Thursday, August 28, 2014
DEEP INTO THE BOWEL OF EPIGENIC PHENOMENA
Deep into the bowel of epigenic phenomena dances important genes dances
Tuesday, August 26, 2014
Thoughts about a Novel approach to cancer treatment
With the success of PDL-1/PD-1 and the suspicion that cancer cells build mechanisms to escape natural immunity from inducing Apoptosis at onset, one is excited to try and restore the avoided mechanisms and see if re-injected cancer cells that have been through plasmid treatments as applied by nobel price winner Yamanaka, the piggyBac tranposon system (wikipedia) applied by other, and miRna guided amplification of specifically suppressed genes in cancer.
The restoration could also involve prominent mutation genes known to be suppressed such as PTEN and E-Cadherins in specific cancer cells cells prior to re-infusion. By restoring these levelsi in cancer cells that have been extracted from patients , Once re-infused, one wonder if this will trigger a response that will extend to unaltered cancer cells in the body. The genes must be relevant and should consider restoration of the HLA-1-type automatic reaction. (or re-stimulating Death Receptor) ...some refinement now needed!
CRBCM, always coming up with new line of attacks against cancers!
WHEN YOU ARE GOOD, YOU COULD BE EXCELLENT: THE CASE OF VELCADE
SOURCE FDA/MEDSCAPE
"The
U.S. Food and Drug Administration has approved Velcade (bortezomib) for
the retreatment of adult patients with multiple myeloma who have
previously received and responded to Velcade therapy and have then
relapsed at least six months after the completion of that treatment.
The drug is a proteasome inhibitor that was first approved for treatment of myeloma in 2003 (OT 8/25/03 issue), and it was approved for injection in 2008 (OT 8/25/08 issue).
Velcade was approved in 2006 for the treatment of patients with mantle
cell lymphoma who have received at least one prior therapy. And, the
drug’s label was updated in 2012 to include the subcutaneous method of
administration in its approved indications including multiple myeloma
and mantle cell lymphoma after at least one prior therapy (OT 2/25/12 issue).
The
recent actions for the drug follow data from the single arm,
open-label, Phase II RETRIEVE trial of 130 patients who had previously
received and responded to Velcade-based therapy and had relapsed at
least six months after that prior Velcade treatment. The data showed one
patient had a complete response and 49 patients had a partial response;
and the median duration of response was 6.5 months.
The
most common adverse effects reported in patients receiving Velcade were
thrombocytopenia, diarrhea, herpes zoster, and pneumonia. Adverse
reactions that led to discontinuation of treatment occurred in 13
percent of the patients. Other common side effects included fever,
decreased appetite, fatigue, and rash.
Velcade is co-developed by Millennium/Takeda and Janssen Pharmaceutical Companies."
CRBCM IS GLAD TO HEAR DR MUYEMBE TAMFUM IS HEADING TO LIBERIA FOR THE EBOLA OUTBREAK THERE!
DR MUYEMBE, WAS FIRST MY MICROBIOLOGY PROFESSOR
AND WAS DEAN OF THE MEDICAL SCHOOL WHILE 1 WAS STILL A STRUGGLING MEDICAL STUDENT, IT IS GOOD TO HEAR THAT 31 YEARS AFTER I GRADUATED FROM THIS SCHOOL, HE IS STILL STRONG ENOUGH TO UNDERTAKE THESE KINDS OF OPERATIONS! ONE THING IS FOR SURE, WHEN YOU ARE GOOD, YOU ARE GOOD....DR MUYEMBE STAYS VERY HIGH IN OUR EYES! MAY GOD BLESS HIM!
AND WAS DEAN OF THE MEDICAL SCHOOL WHILE 1 WAS STILL A STRUGGLING MEDICAL STUDENT, IT IS GOOD TO HEAR THAT 31 YEARS AFTER I GRADUATED FROM THIS SCHOOL, HE IS STILL STRONG ENOUGH TO UNDERTAKE THESE KINDS OF OPERATIONS! ONE THING IS FOR SURE, WHEN YOU ARE GOOD, YOU ARE GOOD....DR MUYEMBE STAYS VERY HIGH IN OUR EYES! MAY GOD BLESS HIM!
And life goes on
Dear Mutombo Kankonde,
Congratulations! Your application to host TEDMED Live has been accepted! We are able to offer you this opportunity through our partnership with American Medical Association. Please make a note of the following:
Your Organization Name: Coalition for the Reversal of Breast Cancer Mortality in African American Women
Your Affiliate Name: TEDMEDLive Coalition for the Reversal of Breast Cancer Mortality in African American Women
Your Affiliate ID: L53193
You will use these credentials to identify your location and access the live simulcast available September 10-12 and the on demand content available September 10-16
Please add emails ending in @tedmed.com to your “safe senders” list to ensure you receive important messages about your TEDMED Live event.
In addition, it is important that you review and adhere to the TEDMED Live Guidelines. These guidelines are new to 2014, so even if you have participated in TEDMED Live before, it is important to be aware of these guidelines.
We are conducting two live streaming tests to simulate the real-time video feed exactly as it will be delivered to you during the days of the event. Please make sure to mark your calendars and participate in both mandatory tests so that you are confident that your connection will run smoothly when we go live.
TEST #1: Tuesday, August 26, 12 AM to 11:59 PM, EST. (24 hours to access)
TEST #2: Tuesday, September 9, 9-11 AM and 4-6 PM, EST. (Two 2-hour options)
For the tests, all you will need to do is go to www.tedmedlive.org from the device and location you will be holding your gathering and login using your Affiliate ID Code.
To ensure your TEDMED Live experience is engaging and memorable, please consider the following suggestions:
Download this year’s schedule here. TEDMED Live is available on demand, so you can choose convenient time(s) for your community to tune in and reserve a place for your gathering.
Think and promote broadly. Download your customizable poster and quarter cards here. We encourage you to distribute widely to create buzz around your gathering. Everyone’s perspective is important, so we encourage you to share the experience with everyone you know – invite your family, friends, peers, and colleagues around the world to join you!
Get a community kick-start. Join our Facebook Group here. Get to know fellow TEDMED Live community members, check out helpful tips and tools and share before, during, and following your experience.
Create an engaging experience. Explore this year’s speakers and session themes to inspire networking, collaboration and furthering of ideas you hear from the TEDMED stage. We suggest that you invite key community members to lead discussions during the breaks.
Get your cameras and social storytellers ready. We want your story to be heard! Be sure to capture your experience in image and word, share it with our greater community and see what your fellow Affiliates are doing via Twitter, Facebook, Google+
Stay up-to-date by following @TEDMED on Twitter and checking out the TEDMED blog.
We will send you emails with more information from time to time. If you need to contact us in the meantime, please do so via email at tedmedlive@tedmed.com.
Sincerely,
The TEDMED Live Admissions Team
Congratulations! Your application to host TEDMED Live has been accepted! We are able to offer you this opportunity through our partnership with American Medical Association. Please make a note of the following:
Your Organization Name: Coalition for the Reversal of Breast Cancer Mortality in African American Women
Your Affiliate Name: TEDMEDLive Coalition for the Reversal of Breast Cancer Mortality in African American Women
Your Affiliate ID: L53193
You will use these credentials to identify your location and access the live simulcast available September 10-12 and the on demand content available September 10-16
Please add emails ending in @tedmed.com to your “safe senders” list to ensure you receive important messages about your TEDMED Live event.
In addition, it is important that you review and adhere to the TEDMED Live Guidelines. These guidelines are new to 2014, so even if you have participated in TEDMED Live before, it is important to be aware of these guidelines.
We are conducting two live streaming tests to simulate the real-time video feed exactly as it will be delivered to you during the days of the event. Please make sure to mark your calendars and participate in both mandatory tests so that you are confident that your connection will run smoothly when we go live.
TEST #1: Tuesday, August 26, 12 AM to 11:59 PM, EST. (24 hours to access)
TEST #2: Tuesday, September 9, 9-11 AM and 4-6 PM, EST. (Two 2-hour options)
For the tests, all you will need to do is go to www.tedmedlive.org from the device and location you will be holding your gathering and login using your Affiliate ID Code.
To ensure your TEDMED Live experience is engaging and memorable, please consider the following suggestions:
Download this year’s schedule here. TEDMED Live is available on demand, so you can choose convenient time(s) for your community to tune in and reserve a place for your gathering.
Think and promote broadly. Download your customizable poster and quarter cards here. We encourage you to distribute widely to create buzz around your gathering. Everyone’s perspective is important, so we encourage you to share the experience with everyone you know – invite your family, friends, peers, and colleagues around the world to join you!
Get a community kick-start. Join our Facebook Group here. Get to know fellow TEDMED Live community members, check out helpful tips and tools and share before, during, and following your experience.
Create an engaging experience. Explore this year’s speakers and session themes to inspire networking, collaboration and furthering of ideas you hear from the TEDMED stage. We suggest that you invite key community members to lead discussions during the breaks.
Get your cameras and social storytellers ready. We want your story to be heard! Be sure to capture your experience in image and word, share it with our greater community and see what your fellow Affiliates are doing via Twitter, Facebook, Google+
Stay up-to-date by following @TEDMED on Twitter and checking out the TEDMED blog.
We will send you emails with more information from time to time. If you need to contact us in the meantime, please do so via email at tedmedlive@tedmed.com.
Sincerely,
The TEDMED Live Admissions Team
Monday, August 25, 2014
Unveiling the Cytokines!
It is increasingly suggested that the role of what we call the Cytokines, once looked at closely, is much broader and remains one of the insufficiently explored phenomena of life. The key to their "secrecy" and unexplored facet is linked to their Multi-plurality (indeed there are many Cytokines), their ability to act at low quantity level (they act on specific receptors) and act insidiously (3 years after a Brain injury, Cytokine manifestation is through lack of memory, or decreased focus on things, or even change in weight)!
The effect is often not patent but definitely present such as minimal fever, minimal diarrhea or some joint pains! But it is the Cytokines at work.
In COPD, the "thin puffer"is an example of a clinical presentation of Cytokine at play! One tend to brush out the deleterious effects of smoking because one did not develop "COPD" or lung cancer. This even a woman who had a stroke 20 years ago...and looks older then people of her age. The deleterious effects of smoking can vary according to our gene background among other things, and of course also, according to the various receptors that an individual has! While some may indeed develop lung cancers, many other will develop Bladder cancer, or simply get old faster, or develop memory problems, or lack of ability to gain weight ! Its all depend on many factors including the production of Cytokines!
*Role in Traumatic Brain Injury:
This where the effect is dramatic, indeed after a brain injury, there is a healing on location, and science has shown that even if the area directly involved may control movement, science has observed that individual afflicted by trauma may several years later develop Post Traumatic Syndrome (PTSD) with lack of sleep, and memory problems even if the Hippocampus was not involved in the original trauma:
" Humans and other mammals have two hippocampi, one in each side of the brain. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. The hippocampus is located under the cerebral cortex;[1] and in primates it is located in the medial temporal lobe, underneath the cortical surface. It contains two main interlocking parts: Ammon's horn[2] and the dentate gyrus." wikipedia
Meaning that after the trauma had occurred, further distruction to the Hippocampus will result independently in susceptible individuals. Science has learned that Macrophages that come to clean-up to debris and scavenge the abnormalities, will also liberate Cytokines that, for repair efforts mainly, but for lack of specificity to receptors, and by being discharged in distant milieu, will induce the PTSD! These effects are most dramatic in the post-synaptic nerve cell distant from the trauma location! Suffice is to say that Various interventions are trying to minimize to slow the processes at the trauma occurrence and subsequently...The department of defense (DOD) is working feverishly of some of these questions (at least we hope!). The thing is it is the Cytokines we are most focused on!
POST RADIATION TO THE BRAIN, "PTSD" happens. It is well known that patient who underwent Radiation to the Brain for any reasons may end-up with "post radiation dementia" This is one of the many reason some balk at Radiation post a successful treatment in limited stage small cell lung cancer despite the standard recommendation of PCI (premature Cranial Irradiation) at completion of treatment!
In COPD!
almost a parallel thing happens!
Indeed as a result of insults from smoking, and constant havocs by smoking occasions, inflammations and subsequent scars are caused to happens by our friendly smokers! And innocent bystanders experience the wrath of the phenomena we come to know as the "secondary smoking". And well beyond the inflammatory insults of smoking, well beyond the scarring of the lungs from smoking, there is a secondary secretion of cytokines to the presence of the "scars". Indeed, when you think of the scars as a inert "object", in a living cellular environment, scars are made of chemical substances that the cell continue to (in a reflex) interact with
and somewhere in there cytokines of certain different kinds are constantly being secreted, affecting receptors including some at distant locations! It is believed that this is how aging and certain diseases noted in elderly are generated...
TO BE CONTINUED!
The effect is often not patent but definitely present such as minimal fever, minimal diarrhea or some joint pains! But it is the Cytokines at work.
In COPD, the "thin puffer"is an example of a clinical presentation of Cytokine at play! One tend to brush out the deleterious effects of smoking because one did not develop "COPD" or lung cancer. This even a woman who had a stroke 20 years ago...and looks older then people of her age. The deleterious effects of smoking can vary according to our gene background among other things, and of course also, according to the various receptors that an individual has! While some may indeed develop lung cancers, many other will develop Bladder cancer, or simply get old faster, or develop memory problems, or lack of ability to gain weight ! Its all depend on many factors including the production of Cytokines!
*Role in Traumatic Brain Injury:
This where the effect is dramatic, indeed after a brain injury, there is a healing on location, and science has shown that even if the area directly involved may control movement, science has observed that individual afflicted by trauma may several years later develop Post Traumatic Syndrome (PTSD) with lack of sleep, and memory problems even if the Hippocampus was not involved in the original trauma:
" Humans and other mammals have two hippocampi, one in each side of the brain. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. The hippocampus is located under the cerebral cortex;[1] and in primates it is located in the medial temporal lobe, underneath the cortical surface. It contains two main interlocking parts: Ammon's horn[2] and the dentate gyrus." wikipedia
Meaning that after the trauma had occurred, further distruction to the Hippocampus will result independently in susceptible individuals. Science has learned that Macrophages that come to clean-up to debris and scavenge the abnormalities, will also liberate Cytokines that, for repair efforts mainly, but for lack of specificity to receptors, and by being discharged in distant milieu, will induce the PTSD! These effects are most dramatic in the post-synaptic nerve cell distant from the trauma location! Suffice is to say that Various interventions are trying to minimize to slow the processes at the trauma occurrence and subsequently...The department of defense (DOD) is working feverishly of some of these questions (at least we hope!). The thing is it is the Cytokines we are most focused on!
POST RADIATION TO THE BRAIN, "PTSD" happens. It is well known that patient who underwent Radiation to the Brain for any reasons may end-up with "post radiation dementia" This is one of the many reason some balk at Radiation post a successful treatment in limited stage small cell lung cancer despite the standard recommendation of PCI (premature Cranial Irradiation) at completion of treatment!
In COPD!
almost a parallel thing happens!
Indeed as a result of insults from smoking, and constant havocs by smoking occasions, inflammations and subsequent scars are caused to happens by our friendly smokers! And innocent bystanders experience the wrath of the phenomena we come to know as the "secondary smoking". And well beyond the inflammatory insults of smoking, well beyond the scarring of the lungs from smoking, there is a secondary secretion of cytokines to the presence of the "scars". Indeed, when you think of the scars as a inert "object", in a living cellular environment, scars are made of chemical substances that the cell continue to (in a reflex) interact with
and somewhere in there cytokines of certain different kinds are constantly being secreted, affecting receptors including some at distant locations! It is believed that this is how aging and certain diseases noted in elderly are generated...
TO BE CONTINUED!
Friday, August 22, 2014
Focus of the RCC1 gene
RCC1----Crm1---Ran guanine nucleotide exchange factor
according to Nemergut:" RanBP3 acts as a scaffold protein to promote the efficient assembly of export complexes."
from REN : "These results are consistent with the hypothesis that Ran functions directly in at least two pathways, one, dependent on RanBP1, that affects cell cycle progression and RNA export, and another, independent of RanBP1, that affects nuclear protein import."
Paschal et al :"
the nuclear guanine nucleotide exchange factor (RanGEF), and the Ran import receptor (NTF2). The recent identification of the Saccharomyces cerevisiae protein Mog1p as a suppressor of temperature-sensitive Ran mutations suggests that additional regulatory proteins remain to be characterized."
Dig this by REN et al! and you will understand that the anti-VEGF is still the begining of the membrane The small Ras-related GTP binding and hydrolyzing protein Ran has been implicated in a variety of processes, including cell cycle progression, DNA synthesis, RNA processing, and nuclear-cytosolic trafficking of both RNA and proteins. Like other small GTPases, Ran appears to function as a switch: Ran-GTP and Ran-GDP levels are regulated both by guanine nucleotide exchange factors and GTPase activating proteins, and Ran-GTP and Ran-GDP interact differentially with one or more effectors.story:
"
according to Nemergut:" RanBP3 acts as a scaffold protein to promote the efficient assembly of export complexes."
from REN : "These results are consistent with the hypothesis that Ran functions directly in at least two pathways, one, dependent on RanBP1, that affects cell cycle progression and RNA export, and another, independent of RanBP1, that affects nuclear protein import."
Paschal et al :"
the nuclear guanine nucleotide exchange factor (RanGEF), and the Ran import receptor (NTF2). The recent identification of the Saccharomyces cerevisiae protein Mog1p as a suppressor of temperature-sensitive Ran mutations suggests that additional regulatory proteins remain to be characterized."
Dig this by REN et al! and you will understand that the anti-VEGF is still the begining of the membrane The small Ras-related GTP binding and hydrolyzing protein Ran has been implicated in a variety of processes, including cell cycle progression, DNA synthesis, RNA processing, and nuclear-cytosolic trafficking of both RNA and proteins. Like other small GTPases, Ran appears to function as a switch: Ran-GTP and Ran-GDP levels are regulated both by guanine nucleotide exchange factors and GTPase activating proteins, and Ran-GTP and Ran-GDP interact differentially with one or more effectors.story:
"
No CPRIT No Problem!
We have submitted all kinds of research projects
we have tried to compete, we have teased congressmen
we have met all kinds of people who have promised to help
but what we understood is that these political Texas institutions will not help us,
the need for cancer patients is great, and CRBCM needs to grow parallel to these institutions,
Greater East Cancer Center is growing, we got to grow without their help...
We are going to have to grow free of these political institutions
because our cause is just...cancer needs a response that we can mount...lets progress beside them!
we have tried to compete, we have teased congressmen
we have met all kinds of people who have promised to help
but what we understood is that these political Texas institutions will not help us,
the need for cancer patients is great, and CRBCM needs to grow parallel to these institutions,
Greater East Cancer Center is growing, we got to grow without their help...
We are going to have to grow free of these political institutions
because our cause is just...cancer needs a response that we can mount...lets progress beside them!
To not waste time
At least 2 projects that will get funding from CPRIT will join ideas developed here already and have been addressed here. the MDM-2 as a source of neoplasia transformation and being one of the genes to be included in our proposed kit for early cancer detection. What is important though, that further work performed by DR Zhang and DR CHOI at UTEP has advanced several 10 additional co-genes that also participate in the same neoplastic transformation and needs to be looked at the same time in order to really advance otherwise 3 years from now they will find what we already have found! This team needs to see us rapidly to combine efforts for advancement!
Thursday, August 21, 2014
Shifting sand!
Until we define clear biomarkers, Lupus and related autoimmune diseases will remain shifting sands, and experts don't help either, just read the statement pertaining to how to categorize:
ON LUPUS
"Several instruments have been developed for this purpose, including the British Isles Lupus Assessment Group (BILAG) index,[13] the European Consensus Lupus Activity Measurement (ECLAM),[14] and the SLE Disease Activity Index (SLEDAI).[15]" (MEDSCAPE)
how to compare the outcomes is also subsequently in flux
genetic biomarkers are still in the works!
ON LUPUS
"Several instruments have been developed for this purpose, including the British Isles Lupus Assessment Group (BILAG) index,[13] the European Consensus Lupus Activity Measurement (ECLAM),[14] and the SLE Disease Activity Index (SLEDAI).[15]" (MEDSCAPE)
how to compare the outcomes is also subsequently in flux
genetic biomarkers are still in the works!
And CPRIT Continua
The new CPRIT round of grants have been given and nominated
one thing for sure, they are just as diverse as they can be
and went to the usual suspects (the suspects created CPRIT). Telling the observers that although the leadership has changed,
much of what constituted the pool of reviewers and supportive staff did not at CPRIT.
When one look at the different topics selected and funded, it is hard to get a theme. This point to 2 majors conclusions, one,that in general CPRIT's own scientific board has no major theme to pull or drive research to, leaving itself to the will of individual institutions to come up with the theme and objects . And second, the clear departure from themes that are currently driving Oncology practice (probably avoiding relevancy in some ways?). Indeed, most of Oncology has been lately versed into immunology and its various uses in Cancer. From Ibrutinib, Pembrolizumab and the spileucel-T, to immune system infiltration of Breast cancer tissue as a marker of response to therapy, all these interesting developments seem to have not capture CPRIT scientific panel's attention arguably enough to drive their intent. There is a lot of opportunities lost in a time of minimal research resources. Two to 3 years from now we will still have interesting findings that we should have had 10 years ago, meaning they (some of the current researches) will require further investmentsin order to become of meaning to say the least!
Although basic research is still needed in some areas, the thrust should now be to learn more on some of the meanings of latest advances! Indeed over the last few years, we have discover the modulators of immunity (Revlimid, thalidomide) and major drugs that have been developed against Basal cell cancer, renal and Myeloma, there are many aspects of these new drugs that need to be explored to improve their use and maximize their combination. These efforts remain to be made, and unless our funding sources think to force research into these aspects, progress will be slow. Progress in the control of epigenic events (Verinostat) where some of the important progresses have been made, skipped! (CPRIT funding any theses?)
In our blog yesterday, we clearly explained how the quantity of expression of genes may affect the entire cellular metabolism (excitatory at low level and inhibitory at greater level) these important aspects are not fully explored and detailed. It seems that we discover and run instead of teasing fully the full nuances of scientific phenomena uncovered by some of our researches. We need how funding sources to push us further into these details because that where the truth of noted events is hiding! This is true for c-FOS, FOX3 and many genes that we pretend we know without fully teasing to meaningful ways!
Should we wait for another shoe to drop at CPRIT in order to sharpen the mission...may be not! Just keep on sharpening the mission by tightening what this organization may want from the Researcher community...!
one thing for sure, they are just as diverse as they can be
and went to the usual suspects (the suspects created CPRIT). Telling the observers that although the leadership has changed,
much of what constituted the pool of reviewers and supportive staff did not at CPRIT.
When one look at the different topics selected and funded, it is hard to get a theme. This point to 2 majors conclusions, one,that in general CPRIT's own scientific board has no major theme to pull or drive research to, leaving itself to the will of individual institutions to come up with the theme and objects . And second, the clear departure from themes that are currently driving Oncology practice (probably avoiding relevancy in some ways?). Indeed, most of Oncology has been lately versed into immunology and its various uses in Cancer. From Ibrutinib, Pembrolizumab and the spileucel-T, to immune system infiltration of Breast cancer tissue as a marker of response to therapy, all these interesting developments seem to have not capture CPRIT scientific panel's attention arguably enough to drive their intent. There is a lot of opportunities lost in a time of minimal research resources. Two to 3 years from now we will still have interesting findings that we should have had 10 years ago, meaning they (some of the current researches) will require further investmentsin order to become of meaning to say the least!
Although basic research is still needed in some areas, the thrust should now be to learn more on some of the meanings of latest advances! Indeed over the last few years, we have discover the modulators of immunity (Revlimid, thalidomide) and major drugs that have been developed against Basal cell cancer, renal and Myeloma, there are many aspects of these new drugs that need to be explored to improve their use and maximize their combination. These efforts remain to be made, and unless our funding sources think to force research into these aspects, progress will be slow. Progress in the control of epigenic events (Verinostat) where some of the important progresses have been made, skipped! (CPRIT funding any theses?)
In our blog yesterday, we clearly explained how the quantity of expression of genes may affect the entire cellular metabolism (excitatory at low level and inhibitory at greater level) these important aspects are not fully explored and detailed. It seems that we discover and run instead of teasing fully the full nuances of scientific phenomena uncovered by some of our researches. We need how funding sources to push us further into these details because that where the truth of noted events is hiding! This is true for c-FOS, FOX3 and many genes that we pretend we know without fully teasing to meaningful ways!
Should we wait for another shoe to drop at CPRIT in order to sharpen the mission...may be not! Just keep on sharpening the mission by tightening what this organization may want from the Researcher community...!
Wednesday, August 20, 2014
reflexion at CRBCM!
What if the Universe was a man, a living giant organism, how can we talk to this man!
how can we make our voice heard? Is it important? what should we say that will better us?
EH! send us a new mineral? is this what we really need? Hell, let us cope with MOTHER EARTH!
how can we make our voice heard? Is it important? what should we say that will better us?
EH! send us a new mineral? is this what we really need? Hell, let us cope with MOTHER EARTH!
Je disais que: DCK gene: lack of this gene protect most dangerous cancers!
An important pathway is what actually matter, has clinical relevance and plays an important role. In Cancers, what may impact clinical outcome of patients matter! And here come the DCK gene!
it involves some of the most resistant diseases: Hepatoma and Myelo-lymphoproliferative disorders
if you know it (the DCK gene) is not there, the disease is critically resistant!
we got to make sure it is there! And for that its promoter better be stimulated!
"both Sp1 and USF1 stimulated dCK promoter"(Yubin et al)
To make sure the things get complicated, the role of Sp1 must be twisted"
and keep on twisting it until human comprehension is lost: "Combined Sp1 and USF1 showed additive transactivation at lower concentrations of Sp1. Sp1 was inhibitory at higher levels. Stimulation by combined USF1/USF2a with Sp1 was similar to that for USF1 alone with Sp1, whereas transactivation by Sp1 and USF2a without USF1 was synergistic." (Yubin et al) So you have to have just the Sp1 needed!(so let remove the SP1 at the right dose and Mutation of the Sp1 is not good for this very reason!
but stay on the ball:"Deficiency of DCK is associated with resistance to antiviral and anticancer chemotherapeutic agents." wikipedia... so avoid the deficiency but don't give it Intravenously either or should you!
Could ARA-C (high dose) and Gemzar combination add control of resistant disease
or should Cisplatin (OXALIPLATIN, A sexier option) be added to the dance?
should depletion of DCK be more followed as a Biomarker?
SHOULD THEREFORE DCK GENE BE MORE RELIABLE IN DISEASE WHERE THE NF-kB IS AMPLIFIED SUCH AS THE GASTRIC CANCERS OF THE WORLD! In other words? should drug activity or resistance be correlated with DCK expression? (This remind me of our association of Triple negative Breast cancers with CASEIN the powerful phosphorylator!) does the triple negative cancer resistance has something to do with DCK gene?
" The phosphorylation of CdA in crude extracts showed a close correlation to the dCK polypeptide level."spasokoukotskaja et al! Giving us a way to measure this!
CRBCM, BEATING A NEW PATH EVERYDAY!
What are the Cytokines expressing the level of DNA integrity. ( DCK determine DNA integrity)
When the integrity of the gene is not preserved, do the cytokines trigger programmed death, is it through the Death Receptors?
In Sarcoma, can TK2 and DGK BE legitimate Target, what are these last gene have to do with the MTOR and life span? Is there such thing as tagging phosphorylation to determine where it has to go? or is phosphorylation just random?
it involves some of the most resistant diseases: Hepatoma and Myelo-lymphoproliferative disorders
if you know it (the DCK gene) is not there, the disease is critically resistant!
we got to make sure it is there! And for that its promoter better be stimulated!
"both Sp1 and USF1 stimulated dCK promoter"(Yubin et al)
To make sure the things get complicated, the role of Sp1 must be twisted"
and keep on twisting it until human comprehension is lost: "Combined Sp1 and USF1 showed additive transactivation at lower concentrations of Sp1. Sp1 was inhibitory at higher levels. Stimulation by combined USF1/USF2a with Sp1 was similar to that for USF1 alone with Sp1, whereas transactivation by Sp1 and USF2a without USF1 was synergistic." (Yubin et al) So you have to have just the Sp1 needed!(so let remove the SP1 at the right dose and Mutation of the Sp1 is not good for this very reason!
but stay on the ball:"Deficiency of DCK is associated with resistance to antiviral and anticancer chemotherapeutic agents." wikipedia... so avoid the deficiency but don't give it Intravenously either or should you!
Could ARA-C (high dose) and Gemzar combination add control of resistant disease
or should Cisplatin (OXALIPLATIN, A sexier option) be added to the dance?
should depletion of DCK be more followed as a Biomarker?
SHOULD THEREFORE DCK GENE BE MORE RELIABLE IN DISEASE WHERE THE NF-kB IS AMPLIFIED SUCH AS THE GASTRIC CANCERS OF THE WORLD! In other words? should drug activity or resistance be correlated with DCK expression? (This remind me of our association of Triple negative Breast cancers with CASEIN the powerful phosphorylator!) does the triple negative cancer resistance has something to do with DCK gene?
" The phosphorylation of CdA in crude extracts showed a close correlation to the dCK polypeptide level."spasokoukotskaja et al! Giving us a way to measure this!
CRBCM, BEATING A NEW PATH EVERYDAY!
What are the Cytokines expressing the level of DNA integrity. ( DCK determine DNA integrity)
When the integrity of the gene is not preserved, do the cytokines trigger programmed death, is it through the Death Receptors?
In Sarcoma, can TK2 and DGK BE legitimate Target, what are these last gene have to do with the MTOR and life span? Is there such thing as tagging phosphorylation to determine where it has to go? or is phosphorylation just random?
Saturday, August 16, 2014
JUST AS YOU THOUGHT YOU HAVE SEEN ALL ABOUT AVASTIN!
BEVACIZUMAB HAS BEEN APPROVED FOR METASTATIC CERVICAL CANCER IN COMBINATION WITH TOPOTECAN TAXOL AND CISPLATIN BECAUSE OF INCREASE IN OVERALL SURVIVAL...AND THE FDA APPROVED!
THE POWER OF VGEF IS ONCE AGAIN DEMONSTRATED...
THE POWER OF VGEF IS ONCE AGAIN DEMONSTRATED...
Bevacizumab
for Advanced Cervical Cancer Approved by FDA - See more at:
http://www.targetedonc.com/articles/Bevacizumab-for-Advanced-Cervical-Cancer-Approved?utm_source=Informz&utm_medium=Targeted+Onc&utm_campaign=Targeted+Breaking+News+8%2F14%2F14&utm_term=Targeted+Breaking+News+8%2F14%2F14#sthash.6xXgjV1K.dpuf
Bevacizumab
for Advanced Cervical Cancer Approved by FDA - See more at:
http://www.targetedonc.com/articles/Bevacizumab-for-Advanced-Cervical-Cancer-Approved?utm_source=Informz&utm_medium=Targeted+Onc&utm_campaign=Targeted+Breaking+News+8%2F14%2F14&utm_term=Targeted+Breaking+News+8%2F14%2F14#sthash.6xXgjV1K.dpuf
CRBCM ON THE ROAD AGAIN, continuing to meet its requirements!
Hi Dr. Kankonde,
I have everything booked for your assignment starting August 18, 2014. Below is the detailed information you will need.
Please
note: Our Company is no longer permitted to use any store other than
FedEx Office to send daily assignments to our physicians. There is no
FedEx Office store located near the hotel in Bedford. Therefore, I will
be sending
your schedule and evaluation forms to the print center listed below,
and they will ship your assignments directly to your hotel. The package
will be waiting for you at the front desk each afternoon for the next
day’s work. You should return your evaluations
to the FedEx Drop Box listed below. I apologize for any inconvenience
this may cause.
Information regarding your rental car and flight is attached.
*Please
return your rental vehicle with the same amount of fuel as you began
the rental with. This will help prevent a refueling charge. etc...
Wednesday, August 13, 2014
Keep on asking myself!
"Lucitanib has 50% Response (PR) in FGF-amplified Breast Cancer"
given FGF amplification requirement, and the involvement of Heparan sulfate the great cover of receptor, how this drug may interact with Hormone replacement therapy?
given FGF amplification requirement, and the involvement of Heparan sulfate the great cover of receptor, how this drug may interact with Hormone replacement therapy?
questions?
From ASCO,
for Extensive disease, CISPLATIN - Etoposide has become standard of care
but in Bulky Mediastinal disease, new study propose Radiation after the 4 cycles of chemotherapy
wonder if concurrent chemotherapy radiation will ultimately be better as known in NSCL?
PCI now known for Limited stage small cell, seems good for Extensive stage also? yes expert says now! Go figure. All for a PCI that do not prolong survival?
In Pancreatic Cancer,
adding Ruxolitinib (Anti-JAK1,2) to Xeloda will increase response rate! Hummm.....JAK1,2.....
Samstein et al " Foxp3 is induced during thymic differentiation or upon activation of peripheral CD4+ T cells in response to T cell receptor (TCR) stimulation in combination with several other signals, including IL-2 and TGF-β. Furthermore, forced expression of Foxp3 confers suppressor function to Treg precursor cells, and Foxp3 ablation in mature Treg cells results in loss of lineage identity and immunosuppressive phenotype (Fontenot et al., 2003; Williams and Rudensky, 2007). However, an understanding of how Foxp3 coordinates the differentiation of Treg cells and their distinct suppression program is lacking."
Or is it the RUNX?
NO they say it is STAT3! The activator of Cahexia, If you amplify STAT3, you lose weight? That's should be on demande everywhere!But be careful it waste muscle and probably not the fat (a composition of tissue issue!)
for Extensive disease, CISPLATIN - Etoposide has become standard of care
but in Bulky Mediastinal disease, new study propose Radiation after the 4 cycles of chemotherapy
wonder if concurrent chemotherapy radiation will ultimately be better as known in NSCL?
PCI now known for Limited stage small cell, seems good for Extensive stage also? yes expert says now! Go figure. All for a PCI that do not prolong survival?
In Pancreatic Cancer,
adding Ruxolitinib (Anti-JAK1,2) to Xeloda will increase response rate! Hummm.....JAK1,2.....
Samstein et al " Foxp3 is induced during thymic differentiation or upon activation of peripheral CD4+ T cells in response to T cell receptor (TCR) stimulation in combination with several other signals, including IL-2 and TGF-β. Furthermore, forced expression of Foxp3 confers suppressor function to Treg precursor cells, and Foxp3 ablation in mature Treg cells results in loss of lineage identity and immunosuppressive phenotype (Fontenot et al., 2003; Williams and Rudensky, 2007). However, an understanding of how Foxp3 coordinates the differentiation of Treg cells and their distinct suppression program is lacking."
Or is it the RUNX?
NO they say it is STAT3! The activator of Cahexia, If you amplify STAT3, you lose weight? That's should be on demande everywhere!But be careful it waste muscle and probably not the fat (a composition of tissue issue!)
Monday, August 11, 2014
Facts: SOME POSITIVE TRIALS! (from ASCO)
*Multicenter phase II trial in RECURRENT Ovarian Cancer
Cediranib 30 mg daily + Olaprib 200mg PO BID Vs Olaparib 400 mg BID
POSITIVE TRIAL, EVEN IN PATIENT WITHOUT BRCA MUTATION!
and quite a big difference PFS 17 months Vs 9 months
*In Head and neck, Cisplatin-RT is king for treatment
BUT ADD CETUXIMAB IN KRAS variant group
*In Medullary Thyroid cancer
Vandetanib Objective response 45%
30 months PFS Vs Placebo 19 months
-RET Mutation in FAMILIAL or HEREDITARY Medullary Thyroid cancer
also effective Motezanil, Cabozantinib, Sorafenib, Axitinib (MOUTH FULL!!!!)
*IODINE THERAPY FOR METASTATIC THYROID CANCER
RR 70%
for those refractory to Iodine RT
1. Chemotherapy gives Median survival 5 months
2. Lenvatinib 24 mg PO daily OR 65%
and PFS 18.3 months (read up on side effects)
Nexavar, an option in this disease!
*MPDL3280A, by inhibiting PD-L1, will have significant activity in Metastatic Urothelial Bladder cancer.
Cediranib 30 mg daily + Olaprib 200mg PO BID Vs Olaparib 400 mg BID
POSITIVE TRIAL, EVEN IN PATIENT WITHOUT BRCA MUTATION!
and quite a big difference PFS 17 months Vs 9 months
*In Head and neck, Cisplatin-RT is king for treatment
BUT ADD CETUXIMAB IN KRAS variant group
*In Medullary Thyroid cancer
Vandetanib Objective response 45%
30 months PFS Vs Placebo 19 months
-RET Mutation in FAMILIAL or HEREDITARY Medullary Thyroid cancer
also effective Motezanil, Cabozantinib, Sorafenib, Axitinib (MOUTH FULL!!!!)
*IODINE THERAPY FOR METASTATIC THYROID CANCER
RR 70%
for those refractory to Iodine RT
1. Chemotherapy gives Median survival 5 months
2. Lenvatinib 24 mg PO daily OR 65%
and PFS 18.3 months (read up on side effects)
Nexavar, an option in this disease!
*MPDL3280A, by inhibiting PD-L1, will have significant activity in Metastatic Urothelial Bladder cancer.
Sunday, August 10, 2014
Most unpredictable compounds: the cytokines!
They are numerous, most insidious and varied, yet impact the trends of our life in a deep, multiple ways. And we are just now trying to dig deeper in our understanding of these molecules. The Cytokines affect almost all aspects of our lives but unlike the hormones which induces changes at organs, tissues and system levels, they act at cellular level. Their functions are poorly defined because of this cellular level of action. But it is them that act on most receptors and ions channels to induce some the most vile and irreversible changes in cells, tissues and organs. And yet they remain unknown to the common living being!
A man asked, why we get fever during the course of an infection? I answered "your Cytokines"
Why I can't put up some weight when I have cancer or an autoimmune disease? once again the "cytokines"
Why people develop Post traumatic syndrome ? the Cytokines
why cancer cells get a growth advantage over local tissue in Metastatic cancers? if you guessed "Cytokines" you are right!
What do we give in adjuvant therapy after Melanoma resection? the Cytokine
What can cure Renal cell cancer? the CYTOKINES
What affects our Joints or induce Arthropathies when cholesterol is high (hyperlipidemia)? Cytokines for god sakes!
Why we get the features of getting old even in hiding? Cytokines....
and where in hell are your doctors not measuring these Cytokines....
The thing is that even we know they exist, nobody really knows to catch all of them, study them to their fullness...and use then to their potentials. And now that we are going molecular or I should say genetic with target therapy, we can probably make them synthetically...And I suspect their make up will be varied since they come from genes that are notoriously varied....
Cytokine banks are needed, and plasma centers collect them daily! put these facts together and make the math!
A man asked, why we get fever during the course of an infection? I answered "your Cytokines"
Why I can't put up some weight when I have cancer or an autoimmune disease? once again the "cytokines"
Why people develop Post traumatic syndrome ? the Cytokines
why cancer cells get a growth advantage over local tissue in Metastatic cancers? if you guessed "Cytokines" you are right!
What do we give in adjuvant therapy after Melanoma resection? the Cytokine
What can cure Renal cell cancer? the CYTOKINES
What affects our Joints or induce Arthropathies when cholesterol is high (hyperlipidemia)? Cytokines for god sakes!
Why we get the features of getting old even in hiding? Cytokines....
and where in hell are your doctors not measuring these Cytokines....
The thing is that even we know they exist, nobody really knows to catch all of them, study them to their fullness...and use then to their potentials. And now that we are going molecular or I should say genetic with target therapy, we can probably make them synthetically...And I suspect their make up will be varied since they come from genes that are notoriously varied....
Cytokine banks are needed, and plasma centers collect them daily! put these facts together and make the math!
Thursday, August 7, 2014
Major advances in Oncology. and CRBCM on the move!
1.In lung cancer, Pembrolizumab, the PD-1 humanized antibody made the Breakthrough cut but keeping activity in first line as well advanced Non small cell lung cancer. Given at 10mg/kg every 3 to 3 weeks,
at least half of the patient will respond whae they have the PDL-1 receptor!
No patient today should die of this disease if they have the receptor, without seeing PEMBRO!
2.In ALL, CD19 targeted chimeric Antigen Receptor (CAR received Breakthrough designation and Blinatomomab....These are huge discoveries to say the least and in deisease notoriously mortal! With unprecedented response rates 80 to 100 % according to study populations !And manageable side effects!
3.The excellent Ibrutinib is "tripling" disease free survival and doubling survival in certain CLL....these are again unprecedented results of new target therapy
the standard chemotherapy is soon becoming remotely cited in current Oncology journal
and there is more to come....
Lenvatinib----Thyroid cancer
Bladder cancers----MPDL328A
Now Jakafi -Xelaoda in pancreatic cancer!!!
behind PEMBRO, NECITUMUMAB sneaking in NSCL cancers!
Belinostat for Peripheral T-cell lymphoma
Finally we see the Anti-BCL2 working in CLL--ABT-199, here we are acing the mechanism of non dying cells!
And embracing the 2nd generation anti -EGFR!!!! science is on the Go....enemies working their best to politicize science...CRBCM working hard despite ....
at least half of the patient will respond whae they have the PDL-1 receptor!
No patient today should die of this disease if they have the receptor, without seeing PEMBRO!
2.In ALL, CD19 targeted chimeric Antigen Receptor (CAR received Breakthrough designation and Blinatomomab....These are huge discoveries to say the least and in deisease notoriously mortal! With unprecedented response rates 80 to 100 % according to study populations !And manageable side effects!
3.The excellent Ibrutinib is "tripling" disease free survival and doubling survival in certain CLL....these are again unprecedented results of new target therapy
the standard chemotherapy is soon becoming remotely cited in current Oncology journal
and there is more to come....
Lenvatinib----Thyroid cancer
Bladder cancers----MPDL328A
Now Jakafi -Xelaoda in pancreatic cancer!!!
behind PEMBRO, NECITUMUMAB sneaking in NSCL cancers!
Belinostat for Peripheral T-cell lymphoma
Finally we see the Anti-BCL2 working in CLL--ABT-199, here we are acing the mechanism of non dying cells!
And embracing the 2nd generation anti -EGFR!!!! science is on the Go....enemies working their best to politicize science...CRBCM working hard despite ....
Sunday, August 3, 2014
Good update to have in hematologic malignancy, and may be a chance to visit the POLO-like kinases! take a plunge!
CONTINUING MEDICAL EDUCATION CERTIFICATE
certifies that
Mutombo Kankonde, MD
2400 Trawood Drive
Suite 303
El Paso, TX 79936
2400 Trawood Drive
Suite 303
El Paso, TX 79936
has participated in the enduring material titled
Pivotal Data Highlights on MPN and AML From the 2014 Summer Hematology Congresses
August 3, 2014
and is awarded
0.75
AMA PRA Category 1 Credit(s)™.
Medscape, LLC designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Medscape, LLC is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to provide continuing medical
education for physicians.
For information on
applicability and acceptance of continuing education credit for this
activity, please consult your professional licensing board.
| Certificate Number: 48368018 |  Cyndi Grimes Director, Continuing Medical Education Medscape, LLC |
Big good
CONTINUING MEDICAL EDUCATION CERTIFICATE
certifies that
Mutombo Kankonde, MD
2400 Trawood Drive
Suite 303
El Paso, TX 79936
2400 Trawood Drive
Suite 303
El Paso, TX 79936
has participated in the enduring material titled
Management of Follicular Lymphoma
August 3, 2014
and is awarded
1.75
AMA PRA Category 1 Credit(s)™.
Medscape, LLC designates this enduring material for a maximum of 1.75 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Medscape, LLC is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to provide continuing medical
education for physicians.
For information on
applicability and acceptance of continuing education credit for this
activity, please consult your professional licensing board.
| Certificate Number: 48367244 | Cyndi Grimes Director, Continuing Medical Education Medscape, LLC |
Thursday, July 31, 2014
With Anti-PD1, and Ibrutinib, we have entered the new world of therapy in cancers
The time of dirty bomb that standard Chemotherapy represented, has quickly led to major side effects and of course given us partial results. Cure was not achieved most of the times except in rare chemotherapy successes such as in Hodgkin disease and some cases where disease was limited, and surgery with adjuvant chemotherapy plus or minus Radiation allowed the cancer patients to survive. Even in these rare cure cases, Doctors remained on the look-out using Biomarkers that most of the time "only God knows "worked. Recurrences and secondary cancers were clearly unpredictable and random, we could not come up with decent explanation, except for a conclusion that the earlier therapeutic intervention may have precipitated them or have something to do with them.
Today, with our increasing knowledge of cellular pathways, we live one step forward, an exciting time in Oncology and hematology/Immunology/Rheumatology. The discovery that target therapy unveils new cures has the Oncology community bubbling with excitements (at least they (Oncologists) should!). We are now tackling newly cancers such as Melanoma and refractory lung cancers with further excitement then before. Indeed we are curious to know whether the promise of target therapy will be achieved in every new cancers we encounter. We suspected without clear knowledge that Target therapy would work since the effect of IL-2 in renal cancer has never been matched by standard chemotherapy, and the striking fact that only high dose Interferon worked in adjuvant treatment of Melanoma. Furthermore, our suspicion was that these agents were acting by boosting the immune system against cancer cells. No need to say or emphasize that this effect was so profound that cure was achieved in some difficult cancers. Our limitations and fear to pursue this line of attack against cancer cells were mainly limited because of the unexpected side effects (the vascular disturbance and resulting extravasation syndrome induced by these agents at high dose). And it acted as a Dirty bomb by overwhelming the cancer cells hidden paths to Apoptosis. Today however, we have gotten smarter hitting check point targets "at will" and more "surgically". And Oncologists have become a little abrasive and more confident. Expression such as "Up front, hit hard, and don't stop" is being published (Sandra Ker) about the use of Target therapies! The surprising effect of anti-PD-1/ PDL1 and their relative lack of dramatic side effects is a feast we should enjoy! Are they the receptors stimulated non-specifically by these previous high dose Interleukin-2 and Interferon...research is underway to figure that one out with certainty. But already combining these old strategies (IL-2, Interferon) with the new Ibrutinib and Nivolumab is on the mind of researchers to try to tease the new unveiled therapeutic concepts.
Many (include this authors) believe that the success of the AntiPDL-1 actually lies in a well known concept that, on a daily basis, cells that go awry end up being removed from our system by the army of white blood cells that we have, and this is why the cancer cells will work hard to hide themselves from the Lymphocytes. The discovery of ways to activates the White Blood cells against tumors seem to offer a winning approach in cancer management and therapy! The approaches tackling PD-1, PDL-1, and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), all seem to work...When in Breast cancer lymphocyte infiltration seems to predict response to chemotherapy, we know another "volet " (french for compartment) is being unveiled in the story of White blood cells and cancers!
One thing for sure, and clearly another challenge to confront now, is the build up of escape mechanisms against these new therapeutic avenues. We have come to realize, that we can't tell cells including cancer cells that it is alright to die now! Cancer cells like all cells continue to figure that our therapeutic interventions are a new "environmental" challenge and continue to figure new escape mechanisms (pathways to resistance cancers) forcing us to have to design a multiple step strategy to achieve the cure. Indeed "2 or multiple punches" strategy is needed sometime to achieve longer progression free survival or Overall survival (OS) by sequencing or concurrently using available drugs! But now that is another "Volet".....CRBCM is hard at work!
Today, with our increasing knowledge of cellular pathways, we live one step forward, an exciting time in Oncology and hematology/Immunology/Rheumatology. The discovery that target therapy unveils new cures has the Oncology community bubbling with excitements (at least they (Oncologists) should!). We are now tackling newly cancers such as Melanoma and refractory lung cancers with further excitement then before. Indeed we are curious to know whether the promise of target therapy will be achieved in every new cancers we encounter. We suspected without clear knowledge that Target therapy would work since the effect of IL-2 in renal cancer has never been matched by standard chemotherapy, and the striking fact that only high dose Interferon worked in adjuvant treatment of Melanoma. Furthermore, our suspicion was that these agents were acting by boosting the immune system against cancer cells. No need to say or emphasize that this effect was so profound that cure was achieved in some difficult cancers. Our limitations and fear to pursue this line of attack against cancer cells were mainly limited because of the unexpected side effects (the vascular disturbance and resulting extravasation syndrome induced by these agents at high dose). And it acted as a Dirty bomb by overwhelming the cancer cells hidden paths to Apoptosis. Today however, we have gotten smarter hitting check point targets "at will" and more "surgically". And Oncologists have become a little abrasive and more confident. Expression such as "Up front, hit hard, and don't stop" is being published (Sandra Ker) about the use of Target therapies! The surprising effect of anti-PD-1/ PDL1 and their relative lack of dramatic side effects is a feast we should enjoy! Are they the receptors stimulated non-specifically by these previous high dose Interleukin-2 and Interferon...research is underway to figure that one out with certainty. But already combining these old strategies (IL-2, Interferon) with the new Ibrutinib and Nivolumab is on the mind of researchers to try to tease the new unveiled therapeutic concepts.
Many (include this authors) believe that the success of the AntiPDL-1 actually lies in a well known concept that, on a daily basis, cells that go awry end up being removed from our system by the army of white blood cells that we have, and this is why the cancer cells will work hard to hide themselves from the Lymphocytes. The discovery of ways to activates the White Blood cells against tumors seem to offer a winning approach in cancer management and therapy! The approaches tackling PD-1, PDL-1, and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), all seem to work...When in Breast cancer lymphocyte infiltration seems to predict response to chemotherapy, we know another "volet " (french for compartment) is being unveiled in the story of White blood cells and cancers!
One thing for sure, and clearly another challenge to confront now, is the build up of escape mechanisms against these new therapeutic avenues. We have come to realize, that we can't tell cells including cancer cells that it is alright to die now! Cancer cells like all cells continue to figure that our therapeutic interventions are a new "environmental" challenge and continue to figure new escape mechanisms (pathways to resistance cancers) forcing us to have to design a multiple step strategy to achieve the cure. Indeed "2 or multiple punches" strategy is needed sometime to achieve longer progression free survival or Overall survival (OS) by sequencing or concurrently using available drugs! But now that is another "Volet".....CRBCM is hard at work!
Monday, July 28, 2014
Interesting find in the literature, not from CRBCM but tie our life up completely!
This can be found in the literature
110 interacting genes: ACTG1 ACTN2 AGTPBP1 AKAP6 AKAP9 ARIH2 ATF4 ATF5 ATF7IP BICD1 C14orf166 CCDC136 CCDC141 CCDC24 CCDC88A CDC5L CDK5RAP3 CEP170 CEP57L1 CEP63 CIT CLU COL4A1 DCTN1 DCTN2 DMD DNAJC7 DPYSL2 DPYSL3 DST DYNC1H1 EEF2 EIF3H EXOC1 EXOC4 EXOC7 FBXO41 FEZ1 FRYL GNB1 GNPTAB GPRASP2 HERC2P2 IFT20 IMMT ITSN1 KALRN KANSL1 KCNQ5 KIAA1377 KIF3A KIF3C KIFAP3 MACF1 MAP1A MATR3 MEMO1 MLLT10 MPPED1 MYO1A MYT1L NDEL1 NEFM NUP160 OLFM1 PAFAH1B1 PCNT PCNXL4 PDE4B PGK1 PPM1E PPP4R1 PPP5C RABGAP1 RAD21 RANBP9 RASSF7 ROGDI SH3BP5 SMARCE1 SMC2 SMC3 SNX6 SPARCL1 SPTAN1 SPTBN1 SPTBN4 SRGAP2 SRGAP3 STX18 SYBU SYNE1 TFIP11 TIAM2 TNIK TNKS TRAF3IP1 TRIO TUBB TUBB2A UTRN XPNPEP1 XRN2 YWHAE YWHAG YWHAQ YWHAZ ZFYVE20 ZNF197 ZNF365
72 interacting genes: ACTB ACTC1 ACTG1 ALDOA B3GALT4 BCAS1 BCL2L11 BMF C14orf1 CA2 CACNB1 CLIP2 CS DAZ1 DLG4 DLGAP1 DNAJB9 DNM2 DNM3 DNMT1 DYNC1H1 DYNC1I1 EEF1A1 GAPDH GLUD1 GLUL GNB2L1 GPHN GRIN3A HIP1R HSPA8 INPP1 LDHA MAP1B MARK3 MAST2 ME2 MTA1 MTR MYO10 MYO5A NDUFA4L2 NFKBIA NOS1 NRF1 NTRK1 NTRK2 NTRK3 PAK1 PAN2 PARD3 PAX6 PFKM PFKP PKIA PKIB PKIG POLH RAB4A RGS2 SHROOM3 TERT THAP8 TNFRSF14 TP53BP1 TUBA3C TUBB TXNDC17 VIM ZHX1 ZMYND11 ZNF354A
Disclaimer, we are not the maker of this list,
but love to review these genes individually
something is hidden here
I don't know what or where
but I can feel it
A little work will just go a long way to decipher what !
And let's get to it then....
CRBCM working despite the " intemperies" and adversities of the moment! We believe in our cause while the enemies are hard at work to stop science!
110 interacting genes: ACTG1 ACTN2 AGTPBP1 AKAP6 AKAP9 ARIH2 ATF4 ATF5 ATF7IP BICD1 C14orf166 CCDC136 CCDC141 CCDC24 CCDC88A CDC5L CDK5RAP3 CEP170 CEP57L1 CEP63 CIT CLU COL4A1 DCTN1 DCTN2 DMD DNAJC7 DPYSL2 DPYSL3 DST DYNC1H1 EEF2 EIF3H EXOC1 EXOC4 EXOC7 FBXO41 FEZ1 FRYL GNB1 GNPTAB GPRASP2 HERC2P2 IFT20 IMMT ITSN1 KALRN KANSL1 KCNQ5 KIAA1377 KIF3A KIF3C KIFAP3 MACF1 MAP1A MATR3 MEMO1 MLLT10 MPPED1 MYO1A MYT1L NDEL1 NEFM NUP160 OLFM1 PAFAH1B1 PCNT PCNXL4 PDE4B PGK1 PPM1E PPP4R1 PPP5C RABGAP1 RAD21 RANBP9 RASSF7 ROGDI SH3BP5 SMARCE1 SMC2 SMC3 SNX6 SPARCL1 SPTAN1 SPTBN1 SPTBN4 SRGAP2 SRGAP3 STX18 SYBU SYNE1 TFIP11 TIAM2 TNIK TNKS TRAF3IP1 TRIO TUBB TUBB2A UTRN XPNPEP1 XRN2 YWHAE YWHAG YWHAQ YWHAZ ZFYVE20 ZNF197 ZNF365
72 interacting genes: ACTB ACTC1 ACTG1 ALDOA B3GALT4 BCAS1 BCL2L11 BMF C14orf1 CA2 CACNB1 CLIP2 CS DAZ1 DLG4 DLGAP1 DNAJB9 DNM2 DNM3 DNMT1 DYNC1H1 DYNC1I1 EEF1A1 GAPDH GLUD1 GLUL GNB2L1 GPHN GRIN3A HIP1R HSPA8 INPP1 LDHA MAP1B MARK3 MAST2 ME2 MTA1 MTR MYO10 MYO5A NDUFA4L2 NFKBIA NOS1 NRF1 NTRK1 NTRK2 NTRK3 PAK1 PAN2 PARD3 PAX6 PFKM PFKP PKIA PKIB PKIG POLH RAB4A RGS2 SHROOM3 TERT THAP8 TNFRSF14 TP53BP1 TUBA3C TUBB TXNDC17 VIM ZHX1 ZMYND11 ZNF354A
Disclaimer, we are not the maker of this list,
but love to review these genes individually
something is hidden here
I don't know what or where
but I can feel it
A little work will just go a long way to decipher what !
And let's get to it then....
CRBCM working despite the " intemperies" and adversities of the moment! We believe in our cause while the enemies are hard at work to stop science!
Medicine of the future!
Medicine of the future
The way we see it, in the near future, 3 main factors will determine what will be driving medicine in the future.
1.The patient genome which determine the patient potential to survive and cope with his environment.
2.Presence in that genome of favorable Heterogeneic Alleles or genes to both treatment and environmental stimulants.
3.more powerful computers to process various integrals of gene, receptors,and cytokines patterns. This suppose detectors of thin nuances in molecular behaviors at cellular and nano-molecular levels. Yes we know the main pathways and probably several secondary pathways of significance, but our ability to interpret, quantify, and draw meaningful conclusions, is still preliminary and at the dawn of what will be medicine of tomorrow (ie. the change of various membrane receptors when a neoplastic process is engaged in a cell.) We have yet to define clear bio-markers for most diseases and of life determinants in general. We are still linking the fact that we survive to what our neighbors and boss do, our work environment, what we drink is sweet or not, when the cell, where life is really determined sees everything as a chemical stimulant!
Other secondary factors:
1-known new target therapies
2-Telomere status
3-new chemicals created by our "smart" engineers
4-potential new pathogens and how they will enter the frey of our world
etc...
Globally,
Each step of cellular gene and metabolism will need to be carefully studied and perfectly understood to reach the medicine of the future.
example of a visit in the future:
Mrs Freddy comes to DR Pizzazz complaining of headache. She gives him a chip containing all her genes.
The chip is introduced in a smart computer and with a sample of blood, the computer tells the DR that indeed the migraine came from an undetected Vasculitis based on these facts (ie.pattern of the patient cytokines, gene amplifications and ....), and that Prednisone would be dangerous for this lady because of the presence of a close by Receptor gene that may induce an irreversible chemical disturbance of membrane lipids and that Aleve would be best in this case. And by the way there is a secondary gene that will accelerate destruction of Telomeres'tails....and so on....!
This is the kind of Medicine we are aiming at....and all we don't know to reach there is a GAP TO FILL!
CRBCM advancing in the current darkness with a clear vision...
The way we see it, in the near future, 3 main factors will determine what will be driving medicine in the future.
1.The patient genome which determine the patient potential to survive and cope with his environment.
2.Presence in that genome of favorable Heterogeneic Alleles or genes to both treatment and environmental stimulants.
3.more powerful computers to process various integrals of gene, receptors,and cytokines patterns. This suppose detectors of thin nuances in molecular behaviors at cellular and nano-molecular levels. Yes we know the main pathways and probably several secondary pathways of significance, but our ability to interpret, quantify, and draw meaningful conclusions, is still preliminary and at the dawn of what will be medicine of tomorrow (ie. the change of various membrane receptors when a neoplastic process is engaged in a cell.) We have yet to define clear bio-markers for most diseases and of life determinants in general. We are still linking the fact that we survive to what our neighbors and boss do, our work environment, what we drink is sweet or not, when the cell, where life is really determined sees everything as a chemical stimulant!
Other secondary factors:
1-known new target therapies
2-Telomere status
3-new chemicals created by our "smart" engineers
4-potential new pathogens and how they will enter the frey of our world
etc...
Globally,
Each step of cellular gene and metabolism will need to be carefully studied and perfectly understood to reach the medicine of the future.
example of a visit in the future:
Mrs Freddy comes to DR Pizzazz complaining of headache. She gives him a chip containing all her genes.
The chip is introduced in a smart computer and with a sample of blood, the computer tells the DR that indeed the migraine came from an undetected Vasculitis based on these facts (ie.pattern of the patient cytokines, gene amplifications and ....), and that Prednisone would be dangerous for this lady because of the presence of a close by Receptor gene that may induce an irreversible chemical disturbance of membrane lipids and that Aleve would be best in this case. And by the way there is a secondary gene that will accelerate destruction of Telomeres'tails....and so on....!
This is the kind of Medicine we are aiming at....and all we don't know to reach there is a GAP TO FILL!
CRBCM advancing in the current darkness with a clear vision...
Sunday, July 27, 2014
working hard to meet the needs of our patients
Mutombo Kankonde, MD, MPH
Oncology
11601 Pellicano Drive
Suite A2
El Paso, TX 79936
Suite A2
El Paso, TX 79936
(915) 307-3354
Hitch a hike towards a comprehensive Cytokine Bank and Manufacturing Unit
The Protein Data Bank funded by several great institutions is a good starting point:
http://www.rcsb.org/pdb/home/home.do
http://www.rcsb.org/pdb/home/home.do
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