Many patients that I meet these days stress during my interview with them that their own parents died of "old age". Meaning that there seems to be a certain finality to life of humans. There will be a time when despite good care and prevention, human life will end. Patients deny their parents died of heart failure, stroke or any other cause but "old age" as if at some point we are doomed to a programmed death. Inquisition into people who live longer (more then a hundred years) point to the existence of a gene, a particular variant FOXO3 (see below). DO YOU KNOW YOUR FOXO3 VARIANT?
Evidence abounds now that how long we shall live is encrypted in our genes, but no one seems to rush to offer this option of an approach to care because it is not as simple as that! But I still believe that for proper "advance directives" preparation of this information should be included as we gauge our sens of survival! At the individual cellular level, basically this FOXO3,4,6 upregulates BIM and PUMA (wild animal in us keeping us alive!) and downregulates (FLIP) to slow programmed cellular death (Apoptosis). The interesting thing is this FOX ability to work is very tightly linked to energy! Yes, when you touch the FOXO, Galactose and Insulin metabolisms come right at you! As if telling you if you monitor me closely (as in Biomarkers) you may know what FOXY is doing. In other words, the GALT gene is a good Biomarker of FOXO3. And may tell you the status of cancer cells! (think carefully) during and after treatments!"
A variant of FOXO3 has been shown to be associated with longevity in humans. It is found in most centenarians across a variety of ethnic groups around the world.[7][8] The homologous genes daf-16 in the nematode C. elegans and dFOXO in the fruit fly are also associated with longevity in those organisms."
DAF-16 is the sole ortholog of the FOXO family of transcription factors in the nematode Caenorhabditis elegans.[1]
DAF-16 is notable for being the primary transcription factor required
for the profound lifespan extension observed upon mutation of the insulin-like receptor daf-2.[2] Moreover, the tractability of C. elegans as a model and interest in teasing out this conserved aging-associated genetic pathway allowed the intricacies of Insulin and Insulin-like growth factor (IGF) Signaling (IIS) to be thoroughly characterized primarily through studies using this model organism.[3]wikipedia
"The expression of GALT is controlled by the actions of the FOXO3 gene.
The absence of this enzyme results in classic galactosemia in humans and
can be fatal in the newborn period if lactose is not removed from the
diet. The pathophysiology of galactosemia has not been clearly defined.[1]wikipedia"
A blog about research, awareness, prevention, treatment and survivorship of Breast Cancer and all cancers, including targeted scientific research and a grassroots approach to increase screening for cancer, especially in the low income and under-insured population of El Paso, Texas, with a view to expand this new health care model to many other 'minority' populations across the United States and beyond
Showing posts with label crbcm. Show all posts
Showing posts with label crbcm. Show all posts
Tuesday, September 24, 2013
Monday, September 23, 2013
Major implication of the Gli-1
I. The Gli-1 gene
affects the following other genes
---PDGFR in mesenchymal tissue
---FOXM1
---Sufu
---SP1, USF1
---Twist1
---CyclinD2
---Plakoglobulin
---Shh
II. PTCH1: Act as a receptor to the Hedgehog ---the contact releases the SMO
Revant Info-Vismodegib
"The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the hedgehog signaling pathway.[2] SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway.[4] This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.[5]"wikipedia
link to chondrosarcoma is most puzzling
role in bladder cancer still to be explored, mostly I guess in the squamous type?
in Medulloblastoma?
affects the following other genes
---PDGFR in mesenchymal tissue
---FOXM1
---Sufu
---SP1, USF1
---Twist1
---CyclinD2
---Plakoglobulin
---Shh
II. PTCH1: Act as a receptor to the Hedgehog ---the contact releases the SMO
Revant Info-Vismodegib
"The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the hedgehog signaling pathway.[2] SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway.[4] This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.[5]"wikipedia
link to chondrosarcoma is most puzzling
role in bladder cancer still to be explored, mostly I guess in the squamous type?
in Medulloblastoma?
Sunday, September 22, 2013
"Bigger is better"
New York
— Memorial Sloan-Kettering Cancer Center has launched a transformative
initiative to improve the quality of cancer care and the lives of cancer
patients. Hartford HealthCare, a multi-hospital health care system in
Connecticut, was selected as a pioneering member of the newly formed
Memorial Sloan-Kettering Cancer Alliance.
The MSK Cancer Alliance is designed to enable an ongoing, living, breathing dynamic partnership between the comprehensive cancer center and community oncology providers, in order to bring the newest knowledge into the community setting.
The critical need for such an Alliance can be found in a report recently issued by the Institute of Medicine (IOM) that described the challenge of delivering high-quality cancer care as a national “crisis” and noted advances in treatment may be unavailable to patients who lack access to sophisticated genetic tests or clinical trials.
The MSK Cancer Alliance is designed to enable an ongoing, living, breathing dynamic partnership between the comprehensive cancer center and community oncology providers, in order to bring the newest knowledge into the community setting.
The critical need for such an Alliance can be found in a report recently issued by the Institute of Medicine (IOM) that described the challenge of delivering high-quality cancer care as a national “crisis” and noted advances in treatment may be unavailable to patients who lack access to sophisticated genetic tests or clinical trials.
“Currently,
the vast majority of cancer care in the United States is delivered by
community oncologists, but cancer advances can take years to be adopted
in a community setting,” said José Baselga, MD, Physician-in-Chief of
Memorial Sloan-Kettering, who notes that ongoing, interactive real-time
relationships are needed to effectively close this gap. “We want to
rapidly accelerate the pace of integrating the latest advances of cancer
care into a community setting. This unprecedented approach will
demonstrate real value to both organizations and most importantly will
improve the lives of cancer patients,” he added.
=======================================================
BUT HERE AT THE CRBCM WE BELIEVE :
THE MORE VERSATILE, COST EFFICIENT SMALLER CLINIC IS THE ANSWER FOR BETTER STREAMLINING OF CANCER RESEARCH AND APPLICATION OF NEW KNOWLEDGE. THE PROBLEM IS NOT THE COMMUNITY ONCOLOGIST'S LACK OF WILLINGNESS TO LEARN, BUT INDEED THE MEANS OF COMMUNICATION WITH RESEARCHERS IN THE FIELD.
Researchers are taking over main Oncology publications by publishing non readily useable information while support for conferences is dwindling. It is amazing how many Oncologists do not read Blood or JCO because the immediate relevancy of information/articles are perceived as relevant to day to day practice. Among oncologists, FDA approval and whether a randomized phase III trial has demonstrated benefits, seems to be the overwhelming standard for adoption of new therapeutics. Of course the input from trusted authors and opinions from their local referral center also drives the practice.
Larger Institutions could serve a purpose of streamlining referrals if carefully orchestrated, however something may be lost in quality of care (may be because staff there lose a bit of compassion) and money and administrative weight increase dramatically to impair the quick delivery of care they mean to better!
The weight of overheads, the number of meetings, size of committees and political infighting, tends to slow the process by the nature of the beast! These larger institutions attract more research money for a relatively poor output. The CPRIT experience proves this case. Over half of the money given to date went to large institutions in Texas, we are still waiting for the return on investment, and communities overall have still to see lingering effects.
At the CRBCM we like the idea of smaller, more versatile organizations with more effect and efficiency. We believe that science does not belong to any particular institution, and that we can not lead from behind and that we absolutely need to create new paths. This is driving how we perceive new scientific progress results, and most of all how readers will note that our interpretation of facts may be at odds, but that is deliberate and ready to open new approaches! And at least open the debate! If we have not progressed as fast as wished, it is because of political elephants in the room!
Friday, August 23, 2013
BRUSHING FURTHER!
Dear Mutombo,
Thank you for attending Genetics and Genomics BioConference Live!
We have great news! The event was so successful that it will now be available on-demand until January 2, 2014.
Feel free to log in to attend the webcasts, visit exhibitor booths, and exchange messages with experts and sponsors.
Earn CME, CE, and CEU Credits. Learn more by clicking here.
Thank you for your participation! We look forward to seeing you at the next event!
- the BioConference Live team
- the BioConference Live team
Need technical support?
Email support@bioconferencelive.com
Phone: +1-714-463-4673
See our Frequently Asked Questions
Email support@bioconferencelive.com
Phone: +1-714-463-4673
See our Frequently Asked Questions
Questions in Hodgkin Disease
QUESTIONS IN HODGKIN DISEASE
1.WHY A BIMODAL INCIDENCE BY AGE ?
2.WHY HX OF MONONUCLEOSIS INCREASES 3X THE RISK OF HODGKIN DISEASE ?
3.THE INFECTIOUS PROCESS MUST LEAVE A DEFICIENCY FOR HODGKIN LYMPHOMA TO DEVELOP (HIV, EBV, BONE MARROW TRANSPLANT) ?CD8, HLA DR (ACQUIRED IMMUNITY) ?
4.DOES EXTRANODAL INFILTRATION MEAN T-CELL INVOLVEMENT OR JUST FAILURE OF A BLOOD VESSEL ?
(to be continued)
1.WHY A BIMODAL INCIDENCE BY AGE ?
2.WHY HX OF MONONUCLEOSIS INCREASES 3X THE RISK OF HODGKIN DISEASE ?
3.THE INFECTIOUS PROCESS MUST LEAVE A DEFICIENCY FOR HODGKIN LYMPHOMA TO DEVELOP (HIV, EBV, BONE MARROW TRANSPLANT) ?CD8, HLA DR (ACQUIRED IMMUNITY) ?
4.DOES EXTRANODAL INFILTRATION MEAN T-CELL INVOLVEMENT OR JUST FAILURE OF A BLOOD VESSEL ?
(to be continued)
THE "CHELOID FACTOR" AT THE CELLULAR MEMBRANE!
We tend to be excited about intracellular pathways as they travel through the Cytosol and affect epigenetic and nuclear phenomena. And our excitement has been justified since we have been able to affect cellular life by targeting various pathway molecules. But one should stress a particular event occurring at the membrane that mimics "wound phenomena". Aside for providing a physical boundary of the cell, the membrane is one of the most important "organs" of the cell. It is in itself a very chemically vibrant living "cellular tissue ". When you start reading about the cell they tell you about the layers of proteins and lipids that make up the cellular membranes. But this picture is far from the truth, the membrane is like the wall of a brick house. With each brick different from the next. Some of these bricks are called Integrins (I guess because they are an integral part of the membrane). Some of these bricks have a Cyclin, some have a growth factor! In fact, the membrane here serves as a reserve of these molecules. Some bricks can be divided in 2 portions. One portion that can "FLIP" inside when needed (This portion contains the cyclin, for example) and one portion that can "FLOP" outside (this portion contains a Metalloprotease). (see my post on FLIPPASE and FLOPPASE) The point is that once the brick is used there remains a hole with sharp edges. These edges are called "FOCAL ADHESION Molecules" (KINASES) in a cell and are governed by the PTK2 gene! (and of course PYK2)
PTK2 protein tyrosine kinase 2 (PTK2), also known as Focal Adhesion Kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene.[2] PTK2 is a focal adhesion-associated protein kinase
involved in cellular adhesion (how cells stick to each other and their
surroundings) and spreading processes (how cells move around).[3] It has been shown that when FAK was blocked, breast cancer cells became less metastastic due to decreased mobility.[4](Wikepedia
=============================================================================
AND THEY ARE PLENTY TALKED ABOUT!
=============================================================== I.E....
PTK2:
From Wikipedia, the free encyclopedia
Jump to: navigation, search
Protein tyrosine kinase 2 | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
PDB rendering of the C-terminal FAT domain based on 1k04[1]. |
|||||||||||
|
|||||||||||
Identifiers | |||||||||||
Symbols | PTK2; FADK; FAK; FAK1; FRNK; PPP1R71; p125FAK; pp125FAK | ||||||||||
External IDs | OMIM: 600758 MGI: 95481 HomoloGene: 7314 ChEMBL: 2695 GeneCards: PTK2 Gene | ||||||||||
EC number | 2.7.10.2 | ||||||||||
|
|||||||||||
RNA expression pattern | |||||||||||
More reference expression data | |||||||||||
Orthologs | |||||||||||
Species | Human | Mouse | |||||||||
Entrez | 5747 | 14083 | |||||||||
Ensembl | ENSG00000169398 | ENSMUSG00000022607 | |||||||||
UniProt | Q05397 | P34152 | |||||||||
RefSeq (mRNA) | NM_001199649 | NM_001130409 | |||||||||
RefSeq (protein) | NP_001186578 | NP_001123881 | |||||||||
Location (UCSC) | Chr 8: 141.67 – 142.01 Mb |
Chr 15: 73.21 – 73.42 Mb |
|||||||||
PubMed search | [1] | [2] | |||||||||
=============================================================================
AND THEY ARE PLENTY TALKED ABOUT!
=============================================================== I.E....
"Integrin-dependent translocation of phosphoinositide 3-kinase to the cytoskeleton of thrombin-activated platelets involves specific interactions of p85 alpha with actin filaments and focal adhesion kinase(JCB)"
The point is that at the membrane healing should occur after the "integrin" has been plucked off, but failure to heal may trigger the "cheloid effect". In the cell, this is where the Src gene is, the Wnt (catenins) and the Notch are here, Caspase 3 is present, and death Receptors,etc... (things can get complicated really fast with these guys around! unless of course phosphorylation or other taming mechanisms come to play!)
Focal Adhesion kinases (FAK)
". FAK is typically located at structures known as focal adhesions, these are multi-protein structures that link the extracellular matrix (ECM) to the cytoplasmic cytoskeleton. Additional components of focal adhesions include actin, filamin, vinculin, talin, paxillin, tensin[7] and RSU-1." This is what Taxol and Taxotere find their might! (components of microtubules)
remember tensin is same as PTEN
NIH
" PTEN1
- Also known as
- BZS; DEC; CWS1; GLM2; MHAM; TEP1; MMAC1; PTEN1; 10q23del
- Summary
- This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. [provided by RefSeq, Jul 2008]"
Thursday, August 22, 2013
Processes of cancerization
One of the most intriguing steps in the neoplastic transformation is determining the actual event that led to its occurrence. We all have the perception that because of what we ingest unfortunately on a continuous basis (medications or foods we like - man clings to habits) something will get either amplified or suppressed. Certain amplifications can be deleterious or beneficial depending of where they occur or what gene is involved. It is apparent that involvement of "wild genes" (those with multiple interactions with others, including genes involved in shaping the body) are more likely to lead to malignant transformation (ie. the Androgen gene, FYN,Grb2, MTIF, etc). Secondly, knocking out break to proliferation (P53, Rb1, PTEN, and the many CDK) seems also to be a prelude to a neoplastic transformation. Alteration in "switch" genes (SOS) and molecules intermediary to various cellular/membrane events can also trigger a persistent stimulation or suppression that could affect cellular processes enough to upset a balance. Chronic hypoxia has emerged to be a potent neoplastic process inducer....(to be continued)
Wednesday, August 21, 2013
Science without Borders!
Readers from 10 different countries visited the CRBCM blog today!
Thank you, friends and like-minded research fellows around the World,
including the USA, France, China, the United Kingdom, India, Malaysia,
the Netherlands, the Philippines and Serbia.
Your feedback matters to us, thank you, again!
Thank you, friends and like-minded research fellows around the World,
including the USA, France, China, the United Kingdom, India, Malaysia,
the Netherlands, the Philippines and Serbia.
Your feedback matters to us, thank you, again!
Thursday, May 2, 2013
The MEANING OF THE MDHonors AWARD for CRBCM.
MEANING OF THE MDHonors AWARD for CRBCM.
The CRBCM would like to thank MDHonors for the Research award given to our Coalition and young clinic (Greater East cancer Center of El Paso Texas). This award will allow to build our institution's primary steps into the research power house we intend to become. It will formalize in practical terms (working on a tangible research project) some of our collaboration attempts with the University Medical Center in El Paso, and the UTEP (University of Texas in El Paso). With this award, the CRBCM will continue to march toward the cure day by day, and with confidence and focused vision. And with this steady progression, victory is certain. MDHonors revived our hope in the belief that we still have a chance to succeed if we try hard enough!
The cure is within reach, we got to keep on believing that it is reachable, and not get discouraged by politicians and malicious institutions which are distracting our progress toward the cure!
We can not thank MDHonors enough ; for now let's go to work as we face international scrutiny and the true challenge of a cure for cancers!
And God Bless CRBCM
La lucha continua !
Dr Kankonde.
The CRBCM would like to thank MDHonors for the Research award given to our Coalition and young clinic (Greater East cancer Center of El Paso Texas). This award will allow to build our institution's primary steps into the research power house we intend to become. It will formalize in practical terms (working on a tangible research project) some of our collaboration attempts with the University Medical Center in El Paso, and the UTEP (University of Texas in El Paso). With this award, the CRBCM will continue to march toward the cure day by day, and with confidence and focused vision. And with this steady progression, victory is certain. MDHonors revived our hope in the belief that we still have a chance to succeed if we try hard enough!
The cure is within reach, we got to keep on believing that it is reachable, and not get discouraged by politicians and malicious institutions which are distracting our progress toward the cure!
We can not thank MDHonors enough ; for now let's go to work as we face international scrutiny and the true challenge of a cure for cancers!
And God Bless CRBCM
La lucha continua !
Dr Kankonde.
Wednesday, May 1, 2013
A novel virus genome discovered in an extreme environment suggests recombination between unrelated groups of RNA and DNA viruses
A novel virus genome discovered in an extreme environment suggests recombination between unrelated groups of RNA and DNA viruses
Geoffrey S Diemer and Kenneth M Stedman*
GO to the article !
This story truly deserve the reward given to those scientists
it is the story introducing the 9th law of nature
which is the law of adaptation to unusual conditions by adjusting genetic potential, by the power of recombination, and using cellular heterogeneity, and by activating NF-kB.
cells have an incredible versatility potential if given the time and if the programmed death is not triggered by an overwhelming stimulant... to adapt and develop new function ready to deal with change in the environment. These changes could be dramatic! ie we lost our tail for god sake!
The reversal of mesenchymal transformation is another of change to adaptation and is the underlying reason of deviation of epithelialization driving the Barrett transformation in the lower 3rd of the Esophagus. These changes are benign until receptor become desensitized to an overwhelming and relentless stimulation leading to the HSP (heat stroke protein ) gets as well as the provoked! Prevention of progression to cancer should dampen growth factors and decrease HSP actions!
We have recently hypothesized that the MEK action as well as the Wnt were membrane located and followed the Reticulum Endothelium tract to reach the nucleus. With the involvement of the Hedgehog, Basaloid morphology resulted in triple negative breast cancer! (Again if it is strong enough to induce a morphologic change, it is strong enough to cause an abnormality so significant as a neoplastic process.-even Fanconi abnormality associated with morphology changes (microcephaly) will lead to a Myelodysplastic Syndrome. (and we contend that these type of syndrome will respond to Revlimid and Thalidomide type of drugs). We promise to discuss the gene involved in the 9th law soon but this text tells you already where we are going to fish them!
This story truly deserve the reward given to those scientists
it is the story introducing the 9th law of nature
which is the law of adaptation to unusual conditions by adjusting genetic potential, by the power of recombination, and using cellular heterogeneity, and by activating NF-kB.
cells have an incredible versatility potential if given the time and if the programmed death is not triggered by an overwhelming stimulant... to adapt and develop new function ready to deal with change in the environment. These changes could be dramatic! ie we lost our tail for god sake!
The reversal of mesenchymal transformation is another of change to adaptation and is the underlying reason of deviation of epithelialization driving the Barrett transformation in the lower 3rd of the Esophagus. These changes are benign until receptor become desensitized to an overwhelming and relentless stimulation leading to the HSP (heat stroke protein ) gets as well as the provoked! Prevention of progression to cancer should dampen growth factors and decrease HSP actions!
We have recently hypothesized that the MEK action as well as the Wnt were membrane located and followed the Reticulum Endothelium tract to reach the nucleus. With the involvement of the Hedgehog, Basaloid morphology resulted in triple negative breast cancer! (Again if it is strong enough to induce a morphologic change, it is strong enough to cause an abnormality so significant as a neoplastic process.-even Fanconi abnormality associated with morphology changes (microcephaly) will lead to a Myelodysplastic Syndrome. (and we contend that these type of syndrome will respond to Revlimid and Thalidomide type of drugs). We promise to discuss the gene involved in the 9th law soon but this text tells you already where we are going to fish them!
Tuesday, April 30, 2013
AAPS Sues over Maintenance of Certification
SOMEBODY HAD TO SPEAK UP AS THIS CERTIFICATION PROCESS HAS BECOME ALMOST UN-DO-ABLE with intricacies and often undisclosed PASS MARK LEVELS... !
Who in his healthy mind would want to pay dearly and take a very tough exam for which nobody knows what the requirements are to pass (number or % of questions answered correctly) .As a rule now, the exams take place, then all the individual physician's results of the session get corrected and average is computed, to which they then apply a mysterious and never publicized pass mark and then send out the "Pass" and "Fail" letters. We suspect that the computer program is set to always "Fail" at least 33 % of the candidates to assure repeat cash flow thanks to failed candidates having to re-register for an upcoming session. The hospital's requirement of board certification puts undue pressure on specialist and experts of long and good standing and thus deprives the population of valuable medical knowledge and best treatment options.
----------------------
Blog | April 28, 2013 | Healthcare Careers, Performance, Training
Who in his healthy mind would want to pay dearly and take a very tough exam for which nobody knows what the requirements are to pass (number or % of questions answered correctly) .As a rule now, the exams take place, then all the individual physician's results of the session get corrected and average is computed, to which they then apply a mysterious and never publicized pass mark and then send out the "Pass" and "Fail" letters. We suspect that the computer program is set to always "Fail" at least 33 % of the candidates to assure repeat cash flow thanks to failed candidates having to re-register for an upcoming session. The hospital's requirement of board certification puts undue pressure on specialist and experts of long and good standing and thus deprives the population of valuable medical knowledge and best treatment options.
----------------------
Blog | April 28, 2013 | Healthcare Careers, Performance, Training
The
Association of American Physicians & Surgeons (AAPS) filed suit
April 23, 2013, against the American Board of Medical Specialties (ABMS)
over their maintenance of certification program. The suit, filed in a
New Jersey federal court, alleges that the ABMS is restraining trade and
causing a reduction in patient access due to burdensome recertification
processes.
Jane Orient, MD, the AAPS' executive director, graciously agreed to discuss the issues with me.
Martin Merritt: I understand maintenance of certification (MOC) is one of the hottest topics in the field of medicine today?
Jane Orient: Yes. Many physicians are outraged, not only by the cost an expense which must be incurred to maintain certification, but also by the fear that MOC is being advanced as a requirement for hospital privileges, and perhaps even maintenance of licensure (MOL).
MM: The public might think the ABMS is a government entity?
JO: The ABMS is a not-for-profit corporation. According to the lawsuit filed by AAPS, the ABMS seems to exist to enrich its own executives, with little appreciable evidence that the MOC program has an effect on the quality of care.
MM: How does the ABMS MOC program actually work?
JO: I can mostly speak about what the lawsuit contains. ABMS and 24 separate corporations, which make up the 24 recognized board-certified specialties have agreed to impose on physicians a recertification program called the ABMS Maintenance of Certification. At one time, a physician could voluntarily choose to become board certified, and upon completion of the process, he or she was board certified for life. Now, the ABMS has decided to force board certified physicians to purchase its products every 10 years. If a physician cannot afford the time or the expense of recertification, he or she may be designated as "not meeting" the requirements of the ABMS, which tends to imply that a physician is less than qualified to care for patients.
MM: What is the AAPS seeking in the suit?
JO: AAPS’ lawsuit, seeks declaratory and injunctive relief to enjoin ABMS’s continuing violations of antitrust law and misrepresentations about the medical skills of physicians who decline to purchase and spend time on its program. AAPS also seeks a refund of fees paid by its members to ABMS and its 24 other corporations as a result of ABMS’ conduct.
Again, the lawsuit itself is the best source for information about the relief requested, but in a nutshell, what we are worried about is the fact that perfectly capable physicians are being black-balled, or locked out of the ability to treat patients, because they do not have the time, or inclination to purchase a product from a private corporation, which has nothing to do with the physician’s ability to treat patients.
MM. You cite an example in the lawsuit, I believe.
JO: In a case cited in this lawsuit, a first-rate physician in New Jersey was excluded from the medical staff at a hospital in his state simply because he had not paid for and spent time on recertification with one of these private corporations. He runs a charity clinic that has logged more than 30,000 visits, but now none of those patients can see him at the local hospital because of the money-making scheme of recertification.
MM: I would like to thank Dr. Orient for speaking with us. You can follow this lawsuit and other issues of concern at the AAPS website.
Martin Merritt: I understand maintenance of certification (MOC) is one of the hottest topics in the field of medicine today?
Jane Orient: Yes. Many physicians are outraged, not only by the cost an expense which must be incurred to maintain certification, but also by the fear that MOC is being advanced as a requirement for hospital privileges, and perhaps even maintenance of licensure (MOL).
MM: The public might think the ABMS is a government entity?
JO: The ABMS is a not-for-profit corporation. According to the lawsuit filed by AAPS, the ABMS seems to exist to enrich its own executives, with little appreciable evidence that the MOC program has an effect on the quality of care.
MM: How does the ABMS MOC program actually work?
JO: I can mostly speak about what the lawsuit contains. ABMS and 24 separate corporations, which make up the 24 recognized board-certified specialties have agreed to impose on physicians a recertification program called the ABMS Maintenance of Certification. At one time, a physician could voluntarily choose to become board certified, and upon completion of the process, he or she was board certified for life. Now, the ABMS has decided to force board certified physicians to purchase its products every 10 years. If a physician cannot afford the time or the expense of recertification, he or she may be designated as "not meeting" the requirements of the ABMS, which tends to imply that a physician is less than qualified to care for patients.
MM: What is the AAPS seeking in the suit?
JO: AAPS’ lawsuit, seeks declaratory and injunctive relief to enjoin ABMS’s continuing violations of antitrust law and misrepresentations about the medical skills of physicians who decline to purchase and spend time on its program. AAPS also seeks a refund of fees paid by its members to ABMS and its 24 other corporations as a result of ABMS’ conduct.
Again, the lawsuit itself is the best source for information about the relief requested, but in a nutshell, what we are worried about is the fact that perfectly capable physicians are being black-balled, or locked out of the ability to treat patients, because they do not have the time, or inclination to purchase a product from a private corporation, which has nothing to do with the physician’s ability to treat patients.
MM. You cite an example in the lawsuit, I believe.
JO: In a case cited in this lawsuit, a first-rate physician in New Jersey was excluded from the medical staff at a hospital in his state simply because he had not paid for and spent time on recertification with one of these private corporations. He runs a charity clinic that has logged more than 30,000 visits, but now none of those patients can see him at the local hospital because of the money-making scheme of recertification.
MM: I would like to thank Dr. Orient for speaking with us. You can follow this lawsuit and other issues of concern at the AAPS website.
Sunday, April 28, 2013
MASTERING OF SOME GENES CONTROLLING RECEPTOR FUNCTIONS!
1.SLIT 2 Slit homolog 2 protein is a protein that in humans is encoded by the SLIT2 gene
SLIT2 has been shown to interact with Glypican 1
Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation.[2] WIKIPEDIA
IF YOU RECALL OUR DISCUSSION ABOUT RECEPTOR FAILURE, TUMOR GROWTH FACTOR FAILED TO STIMULATE OUR RECEPTOR BECAUSE OF LACK OF DERENGEMENT OF GLYCOSYLATION AND HEPARAN WAS THE FAILURE. THIS PUT SLIT 2 AT THE RECEPTOR PARTICULARLY IN THE CENTRAL NERVOUS SYSTEM!
2.MIG6: The cytoplasmic protein MIG6 (mitogen-induced gene 6; also known as ERRFI1) interacts with and inhibits the kinase domains of EGFR and ERBB2 (refs 3–5). Crystal structures of complexes between the EGFR kinase domain and a fragment of MIG6 show that a 25-residue epitope (segment 1) from MIG6 binds to the distal surface of the C lobe of the kinase domain. Biochemical and cell-based analyses confirm that this interaction contributes to EGFR inhibition by blocking the formation of the activating dimer interface.(ZANG ET AL!)
MIG-6 Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development. Interacts with ERBB2. Interacts with EGFR. Levels are very low in quiescent cells. Up-regulated by mitogens. Belongs to the MIG6 family. Note: This description may include information from UniProtKB.
3. SATB1 HERE BECAUSE OF THE CONNECTION WITH NUCLEAR MATERIAL. interferon gamma act through here!
4. SMAD6
Another powerful decoy
" Smad6 specifically competes with Smad4 for binding to receptor-activated Smad1, yielding an apparently inactive Smad1-Smad6 complex. Therefore, Smad6 selectively antagonizes BMP-activated Smad1 by acting as a Smad4 decoy." Hata et al
-------------------------------------------------------------------------------------------------
LTB4, because of its interactions with
Peroxisome proliferator-activated receptor gamma has been shown to interact with:
Many insulin sensitizing drugs (namely, the thiazolidinediones) used in the treatment of diabetes target PPARG as a means to lower serum glucose without increasing pancreatic insulin secretion.
A fusion protein of PPAR-γ1 and the thyroid transcription factor PAX8 is present in approximately one-third of follicular thyroid carcinomas, to be specific those cancers with a chromosomal translocation of t(2;3)(q13;p25), which permits juxtaposition of portions of both genes.[21] [22]
Recently pioglitazone, a PPAR-γ agonist has been shown to be effective in reducing inflammation in Parkinson's Disease models. Levels of MMPs and microglia (and therefore TNF-α and other cytokine levels) were found to be reduced. Thus it has been shown to be neuroprotective in MPTP mouse models.
BMP2
SLIT2 has been shown to interact with Glypican 1
Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation.[2] WIKIPEDIA
IF YOU RECALL OUR DISCUSSION ABOUT RECEPTOR FAILURE, TUMOR GROWTH FACTOR FAILED TO STIMULATE OUR RECEPTOR BECAUSE OF LACK OF DERENGEMENT OF GLYCOSYLATION AND HEPARAN WAS THE FAILURE. THIS PUT SLIT 2 AT THE RECEPTOR PARTICULARLY IN THE CENTRAL NERVOUS SYSTEM!
2.MIG6: The cytoplasmic protein MIG6 (mitogen-induced gene 6; also known as ERRFI1) interacts with and inhibits the kinase domains of EGFR and ERBB2 (refs 3–5). Crystal structures of complexes between the EGFR kinase domain and a fragment of MIG6 show that a 25-residue epitope (segment 1) from MIG6 binds to the distal surface of the C lobe of the kinase domain. Biochemical and cell-based analyses confirm that this interaction contributes to EGFR inhibition by blocking the formation of the activating dimer interface.(ZANG ET AL!)
MIG-6 Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development. Interacts with ERBB2. Interacts with EGFR. Levels are very low in quiescent cells. Up-regulated by mitogens. Belongs to the MIG6 family. Note: This description may include information from UniProtKB.
3. SATB1 HERE BECAUSE OF THE CONNECTION WITH NUCLEAR MATERIAL. interferon gamma act through here!
4. SMAD6
Another powerful decoy
" Smad6 specifically competes with Smad4 for binding to receptor-activated Smad1, yielding an apparently inactive Smad1-Smad6 complex. Therefore, Smad6 selectively antagonizes BMP-activated Smad1 by acting as a Smad4 decoy." Hata et al
-------------------------------------------------------------------------------------------------
LTB4, because of its interactions with
Peroxisome proliferator-activated receptor gamma has been shown to interact with:
Clinical relevance
PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis, and cancer. PPAR-gamma agonists have been used in the treatment of hyperlipidaemia and hyperglycemia.[18] PPAR-gamma decreases the inflammatory response of many cardiovascular cells, particularly endothelial cells.[19] PPAR-gamma activates the PON1 gene, increasing synthesis and release of paraoxonase 1 from the liver, reducing atherosclerosis.[20]Many insulin sensitizing drugs (namely, the thiazolidinediones) used in the treatment of diabetes target PPARG as a means to lower serum glucose without increasing pancreatic insulin secretion.
A fusion protein of PPAR-γ1 and the thyroid transcription factor PAX8 is present in approximately one-third of follicular thyroid carcinomas, to be specific those cancers with a chromosomal translocation of t(2;3)(q13;p25), which permits juxtaposition of portions of both genes.[21] [22]
Recently pioglitazone, a PPAR-γ agonist has been shown to be effective in reducing inflammation in Parkinson's Disease models. Levels of MMPs and microglia (and therefore TNF-α and other cytokine levels) were found to be reduced. Thus it has been shown to be neuroprotective in MPTP mouse models.
BMP2
- The protein encoded by this gene belongs to the transforming growth factor-beta (TGFB) superfamily. The encoded protein acts as a disulfide-linked homodimer and induces bone and cartilage formation. [provided by RefSeq, Jul 2008]
Friday, April 26, 2013
KNOW THIS: A little bit of good news in the nation !
"Diabetes report card chronicling how the United States is faring
in terms of management of the condition in adults, based on data to
2010, shows that there has been improvement, but there are still
large gaps in terms of the control of 2 important risk factors, smoking
and hypertension." (Medscape)".
CONSIDERATIONS IN RECURRENT OVARIAN CANCER TREATMENT:
Nice discussion by
By Edward Tanner, MD1, Deborah K. Armstrong, MD2 | April 15, 2013
In summary, and I hope I dig this right!
That one thing you look at in recurrent Ovarian cancer:
ASSUMING YOUR FIRST TREATMENT WAS PLATINUM BASED, WHICH IS MOST OF THE TIME THE CASE, the disease free interval of more than 6 months (not 12 months) determines whether the disease is platinum sensitive. Because re-treatment should include platinum in those with the disease still sensitive!
The other sensitive notion was the issue of Cytoreduction, according to these authors, Cytoreduction in recurrent disease makes sens only if the Progression free interval was more than 1 year (here "12 months" is needed), and when the lesions could be realistically resected! ("gross resection is achievable")
The discussion on Target therapy was limited to:
1. Adding Avastin to Gemzar +platinum which has shown to increase progression free survival
2. to using PARP inhibitors for those with BRCA Mutation
---------------------------------------------------------------
In other news!
"Similarities Between Ovarian and Basal-Like Breast Cancers:
In a copy number and genomic mutation analysis of all four breast cancer subtypes and ovarian cancer tumor samples, basal-like breast cancer and ovarian cancer were found to be most similar. The authors highlight that the similarities between basal-like breast cancer and serous ovarian cancers indicate that these two difficult-to-treat cancer types may be able to be treated with the same therapies—chemotherapy drugs, anti-angiogenesis agents, and others in development."
No comment was reported about the difference on MUCIN genes!
" For both ovarian and basal-like breast cancer, TP53 was found mutated in 80% of tumors," pointing to the Receptor failure theory developed here!
"Basal-like breast cancers and ovarian cancers had similar rates of mutation and a similar spectrum of mutations. The basal-like tumors had a high frequency of mutations in the ATM, BRCA1, BRCA2, as well as RB1 loss and cyclin E1 amplification—the same mutations identified for ovarian cancers.
About 20% of basal-like breast tumors had a germline or somatic mutation in either BRCA1 or BRCA2. The authors suggest that these BRCA-mutated patients could potentially respond to Poly (ADP-ribose) polymerase (PARP) inhibitors. The analysis also showed various copy number amplifications and deletions that may be therapeutic targets."
For more, go to:
By Anna Azvolinsky, PhD1
----------------------------------------------------------------------------------------------------------------------
AND ALSO READ THIS:
By Edward Tanner, MD1, Deborah K. Armstrong, MD2 | April 15, 2013
In summary, and I hope I dig this right!
That one thing you look at in recurrent Ovarian cancer:
ASSUMING YOUR FIRST TREATMENT WAS PLATINUM BASED, WHICH IS MOST OF THE TIME THE CASE, the disease free interval of more than 6 months (not 12 months) determines whether the disease is platinum sensitive. Because re-treatment should include platinum in those with the disease still sensitive!
The other sensitive notion was the issue of Cytoreduction, according to these authors, Cytoreduction in recurrent disease makes sens only if the Progression free interval was more than 1 year (here "12 months" is needed), and when the lesions could be realistically resected! ("gross resection is achievable")
The discussion on Target therapy was limited to:
1. Adding Avastin to Gemzar +platinum which has shown to increase progression free survival
2. to using PARP inhibitors for those with BRCA Mutation
---------------------------------------------------------------
In other news!
"Similarities Between Ovarian and Basal-Like Breast Cancers:
In a copy number and genomic mutation analysis of all four breast cancer subtypes and ovarian cancer tumor samples, basal-like breast cancer and ovarian cancer were found to be most similar. The authors highlight that the similarities between basal-like breast cancer and serous ovarian cancers indicate that these two difficult-to-treat cancer types may be able to be treated with the same therapies—chemotherapy drugs, anti-angiogenesis agents, and others in development."
No comment was reported about the difference on MUCIN genes!
" For both ovarian and basal-like breast cancer, TP53 was found mutated in 80% of tumors," pointing to the Receptor failure theory developed here!
"Basal-like breast cancers and ovarian cancers had similar rates of mutation and a similar spectrum of mutations. The basal-like tumors had a high frequency of mutations in the ATM, BRCA1, BRCA2, as well as RB1 loss and cyclin E1 amplification—the same mutations identified for ovarian cancers.
About 20% of basal-like breast tumors had a germline or somatic mutation in either BRCA1 or BRCA2. The authors suggest that these BRCA-mutated patients could potentially respond to Poly (ADP-ribose) polymerase (PARP) inhibitors. The analysis also showed various copy number amplifications and deletions that may be therapeutic targets."
For more, go to:
Study Finds Ovarian and Basal-Like/Triple-Negative Breast Cancers Genetically Similar
----------------------------------------------------------------------------------------------------------------------
AND ALSO READ THIS:
ONCOLOGY.
Vol. 27
No. 1
mTOR Inhibitors in the Treatment of Breast Cancer
By Shaveta Vinayak, MD, MS1,
Robert W. Carlson, MD1 |
January 15, 2013
1Department of Medicine, Stanford University School of Medicine, Stanford, California
ABSTRACT: The phosphatidylinositol 3-kinase/mammalian target
of rapamycin (PI3K/mTOR) pathway is commonly dysregulated in breast
cancer. In preclinical studies, hyperactivation of the PI3K pathway has
been linked to resistance to both endocrine therapy and trastuzumab(Drug information on trastuzumab)
(Herceptin). Rapalogs, agents that primarily inhibit mTOR-raptor
complex 1, have been studied in combination with endocrine therapy to
overcome endocrine resistance. Trials of combination endocrine therapy
and rapalogs in metastatic hormone receptor–positive breast cancer have
demonstrated variable results. However, two independent trials have
recently shown that combination everolimus (Afinitor) and tamoxifen(Drug information on tamoxifen) or combination everolimus and exemestane(Drug information on exemestane)
(Aromasin) is more effective than either endocrine agent alone. These
trials selected patients with cancer refractory to endocrine therapy,
which may be important in sensitizing tumors to inhibition of this
pathway. In human epidermal growth factor receptor 2 (HER2)-positive
breast cancer, the early clinical data with combinations of PI3K/mTOR
inhibitors and anti-HER2 therapies are encouraging.
|
Thursday, April 25, 2013
NEW OPTIMISM IN RECURRENT OVARIAN CANCER
" There is reason to be optimistic about the future of therapy for
patients with recurrent ovarian cancer. Inhibition of Wee-1 may target
the universal p53 aberrations observed in high-grade serous
cancers, and Wee-1 inhibitors are being developed. Objective responses
to a variety of immune therapies have been observed, such as an antibody
against cytotoxic T-lymphocyte protein 4 (CTLA 4) (see reference 66
from Vaughn et al[9]) or BMS-936559, and antiprogrammed death ligand-1
(PDL-1) monoclonal antibody[15] and immune therapies are a promising
area for development. Aberrant DNA methylation is a frequent epigenetic
event in ovarian cancer, and the use of chemotherapy plus epigenetic
modulators such as demethylating agents or histone deacetylase
inhibitors is being studied. The ability to analyze complex genomic data
is rapidly increasing, and ovarian cancer is fairly readily biopsiable.
More than ever, patients with recurrent disease should consider
participation in high quality research trials."
"the addition of PARP inhibitors to chemotherapy in women with recurrent disease has so far failed to improve survival.[14] Front-line trials with PARP inhibitors are being planned, and may yield better results"
FROM:
Management of Recurrent EOC: The State of the Art
WE ARE GOING TO FURTHER COMMENTS OF THESE NEW OPTIONS AS WE LEARN MORE!
MAY BE WE SHOULD BE ADDING INHIBITORS OF AURORA (s) INSTEAD !
"the addition of PARP inhibitors to chemotherapy in women with recurrent disease has so far failed to improve survival.[14] Front-line trials with PARP inhibitors are being planned, and may yield better results"
FROM:
Management of Recurrent EOC: The State of the Art
By Gini F. Fleming, MD1 |
April 15, 2013
---------------------------------------------------------------------------------------WE ARE GOING TO FURTHER COMMENTS OF THESE NEW OPTIONS AS WE LEARN MORE!
MAY BE WE SHOULD BE ADDING INHIBITORS OF AURORA (s) INSTEAD !
SOME FACTS ABOUT LUNG CANCER
It is the leading cause of death in many countries,
in the US almost 160,000 deaths per year now,
80% are non small cell cancer of the lung,
some are derived from the Pneumocyte type II (Broncho alveolar),
some from very heavy smoking (small cell characterized by Keratin Pearls and hypercalcemia),
20% localized at diagnosis while more than 50% are already distant at diagnosis, the rest have regional spread.
Smoking provides over 300 Chemicals of which at least 10% are potent carcinogens susceptible of changing genes and receptors on cellular membranes including MUCIN genes. The Carcinogens create DNA adducts, some will stimulate the AKT pathway directly. Mutation of P53 can happen during MUCIN gene alterations as described. c-MYC, the gene proliferation amplifier, is often found secondarily activated.
Currently testing is completed for EGFR, ROS-1, ALK, (and in some cases K-RAS in Adenocarcinomas).
(to be continued)
in the US almost 160,000 deaths per year now,
80% are non small cell cancer of the lung,
some are derived from the Pneumocyte type II (Broncho alveolar),
some from very heavy smoking (small cell characterized by Keratin Pearls and hypercalcemia),
20% localized at diagnosis while more than 50% are already distant at diagnosis, the rest have regional spread.
Smoking provides over 300 Chemicals of which at least 10% are potent carcinogens susceptible of changing genes and receptors on cellular membranes including MUCIN genes. The Carcinogens create DNA adducts, some will stimulate the AKT pathway directly. Mutation of P53 can happen during MUCIN gene alterations as described. c-MYC, the gene proliferation amplifier, is often found secondarily activated.
Currently testing is completed for EGFR, ROS-1, ALK, (and in some cases K-RAS in Adenocarcinomas).
(to be continued)
Tuesday, April 23, 2013
THE Wnt PATHWAY
THE Wnt PATHWAY
It is one of the most complex and versatile pathways. It is a powerful pathway because Mutations here have direct impact on cell totipotentiality, metastasis and cell differentiation and survival. It involves the most genes .
1.The Wnt interacts with E-Cadherin and therefore intervenes in the Cell Adhesion and Metastatic spread of cancers.
2. The Wnt influences Calcium concentration in the cell.
Remenber Calcium have influence on Calmodulin function and in Alzheimer dementia, microtubule entanglement is worsened by influx of Calcium
3. Interaction with the Frizzled assure membrane polarity
?control of the flippase or calcium channels?
4. It has nuclear effect through activation of beta-Catenin (through activation OCT4) which is normally degraded by Ubiquitination, therefore opening the door to Velcade
5. Totipotentiality of cells comes back through the Wnt (through Nanog derepression by removing TCF3 influence)
6. Activate the MTOR to ensure cell survival (through GSK)
8. It controls Mesodermal differentiation (through FLK1)
9. It attenuates the Sonic HedgeHog (through GSK)
10. It has full control of the Neurologic sytem of the cell, and through is wingless system, determines where the function will be displayed
11. It is a stimulator of the c-JUN through RAC-1
12. It confers the status of Neuroendocrine differentiation, control where nerves go or do not go!
It is why Cisplatin has a role in in Neuroendocrine differentiated tumor
13. It is the master of Embryonal Gastrulation
Watch out: attacking Wnt can activate the cancer because of its c-JUN connection which leads to Tumor Growth factor!
14. Viral penetration involves the Wnt
15. It controls cell morphology, migration, endocytosis and cell cycle progression (through Cdc42)
I have to stop to spare you! Look, I have not started to talk about how it leads to Metastasis...I just have to stop. The Wnt, a powerful pathway!
It is one of the most complex and versatile pathways. It is a powerful pathway because Mutations here have direct impact on cell totipotentiality, metastasis and cell differentiation and survival. It involves the most genes .
1.The Wnt interacts with E-Cadherin and therefore intervenes in the Cell Adhesion and Metastatic spread of cancers.
2. The Wnt influences Calcium concentration in the cell.
Remenber Calcium have influence on Calmodulin function and in Alzheimer dementia, microtubule entanglement is worsened by influx of Calcium
3. Interaction with the Frizzled assure membrane polarity
?control of the flippase or calcium channels?
4. It has nuclear effect through activation of beta-Catenin (through activation OCT4) which is normally degraded by Ubiquitination, therefore opening the door to Velcade
5. Totipotentiality of cells comes back through the Wnt (through Nanog derepression by removing TCF3 influence)
6. Activate the MTOR to ensure cell survival (through GSK)
8. It controls Mesodermal differentiation (through FLK1)
9. It attenuates the Sonic HedgeHog (through GSK)
10. It has full control of the Neurologic sytem of the cell, and through is wingless system, determines where the function will be displayed
11. It is a stimulator of the c-JUN through RAC-1
12. It confers the status of Neuroendocrine differentiation, control where nerves go or do not go!
It is why Cisplatin has a role in in Neuroendocrine differentiated tumor
13. It is the master of Embryonal Gastrulation
Watch out: attacking Wnt can activate the cancer because of its c-JUN connection which leads to Tumor Growth factor!
14. Viral penetration involves the Wnt
15. It controls cell morphology, migration, endocytosis and cell cycle progression (through Cdc42)
I have to stop to spare you! Look, I have not started to talk about how it leads to Metastasis...I just have to stop. The Wnt, a powerful pathway!
Sunday, April 21, 2013
ONE IMPORTANT MECHANISM OF NEOPLASTIC TRANSFORMATION COMING OUT OF OUR OBSERVATION:
ONE IMPORTANT MECHANISM OF NEOPLASTIC TRANSFORMATION COMING OUT
OF OUR OBSERVATION: THE FAILURE OF RECEPTORS
LET US TAKE THIS EXAMPLE!
---------------------------------------------------------------------------------------------
------------------------------------------------------------------------------------------
LET'S ASSUME
THAT A GROWTH FACTOR HAS 2 PRINCIPAL RECEPTORS AND 2 SECONDARY RECEPTORS
(IN THIS EXAMPLE TNF- alpha IS SAID TO HAVE A "NUMBER OF TARGET GENES")
IF FOR SOME REASONS THE GROWTH FACTOR FAILED TO ACTIVATE ITS PRINCIPAL RECEPTORS, 2 THINGS HAPPEN:
1. THE PRINCIPAL RECEPTOR
initiates a stress like response which will involve the HP90, exacerbating the NF- kB
resulting in further activation of promoter genes and formation of MORE TNF- alpha
2. MORE TNF-alpha will exacerbate the effect on SECONDARY receptors still sensitive, leading to the activation/amplification of unwanted genes,
- Amplification of MUC-1 leads to an Adenoma and eventually Adenocarcinoma.
- Amplification of MUC-2 leads to a pseudomyxoma.
- May be MUC-7 will be lung and bladder Cancer?
PICK A NUMBER AND YOU WILL FIND WHERE THE CANCER WILL BE. THIS IS THE POWER OF RECEPTORS AND THE POWER OF GENE POLYMORPHISM!
Let's play:
Full Name mucin 10, submandibular gland salivary mucin
Ubiquitous cytoplasmic expression in all tissues at variable levels. Highest expression in gastrointestinal tract.
‹silver
HPA027769; HPA023835
THIS EXERCISE CAN BE DONE WITH ALL ADENOCARCINOMAS!
DO YOU SEE PORTRAYED HERE A TARGET FOR THERAPY OR DIAGNOSIS?
LET'S GO TO WORK!
In Summary,
Epithelial covers of Mucosa secrete a Mucine to protect it against infection and immune system exactions
and depending on localization the MUCINE is made a different family member of MUC -x gene
this is helpful when you have a carcinoma of unknown primary, look at the MUC gene amplified
YOU reach the door of MESENCHYMALIZATION when you reach MUC-20, this is where epidermal and endothelial switch, where squamous switch to adenocarcinoma, where the MEK gene is located!
OF OUR OBSERVATION: THE FAILURE OF RECEPTORS
LET US TAKE THIS EXAMPLE!
---------------------------------------------------------------------------------------------
Tumor necrosis factor-alpha induces mucin hypersecretion and MUC-2 gene expression by human airway epithelial cells.
Source
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1662.Abstract
Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional, pro-inflammatory cytokine that is capable of activating a diverse number of target genes within multiple cell types. Little information is known regarding the role of TNF-alpha in the regulation of human airway mucin hypersecretion and MUC-2 gene expression.------------------------------------------------------------------------------------------
LET'S ASSUME
THAT A GROWTH FACTOR HAS 2 PRINCIPAL RECEPTORS AND 2 SECONDARY RECEPTORS
(IN THIS EXAMPLE TNF- alpha IS SAID TO HAVE A "NUMBER OF TARGET GENES")
IF FOR SOME REASONS THE GROWTH FACTOR FAILED TO ACTIVATE ITS PRINCIPAL RECEPTORS, 2 THINGS HAPPEN:
1. THE PRINCIPAL RECEPTOR
initiates a stress like response which will involve the HP90, exacerbating the NF- kB
resulting in further activation of promoter genes and formation of MORE TNF- alpha
2. MORE TNF-alpha will exacerbate the effect on SECONDARY receptors still sensitive, leading to the activation/amplification of unwanted genes,
- Amplification of MUC-1 leads to an Adenoma and eventually Adenocarcinoma.
- Amplification of MUC-2 leads to a pseudomyxoma.
- May be MUC-7 will be lung and bladder Cancer?
Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species.
Source
Division of Pediatric Pulmonary Diseases, Duke University Medical Center, Durham, North Carolina 27710, USA.Abstract
Neutrophil-predominant airway inflammation and mucus obstruction of the airways are major pathologic features of chronic airway diseases, including cystic fibrosis and chronic bronchitis. Neutrophils release elastase, a serine protease that impairs mucociliary clearance and stimulates goblet cell metaplasia and mucin production. We previously reported that neutrophil elastase increases expression of a major respiratory mucin gene, MUC5AC, by enhancing mRNA stability. However, the molecular mechanisms of elastase-regulated MUC5AC expression are not known. We hypothesized that reactive oxygen species, generated by elastase treatment, mediate MUC5AC gene expression.MUC4 gene polymorphisms associate with endometriosis development and endometriosis-related infertility.
Source
Human Genetic Center, China Medical University Hospital, Taichung, Taiwan.Abstract
BACKGROUND:
Mucin 4 (MUC4) plays an important role in protecting and lubricating the epithelial surface of reproductive tracts, but its role in the pathogenesis of endometriosis is largely unknown.MUC3 human intestinal mucin. Analysis of gene structure, the carboxyl terminus, and a novel upstream repetitive region.
Source
Gastrointestinal Research Laboratory (151M2), Department of Veterans Affairs Medical Center, University of California, San Francisco, California 94121, USA.Abstract
MUC3 is a large mucin glycoprotein expressed by the human intestine and gall bladder.MUC6 - Wikipedia, the free encyclopedia
Reid CJ, Harris A (1999). "Expression of the MUC 6 mucin gene in development of the human kidney and male genital ducts.".PICK A NUMBER AND YOU WILL FIND WHERE THE CANCER WILL BE. THIS IS THE POWER OF RECEPTORS AND THE POWER OF GENE POLYMORPHISM!
Let's play:
Full Name mucin 10, submandibular gland salivary mucin
MUC12 »
Mucin-12
(MUC-12)
Protein also known as:
Mucin-11 (MUC-11).
Gene name:
MUC12
This protein has been shown to exist at protein level
Expression
Ubiquitous, with higher expression in colon. Down-regulated in
colorectal cancer as well as in the colon of patients with ulcerative
colitis (UC) and Crohn's disease (CD).
- CuratedUniProtKB
THIS EXERCISE CAN BE DONE WITH ALL ADENOCARCINOMAS!
DO YOU SEE PORTRAYED HERE A TARGET FOR THERAPY OR DIAGNOSIS?
LET'S GO TO WORK!
In Summary,
Epithelial covers of Mucosa secrete a Mucine to protect it against infection and immune system exactions
and depending on localization the MUCINE is made a different family member of MUC -x gene
this is helpful when you have a carcinoma of unknown primary, look at the MUC gene amplified
YOU reach the door of MESENCHYMALIZATION when you reach MUC-20, this is where epidermal and endothelial switch, where squamous switch to adenocarcinoma, where the MEK gene is located!
Saturday, April 20, 2013
DOES HAIR COLOR CHANGE COMES FROM METHIONINE MALABSORPTION ???
DOES HAIR COLOR CHANGE COMES FROM METHIONINE MALABSORPTION ???
"The following Votrient side effects are common (occurring in greater than 30%) for patients taking Votrient:
This list includes common and less common side effects for those taking Votrient. Votrient's side effects that are very rare -- occurring in less than about 10 percent of patients -- are not listed here. Always inform your health care provider if you experience any unusual symptoms."
(SCOTT HAMILTON CARES )
"The following Votrient side effects are common (occurring in greater than 30%) for patients taking Votrient:
- Diarrhea
- Hypertension
- Hair color changes
- Low blood counts (low white blood cells, low platelets)
- Elevated liver function tests (AST, ALT)
- Elevated bilirubin level
- Blood test abnormalities (low phosphorus, low sodium, increased glucose)
This list includes common and less common side effects for those taking Votrient. Votrient's side effects that are very rare -- occurring in less than about 10 percent of patients -- are not listed here. Always inform your health care provider if you experience any unusual symptoms."
(SCOTT HAMILTON CARES )
Error of metabolism points to interesting targets to be used in T cell rearrangement strategy
Error of metabolism points to interesting targets to be used in T cell rearrangement strategy
Glut 2 ----To be looked at in Pancreatic Cancer (No CNS involvement)
Glut 4
Gs alpha----(To be looked at in Sarcoma)
IRS 1
Biopterin Synthesis
FMR1
GNB
Adenyl Cyclase
===================================================
GENES INVOLVED IN SURVIVAL (ADAPTATION)
RAG 1
RAG 2
(TRANSPOSASE)
DNA -PK
XRCC4
XLF
ARTEMIS
CERNUNNOS
LAMBDA AND MU
VDJ
----------------------------------------------------------
RECEPTOR FOR ALPHA AND BETA CHAIN
CDR, 1-4
TCR
-------------------------------
MGAT2
--------------------------
GENES INVOLVED IN GLYCOSYLATION
Neu5Ac
Neu 5GC
CMAH
MGAT
FUT8
CHO-STGAL
CHOK1
TRANSFERRIN
LYSOZOMAL LEVEL
GDP MANNOSE
----------------------------
PMM2
MPI
----------------------------
GENES OF MUSCLE DYSTROPHY
POMT1
POMGNT1
DYSTROGLYCAN
FKRP
------------------------------------
GALNT3 MODIFIES FGF23
COSMC FOLDING OF GLYCAN
Glut 2 ----To be looked at in Pancreatic Cancer (No CNS involvement)
Glut 4
Gs alpha----(To be looked at in Sarcoma)
IRS 1
Biopterin Synthesis
FMR1
GNB
Adenyl Cyclase
===================================================
GENES INVOLVED IN SURVIVAL (ADAPTATION)
RAG 1
RAG 2
(TRANSPOSASE)
DNA -PK
XRCC4
XLF
ARTEMIS
CERNUNNOS
LAMBDA AND MU
VDJ
----------------------------------------------------------
RECEPTOR FOR ALPHA AND BETA CHAIN
CDR, 1-4
TCR
-------------------------------
MGAT2
--------------------------
GENES INVOLVED IN GLYCOSYLATION
Neu5Ac
Neu 5GC
CMAH
MGAT
FUT8
CHO-STGAL
CHOK1
TRANSFERRIN
LYSOZOMAL LEVEL
GDP MANNOSE
----------------------------
PMM2
MPI
----------------------------
GENES OF MUSCLE DYSTROPHY
POMT1
POMGNT1
DYSTROGLYCAN
FKRP
------------------------------------
GALNT3 MODIFIES FGF23
COSMC FOLDING OF GLYCAN
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