"Lucitanib has 50% Response (PR) in FGF-amplified Breast Cancer"
given FGF amplification requirement, and the involvement of Heparan sulfate the great cover of receptor, how this drug may interact with Hormone replacement therapy?
Wednesday, August 13, 2014
questions?
From ASCO,
for Extensive disease, CISPLATIN - Etoposide has become standard of care
but in Bulky Mediastinal disease, new study propose Radiation after the 4 cycles of chemotherapy
wonder if concurrent chemotherapy radiation will ultimately be better as known in NSCL?
PCI now known for Limited stage small cell, seems good for Extensive stage also? yes expert says now! Go figure. All for a PCI that do not prolong survival?
In Pancreatic Cancer,
adding Ruxolitinib (Anti-JAK1,2) to Xeloda will increase response rate! Hummm.....JAK1,2.....
Samstein et al " Foxp3 is induced during thymic differentiation or upon activation of peripheral CD4+ T cells in response to T cell receptor (TCR) stimulation in combination with several other signals, including IL-2 and TGF-β. Furthermore, forced expression of Foxp3 confers suppressor function to Treg precursor cells, and Foxp3 ablation in mature Treg cells results in loss of lineage identity and immunosuppressive phenotype (Fontenot et al., 2003; Williams and Rudensky, 2007). However, an understanding of how Foxp3 coordinates the differentiation of Treg cells and their distinct suppression program is lacking."
Or is it the RUNX?
NO they say it is STAT3! The activator of Cahexia, If you amplify STAT3, you lose weight? That's should be on demande everywhere!But be careful it waste muscle and probably not the fat (a composition of tissue issue!)
for Extensive disease, CISPLATIN - Etoposide has become standard of care
but in Bulky Mediastinal disease, new study propose Radiation after the 4 cycles of chemotherapy
wonder if concurrent chemotherapy radiation will ultimately be better as known in NSCL?
PCI now known for Limited stage small cell, seems good for Extensive stage also? yes expert says now! Go figure. All for a PCI that do not prolong survival?
In Pancreatic Cancer,
adding Ruxolitinib (Anti-JAK1,2) to Xeloda will increase response rate! Hummm.....JAK1,2.....
Samstein et al " Foxp3 is induced during thymic differentiation or upon activation of peripheral CD4+ T cells in response to T cell receptor (TCR) stimulation in combination with several other signals, including IL-2 and TGF-β. Furthermore, forced expression of Foxp3 confers suppressor function to Treg precursor cells, and Foxp3 ablation in mature Treg cells results in loss of lineage identity and immunosuppressive phenotype (Fontenot et al., 2003; Williams and Rudensky, 2007). However, an understanding of how Foxp3 coordinates the differentiation of Treg cells and their distinct suppression program is lacking."
Or is it the RUNX?
NO they say it is STAT3! The activator of Cahexia, If you amplify STAT3, you lose weight? That's should be on demande everywhere!But be careful it waste muscle and probably not the fat (a composition of tissue issue!)
Monday, August 11, 2014
Facts: SOME POSITIVE TRIALS! (from ASCO)
*Multicenter phase II trial in RECURRENT Ovarian Cancer
Cediranib 30 mg daily + Olaprib 200mg PO BID Vs Olaparib 400 mg BID
POSITIVE TRIAL, EVEN IN PATIENT WITHOUT BRCA MUTATION!
and quite a big difference PFS 17 months Vs 9 months
*In Head and neck, Cisplatin-RT is king for treatment
BUT ADD CETUXIMAB IN KRAS variant group
*In Medullary Thyroid cancer
Vandetanib Objective response 45%
30 months PFS Vs Placebo 19 months
-RET Mutation in FAMILIAL or HEREDITARY Medullary Thyroid cancer
also effective Motezanil, Cabozantinib, Sorafenib, Axitinib (MOUTH FULL!!!!)
*IODINE THERAPY FOR METASTATIC THYROID CANCER
RR 70%
for those refractory to Iodine RT
1. Chemotherapy gives Median survival 5 months
2. Lenvatinib 24 mg PO daily OR 65%
and PFS 18.3 months (read up on side effects)
Nexavar, an option in this disease!
*MPDL3280A, by inhibiting PD-L1, will have significant activity in Metastatic Urothelial Bladder cancer.
Cediranib 30 mg daily + Olaprib 200mg PO BID Vs Olaparib 400 mg BID
POSITIVE TRIAL, EVEN IN PATIENT WITHOUT BRCA MUTATION!
and quite a big difference PFS 17 months Vs 9 months
*In Head and neck, Cisplatin-RT is king for treatment
BUT ADD CETUXIMAB IN KRAS variant group
*In Medullary Thyroid cancer
Vandetanib Objective response 45%
30 months PFS Vs Placebo 19 months
-RET Mutation in FAMILIAL or HEREDITARY Medullary Thyroid cancer
also effective Motezanil, Cabozantinib, Sorafenib, Axitinib (MOUTH FULL!!!!)
*IODINE THERAPY FOR METASTATIC THYROID CANCER
RR 70%
for those refractory to Iodine RT
1. Chemotherapy gives Median survival 5 months
2. Lenvatinib 24 mg PO daily OR 65%
and PFS 18.3 months (read up on side effects)
Nexavar, an option in this disease!
*MPDL3280A, by inhibiting PD-L1, will have significant activity in Metastatic Urothelial Bladder cancer.
Sunday, August 10, 2014
Most unpredictable compounds: the cytokines!
They are numerous, most insidious and varied, yet impact the trends of our life in a deep, multiple ways. And we are just now trying to dig deeper in our understanding of these molecules. The Cytokines affect almost all aspects of our lives but unlike the hormones which induces changes at organs, tissues and system levels, they act at cellular level. Their functions are poorly defined because of this cellular level of action. But it is them that act on most receptors and ions channels to induce some the most vile and irreversible changes in cells, tissues and organs. And yet they remain unknown to the common living being!
A man asked, why we get fever during the course of an infection? I answered "your Cytokines"
Why I can't put up some weight when I have cancer or an autoimmune disease? once again the "cytokines"
Why people develop Post traumatic syndrome ? the Cytokines
why cancer cells get a growth advantage over local tissue in Metastatic cancers? if you guessed "Cytokines" you are right!
What do we give in adjuvant therapy after Melanoma resection? the Cytokine
What can cure Renal cell cancer? the CYTOKINES
What affects our Joints or induce Arthropathies when cholesterol is high (hyperlipidemia)? Cytokines for god sakes!
Why we get the features of getting old even in hiding? Cytokines....
and where in hell are your doctors not measuring these Cytokines....
The thing is that even we know they exist, nobody really knows to catch all of them, study them to their fullness...and use then to their potentials. And now that we are going molecular or I should say genetic with target therapy, we can probably make them synthetically...And I suspect their make up will be varied since they come from genes that are notoriously varied....
Cytokine banks are needed, and plasma centers collect them daily! put these facts together and make the math!
A man asked, why we get fever during the course of an infection? I answered "your Cytokines"
Why I can't put up some weight when I have cancer or an autoimmune disease? once again the "cytokines"
Why people develop Post traumatic syndrome ? the Cytokines
why cancer cells get a growth advantage over local tissue in Metastatic cancers? if you guessed "Cytokines" you are right!
What do we give in adjuvant therapy after Melanoma resection? the Cytokine
What can cure Renal cell cancer? the CYTOKINES
What affects our Joints or induce Arthropathies when cholesterol is high (hyperlipidemia)? Cytokines for god sakes!
Why we get the features of getting old even in hiding? Cytokines....
and where in hell are your doctors not measuring these Cytokines....
The thing is that even we know they exist, nobody really knows to catch all of them, study them to their fullness...and use then to their potentials. And now that we are going molecular or I should say genetic with target therapy, we can probably make them synthetically...And I suspect their make up will be varied since they come from genes that are notoriously varied....
Cytokine banks are needed, and plasma centers collect them daily! put these facts together and make the math!
Thursday, August 7, 2014
Major advances in Oncology. and CRBCM on the move!
1.In lung cancer, Pembrolizumab, the PD-1 humanized antibody made the Breakthrough cut but keeping activity in first line as well advanced Non small cell lung cancer. Given at 10mg/kg every 3 to 3 weeks,
at least half of the patient will respond whae they have the PDL-1 receptor!
No patient today should die of this disease if they have the receptor, without seeing PEMBRO!
2.In ALL, CD19 targeted chimeric Antigen Receptor (CAR received Breakthrough designation and Blinatomomab....These are huge discoveries to say the least and in deisease notoriously mortal! With unprecedented response rates 80 to 100 % according to study populations !And manageable side effects!
3.The excellent Ibrutinib is "tripling" disease free survival and doubling survival in certain CLL....these are again unprecedented results of new target therapy
the standard chemotherapy is soon becoming remotely cited in current Oncology journal
and there is more to come....
Lenvatinib----Thyroid cancer
Bladder cancers----MPDL328A
Now Jakafi -Xelaoda in pancreatic cancer!!!
behind PEMBRO, NECITUMUMAB sneaking in NSCL cancers!
Belinostat for Peripheral T-cell lymphoma
Finally we see the Anti-BCL2 working in CLL--ABT-199, here we are acing the mechanism of non dying cells!
And embracing the 2nd generation anti -EGFR!!!! science is on the Go....enemies working their best to politicize science...CRBCM working hard despite ....
at least half of the patient will respond whae they have the PDL-1 receptor!
No patient today should die of this disease if they have the receptor, without seeing PEMBRO!
2.In ALL, CD19 targeted chimeric Antigen Receptor (CAR received Breakthrough designation and Blinatomomab....These are huge discoveries to say the least and in deisease notoriously mortal! With unprecedented response rates 80 to 100 % according to study populations !And manageable side effects!
3.The excellent Ibrutinib is "tripling" disease free survival and doubling survival in certain CLL....these are again unprecedented results of new target therapy
the standard chemotherapy is soon becoming remotely cited in current Oncology journal
and there is more to come....
Lenvatinib----Thyroid cancer
Bladder cancers----MPDL328A
Now Jakafi -Xelaoda in pancreatic cancer!!!
behind PEMBRO, NECITUMUMAB sneaking in NSCL cancers!
Belinostat for Peripheral T-cell lymphoma
Finally we see the Anti-BCL2 working in CLL--ABT-199, here we are acing the mechanism of non dying cells!
And embracing the 2nd generation anti -EGFR!!!! science is on the Go....enemies working their best to politicize science...CRBCM working hard despite ....
Sunday, August 3, 2014
Good update to have in hematologic malignancy, and may be a chance to visit the POLO-like kinases! take a plunge!
CONTINUING MEDICAL EDUCATION CERTIFICATE
certifies that
Mutombo Kankonde, MD
2400 Trawood Drive
Suite 303
El Paso, TX 79936
2400 Trawood Drive
Suite 303
El Paso, TX 79936
has participated in the enduring material titled
Pivotal Data Highlights on MPN and AML From the 2014 Summer Hematology Congresses
August 3, 2014
and is awarded
0.75
AMA PRA Category 1 Credit(s)™.
Medscape, LLC designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Medscape, LLC is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to provide continuing medical
education for physicians.
For information on
applicability and acceptance of continuing education credit for this
activity, please consult your professional licensing board.
| Certificate Number: 48368018 |  Cyndi Grimes Director, Continuing Medical Education Medscape, LLC |
Big good
CONTINUING MEDICAL EDUCATION CERTIFICATE
certifies that
Mutombo Kankonde, MD
2400 Trawood Drive
Suite 303
El Paso, TX 79936
2400 Trawood Drive
Suite 303
El Paso, TX 79936
has participated in the enduring material titled
Management of Follicular Lymphoma
August 3, 2014
and is awarded
1.75
AMA PRA Category 1 Credit(s)™.
Medscape, LLC designates this enduring material for a maximum of 1.75 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Medscape, LLC is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to provide continuing medical
education for physicians.
For information on
applicability and acceptance of continuing education credit for this
activity, please consult your professional licensing board.
| Certificate Number: 48367244 | Cyndi Grimes Director, Continuing Medical Education Medscape, LLC |
Thursday, July 31, 2014
With Anti-PD1, and Ibrutinib, we have entered the new world of therapy in cancers
The time of dirty bomb that standard Chemotherapy represented, has quickly led to major side effects and of course given us partial results. Cure was not achieved most of the times except in rare chemotherapy successes such as in Hodgkin disease and some cases where disease was limited, and surgery with adjuvant chemotherapy plus or minus Radiation allowed the cancer patients to survive. Even in these rare cure cases, Doctors remained on the look-out using Biomarkers that most of the time "only God knows "worked. Recurrences and secondary cancers were clearly unpredictable and random, we could not come up with decent explanation, except for a conclusion that the earlier therapeutic intervention may have precipitated them or have something to do with them.
Today, with our increasing knowledge of cellular pathways, we live one step forward, an exciting time in Oncology and hematology/Immunology/Rheumatology. The discovery that target therapy unveils new cures has the Oncology community bubbling with excitements (at least they (Oncologists) should!). We are now tackling newly cancers such as Melanoma and refractory lung cancers with further excitement then before. Indeed we are curious to know whether the promise of target therapy will be achieved in every new cancers we encounter. We suspected without clear knowledge that Target therapy would work since the effect of IL-2 in renal cancer has never been matched by standard chemotherapy, and the striking fact that only high dose Interferon worked in adjuvant treatment of Melanoma. Furthermore, our suspicion was that these agents were acting by boosting the immune system against cancer cells. No need to say or emphasize that this effect was so profound that cure was achieved in some difficult cancers. Our limitations and fear to pursue this line of attack against cancer cells were mainly limited because of the unexpected side effects (the vascular disturbance and resulting extravasation syndrome induced by these agents at high dose). And it acted as a Dirty bomb by overwhelming the cancer cells hidden paths to Apoptosis. Today however, we have gotten smarter hitting check point targets "at will" and more "surgically". And Oncologists have become a little abrasive and more confident. Expression such as "Up front, hit hard, and don't stop" is being published (Sandra Ker) about the use of Target therapies! The surprising effect of anti-PD-1/ PDL1 and their relative lack of dramatic side effects is a feast we should enjoy! Are they the receptors stimulated non-specifically by these previous high dose Interleukin-2 and Interferon...research is underway to figure that one out with certainty. But already combining these old strategies (IL-2, Interferon) with the new Ibrutinib and Nivolumab is on the mind of researchers to try to tease the new unveiled therapeutic concepts.
Many (include this authors) believe that the success of the AntiPDL-1 actually lies in a well known concept that, on a daily basis, cells that go awry end up being removed from our system by the army of white blood cells that we have, and this is why the cancer cells will work hard to hide themselves from the Lymphocytes. The discovery of ways to activates the White Blood cells against tumors seem to offer a winning approach in cancer management and therapy! The approaches tackling PD-1, PDL-1, and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), all seem to work...When in Breast cancer lymphocyte infiltration seems to predict response to chemotherapy, we know another "volet " (french for compartment) is being unveiled in the story of White blood cells and cancers!
One thing for sure, and clearly another challenge to confront now, is the build up of escape mechanisms against these new therapeutic avenues. We have come to realize, that we can't tell cells including cancer cells that it is alright to die now! Cancer cells like all cells continue to figure that our therapeutic interventions are a new "environmental" challenge and continue to figure new escape mechanisms (pathways to resistance cancers) forcing us to have to design a multiple step strategy to achieve the cure. Indeed "2 or multiple punches" strategy is needed sometime to achieve longer progression free survival or Overall survival (OS) by sequencing or concurrently using available drugs! But now that is another "Volet".....CRBCM is hard at work!
Today, with our increasing knowledge of cellular pathways, we live one step forward, an exciting time in Oncology and hematology/Immunology/Rheumatology. The discovery that target therapy unveils new cures has the Oncology community bubbling with excitements (at least they (Oncologists) should!). We are now tackling newly cancers such as Melanoma and refractory lung cancers with further excitement then before. Indeed we are curious to know whether the promise of target therapy will be achieved in every new cancers we encounter. We suspected without clear knowledge that Target therapy would work since the effect of IL-2 in renal cancer has never been matched by standard chemotherapy, and the striking fact that only high dose Interferon worked in adjuvant treatment of Melanoma. Furthermore, our suspicion was that these agents were acting by boosting the immune system against cancer cells. No need to say or emphasize that this effect was so profound that cure was achieved in some difficult cancers. Our limitations and fear to pursue this line of attack against cancer cells were mainly limited because of the unexpected side effects (the vascular disturbance and resulting extravasation syndrome induced by these agents at high dose). And it acted as a Dirty bomb by overwhelming the cancer cells hidden paths to Apoptosis. Today however, we have gotten smarter hitting check point targets "at will" and more "surgically". And Oncologists have become a little abrasive and more confident. Expression such as "Up front, hit hard, and don't stop" is being published (Sandra Ker) about the use of Target therapies! The surprising effect of anti-PD-1/ PDL1 and their relative lack of dramatic side effects is a feast we should enjoy! Are they the receptors stimulated non-specifically by these previous high dose Interleukin-2 and Interferon...research is underway to figure that one out with certainty. But already combining these old strategies (IL-2, Interferon) with the new Ibrutinib and Nivolumab is on the mind of researchers to try to tease the new unveiled therapeutic concepts.
Many (include this authors) believe that the success of the AntiPDL-1 actually lies in a well known concept that, on a daily basis, cells that go awry end up being removed from our system by the army of white blood cells that we have, and this is why the cancer cells will work hard to hide themselves from the Lymphocytes. The discovery of ways to activates the White Blood cells against tumors seem to offer a winning approach in cancer management and therapy! The approaches tackling PD-1, PDL-1, and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), all seem to work...When in Breast cancer lymphocyte infiltration seems to predict response to chemotherapy, we know another "volet " (french for compartment) is being unveiled in the story of White blood cells and cancers!
One thing for sure, and clearly another challenge to confront now, is the build up of escape mechanisms against these new therapeutic avenues. We have come to realize, that we can't tell cells including cancer cells that it is alright to die now! Cancer cells like all cells continue to figure that our therapeutic interventions are a new "environmental" challenge and continue to figure new escape mechanisms (pathways to resistance cancers) forcing us to have to design a multiple step strategy to achieve the cure. Indeed "2 or multiple punches" strategy is needed sometime to achieve longer progression free survival or Overall survival (OS) by sequencing or concurrently using available drugs! But now that is another "Volet".....CRBCM is hard at work!
Monday, July 28, 2014
Interesting find in the literature, not from CRBCM but tie our life up completely!
This can be found in the literature
110 interacting genes: ACTG1 ACTN2 AGTPBP1 AKAP6 AKAP9 ARIH2 ATF4 ATF5 ATF7IP BICD1 C14orf166 CCDC136 CCDC141 CCDC24 CCDC88A CDC5L CDK5RAP3 CEP170 CEP57L1 CEP63 CIT CLU COL4A1 DCTN1 DCTN2 DMD DNAJC7 DPYSL2 DPYSL3 DST DYNC1H1 EEF2 EIF3H EXOC1 EXOC4 EXOC7 FBXO41 FEZ1 FRYL GNB1 GNPTAB GPRASP2 HERC2P2 IFT20 IMMT ITSN1 KALRN KANSL1 KCNQ5 KIAA1377 KIF3A KIF3C KIFAP3 MACF1 MAP1A MATR3 MEMO1 MLLT10 MPPED1 MYO1A MYT1L NDEL1 NEFM NUP160 OLFM1 PAFAH1B1 PCNT PCNXL4 PDE4B PGK1 PPM1E PPP4R1 PPP5C RABGAP1 RAD21 RANBP9 RASSF7 ROGDI SH3BP5 SMARCE1 SMC2 SMC3 SNX6 SPARCL1 SPTAN1 SPTBN1 SPTBN4 SRGAP2 SRGAP3 STX18 SYBU SYNE1 TFIP11 TIAM2 TNIK TNKS TRAF3IP1 TRIO TUBB TUBB2A UTRN XPNPEP1 XRN2 YWHAE YWHAG YWHAQ YWHAZ ZFYVE20 ZNF197 ZNF365
72 interacting genes: ACTB ACTC1 ACTG1 ALDOA B3GALT4 BCAS1 BCL2L11 BMF C14orf1 CA2 CACNB1 CLIP2 CS DAZ1 DLG4 DLGAP1 DNAJB9 DNM2 DNM3 DNMT1 DYNC1H1 DYNC1I1 EEF1A1 GAPDH GLUD1 GLUL GNB2L1 GPHN GRIN3A HIP1R HSPA8 INPP1 LDHA MAP1B MARK3 MAST2 ME2 MTA1 MTR MYO10 MYO5A NDUFA4L2 NFKBIA NOS1 NRF1 NTRK1 NTRK2 NTRK3 PAK1 PAN2 PARD3 PAX6 PFKM PFKP PKIA PKIB PKIG POLH RAB4A RGS2 SHROOM3 TERT THAP8 TNFRSF14 TP53BP1 TUBA3C TUBB TXNDC17 VIM ZHX1 ZMYND11 ZNF354A
Disclaimer, we are not the maker of this list,
but love to review these genes individually
something is hidden here
I don't know what or where
but I can feel it
A little work will just go a long way to decipher what !
And let's get to it then....
CRBCM working despite the " intemperies" and adversities of the moment! We believe in our cause while the enemies are hard at work to stop science!
110 interacting genes: ACTG1 ACTN2 AGTPBP1 AKAP6 AKAP9 ARIH2 ATF4 ATF5 ATF7IP BICD1 C14orf166 CCDC136 CCDC141 CCDC24 CCDC88A CDC5L CDK5RAP3 CEP170 CEP57L1 CEP63 CIT CLU COL4A1 DCTN1 DCTN2 DMD DNAJC7 DPYSL2 DPYSL3 DST DYNC1H1 EEF2 EIF3H EXOC1 EXOC4 EXOC7 FBXO41 FEZ1 FRYL GNB1 GNPTAB GPRASP2 HERC2P2 IFT20 IMMT ITSN1 KALRN KANSL1 KCNQ5 KIAA1377 KIF3A KIF3C KIFAP3 MACF1 MAP1A MATR3 MEMO1 MLLT10 MPPED1 MYO1A MYT1L NDEL1 NEFM NUP160 OLFM1 PAFAH1B1 PCNT PCNXL4 PDE4B PGK1 PPM1E PPP4R1 PPP5C RABGAP1 RAD21 RANBP9 RASSF7 ROGDI SH3BP5 SMARCE1 SMC2 SMC3 SNX6 SPARCL1 SPTAN1 SPTBN1 SPTBN4 SRGAP2 SRGAP3 STX18 SYBU SYNE1 TFIP11 TIAM2 TNIK TNKS TRAF3IP1 TRIO TUBB TUBB2A UTRN XPNPEP1 XRN2 YWHAE YWHAG YWHAQ YWHAZ ZFYVE20 ZNF197 ZNF365
72 interacting genes: ACTB ACTC1 ACTG1 ALDOA B3GALT4 BCAS1 BCL2L11 BMF C14orf1 CA2 CACNB1 CLIP2 CS DAZ1 DLG4 DLGAP1 DNAJB9 DNM2 DNM3 DNMT1 DYNC1H1 DYNC1I1 EEF1A1 GAPDH GLUD1 GLUL GNB2L1 GPHN GRIN3A HIP1R HSPA8 INPP1 LDHA MAP1B MARK3 MAST2 ME2 MTA1 MTR MYO10 MYO5A NDUFA4L2 NFKBIA NOS1 NRF1 NTRK1 NTRK2 NTRK3 PAK1 PAN2 PARD3 PAX6 PFKM PFKP PKIA PKIB PKIG POLH RAB4A RGS2 SHROOM3 TERT THAP8 TNFRSF14 TP53BP1 TUBA3C TUBB TXNDC17 VIM ZHX1 ZMYND11 ZNF354A
Disclaimer, we are not the maker of this list,
but love to review these genes individually
something is hidden here
I don't know what or where
but I can feel it
A little work will just go a long way to decipher what !
And let's get to it then....
CRBCM working despite the " intemperies" and adversities of the moment! We believe in our cause while the enemies are hard at work to stop science!
Medicine of the future!
Medicine of the future
The way we see it, in the near future, 3 main factors will determine what will be driving medicine in the future.
1.The patient genome which determine the patient potential to survive and cope with his environment.
2.Presence in that genome of favorable Heterogeneic Alleles or genes to both treatment and environmental stimulants.
3.more powerful computers to process various integrals of gene, receptors,and cytokines patterns. This suppose detectors of thin nuances in molecular behaviors at cellular and nano-molecular levels. Yes we know the main pathways and probably several secondary pathways of significance, but our ability to interpret, quantify, and draw meaningful conclusions, is still preliminary and at the dawn of what will be medicine of tomorrow (ie. the change of various membrane receptors when a neoplastic process is engaged in a cell.) We have yet to define clear bio-markers for most diseases and of life determinants in general. We are still linking the fact that we survive to what our neighbors and boss do, our work environment, what we drink is sweet or not, when the cell, where life is really determined sees everything as a chemical stimulant!
Other secondary factors:
1-known new target therapies
2-Telomere status
3-new chemicals created by our "smart" engineers
4-potential new pathogens and how they will enter the frey of our world
etc...
Globally,
Each step of cellular gene and metabolism will need to be carefully studied and perfectly understood to reach the medicine of the future.
example of a visit in the future:
Mrs Freddy comes to DR Pizzazz complaining of headache. She gives him a chip containing all her genes.
The chip is introduced in a smart computer and with a sample of blood, the computer tells the DR that indeed the migraine came from an undetected Vasculitis based on these facts (ie.pattern of the patient cytokines, gene amplifications and ....), and that Prednisone would be dangerous for this lady because of the presence of a close by Receptor gene that may induce an irreversible chemical disturbance of membrane lipids and that Aleve would be best in this case. And by the way there is a secondary gene that will accelerate destruction of Telomeres'tails....and so on....!
This is the kind of Medicine we are aiming at....and all we don't know to reach there is a GAP TO FILL!
CRBCM advancing in the current darkness with a clear vision...
The way we see it, in the near future, 3 main factors will determine what will be driving medicine in the future.
1.The patient genome which determine the patient potential to survive and cope with his environment.
2.Presence in that genome of favorable Heterogeneic Alleles or genes to both treatment and environmental stimulants.
3.more powerful computers to process various integrals of gene, receptors,and cytokines patterns. This suppose detectors of thin nuances in molecular behaviors at cellular and nano-molecular levels. Yes we know the main pathways and probably several secondary pathways of significance, but our ability to interpret, quantify, and draw meaningful conclusions, is still preliminary and at the dawn of what will be medicine of tomorrow (ie. the change of various membrane receptors when a neoplastic process is engaged in a cell.) We have yet to define clear bio-markers for most diseases and of life determinants in general. We are still linking the fact that we survive to what our neighbors and boss do, our work environment, what we drink is sweet or not, when the cell, where life is really determined sees everything as a chemical stimulant!
Other secondary factors:
1-known new target therapies
2-Telomere status
3-new chemicals created by our "smart" engineers
4-potential new pathogens and how they will enter the frey of our world
etc...
Globally,
Each step of cellular gene and metabolism will need to be carefully studied and perfectly understood to reach the medicine of the future.
example of a visit in the future:
Mrs Freddy comes to DR Pizzazz complaining of headache. She gives him a chip containing all her genes.
The chip is introduced in a smart computer and with a sample of blood, the computer tells the DR that indeed the migraine came from an undetected Vasculitis based on these facts (ie.pattern of the patient cytokines, gene amplifications and ....), and that Prednisone would be dangerous for this lady because of the presence of a close by Receptor gene that may induce an irreversible chemical disturbance of membrane lipids and that Aleve would be best in this case. And by the way there is a secondary gene that will accelerate destruction of Telomeres'tails....and so on....!
This is the kind of Medicine we are aiming at....and all we don't know to reach there is a GAP TO FILL!
CRBCM advancing in the current darkness with a clear vision...
Sunday, July 27, 2014
working hard to meet the needs of our patients
Mutombo Kankonde, MD, MPH
Oncology
11601 Pellicano Drive
Suite A2
El Paso, TX 79936
Suite A2
El Paso, TX 79936
(915) 307-3354
Hitch a hike towards a comprehensive Cytokine Bank and Manufacturing Unit
The Protein Data Bank funded by several great institutions is a good starting point:
http://www.rcsb.org/pdb/home/home.do
http://www.rcsb.org/pdb/home/home.do
Saturday, July 26, 2014
Freedom of Information worked one more time!
The revelation that Dabigatran (Pradaxa) level should be monitored to reduce bleeding risk
has shaken the medical community. greed has once again obfuscated the truth. The makers of the drug
have hidden the solemn truth, you got to keep a level per Crystal Phend: "Boehringer Ingelheim determined that keeping plasma levels within the optimal 40-to-200 ng/mL range could cut bleeding risk by up to 20% compared with unadjusted use and by 40% compared with well-controlled warfarin (Coumadin) without sacrificing effectiveness in cutting risk of ischemic stroke in atrial fibrillation."
This is just disappointing that once again, greed may have won over patient safety! Someone please come to me with proof to the contrary before I protest vigorously!
has shaken the medical community. greed has once again obfuscated the truth. The makers of the drug
have hidden the solemn truth, you got to keep a level per Crystal Phend: "Boehringer Ingelheim determined that keeping plasma levels within the optimal 40-to-200 ng/mL range could cut bleeding risk by up to 20% compared with unadjusted use and by 40% compared with well-controlled warfarin (Coumadin) without sacrificing effectiveness in cutting risk of ischemic stroke in atrial fibrillation."
This is just disappointing that once again, greed may have won over patient safety! Someone please come to me with proof to the contrary before I protest vigorously!
Monday, July 21, 2014
Miscellaneous updates
1.Watch out now with patient being readmitted for a new cycle of chemotherapy may be counted as a readmission...the EHR has been diagnosed to make this mistake!
2.Is it true that the only people who like CERNER are the hospital administrators because of its instant billing feature!
3.Is it true that the Practice of "Time out" for last checks reduces Medical errors?
In Breast cancer:
===========
1.Salsa Trial: 10 years for Tamoxifen in adjuvant setting
2.ABCSG: Obesity may portend poor outcome in patients receiving Aromatase Inhibitors in Breast cancer treatment.
3.POEMS: Chemotherapy alone Vs Chemotherapy + Goserelin (the combination of chemo+Goserelin showed better fertility protection)
4. The combination of Dual Trastuzumab and Lapatinib failed to increase survival
Oncologists are awaiting resulst of Pertuzumab + Trastuzumab!for a final conclusion on these issues!
5.In breast cancers that are small and Her-2 positive, T<2cm weekly Taxol+Herceptin gives >=95% survival, just do this don't wait for a non coming trial! Please treat because the Mortality may be as high as 20-25%------give Herceptin as described
2.Is it true that the only people who like CERNER are the hospital administrators because of its instant billing feature!
3.Is it true that the Practice of "Time out" for last checks reduces Medical errors?
In Breast cancer:
===========
1.Salsa Trial: 10 years for Tamoxifen in adjuvant setting
2.ABCSG: Obesity may portend poor outcome in patients receiving Aromatase Inhibitors in Breast cancer treatment.
3.POEMS: Chemotherapy alone Vs Chemotherapy + Goserelin (the combination of chemo+Goserelin showed better fertility protection)
4. The combination of Dual Trastuzumab and Lapatinib failed to increase survival
Oncologists are awaiting resulst of Pertuzumab + Trastuzumab!for a final conclusion on these issues!
5.In breast cancers that are small and Her-2 positive, T<2cm weekly Taxol+Herceptin gives >=95% survival, just do this don't wait for a non coming trial! Please treat because the Mortality may be as high as 20-25%------give Herceptin as described
Sunday, July 20, 2014
PDL-1 Inhibitors, the WOW of the moment!
Beside starting the neoplastic process which involves rapid uncontrolled multiplication through installing transcription factors and related machinery to multiply genetic cancer materials and set the stage to metastasis, science has unveiled a critical point that favor the unedited expression of solid Neoplasms: the PDL1 or CD274.
Indeed during the neoplastic transformation, the cell undergoes several molecular transformations that changes drastically molecular membranes sufficiently to trigger autoimmunity our natural protector against cancer development. It is therefore painstakingly that all successful cancers will take control of this Cluster of differentiation 274 to escape or block autoimmunity.
The importance of PDL1 is critical when you look at the downstream pathway of this molecule:
1. It has control on the IL-2 production, the same IL-2 which in high dose CURES renal cancer!
By stopping or mitigating IL-2, this PDL-1 removes this outcome for cancers....
2. It impacts BCL-2, the gene that allow cells to escape sensitivity to many chemotherapy by ultimately blocking caspases'stimulation mainly at Mitochondrial level.
3. It decrease stimulation of the NF-kB and the AP-1 subsequently, basically reducing abnormal noises that could trigger the immune response to wake-up!
With the Ibrutinib receptor for hematologic Malignancies, PDL-1 is at this time the most prominent find in solid tumor to date. And soon, no chemotherapy may be given without it in solid tumor. It is the Velcade of the Multiple Myeloma.
Indeed during the neoplastic transformation, the cell undergoes several molecular transformations that changes drastically molecular membranes sufficiently to trigger autoimmunity our natural protector against cancer development. It is therefore painstakingly that all successful cancers will take control of this Cluster of differentiation 274 to escape or block autoimmunity.
The importance of PDL1 is critical when you look at the downstream pathway of this molecule:
1. It has control on the IL-2 production, the same IL-2 which in high dose CURES renal cancer!
By stopping or mitigating IL-2, this PDL-1 removes this outcome for cancers....
2. It impacts BCL-2, the gene that allow cells to escape sensitivity to many chemotherapy by ultimately blocking caspases'stimulation mainly at Mitochondrial level.
3. It decrease stimulation of the NF-kB and the AP-1 subsequently, basically reducing abnormal noises that could trigger the immune response to wake-up!
With the Ibrutinib receptor for hematologic Malignancies, PDL-1 is at this time the most prominent find in solid tumor to date. And soon, no chemotherapy may be given without it in solid tumor. It is the Velcade of the Multiple Myeloma.
Wednesday, July 16, 2014
check your sources, Are we in the belly of the beast!
When you study Arterosclerosis
when you study Breast cancer
Molecular movement inside the cell is important
then you come across this:
"
On binding a ligand the protein and ligand are internalized. This internalization is independent of macropinocytosis and occurs by an actin dependent mechanism requiring the activation Src-family kinases, JNK and Rho-family GTPases.[29] Unlike macropinocytosis this process is not affected by inhibitors of phosphatidylinositol 3-kinase or Na+/H+ exchange.
CD36 ligands have also been shown to promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer.[30]
Recently, CD36 was linked to store-operated calcium flux, phospholipase A2 activation, and production of prostaglandin E2[31]" wikipedia
this is about CD36
and you start thinking, am I in the belly of the Beast.
Research has shown!
PERK
!
!
Phosphorylate
!
!
PABP(interaction)---elf4 (ternary complex) which activates IRES (HnRNPC1)
CD36-------Glucose
!
!
Reinitiation of protein translation
then there is a GNC4
a general initiation factor
A general translation factor
ATF4
work to do!
when you study Breast cancer
Molecular movement inside the cell is important
then you come across this:
"
On binding a ligand the protein and ligand are internalized. This internalization is independent of macropinocytosis and occurs by an actin dependent mechanism requiring the activation Src-family kinases, JNK and Rho-family GTPases.[29] Unlike macropinocytosis this process is not affected by inhibitors of phosphatidylinositol 3-kinase or Na+/H+ exchange.
CD36 ligands have also been shown to promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer.[30]
Recently, CD36 was linked to store-operated calcium flux, phospholipase A2 activation, and production of prostaglandin E2[31]" wikipedia
this is about CD36
and you start thinking, am I in the belly of the Beast.
Research has shown!
PERK
!
!
Phosphorylate
!
!
PABP(interaction)---elf4 (ternary complex) which activates IRES (HnRNPC1)
CD36-------Glucose
!
!
Reinitiation of protein translation
then there is a GNC4
a general initiation factor
A general translation factor
ATF4
work to do!
Monday, July 14, 2014
What is this finding worth in Breast cancer
Now we are learning that immunology could be prognostic in Breast cancer
pathologic finding of tumor infiltration by lymphocytes could announce susceptibility to
chemotherapy drugs...always ask now pathologist to describe lymphocyte infiltration of Breast cancer tissue!
Susman reported:
"For every 10% increase in stromal tumor-infiltrating lymphocytes found in the breast cancer tissue, there is a corresponding 16% increase in the chance that a woman will achieve a pathological complete response to therapy (P=0.038), said Sherene Loi, MD, PhD, head of the Translational Breast Cancer Genomics Lab at the Peter MacCallum Cancer Centre in Melbourne, Australia."
Already Oncologists who neglected their Immunology are confronted by reality, we are entering immunology at a fast pace, read up!ASCO is cool with this!
pathologic finding of tumor infiltration by lymphocytes could announce susceptibility to
chemotherapy drugs...always ask now pathologist to describe lymphocyte infiltration of Breast cancer tissue!
Susman reported:
"For every 10% increase in stromal tumor-infiltrating lymphocytes found in the breast cancer tissue, there is a corresponding 16% increase in the chance that a woman will achieve a pathological complete response to therapy (P=0.038), said Sherene Loi, MD, PhD, head of the Translational Breast Cancer Genomics Lab at the Peter MacCallum Cancer Centre in Melbourne, Australia."
Already Oncologists who neglected their Immunology are confronted by reality, we are entering immunology at a fast pace, read up!ASCO is cool with this!
Sunday, July 13, 2014
Progress in Cancer
Despite the rise of Ramucirumab released by the FDA in 4/2014,
"- Eli Lilly and Company (NYSE: LLY) announced today that the U.S. Food and Drug Administration (FDA) has approved CYRAMZA™ (ramucirumab) as a single-agent treatment for patients with advanced or metastatic gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. With this approval, CYRAMZA becomes the first FDA-approved treatment for patients in this setting." press release by Lilly,
There are 2 major progress events noted in Oncology,
1. is the rise of PD1 /PDL1 inhibitor for solid tumors
2. the rise of Ibrutinib in Hematologic diseases
With the the Inhibitor of PD1/PDL1, science has found the best way to harness immunity against tumor, and doing so in most cases without significant side effects. Indeed, these therapeutic interventions have proven to be for most patient achievable and well tolerated. What the PD1 Inhibitors have been able to achieve is what we intended by Using IL-2 or Interferon (non specific global action of all old therapeutic interventions) versus a new sophisticated well targeted therapy with Activated Lymphocytes. Cancer cells try to escape surveillance by our immune system, and we are trying to say NO. And ladies and gentlemen, this time it worked, and working in most recalcitrant cancers! The Melanomas of the days will no longer escape our reach, and now respond in unprecedented number and for unprecedented length of time...this period is worth living! Literally, These drugs can be tried in almost every solid tumors with some legitimate relative success, and quite frankly within days, we might end up with groups of solid tumor described of those PD-1 inhibitor sensitive, and those which are not! And what is great, the addition of Modalities involving the immune system, seems additive in global effect. So nothing stop you but the price, adding Ipilimumab to the Anti-PDL1 and the effect follows! And of course clinicians follow ....
The success of Ibrutinib is just as incredible but hits one principle that we knew long time ago, and that is cells of the hematologic lineage, particurlarly white cells, stop differentiation and this simple fact protect them from natural maturation and simply dying of Apoptosis that awaits all mature cell. Indeed in the treatment using this modality, there is a sharp Lymphocytosis that scientist has attributed to delocalization a normal step into maturation toward Apoptosis! The drug has done what we intend to achieve when we say Cure, asking a cell to choose the natural way or pathway to death. Because we can't bomb every cell but asking to follow its fate is the only way to the cure!
"- Eli Lilly and Company (NYSE: LLY) announced today that the U.S. Food and Drug Administration (FDA) has approved CYRAMZA™ (ramucirumab) as a single-agent treatment for patients with advanced or metastatic gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. With this approval, CYRAMZA becomes the first FDA-approved treatment for patients in this setting." press release by Lilly,
There are 2 major progress events noted in Oncology,
1. is the rise of PD1 /PDL1 inhibitor for solid tumors
2. the rise of Ibrutinib in Hematologic diseases
With the the Inhibitor of PD1/PDL1, science has found the best way to harness immunity against tumor, and doing so in most cases without significant side effects. Indeed, these therapeutic interventions have proven to be for most patient achievable and well tolerated. What the PD1 Inhibitors have been able to achieve is what we intended by Using IL-2 or Interferon (non specific global action of all old therapeutic interventions) versus a new sophisticated well targeted therapy with Activated Lymphocytes. Cancer cells try to escape surveillance by our immune system, and we are trying to say NO. And ladies and gentlemen, this time it worked, and working in most recalcitrant cancers! The Melanomas of the days will no longer escape our reach, and now respond in unprecedented number and for unprecedented length of time...this period is worth living! Literally, These drugs can be tried in almost every solid tumors with some legitimate relative success, and quite frankly within days, we might end up with groups of solid tumor described of those PD-1 inhibitor sensitive, and those which are not! And what is great, the addition of Modalities involving the immune system, seems additive in global effect. So nothing stop you but the price, adding Ipilimumab to the Anti-PDL1 and the effect follows! And of course clinicians follow ....
The success of Ibrutinib is just as incredible but hits one principle that we knew long time ago, and that is cells of the hematologic lineage, particurlarly white cells, stop differentiation and this simple fact protect them from natural maturation and simply dying of Apoptosis that awaits all mature cell. Indeed in the treatment using this modality, there is a sharp Lymphocytosis that scientist has attributed to delocalization a normal step into maturation toward Apoptosis! The drug has done what we intend to achieve when we say Cure, asking a cell to choose the natural way or pathway to death. Because we can't bomb every cell but asking to follow its fate is the only way to the cure!
Thursday, July 10, 2014
Help us with the Cytokines
If you really want to know how to lose weight, help us with investment into the cytokines
that is where nature has hidden with loss measures
but before we tell you which the right way is to have clear biomarkers of toxicity
because they affect the CREB genes
and many other receptors
they are overexpressed in specific Autoimmune disease
and could induce IBD and therefore neoplasms particularly of the Gallbladder
monitoring must be implemented prior to release!
that is where nature has hidden with loss measures
but before we tell you which the right way is to have clear biomarkers of toxicity
because they affect the CREB genes
and many other receptors
they are overexpressed in specific Autoimmune disease
and could induce IBD and therefore neoplasms particularly of the Gallbladder
monitoring must be implemented prior to release!
Tomorrow is even better!
By developing new techniques to measure protein elasticity as part of progress in nanobiotechnology,
the French are pushing the envelop that will soon define Medicine of the future. The prospect of finally projecting a molecule and studying its elasticity brings our knowledge in the belly of the beast even closer.
Already the prospect that we could first interrogate Core Binding Proteins, and than know to change their elasticity and movements, and more likely unveiling new attachment sites to molecule of our choosing, open prospects of new medical interventions like never before!
If you could image AP-1 or the GAG-MYD-ETS molecule as if examining the international space station, I am sure you will find even more interesting location where you could stack things that may affect its global functions in way that cannot be suspected...this is a critical way to impact disease that are today impenetrable such as the MDS and the leukemia...we will follow these efforts carefully...tomorrow is brighter in Medicine as we see it from here...
the French are pushing the envelop that will soon define Medicine of the future. The prospect of finally projecting a molecule and studying its elasticity brings our knowledge in the belly of the beast even closer.
Already the prospect that we could first interrogate Core Binding Proteins, and than know to change their elasticity and movements, and more likely unveiling new attachment sites to molecule of our choosing, open prospects of new medical interventions like never before!
If you could image AP-1 or the GAG-MYD-ETS molecule as if examining the international space station, I am sure you will find even more interesting location where you could stack things that may affect its global functions in way that cannot be suspected...this is a critical way to impact disease that are today impenetrable such as the MDS and the leukemia...we will follow these efforts carefully...tomorrow is brighter in Medicine as we see it from here...
Wednesday, July 9, 2014
focus on ETS gene
1.Could a combination of Thyroid and retinoic acid be effective in MDS under expressing ETS gene
Rascle et al :
" We show here that Myb-Ets inhibits both RAR and c-ErbA activities on specific hormone response elements in transient-expression assays. Moreover, Myb-Ets abrogates the inactivation of transcription factor AP-1 by RAR and T3R, another feature shared with v-ErbA. Myb-Ets also antagonizes the biological response of erythrocytic progenitor cells to retinoic acid and T3."
2. E26 amplified in P.Vera?
3.What is the effect of Jakafi on the ETS gene expression.
4.Blocking GAG-ETS interaction could prove a major intervention in Myeloproliferative disorders and viral multipliction
It all looks like that this ETS is a way of directing the cell to a more vigourous multiplication particularly in the neoplastic process and Viral Multiplication through amplification and interactions with regulatory GENES. (don't ask me now where is the miRNA). This gene is so effective in its work, human cell adopted it.
and the shameless HIV comes in and uses it through the ENV-POL-GAG as mentioned!
Rascle et al :
" We show here that Myb-Ets inhibits both RAR and c-ErbA activities on specific hormone response elements in transient-expression assays. Moreover, Myb-Ets abrogates the inactivation of transcription factor AP-1 by RAR and T3R, another feature shared with v-ErbA. Myb-Ets also antagonizes the biological response of erythrocytic progenitor cells to retinoic acid and T3."
2. E26 amplified in P.Vera?
3.What is the effect of Jakafi on the ETS gene expression.
4.Blocking GAG-ETS interaction could prove a major intervention in Myeloproliferative disorders and viral multipliction
It all looks like that this ETS is a way of directing the cell to a more vigourous multiplication particularly in the neoplastic process and Viral Multiplication through amplification and interactions with regulatory GENES. (don't ask me now where is the miRNA). This gene is so effective in its work, human cell adopted it.
and the shameless HIV comes in and uses it through the ENV-POL-GAG as mentioned!
Watched a Video on Vitamin D on Medscape
I am puzzled by a Video on Medscape on Vitamin D. I did hope I will learn more about Vitamin D
I came out just as confused...and indeed more puzzled by this question than ever. Now I wonder what is the background of the man...The most sobering is that he did not have an answer for us and in fact added to the controversy. Whenever this happens, it points to not only we need to know more, but that the analysis on itself was superflous...The notion that Vitamin D help for cellular growth and kinetic was the most insightful, the rest was globally speculative at best.
Several aspects where not discussed and goes to fundamental questions we struggle with:
Vitamin D has a known membrane receptor and one needs to define
genes downstream this Receptor
what other receptors are modulated by Vitamin D particularly when used at high dose as it is now fashonable
why is it that Vitamin D deficiency is associated with Autoimmune disease
what is the effect of Vitamin D on genes at epigenetic Zone
What are the Cytokines involved in various states of Vitamin D presence
Can high exposure of Vitamin D affect Methylation of genes or Acetylation of Histones
Can that Acetylation or Methylation be permanent as to realy induce Neoplastic performance
At which doses these permanent genetic changes are actually induced
and what are the risks of chronic versus intermittent exposure to Vitamin
at which doses there could be a problem
and what gene (heterozygosity) predispositions the carrier to genetic insults
is there relation with the lipid receptors and genes
Is there relation with the Insulin Receptors and genes
Is there relation with genes at the epigenetic Zone,
ONLY STUDIES AT THESE LEVELS, ANSWERING AT LEAST HALF OF THESE QUESTIONS, DESERVE VIDEO BEING SELECTED FOR CONSUMPTION IN A MEDICAL MEDIA...
I came out just as confused...and indeed more puzzled by this question than ever. Now I wonder what is the background of the man...The most sobering is that he did not have an answer for us and in fact added to the controversy. Whenever this happens, it points to not only we need to know more, but that the analysis on itself was superflous...The notion that Vitamin D help for cellular growth and kinetic was the most insightful, the rest was globally speculative at best.
Several aspects where not discussed and goes to fundamental questions we struggle with:
Vitamin D has a known membrane receptor and one needs to define
genes downstream this Receptor
what other receptors are modulated by Vitamin D particularly when used at high dose as it is now fashonable
why is it that Vitamin D deficiency is associated with Autoimmune disease
what is the effect of Vitamin D on genes at epigenetic Zone
What are the Cytokines involved in various states of Vitamin D presence
Can high exposure of Vitamin D affect Methylation of genes or Acetylation of Histones
Can that Acetylation or Methylation be permanent as to realy induce Neoplastic performance
At which doses these permanent genetic changes are actually induced
and what are the risks of chronic versus intermittent exposure to Vitamin
at which doses there could be a problem
and what gene (heterozygosity) predispositions the carrier to genetic insults
is there relation with the lipid receptors and genes
Is there relation with the Insulin Receptors and genes
Is there relation with genes at the epigenetic Zone,
ONLY STUDIES AT THESE LEVELS, ANSWERING AT LEAST HALF OF THESE QUESTIONS, DESERVE VIDEO BEING SELECTED FOR CONSUMPTION IN A MEDICAL MEDIA...
Tuesday, July 8, 2014
Monday, July 7, 2014
Events at the Zone!
Certainly we know that a number of diseases could be prevented by stopping a number of mechanisms at the epigenetic level, we know that certain genes are very active at this levels such the Dnmt1, but also
HAT, HDAC, Histone H3 lys9 methyltranferase. These genes could lead us to make certain conclusions on the state of the epigenetic zone. Globally we understand that Hypomethylation is good for you because it is a state of non silenced genes, and for tumor repressors, it means a state of activity suppressing neoplastic transformation...And of course hypermethylation will silence these genes and lead to inactivity of tumor suppressor genes and most likely to overstimulation of cancer inducing genes. This of course explains the effectiveness of drug such as Vidaza (in MDS). At the zone, there is Methylation or Hypomethylation but this to occur Histone activity has to occur to allow it to happen for those genes that are covered...
Many steps remain to be clarified
but it is now established that Dnmt1-3: maintenance of Methyl transferase and therefore favors methylation. That aging is associated with increased detectable methylation. Length of the Telomeres may be associated with activity at this epigenetic level, and that Methylation of important genes may leed to dementia (see RTT syndrome and schizophrenia) and methylation of important genes such has the Reelin gene
with impact on DAB1, GSK3B, NUDEL, TBR1 and of course Tau and CDK5.(PER WIKIPEDIA) (and there comes the trouble of PTSD)
There is a global increase in Cytokines particularly IL4 which :"IL-4 also has been shown to drive mitogenesis, dedifferentiation, and metastasis in rhabdomyosarcoma.[10]" wikipedia
And there comes the consequences....
Genes to watch summarized by our friends at wikipidea
"
SUV39H1 has been shown to interact with HDAC9,[3] HDAC1,[4] Histone deacetylase 2,[4] Retinoblastoma protein,[5][6] CBX5,[3][7][8] HDAC3,[4] DNMT3A,[9] MBD1,[7] RUNX1,[10] SBF1[11] and CBX1.[1]"
AND IF SP1 IS NOT MENTIONED IT IS A MISTAKE!
AND EVERYTHING IS CLEAR NOW!
HAT, HDAC, Histone H3 lys9 methyltranferase. These genes could lead us to make certain conclusions on the state of the epigenetic zone. Globally we understand that Hypomethylation is good for you because it is a state of non silenced genes, and for tumor repressors, it means a state of activity suppressing neoplastic transformation...And of course hypermethylation will silence these genes and lead to inactivity of tumor suppressor genes and most likely to overstimulation of cancer inducing genes. This of course explains the effectiveness of drug such as Vidaza (in MDS). At the zone, there is Methylation or Hypomethylation but this to occur Histone activity has to occur to allow it to happen for those genes that are covered...
Many steps remain to be clarified
but it is now established that Dnmt1-3: maintenance of Methyl transferase and therefore favors methylation. That aging is associated with increased detectable methylation. Length of the Telomeres may be associated with activity at this epigenetic level, and that Methylation of important genes may leed to dementia (see RTT syndrome and schizophrenia) and methylation of important genes such has the Reelin gene
with impact on DAB1, GSK3B, NUDEL, TBR1 and of course Tau and CDK5.(PER WIKIPEDIA) (and there comes the trouble of PTSD)
There is a global increase in Cytokines particularly IL4 which :"IL-4 also has been shown to drive mitogenesis, dedifferentiation, and metastasis in rhabdomyosarcoma.[10]" wikipedia
And there comes the consequences....
Genes to watch summarized by our friends at wikipidea
"
SUV39H1 has been shown to interact with HDAC9,[3] HDAC1,[4] Histone deacetylase 2,[4] Retinoblastoma protein,[5][6] CBX5,[3][7][8] HDAC3,[4] DNMT3A,[9] MBD1,[7] RUNX1,[10] SBF1[11] and CBX1.[1]"
AND IF SP1 IS NOT MENTIONED IT IS A MISTAKE!
AND EVERYTHING IS CLEAR NOW!
Saturday, July 5, 2014
Belinostat enters the Battle!
With the release of Belinostat, the FDA has made a big step forward, and once again points to the
importance of Oncology medications in the Histone deacetylators or drugs affecting primarily the epigenetic phenomena. The challenge with these drugs is not only how to quantify the level of de-acetylation or methylation in the epigenetic zone, but measure some of the genes known to be located in the area and how they are affected. How DNMT1/DMAP1 react to these drugs (quantification needed...) (not to confuse with DMT1, another total ball game altogether!)
De-acetylators have demonstrated activity in Leukemias, but this one was also tested in unknown primaries and lung cancers. A question also remains, are these important in NF-kB driven diseases or HSP90 overexpressions (Gastric cancers?). Belinostat has been approved in Peripheral T cell lymphoma. (see also Vorinostat, released for Cutaneous T cell lymphoma).
importance of Oncology medications in the Histone deacetylators or drugs affecting primarily the epigenetic phenomena. The challenge with these drugs is not only how to quantify the level of de-acetylation or methylation in the epigenetic zone, but measure some of the genes known to be located in the area and how they are affected. How DNMT1/DMAP1 react to these drugs (quantification needed...) (not to confuse with DMT1, another total ball game altogether!)
De-acetylators have demonstrated activity in Leukemias, but this one was also tested in unknown primaries and lung cancers. A question also remains, are these important in NF-kB driven diseases or HSP90 overexpressions (Gastric cancers?). Belinostat has been approved in Peripheral T cell lymphoma. (see also Vorinostat, released for Cutaneous T cell lymphoma).
Wednesday, July 2, 2014
Gastric cancer treatment moving along!
Week's Best Articles: Oncology |
And they went ahead and did it.
combining Rilotumumab with standard ECX in gastric cancer in patients who are MET positive
" dose de-escalation study to identify a safe dose of rilotumumab
(initial dose 15 mg/kg intravenously on day 1) plus ECX (epirubicin 50
mg/m2 intravenously on day 1, cisplatin 60 mg/m2 intravenously on day 1,
capecitabine 625 mg/m2 twice a day orally on days 1—21, respectively),
administered every 3 weeks." MDLINKS
the NIH reported:
"
rilotumumab
A fully human IgG2 monoclonal antibody directed against the human hepatocyte growth factor (HGF) with potential antineoplastic activity. Rilotumumab binds to and neutralizes HGF, preventing the binding of HGF to its receptor c-Met and so c-Met activation; inhibition of c-Met-mediated signal transduction may result in the induction of apoptosis in cells expressing c-Met. c-Met (HGF receptor or HGFR), a receptor tyrosine kinase overexpressed or mutated in a variety of epithelial cancer cell types, plays a key role in cancer cell growth, survival, angiogenesis, invasion, and metastasis."
================
This will mark progress in Gastric cancer
next will see Ramucirumab (VEGF) combined to this same combination in the same disease...
and may be we will see progress in Gastric Cancer after all
|
Tuesday, July 1, 2014
A burst of Target therapies
In certain diseases such as Melanoma, standard chemotherapy had failed miserably, yes indeed Cisplatin and the Adriamycin of the world had failed to give us a result and combining them did not help either. For a while there, non specific immuno-modulation with interferon had been the standard approach but those days are gone also. Today it is the PD-1...and already Ipilimumab that enjoyed the center case in Metastatic Melanoma is moved a bit by the storm of Pembrolizumab and the Nivolumab. Clinician wonder now what to give first to a newly diagnosed patient, and whether clinical setting such as the location of the primary lesion should guide the drug selection. For the BRAF of the world, Vemurafenib/Zelboraf have had their time, but this drug effect is short lived given the relatively quick return of the lesion, and the need to remove surgically the eventual squamous (kerato-acantomatous )lesion that may result of their use. Like the Ibrutinib foe CLL, Pembrolizumab is now king in Melanoma. (and Nivolumab is moving already to lung cancers). The land is shifting, it is exciting to keep up. But frankly, is it right to treat liver infested by Melanoma from the skin, versus Melanoma from the Uveal origin when we know that one has the GNAQ gene. Yesterday I met a lady who had recurrent Melanoma in the Nostril...a PET is awaited. should I be able to offer directly Pembrolizumab arguing that the drug is said to be very easy on patients? (should my case turned to be Metastatic of course). Can the first treatment be a combination with Ipilimumab? Or is it too expensive...what cost can we afford?
In the Ovarian setting, anti-PARP are trying to enter the maintenance setting in Platinum sensitive disease, and BRCA status is pointing to responsive patients...should we use BRCA to make a case for Maintenance disease control with Olaparib. The FDA is waiting for result of a larger study...not the "19" study they say!!!! But May be this story is yet to be written...
On the Her-2 front, 2 is not better than 1 or is it?
and I could go on all night long....we live an exciting time in Oncology!
with news like this coming along: " Top Stories
Ibrutinib Stands Center Stage in CLL" (medscape)
In the Ovarian setting, anti-PARP are trying to enter the maintenance setting in Platinum sensitive disease, and BRCA status is pointing to responsive patients...should we use BRCA to make a case for Maintenance disease control with Olaparib. The FDA is waiting for result of a larger study...not the "19" study they say!!!! But May be this story is yet to be written...
On the Her-2 front, 2 is not better than 1 or is it?
and I could go on all night long....we live an exciting time in Oncology!
with news like this coming along: " Top Stories
 |
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