Community Oncologist Education and Support Systems ‐
Renal Cell Carcinoma and Hematologic Malignancies
Request for Proposals
National Comprehensive Cancer Network and
Pfizer Independent Grants for Learning & Change
Pfizer
and National Comprehensive Cancer Network (NCCN) are collaborating
to offer a new grant opportunity focused on improving care for patients with rare types of cancer such as renal cell carcinoma (RCC) and certain hematologic malignancies, where treatment options are complex and rapidly advancing.
The
mission of Pfizer Independent Grants for Learning & Change
(IGL&C) is
to accelerate the adoption of evidence‐based innovations that align the mutual interests of patients, healthcare professionals, and Pfizer, through support of independent professional education activities. The term “independent” means the initiatives funded by Pfizer are the full responsibility of the recipient organization. Pfizer has no influence over any aspect of the initiatives, and only asks for reports about the results and impact of the initiatives, which it may share publicly.
NCCN,
a not‐for‐profit alliance of twenty‐three (23) of the world’s leading
cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. NCCN has access, through its member institutions, to the world’s leading thought leaders in all areas and aspects of oncology who are integral to the execution of this program.
This
Request for Proposals (RFP) is being issued by both organizations. NCCN
is
the lead organization for review and evaluation of applications. A review committee, led by NCCN, will make decisions on which proposals will receive funding. Grant funding will be provided by Pfizer. Collectively, up to $2 million is available for the program.
Once announced through this distribution list, the RFP
will also be
posted on our website at www.pfizer.com/ refer to the full text of the RFP for various key dates and submission instructions.
Please send an email to
IGLC@pfizer.com to unsubscribe from this distribution.
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Thursday, October 24, 2013
BY COMMUNITY ONCOLOGIST, THE CRBCM IS CLEARLY NOT INCLUDED! THEY KNOW WHO THEY MEAN!
Bubbling with excitements!
A Message from Medical Center of the Americas:
Dear BIOMED Registrants:
We look forward to seeing you at the region’s upcoming BIOMED Symposium on October 26, 2013
at the Camino Real Hotel located at 101 South El Paso Street in
Downtown El Paso. And, we are excited to announce that we have surpassed
our original registration expectation of 150 participants; we are now
expecting approximately 350 participants! Thank you for already helping
to make this event a success through great participation! We do want to
note, however, that this unexpected level of participation may result in
a few logistical problems at the events. Furthermore, we will be
experimenting with different types of sessions and events to determine
what works best. We request that you be patient with us as we work hard
to make this first year event successful. We will have evaluation forms
available and hope that you provide honest feedback to so that we can
improve the
event in future years.
Below
are a few reminders and updates regarding the Symposium that should
help to make things run smoothly over the next couple of days.
OCTOBER 25, 2013: PRE-SYMPOSIUM NETWORKING MIXER INFORMATION
OCTOBER 25, 2013: PRE-SYMPOSIUM NETWORKING MIXER INFORMATION
We hope you will consider attending BIOMED’s Pre-Symposium Networking Mixer on October 25, 2013 from 5:30pm-7:30pm at the El Paso Club, 18th floor, Chase Building, 201 East Main Drive, Downtown El Paso.
Network with over 200 of the region’s researchers, clinicians and
nurses, future leaders and other healthcare professionals. Valet parking
is available in the Chase Building garage, accessible via Mesa Street.
Simply bring your parking ticket to the El Paso Club for validation. Please RSVP to nsehgal@bmiamericas.org by 5 pm on Thursday, October 24, 2013.
OCTOBER 26: 2013: BIOMED SYMPOSIUM INFORMATION
Symposium Registration
Check-In Table
If you have pre-registered, please come to the Check-In Table on the Mezzanine (2nd Floor). Do not forget to bring your ticket and a form of identification. We will be providing a complimentary drink ticket to the first 180 people for the Collaboration Grant and Networking Reception from 3:30pm-4:30pm in the Ballroom.
Check-In Table
If you have pre-registered, please come to the Check-In Table on the Mezzanine (2nd Floor). Do not forget to bring your ticket and a form of identification. We will be providing a complimentary drink ticket to the first 180 people for the Collaboration Grant and Networking Reception from 3:30pm-4:30pm in the Ballroom.
Media & VIP Table
If you are affiliated with the Press, please collect your “Press Pass” from the Media & VIP Table on the Mezzanine (2nd Floor).
If you are affiliated with the Press, please collect your “Press Pass” from the Media & VIP Table on the Mezzanine (2nd Floor).
If you are a VIP
(speakers, exhibitors, moderators, judges, elected officials, head of
institutions, volunteers, and BMIA or MCA board members), please
check-in at the Media & VIP Table on the Mezzanine (2nd Floor).
**Please remember that this is a networking event, so bring lots of your business cards to trade with new contacts you make.
Hotel AccommodationsWe have reserved a block of rooms at the Camino Real Hotel located at 101 South El Paso Street and DoubleTree Hotel located at 600 North El Paso Street in Downtown El Paso at a discounted rate. Please make hotel reservations as soon as possible, as we anticipate the hotels will up fast. When you call to make a reservation, please indicate to the hotel clerk that you are making a reservation for the “BIOMED Symposium” so that you receive the discounted rate.
Symposium Parking & Directions
Parking
JUST GO AHEAD AND HELP OUT FOLKS (PHYSICIANS)!
|
October 16, 2013
Dear Indiana Licensed Controlled Substance Prescribers and Dispensers,
On
behalf of the Indiana Professional Licensing Agency, the Indiana State
Department of Health, and the Attorney General’s Prescription Drug Abuse
Prevention Task Force, we request your assistance in achieving our
mutual goals to address the increasing problem of prescription drug
addiction in Indiana.
The
survey is completely anonymous, and we will have no ability to track
participants’ identities. The instrument will take approximately 10-15
minutes to complete.
The
survey was created in collaboration with the Indiana Professional
Licensing Agency, the Center for Health Policy, the Indiana State
Department of Health, and the Attorney General’s Prescription Drug Abuse
Prevention Task Force.
The
survey is being administered through the Center for Health Policy at
the IU Richard M. Fairbanks School of Public Health at IUPUI.
The
Center for Health Policy will be solely responsible for analyzing the
data and preparing a public report that summarizes the findings from
this research. The final report will be distributed electronically and
be available on the Center’s website: www.healthpolicy.iupui.edu in early 2014. Their report will be used to improve the INSPECT program and provide better support to healthcare providers.
Please click on the link below for additional details and to begin the survey.
Thank you in advance for your vital assistance with this endeavor!
Sincerely,
Greg Pachmayr
INSPECT Director Indiana Professional Licensing Agency 402 W Washington St RM W072 Indianapolis, IN 46204 |
A very important read!
Arkadia Activates Smad3/Smad4-Dependent Transcription by Triggering Signal-Induced SnoN Degradation▿†
- Laurence Levy1,
- Michael Howell1,
- Debipriya Das1,
- Sean Harkin1,
- Vasso Episkopou2 and
- Caroline S. Hill1,*
+ Author Affiliations
ABSTRACT
E3 ubiquitin ligases play important roles
in regulating transforming growth factor β (TGF-β)/Smad signaling.
Screening of
an E3 ubiquitin ligase small interfering RNA
library, using TGF-β induction of a Smad3/Smad4-dependent luciferase
reporter
as a readout, revealed that Arkadia is an E3
ubiquitin ligase that is absolutely required for this TGF-β response.
Knockdown
of Arkadia or overexpression of a dominant-negative
mutant completely abolishes transcription from Smad3/Smad4-dependent
reporters,
but not from Smad1/Smad4-dependent reporters or
from reporters driven by Smad2/Smad4/FoxH1 complexes. We show that
Arkadia
specifically activates transcription via
Smad3/Smad4 binding sites by inducing degradation of the transcriptional
repressor
SnoN. Arkadia is essential for TGF-β-induced SnoN
degradation, but it has little effect on SnoN levels in the absence of
signal.
Arkadia interacts with SnoN and induces its
ubiquitination irrespective of TGF-β/Activin signaling, but SnoN is
efficiently
degraded only when it forms a complex with both
Arkadia and phosphorylated Smad2 or Smad3. Finally, we describe an
esophageal
cancer cell line (SEG-1) that we show has lost
Arkadia expression and is deficient for SnoN degradation. Reintroduction
of
wild-type Arkadia restores TGF-β-induced
Smad3/Smad4-dependent transcription and SnoN degradation in these cells,
raising
the possibility that loss of Arkadia function may
be relevant in cancer.
=================================================================
This is very important because,
1. we are not very good at activating genes, so this is one important way. (all we do is inhibit genes and their protein derivative-that we know!)
2. cancer decreases SMAD to induce lack of proliferation control (through CDK1 for SMAD3 suppression) and disturbance of Ubiquitilation (E3 for SMAD3). Increasing SMAD is taking away cancer "aggressiveness" a new modality of treatment!! very closely followed at CRBCM- This is to be proposed in Metastatic prone diseases such as triple negative breast cancer, pancreatic cancer and few others!
Disruption (suppression) at SMADs is a major biomarker of bad Prostate cancers!!!
=================================================================
This is very important because,
1. we are not very good at activating genes, so this is one important way. (all we do is inhibit genes and their protein derivative-that we know!)
2. cancer decreases SMAD to induce lack of proliferation control (through CDK1 for SMAD3 suppression) and disturbance of Ubiquitilation (E3 for SMAD3). Increasing SMAD is taking away cancer "aggressiveness" a new modality of treatment!! very closely followed at CRBCM- This is to be proposed in Metastatic prone diseases such as triple negative breast cancer, pancreatic cancer and few others!
Disruption (suppression) at SMADs is a major biomarker of bad Prostate cancers!!!
A dangerous gene PTPRT (PTPrho)
If you follow our blogs, you will be aware of 3 things about why a gene could be dangerous,
1. Its ability to induce malformation once absent
2. Its interaction with either multiple other genes but particularly its involvement with a "wild gene", genes that are cofactors to anything happening in the cell (Gerb2,FYN) or globally a gene that have just too many interactions with other genes (Androgen related gene).
3.In terms of cancer metastasis and non-curability, the gene involvement with the Wnt (cathenin) and the Notch. Involvement with the Rho increases the rate of multiplication.
Based on these criteria, PTPRT (PTPrho) wins the cake!
It is stimulated by Actinin alpha 1
which itself interacts with:
Actinin, alpha 1 has been shown to interact with:
Receptor-type tyrosine-protein phosphatase T is an enzyme that in humans is encoded by the PTPRT gene.[1][2][3]
PTPRT is also known as PTPrho, PTPρ and human accelerated region 9. The human accelerated regions are 49 regions of the human genome that are conserved among vertebrates, but in humans show significant distinction from other vertebrates. This region may, therefore, have played a key role in differentiating humans from apes.[4]
PTPrho is phosphorylated on tyrosine 912 in the wedge region of its first catalytic domain by Fyn tyrosine kinase. Phosphorylation at this site attenuates synapse formation in cultured neurons. When PTPrho is phosphorylated by Fyn, PTPrho appears to form homophilic multimerizations, likely in cis, which appear to decrease PTPrho association with neuroligins and neurexins. The reduction of cis interactions with neuroligins and neurexons is hypothesized to ultimately lead to the reduction in synapse formation.[12]
Evaluation of the 5’untranslated regions of PTPrho (PTPRT) cDNA indicate a number of transcription factor binding site consensus sequences, including those for AP-2, c-Myb, NF-1, sox-5, and Sp-1, Oct-1, CdxA, C/EBP, En-1, GATA-1, GATA-2, GKLF, HoxA3, Ik-2, Msx-1, Pax-4 and SRY.[5]
(RE1-silencing transcription factor) (REST) is a transcription repressor that binds to REST DNA recognition element (RE-1) in 5’UTRs. A screen of single nucleotide polymorphic genetic changes within the REST binding regions of DNA sequences revealed a polymorphism in the RE-1 of PTPrho (PTPRT). This SNP would result in less REST repressor activity, which could lead to increased expression of PTPrho (PTPRT) in cells that harbored this SNP.[15]
PTPrho is also upregulated in estrogen receptor alpha positive breast tumor samples versus estrogen receptor alpha negative tumor samples.[18] The authors evaluated 560 selected genes by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) in estrogen receptor alpha positive tissue and compared it to estrogen receptor alpha negative tissue, and found that PTPrho(PTPRT) was upregulated in the estrogen receptor alpha tissue, suggesting a non-tumor suppressor role for PTPrho. [18]"
1. Its ability to induce malformation once absent
2. Its interaction with either multiple other genes but particularly its involvement with a "wild gene", genes that are cofactors to anything happening in the cell (Gerb2,FYN) or globally a gene that have just too many interactions with other genes (Androgen related gene).
3.In terms of cancer metastasis and non-curability, the gene involvement with the Wnt (cathenin) and the Notch. Involvement with the Rho increases the rate of multiplication.
Based on these criteria, PTPRT (PTPrho) wins the cake!
It is stimulated by Actinin alpha 1
which itself interacts with:
Actinin, alpha 1 has been shown to interact with:
- CDK5R1,[3]
- CDK5R2,[3]
- Collagen, type XVII, alpha 1,[4]
- GIPC1,[5]
- PDLIM1,[6][7]
- Protein kinase N1,[8]
- SSX2IP,[9] and
- Zyxin.[10][11]
- PTPRT(PTPrho)[12] wikipedia
- The involvement with GIPC1 needs to be noted! because it provide the link to DAB2, a gene suppressed in Ovarian cancers! GIPC1 reaches DAB2 through MYO-6.
- well Actinin
Receptor-type tyrosine-protein phosphatase T is an enzyme that in humans is encoded by the PTPRT gene.[1][2][3]
PTPRT is also known as PTPrho, PTPρ and human accelerated region 9. The human accelerated regions are 49 regions of the human genome that are conserved among vertebrates, but in humans show significant distinction from other vertebrates. This region may, therefore, have played a key role in differentiating humans from apes.[4]
PTPrho is phosphorylated on tyrosine 912 in the wedge region of its first catalytic domain by Fyn tyrosine kinase. Phosphorylation at this site attenuates synapse formation in cultured neurons. When PTPrho is phosphorylated by Fyn, PTPrho appears to form homophilic multimerizations, likely in cis, which appear to decrease PTPrho association with neuroligins and neurexins. The reduction of cis interactions with neuroligins and neurexons is hypothesized to ultimately lead to the reduction in synapse formation.[12]
Evaluation of the 5’untranslated regions of PTPrho (PTPRT) cDNA indicate a number of transcription factor binding site consensus sequences, including those for AP-2, c-Myb, NF-1, sox-5, and Sp-1, Oct-1, CdxA, C/EBP, En-1, GATA-1, GATA-2, GKLF, HoxA3, Ik-2, Msx-1, Pax-4 and SRY.[5]
(RE1-silencing transcription factor) (REST) is a transcription repressor that binds to REST DNA recognition element (RE-1) in 5’UTRs. A screen of single nucleotide polymorphic genetic changes within the REST binding regions of DNA sequences revealed a polymorphism in the RE-1 of PTPrho (PTPRT). This SNP would result in less REST repressor activity, which could lead to increased expression of PTPrho (PTPRT) in cells that harbored this SNP.[15]
PTPrho is also upregulated in estrogen receptor alpha positive breast tumor samples versus estrogen receptor alpha negative tumor samples.[18] The authors evaluated 560 selected genes by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) in estrogen receptor alpha positive tissue and compared it to estrogen receptor alpha negative tissue, and found that PTPrho(PTPRT) was upregulated in the estrogen receptor alpha tissue, suggesting a non-tumor suppressor role for PTPrho. [18]"
Wednesday, October 23, 2013
SOME MOVEMENTS FROM CPRIT
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Unsubscribe from this list | Forward to a friend| Update your profile Our mailing address is:
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our movie project moving forward!
Hi kanko1,
The project you are following "A WHITE WOMAN TO THE CONGO" has reached level 4!
Click on the following link to view the latest update of the project now!
http://juntoboxfilms.com/projects/a-white-woman-to-the-congo
http://juntoboxfilms.com/projects/a-white-woman-to-the-congo
join us at the BIOMED RESEARCH CONFERENCE /MEDICAL CENTER OF THE AMERICAS/CRBCM WILL BE PRESENT!
A Message from Medical Center of the Americas:
Dear BIOMED Registrants:
We hope you will consider attending BIOMED’s Pre-Symposium Networking Mixer on October 25, 2013 from 5:30pm-7:30pm at the El Paso Club, 18th floor, Chase Building, 201 East Main Drive, Downtown El Paso.
Network with over 200 of the region’s researchers, clinicians and
nurses, future leaders and other healthcare professionals. Valet parking
is available in the Chase Building garage. Simply bring your parking
ticket to the El Paso Club for validation. Please RSVP to nsehgal@bmiamericas.org by 5 pm on Thursday, October 24, 2013.
Sincerely,
Neyha Sehgal
BIOMED Organizer
BIOMED Organizer
Imperfection of current tools for genetic evaluations
It is quite evident that despite major advances in genetic studies through the PCR and other sequencing measures, the evaluation of genes and their effects still require highly qualified technicians using sophisticated equipments. One of the implications of this fact is that when one wants to try to look into any scientific fact, a battery of scientists need to be mobilized!
For example, we know that when patients are exposed to a new medication (ie. chemotherapy drug), some patient will have inherent resistance to the drug. That is they are promptly rejecting the drug, while other will respond first and then develop mechanisms of resistance. To date, they are no ways of determining which patient is doing what when exposed to the drug! And this despite our advances in technology.
Our current practice is to give the drug, and wait 3-6 months and check through radiologic and biomarker means if the tumor grow despite the drug. During the 3 to 6 months, refractory tumors have time to build in new genetic mutations giving them new mechanisms of escape, defense and otherwise eluding future attacks, and most importantly metastasize to new sites in the host, complicating our battle and making full eradication impossible and dooming our chance for a cure! Indeed with tumors of "aggressive" tendencies, 6 months is a lifetime of opportunities to settle in and impose a toll of reversible and irreversible disruptions into the host!
This strategy is not good for us.
This is happening despite our knowledge of many facts that could help us avoid this current practice. we know already many pathways and mechanisms of resistance (ie. the MDR gene) but we don't use them for our relevant patients. We try it on dogs however!
--------------------------------------------------------------------------------------------------------
-----------------------------------------------------------------------------------------------------
We know that pathways get underway through consumption of measurable co-factors and obligatory steps that we can promptly measure and determine that the drug is being used or allowed to act at cellular level. Is it the lack of will, or the sense of desperation because of limitations in our available options that make us afraid to know the truth early. The point is we cannot go on avoiding to know what is in store for the patients!
Many drugs act through Adenyl Cyclase, many drugs use the Gerb-2, Gab1, etc....why can't we use these available biomarkers of drug actions. DNMT1 AT EPIGENETIC LEVEL (OR SIMILAR MOLECULES)
-----------------------------------------------------------------------
DNA (cytosine-5)-methyltransferase 1 is an enzyme that in humans is encoded by the DNMT1 gene.[1]
DNA (cytosine-5-)-methyltransferase 1 has a role in the establishment and regulation of tissue-specific patterns of methylated cytosine residues. Aberrant methylation patterns are associated with certain human tumors and developmental abnormalities.[2][3]" wikipedia
-----------------------------------------------------------------------------------------------------------------------------------
has been proposed as a way to gauge imprinted information
can we try this as a biomarker of drug effect?
SUFFICE IS TO SAY WE CAN'T GO ON FOOLING OUR PATIENTS INTO INEFFECTIVE DRUG TRIALS! THE TIME TO KNOW IS NOW! AND HERE WE GO AGAIN, A TEAM OF INVESTIGATORS WITH SOPHISTICATED MACHINES NEED TO GO BACK TO WORK AGAIN ON THIS NEW LEAD! THE ANSWER IN 5 YEARS!
For example, we know that when patients are exposed to a new medication (ie. chemotherapy drug), some patient will have inherent resistance to the drug. That is they are promptly rejecting the drug, while other will respond first and then develop mechanisms of resistance. To date, they are no ways of determining which patient is doing what when exposed to the drug! And this despite our advances in technology.
Our current practice is to give the drug, and wait 3-6 months and check through radiologic and biomarker means if the tumor grow despite the drug. During the 3 to 6 months, refractory tumors have time to build in new genetic mutations giving them new mechanisms of escape, defense and otherwise eluding future attacks, and most importantly metastasize to new sites in the host, complicating our battle and making full eradication impossible and dooming our chance for a cure! Indeed with tumors of "aggressive" tendencies, 6 months is a lifetime of opportunities to settle in and impose a toll of reversible and irreversible disruptions into the host!
This strategy is not good for us.
This is happening despite our knowledge of many facts that could help us avoid this current practice. we know already many pathways and mechanisms of resistance (ie. the MDR gene) but we don't use them for our relevant patients. We try it on dogs however!
--------------------------------------------------------------------------------------------------------
"Get Your Dog Tested*
Blood sample or cheek swab?
DNA obtained from a dog’s blood is the same DNA that would be obtained from that dog’s cheek cells using a swab. We allow submission of either sample because blood is often the sample preferred by veterinary hospitals while cheek swabs are generally preferred by dog owners."College of Veterinary Medicine
Veterinary Clinical Pharmacology Lab
-----------------------------------------------------------------------------------------------------
We know that pathways get underway through consumption of measurable co-factors and obligatory steps that we can promptly measure and determine that the drug is being used or allowed to act at cellular level. Is it the lack of will, or the sense of desperation because of limitations in our available options that make us afraid to know the truth early. The point is we cannot go on avoiding to know what is in store for the patients!
Many drugs act through Adenyl Cyclase, many drugs use the Gerb-2, Gab1, etc....why can't we use these available biomarkers of drug actions. DNMT1 AT EPIGENETIC LEVEL (OR SIMILAR MOLECULES)
-----------------------------------------------------------------------
DNA (cytosine-5)-methyltransferase 1 is an enzyme that in humans is encoded by the DNMT1 gene.[1]
DNA (cytosine-5-)-methyltransferase 1 has a role in the establishment and regulation of tissue-specific patterns of methylated cytosine residues. Aberrant methylation patterns are associated with certain human tumors and developmental abnormalities.[2][3]" wikipedia
-----------------------------------------------------------------------------------------------------------------------------------
has been proposed as a way to gauge imprinted information
can we try this as a biomarker of drug effect?
SUFFICE IS TO SAY WE CAN'T GO ON FOOLING OUR PATIENTS INTO INEFFECTIVE DRUG TRIALS! THE TIME TO KNOW IS NOW! AND HERE WE GO AGAIN, A TEAM OF INVESTIGATORS WITH SOPHISTICATED MACHINES NEED TO GO BACK TO WORK AGAIN ON THIS NEW LEAD! THE ANSWER IN 5 YEARS!
Sunday, October 20, 2013
EVEN HYPERTENSION IS CYTOKINE INDUCED
e-MED:
"Due to investigations into the pathophysiology of hypertension, both in animals and humans, growing evidence suggests that hypertension may have an immunological basis. Studies have revealed that hypertension is associated with renal infiltration of immune cells and that pharmacologic immunosuppression (such as with the drug mycophenolate mofetil) or pathologic immunosuppression (such as occurs with HIV) results in reduced blood pressure in animals and humans. Evidence suggests that T lymphocytes and T-cell derived cytokines (eg, interleukin 17, tumor necrosis factor alpha) play an important role in hypertension. One hypotehesis is that prehypertension results in oxidation and altered mechanical forces that lead to the formation of neoantigens, which are then presented to T cells, leading to T-cell activation and infiltration of critical organs (eg, kidney, vasculature). This results in persistent or severe hypertension and end organ damage. promote T-lymphocyte activation and infiltration and contribute to the pathophysiology of hypertension."
"Due to investigations into the pathophysiology of hypertension, both in animals and humans, growing evidence suggests that hypertension may have an immunological basis. Studies have revealed that hypertension is associated with renal infiltration of immune cells and that pharmacologic immunosuppression (such as with the drug mycophenolate mofetil) or pathologic immunosuppression (such as occurs with HIV) results in reduced blood pressure in animals and humans. Evidence suggests that T lymphocytes and T-cell derived cytokines (eg, interleukin 17, tumor necrosis factor alpha) play an important role in hypertension. One hypotehesis is that prehypertension results in oxidation and altered mechanical forces that lead to the formation of neoantigens, which are then presented to T cells, leading to T-cell activation and infiltration of critical organs (eg, kidney, vasculature). This results in persistent or severe hypertension and end organ damage. promote T-lymphocyte activation and infiltration and contribute to the pathophysiology of hypertension."
Protease inhibitors could play a role in 2nd line ER positive breast cancer by blocking cytokine formation
"
Researchers are investigating whether protease inhibitors could possibly be used to treat cancer. For example, nelfinavir and atazanavir are able to kill tumor cells in culture (in a Petri dish).[10][11] This effect has not yet been examined in humans; but studies in laboratory mice have shown that nelfinavir is able to suppress the growth of tumors in these animals, which represents a promising lead towards testing this drug in humans as well.[11]
Inhibitors of the proteasome, such as Velcade/Bortezomib are now front-line drugs for the treatment of various cancers, notably Multiple Myeloma." wikipedia
could you imagine blocking formation of undesirable cytokines, you could prevent resistance to to AIs., you could delay resistance to hormone based treatment modalities!
Researchers are investigating whether protease inhibitors could possibly be used to treat cancer. For example, nelfinavir and atazanavir are able to kill tumor cells in culture (in a Petri dish).[10][11] This effect has not yet been examined in humans; but studies in laboratory mice have shown that nelfinavir is able to suppress the growth of tumors in these animals, which represents a promising lead towards testing this drug in humans as well.[11]
Inhibitors of the proteasome, such as Velcade/Bortezomib are now front-line drugs for the treatment of various cancers, notably Multiple Myeloma." wikipedia
could you imagine blocking formation of undesirable cytokines, you could prevent resistance to to AIs., you could delay resistance to hormone based treatment modalities!
Saturday, October 19, 2013
other puzzling roles of cytokines!
It is not hard to believe that reactivation of TB under Infliximab therapy would be linked to some cytokine or that pain and increased risk of Achille's tendon rupture following chronic use of Ciprofloxacin would be under the doing by cytokines. And that any disease state associated with the so called "constitutional symptoms would be also a manifestation of Cytokines'effect. What surprise the most is how little we do ot care to determine exactly which one. We instead jump to give NSAID and related compound (steroids or Interferons) without further characterization of these cytokine. No wonder why we meet several side effcts that are unforseen such as increase of strokes and cardiovascular disorders or even bleeding! Cytokines are notorious in inducing vascular disturbances! Just ask Wegener or Paget for that matter!
Role of Cyclins in ER positive Breast cancers resistance
Now it is increasingly apparent that cyclins may have an increased presumptive role in the resistance to Aromatase inhibitors and hormone driven therapy for ER positive breast cancer. Yes as you apply pressure on the cancer cell by Blocking Receptor ultimately the cell will desensitize itself from this deadly lack of stimulation. Cancer cells want to survive, Increasing evidences suggest that cell desensitization is by way of the cytokines. It is not by mistake that disruption of epigenetic events by Entinostat which ultimately change significantly the profile of cyclins produced by the cell will lead to breaking of cancerous cell resistance to Hormone receptor driven target therapy. The cancerous cell uses the NF-kB and c-jun (stress related PI3K/AKT/MTOR) for survival and we know what happens when these pathways reach the epigenetic zone, new cyclins are metabolized to induce resistance. The proof is in the pudding, only MTOR inhibitors, and anti-CDK break the resistance to AI or SERMs.
Which Cytokines affects induce desensitization is a hot question, and the mechanism trggering the need for desensitization need to be aggressively pursued. Assumption is that dying cells may through the Wnt and Notch give information that eventually leads to resistance in surviving cells. How ? when? remember cell since they are born have the instinctive reflex to survive. It is their mission, it is their commitment! Dying cancer cells will have to tell somehow the living cells how and why they are dying for those uninvolved to be prepared and possibly a global cellular desensitization of growth inducing receptor is a reflex. Indeed it has been shown that cancer cells significantly reduce dependency on growth factor stimulation for an internal "stress" like metabolism. What trigger this alternative "mode de vie" is in itself a pathway to global resistance to outside stimulation and death inducing external compounds!
On epigenetic level, a switch in transcription, would be enough to alter the cytokines with a resulting resistant change in effects at the receptors!
Here at the CRBCM, work is increasing daily as leads multiply.
The main question is should we incrementally add these agents in a sequential way, or should we give these agents together or all 3 for greater good. will concurrent use actually disrupt the effect of the other, in other words, should we wait for the resistance to develop in order to add the other mode of of targeting agents when the cancer is counting on it the most? Adding the MTOR after Avastin failure has proven to be supportive of the sequential intervention by some reports whereas giving them concurrently may not be additive! Why? by now receptor site of Avastin is "desensitize" while the surviving cell use the PI3K/MTOR to survive, hit it now with MTOR inhibitor, and Histone deacetylator inhibitor like we are doing now with ER positive breast cancers!
Which Cytokines affects induce desensitization is a hot question, and the mechanism trggering the need for desensitization need to be aggressively pursued. Assumption is that dying cells may through the Wnt and Notch give information that eventually leads to resistance in surviving cells. How ? when? remember cell since they are born have the instinctive reflex to survive. It is their mission, it is their commitment! Dying cancer cells will have to tell somehow the living cells how and why they are dying for those uninvolved to be prepared and possibly a global cellular desensitization of growth inducing receptor is a reflex. Indeed it has been shown that cancer cells significantly reduce dependency on growth factor stimulation for an internal "stress" like metabolism. What trigger this alternative "mode de vie" is in itself a pathway to global resistance to outside stimulation and death inducing external compounds!
On epigenetic level, a switch in transcription, would be enough to alter the cytokines with a resulting resistant change in effects at the receptors!
Here at the CRBCM, work is increasing daily as leads multiply.
The main question is should we incrementally add these agents in a sequential way, or should we give these agents together or all 3 for greater good. will concurrent use actually disrupt the effect of the other, in other words, should we wait for the resistance to develop in order to add the other mode of of targeting agents when the cancer is counting on it the most? Adding the MTOR after Avastin failure has proven to be supportive of the sequential intervention by some reports whereas giving them concurrently may not be additive! Why? by now receptor site of Avastin is "desensitize" while the surviving cell use the PI3K/MTOR to survive, hit it now with MTOR inhibitor, and Histone deacetylator inhibitor like we are doing now with ER positive breast cancers!
FROM MEDSCAPE
Important Safety Information |
Full Prescribing Information
KADCYLA showed treatment benefit in HER2+ metastatic breast cancer (MBC)
in overall survival (OS) and progression-free survival (PFS) vs lapatinib + capecitabine1
For more details about these and other EMILIA trial endpoints, visit KADCYLA.com.
Indication
KADCYLA®
(ado-trastuzumab emtansine), as a single agent, is indicated for the
treatment of patients with
HER2-positive (HER2+), metastatic breast cancer (MBC) who previously
received trastuzumab and a taxane, separately or in combination.
Patients should have either:
- Received prior therapy for metastatic disease, or
- Developed disease recurrence during or within six months of completing adjuvant therapy
KADCYLA extended median OS by nearly 6 months1
50% improvement in median PFS for KADCYLA vs lapatinib + capecitabine1
- 9.6 months vs 6.4 months; HR=0.650; 95% CI: 0.549, 0.771; P<0.0001
Important Safety Information
Boxed WARNINGS: HEPATOTOXICITY, CARDIAC TOXICITY, EMBRYO-FETAL TOXICITY
- Do Not Substitute KADCYLA for or with Trastuzumab
- Hepatotoxicity: Serious hepatotoxicity has been reported, including liver failure and death in patients treated with KADCYLA. Monitor serum transaminases and bilirubin prior to initiation of KADCYLA treatment and prior to each KADCYLA dose. Reduce dose or discontinue KADCYLA as appropriate in cases of increased serum transaminases or total bilirubin
- Cardiac Toxicity: KADCYLA administration may lead to reductions in left ventricular ejection fraction (LVEF). Evaluate left ventricular function in all patients prior to and during treatment with KADCYLA. Withhold treatment for clinically significant decrease in left ventricular function
- Embryo-Fetal Toxicity: Exposure to KADCYLA can result in embryo-fetal death or birth defects. Advise patients of these risks and the need for effective contraception
Additional Important Safety Information
Left Ventricular Dysfunction (LVD)
- Patients treated with KADCYLA are at increased risk of developing LVD. In EMILIA, LVD occurred in 1.8% of patients in the KADCYLA-treated group and in 3.3% in the comparator group. Permanently discontinue KADCYLA if LVEF has not improved or has declined further
Pregnancy Registry
- Advise patients to contact their healthcare provider immediately if they suspect they may be pregnant. Encourage women who may be exposed to KADCYLA during pregnancy to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720
Pulmonary Toxicity
- Cases of interstitial lung disease (ILD), including pneumonitis, some leading to acute respiratory distress syndrome or fatal outcome have been reported in clinical trials with KADCYLA. In EMILIA, the overall frequency of pneumonitis was 1.2%
- Treatment with KADCYLA should be permanently discontinued in patients diagnosed with ILD or pneumonitis
Infusion-Related Reactions, Hypersensitivity Reactions
- Treatment with KADCYLA has not been studied in patients who had trastuzumab permanently discontinued due to infusion-related reactions (IRR) and/or hypersensitivity reactions; treatment with KADCYLA is not recommended for these patients. In EMILIA, the overall frequency of IRRs in patients treated with KADCYLA was 1.4%
- KADCYLA treatment should be interrupted in patients with severe IRR and permanently discontinued in the event of a life-threatening IRR. Patients should be closely monitored for IRR reactions, especially during the first infusion
Thrombocytopenia
- In EMILIA, the incidence of ≥ Grade 3 thrombocytopenia was 14.5% in the KADCYLA-treated group and 0.4% in the comparator group (overall incidence 31.2% and 3.3%, respectively)
- Monitor platelet counts prior to initiation of KADCYLA and prior to each KADCYLA dose. Institute dose modifications as appropriate
Neurotoxicity
- In EMILIA, the incidence of ≥ Grade 3 peripheral neuropathy was 2.2% in the KADCYLA-treated group and 0.2% in the comparator group (overall incidence 21.2% and 13.5%, respectively)
- Monitor for signs or symptoms of neurotoxicity. KADCYLA should be temporarily discontinued in patients experiencing Grade 3 or 4 peripheral neuropathy until resolution to ≤ Grade 2
HER2 Testing
- Detection of HER2 protein overexpression or gene amplification is necessary for selection of patients appropriate for KADCYLA. Perform using FDA approved tests by laboratories with demonstrated proficiency
Extravasation
- In KADCYLA clinical studies, reactions secondary to extravasation have been observed and were generally mild. The infusion site should be closely monitored for possible subcutaneous infiltration during drug administration. Specific treatment for KADCYLA extravasation is unknown
Nursing Mothers
- Discontinue nursing or discontinue KADCYLA taking into consideration the importance of the drug to the mother
Adverse Reactions
- The most common ADRs seen with KADCYLA in EMILIA (frequency > 25%) were nausea, fatigue, musculoskeletal pain, thrombocytopenia, increased transaminases, headache, and constipation. The most common NCI-CTCAE (version 3) ≥ Grade 3 ADRs (frequency >2%) were thrombocytopenia, increased transaminases, anemia, hypokalemia, peripheral neuropathy and fatigue
You are encouraged to report side effects to Genentech and the FDA. You may contact Genentech by
calling 1-888-835-2555. You may contact the FDA by visiting www.fda.gov/medwatch or
calling 1-800-FDA-1088.
Click here for full
Prescribing Information for additional important safety information, including Boxed WARNINGS.
Reference:
1. KADCYLA Prescribing Information. Genentech, Inc. May 2013.
© 2013 Genentech USA, Inc. All rights reserved. TDM0001957100
Genentech USA, Inc.
1 DNA Way
South San Francisco, CA
94080-4990
Genentech USA, Inc.
1 DNA Way
South San Francisco, CA
94080-4990
FDA PAGE on scleroderma!
"FDA approves Opsumit to treat pulmonary arterial hypertension
The U.S. Food and Drug Administration today approved Opsumit (macitentan), a new drug to treat adults with pulmonary arterial hypertension (PAH), a chronic, progressive and debilitating disease that can lead to death or the need for lung transplantation.
PAH is high blood pressure that occurs in the arteries that connect the heart to the lungs. It causes the right side of the heart to work harder than normal, which can lead to limitations on exercise ability and shortness of breath. Opsumit belongs to a class of drugs called endothelin receptor blockers, which act to relax the pulmonary arteries, decreasing blood pressure in the lungs.
Opsumit’s safety and effectiveness were established in a long-term clinical trial where 742 participants were randomly assigned to take Opsumit or placebo. The average treatment duration was about two years. In the study, Opsumit was effective in delaying disease progression, a finding that included a decline in exercise ability, worsening symptoms of PAH or need for additional PAH medication.
Similar to other members of its drug class, Opsumit carries a Boxed Warning alerting patients and health care professionals that the drug should not be used in pregnant women because it can harm the developing fetus. Female patients can receive the drug only through the Opsumit Risk Evaluation and Mitigation Strategy (REMS) Program. This restricted-distribution program requires prescribers to be certified by enrolling in the program; all female patients to be enrolled in the program and comply with applicable pregnancy testing and contraception requirements before initiating treatment; and pharmacies to be certified and to dispense Opsumit only to patients who are authorized to receive it.
Common side effects observed in those treated with Opsumit include low red blood cell count (anemia), common cold-like symptoms (nasopharyngitis), sore throat, bronchitis, headache, flu and urinary tract infection.
Opsumit is marketed by San Francisco-based Actelion Pharmaceuticals US, Inc."
GO TO FDA PAGE WHERE THIS NEWS COMES FROM!
The U.S. Food and Drug Administration today approved Opsumit (macitentan), a new drug to treat adults with pulmonary arterial hypertension (PAH), a chronic, progressive and debilitating disease that can lead to death or the need for lung transplantation.
PAH is high blood pressure that occurs in the arteries that connect the heart to the lungs. It causes the right side of the heart to work harder than normal, which can lead to limitations on exercise ability and shortness of breath. Opsumit belongs to a class of drugs called endothelin receptor blockers, which act to relax the pulmonary arteries, decreasing blood pressure in the lungs.
Opsumit’s safety and effectiveness were established in a long-term clinical trial where 742 participants were randomly assigned to take Opsumit or placebo. The average treatment duration was about two years. In the study, Opsumit was effective in delaying disease progression, a finding that included a decline in exercise ability, worsening symptoms of PAH or need for additional PAH medication.
Similar to other members of its drug class, Opsumit carries a Boxed Warning alerting patients and health care professionals that the drug should not be used in pregnant women because it can harm the developing fetus. Female patients can receive the drug only through the Opsumit Risk Evaluation and Mitigation Strategy (REMS) Program. This restricted-distribution program requires prescribers to be certified by enrolling in the program; all female patients to be enrolled in the program and comply with applicable pregnancy testing and contraception requirements before initiating treatment; and pharmacies to be certified and to dispense Opsumit only to patients who are authorized to receive it.
Common side effects observed in those treated with Opsumit include low red blood cell count (anemia), common cold-like symptoms (nasopharyngitis), sore throat, bronchitis, headache, flu and urinary tract infection.
Opsumit is marketed by San Francisco-based Actelion Pharmaceuticals US, Inc."
GO TO FDA PAGE WHERE THIS NEWS COMES FROM!
speculative gene Biomarkers!
Can amplification of FAK gene predicts for higher risk of Bacterial endocarditis in the right scenario patient?
can FAK level be an important biomarker for healing, senescence monitoring as it could be a result of cytokine effect, of general health status?
DOES FAK EXPRESSION INCREASE BACTERIAL ATTACHMENT OR INCREASE THROMBOTIC STATE?
can FAK level be an important biomarker for healing, senescence monitoring as it could be a result of cytokine effect, of general health status?
DOES FAK EXPRESSION INCREASE BACTERIAL ATTACHMENT OR INCREASE THROMBOTIC STATE?
Friday, October 18, 2013
CYTOKINE STORM!
Now comes an interesting observation, a cytokine storm can be observed when an antibody attacks the CD3 receptor such as achieved by OKT3. There is a massive cytokine release leading to fevers,nausea,vomiting severe headche chest pain,dyspnea and even pulmonary edema. and this syndrome is triggered by the engagement by OKT3 of TCR. Go figure, these Cytokine are really the effectors of disease! The affect immunity deeply, always give CMV prophylaxis if you go with the OKT3 option!
WHAT IS IT ABOUT CD3 THAT MAKES IT SO SPECIAL IN STORM TRIGERRING, THE COMPANY IT KEEPS?
WHAT IS IT ABOUT CD3 THAT MAKES IT SO SPECIAL IN STORM TRIGERRING, THE COMPANY IT KEEPS?
Thursday, October 17, 2013
THE WORLD OF CYCLINS HAS ABUNDANT INTEREST!
SOME OF THE MANY IMPLICATIONS, /THE IMPACT AND INTEREST BY RESEARCHERS THAT CAUGHT OUR ATTENTION AT CRBCM!
The activities of six synthetic CC chemokines, MCP-1, MCP-2, MCP-3,
RANTES, MIP-1α and MIP-1β on human blood monocytes were studied. All CC
chemokines elicited a bimodal migration response in vitro.
Highest numbers of migrating cells were obtained with the monocyte
chemotactic proteins (MCP) and RANTES, somewhat lower numbers with
MIP-1α, and only weak migration with MIP-1β. The most potent attractants
were MCP-1 and MIP-1α which reached maximum efficacy at 0.1 to 1 nM.
All CC chemokines also induced the release of
N-acetyl-β-D-glucosaminidase from cytochalasin B-pretreated monocytes.
The MCP were most effective (MCP-1 > MCP-3 > MCP-2), RANTES and
MIP-1α showed moderate (1/3 of MCP-1 activity), and MIP-1β only minimal
activity. Cytosolic free Ca2+ changes and exocytosis were
used to monitor receptor desensitization. Marked cross-desensitization
was observed among MCP-1, MCP-2 and MCP-3 on the one hand, and RANTES,
MIP-1α and MIP-1β on the other, indicating receptor sharing within these
two subgroups of CC chemokines. The responses to RANTES, MIP-1α and
MIP-1β were also moderately to markedly desensitized by pretreatment
with MCP-1, MCP-2 or MCP-3, while the responses to the MCP were
virtually unaffected by pretreatment with RANTES, MIP-1α and MIP-1β.
These results suggest that the MCP also interact with receptors
recognized by RANTES, MIP-1α and MIP-1β, but not vice versa. Binding
studies were performed with radiolabeled MCP-1 or MIP-1α. All MCP
competed readily for labeled MCP-1 yielding a concentration-dependent
sigmoidal displacement curve. Displacement with RANTES, MIP-1α and
MIP-1β was observed at higher concentrations, but was not complete.
Radiolabeled MIP-1α was displaced efficiently by MIP-1α or MIP-1β, but
only partially by RANTES. Of the MCP, only MC-3 completely displaced
MIP-1α, while only partial displacement was observed with MCP-1 and
MCP-2.
---------------------------------------------------------------------
Actions of the chemotactic cytokines MCP-1, MCP-2, MCP-3, RANTES, MIP-1α and MIP-1β on human monocytes
---------------------------------------------------------------------
Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2
This article has been cited by other articles in PMC.
Abstract
Monocyte
chemoattractant protein 1 (MCP-1) is a member of the chemokine cytokine
family, whose physiological function is mediated by binding to the CCR2
and CCR4 receptors, which are members of the G protein-coupled receptor
family. MCP-1 plays a critical role in both activation and migration of
leukocytes. Rapid chemokine receptor desensitization is very likely
essential for accurate chemotaxis. In this report, we show that MCP-1
binding to the CCR2 receptor in Mono Mac 1 cells promotes the rapid
desensitization of MCP-1-induced calcium flux responses. This
desensitization correlates with the Ser/Thr phosphorylation of the
receptor and with the transient translocation of the G protein-coupled
receptor kinase 2 (GRK2, also called β-adrenergic kinase 1 or βARK1) to
the membrane. We also demonstrate that GRK2 and the uncoupling protein
β-arrestin associate with the receptor, forming a macromolecular complex
shortly after MCP-1 binding. Calcium flux responses to MCP-1 in HEK293
cells expressing the CCR2B receptor were also markedly reduced upon
cotransfection with GRK2 or the homologous kinase GRK3. Nevertheless,
expression of the GRK2 dominant-negative mutant βARK-K220R did not
affect the initial calcium response, but favored receptor response to a
subsequent challenge by agonists. The modulation of the CCR2B receptor
by GRK2 suggests an important role for this kinase in the regulation of
monocyte and lymphocyte response to chemokines.
==========================================================
Proteasomal regulation of betac signaling reveals a novel mechanism for cytokine receptor heterotypic desensitization.
Source
Baylor College of Medicine, Departments of Medicine and Immunology, Biology of Inflammation Center, Houston, Texas 77030, USA.Abstract
IL-5,
IL-3, and GM-CSF are hematopoietic cytokines that are key mediators of
the allergic inflammatory response. The receptors for these three
cytokines consist of a cytokine-specific alpha (Ralpha) chain and a
shared common beta (betac) chain. Herein, we demonstrate that agonistic
ligation of these receptor subunits rapidly induces proteasomal
degradation of the betac, but not the Ralpha, cytoplasmic domain,
resulting in termination of signal transduction and yielding a truncated
betac isoform ligated to the Ralpha subunit. Proteasomal degradation of
the betac cytoplasmic domain was also a prerequisite for endocytosis
and lysosomal degradation of the ligated receptor subunits. Moreover,
proteasome-dependent termination of signaling induced by one
betac-engaging cytokine resulted in cellular desensitization to signal
transduction by subsequent stimulation with another betac-engaging
cytokine. These data provide the first evidence for ligand-dependent
proteasomal degradation of the betac cytoplasmic domain, and they
establish a novel mechanism for heterotypic desensitization of shared
cytokine receptor signaling.
========================================================
========================================================
Proteasomal regulation of βc signaling reveals a novel mechanism for cytokine receptor heterotypic desensitization
This article has been cited by other articles in PMC.
Abstract
IL-5,
IL-3, and GM-CSF are hematopoietic cytokines that are key mediators of
the allergic inflammatory response. The receptors for these three
cytokines consist of a cytokine-specific α (Rα) chain and a shared
common β (βc) chain. Herein, we demonstrate that agonistic ligation of
these receptor subunits rapidly induces proteasomal degradation of the
βc, but not the Rα, cytoplasmic domain, resulting in termination of
signal transduction and yielding a truncated βc isoform ligated to the
Rα subunit. Proteasomal degradation of the βc cytoplasmic domain was
also a prerequisite for endocytosis and lysosomal degradation of the
ligated receptor subunits. Moreover, proteasome-dependent termination of
signaling induced by one βc-engaging cytokine resulted in cellular
desensitization to signal transduction by subsequent stimulation with
another βc-engaging cytokine. These data provide the first evidence for
ligand-dependent proteasomal degradation of the βc cytoplasmic domain,
and they establish a novel mechanism for heterotypic desensitization of
shared cytokine receptor signaling.
Collaborative role of E2F transcriptional activity and G1 cyclindependent kinase activity in the induction of S phase.
Source
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.Abstract
A
considerable body of evidence points to a role for both cyclin
E/cyclin-dependent kinase (cdk)2 activity and E2F transcription activity
in the induction of S phase. We show that overexpression of cyclin
E/cdk2 in quiescent cells induces S phase, that this coincides with an
induction of E2F activity, and that coexpression of E2F enhances the
cyclin E/cdk2-mediated induction of S phase. Likewise, E2F
overexpression can induce S phase and does so in the apparent absence of
cyclin E/cdk2 activity. In addition, although the inhibition of cyclin
E/cdk2 activity blocks the induction of S phase after growth stimulation
of normal mouse embryo fibroblasts, inhibition of cyclin E/cdk2 does
not block S phase induction in Rb-/- cells where E2F activity is
deregulated. These results point to the important roles for E2F and
cyclin E/cdk2 in the induction of S phase. Moreover, the nature of the
E2F targets and the suspected targets for cyclin E/cdk2 suggests a
potential molecular mechanism for the collaborative action of cyclin
E/cdk2 and E2F in the induction of S phase.
STATE OF UNSTABLE HOMEOSTASIS: are your cytokines in a balanced state?
You can be thin, you can be average, you BETTER NOT BE OBESE LIKE SOME OF US! What is important a question is "are your cytokine in balanced state". Yesterday I met a man who run 7 miles a day, looks fit like a young marine (he is 68 years old) he showed me a certificate he earned from climbing the Kilimajaro a month ago, (If you go to Kilimanjaro get me an extra certificate!) but he was unhappy! He indeed has noted that he can't built his muscle up, has been losing weight without dieting, and now has tingling sensations in the fingers bilaterally, A buff of nutrition, he has been consuming a bunch of Vitamin B (B1,B6, B12 and the so called "complex") to no avail. His neurologist at a loss. Neck radiology clean and Carpal tunnel syndrome Ruled out, I told him its all about the Cytokines!
How do I know about my cytokine state? he asked...
"If you arrived at that question, you understand the crux of the problem" NOBODY MEASURE THE CYTOKINES IN A CLINICAL USEFUL WAY EVEN THOUGH THEY ARE THE EFFECTOR OF ALL PHYSIOLOGIC STATES!
IF YOU LOOK HEALTHY BUT YOUR CYTOKINES IS HIGH, YOU WILL END UP DYING PREMATURELY BECAUSE OF YOUR HOMEOSTASIS IS BASED ON FOUL STATE OF CYTOKINES! LET BE ANADID ABOUT THIS! SOON OR LATER, THE UNRAVELING WILL HAPPEN. WHY, BECAUSE CYTOKINES STIMULATES MANY OTHER UNINTENDED RECEPTORS, GENES, PATHWAYS AND MORE CYTOKINES!
How do I know about my cytokine state? he asked...
"If you arrived at that question, you understand the crux of the problem" NOBODY MEASURE THE CYTOKINES IN A CLINICAL USEFUL WAY EVEN THOUGH THEY ARE THE EFFECTOR OF ALL PHYSIOLOGIC STATES!
IF YOU LOOK HEALTHY BUT YOUR CYTOKINES IS HIGH, YOU WILL END UP DYING PREMATURELY BECAUSE OF YOUR HOMEOSTASIS IS BASED ON FOUL STATE OF CYTOKINES! LET BE ANADID ABOUT THIS! SOON OR LATER, THE UNRAVELING WILL HAPPEN. WHY, BECAUSE CYTOKINES STIMULATES MANY OTHER UNINTENDED RECEPTORS, GENES, PATHWAYS AND MORE CYTOKINES!
Activities at CRBCM
One may have noted the slowing down of blog activiTy
we are are planning to sit one more time for Boards
and it is a time occupying deal
CRBCM is meeting contractual obligation in El Paso, same as it did in Houston,
and Austin and Indiana. Now for the forseeable 6-8 weeks we are anchordown in El Paso.
Business getting stronger.
We are excited about the first about, the 1st Biomed research conference, join us!
![]()
One may have noted the slowing down of blog activiTy
we are are planning to sit one more time for Boards
and it is a time occupying deal
CRBCM is meeting contractual obligation in El Paso, same as it did in Houston,
and Austin and Indiana. Now for the forseeable 6-8 weeks we are anchordown in El Paso.
Business getting stronger.
We are excited about the first about, the 1st Biomed research conference, join us!
| A Message from Medical Center of the Americas: Dear Attendees:
We look forward to seeing you at the region’s upcoming BIOMED Symposium on October 26, 2013.
Pre-Symposium Networking Mixer
We would like to invite you to our Pre-Symposium Networking Mixer on October 25, 2013 from 5:30pm-7:30pm at the El Paso Club located at 201 East Main Drive, Suite 1204 in Downtown El Paso. Network with over 200 of the region’s researchers, clinicians and nurses, future leaders and other healthcare professionals.
Symposium Venue & Hotel Accommodations
Venue The 1st Annual BIOMED Symposium will be held at Camino Real Hotel located at 101 South El Paso Street in Downtown El Paso.
Accommodations
We have reserved a block of rooms at the Camino Real Hotel located at 101 South El Paso Street and DoubleTree Hotel located at 600 North El Paso Street in Downtown El Paso at a discounted rate. Please make hotel reservations as soon as possible, as we anticipate the hotels to fill up fast. When you call to make a reservation, please indicate to the hotel clerk that you are making a reservation for the “BIOMED Symposium” so that you receive the discounted rate.
Symposium Directions & Parking
Directions To Camino Real Hotel from Del Sol Medical Center (Driving)
To Camino Real Hotel from Texas Tech University Health Sciences Center (Driving)
To Camino Real Hotel from University of El Paso (Driving)
To Camino Real Hotel from New Mexico State University (Driving)
To Camino Real Hotel from New Mexico Institute of Mining and Technology (Driving)
To Camino Real Hotel from Instituto Technologico y de Estudios Superiores de Monterrey, Campus Chihuahua (Driving)
To Camino Real Hotel from DoubleTree Hotel (Walking)
Parking
Parking is available at the Camino Real Hotel parking lot and is first-come first-served basis. The rate for the day is $4. Additional parking is available at nearby garages for a charge and free parking is available on the street.
Please contact me at nsehgal@bmiamericas.org if you have any additional questions. We look forward to seeing you at the Symposium.
Sincerely, Neyha Sehgal | Assistant Director of Market Analysis BioMedical Institute of the Americas 201 East Main Street, Suite 401 (P): (915) 773-5804 (F): (915) 231-1949
|
||||||||||
| This invitation was sent to drkcancerclinic@gmail.com by Medical Center of the Americas the organizer. To stop receiving invitations from this organizer, you can unsubscribe. |
|
| Eventbrite | 651 Brannan St. Suite 110 | San Francisco, CA 94107 |
Tuesday, October 15, 2013
11 GENES AND RELATED COMPOUND TO INVESTIGATE IN SARCOMA
1. TGF BETA 1
2.SOST GENE
3.LIPOFUSCIN
4.RANKL AND RANK
5.CHLORIDE CHANNEL GENE
6 CTSK GENE
7.PORCN GENE
8. LEMD3
9. GNAS GENE
10. FGFR 3
11, INSULIN
THESE ARE MALFORMATION INDUCING GENES.
THE MOST DANGEROUS ARE THE ONE CONNECTED TO ANGIOGENIC GENES, THEY RAISE THE STAKE! LET'S FIND THEM!
2.SOST GENE
3.LIPOFUSCIN
4.RANKL AND RANK
5.CHLORIDE CHANNEL GENE
6 CTSK GENE
7.PORCN GENE
8. LEMD3
9. GNAS GENE
10. FGFR 3
11, INSULIN
THESE ARE MALFORMATION INDUCING GENES.
THE MOST DANGEROUS ARE THE ONE CONNECTED TO ANGIOGENIC GENES, THEY RAISE THE STAKE! LET'S FIND THEM!
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