Op Ed from Vice Chair Barbara Canales
3:14 PM (49 minutes ago)
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Friday, January 25, 2013
Op Ed from Vice Chair Barbara Canales
FDA Approves Imatinib for Pediatric ALL
Editors' Recommendations
The US Food and Drug Administration (FDA) today approved imatinib (Gleevec,
Novartis) for the treatment of newly diagnosed pediatric acute
lymphoblastic leukemia (ALL) that is Philadelphia chromosome (Ph)
positive.
"We are pleased that the number of cancer medications for children is on the rise," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA Center for Drug Evaluation and Research, in a press statement.
In 2011, imatinib was approved to treat children newly diagnosed with Ph-positive chronic myeloid leukemia (CML).
However, ALL is the most common type of pediatric cancer, affecting approximately 2900 children annually, according to the FDA.
The safety and effectiveness of imatinib for pediatric patients with Ph-positive ALL were established in a clinical trial that enrolled children (1 year and older) and young adults with very-high-risk ALL (>45% chance of experiencing complications from their disease within 5 years of treatment).
The 92 patients with Ph-positive ALL enrolled in the trial were divided into 5 treatment groups, with each successive group receiving imatinib plus chemotherapy for a longer period.
Fifty of the Ph-positive ALL patients received imatinib for the longest period, and 70% of these patients did not experience relapse or death within 4 years. In addition, patient deaths decreased with the increasing duration of imatinib treatment in combination with chemotherapy, according to the FDA.
The most common adverse effects observed in children with Ph-positive ALL treated with imatinib plus chemotherapy were decreased neutrophil levels, decreased blood platelets levels, liver toxicity, and infection.
Imatinib is a tyrosine kinase inhibitor that blocks cancer-promoting proteins, and should be used in combination with chemotherapy to treat pediatric Ph-positive ALL.
Imatinib has been a practice-changing drug in this setting,
according to the Children's Oncology Group, which conducted the pivotal
clinical trial.
According to the group's Web site, the preferred treatment for Ph-positive ALL before imatinib was stem cell transplantation followed by 3 to 6 months of chemotherapy. However, cure rates were less than 50% with this approach. Imatinib in combination with chemotherapy has doubled cure rates, and stem cell transplantation is no longer automatically considered to be the best way to treat children with Ph-positive ALL.
Imatinib was granted accelerated approval in 2001 by the FDA to treat patients with blast-crisis, accelerated-phase, or chronic-phase Ph-positive CML who have failed interferon-alpha therapy. The drug was also approved in 2012 for the treatment of adults whose Kit (CD117)-positive gastrointestinal stromal tumors (GIST) had been surgically removed.
"We are pleased that the number of cancer medications for children is on the rise," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA Center for Drug Evaluation and Research, in a press statement.
In 2011, imatinib was approved to treat children newly diagnosed with Ph-positive chronic myeloid leukemia (CML).
However, ALL is the most common type of pediatric cancer, affecting approximately 2900 children annually, according to the FDA.
The safety and effectiveness of imatinib for pediatric patients with Ph-positive ALL were established in a clinical trial that enrolled children (1 year and older) and young adults with very-high-risk ALL (>45% chance of experiencing complications from their disease within 5 years of treatment).
The 92 patients with Ph-positive ALL enrolled in the trial were divided into 5 treatment groups, with each successive group receiving imatinib plus chemotherapy for a longer period.
Fifty of the Ph-positive ALL patients received imatinib for the longest period, and 70% of these patients did not experience relapse or death within 4 years. In addition, patient deaths decreased with the increasing duration of imatinib treatment in combination with chemotherapy, according to the FDA.
The most common adverse effects observed in children with Ph-positive ALL treated with imatinib plus chemotherapy were decreased neutrophil levels, decreased blood platelets levels, liver toxicity, and infection.
Imatinib is a tyrosine kinase inhibitor that blocks cancer-promoting proteins, and should be used in combination with chemotherapy to treat pediatric Ph-positive ALL.
According to the group's Web site, the preferred treatment for Ph-positive ALL before imatinib was stem cell transplantation followed by 3 to 6 months of chemotherapy. However, cure rates were less than 50% with this approach. Imatinib in combination with chemotherapy has doubled cure rates, and stem cell transplantation is no longer automatically considered to be the best way to treat children with Ph-positive ALL.
Imatinib was granted accelerated approval in 2001 by the FDA to treat patients with blast-crisis, accelerated-phase, or chronic-phase Ph-positive CML who have failed interferon-alpha therapy. The drug was also approved in 2012 for the treatment of adults whose Kit (CD117)-positive gastrointestinal stromal tumors (GIST) had been surgically removed.
Latest in Hematology-Oncology
FREE CPRIT MOVEMENT HAS BEEN CREATED!
PEOPLE AND INSTITUTIONS NEEDING FUNDING FOR CANCER RESEARCH CAN'T WAIT TO SEE CPRIT FREED FROM POWERS !
TALK TO YOUR LEGISLATORS ABOUT CPRIT FREEDOM!
In the meantime, Senator Kevin Eltife from Tyler is introducing legislation to stop CPRIT funding through sale of bonds. He believes that CPRIT should plead its case yearly asking for general fund with a dance before the Finance and and Appropriation Committee. He reportedly believes tha,t with that dance, the scrutiny level will increase. This point is as debatable as can be and may miss the point all together. The Senate was there with their eyes opened when the deals were going on! Somehow an annual report to the Senate cannot be hiding the bad deed? No, you need just good old honesty in CPRIT leaders and fair balanced processes to solve the issues at hand at CPRIT! One thing for sure, the Senator is reported to be consistent. He had similar position reportedly before the creation and passage of the law about CPRIT. Give him that!
PEOPLE AND INSTITUTIONS NEEDING FUNDING FOR CANCER RESEARCH CAN'T WAIT TO SEE CPRIT FREED FROM POWERS !
TALK TO YOUR LEGISLATORS ABOUT CPRIT FREEDOM!
In the meantime, Senator Kevin Eltife from Tyler is introducing legislation to stop CPRIT funding through sale of bonds. He believes that CPRIT should plead its case yearly asking for general fund with a dance before the Finance and and Appropriation Committee. He reportedly believes tha,t with that dance, the scrutiny level will increase. This point is as debatable as can be and may miss the point all together. The Senate was there with their eyes opened when the deals were going on! Somehow an annual report to the Senate cannot be hiding the bad deed? No, you need just good old honesty in CPRIT leaders and fair balanced processes to solve the issues at hand at CPRIT! One thing for sure, the Senator is reported to be consistent. He had similar position reportedly before the creation and passage of the law about CPRIT. Give him that!
NICE QUOTES FROM THE LANCET!
VOLTAIRE : "The art of Medicine consists of amusing the patient while nature cures the disease".
even then, the new the truth, we have been found out! patient have build in defense! we are just distracting him.....
PARCELSUS : "The art of healing comes from nature and not from the physician; Therefore, the physician must start from nature with an open mind"....
And here I am throwing the kitchen sink of chemotherapy instead of Target therapy. Cure will come from the mastering of law of nature at cellular level . READ CAREFULLY! CURE IS WITH US, LET'S OPEN OUR MIND!
CREDIT TO DANIEL KRELL, JUSTIN STEBBING!
VOLTAIRE : "The art of Medicine consists of amusing the patient while nature cures the disease".
even then, the new the truth, we have been found out! patient have build in defense! we are just distracting him.....
PARCELSUS : "The art of healing comes from nature and not from the physician; Therefore, the physician must start from nature with an open mind"....
And here I am throwing the kitchen sink of chemotherapy instead of Target therapy. Cure will come from the mastering of law of nature at cellular level . READ CAREFULLY! CURE IS WITH US, LET'S OPEN OUR MIND!
CREDIT TO DANIEL KRELL, JUSTIN STEBBING!
IN DEPTH INVESTIGATION, BRAIN INJURY--CRBCM
(THIS IS PART OF A PROTOCOL SUBMITTED FOR RESEARCH)
After a trauma to the brain, and in a mature brain, excitatory messages or stimuli lead to the release of Glutamate at the pre-synaptic membrane. Glutamate released forthwith, will go on to stimulate those well known post-synaptic ionotropic receptors (AMPAR and NMDAR).
The intensity of the post-synaptic stimulation is in fact related to the amount of receptors clustered in the involved region of the post-synaptic membrane, and the intensity of the ion traffic in the ionotropic channels, leading to variation in the voltage dependent activation of post synaptic events. This variation of activation and electric status linked to ion displacement has been summarized in the concept: "SYNAPTIC PLASTICITY".
Depending on the nature of subunits of the post-synaptic Receptor (content in NR2B), the post-synaptic event can be inhibitory or activating. A global positive influx of Calcium through the channels mentioned above lead ultimately to a post-synaptic phosphorylation of the powerful ERK-MAP-Kinase signal transduction pathways with significant physiological consequences.
See, when stress is the initiating event, a particular member of the MAPK family called the C-jun will be awakened up. The C-Jun terminal protein (JNK) will unveil all its might and strike by way of phosphorylation various substrates in the Nucleus, the Mitochondria and right there in the Cytosol.
In the Mitochondria, the stress and toxic induced C-jun lead to loss of MMP and induce Cytochrome C release into the Cytosol with resulting activation of the Caspase cascade which leads to Apoptosis or NEURONAL DEATH.
At Nuclear and Cytoplasmic levels, C-jun downregulate Bcl-2, (and MCL-1), up regulate BAX which are pro-Apototic moves or processes, but it also induce pro-inflammatory (TNF alpha, Interleukin 6,8) Cyclins to cause death by Necrosis. At Glial level, these pro-inflammatory cyclins leads to Neuro-Degeneration.
At CRBCM we believe that in this day in age, letting neurodegeneration set in without intervention is not only ignorant, but not responsible!!!!! We got to act...respond somehow...our leaders are holding funds and holding us back! SAY SOMETHING!! MY READERS !
FREE CPRIT MOVEMENT HAS BEEN CREATED!
(THIS IS PART OF A PROTOCOL SUBMITTED FOR RESEARCH)
After a trauma to the brain, and in a mature brain, excitatory messages or stimuli lead to the release of Glutamate at the pre-synaptic membrane. Glutamate released forthwith, will go on to stimulate those well known post-synaptic ionotropic receptors (AMPAR and NMDAR).
The intensity of the post-synaptic stimulation is in fact related to the amount of receptors clustered in the involved region of the post-synaptic membrane, and the intensity of the ion traffic in the ionotropic channels, leading to variation in the voltage dependent activation of post synaptic events. This variation of activation and electric status linked to ion displacement has been summarized in the concept: "SYNAPTIC PLASTICITY".
Depending on the nature of subunits of the post-synaptic Receptor (content in NR2B), the post-synaptic event can be inhibitory or activating. A global positive influx of Calcium through the channels mentioned above lead ultimately to a post-synaptic phosphorylation of the powerful ERK-MAP-Kinase signal transduction pathways with significant physiological consequences.
See, when stress is the initiating event, a particular member of the MAPK family called the C-jun will be awakened up. The C-Jun terminal protein (JNK) will unveil all its might and strike by way of phosphorylation various substrates in the Nucleus, the Mitochondria and right there in the Cytosol.
In the Mitochondria, the stress and toxic induced C-jun lead to loss of MMP and induce Cytochrome C release into the Cytosol with resulting activation of the Caspase cascade which leads to Apoptosis or NEURONAL DEATH.
At Nuclear and Cytoplasmic levels, C-jun downregulate Bcl-2, (and MCL-1), up regulate BAX which are pro-Apototic moves or processes, but it also induce pro-inflammatory (TNF alpha, Interleukin 6,8) Cyclins to cause death by Necrosis. At Glial level, these pro-inflammatory cyclins leads to Neuro-Degeneration.
At CRBCM we believe that in this day in age, letting neurodegeneration set in without intervention is not only ignorant, but not responsible!!!!! We got to act...respond somehow...our leaders are holding funds and holding us back! SAY SOMETHING!! MY READERS !
FREE CPRIT MOVEMENT HAS BEEN CREATED!
QUIZARTINIB ALLOWS TO BUY TIME BEFORE TRANSPLANT IN AML.
In AML patient with FLT3-ITD
46% complete response reported
27% partial response
--------------------------------------
73% total response rate per this account
IF you do not have the FLT3-ITD
32% CR
16% PR
----------------------------------
48% RR
Median duration of response 3 months for FLT3 positive
and 1.5 month for FLT3 negative
the drug is reported to be well tolerated.
*> In other Major news,
Eribulin had failed to best Xeloda overall
there was a positive trend in triple negative breast cancer which is the focus of CRBCM
*Apixaban may become a valid option for DVT treatment
since it does not require monitoring
and it is not cleared by the Kidneys and therefore could be used in kidney failure patients!
In AML patient with FLT3-ITD
46% complete response reported
27% partial response
--------------------------------------
73% total response rate per this account
IF you do not have the FLT3-ITD
32% CR
16% PR
----------------------------------
48% RR
Median duration of response 3 months for FLT3 positive
and 1.5 month for FLT3 negative
the drug is reported to be well tolerated.
*> In other Major news,
Eribulin had failed to best Xeloda overall
there was a positive trend in triple negative breast cancer which is the focus of CRBCM
*Apixaban may become a valid option for DVT treatment
since it does not require monitoring
and it is not cleared by the Kidneys and therefore could be used in kidney failure patients!
SHORT NEWS FROM ASCO POST
*For years we have been telling women that 5 years of Tamoxifen is all they needed in the treatment of ER positive breast cancer. We went on to tell them that prolonging the duration of Tamoxifen could only lead to more side effect. So it is a bit of a surprise that all of the sudden the Oncology community has quickly embraced the new 10 years being recommended without any questions raised. Had we been lying to women all this time? who has been giving Tamoxifen for 10 years behind our back?
Published results suggest : "617 recurrences in women taking Tamoxifen for 10 years Vs 711 recurrences in women treated for 5 years". Total observation time 10-14 years. SO standard today is 10 years of Tamoxifen, no question asked!
*Ponatinib is the new Darling drug in CML and Philadelphia positive ALL
In a study published by DR Cortes 267 evaluated patients
56 % of those in Chronic phase CML achieved Major Cytogenetic response (Most of these were resistant to TKI.
and 57% of those in accelerated phase achieved a major hematologic response and 34% of those in Blast phase responded.
Remember the FDA has already approved the drug!
OMACETAXINE is also active in this disease!
*POMALIDOMIDE is the other wonder but this time in Myeloma
4mg given with 20 mg of Decadron as given in the study!
Also an Oral Proteasome inhibitor MLN9708 is under study with promising results
*For Invasive breast cancer, adjuvant radiation for 3 weeks equivalent to 5 weeks per a UK study! People are still waiting for the RTOG to conclude its trial.
*Ibrutinib is the new darling drug in CLL
at 26 months, 96% progression survival in chemo-naive CLL
and 75% progression free survival in relapse/refractory CLL/SLL
*QUIZARTINIB BUY TIME TO TRANSPLANT
*For years we have been telling women that 5 years of Tamoxifen is all they needed in the treatment of ER positive breast cancer. We went on to tell them that prolonging the duration of Tamoxifen could only lead to more side effect. So it is a bit of a surprise that all of the sudden the Oncology community has quickly embraced the new 10 years being recommended without any questions raised. Had we been lying to women all this time? who has been giving Tamoxifen for 10 years behind our back?
Published results suggest : "617 recurrences in women taking Tamoxifen for 10 years Vs 711 recurrences in women treated for 5 years". Total observation time 10-14 years. SO standard today is 10 years of Tamoxifen, no question asked!
*Ponatinib is the new Darling drug in CML and Philadelphia positive ALL
In a study published by DR Cortes 267 evaluated patients
56 % of those in Chronic phase CML achieved Major Cytogenetic response (Most of these were resistant to TKI.
and 57% of those in accelerated phase achieved a major hematologic response and 34% of those in Blast phase responded.
Remember the FDA has already approved the drug!
OMACETAXINE is also active in this disease!
*POMALIDOMIDE is the other wonder but this time in Myeloma
4mg given with 20 mg of Decadron as given in the study!
Also an Oral Proteasome inhibitor MLN9708 is under study with promising results
*For Invasive breast cancer, adjuvant radiation for 3 weeks equivalent to 5 weeks per a UK study! People are still waiting for the RTOG to conclude its trial.
*Ibrutinib is the new darling drug in CLL
at 26 months, 96% progression survival in chemo-naive CLL
and 75% progression free survival in relapse/refractory CLL/SLL
*QUIZARTINIB BUY TIME TO TRANSPLANT
Study: Enzyme Plays Important Role in CML Stem Cell Reprogramming
By Dave Levitan |
January 18, 2013
Researchers have identified an enzyme that plays an important role in
the reprogramming of malignant progenitor cells in chronic myeloid
leukemia (CML). The enzyme, adenosine(Drug information on adenosine)
deaminase acting on RNA 1 (ADAR1), could represent a target for
selecting and eradicating leukemia stem cells, according to a paper published online ahead of print on December 28, 2012, in Proceedings of the National Academy of Sciences.
 A small, hypolobated megakaryocyte in a bone marrow aspirate, typical of CML; source: Difu Wu, Wikimedia CommonsThey found that increased expression of the ADAR1 p150 isoform in blast crisis CML could be related to inflammatory pathway activation, including cytokines and tumor necrosis factors. The investigators also examined whether limiting expression of ADAR1 could affect the self-renewal capacity of leukemia stem cells. They transplanted human CML cells with ADAR1 expression knocked down into mice and compared with control cells; they found an impaired ability to self-renew in the leukemia stem cells. “Although leukemic burden was not diminished significantly, the [leukemia stem cell] self-renewal capacity was irrevocably reduced by ADAR1 knockdown,” the authors wrote. Together, these data suggest that inflammatory mediator-driven expression of ADAR1 contributes to CML progression. In a press release, Dr. Jamieson noted that this adds further weight to inflammation as “an essential driver of cancer relapse and therapeutic resistance.” In particular, the importance of ADAR1 in CML represents a clear target for therapeutic strategies. “ADAR1 is an enzyme that we may be able to specifically target with a small molecule inhibitor, an approach we have already used effectively with other inhibitors,” Dr. Jamieson said. “If we can block the capacity of leukemia stem cells to use ADAR1, if we can knock down that pathway, maybe we can put stem cells back on the right track and stop malignant cloning.” | |
Thursday, January 24, 2013
EVENTS GOVERNING CELLULAR LIFE
Overall, life at the cellular level enters a new phase as the sperm enters the Ovocyte, here the activity of life is driven by Nuclear events; cell division (and motility of cells) is the driving trend of forces to be amplified and the Embryo formation (Embryogenesis) is the ultimate objective. As the embryo is being formed, there a transition of forces from proliferation to tissue differentiation. This transition from PROLIFERATION with an AMPLIFIED MITOSIS AND MOVEMENT OF CELL FOR POSITIONING IN THE BODY OF THE EMBRYO characterizes early life and is driven by promoter genes, amplified pathways, driven metabolism at Ribosome, histone, and genetic levels. The processing of internal and external stimuli triggers the flow of forces. A change of stimuli eventually occurs, followed by responses imposed by growth factors, variation in needs, and overall cellular communications, and soon enough the trend of forces is toward differentiation. In order to protect future life, SANCTUARY tissues are created to keep DIVISION POTENTIAL ACTIVE (Ovaries, testicles keep proliferative potential and controlled activity). DIFFERENTIATION becomes the name of the game and is AMPLIFIED. To commit resouces to this activity exclusively, proliferation is shut down at genes, enzymes, and chromatin levels to shield proliferation related promoters. Tissue differentiation is pushed to allow life, survival and adaptation leading to races and other phenotypic differentiation. Each step is amplified to perfection (whatever the perfection is or implied). REPRESSION OF A GENE THAT NORMALLY SHOULD BE AMPLIFIED OR STAT TRANSCRIPTION UNDER THESE CIRCUMSTANCES, MEANS ONCOGENIC SUPPRESSION AND A SIGN OF MALIGNANT PROLIFERATION AND POTENTIALLY ASSOCIATED RESUMPTION OF MITOSIS AND MIGRATION (METASTASIS). IT IS ALSO ASSOCIATED WITH LOSS OF DIFFERENTIATION AND ATYPICAL PHENOTYPIC TRANSFORMATION.
This implies that whenever cancerous trending forces are triggered, they happen in a cell which will de-differentiate, but will switch to proliferation, mobility and perfect for survival and adaptation. A cell trained to escape mechanism of local and distant defense, and full of survival and adaptation skills! The ESCAPE include eluding local attacks by change in receptors, glycocalyx and level of pump and MDR gene expression, but also distant (escape Anoikis) cell rejection.
Cancer is a formidable opponent with so many opportunities for target intervention if you know where to touch or block the flow of things for the cure. The timing of change of the flow of forces/trends provides as much opportunity as a check point. One may want to target these events.
CURE IS POSSIBLE WHEN YOU LOOK AT THIS WAY OF THINKING!
WITH EVERY LAW COMES A SET OF SPECIFIC GENES, ENZYMES, REGULATORS, PATHWAYS AND POTENTIAL DRIVERS, WE WILL HUNT THEM, STUDY THEM AND DEVELOP TARGET THERAPY OVER THE NEXT FEW YEARS, FEEL FREE TO DO THE SAME, THE RACE IS ON!!!!!
Overall, life at the cellular level enters a new phase as the sperm enters the Ovocyte, here the activity of life is driven by Nuclear events; cell division (and motility of cells) is the driving trend of forces to be amplified and the Embryo formation (Embryogenesis) is the ultimate objective. As the embryo is being formed, there a transition of forces from proliferation to tissue differentiation. This transition from PROLIFERATION with an AMPLIFIED MITOSIS AND MOVEMENT OF CELL FOR POSITIONING IN THE BODY OF THE EMBRYO characterizes early life and is driven by promoter genes, amplified pathways, driven metabolism at Ribosome, histone, and genetic levels. The processing of internal and external stimuli triggers the flow of forces. A change of stimuli eventually occurs, followed by responses imposed by growth factors, variation in needs, and overall cellular communications, and soon enough the trend of forces is toward differentiation. In order to protect future life, SANCTUARY tissues are created to keep DIVISION POTENTIAL ACTIVE (Ovaries, testicles keep proliferative potential and controlled activity). DIFFERENTIATION becomes the name of the game and is AMPLIFIED. To commit resouces to this activity exclusively, proliferation is shut down at genes, enzymes, and chromatin levels to shield proliferation related promoters. Tissue differentiation is pushed to allow life, survival and adaptation leading to races and other phenotypic differentiation. Each step is amplified to perfection (whatever the perfection is or implied). REPRESSION OF A GENE THAT NORMALLY SHOULD BE AMPLIFIED OR STAT TRANSCRIPTION UNDER THESE CIRCUMSTANCES, MEANS ONCOGENIC SUPPRESSION AND A SIGN OF MALIGNANT PROLIFERATION AND POTENTIALLY ASSOCIATED RESUMPTION OF MITOSIS AND MIGRATION (METASTASIS). IT IS ALSO ASSOCIATED WITH LOSS OF DIFFERENTIATION AND ATYPICAL PHENOTYPIC TRANSFORMATION.
This implies that whenever cancerous trending forces are triggered, they happen in a cell which will de-differentiate, but will switch to proliferation, mobility and perfect for survival and adaptation. A cell trained to escape mechanism of local and distant defense, and full of survival and adaptation skills! The ESCAPE include eluding local attacks by change in receptors, glycocalyx and level of pump and MDR gene expression, but also distant (escape Anoikis) cell rejection.
Cancer is a formidable opponent with so many opportunities for target intervention if you know where to touch or block the flow of things for the cure. The timing of change of the flow of forces/trends provides as much opportunity as a check point. One may want to target these events.
CURE IS POSSIBLE WHEN YOU LOOK AT THIS WAY OF THINKING!
WITH EVERY LAW COMES A SET OF SPECIFIC GENES, ENZYMES, REGULATORS, PATHWAYS AND POTENTIAL DRIVERS, WE WILL HUNT THEM, STUDY THEM AND DEVELOP TARGET THERAPY OVER THE NEXT FEW YEARS, FEEL FREE TO DO THE SAME, THE RACE IS ON!!!!!
EXPERIMENT SUPPORTING THE 4TH LAW.
TAKE YOUR SHOES OFF RIGHT NOW, WEAR THEM BACK BACKWARD OR SIMPLY PUT, WEAR THE RIGHT SHOE ON THE LEFT FOOT, AND PUT THE LEFT SHOE ON THE RIGHT FOOT AND SIT FOR A WHILE. THE BODY HAS ALL THE SUDDEN A NEW SITUATION, THE ABNORMAL SENSATION WILL START AND GROW ON YOU AND WILL NOT LET YOU FORGET IT UNTIL YOU EITHER CORRECT THE ISSUE , DECIDE TO STAY AND ADAPT. SUFFICE IS TO SAY THE BAD SENSATION AND ULTIMATELY DISCOMFORT WILL AMPLIFY AND GROW ON YOU.
ANY NEW STIMULATION WILL GROW AND AMPLIFY. AT CELLULAR LEVEL, GENE TRANSCRIPTION AND NUCLEAR EVENTS LEAD THE WAY. ANY NEW TREND ADOPTED BY THE CELL IN RESPONSE TO SOME EVENT, WILL NEED AMPLIFICATION AND SUSTENANCE TO BE A DRIVER EVENT...
It is because of the 4th law that a coffee will not taste the same at the time it was cooked versus 8 hours later! Things will keep happening in that cup whether you like it or not! That is nature!
TAKE YOUR SHOES OFF RIGHT NOW, WEAR THEM BACK BACKWARD OR SIMPLY PUT, WEAR THE RIGHT SHOE ON THE LEFT FOOT, AND PUT THE LEFT SHOE ON THE RIGHT FOOT AND SIT FOR A WHILE. THE BODY HAS ALL THE SUDDEN A NEW SITUATION, THE ABNORMAL SENSATION WILL START AND GROW ON YOU AND WILL NOT LET YOU FORGET IT UNTIL YOU EITHER CORRECT THE ISSUE , DECIDE TO STAY AND ADAPT. SUFFICE IS TO SAY THE BAD SENSATION AND ULTIMATELY DISCOMFORT WILL AMPLIFY AND GROW ON YOU.
ANY NEW STIMULATION WILL GROW AND AMPLIFY. AT CELLULAR LEVEL, GENE TRANSCRIPTION AND NUCLEAR EVENTS LEAD THE WAY. ANY NEW TREND ADOPTED BY THE CELL IN RESPONSE TO SOME EVENT, WILL NEED AMPLIFICATION AND SUSTENANCE TO BE A DRIVER EVENT...
It is because of the 4th law that a coffee will not taste the same at the time it was cooked versus 8 hours later! Things will keep happening in that cup whether you like it or not! That is nature!
COROLLARY POTENTIAL RESULTING FROM THE 3RD LAW
As DIFFERENTIATION wanes and is finally shut down by a complete silencing of differentiation genes, PROLIFERATION gene expression is amplified through transcription gene and and promoter silencing for differentiation, and promoter stimulation for the proliferation trends and forces. the FORCE AMPLIFICATION AND IMPLEMENTATION LAW enter into effect (4TH LAW OF NATURE)
Any general elected trend of forces need to be amplified, protected, and fully implemented. The implementation should however follow the 5th law, the most important law in the life of the cell, LIFE PRESERVATION. THIS LAW WILL LEAD TO THE 6TH LAW. LAW OF ADOPTION, ADAPTATION AND CONFORMITY OR SURVIVAL LAW.
PROLIFERATION HAS A TRUE COROLLARY EVENT. Indeed during proliferation, the cell show it can return to its young form which means potential of return to totipotential cell. And in some instances, with proliferation comes totipotentiality which is observed in Teratomas. This happens when a set of genes were not fully silenced due to heterogeneity or mutation of genes and defective silencing. A second corollary to the 3rd law, is the return to mobility because among the gene of proliferation, many will impact the Cytoskelton and protection against Anoikis.
Each law and Corollaries will be discussed with genes involved as we move forward.
As DIFFERENTIATION wanes and is finally shut down by a complete silencing of differentiation genes, PROLIFERATION gene expression is amplified through transcription gene and and promoter silencing for differentiation, and promoter stimulation for the proliferation trends and forces. the FORCE AMPLIFICATION AND IMPLEMENTATION LAW enter into effect (4TH LAW OF NATURE)
Any general elected trend of forces need to be amplified, protected, and fully implemented. The implementation should however follow the 5th law, the most important law in the life of the cell, LIFE PRESERVATION. THIS LAW WILL LEAD TO THE 6TH LAW. LAW OF ADOPTION, ADAPTATION AND CONFORMITY OR SURVIVAL LAW.
PROLIFERATION HAS A TRUE COROLLARY EVENT. Indeed during proliferation, the cell show it can return to its young form which means potential of return to totipotential cell. And in some instances, with proliferation comes totipotentiality which is observed in Teratomas. This happens when a set of genes were not fully silenced due to heterogeneity or mutation of genes and defective silencing. A second corollary to the 3rd law, is the return to mobility because among the gene of proliferation, many will impact the Cytoskelton and protection against Anoikis.
Each law and Corollaries will be discussed with genes involved as we move forward.
Wednesday, January 23, 2013
AMD–Aspirin Link: Latest Hint Not the Last Word
Drug & Reference Information
Australian researchers analyzing data from a
large, population-based eye study reported this week finding a
statistically significant association between 15 years of regular
aspirin use and the development of neovascular age-related macular
degeneration (AMD).
Compared with others in the Blue Mountains Eye Study, participants who reported using aspirin at least once a week were twice as likely as nonusers to develop neovascular AMD in the subsequent 15 years, according to the report published online January 21 by JAMA Internal Medicine (formerly Archives of Neurology).
The odds ratio for developing wet AMD was 2.46 among the aspirin users (95% confidence interval [CI], 1.25 - 4.83), after adjustment for several possible confounding variables (age, sex, smoking, history of cardiovascular disease, systolic blood pressure, and body mass index). There was no such association for geographic atrophy, Gerald Liew, PhD, from the Centre for Vision Research, Department of Ophthalmology, University of Sydney, and the Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia, and colleagues report.
The report marked the third large study in the last year to suggest an association between aspirin use and neovascular AMD. Most recently, similar figures were reported for an analysis of data from the Beaver Dam Eye Study.
Frightened to Death?
Continuing publicity about the studies has heightened concerns that elderly people might be frightened literally to their deaths if they stop taking the aspirin they need to prevent heart attack or stroke, said Emily Y. Chew, MD, PhD, deputy director of the Division of Epidemiology and Clinical Applications at the National Eye Institute, Bethesda, Maryland.
"It's a public health issue, because it's clear that the protective effect from aspirin is high. People are going to die because of not taking aspirin for their heart disease. My patients are scared to death right now," Dr. Chew said to Medscape Medical News.
Even if aspirin use were confirmed as an AMD risk factor using more robust study data, Dr. Chew said, it already is apparent that the risk would be quite small in absolute terms, at about 1% for aspirin users, and 0.5% for nonusers.
" 'Doubling' the risk sounds terrible," she said. "But the real risk for late-stage AMD in these people who took aspirin [in the Beaver Dam Study] is 1%, vs half a percent for those who didn't, which is not clinically meaningful."
Dr. Chew noted that her preliminary look at data from a carefully controlled clinical trial that she leads found no extra risk for AMD in aspirin users. On the contrary, aspirin users in the second Age-Related Eye Diseases Study (AREDS2), in which Dr. Chew is principal investigator, had a lower risk for neovascular AMD than control patients, with an odds ratio of 0.61 (95% CI, 0.49 - 0.75; P < .0001), she found in this early analysis, which has been presented at meetings but not yet submitted for publication.
A senior coauthor of the current study acknowledged that the published evidence for an aspirin–AMD link remains inconclusive.
"Our study only generates a hypothesis of a possible side effect of aspirin use, but this needs to be confirmed by future studies. However, any single study adds to the evidence that we have so far," said Jie Jin Wang, PhD, also from the Centre for Vision Research, Department of Ophthalmology, University of Sydney, and the Centre for Eye Research Australia, University of Melbourne, in an interview with Medscape Medical News.
In a commentary that accompanied the Australian study, 2 cardiologists, Sanjay Kaul, MD, and George A. Diamond, MD, from the Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California, urged clinicians to be move cautiously in response as further research continues.
"From a purely science-of-medicine perspective, the strength of evidence is not sufficiently robust to be clinically directive," they write. "However, from an art-of-medicine perspective, based on the limited amount of available evidence, there are some courses of action available to the thoughtful clinician."
They suggest a middle course, individualized to the patient's needs:
JAMA Intern Med. Published online January 21, 2013. Article full text, Commentary full text
Compared with others in the Blue Mountains Eye Study, participants who reported using aspirin at least once a week were twice as likely as nonusers to develop neovascular AMD in the subsequent 15 years, according to the report published online January 21 by JAMA Internal Medicine (formerly Archives of Neurology).
The odds ratio for developing wet AMD was 2.46 among the aspirin users (95% confidence interval [CI], 1.25 - 4.83), after adjustment for several possible confounding variables (age, sex, smoking, history of cardiovascular disease, systolic blood pressure, and body mass index). There was no such association for geographic atrophy, Gerald Liew, PhD, from the Centre for Vision Research, Department of Ophthalmology, University of Sydney, and the Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia, and colleagues report.
The report marked the third large study in the last year to suggest an association between aspirin use and neovascular AMD. Most recently, similar figures were reported for an analysis of data from the Beaver Dam Eye Study.
Frightened to Death?
Continuing publicity about the studies has heightened concerns that elderly people might be frightened literally to their deaths if they stop taking the aspirin they need to prevent heart attack or stroke, said Emily Y. Chew, MD, PhD, deputy director of the Division of Epidemiology and Clinical Applications at the National Eye Institute, Bethesda, Maryland.
"It's a public health issue, because it's clear that the protective effect from aspirin is high. People are going to die because of not taking aspirin for their heart disease. My patients are scared to death right now," Dr. Chew said to Medscape Medical News.
Even if aspirin use were confirmed as an AMD risk factor using more robust study data, Dr. Chew said, it already is apparent that the risk would be quite small in absolute terms, at about 1% for aspirin users, and 0.5% for nonusers.
" 'Doubling' the risk sounds terrible," she said. "But the real risk for late-stage AMD in these people who took aspirin [in the Beaver Dam Study] is 1%, vs half a percent for those who didn't, which is not clinically meaningful."
Dr. Chew noted that her preliminary look at data from a carefully controlled clinical trial that she leads found no extra risk for AMD in aspirin users. On the contrary, aspirin users in the second Age-Related Eye Diseases Study (AREDS2), in which Dr. Chew is principal investigator, had a lower risk for neovascular AMD than control patients, with an odds ratio of 0.61 (95% CI, 0.49 - 0.75; P < .0001), she found in this early analysis, which has been presented at meetings but not yet submitted for publication.
A senior coauthor of the current study acknowledged that the published evidence for an aspirin–AMD link remains inconclusive.
"Our study only generates a hypothesis of a possible side effect of aspirin use, but this needs to be confirmed by future studies. However, any single study adds to the evidence that we have so far," said Jie Jin Wang, PhD, also from the Centre for Vision Research, Department of Ophthalmology, University of Sydney, and the Centre for Eye Research Australia, University of Melbourne, in an interview with Medscape Medical News.
In a commentary that accompanied the Australian study, 2 cardiologists, Sanjay Kaul, MD, and George A. Diamond, MD, from the Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California, urged clinicians to be move cautiously in response as further research continues.
"From a purely science-of-medicine perspective, the strength of evidence is not sufficiently robust to be clinically directive," they write. "However, from an art-of-medicine perspective, based on the limited amount of available evidence, there are some courses of action available to the thoughtful clinician."
They suggest a middle course, individualized to the patient's needs:
- Secondary prevention: Maintain the status quo, because there is strong evidence that its benefits outweigh the risks.
- Primary prevention: Carefully weigh potential risks and benefits. In patients who, under current guidelines, are eligible for treatment because of their 10-year risk of myocardial infarction or stroke, "the presence or absence of strong risk factors for neovascular AMD might tilt treatment decisions in one direction or the other."
- Other uses of aspirin: Be cautious in recommending long-term aspirin to other patients, such as those requiring pain control.
JAMA Intern Med. Published online January 21, 2013. Article full text, Commentary full text
Hello Clement Albert, (or Dr Kankonde) see also ubetoo.com for free listening to over 400 original songs!
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WATCH OUT FOR HYPERTRIGLYCERDEMIA AND PANCREATITIS IN THE EVEROLIMUS TAKING PATIENT AND PROMPTLY INSTITUTE FENOFIBRATE AND REDUCE THE DOSAGE TO SEE IF THIS IS CONTROLLED.
OTHER SIDE EFFECT STOMATITIS, FATIGUE, RASH DIARRHEA AND UPPER RESPIRATORY INFECTIONS. ANEMIA AND HYPERGLYCEMIA HAVE BEEN REPORTED.
OTHER SIDE EFFECT STOMATITIS, FATIGUE, RASH DIARRHEA AND UPPER RESPIRATORY INFECTIONS. ANEMIA AND HYPERGLYCEMIA HAVE BEEN REPORTED.
NOMENCLATURE OF GENES INVOLVED IN CELL PROLIFERATION (PART III)
1. MELK, PK 38
---------Thanks to Jean-Pierre Tassan who published this:
"
1. MELK, PK 38
---------Thanks to Jean-Pierre Tassan who published this:
"
| Note | MELK (Maternal Embryonic Leucine zipper Kinase) belongs to the CAMK serine/threonine protein kinase superfamily. Melk is a protein serine/threonine kinase that is maximally active during mitosis. It is involved in diverse functions such as cell cycle, cytokinesis, mRNA splicing and apoptosis. | |||||
| Description | The full-length protein is 651 amino acids with an estimated molecular weight of approximately 74,5 kDa. | |||||
| Expression | MELK is expressed in cells of various tissue origins. MELK is highly expressed in oocytes, spermatogonia and embryos, which is indicative of a role in the germ-cell development. MELK is highly expressed in a large panel of cancers MELK expression is dependant on cell transformation (Gray et al., 2005). Its expression is strongly dependant on cell-cycle: MELK is undetectable in cells which have exited cell cycle (Badouel et al., 2010). | |||||
| Localisation | Cytoplasm, nucleus and cell cortex. | |||||
| Function | The exact function of MELK is currently unknown, however MELK was shown to be involved in cell cycle progression via the protein phosphatase CDC25B phosphorylation (Blot et al., 2002), in cytokinesis (Le Page et al., 2011), in apoptosis via its interaction with the Bcl-2 family of proapoptotic genes (Lin et al., 2007) and apoptosis signal-regulating kinase (ASK1) (Jung et al., 2008) and in inhibition of mRNA splicing during mitosis via its association with NIPP1 (Vulsteke et al., 2004). MELK function is required for mammary tumorigenesis in vivo (Hebbard et al., 2010). | |||||
| Homology | MELK belongs to the
Kin1/PAR-1/MARK family of protein kinases found from yeast to human.
These kinases are involved in cell polarity, dynamics of microtubules
and intracellular signalisation. ================================== This kinase is the real deal, Choi S suggested it may confer resistance to 5_FU and Radiation in colorectal cancer. It is located at 9p13 In Breast Cancer, it is bad news (prognosis) because it blocks Apoptosis through Bcl-GL (Fau is an associate). =========================================================== 2. CM2 or Minichromosomal Maintenance Complex, location 3q21 regulated by CDC2 and 7 of which we spoke about as needed for cell division this one initiate genome replication, marking proliferation |
FERTILITY PRESERVATION IN YOUNG ONCOLOGY PATIENTS.
We at CRBCM appreciate the article in a recent JNCNN publication :" Optimizing fertility preservation practices for adolescent and young adult cancer patients" by Rebecca Johnson and Leah Kroon.
The article suggest that there 70, 000 young people with cancer (age 15-39) who undergo chemotherapy with significant risk of loss of fertility. And offering them fertility preservation is crucial and obligated step in their management. With the advancement in cancer treatment, over 70 to 80% survive after cancer and have to live with long term psychological distress from infertility.
54% of Oncologists reportedly do not discuss this risk.
80% of Male patients and 48% of female patients recall having discussed the issue with their Oncologist
which is a shame!
Barriers to the issue:
1. Availability of the service
2. Integration of the practice of referring the patient into the routine of the Oncology office
3. knowing that sperm collection can occur while patient is still inpatient
4. Fear of delay to therapy, particularly in female where Ovarian stimulation requires 2 weeks delay/lag of time
We look at this as an integral part of a Survivorship Center.
We at CRBCM appreciate the article in a recent JNCNN publication :" Optimizing fertility preservation practices for adolescent and young adult cancer patients" by Rebecca Johnson and Leah Kroon.
The article suggest that there 70, 000 young people with cancer (age 15-39) who undergo chemotherapy with significant risk of loss of fertility. And offering them fertility preservation is crucial and obligated step in their management. With the advancement in cancer treatment, over 70 to 80% survive after cancer and have to live with long term psychological distress from infertility.
54% of Oncologists reportedly do not discuss this risk.
80% of Male patients and 48% of female patients recall having discussed the issue with their Oncologist
which is a shame!
Barriers to the issue:
1. Availability of the service
2. Integration of the practice of referring the patient into the routine of the Oncology office
3. knowing that sperm collection can occur while patient is still inpatient
4. Fear of delay to therapy, particularly in female where Ovarian stimulation requires 2 weeks delay/lag of time
We look at this as an integral part of a Survivorship Center.
Tuesday, January 22, 2013
The issue of clinical research and participation in clinical trials
Hello
again. I'm John Marshall for Medscape. I want to tackle the beginning
of what will be a very important issue for 2013 and beyond, the issue of
clinical research and participation in clinical trials.
Go back to 2012. If I said, "99%," you would know what I am talking about. If I told you the number "47%," you would know what I am talking about, particularly here in Washington, DC. These are prominent numbers. But if I told you the number "97%," would you know what I am talking about?
That is the number of patients in the United States with cancer who receive the so-called standard of care, meaning that 3% of patients go on clinical trials and 97% receive standard of care -- lemmings that are following the one before them, doing what we did years ago. There is no advancement, no progress. We know the shortcomings of these treatments, but for whatever reason, there is an element of safety and security or a complicated environment where patients are not demanding clinical trials and they are not being offered clinical trials.
So, this year, as part of our Ruesch Center for the Cure of Gastrointestinal Cancers Annual Symposium: Fighting a Smarter War Against Cancer, we tried to tackle this. We tried to bring everybody together in a meeting about a month ago, to get all the key stakeholders -- from the US Food and Drug Administration (FDA), the Cancer Therapy Evaluation Program (CTEP), and industry to patient representatives, patients, and academic folks -- together and ask why we aren't doing a better job with clinical trials. We had a fascinating day in discovery on this and I think some answers may have emerged.
Let's first look at what the priorities are for the different stakeholders. Let's start with the FDA. Their priority is safety and efficacy. That is what they are charged to do. The priority of the payers, the ones funding all the clinical treatment as well as paying for clinical research, is to control costs. Their job is to control cost in an ever more expensive world. Sponsors, pharmaceutical companies, and CTEP want access to high volumes of patients and high-quality data. They want a crisp, pure world in which they can test their drugs to get things moving forward. In community oncology, where most cancer care is delivered, I think you would argue that their stake -- their priority -- is going to be high-quality, highly efficient care. That is success in the community. In academic oncology, we are judged by how many patients go on clinical trials. What percentage of patients can we put on a clinical trial? We do a little bit better in a comprehensive cancer center (10%-20%), but it's nowhere where it needs to be.
As for patients, nobody ever asks them what their motivation is and why they would want to do this. So, at this meeting, we asked them, and it was pretty clear that they don't see what's in it for them to go on one of these clinical trials. They are very put off by the whole placebo thing, even though they don't have a good understanding of what is out there. They have these visions of what this means. They don't see how they are a part of it, how they are helping to drive the answer. We have done a terrible job of educating our public. I think we have done a terrible job of designing clinical trials that have significant value to them. We do these great big clinical trials that result in very small improvements in outcome, which, honestly, are a big waste of time.
We had Deborah Schrag give a wonderful talk on her study in rectal cancer, which challenges the need for radiation in rectal cancer.[1,2] Here is a big study that no one is going to fund -- maybe the federal government, depending on how steeply we go off the cliff -- that is trying to remove a therapy that may be unnecessary in the treatment of colorectal cancers, namely radiation. She spoke about how difficult that study was to put into play. This is a very interesting study that would make things easier for patients, but it took more than a year for the study to get up and running.
There are so many barriers out there. One of the things that really emerged for me was that we need to start over and think about this in a different way. We have some good leads. Take the I-SPY2 clinical trial in breast cancer.[3] This is a great new model for us, a parent protocol where molecular profiling is done and treatment assignment is based on an individual's molecular profile based on our best understanding of the molecular biology.
I think that every single major disease, maybe every disease,
needs exactly this type of parent protocol. In order to do this, we are
going to need better and quicker pathology. We need to change a few laws
around molecular profiling -- the timing, who pays for it, and all of
those things. I think it will require a more centralized pharmacy,
because if everybody is going to participate in this, all of us can't
keep all of these drugs on the shelf. We would need some sort of
centralized management for access to investigational drugs throughout
the community, not just at comprehensive cancer centers but throughout
our medical community. I think the opportunity here is ripe, because
many of our healthcare systems are merging and coming together. One of
the things that we can do as not just academic ivory towers but
corporations is begin to provide the community with this type of
centralized tissue analysis, pharmacy support, and clinical research
support. Then, a patient, no matter where he comes into the system, can
get that tumor analysis. He can get access to what we think is the best
new therapy -- not just improving things a little bit, but trying to
make major leaps forward.
I don't think we are too far away from where we need to be. We have the conceptual protocols in breast cancer and some new ones in lung cancer. I think we need to develop them in colon cancer, pancreas cancer, gastric cancer, and hepatocellular cancer in the gastrointestinal world, and then split the cancers into their individual types and treat patients according to our best guess at the moment, tagging it with drug development and moving forward. It will be biomarker co-development. We will increase our accrual rate from the puny 3% up to 25%, ask good questions, answer them quickly, and then move on.
I think the future is bright for us in clinical research and cancer medicine. It will take some cooperation, but I think that together with our patient partners, we can drive this forward. Looking forward to a bright 2013, I'm John Marshall for Medscape.
Go back to 2012. If I said, "99%," you would know what I am talking about. If I told you the number "47%," you would know what I am talking about, particularly here in Washington, DC. These are prominent numbers. But if I told you the number "97%," would you know what I am talking about?
That is the number of patients in the United States with cancer who receive the so-called standard of care, meaning that 3% of patients go on clinical trials and 97% receive standard of care -- lemmings that are following the one before them, doing what we did years ago. There is no advancement, no progress. We know the shortcomings of these treatments, but for whatever reason, there is an element of safety and security or a complicated environment where patients are not demanding clinical trials and they are not being offered clinical trials.
So, this year, as part of our Ruesch Center for the Cure of Gastrointestinal Cancers Annual Symposium: Fighting a Smarter War Against Cancer, we tried to tackle this. We tried to bring everybody together in a meeting about a month ago, to get all the key stakeholders -- from the US Food and Drug Administration (FDA), the Cancer Therapy Evaluation Program (CTEP), and industry to patient representatives, patients, and academic folks -- together and ask why we aren't doing a better job with clinical trials. We had a fascinating day in discovery on this and I think some answers may have emerged.
Let's first look at what the priorities are for the different stakeholders. Let's start with the FDA. Their priority is safety and efficacy. That is what they are charged to do. The priority of the payers, the ones funding all the clinical treatment as well as paying for clinical research, is to control costs. Their job is to control cost in an ever more expensive world. Sponsors, pharmaceutical companies, and CTEP want access to high volumes of patients and high-quality data. They want a crisp, pure world in which they can test their drugs to get things moving forward. In community oncology, where most cancer care is delivered, I think you would argue that their stake -- their priority -- is going to be high-quality, highly efficient care. That is success in the community. In academic oncology, we are judged by how many patients go on clinical trials. What percentage of patients can we put on a clinical trial? We do a little bit better in a comprehensive cancer center (10%-20%), but it's nowhere where it needs to be.
As for patients, nobody ever asks them what their motivation is and why they would want to do this. So, at this meeting, we asked them, and it was pretty clear that they don't see what's in it for them to go on one of these clinical trials. They are very put off by the whole placebo thing, even though they don't have a good understanding of what is out there. They have these visions of what this means. They don't see how they are a part of it, how they are helping to drive the answer. We have done a terrible job of educating our public. I think we have done a terrible job of designing clinical trials that have significant value to them. We do these great big clinical trials that result in very small improvements in outcome, which, honestly, are a big waste of time.
We had Deborah Schrag give a wonderful talk on her study in rectal cancer, which challenges the need for radiation in rectal cancer.[1,2] Here is a big study that no one is going to fund -- maybe the federal government, depending on how steeply we go off the cliff -- that is trying to remove a therapy that may be unnecessary in the treatment of colorectal cancers, namely radiation. She spoke about how difficult that study was to put into play. This is a very interesting study that would make things easier for patients, but it took more than a year for the study to get up and running.
There are so many barriers out there. One of the things that really emerged for me was that we need to start over and think about this in a different way. We have some good leads. Take the I-SPY2 clinical trial in breast cancer.[3] This is a great new model for us, a parent protocol where molecular profiling is done and treatment assignment is based on an individual's molecular profile based on our best understanding of the molecular biology.
I don't think we are too far away from where we need to be. We have the conceptual protocols in breast cancer and some new ones in lung cancer. I think we need to develop them in colon cancer, pancreas cancer, gastric cancer, and hepatocellular cancer in the gastrointestinal world, and then split the cancers into their individual types and treat patients according to our best guess at the moment, tagging it with drug development and moving forward. It will be biomarker co-development. We will increase our accrual rate from the puny 3% up to 25%, ask good questions, answer them quickly, and then move on.
I think the future is bright for us in clinical research and cancer medicine. It will take some cooperation, but I think that together with our patient partners, we can drive this forward. Looking forward to a bright 2013, I'm John Marshall for Medscape.
Latest in Hematology-Oncology
Medscape Oncology © 2013
WebMD, LLC
Cite this article: Why Are Only 3% of US Cancer Patients in Clinical Trials? Medscape. Jan 17, 2013.
Most Popular Articles
According to ONCOLOGIST/HEMATOLOGISTS
ARSENIC TRIOXIDE COULD SIGNIFICANTLY EXPAND ITS ROLE IN CANCER TREATMENT. AND VITAMIN C AND MICROHYDRIN COULD COME AT THE RESCUE.
Cancer cure is through death of cancer cell. To date, the main way of death for cancer cellis
through Caspase activation cascade. In most cells, we know the main
way the activation of Caspase occurs. That is Cytochrome C is naturally
anchored at the membrane inside the Mitochondria. The Anchor is in fact
a chemical bonding or attachment through electrons like molecules do
attach to each other. We believe there, Cytochrome C is attached to a
Cardiolipin which is part of lipid of the membrane. Just imagine
another molecule showing up with free electron, the free electron could
attract and pull the one involved in the attachment and break free the
Cytochrome C. Cytochrome C electron no longer attached comes out and
activate the Caspase (mostly Caspase 9 which eventually activates
members of its family) and there start the Caspase work to coagulate DNA
and genes start breaking leading to cancer cell death. One of molecule
that produces such disturbing free electrons, is Arsenic Trioxide.
This delivery of free electrons by arsenic trioxide is not limited to
the mitochondria. It occurs through the cytosol (liquid milieu of the
cell) disrupting many cellular pathways, delivering global intracellular
disruption. ( for those savvy people, do remember that the " breaking"
of the anchor could be induced from outside the Mitochondrial membrane
through the AKT or Bax effect--this is where Bcl-2 negative effect is
the strongest ) arsenic trioxide
This global disruption has been established to treat Acute Promyelocytic Leukemia (APL) (by the way, Chinese researchers lead the way on this one). Frankly speaking, this "Global disruption"can be used in any cancer. The problem is that it can occur in any cell, including our normal cells. Giving caution to the amount you use because of a narrow safety index.
Vitamin C and Microhydryn have also free electron, that is why they can cool down free radicals and therefore are called Anti-Oxydants . The free electrons of these compounds seem to add to those of Arsenic Trioxide to Increase toxicity to the cancer cell. It is worth mentioning that, at the DNA level, these free electron break the strand, triggering our first law (activation of P53 and stoppage of cell cycle).
3 main problems
1. Good and bad pathways are stopped, mitigating the effects of global destruction.
2. (non selectivity) Good and bad cells are killed. This effect is worse in patients with poor reserve of free electron clearing molecules (Gluthation based, Superoxide based and others). (CAUTION TO EVERYONE)
3. Arsenic is hard to get rid of, and chronic exposure signs will result.
But frankly speaking, you can use this to kill any Cancer. Research will continue at CRBCM no matter what!
Of Note: Use of this information outside of the topic discussed herein, is not endorsed by the CRBCM
This global disruption has been established to treat Acute Promyelocytic Leukemia (APL) (by the way, Chinese researchers lead the way on this one). Frankly speaking, this "Global disruption"can be used in any cancer. The problem is that it can occur in any cell, including our normal cells. Giving caution to the amount you use because of a narrow safety index.
Vitamin C and Microhydryn have also free electron, that is why they can cool down free radicals and therefore are called Anti-Oxydants . The free electrons of these compounds seem to add to those of Arsenic Trioxide to Increase toxicity to the cancer cell. It is worth mentioning that, at the DNA level, these free electron break the strand, triggering our first law (activation of P53 and stoppage of cell cycle).
3 main problems
1. Good and bad pathways are stopped, mitigating the effects of global destruction.
2. (non selectivity) Good and bad cells are killed. This effect is worse in patients with poor reserve of free electron clearing molecules (Gluthation based, Superoxide based and others). (CAUTION TO EVERYONE)
3. Arsenic is hard to get rid of, and chronic exposure signs will result.
But frankly speaking, you can use this to kill any Cancer. Research will continue at CRBCM no matter what!
Of Note: Use of this information outside of the topic discussed herein, is not endorsed by the CRBCM
NOMENCLATURE OF GENES DISCUSSED IN THE 3RD LAW (CONTINUED)
5. E2F1 VERY IMPORTANT GENE
ITS PROTEIN PROMOTES CD2AP TO AFFECT T CELL FUNCTION AND FUNCTION OF PODOCYTES, DISTURBANCE THEREFORE WILL AFFECT THE KIDNEY IN THE HOST.
IT IS REPRESSED BY THE RETINOBLASTOMA PROTEIN AND LEAD TO SENESCENECE
WHEN INVOLVED IN THE CDK1 PATHWAYS IT IS ALSO REPRESSED. IT IS A VERSATILE GENE OF WHICH PROTEIN IMPORTANT IN CELL CYCLE HAS FUNCTION VARYING WITH ITS POSITION. IT IS KNOWN TO BE AT THE ESTROGEN RECEPTOR.
YOU CANNOT TARGET THIS GENE AND COME UP EMPTY. HMGA GENE INCREASES THIS E2F1. IT HAS INTERACTION WITH SENESCENT CHROMATIN.
6. GEMININ
Geminin therefore is an important player in ensuring that one and only one round of replication occurs during each cell cycle. (WIKIPEDIA)
ITS PROTEIN PROMOTES CD2AP TO AFFECT T CELL FUNCTION AND FUNCTION OF PODOCYTES, DISTURBANCE THEREFORE WILL AFFECT THE KIDNEY IN THE HOST.
IT IS REPRESSED BY THE RETINOBLASTOMA PROTEIN AND LEAD TO SENESCENECE
WHEN INVOLVED IN THE CDK1 PATHWAYS IT IS ALSO REPRESSED. IT IS A VERSATILE GENE OF WHICH PROTEIN IMPORTANT IN CELL CYCLE HAS FUNCTION VARYING WITH ITS POSITION. IT IS KNOWN TO BE AT THE ESTROGEN RECEPTOR.
YOU CANNOT TARGET THIS GENE AND COME UP EMPTY. HMGA GENE INCREASES THIS E2F1. IT HAS INTERACTION WITH SENESCENT CHROMATIN.
6. GEMININ
In Mitosis
During mitosis or M phase, geminin stabilizes the replication factor Cdt1 by protecting it from ubiquitination and therefore subsequent proteolysis, thereby potentially promoting DNA replication during the following cell cycle. Although inhibition of geminin by RNAi leads to destabilization of Cdt1 protein and impairment of DNA replication during the following cell cycle in many cancer cell lines, no such cell cycle defect is seen in primary and immortalized cell lines (although Cdt1 levels are still reduced in these cells).[5]Geminin therefore is an important player in ensuring that one and only one round of replication occurs during each cell cycle. (WIKIPEDIA)
CONTINUE EDUCATION WITH NMCR
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==========================================================
EDUCATION CONTINUA
The CRBCM will be in Chicago to participate in the debate
and update itself in Oncology.
We thank Xcenda for allowing the cancer center to participate,
information is what we need as scientists!
January 22, 2013
Harnessing the Power of HDAC Inhibitors in Ovarian Cancer
Apicidin is a fungal metabolite with antiparasitic activity, and this histone deacetylase (HDAC) inhibitor has shown antiproliferative activity against various cancer cell lines. Korean researchers focused on the molecular mechanisms of apicidin in human ovarian cancer SKOV-3 cells and found that the agent has the potential to hinder cancer cell migration and invasion. They describe the mechanism of action by which apicidin reduced HDAC4 in this particular cancer.
RESULT: Histone
deacetylase inhibitor, apicidin, inhibits human ovarian cancer cell
migration via class II histone deacetylase 4 silencing
Cancer Letters (PubMed) | Dec 28, 2012 (Free abstract. Full text $31.50)
Cancer Letters (PubMed) | Dec 28, 2012 (Free abstract. Full text $31.50)
Platinum-based chemo leads to modest survival benefits in metastatic ovarian cancer so pairing it with other agents may offer a therapeutic boost. To that end, investigators in New York successfully married the experimental HDAC inhibitor panobinostat with doxorubicin and carboplatin. They explain why this triplet of agents proved to be “synergistic” in ovarian cancer cell lines, including SKOV-3.
RESULT: The
histone deacetylase inhibitor panobinostat demonstrates marked synergy
with conventional chemotherapeutic agents in human ovarian cancer cell
lines
Investigational New Drugs (PubMed) | Dec 02, 2011 (Free abstract. Full text $39.50)
Investigational New Drugs (PubMed) | Dec 02, 2011 (Free abstract. Full text $39.50)
==================================
for further reading, go to the source or write us!
FACTORS BEING MONITORED IN THE WELLNESS PROGRAM (part II)
1. AGE
Because with age comes all the trouble. Age is a relative thing. At what age do we start monitoring things?
And 40 years of age appears the most thought of in Western Societies. Mammograms are started and 45 years is a risk factor for men who then ae being monitor for cholesterol. The natural or true age is linked to genetic and environmental factors. Age is linked to the length of Telomeres and to Senescence. Telomeres are these youth protector molecules which keep being clipped and shortened at each cell cycle until the DNA is exposed to Endonucleases (if you get my drift!). Sometime we can fool it and make it a variable by exercising, and then it plays catch-up with you later. Some time, it is not so much of a variable, it is just there to be lived with...Suffice is to say, when you are young you feel invincible, protected. Being old, well, you have a "Risk factor" . Cancer does not like to be old, and works hard to preserve or elongate its Telomeres. This is an area of Target therapy.
2. Cholesterol, we spoke about yesterday-see WELLNESS PART I
3. WEIGHT MANAGEMENT WE WILL SPEAK ABOUT NEXT
4. BLOOD PRESSURE, Hb A1C FOR DIABETIC
5. THYROID FUNCTION (THYROID STIMULATING HORMONE LEVEL)
6. BNP
Brain natriuretic peptide - Wikipedia, the free encyclopedia
Basic natriuretic peptide (BNP), now known as B-type natriuretic peptide (also BNP) or GC-B, is a 32 amino acid polypeptide secreted by the ventricles of the ...
7.RENAL FUNCTION AND CREATININE
8. HEMOGLOBIN LEVEL
9. C-REACTIVE PROTEIN STATUS (AND ANTI NUCLEAR ANTIBODY STATUS)
10. FEV 1 (OR WHETHER YOU FEEL TIRED AND SHORT OF BREATH)
11. OXYGEN SATURATION OR SLEEP APNEA PRESENCE
12. ALBUMIN LEVEL (LOWER THAN 3.5g)
13. MENTAL STATUS / ANXIETY
14. PROTEINURIA
15. ADHESION TO PREVENTION AND IMMUNIZATION
(FLU-SHOT, PNEUMONIA AND NOW SHINGLE SHOT, ANNUAL OPHTHALMO VISIT,MAMMOGRAM,COLONOSCOPY,BONE DENSITY MONITOR, SMOKING CESSATION AND AVOIDANCE OF ALCOHOLI SM)
THESE 15 FACTORS SUM UP YOUR HEALTH. THIS IS THE REPORT CARD YOU SHOULD GET FROM YOUR DOCTOR WITH EVERY VISIT!
WE WILL DISCUSS THEM AS WE GO ALONG
Because with age comes all the trouble. Age is a relative thing. At what age do we start monitoring things?
And 40 years of age appears the most thought of in Western Societies. Mammograms are started and 45 years is a risk factor for men who then ae being monitor for cholesterol. The natural or true age is linked to genetic and environmental factors. Age is linked to the length of Telomeres and to Senescence. Telomeres are these youth protector molecules which keep being clipped and shortened at each cell cycle until the DNA is exposed to Endonucleases (if you get my drift!). Sometime we can fool it and make it a variable by exercising, and then it plays catch-up with you later. Some time, it is not so much of a variable, it is just there to be lived with...Suffice is to say, when you are young you feel invincible, protected. Being old, well, you have a "Risk factor" . Cancer does not like to be old, and works hard to preserve or elongate its Telomeres. This is an area of Target therapy.
2. Cholesterol, we spoke about yesterday-see WELLNESS PART I
3. WEIGHT MANAGEMENT WE WILL SPEAK ABOUT NEXT
4. BLOOD PRESSURE, Hb A1C FOR DIABETIC
5. THYROID FUNCTION (THYROID STIMULATING HORMONE LEVEL)
6. BNP
Brain natriuretic peptide - Wikipedia, the free encyclopedia
Basic natriuretic peptide (BNP), now known as B-type natriuretic peptide (also BNP) or GC-B, is a 32 amino acid polypeptide secreted by the ventricles of the ...7.RENAL FUNCTION AND CREATININE
8. HEMOGLOBIN LEVEL
9. C-REACTIVE PROTEIN STATUS (AND ANTI NUCLEAR ANTIBODY STATUS)
10. FEV 1 (OR WHETHER YOU FEEL TIRED AND SHORT OF BREATH)
11. OXYGEN SATURATION OR SLEEP APNEA PRESENCE
12. ALBUMIN LEVEL (LOWER THAN 3.5g)
13. MENTAL STATUS / ANXIETY
14. PROTEINURIA
15. ADHESION TO PREVENTION AND IMMUNIZATION
(FLU-SHOT, PNEUMONIA AND NOW SHINGLE SHOT, ANNUAL OPHTHALMO VISIT,MAMMOGRAM,COLONOSCOPY,BONE DENSITY MONITOR, SMOKING CESSATION AND AVOIDANCE OF ALCOHOLI SM)
THESE 15 FACTORS SUM UP YOUR HEALTH. THIS IS THE REPORT CARD YOU SHOULD GET FROM YOUR DOCTOR WITH EVERY VISIT!
WE WILL DISCUSS THEM AS WE GO ALONG
CPRIT Foundation and the CPRIT Grant review and approval process
The Cancer Prevention and Research Institute of Texas Foundation serves
as the connecting link for public policy, community, and business
leaders and is committed to strengthening and expanding the fight
against cancer in Texas.
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DetailsMonday, January 21, 2013
WELLNESS PROGRAM (PART 1).
As we set out to prevent Breast Cancer, we need to establish a wellness program for our clinic that would be
part of a comprehensive intervention aimed at decreasing cancer risk but also overall mortality risk for our patients. Estrogenic relative imbalance with noted increase of peripheral estrogenic molecule is suggested in obese patient. This fact is a known Breast cancer risk. And cholesterol management goes along obesity management. This discussion will focus on Cholesterol blood level management.
* LDL=Total Cholesterol - HDL cholesterol - (triglyceride/5)
* new LDL direct measurement can also be achieved directly without need for fasting.
----------------------------------------------------------------------
LDL" Bad cholesterol"
* normal is below 130mg/dL
* above this, lifestyle/diet intervention needed
any time you start intervening, reduce the baseline by 30-40%
To assume almost zero risk for cardiovascular disease reach 40mg/dL or below, but this is may be not a reasonable goal.
-----------------------------------------------------------------------------
In patient with history of Coronary heart disease, peripheral Vascular disease or diabetes, bring cholesterol to less than 100 mg/dL absolutely or better yet 70mg/dL for high risk patients.
-----------------------------------------------------------------------------------
In general the 5 year risk decrease by 1% for every 2mg/dL decrease in LDL
Medication to decrease LDL, pravastatin, Simvastatin, Ezetimibe, Niacin,
watch liver function test, CPK, C reactive protein, check ANA (associated autoimmune disease) and TSH
Definitely no Fish oil that increases LDL (unless the patient is already on medication decreasing LDL and you aimed at decreasing Triglyceride and aiming at anti-inflmmatory effect).
==========================================================
TRIGLYCERIDES
Normal below 150 mg/dL
150- to 200 mg/dL, is consider Borderline
200 to 499 consider high and needing intervention
more than 500mg is considered critical with impending pancreatitis and Chylomicronemia Syndrome and warrant immediate intervention
Intervention here means
1.Smoking Cessation
2.weight loss program
3. Exercising
4. Reduce Cholesterol intake to less than <200mg/day
5. Reduce saturated fat to less than 7% of total calories daily
6. Increase daily fiber to greater than 10g/day
7. consider increased phyto-Stanols and sterols (greater than 2 g/day)
8. start Nicotic Acid or Gemfibrozil or Fenofibrate, Poglitazone, or Roziglitazone (for Diabetic)
remember Colesevelam increases Triglyceride
for Pioglitazone and Roziglitazone, watch for fluid retention and Congestive Heart Failure!
------------------------------REMEMBER, ACHIEVABLE GOAL IS 30-40% REDUCTION-----
NEXT WEIGHT LOSS!
As we set out to prevent Breast Cancer, we need to establish a wellness program for our clinic that would be
part of a comprehensive intervention aimed at decreasing cancer risk but also overall mortality risk for our patients. Estrogenic relative imbalance with noted increase of peripheral estrogenic molecule is suggested in obese patient. This fact is a known Breast cancer risk. And cholesterol management goes along obesity management. This discussion will focus on Cholesterol blood level management.
* LDL=Total Cholesterol - HDL cholesterol - (triglyceride/5)
* new LDL direct measurement can also be achieved directly without need for fasting.
----------------------------------------------------------------------
LDL" Bad cholesterol"
* normal is below 130mg/dL
* above this, lifestyle/diet intervention needed
any time you start intervening, reduce the baseline by 30-40%
To assume almost zero risk for cardiovascular disease reach 40mg/dL or below, but this is may be not a reasonable goal.
-----------------------------------------------------------------------------
In patient with history of Coronary heart disease, peripheral Vascular disease or diabetes, bring cholesterol to less than 100 mg/dL absolutely or better yet 70mg/dL for high risk patients.
-----------------------------------------------------------------------------------
In general the 5 year risk decrease by 1% for every 2mg/dL decrease in LDL
Medication to decrease LDL, pravastatin, Simvastatin, Ezetimibe, Niacin,
watch liver function test, CPK, C reactive protein, check ANA (associated autoimmune disease) and TSH
Definitely no Fish oil that increases LDL (unless the patient is already on medication decreasing LDL and you aimed at decreasing Triglyceride and aiming at anti-inflmmatory effect).
==========================================================
TRIGLYCERIDES
Normal below 150 mg/dL
150- to 200 mg/dL, is consider Borderline
200 to 499 consider high and needing intervention
more than 500mg is considered critical with impending pancreatitis and Chylomicronemia Syndrome and warrant immediate intervention
Intervention here means
1.Smoking Cessation
2.weight loss program
3. Exercising
4. Reduce Cholesterol intake to less than <200mg/day
5. Reduce saturated fat to less than 7% of total calories daily
6. Increase daily fiber to greater than 10g/day
7. consider increased phyto-Stanols and sterols (greater than 2 g/day)
8. start Nicotic Acid or Gemfibrozil or Fenofibrate, Poglitazone, or Roziglitazone (for Diabetic)
remember Colesevelam increases Triglyceride
for Pioglitazone and Roziglitazone, watch for fluid retention and Congestive Heart Failure!
------------------------------REMEMBER, ACHIEVABLE GOAL IS 30-40% REDUCTION-----
NEXT WEIGHT LOSS!
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