB /GLEEVEC ACTS! SRC, CENTER OF METASTASIS, IS AN INTRODUCTION TO OUR FUTURE DISCUSSIONS.
Wikipedia suggests:
Src (gene)
From Wikipedia, the free encyclopedia
 |
This article needs attention from an expert on the subject. (March 2011) |
| V-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 PDB rendering based on 1a07. |
|||||||||||
|
|||||||||||
| Identifiers | |||||||||||
| Symbols | SRC; ASV; SRC1; c-SRC; p60-Src | ||||||||||
| External IDs | OMIM: 190090 MGI: 98397 HomoloGene: 21120 ChEMBL: 267 GeneCards: SRC Gene | ||||||||||
| EC number | 2.7.10.2 | ||||||||||
|
|||||||||||
| RNA expression pattern | |||||||||||
 |
|||||||||||
 |
|||||||||||
| More reference expression data | |||||||||||
| Orthologs | |||||||||||
| Species | Human | Mouse | |||||||||
| Entrez | 6714 | 20779 | |||||||||
| Ensembl | ENSG00000197122 | ENSMUSG00000027646 | |||||||||
| UniProt | P12931 | P05480 | |||||||||
| RefSeq (mRNA) | NM_005417.3 | NM_001025395.2 | |||||||||
| RefSeq (protein) | NP_005408.1 | NP_001020566.1 | |||||||||
| Location (UCSC) | Chr 20: 35.97 – 36.03 Mb |
Chr 2: 157.42 – 157.47 Mb |
|||||||||
| PubMed search | [1] | [2 | |||||||||
Src (pronounced "sarc" as it is short for sarcoma) is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they were awarded the 1989 Nobel Prize in Physiology or Medicine.[2] It belongs to a family of non-receptor tyrosine kinases called Src family kinases. The discovery of Src family proteins has been instrumental to the modern understanding of cancer as a disease where normally healthy cellular signalling has gone awry.
This gene is similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene.[3]
==============================================================
In fact, SRC gene is at the center of Metastatic process through interaction with cell adhesion molecules, growth factors and many signal transduction pathways:
Wikipedia:
Interactions
Src (gene) has been shown to interact with
- AR,[19][20][21]
- ARNT,[22]
- AHR,[22]
- ADRBK1,[23]
- ADRB3,[24]
- BCAR1,[25][26][27][28][29][30]
- CD44,[31]
- DAB2,[32]
- DDEF1,[33]
- DAG1,[34]
- EPHB2,[35][36]
- EGFR,[37][38][39]
- EPS8,[40]
- ESR1,[19][41][42][43]
- ESR2,[19][43]
- GNB2L1,[44]
- GRB2,[23][45]
- GRIN2A,[46][47]
- HNF1A,[48]
- KHDRBS1,[49][50][51][52][53]
- MT-ND2,[54]
- MUC1,[55][56]
- NCOA6,[57][58][59][60]
- PDE6G,[23]
- PLD2,[61]
- PRKCZ,[62]
- PTK2,[26][30][63][64][65][66]
- PTK2B,[38][67][68]
- RAF1,[69]
- RASA1,[70][71]
- RARA,[42][72]
- RICS,[73]
- SRF,[74]
- SHB,[75]
- STAT1,[37][76]
- STAT3,[77] and
- WAS.[78][79]
See also
Genatlas:- c-SRC is non receptor tyrosine kinase, direct effector of G proteins
- c-SRC plays a role in the regulation of embryonic development and cell growth
- c-SRC has an appreciable role in the organization of the Golgi apparatus, which may be linked to its involvement in protein transport from the Golgi apparatus to the endoplasmic reticulum
- c-SRC has an appreciable role in the organization of the Golgi apparatus, which may be linked to its involvement in protein transport from the Golgi apparatus to the endoplasmic reticulum
- monopalmitoylated SFK required for VEGF mitogenic signaling with SRC and FYN, but maintaining distinct properties in the regulation of VEGF-mediated endothelial cell events (Pubmed 16400523)
- c-SRC regulates Golgi structure and KDELR1-dependent retrograde transport to the endoplasmic reticulum
- c-SRC has a key role in the maintenance of epithelial integrity (Pubmed 18305002)
- c-SRC is crucially involved in the ghrelin-mediated Akt activation (Pubmed 19262695)
- non palmitoylated SFK (Src-family tyrosine kinase), rapidly exchanged between the plasma membrane and late endosomes/lysosomes (suggest that SFK trafficking is specified by the palmitoylation state in the SH4 domain) (Pubmed 19258394)
- major kinase implicated in PTK2 phosphorylation, and is directly translocated from focal adhesions to membrane ruffles, thereby promoting formation of new adhesion complexes (Pubmed 19066724)
- interacting with PDLIM4 and PTPN13 (PDLIM4 suppresses SRC activation through interacting with SRC and PTPN13, allowing PTPN13-dependent dephosphorylation of SRC at the activation loop) (Pubmed 19307596)
- c-SRC inhibits SGK1-mediated phosphorylation hereby restoring the WNK4-mediated inhibition of ROMK channels thus suppressing K secretion) (Pubmed 19706464)
- c-SRC binds DVL2, a key phosphoprotein in Wnt signaling, at two positions: an SH3-binding domain and a C-terminal domain (Pubmed 19920076)
- ----------------------------------------------------------------------------------------------
- THIS SRC IS PIVOTAL AND CENTER TO ALL ACTIVITY INVOLVING THE SPREAD AND MAINTENANCE OF CANCER. IT IS SOMEWHAT CELL AND SPECIES SPECIFIC.
- WE PURPOSELY LEFT THE DASATINIB REFERENCE HERE TO INDICATE THAT SCIENTIST ARE TRYING TO TARGET THIS CROSS ROAD MOLECULAR STRUCTURE.
- IT'S ACTIVITY AT THE MET PROTEIN INSURE CANCER GROWTH AND VASCULARIZATION THROUGH MET EFFECT ON ANGIOGENESIS.
- REMEMBER MET DISTURBANCES ARE PROMINENT IN PAPILLARY RENAL CELL CANCER.
MET ACTIVITY INDUCED BY SRC ACTIVATION BY PHOSPHORYLATION SEEMS TO BE DETERMINED BY THE TYPE OF GROWTH FACTOR INDUCED. THROUGH HGFR, IT LEADS TO EMBRYONIC DEVELOPMENT IN THE EARLY CELL, AND TO WOUND HEALING IN RELEVANT TISSUE (SKIN), AND THROUGH HGF, IT LEADS TO MESENCHYMAL DIFFERENTIATION.
THROUGH MET, SRC LEADS TO RAS, PI3K/MAP K AND STAT EFFECTS
PHENOMENA AT THE MEMBRANE, A TRUE HISTORY, STILL UNFOLDING.
PLEASE ALSO NOTE CONFORMATION RAPPROCHEMENT BETWEEN SRC AND THE C-ABL WHERE IMITIMAB /GLEEVEC ACTS! SRC, CENTER OF METASTASIS, IS AN INTRODUCTION TO OUR FUTURE DISCUSSIONS.
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