ACTIVITY AT CRBCM.
1. We are waiting for last word of the contract with the laboratory of Professor Jianying Zhang ( agreement between UTEP and the CRBCM and the Greater East Cancer Center. ) about the early lung cancer detection project.
2. We are conducting field work in fort Wayne Indiana (under contract)
3. AND THE LARGER NEWS TONIGHT IS THAT DR KANKONDE HAS BEEN RETAINED DIRECTOR OF AN IMPORTANT HEMATOLOGY LABORATORY IN EL PASO. HE WILL SOON START FINAL ADAPTED TRAINING. AND YOU WILL BE UPDATED!
4.WE CONTINUE TO SUBMIT GRANT REQUESTS.
5. WE ATTENDED SUCCESSFULLY THE CONFERENCE ON HEMATOLOGIC MALIGNANCIES IN MIAMI SATURDAY AUGUST 10TH, 2013
THE CRBCM IS ADVANCING DAY BY DAY!
Monday, August 12, 2013
Few Clues on Myeloma treatment
Some of the Key points in Myeloma Treatment
1. After the diagnosis of Myeloma, determination of presence of Del 17, and t(4:14) is the first step to treatment. You may be "liable" if Velcade is not included in the first line treatment in patient with del 17.
2. CYBORD is a good induction option
3. Use of Triplets always better than Doublets
4.In clinical practice, Bortezomib Sub Q is now adopted widely despite lack of clinical trial showing equivalency to IV route (in up front treatment) because it leads to somewhat less Neuropathy and thrombocytopenia.
5. Dexamethasone is still a corner stone of Myeloma treatment. Add it even to the newest drug for their full effect to be unleashed (even Pomalidomide has 3 times the effect when Dexamethasone is added!
6.Almost everybody is treating until progression or maintenance therapy is the alternative. As if now are assuming that the driver of the disease are continuously present!`
Now for Maintenance therapy, not only Revlimid, but also Velcade can be given with Dex in Maintenance setting.
7."In myeloma, a CR (or complete response) is a CR no matter how you got there" meaning any CR give the same benefit to the patient in terms of progression frr survival.
8. The idea of Maintenance therapy was further re-enforced by the VPMT forwed by Maintenance MT in cases treated without transplant!
9.Remember Carfilzomib and Pomalidomide are 3rd live as approved by FDA. Meaning 2 treatment have to fail before you can prescribe these meds!
10. With Carfilzomid (approved in July 2012)watch the kidney and cardiac parameters (concerns here)
less Neuropathy noted.
11. With more drugs available, 2 new combination triplets
Carfilzomib/Pom/Dex
Velcade/Pom /Dex meds
12 New drugs to be incorporated " Daratuzumab, Aratuzumab, ARRY520
new combination Len/Carfil/Dex
13 New salvage TD-PACE, VTD-PACE
14. one trial Cytoxan/Carfilzomid?Dex, surprising Cytoxan an option in Renal failure patients!
IN MYELOMA ANY OPTION IS GOOD BUT WATCH FOR DEL 17 PRESENCE! (pom AND velcade ARE THEN SOME OF THE OPTIONS)
1. After the diagnosis of Myeloma, determination of presence of Del 17, and t(4:14) is the first step to treatment. You may be "liable" if Velcade is not included in the first line treatment in patient with del 17.
2. CYBORD is a good induction option
3. Use of Triplets always better than Doublets
4.In clinical practice, Bortezomib Sub Q is now adopted widely despite lack of clinical trial showing equivalency to IV route (in up front treatment) because it leads to somewhat less Neuropathy and thrombocytopenia.
5. Dexamethasone is still a corner stone of Myeloma treatment. Add it even to the newest drug for their full effect to be unleashed (even Pomalidomide has 3 times the effect when Dexamethasone is added!
6.Almost everybody is treating until progression or maintenance therapy is the alternative. As if now are assuming that the driver of the disease are continuously present!`
Now for Maintenance therapy, not only Revlimid, but also Velcade can be given with Dex in Maintenance setting.
7."In myeloma, a CR (or complete response) is a CR no matter how you got there" meaning any CR give the same benefit to the patient in terms of progression frr survival.
8. The idea of Maintenance therapy was further re-enforced by the VPMT forwed by Maintenance MT in cases treated without transplant!
9.Remember Carfilzomib and Pomalidomide are 3rd live as approved by FDA. Meaning 2 treatment have to fail before you can prescribe these meds!
10. With Carfilzomid (approved in July 2012)watch the kidney and cardiac parameters (concerns here)
less Neuropathy noted.
11. With more drugs available, 2 new combination triplets
Carfilzomib/Pom/Dex
Velcade/Pom /Dex meds
12 New drugs to be incorporated " Daratuzumab, Aratuzumab, ARRY520
new combination Len/Carfil/Dex
13 New salvage TD-PACE, VTD-PACE
14. one trial Cytoxan/Carfilzomid?Dex, surprising Cytoxan an option in Renal failure patients!
IN MYELOMA ANY OPTION IS GOOD BUT WATCH FOR DEL 17 PRESENCE! (pom AND velcade ARE THEN SOME OF THE OPTIONS)
Questions in Vascular lesions of the liver, and some oustanding associations rising questions at CRBCM.
*Taking Oral Contraceptive is associated with Hepatic Adenoma.
*Association between chronic Hepatitis, Cirrhosis, and Hepatoma
*Association between Ulcerative Colitis with Primary biliary cholangitis and Cholangiocarcinoma
why Spider Angioma
why Palmar Erythema
why LDH is linked to Lymphoma
Does a patient with multiple large unresectable
Angiosarcoma in the liver candidate for liver transplant if there is no evidence of Metastatsis!
Potential Genes to investigate in liver lesions of Vascular tone/component!
1.VEGF and its corollary the EGFR
yes Avastin works in Angiosarcoma of the liver, and these are vascular lesions. So these genes are in play!
2. VHL, HIF yes these lesions are vascular and hypoxia must be coming in,
3.Estrogen, yes remember the predominance in these lesion in women of child bearing age, and the fact that Oral contraceptive must be discontinued, and avoidance of pregnancy is advised.
4.Androgenic Receptor gene, yes user of Androgenic drugs are at increased risk of Adenoma
5. Wnt (yes the catenin are involved for cellular polarity to be alterated and hypertrophy to occur)
6.Insulin Receptor, There must be in intervention from these genes as most patients with these lesions are obese, with diabetes Mellitus or Glycogen storage disorder particularly type 1A and 3.
7"Irritation/Inflammation such as seen with Hemochromatosis and fibrosis point to hyperactivity of the NF-kB and cyclins (IL 1,6,23)
8. Src gene needs examination because of potential development of sarcomatous lesions.
9. Endothelial involvement gives it DIC propensity (Kasabach-Merritt syndrome) or is-it the ADAMS associated with Cyclines involvedin initiating DIC?
?ROS amplification here give it the Metastatic potentials
(to be continued)
*Association between chronic Hepatitis, Cirrhosis, and Hepatoma
*Association between Ulcerative Colitis with Primary biliary cholangitis and Cholangiocarcinoma
why Spider Angioma
why Palmar Erythema
why LDH is linked to Lymphoma
Does a patient with multiple large unresectable
Angiosarcoma in the liver candidate for liver transplant if there is no evidence of Metastatsis!
Potential Genes to investigate in liver lesions of Vascular tone/component!
1.VEGF and its corollary the EGFR
yes Avastin works in Angiosarcoma of the liver, and these are vascular lesions. So these genes are in play!
2. VHL, HIF yes these lesions are vascular and hypoxia must be coming in,
3.Estrogen, yes remember the predominance in these lesion in women of child bearing age, and the fact that Oral contraceptive must be discontinued, and avoidance of pregnancy is advised.
4.Androgenic Receptor gene, yes user of Androgenic drugs are at increased risk of Adenoma
5. Wnt (yes the catenin are involved for cellular polarity to be alterated and hypertrophy to occur)
6.Insulin Receptor, There must be in intervention from these genes as most patients with these lesions are obese, with diabetes Mellitus or Glycogen storage disorder particularly type 1A and 3.
7"Irritation/Inflammation such as seen with Hemochromatosis and fibrosis point to hyperactivity of the NF-kB and cyclins (IL 1,6,23)
8. Src gene needs examination because of potential development of sarcomatous lesions.
9. Endothelial involvement gives it DIC propensity (Kasabach-Merritt syndrome) or is-it the ADAMS associated with Cyclines involvedin initiating DIC?
?ROS amplification here give it the Metastatic potentials
(to be continued)
Sunday, August 11, 2013
keeping track of CME
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
Secondary Prevention in Patients With ACS and Diabetes: How Can We Optimize Therapy?
August 11, 2013
and is awarded
0.50
AMA PRA Category 1 Credit(s)™.
Medscape, LLC designates this enduring material for a maximum of 0.50 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
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Saturday, August 10, 2013
Triple Negative Breast cancer a result of amplification of the JNK and the wnt
Persistent Failure at the receptors leads to a stressful situation that stimulate continuously the JNK/ERK with 2 implications:
1. Through the Caveolin based molecules will affect p66hc, a regulator maintaining ROS phosphorylated and active on the triple molecule Actin-Caherin and Beta-catenin (CBF). Through the Catenin, PTPRB and ultimately MAGI3 will be affected. CTNN1 leads to loss of polarity and lumen formation, and will activate Angiopoietin 1 Receptor and VGEF amplification, which in turn further amplification of ROS, the agent of metastasis...
2. JNK/ERK will also have epigenetic increasing TGFBeta and NF-kB amplification lead to RUNX3 amplification. Subsequent amplification of PIAS3 and MITF3 will do the rest.
2 main targets! p66Shc and PIAS3, 2 regulators!
(This information results from speculative interpretation of information readily available on the internet)!
JAK2 at the TGF-Beta receptor, Angiopoitin 1 Receptor Tie2, Receptor, VGEF Receptor 2, IQGAP1, ARF6, ROS and its regulator p66Shc, the cadherin, the RUNX3, which:
Are just few of the Targets in the slew of events !
1. Through the Caveolin based molecules will affect p66hc, a regulator maintaining ROS phosphorylated and active on the triple molecule Actin-Caherin and Beta-catenin (CBF). Through the Catenin, PTPRB and ultimately MAGI3 will be affected. CTNN1 leads to loss of polarity and lumen formation, and will activate Angiopoietin 1 Receptor and VGEF amplification, which in turn further amplification of ROS, the agent of metastasis...
2. JNK/ERK will also have epigenetic increasing TGFBeta and NF-kB amplification lead to RUNX3 amplification. Subsequent amplification of PIAS3 and MITF3 will do the rest.
2 main targets! p66Shc and PIAS3, 2 regulators!
(This information results from speculative interpretation of information readily available on the internet)!
JAK2 at the TGF-Beta receptor, Angiopoitin 1 Receptor Tie2, Receptor, VGEF Receptor 2, IQGAP1, ARF6, ROS and its regulator p66Shc, the cadherin, the RUNX3, which:
The RUNX3 Tumor Suppressor Upregulates Bim in Gastric Epithelial Cells Undergoing Transforming Growth Factor β-Induced Apoptosis
Takashi Yano,Are just few of the Targets in the slew of events !
News from Medscape!
*"Hematologist-oncologist Farid Fata, MD, in suburban Detroit,
Michigan, was arrested August 6 and charged with Medicare fraud in a
federal case that stands out from dozens of others recently brought
against healthcare providers.
For one thing, the dollar amount of alleged fraud — $35 million — is higher than most for individual providers charged by the government. The potential physical harm to patients described by prosecutors also is far more substantial. In a criminal complaint filed in a federal district court in Detroit, prosecutors said that the 48-year-old Dr. Fata ordered toxic chemotherapy for patients who did not have cancer or whose cancer was in remission. Doing this "is simply poisoning the patient," prosecutors said in a later court filing." (go to article"
For one thing, the dollar amount of alleged fraud — $35 million — is higher than most for individual providers charged by the government. The potential physical harm to patients described by prosecutors also is far more substantial. In a criminal complaint filed in a federal district court in Detroit, prosecutors said that the 48-year-old Dr. Fata ordered toxic chemotherapy for patients who did not have cancer or whose cancer was in remission. Doing this "is simply poisoning the patient," prosecutors said in a later court filing." (go to article"
Physician Gave Chemo to Patients Without Cancer, Feds Say
Metformin Linked to Fewer Prostate Cancer Deaths in Diabetics
MIAMI CONFERENCE ON HEMATOLOGY MALIGNANCIES
Have completed the conference update here in Miami-Florida. The conference gathered close to 100 Oncologist, In the beautiful Hotel Loews at Corner of 16th Street and Collins avenue.
Subject covered went from Myeloma to Myelofibrosis and will be all make subjects of the upcoming blog this week. Our approach will not only focus GIVING YOU THE HIGHLIGHTS but also discussing how they fit into our perspectives at CRBCM. And what associated assumptions can be made based on fundamemtal knowledge discussed in the conference.
From the CRBCM stand point, 2 speaker stood out, Professor Jerry Spivak, Director of the Johns Hopkins Center for the chronic Myeloproliferative disorders who spoke enthusiastically about Myelofibrosis and the new drug Ruxolitinib, And DR Elias Jabbour, an associate professor in the Leukemia Department at MD Anderson cancer Center.
Once again we will summarize all this week material from this conference starting with Myelodysplasia. We should confess that some drugs earn significant excitement with Ibrutinib in CHronic Lymphocytic Leukemia. We predict that this drug in combination Rituxan will soon become the standard of care because of its effect that appears independent of whatever genetic prognosis factors (activity across the board)! and also because of high rates of responses! Potential Hepatic concerns however call for patient close observation and monitoring. While Pralatrexate is now more chosen in peripheral T cell Lymphoma. Romidepsin is coming a close 2nd in this disease.
Dasatinib won the war against Nilotinib as the choice in practice for the 2nd generation TKI in CML except for those with lung concern as comorbidity. In mantle cell lymphoma, the rise in importance of Ibrutinib can not be ignored. Pomalidomide strength is with Dex, emphasizing further once again the importance of DExamethasone in this disease!
In Chronic Myeloid leukemia, the importance of Bone marrow transplantation has shriken until you specifically looking for a cure (Allogeneic transplant) and until the TKI have failed or that the transformation (by high blast) is occuring. Very exciting to see these new drugs trying to define their places in a filed invaded by Target therapy (Vs conventional chemotherapy which is increasingly pushed-by not forgotten).
Subject covered went from Myeloma to Myelofibrosis and will be all make subjects of the upcoming blog this week. Our approach will not only focus GIVING YOU THE HIGHLIGHTS but also discussing how they fit into our perspectives at CRBCM. And what associated assumptions can be made based on fundamemtal knowledge discussed in the conference.
From the CRBCM stand point, 2 speaker stood out, Professor Jerry Spivak, Director of the Johns Hopkins Center for the chronic Myeloproliferative disorders who spoke enthusiastically about Myelofibrosis and the new drug Ruxolitinib, And DR Elias Jabbour, an associate professor in the Leukemia Department at MD Anderson cancer Center.
Once again we will summarize all this week material from this conference starting with Myelodysplasia. We should confess that some drugs earn significant excitement with Ibrutinib in CHronic Lymphocytic Leukemia. We predict that this drug in combination Rituxan will soon become the standard of care because of its effect that appears independent of whatever genetic prognosis factors (activity across the board)! and also because of high rates of responses! Potential Hepatic concerns however call for patient close observation and monitoring. While Pralatrexate is now more chosen in peripheral T cell Lymphoma. Romidepsin is coming a close 2nd in this disease.
Dasatinib won the war against Nilotinib as the choice in practice for the 2nd generation TKI in CML except for those with lung concern as comorbidity. In mantle cell lymphoma, the rise in importance of Ibrutinib can not be ignored. Pomalidomide strength is with Dex, emphasizing further once again the importance of DExamethasone in this disease!
In Chronic Myeloid leukemia, the importance of Bone marrow transplantation has shriken until you specifically looking for a cure (Allogeneic transplant) and until the TKI have failed or that the transformation (by high blast) is occuring. Very exciting to see these new drugs trying to define their places in a filed invaded by Target therapy (Vs conventional chemotherapy which is increasingly pushed-by not forgotten).
Thursday, August 8, 2013
COULD PHOSPHATONINS EXPLAIN THE CONCURRENCE OF VITAMIN D DEFICIENCY IN AUTOIMMUNE DISEASES
One thing is certain, autoimmune diseases affect Mesenchymal tisues, the tissues that are full of Fibroblast growth factor 23 or Phosphatonins. and we know that Phosphatonins "inhibit both renal tubular phosphate reabsorption and 1-alpha-hydroxylation of 25-hydroxycalciferol' (YU). This fact alone will justify low levels in blood of 1,25-dihydroxycalciferol. Following this assumption, of course the worse the disease the more likely the vitamin deficiency. Therefore Vitamin D levels could be a biomarker gauging the severity of the disease (prognostic).
It is clear that disturbance of Phosphorus could also contributes to other electrolytes inbalances, grossly increasing the risk level of arrhythmia and sudden death. Of course too much Vitamin D is not good for you either.
Aging and Autoimmune diseases are characterized by increased levels of cytokines, all of which can affects these Phosphatonins with deleterious impact on our systems! The levels of Vitamin D receptors could also be directly affected by gene suppression by silencing as a result of epigenetic changes that occurs with the slew of cytokins, and may be the cytokins have a promoter effect on the Phosphatonin gene (s). Proof of concept needed!
It is clear that disturbance of Phosphorus could also contributes to other electrolytes inbalances, grossly increasing the risk level of arrhythmia and sudden death. Of course too much Vitamin D is not good for you either.
Aging and Autoimmune diseases are characterized by increased levels of cytokines, all of which can affects these Phosphatonins with deleterious impact on our systems! The levels of Vitamin D receptors could also be directly affected by gene suppression by silencing as a result of epigenetic changes that occurs with the slew of cytokins, and may be the cytokins have a promoter effect on the Phosphatonin gene (s). Proof of concept needed!
HIDDEN EXCITEMENT ABOUT NANOTECHNOLOGY
One of the thing that stops progress to its full expansion, is some time the secrecy that researchers keep around really exciting things happening today in order to reveal only when things are ripe and ready for a "big" disclosure! Also, the sense that we own technology and fight hands and teeth to keep findings that can save life for ourselves so we can rip the most profits. It is just a shame that technology brought about by Taxpayers through NIH is bundle up in a patent. We are still seeing the unfolding the BRCA fight which is still going on. We just hope that people will come to their sense and free progress in technology for the good of the world!
One thing excited going on in New York is this development of Nanotechnology, it is my understanding that the State gave money and several biotech companies are now pitching in to possess and develop further this area of science, so that the benefit reach us all in time, at least we hope! In this world of greed, we still should expect another round of fight over this technology! Brace for it!
One of the way this technology will make a significant difference is the improved specific delivery of potent chemotherapy drugs to specific area of certain cells! This is a major problem in Oncology since lack of control where the chemotherapy goes lead to devastating and uncontrolled side effects! It's like a smart Bomb versus a dumb bomb! This is target therapy at its best.
Researchers are targeting tough cancers with this technology. (ie melanoma, sarcoma and Pancreatic cancers).
The miRNA-708 story stands out in my mind! That story reported that there is in triple negative breast cancer this miRNA 708 that inhibit Metastatic lesions from Breast cancer. And because it is a suppressor "gene" for Metastatic breast cancer, it is its lack or deficiency that leads to promotion of metastasis. The reports suggested that increasing delivery of synthetic genes could restore the inhibition of Metastasis, and Nanotechnology could come to the rescue as a transport of gene here to help us fight advanced Breast cancer.
The story is even bigger when you think back about the implications of better controlling this technology!
It is increasingly recognized that some if not most, are caused by a gene suppression! PTEN, E-Cadherin, P53, Rb1 to name just a few...One of the toughest thing is restoring a gene level! Creating a inhibitor is the stuff we know how to do. We have all kinds of inhibitors But gene reamplification and activity restoration is a challenge. NANOTECHNOLOGY will come to the rescue, that is if we have the gene to restore ready for delivery. Other way to restore is by regulating the gene promoter, or through Liposomes (lamelle technology and E-coli-mechanistic ways!) Never mind these, nanotechnology is the new way, and it is hugely promising! (Lawyers, brace yourselves!)
One thing excited going on in New York is this development of Nanotechnology, it is my understanding that the State gave money and several biotech companies are now pitching in to possess and develop further this area of science, so that the benefit reach us all in time, at least we hope! In this world of greed, we still should expect another round of fight over this technology! Brace for it!
One of the way this technology will make a significant difference is the improved specific delivery of potent chemotherapy drugs to specific area of certain cells! This is a major problem in Oncology since lack of control where the chemotherapy goes lead to devastating and uncontrolled side effects! It's like a smart Bomb versus a dumb bomb! This is target therapy at its best.
Researchers are targeting tough cancers with this technology. (ie melanoma, sarcoma and Pancreatic cancers).
The miRNA-708 story stands out in my mind! That story reported that there is in triple negative breast cancer this miRNA 708 that inhibit Metastatic lesions from Breast cancer. And because it is a suppressor "gene" for Metastatic breast cancer, it is its lack or deficiency that leads to promotion of metastasis. The reports suggested that increasing delivery of synthetic genes could restore the inhibition of Metastasis, and Nanotechnology could come to the rescue as a transport of gene here to help us fight advanced Breast cancer.
The story is even bigger when you think back about the implications of better controlling this technology!
It is increasingly recognized that some if not most, are caused by a gene suppression! PTEN, E-Cadherin, P53, Rb1 to name just a few...One of the toughest thing is restoring a gene level! Creating a inhibitor is the stuff we know how to do. We have all kinds of inhibitors But gene reamplification and activity restoration is a challenge. NANOTECHNOLOGY will come to the rescue, that is if we have the gene to restore ready for delivery. Other way to restore is by regulating the gene promoter, or through Liposomes (lamelle technology and E-coli-mechanistic ways!) Never mind these, nanotechnology is the new way, and it is hugely promising! (Lawyers, brace yourselves!)
Wednesday, August 7, 2013
If you don't take magnesium, take it!
There are so many ways of losing Magnesium, that it is surprising we may still have magnesium in our body any more! every single thing we do to enjoy life and fight aliment seems to remove magnesium from our body. You run and sweat, you lose magnesium, you take proton pump inhibitor to reduce acid from our stomach due to stressful life, you lose more magnesium, you take a diuretic to fight high blood pressure, you lose potassium and magnesium, you eat fatty food, well you lose magnesium. you take a stool softner, laxative, you lose magnesium. Many chemotherapy drug will increase your loss of magnesium (Cetuximab, Tacrolimus, Cisplatin, cyclosporine,Panitumumab)
And the blood test do not reveal the story,you have to be fully depleted of magnesium before your blood level changes. So by the time your blood level changes, it is too late! So please just eat your green vegetables, nuts, and whole grain cereals, milk and seafood to keep up.
Now if your DR told you you have renal failure or Irritable Bowel disease, magnesium intake can be dangerous as it may lead to toxicity! You may be a high absorber man or not lose enough to keep you balanced ...you need your DR help here to monitor this more closely...
And the blood test do not reveal the story,you have to be fully depleted of magnesium before your blood level changes. So by the time your blood level changes, it is too late! So please just eat your green vegetables, nuts, and whole grain cereals, milk and seafood to keep up.
Now if your DR told you you have renal failure or Irritable Bowel disease, magnesium intake can be dangerous as it may lead to toxicity! You may be a high absorber man or not lose enough to keep you balanced ...you need your DR help here to monitor this more closely...
DRUG WITH POTENTIAL MARKED EPIGENETIC EFFECTS
There are medications of which role or mechanism of action needs clearly further clarification because they may prevent cancer from occuring. One such medication is: (from mayo site) Imiquimod.
"Imiquimod topical is used to treat external warts around the genital and rectal areas called condyloma acuminatum. It is not used on warts inside the vagina, penis, or rectum. Imiquimod is also used to treat a skin condition of the face and scalp called actinic keratosis (AK), which is caused by too much sun exposure. Imiquimod may be used to treat certain types of skin cancer called superficial basal cell carcinoma (sBCC).
Imiquimod works on the immune system to help the body fight viruses that cause warts. It does not destroy the viruses directly. It is not known how imiquimod works for actinic keratosis or skin cancer."
Understanding the mode of action of this drug in better detail appears critical for further development of target therapy that may help prevent certain cancers induced by chronic irritation and viral drive!
(another Medication used for same pathology is Podophyllin)
All they say is "Podophyllin is a cytotoxic agent that has been used topically in the treatment of genital warts. It arrests mitosis in metaphase, an effect it shares with other cytotoxic agents such as the vinca alkaloids(2). The active agent is podophyllotoxin, whose concentration varies with the type of podophyllin used; the American source normally containing one-fourth the amount of podophyllotoxin as the Indian source(3)."
==========================================================
One thing for sure, viral driven neoplastic diseases can be caused by integral incorporation of the viral genome in that of the host, or induce molecular disturbances changing the course of Metabolism and gene amplification or overexpression of transcription factors by affecting modulator or regulatory genes. Abnormality of splicing will alter major functional core binding molecules, giving new patterns to metabolic events, boosting hypertrophy (by loss of sense of cell limits and perturbances at adhesion molecules) and proliferation. And if the the" foreign" (antigen) sense of the viral presence is not completely suppressed, the cell will be superexcited and the NF-kB on overdrive inducing significant epigenetic events including hyperproduction of Cyclins, Tumor growth factors and disturbances at miRNAs and polymerases (RNA--->DNAs).
All in all significant epigenetic events ensue. Drugs that will affect epigenetic events must have a role in the control or modulation of these events. We have to assume that Imiquimod and Podophyllin must have significant tampering effects of epigenetic events. Indeed Etoposide is known to control these kind of diseases. And it is not because of its topoisomerase II activity and DNA attack, but this drug must have significant epigenetic effects, that is why it can tamper even other epigenetic driven pathologies such as the leukemias. It is surprising that CPT-11 is not as used as Etoposide. Pointing to role of heterogeneity in variation of pathologic expression of epigenetic events!
One thing for sure, medications important in control of these epigenetic events have the bad side effects of causing pulmonary fibrosis (Mitomycin). This point to the conclusion that some Cyclins/ TGF (Interleukins in particular) are over expressed leading to fibrosis. And we still don't screen these Cyclins as biomarkers for detections. But we know it (pulmonary fibrosis) is dose dependent! Head in a sand situation again!
(Written on the go at CRBCM...)
"Imiquimod topical is used to treat external warts around the genital and rectal areas called condyloma acuminatum. It is not used on warts inside the vagina, penis, or rectum. Imiquimod is also used to treat a skin condition of the face and scalp called actinic keratosis (AK), which is caused by too much sun exposure. Imiquimod may be used to treat certain types of skin cancer called superficial basal cell carcinoma (sBCC).
Imiquimod works on the immune system to help the body fight viruses that cause warts. It does not destroy the viruses directly. It is not known how imiquimod works for actinic keratosis or skin cancer."
Understanding the mode of action of this drug in better detail appears critical for further development of target therapy that may help prevent certain cancers induced by chronic irritation and viral drive!
(another Medication used for same pathology is Podophyllin)
All they say is "Podophyllin is a cytotoxic agent that has been used topically in the treatment of genital warts. It arrests mitosis in metaphase, an effect it shares with other cytotoxic agents such as the vinca alkaloids(2). The active agent is podophyllotoxin, whose concentration varies with the type of podophyllin used; the American source normally containing one-fourth the amount of podophyllotoxin as the Indian source(3)."
==========================================================
One thing for sure, viral driven neoplastic diseases can be caused by integral incorporation of the viral genome in that of the host, or induce molecular disturbances changing the course of Metabolism and gene amplification or overexpression of transcription factors by affecting modulator or regulatory genes. Abnormality of splicing will alter major functional core binding molecules, giving new patterns to metabolic events, boosting hypertrophy (by loss of sense of cell limits and perturbances at adhesion molecules) and proliferation. And if the the" foreign" (antigen) sense of the viral presence is not completely suppressed, the cell will be superexcited and the NF-kB on overdrive inducing significant epigenetic events including hyperproduction of Cyclins, Tumor growth factors and disturbances at miRNAs and polymerases (RNA--->DNAs).
All in all significant epigenetic events ensue. Drugs that will affect epigenetic events must have a role in the control or modulation of these events. We have to assume that Imiquimod and Podophyllin must have significant tampering effects of epigenetic events. Indeed Etoposide is known to control these kind of diseases. And it is not because of its topoisomerase II activity and DNA attack, but this drug must have significant epigenetic effects, that is why it can tamper even other epigenetic driven pathologies such as the leukemias. It is surprising that CPT-11 is not as used as Etoposide. Pointing to role of heterogeneity in variation of pathologic expression of epigenetic events!
One thing for sure, medications important in control of these epigenetic events have the bad side effects of causing pulmonary fibrosis (Mitomycin). This point to the conclusion that some Cyclins/ TGF (Interleukins in particular) are over expressed leading to fibrosis. And we still don't screen these Cyclins as biomarkers for detections. But we know it (pulmonary fibrosis) is dose dependent! Head in a sand situation again!
(Written on the go at CRBCM...)
Tuesday, August 6, 2013
New study on older women with early Breast cancer, Role of Radiation...GO TO MEDSCAPE FOR FULL ARTICLE!
Lumpectomy Plus Tamoxifen With or Without Irradiation in Women Age 70 Years or Older With Early Breast Cancer: Long-term Follow-up of CALGB 9343
Hughes KS, Schnaper LA, Bellon JR, et al"
Women over the age of 70 years with early ER-positive invasive breast cancer (tumor measuring no more than 2 cm) and clinically negative axillae were enrolled between 1994 and 1999. A total of 636 participants with stage I breast cancer who were all treated with lumpectomy (axillary exploration was left to the discretion of the treating surgeon) were randomly assigned to receive tamoxifen plus radiation therapy or tamoxifen alone. Primary endpoints were time to local or regional recurrence, frequency of mastectomy, breast cancer-specific survival, time to distant metastasis, and overall survival.
After a median follow-up of 12.6 years, investigators found no significant differences in time to mastectomy, time to distant recurrence, breast cancer-specific survival, or overall survival. At 10 years, 98% of patients who received dual-modality therapy were free from locoregional recurrence as compared with 90% in the group treated with tamoxifen alone. In the group that received tamoxifen alone, 42 of 319 women relapsed, compared with 23 of 317 in the group that received tamoxifen plus radiation therapy. More women in the tamoxifen group had local and regional relapses and were treated with surgery or radiation at the time of relapse. There was no significant difference in the number of distant relapses between the 2 treatment groups."
YOU BE THE JUDGE!
AND HERE HE COMES FROM BRISTOL MEYERS SQUIBB: CETUXIMAB
CRYSTAL REGIMEN IN FIRST LINE KRAS MUTATION NEGATIVE (WILD TYPE) EGFR EXPRESSING METASTATIC COLORECTAL CANCER...
------------------------------------------------------------------------------------------------
Crystal regimen vs Folfiri alone
Median survival 23.5 months Vs 19.5 months
Objective response 57% Vs 39%
Median PFS 9.5 months Vs 8.1 months
-----------------------------------------------------------------------------------------------
higher chance to respond to treatment, and higher survival, when you add Cetuximab to FOLFIRI.
Side effects:
Acne-like RASH 86% Vs 13%
Diarrhea 66% Vs 60
Neutropenia 31% Vs 24%
Making Acnee-like-rash the most specific side effect to cetuximab! Why is a good question for the CRCBM.
------------------------------------------------------------------------------------------------
Crystal regimen vs Folfiri alone
Median survival 23.5 months Vs 19.5 months
Objective response 57% Vs 39%
Median PFS 9.5 months Vs 8.1 months
-----------------------------------------------------------------------------------------------
higher chance to respond to treatment, and higher survival, when you add Cetuximab to FOLFIRI.
Side effects:
Acne-like RASH 86% Vs 13%
Diarrhea 66% Vs 60
Neutropenia 31% Vs 24%
Making Acnee-like-rash the most specific side effect to cetuximab! Why is a good question for the CRCBM.
Theories in Prostate cancer
The notion that over 70% of Autopsy specimens in male will reveal some form of prostate cancer point to the fact the Neoplastic transformation should be expected in most men, and could be described as part of abnormal aging. The challenge to Oncologist and geneticists before each cancer is to determine which "prostate cancer" is before them in each specific elderly.
The current understanding is that the difference in aggressive versus "indolent" cancer rests in the patterns of genes or mutations that each cancer displayed. With the abundance of genes that can go wrong and ultimately start a neoplastic transformation, one is left left with many choices.
It is apparent that a scientific observer needs to control certain parameters and see if a theory can be verified.
One such approach is to assume that certain cancers develop as part of normal senescence and follow where the theory leads us. We need to inventory senescence mechanism at gene level, and see how they can relate or happen in the context of the Prostate gland, and project how that model could lead to a neoplastic transformation, and compare those projection with prostatic tissue of known random cancers, and autopsy specimens in elderly. May be variations will give us conclusive remarks that may help sort out things and improve our knowledge a bit.
The development of the increased availability of tissue banks will improve our potential in conducting research work and reducing specimen collection time and reduce the randomness of specimens. It may help control some variable since you can now specify the race, age, and many other parameter during the observation. Now you can have the bank offer you fresh frozen specimen, or other types of format, or even just the genes already extracted for your observation!
The current understanding is that the difference in aggressive versus "indolent" cancer rests in the patterns of genes or mutations that each cancer displayed. With the abundance of genes that can go wrong and ultimately start a neoplastic transformation, one is left left with many choices.
It is apparent that a scientific observer needs to control certain parameters and see if a theory can be verified.
One such approach is to assume that certain cancers develop as part of normal senescence and follow where the theory leads us. We need to inventory senescence mechanism at gene level, and see how they can relate or happen in the context of the Prostate gland, and project how that model could lead to a neoplastic transformation, and compare those projection with prostatic tissue of known random cancers, and autopsy specimens in elderly. May be variations will give us conclusive remarks that may help sort out things and improve our knowledge a bit.
The development of the increased availability of tissue banks will improve our potential in conducting research work and reducing specimen collection time and reduce the randomness of specimens. It may help control some variable since you can now specify the race, age, and many other parameter during the observation. Now you can have the bank offer you fresh frozen specimen, or other types of format, or even just the genes already extracted for your observation!
Monday, August 5, 2013
Earned it!
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
Practical Solutions to Current Clinical Challenges in Relapsed/Refractory Multiple Myeloma
August 5, 2013
and is awarded
0.50
AMA PRA Category 1 Credit(s)™.
Medscape, LLC designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
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Continuing Medical Education (ACCME) to provide continuing medical
education for physicians.
For information on
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| Certificate Number: 43827518 | Cyndi Grimes Director, Continuing Medical Education Medscape, LLC |
Plethora of Agents in Refractory Myeloma
There is no hematologic disease with so many new active medications
If you give standard chemotherapy agents in this disease, you will be looked upon with strange eyes in this day in age!
If you treat without knowing Cytogenetic changes in plasma cell, shame on you they say
Patient has to classified as "High Risk (del 17p)" Vs "standard risk"
(Velcade needed absolutely) Vs (possible REVLIMID-DEX)
For those with Relapsed or refractory, a plethora of choices
1. Elotuzumab + Revlimid + DEX
2. Elotuzumab + Velcade + DEX
3. Carfilzomib + Dex
4. Pomalidomide + Bortezomib + DEX
Despite this you still have new agents
1. ARRY-520
2.Daratumumab
3.Panobinostat
4.Ixazomib
to try!
(Vorinostat said to "disappointing")
(Medscape) go to talk for a full more reliable discussion! None of the above should be used unless you recheck the info!
There is no hematologic disease with so many new active medications
If you give standard chemotherapy agents in this disease, you will be looked upon with strange eyes in this day in age!
If you treat without knowing Cytogenetic changes in plasma cell, shame on you they say
Patient has to classified as "High Risk (del 17p)" Vs "standard risk"
(Velcade needed absolutely) Vs (possible REVLIMID-DEX)
For those with Relapsed or refractory, a plethora of choices
1. Elotuzumab + Revlimid + DEX
2. Elotuzumab + Velcade + DEX
3. Carfilzomib + Dex
4. Pomalidomide + Bortezomib + DEX
Despite this you still have new agents
1. ARRY-520
2.Daratumumab
3.Panobinostat
4.Ixazomib
to try!
(Vorinostat said to "disappointing")
(Medscape) go to talk for a full more reliable discussion! None of the above should be used unless you recheck the info!
HOW FAST MEMBRANE EVENTS REACH THE NUCLEUS, LIKE LIGHTNING FAST!
"Dancing in and out of the nucleus: p120(ctn) and the transcription factor Kaiso.
Source
Department of Biology, LSB-331, McMaster University, 1280 Main St. West, Hamilton, ON, Canada L8S 4K1. danielj@mcmaster.caAbstract
The
catenin p120 (hereafter p120(ctn)) was first identified as a Src kinase
substrate and subsequently characterized as an Armadillo catenin member
of the cell-cell adhesion cadherin-catenin complex. In the past decade,
many studies have revealed roles for p120(ctn) in regulating Rho family
GTPase activity and E-cadherin stability and turnover, events that
occur predominantly at the plasma membrane or in the cytoplasm. However,
the recent discovery of the nuclear BTB/POZ-ZF transcription factor
Kaiso as a p120(ctn) binding partner, coupled with the detection of
p120(ctn) in the nucleus of some cell lines and tumor tissues, suggested
that like the classical beta-catenin, p120(ctn) undergoes
nucleocytoplasmic trafficking and regulates gene expression. Indeed,
p120(ctn) has a classic nuclear localization signal and does traffic to
the nucleus. Moreover, nuclear p120(ctn) regulates Kaiso DNA-binding and
transcriptional activity, similar to beta-catenin's modulation of
TCF/LEF transcription activity. However unlike beta-catenin, p120(ctn)
does not appear to be a transcriptional activator. Hence it remains to
be determined whether the sole role of nuclear p120(ctn) is regulation
of Kaiso or whether p120(ctn) binds and regulates other transcription
factors or nuclear proteins."
======================================================
This article, easily found on Google, is an important example of how fast events happening at the membrane reach the the depth of the cell at nuclear level. Indeed E-cadherin is an adhesion protein which is found at the cellular surface, intervening in the the cell to cell interaction. YET, its interaction with the Kaiso "as a binding partner", put it center to epigenetic events in the cell making the Kaiso a target to stop nuclear effects of E-Cadherins.
Regulation of the Rho is indeed another very significant point, since the Rho is now well known to heavily contribute to proliferation and metastatic potential of malignant cells.
The Kaiso is known to : (Wipedia)
"ZBTB33 has been shown to interact with HDAC3,[2] Nuclear receptor co-repressor 1[2] and CTNND1.[3]"
======================================================
This article, easily found on Google, is an important example of how fast events happening at the membrane reach the the depth of the cell at nuclear level. Indeed E-cadherin is an adhesion protein which is found at the cellular surface, intervening in the the cell to cell interaction. YET, its interaction with the Kaiso "as a binding partner", put it center to epigenetic events in the cell making the Kaiso a target to stop nuclear effects of E-Cadherins.
Regulation of the Rho is indeed another very significant point, since the Rho is now well known to heavily contribute to proliferation and metastatic potential of malignant cells.
The Kaiso is known to : (Wipedia)
"ZBTB33 has been shown to interact with HDAC3,[2] Nuclear receptor co-repressor 1[2] and CTNND1.[3]"
again re-enforcing the notion that membrane events can join the epigenetic ones in a FLASH!
We thank these researchers for advancing medicine !
(careful now if you hit the Ku Antigen, you will affect, the PARP1, G quadruplex, and c-MYC, the amplifier ! and therefore KRAS at the membrane, again!)
We thank these researchers for advancing medicine !
(careful now if you hit the Ku Antigen, you will affect, the PARP1, G quadruplex, and c-MYC, the amplifier ! and therefore KRAS at the membrane, again!)
Important clinical questions!
Can lipoxins and IL-4 be used as Biomarkers in Hematologic Malignancy
They point to end of inflammatory process
does their "suppression or absence" points to the severity of leukemic process?
Lipoxins are the most recent addition to the family of bioactive products generated from Arachidonic Acid (AA). They have a number of proinflammatory and anti-inflammatory actions. Lipoxins are short lived endogenously produced nonclassic eicosanoids whose appearance in inflammation signals the resolution of inflammation. They are abbreviated as LX, an acronym for lipoxygenase (LO) interaction products. At present two lipoxins have been identified; lipoxin A4 (LXA4) and lipoxin B4 (LXB4). (wikipedia) During inflammation, cells die by apoptosis. As part of resolution, lipoxins signal macrophages to the remains of these cells (phagocytosis).[6] During the acute inflammatory process, the proinflammatory cytokines such as IFN-γ and IL-1β can induce the expression of anti-inflammatory mediators such as lipoxins and IL-4, which promote the resolution phase of inflammation.[7]
=====================================================================
Should Inhibitor of PARP-1 affect cellular levels of superoxide ? and what would be the effect in patient taking anti-oxide.
Can conceptually use of Inhibitor of PARP-1, inhibit the MTOR inhibitors since it impact Mitochondrial Glycolytic state?
And the answer comes from Chantal Ethier et al
"Phosphorylation of the mTORC1 target S6 is decreased as well as the phosphorylation of the mTORC2 component Rictor on Thr1135. Finally, Akt phosphorylation on Ser473 is lost and then, cell death by necrosis occurs. Inhibition of PARP-1 with the potent PARP inhibitor AG14361 prevents all of these events. Moreover, the antioxidant N-acetyl-L-cysteine (NAC) can also abrogate all the signaling events caused by MNNG exposure suggesting that reactive oxygen species (ROS) production is involved in PARP-1 activation and modulation of mTOR signaling. In this study, we show that PARP-1 activation and PAR synthesis affect the energetic status of cells, inhibit the mTORC1 signaling pathway and possibly modulate the mTORC2 complex affecting cell fate."
Other interactions?
Go to article!
They point to end of inflammatory process
does their "suppression or absence" points to the severity of leukemic process?
Lipoxins are the most recent addition to the family of bioactive products generated from Arachidonic Acid (AA). They have a number of proinflammatory and anti-inflammatory actions. Lipoxins are short lived endogenously produced nonclassic eicosanoids whose appearance in inflammation signals the resolution of inflammation. They are abbreviated as LX, an acronym for lipoxygenase (LO) interaction products. At present two lipoxins have been identified; lipoxin A4 (LXA4) and lipoxin B4 (LXB4). (wikipedia) During inflammation, cells die by apoptosis. As part of resolution, lipoxins signal macrophages to the remains of these cells (phagocytosis).[6] During the acute inflammatory process, the proinflammatory cytokines such as IFN-γ and IL-1β can induce the expression of anti-inflammatory mediators such as lipoxins and IL-4, which promote the resolution phase of inflammation.[7]
=====================================================================
Should Inhibitor of PARP-1 affect cellular levels of superoxide ? and what would be the effect in patient taking anti-oxide.
Can conceptually use of Inhibitor of PARP-1, inhibit the MTOR inhibitors since it impact Mitochondrial Glycolytic state?
And the answer comes from Chantal Ethier et al
"Phosphorylation of the mTORC1 target S6 is decreased as well as the phosphorylation of the mTORC2 component Rictor on Thr1135. Finally, Akt phosphorylation on Ser473 is lost and then, cell death by necrosis occurs. Inhibition of PARP-1 with the potent PARP inhibitor AG14361 prevents all of these events. Moreover, the antioxidant N-acetyl-L-cysteine (NAC) can also abrogate all the signaling events caused by MNNG exposure suggesting that reactive oxygen species (ROS) production is involved in PARP-1 activation and modulation of mTOR signaling. In this study, we show that PARP-1 activation and PAR synthesis affect the energetic status of cells, inhibit the mTORC1 signaling pathway and possibly modulate the mTORC2 complex affecting cell fate."
Other interactions?
Histone deacetylase inhibitor potentiated the ability of MTOR inhibitor to induce autophagic cell death in Burkitt leukemia/lymphoma
Li Hua Dong1†Go to article!
Sunday, August 4, 2013
IRON DEFICIENCY ANEMIA, added insult to the body
*FROM NEWSmax.health
?Anemia increase risk for dementia in elderly
wonder if it is all anemia or Iron deficiency
breakdown would have been more informative.
*Alentuzumab (Anti-CD52) for the treatment of Hypereosinophilic syndrome led to "brisk elimination of symptoms" . Caveat: Alentuzumab side effect. and questionable effect in clearing the bone marrow. Prophylaxis for CMV and Zoster recommended.
"The makers of Alemtuzumab have reportedly withdraw the medication from the united states to prepare for a relaunch in lower dosage" for treatment of refractory Myeloma" (Strati et al...)
Use of GLEEVEC IS DISCUSSEDIN THE ARTICLE
?Anemia increase risk for dementia in elderly
wonder if it is all anemia or Iron deficiency
breakdown would have been more informative.
*Alentuzumab (Anti-CD52) for the treatment of Hypereosinophilic syndrome led to "brisk elimination of symptoms" . Caveat: Alentuzumab side effect. and questionable effect in clearing the bone marrow. Prophylaxis for CMV and Zoster recommended.
"The makers of Alemtuzumab have reportedly withdraw the medication from the united states to prepare for a relaunch in lower dosage" for treatment of refractory Myeloma" (Strati et al...)
Use of GLEEVEC IS DISCUSSEDIN THE ARTICLE
CASE IN POINT ABOUT FLIPPASE-FLOPPASE
Conceptually, most proteins of physiologic importance made in the cells are stored at the cellular membrane either as an integral part of the membrane called Integrins or anchored to it and in need of Secretases for secretion.
Most of the Integrins are attached to a Metalloproteinases (ADAMS10)
let say Epo, TNF,TGF or Cyclin-D are attached to the membrane, with an cytoplasmic stimulation which liberates the TNF from its attachment, The TNF is" flipped" into the cell, and its related Metalloproteinase (2,9) is "Flopped" outside the cell.
The TNF will go on to influence epigenetic events such as increase transcription factors, The metalloprotease will go out to influence extracellular events. Autoimmunes diseases that are associated with high Cytokines levels intracellularly, are also associated with high Metalloproteinnases extracellularly. And cellular destruction of joint surfaces is in part due to Metalloproteinases doing their job of modifying the extracellular matrix in excess.
In sepsis for example, controlling the Metalloproteinases by a modified Tetracycline has proved to tamper the cellular attacks in this syndrome.
Remember not all proteins is attached to same Metalloproteinase since there are several class. And all Metalloproteinases are not equal in what they do. So it is important to inventory the Metalloproteinase by proteins to which they are attached, and to clearly major in each disease process which Metalloproteinase is increased.
Now because we are bound to secrete Metalloproteinase through the Flippase-Floppase process, our cells need to protect themselves from the Metalloproeinases they produce. So each cell has anti-metalloproteinase "cover" to shield itself from its own production. Lack of such protection lead to dangerous clotting events called TTP and HUD, events so dramatic that every Hematologist fear a call each time a patient present with low platelet! The treatment is known, remove the Metalloproteases and other auto-antibodies through pharesis...
Yet Insurers will fight you if you want to know the level of Cytokines and their related Metalloproteinases. No wonder that the NCI is calling for new Biomarkers in Autoimmune disease, opening the door for the future in Medicine...!
Most of the Integrins are attached to a Metalloproteinases (ADAMS10)
let say Epo, TNF,TGF or Cyclin-D are attached to the membrane, with an cytoplasmic stimulation which liberates the TNF from its attachment, The TNF is" flipped" into the cell, and its related Metalloproteinase (2,9) is "Flopped" outside the cell.
The TNF will go on to influence epigenetic events such as increase transcription factors, The metalloprotease will go out to influence extracellular events. Autoimmunes diseases that are associated with high Cytokines levels intracellularly, are also associated with high Metalloproteinnases extracellularly. And cellular destruction of joint surfaces is in part due to Metalloproteinases doing their job of modifying the extracellular matrix in excess.
In sepsis for example, controlling the Metalloproteinases by a modified Tetracycline has proved to tamper the cellular attacks in this syndrome.
Remember not all proteins is attached to same Metalloproteinase since there are several class. And all Metalloproteinases are not equal in what they do. So it is important to inventory the Metalloproteinase by proteins to which they are attached, and to clearly major in each disease process which Metalloproteinase is increased.
Now because we are bound to secrete Metalloproteinase through the Flippase-Floppase process, our cells need to protect themselves from the Metalloproeinases they produce. So each cell has anti-metalloproteinase "cover" to shield itself from its own production. Lack of such protection lead to dangerous clotting events called TTP and HUD, events so dramatic that every Hematologist fear a call each time a patient present with low platelet! The treatment is known, remove the Metalloproteases and other auto-antibodies through pharesis...
Yet Insurers will fight you if you want to know the level of Cytokines and their related Metalloproteinases. No wonder that the NCI is calling for new Biomarkers in Autoimmune disease, opening the door for the future in Medicine...!
NEWS FROM OTHER SOURCES
*from MEDCSCAPE
" AP26113 is a second-generation ALK and ROS1 inhibitor that seems in vitro to also have some activity against the activating epidermal growth factor receptor (EGFR) mutations and T790M."..." We are showing the results from the phase 1 dose-escalation study[1] across a broad dose range.
In the ALK patients, most of whom have not responded to crizotinib, we are seeing fantastic activity: a 75% response rate in patients who had progressed on crizotinib. That is occurring at doses from 60 mg all the way up to 240 mg. They are now taking 180 mg forward as the recommended phase 2 dose. It seems to be very well tolerated. One case of pneumonitis occurred at one of the lower doses, and some other patients with low performance status did relatively badly. But after pausing, tightening up on the inclusion criteria, and adding extra patients to those cohorts, "
*"Other monoclonal antibodies being evaluated for relapse and refractory indolent non Hodgkin Lymphoma include Epratuzumab (Anti-CD22) Galiximab (anti-CD80), Dacetuzumab (anti-CD40) and a number of humanized anti CD20 monoclonal antibodies." (ASCO)
*"High levels of soluble IL-2 Receptors (>5 times normal) are present in the sera of almost all patients with Hairy cell leukemia " (Hagop Kantargian and Susan Obrien) The disease is characterized by Cytopenia and impaired skin test reactivity. inversion of CD4/CD8.
This the driver force in this disease? or is-it a consequence of epigenic phenomena? Insurer will fight you if you try to make this a biomarker? And we forgot to measure the METALLOPROTEINASES HERE!
The point is that the response to 2-CDA, Pentostatin, and Interferon suggest the IL-2Ra is most likely causative since these agents have profound epigenetic effects.
BY THE WAY, EPRATUZUMAB IS AN ANTI-CD22, WHICH IS ALSO PRESENT IN HAIRY CELL! (proof of concept)
" AP26113 is a second-generation ALK and ROS1 inhibitor that seems in vitro to also have some activity against the activating epidermal growth factor receptor (EGFR) mutations and T790M."..." We are showing the results from the phase 1 dose-escalation study[1] across a broad dose range.
In the ALK patients, most of whom have not responded to crizotinib, we are seeing fantastic activity: a 75% response rate in patients who had progressed on crizotinib. That is occurring at doses from 60 mg all the way up to 240 mg. They are now taking 180 mg forward as the recommended phase 2 dose. It seems to be very well tolerated. One case of pneumonitis occurred at one of the lower doses, and some other patients with low performance status did relatively badly. But after pausing, tightening up on the inclusion criteria, and adding extra patients to those cohorts, "
*"Other monoclonal antibodies being evaluated for relapse and refractory indolent non Hodgkin Lymphoma include Epratuzumab (Anti-CD22) Galiximab (anti-CD80), Dacetuzumab (anti-CD40) and a number of humanized anti CD20 monoclonal antibodies." (ASCO)
*"High levels of soluble IL-2 Receptors (>5 times normal) are present in the sera of almost all patients with Hairy cell leukemia " (Hagop Kantargian and Susan Obrien) The disease is characterized by Cytopenia and impaired skin test reactivity. inversion of CD4/CD8.
This the driver force in this disease? or is-it a consequence of epigenic phenomena? Insurer will fight you if you try to make this a biomarker? And we forgot to measure the METALLOPROTEINASES HERE!
The point is that the response to 2-CDA, Pentostatin, and Interferon suggest the IL-2Ra is most likely causative since these agents have profound epigenetic effects.
BY THE WAY, EPRATUZUMAB IS AN ANTI-CD22, WHICH IS ALSO PRESENT IN HAIRY CELL! (proof of concept)
Saturday, August 3, 2013
FAILURE IN CURRENT ONCOLOGY PRACTICE: THE CANCER SURVIVOR STORY
"The American Association for Cancer Research has released its second Annual Report on Cancer Survivorship in the United States. The report, published in the AACR’s journal Cancer Epidemiology, Biomarkers & Prevention,
shows that as of January 2012, there were approximately 13.7 million
cancer survivors in the United States, a number that is expected to rise
by 31 percent to 18 million by 2022."(NCSD)
It is quite apparant that one of the shame in Oncology practice is the poor services that we provide to our cancer survivors. Given the current state of knowledge, it is evident that what we do for survivor is small, fragmented and insufficient! And the service is more insufficient in patient who had been the more treated.
If one had surgery alone, the moral toll of losing a breast, burden of future relationship, perceived Disfiguration and related psychological detrimental effect is a tremendous burden to cope with...Consequences of true anatomic sequelae of surgeries are countless and a huge burden affecting the lives of survivors. And there are not enough trained psychologist or internists for that matter to meet the demand imposed by cancer on survivors.
If a survivor had Radiation, an additional toll occurs. Now on top of thyroid dysfunction, Xerostomia, chronic fatigue, and disfiguration, secondary cancer is added. Suppression of bone marrow after a localized radiation has always pointed out that although Radiation is localized, it has systemic implications. That is some altered protein escape the area to induce deleterious effects / stressful events at the distance. fatigue and sometimes nausea result from Radiation. Myocardial infarction, loss of hair and salivation are most of the time a result of a direct exposure to Radiation, and Anemia/Myelodysplasia can result from pelvic radiation.
And if chemotherapy was part of the treatment, and particularly if it contained Cisplatin or Alkylating agents, Leukemia and secondary cancers become a real possibility. Lung, renal and hearing toxicities become real. Chemotherapy induced encephalopaties of various level are present. Thyroid and fertility disturbances, Dysplasias or all kinds, and the overall neuro-psychiatric background is disturbed. Globally all senses are disturbed. Alterations of the immune system are poorly evaluated and understood.
Where we fail is in our correct evaluation of these disturbances and risk of future events in order to make a difference in the life of survivors. Our biomarkers are not up to what the should be for cancer early detection of secondary cancers,minor but significant side effcts are poorly measured and meaningful preventive or therapeutic measures are often lacking!
The point is that under the satisfaction of response to therapy, we fail to address what is to come for our survivors who often found themselves alone and unprepared to what is to come. The oncologist challenge is compounded by the fact that some of the services needed are not covered by insurers unless packaged in a certain smart fashion. Insurers who have paid for the treatment, want to run from the demanding patients! The lack of evidence based supportive treatment does not help either!
As to secondary cancers:
The point is that we know which cancers develop after chemotherapy
AML (CBF LIKE MOLECULE, GENETIC PROFILE OF BONE MARROW 1 YEAR POST TREATEMT?)
Myelodysplasia (genetic profile of Bone marrow
Colon Cancers( Microsattelite, MUC,
Lung cancers (HIF-1a, MUC...,EGFR)
Breast Cancers (WISP3,BRCA1,2...P53 mutation)
Lymphoma (appropriate gene translocations)
Sarcoma (WT-1, secretases)
and even Melanoma (p16,KIT,PTEN
But No one is delving into preventive detection of of genes!
Renal toxicity (NPHS2 gene, ACTN4
Ototoxicity same as renal (may be!)
scars (Metallopreoteases and their inhibition)
Many studies needed for "PROOF OF CONCEPT"
The skeptical will add "is this going to improve survival" just be in the shoes of survivors once and you will see the need for this testing!
It is quite apparant that one of the shame in Oncology practice is the poor services that we provide to our cancer survivors. Given the current state of knowledge, it is evident that what we do for survivor is small, fragmented and insufficient! And the service is more insufficient in patient who had been the more treated.
If one had surgery alone, the moral toll of losing a breast, burden of future relationship, perceived Disfiguration and related psychological detrimental effect is a tremendous burden to cope with...Consequences of true anatomic sequelae of surgeries are countless and a huge burden affecting the lives of survivors. And there are not enough trained psychologist or internists for that matter to meet the demand imposed by cancer on survivors.
If a survivor had Radiation, an additional toll occurs. Now on top of thyroid dysfunction, Xerostomia, chronic fatigue, and disfiguration, secondary cancer is added. Suppression of bone marrow after a localized radiation has always pointed out that although Radiation is localized, it has systemic implications. That is some altered protein escape the area to induce deleterious effects / stressful events at the distance. fatigue and sometimes nausea result from Radiation. Myocardial infarction, loss of hair and salivation are most of the time a result of a direct exposure to Radiation, and Anemia/Myelodysplasia can result from pelvic radiation.
And if chemotherapy was part of the treatment, and particularly if it contained Cisplatin or Alkylating agents, Leukemia and secondary cancers become a real possibility. Lung, renal and hearing toxicities become real. Chemotherapy induced encephalopaties of various level are present. Thyroid and fertility disturbances, Dysplasias or all kinds, and the overall neuro-psychiatric background is disturbed. Globally all senses are disturbed. Alterations of the immune system are poorly evaluated and understood.
Where we fail is in our correct evaluation of these disturbances and risk of future events in order to make a difference in the life of survivors. Our biomarkers are not up to what the should be for cancer early detection of secondary cancers,minor but significant side effcts are poorly measured and meaningful preventive or therapeutic measures are often lacking!
The point is that under the satisfaction of response to therapy, we fail to address what is to come for our survivors who often found themselves alone and unprepared to what is to come. The oncologist challenge is compounded by the fact that some of the services needed are not covered by insurers unless packaged in a certain smart fashion. Insurers who have paid for the treatment, want to run from the demanding patients! The lack of evidence based supportive treatment does not help either!
As to secondary cancers:
The point is that we know which cancers develop after chemotherapy
AML (CBF LIKE MOLECULE, GENETIC PROFILE OF BONE MARROW 1 YEAR POST TREATEMT?)
Myelodysplasia (genetic profile of Bone marrow
Colon Cancers( Microsattelite, MUC,
Lung cancers (HIF-1a, MUC...,EGFR)
Breast Cancers (WISP3,BRCA1,2...P53 mutation)
Lymphoma (appropriate gene translocations)
Sarcoma (WT-1, secretases)
and even Melanoma (p16,KIT,PTEN
But No one is delving into preventive detection of of genes!
Renal toxicity (NPHS2 gene, ACTN4
Ototoxicity same as renal (may be!)
scars (Metallopreoteases and their inhibition)
Many studies needed for "PROOF OF CONCEPT"
The skeptical will add "is this going to improve survival" just be in the shoes of survivors once and you will see the need for this testing!
Friday, August 2, 2013
MINIATURE BUSES TO DELIVER CHEMOTHERAPY WHERE WE WANT IT IN A CELL
"Research News: Breakthrough in Nano-Medicine Chemotherapy Drug Delivery in Phase II Trials"
NO KIDDING AROUND ANYMORE, ALL WE NEED TO KNOW IS A SPECIFIC ADDRESS IN A CELL AND THE BUS IS ON ITS WAY WITH WHATEVER THE CHEMOTHERAPY LOAD. THIS IS PRECISION MEDICINE/ONCOLOGY.
NANO PARTICLE TECHNOLOGY AT WORK FOR IMPROVED MEDICINE!
GO TO ARTICLE!
PUZZLING EXPERIENCE!
2 YEARS AGO I WAS SEEING A PATIENT WHO WAS FOUND WITH METASTATIC RENAL CANCER, I TALKED TO THE PATIENT ABOUT VARIOUS OPTIONS AT THE TIME
HIGH DOSE IL-2, THE MTOR INHIBITORS ETC...
SHE WAS AFRAID OF SIDE EFFECTS AND ASKED ME TO WAIT...
SHE CAME BACK 3 MONTHS LATER..FEARING PROGRESSION, I QUICKLY REQUESTED RADIOLOGIC EVALUATION
LESIONS WERE THE SAME...THIS CONVINCED ME AND THE PATIENT THAT ANOTHER 3
MONTHS OBSERVATION WAS REASONABLE....
3 MONTHS LATER ....SAME RESULTS
BY 9 MONTHS INTO THIS, I HAD TO ASK MY PATIENT TO CONFESS SINCE NOW I WAS IN DOUBT OF MY DIAGNOSIS:
SHE TOLD ME I AM TAKING "Echinacea"
"The immunomodulatory effects of echinacea preparations are likely caused by fat-soluble alkylamides (alkamides), which occur mostly in E. angustifolia and E. purpurea but not in E. pallida.[22] Alkylamides bind particularly to human CB2 and to a much lesser degree to CB1 cannabinoid receptors; as a result they are implicated in a variety of modulatory functions, including immune suppression, induction of apoptosis, cell migration and inhibition of tumor necrosis factor α TNF-alpha[23] These Alkylamides have similar potency to that of THC at the CB2 receptor, with THC being around 1.5 times stronger (~40 nm vs ~60 nm affinities). However, potency is dramatically less than that of THC at the psychoactive CB1 receptor (~40 nm vs ~ >1500 nm affinities).
As with any herbal preparation, individual doses may vary significantly in active chemical composition. In addition to poor process control which may affect inter- and intra-batch homogeneity, species, plant part, extraction method, and contamination or adulteration with other products all lead to variability between products.[24][25]"
Echinacea extracts inhibited growth of three species of trypanosomatids: Leishmania donovani, Leishmania major, and Trypanosoma brucei.[35]
========================================================================
Like the CB1 receptors, CB2 receptors inhibit the activity of adenylyl cyclase through their Gi/Goα subunits.[9][10] Through their Gβγ subunits, CB2 receptors are also known to be coupled to the MAPK-ERK pathway,[9][10][11] a complex and highly conserved signal transduction pathway, which critically regulates a number of important cellular processes in both mature and developing tissues.[12] Activation of the MAPK-ERK pathway by CB2 receptor agonists acting through the Gβγ subunit ultimately results in changes in cell migration[13] as well as in an induction of the growth-related gene Zif268 (also known as Krox-24, NGFI-A, and egr-1).[11] The Zifi268 gene encodes a transcriptional regulator implicated in neuroplasticity and long term memory formation.[14]
At present, there are five recognized cannabinoids produced endogenously throughout the body: Arachidonoylethanolamine (anandamide), 2-arachidonoyl glycerol (2-AG), 2-arachidonyl glyceryl ether (noladin ether), virodhamine,[9] as well as the recently-discovered N-arachidonoyl-dopamine (NADA).[15] Many of these ligands appear to exhibit properties of functional selectivity at the CB2 receptor: 2-AG preferentially activates the MAPK-ERK pathway, while noladin preferentially inhibits adenylyl cyclase.[9] Like noladin, the synthetic ligand CP-55,940 has also been shown to preferentially inhibit adenylyl cyclase in CB2 receptors.[9] Together, these results support the emerging concept of agonist-directed trafficking at the cannabinoid receptors." wikipedia
===============================
HIGH DOSE IL-2, THE MTOR INHIBITORS ETC...
SHE WAS AFRAID OF SIDE EFFECTS AND ASKED ME TO WAIT...
SHE CAME BACK 3 MONTHS LATER..FEARING PROGRESSION, I QUICKLY REQUESTED RADIOLOGIC EVALUATION
LESIONS WERE THE SAME...THIS CONVINCED ME AND THE PATIENT THAT ANOTHER 3
MONTHS OBSERVATION WAS REASONABLE....
3 MONTHS LATER ....SAME RESULTS
BY 9 MONTHS INTO THIS, I HAD TO ASK MY PATIENT TO CONFESS SINCE NOW I WAS IN DOUBT OF MY DIAGNOSIS:
SHE TOLD ME I AM TAKING "Echinacea"
TO THIS DAY I AM STILL PUZZLED!
They could be truth to this, it can be anti-opoptotic and anti-TNF.
Is it a lipoxin? because this LIPOXIN could do wonders in asthma!
THE CRBCM IS HARD AT WORK!
CAUTION:PROOF OF CONCEPT NEEDED!
Echinacea
from Wikipedia"The immunomodulatory effects of echinacea preparations are likely caused by fat-soluble alkylamides (alkamides), which occur mostly in E. angustifolia and E. purpurea but not in E. pallida.[22] Alkylamides bind particularly to human CB2 and to a much lesser degree to CB1 cannabinoid receptors; as a result they are implicated in a variety of modulatory functions, including immune suppression, induction of apoptosis, cell migration and inhibition of tumor necrosis factor α TNF-alpha[23] These Alkylamides have similar potency to that of THC at the CB2 receptor, with THC being around 1.5 times stronger (~40 nm vs ~60 nm affinities). However, potency is dramatically less than that of THC at the psychoactive CB1 receptor (~40 nm vs ~ >1500 nm affinities).
As with any herbal preparation, individual doses may vary significantly in active chemical composition. In addition to poor process control which may affect inter- and intra-batch homogeneity, species, plant part, extraction method, and contamination or adulteration with other products all lead to variability between products.[24][25]"
Echinacea extracts inhibited growth of three species of trypanosomatids: Leishmania donovani, Leishmania major, and Trypanosoma brucei.[35]
========================================================================
Like the CB1 receptors, CB2 receptors inhibit the activity of adenylyl cyclase through their Gi/Goα subunits.[9][10] Through their Gβγ subunits, CB2 receptors are also known to be coupled to the MAPK-ERK pathway,[9][10][11] a complex and highly conserved signal transduction pathway, which critically regulates a number of important cellular processes in both mature and developing tissues.[12] Activation of the MAPK-ERK pathway by CB2 receptor agonists acting through the Gβγ subunit ultimately results in changes in cell migration[13] as well as in an induction of the growth-related gene Zif268 (also known as Krox-24, NGFI-A, and egr-1).[11] The Zifi268 gene encodes a transcriptional regulator implicated in neuroplasticity and long term memory formation.[14]
At present, there are five recognized cannabinoids produced endogenously throughout the body: Arachidonoylethanolamine (anandamide), 2-arachidonoyl glycerol (2-AG), 2-arachidonyl glyceryl ether (noladin ether), virodhamine,[9] as well as the recently-discovered N-arachidonoyl-dopamine (NADA).[15] Many of these ligands appear to exhibit properties of functional selectivity at the CB2 receptor: 2-AG preferentially activates the MAPK-ERK pathway, while noladin preferentially inhibits adenylyl cyclase.[9] Like noladin, the synthetic ligand CP-55,940 has also been shown to preferentially inhibit adenylyl cyclase in CB2 receptors.[9] Together, these results support the emerging concept of agonist-directed trafficking at the cannabinoid receptors." wikipedia
===============================
Cancer prevention: A gobal failure of our current approach!
Our basic understanding of prevention is 2 fold or can be summarized in 2 main understanding scenarios
1: Stopping a continuous stimulation, or repression for that matter, of critical genes could prevent cancer:
- one suggests that the increasing rate of certain cancers can be justified by chronic stimulation of genes until an additional event happens to give an irreversible path to Neoplasia. This understanding is prominent among Oncologists and the public for that matter, but our reaction is rather confused or ineffective.
The insufficiency of response is mainly justified by our limitation of understanding of what follows the the prolong exposure or stimulation, which form of gene (heterogeneic type) is more susceptible and therefore requires early preventive measure, what gene actually triggers the neoplastic amplification, how long an exposure is critical for any specific individual, what other concurrent failure needs to be there to induce or help the neoplastic transformation (ie. mutation of CYP gene) and so on so forth...before these many questions, the human brain albeit scientific, has to stop. And our stopping to computer these events has worked for cancers to keep killing.
IT IS TIME TO USE MORE COMPUTER POWERS TO PREDICT NEOPLASTIC DEVELOPMENT TO ACTUALLY INTERVENE BASED ON COMPUTER MODELS THAT WE NEED TO CREATE RAPIDOS TO STOP CANCER DEVELOPMENT.
Once and for all, we need to stop reading this:
The incidence of liver cancer is rising worldwide and in the U.S. mostly due to the concomitant rise in hepatitis C viral infection. Because liver cancer occurs in the background of cirrhosis, preservation of healthy liver tissue is critically important. Liver cancer arising from the hepatocytes ....(johns Hopkins)
THIS STATEMENT ACKNOWLEDGES THE FACT THAT WE KNOW THE CAUSE OF THE INCREASE INCIDENCE OF LIVER CANCER BUT THERE IS NOT MUCH WE CAN DO TODAY DESPITE OUR ADVANCES. WE KNOW HEPATITIS C IS THE DRIVING FORCE BUT THERE LITTLE WE HAVE DONE SO FAR TO SQUARELY MEET THIS CHALLENGE. VACCINE ARE ONE WAY...BUT FOR HEPATITIS C IT IS NOT AVAILABLE!
"
A hepatitis C vaccine, a vaccine capable of protecting against hepatitis C, is not available. Although vaccines exist for hepatitis A and hepatitis B, development of a hepatitis C vaccine has presented challenges.[1] No vaccine is currently available, but several vaccines are currently under development.[2]
One effort has involved use of the hepatitis B core antigen.[3] In a 2006 study, 60 patients received four different doses of an experimental hepatitis C vaccine. All the patients produced antibodies that the researchers believe could protect them from the virus.[4] Nevertheless, as of 2008 vaccines are still being tested.[5][6] Some efforts have entered Phase I/II human clinical trials.[7]
SynCon will test a new HCV vaccine in humans in 2013. SyCon's HCV vaccine can generate robust T-cell responses not only in the blood, but also in the liver—an organ known to suppress T-cell activity."WIKIPEDIA....
For cancer of the Gatro-esophageal (GE) junction, we read:
"The possible reasons of the rise (in the incidence of this cancer) include the prevalence of obesity. elevated body mass index with increased incidence of GERD, and caloric consumption" the author even suggests "Use of Aspirin and other non steroidal anti-inflammatory agents has been associated with lower risk of cancers of the GE junction and other gastrointestinal tumors"(Grothey) YET THERE ARE NO NATIONAL COMPREHENSIVE PLAN TO USE THIS KNOWLEDGE.
REASON: Insufficient knowledge about what else these medications can cause, from bleeding to predisposing to arrhythmia in some of us on various medications. these fears block us from stopping these cancers.
IT IS TIME TO BRING IN THE POWER OF COMPUTER MODELS TO PLAN OUR APPROACHES!
(an exanple of gene suppression: CONTINUED SUPPRESSION OF PTEN! A PRECEDENT TO MANY DANGEROUS CANCERS! OR DECREASE OF E-CADHERIN...)
2. 2ND MAIN SCENARIO
IS USING FOOD SUPPLEMENT TO DAMPEN THESE STIMULATIONS OF GENE.
HERE THE ROLE ANTI-OXIDANTS IS CRITICAL.
WHAT I AM NOT SURE ABOUT IS WHETHER "FDA APPROVAL" STANDARD HAS HELPED OR DISCOURAGED PROGRESS IN THIS AREA...FURTHER PROOF OF CONCEPTS ARE NEEDED. THE SUGGESTION THAT STATUS OF IRON, ZINC, MAGNESIUM AND OTHER MINERALS CAN MODIFY THE EFFECTS OF ANTI-OXIDANTS HAS BEEN INSUFFICIENTLY STUDIED. SUSPICIONS ARE THAT WHAT IS GENERALLY GOOD AN INTERVENTION (TAKING VITAMINS, AND ANTI-OXIDANT FOOD STUFFS OR STAPLES, CAN BECOME DANGEROUS ! INDEED EVEN THE RATE OF CORRECTION OF IRON DEFICIENCY COULD BE DANGEROUS....DON'T GO TO FAST!) ONLY WELL DESIGNED COMPUTER MODELS CAN HELP US MANAGE ALL THESE PARAMETERS...AND WE ARE STILL NOWHERE NEAR THE GOAL!
WE NEED NEW BIOMARKERS FOR AUTOIMMUNE DISEASES...AGAIN COMPUTERS ARE NEEDED...WE CAN'T HANDLE THESE THINGS ON OUR OWN...THE EARLIER WE REALIZE THIS...THE BETTER!
CRBCM, WORKING ALWAYS!
1: Stopping a continuous stimulation, or repression for that matter, of critical genes could prevent cancer:
- one suggests that the increasing rate of certain cancers can be justified by chronic stimulation of genes until an additional event happens to give an irreversible path to Neoplasia. This understanding is prominent among Oncologists and the public for that matter, but our reaction is rather confused or ineffective.
The insufficiency of response is mainly justified by our limitation of understanding of what follows the the prolong exposure or stimulation, which form of gene (heterogeneic type) is more susceptible and therefore requires early preventive measure, what gene actually triggers the neoplastic amplification, how long an exposure is critical for any specific individual, what other concurrent failure needs to be there to induce or help the neoplastic transformation (ie. mutation of CYP gene) and so on so forth...before these many questions, the human brain albeit scientific, has to stop. And our stopping to computer these events has worked for cancers to keep killing.
IT IS TIME TO USE MORE COMPUTER POWERS TO PREDICT NEOPLASTIC DEVELOPMENT TO ACTUALLY INTERVENE BASED ON COMPUTER MODELS THAT WE NEED TO CREATE RAPIDOS TO STOP CANCER DEVELOPMENT.
Once and for all, we need to stop reading this:
The incidence of liver cancer is rising worldwide and in the U.S. mostly due to the concomitant rise in hepatitis C viral infection. Because liver cancer occurs in the background of cirrhosis, preservation of healthy liver tissue is critically important. Liver cancer arising from the hepatocytes ....(johns Hopkins)
THIS STATEMENT ACKNOWLEDGES THE FACT THAT WE KNOW THE CAUSE OF THE INCREASE INCIDENCE OF LIVER CANCER BUT THERE IS NOT MUCH WE CAN DO TODAY DESPITE OUR ADVANCES. WE KNOW HEPATITIS C IS THE DRIVING FORCE BUT THERE LITTLE WE HAVE DONE SO FAR TO SQUARELY MEET THIS CHALLENGE. VACCINE ARE ONE WAY...BUT FOR HEPATITIS C IT IS NOT AVAILABLE!
"
A hepatitis C vaccine, a vaccine capable of protecting against hepatitis C, is not available. Although vaccines exist for hepatitis A and hepatitis B, development of a hepatitis C vaccine has presented challenges.[1] No vaccine is currently available, but several vaccines are currently under development.[2]
One effort has involved use of the hepatitis B core antigen.[3] In a 2006 study, 60 patients received four different doses of an experimental hepatitis C vaccine. All the patients produced antibodies that the researchers believe could protect them from the virus.[4] Nevertheless, as of 2008 vaccines are still being tested.[5][6] Some efforts have entered Phase I/II human clinical trials.[7]
SynCon will test a new HCV vaccine in humans in 2013. SyCon's HCV vaccine can generate robust T-cell responses not only in the blood, but also in the liver—an organ known to suppress T-cell activity."WIKIPEDIA....
For cancer of the Gatro-esophageal (GE) junction, we read:
"The possible reasons of the rise (in the incidence of this cancer) include the prevalence of obesity. elevated body mass index with increased incidence of GERD, and caloric consumption" the author even suggests "Use of Aspirin and other non steroidal anti-inflammatory agents has been associated with lower risk of cancers of the GE junction and other gastrointestinal tumors"(Grothey) YET THERE ARE NO NATIONAL COMPREHENSIVE PLAN TO USE THIS KNOWLEDGE.
REASON: Insufficient knowledge about what else these medications can cause, from bleeding to predisposing to arrhythmia in some of us on various medications. these fears block us from stopping these cancers.
IT IS TIME TO BRING IN THE POWER OF COMPUTER MODELS TO PLAN OUR APPROACHES!
(an exanple of gene suppression: CONTINUED SUPPRESSION OF PTEN! A PRECEDENT TO MANY DANGEROUS CANCERS! OR DECREASE OF E-CADHERIN...)
2. 2ND MAIN SCENARIO
IS USING FOOD SUPPLEMENT TO DAMPEN THESE STIMULATIONS OF GENE.
HERE THE ROLE ANTI-OXIDANTS IS CRITICAL.
WHAT I AM NOT SURE ABOUT IS WHETHER "FDA APPROVAL" STANDARD HAS HELPED OR DISCOURAGED PROGRESS IN THIS AREA...FURTHER PROOF OF CONCEPTS ARE NEEDED. THE SUGGESTION THAT STATUS OF IRON, ZINC, MAGNESIUM AND OTHER MINERALS CAN MODIFY THE EFFECTS OF ANTI-OXIDANTS HAS BEEN INSUFFICIENTLY STUDIED. SUSPICIONS ARE THAT WHAT IS GENERALLY GOOD AN INTERVENTION (TAKING VITAMINS, AND ANTI-OXIDANT FOOD STUFFS OR STAPLES, CAN BECOME DANGEROUS ! INDEED EVEN THE RATE OF CORRECTION OF IRON DEFICIENCY COULD BE DANGEROUS....DON'T GO TO FAST!) ONLY WELL DESIGNED COMPUTER MODELS CAN HELP US MANAGE ALL THESE PARAMETERS...AND WE ARE STILL NOWHERE NEAR THE GOAL!
WE NEED NEW BIOMARKERS FOR AUTOIMMUNE DISEASES...AGAIN COMPUTERS ARE NEEDED...WE CAN'T HANDLE THESE THINGS ON OUR OWN...THE EARLIER WE REALIZE THIS...THE BETTER!
CRBCM, WORKING ALWAYS!
Thursday, August 1, 2013
GLAD TO FIND THE ANSWER TO THE SILENCE AT CPRIT
CPRIT Updates
Roadmap to Resuming Grant Awards
Since the legislature passed SB 149, CPRIT has been moving ahead with efforts to resume the agency’s grant awards process. View the CPRIT Roadmap to Resuming Grant Awards for a timeline and summary of activities and priorities critical for the agency to resume the grant awards process with deliberate purpose, accountability and transparency. As we continue to make progress, check back for updates on the status of individual activities and priorities.GO TO THE ROADMAP TO KNOW WHERE THEY ARE AT CPRIT!
Letter to the Texas Governor
RE: Citizen's Right to Petition that "No City Should be left Behind" by CPRIT.
As CPRIT is being restructured, The Coalition for the Reversal of Breast Cancer Mortality in African American Women (CRBCM), an IRS approved non profit Texan organization, and a responsible Citizen of this great state, would like to petition its Governor, influential Senators and the new Leaders at CPRIT to give El Paso finally a greater chance to participate in CPRIT's dream: Finding the cure for Cancer! We believe that until there is an overarching political will to meet the challenges of unfairness, disparity and gap in health care access, and the idea of the whole state of Texas, the participation in the CPRIT research funding program will remain fragmented and El Paso, once again, will be left behind.
Of the first almost one billion of dollars spent by CPRIT, less than one percent (1%) went to El Paso, the 6th City of Texas, population wise. The research community in El Paso has been left perplexed. There is a growing sense that this city is being "left behind" despite its size! It is not a contested fact that the major universities are located in the 3 major cities and have taken the lion share of CPRIT investments. We call, however, for a deliberate political regional intent and approach by the Texas Government in order to balance and promote development across all of Texas. We believe that a funded regional CPRIT office with focus on the WEST part of Texas will give us a better chance to participate in CPRIT efforts to reach the cure. While it is true that most El Paso institutions could not have matching funds to benefit from some CPRIT projects, it turns out that even some of the beneficiaries of CPRIT funding in other cities, eventually never proved the existence of the promised matching funds, and El Paso missed out on false pretenses as it turned out!
What we know for sure is that unless there is a political will to balance development in Texas and overcome the various disparities, the gap in development among cities will grow even more blatant! This is the reason for our petition! Even companies that were relocated to Texas as part of the CPRIT commercialization program, all flocked to Houston and Austin, (adding to the Houston traffic). None of significance stayed in El Paso! But El Paso is Texas, too! A rise of El Paso's share in CPRIT funding to 5% would be an impressive achievement and is not too much to ask for the 6th City in Texas!
We call your attention to this matter, NO CITY SHOULD BE LEFT BEHIND IN TEXAS, and your will can make a difference, a regional approach is called for.
Sincerely yours,
for the CRBCM, an El Paso institution
Dr Kankonde,
Oncologist and CEO
As CPRIT is being restructured, The Coalition for the Reversal of Breast Cancer Mortality in African American Women (CRBCM), an IRS approved non profit Texan organization, and a responsible Citizen of this great state, would like to petition its Governor, influential Senators and the new Leaders at CPRIT to give El Paso finally a greater chance to participate in CPRIT's dream: Finding the cure for Cancer! We believe that until there is an overarching political will to meet the challenges of unfairness, disparity and gap in health care access, and the idea of the whole state of Texas, the participation in the CPRIT research funding program will remain fragmented and El Paso, once again, will be left behind.
Of the first almost one billion of dollars spent by CPRIT, less than one percent (1%) went to El Paso, the 6th City of Texas, population wise. The research community in El Paso has been left perplexed. There is a growing sense that this city is being "left behind" despite its size! It is not a contested fact that the major universities are located in the 3 major cities and have taken the lion share of CPRIT investments. We call, however, for a deliberate political regional intent and approach by the Texas Government in order to balance and promote development across all of Texas. We believe that a funded regional CPRIT office with focus on the WEST part of Texas will give us a better chance to participate in CPRIT efforts to reach the cure. While it is true that most El Paso institutions could not have matching funds to benefit from some CPRIT projects, it turns out that even some of the beneficiaries of CPRIT funding in other cities, eventually never proved the existence of the promised matching funds, and El Paso missed out on false pretenses as it turned out!
What we know for sure is that unless there is a political will to balance development in Texas and overcome the various disparities, the gap in development among cities will grow even more blatant! This is the reason for our petition! Even companies that were relocated to Texas as part of the CPRIT commercialization program, all flocked to Houston and Austin, (adding to the Houston traffic). None of significance stayed in El Paso! But El Paso is Texas, too! A rise of El Paso's share in CPRIT funding to 5% would be an impressive achievement and is not too much to ask for the 6th City in Texas!
We call your attention to this matter, NO CITY SHOULD BE LEFT BEHIND IN TEXAS, and your will can make a difference, a regional approach is called for.
Sincerely yours,
for the CRBCM, an El Paso institution
Dr Kankonde,
Oncologist and CEO
IN RESPONSE TO VIEWERS'S QUESTIONS ABOUT CPRIT
Yes, CPRIT is going to resume operations soon!
We cannot tell when.
There has been complete silence from the Organization.
Activities and news about CPRIT have focused on the lack of actual oversight by the District Attorney Greg Abott who had appointed someone who missed a third of CPRIT critical meetings. DA Abott is now runing for the governorship in Texas!
CPRIT has 595 Millions in its coffers to give to mostly University projects. So we will hear sooner or later about this organization before the year ends. Based on its past performance, we expect that close to half of the money will go to 3 universities. We refuse to comment on the rest. There is no official news at CPRIT but you know the grapevine is still hard at work. We refuse to add to speculations. But we should mention that El Paso did not get its fair share the first time around with less than 1% of CPRIT grant attribution gone to the 4th City in Texas! And don't say we did not try to apply! CRBCM alone submitted 7 grant applications, none met somehow the political muscle requirements for funding! Now we are thinking we have a better chance with Deutche Krebshiffe, the Swiss Federal Government and Bundes Ministerium fur Bildung und Forschung than from CPRIT! In fact we got a UK funding for our genetic research being completed with UTEP help! The same project kindly declined by CPRIT!
How the new CPRIT will meet its expected many " raisons d'etre" is still to be seen. Abandoning its mission to Universities was the first achievement of the first dance...and we know what it led us to...let's wait and see the 2nd round...lets see how it meets the disparity challenge, and how it meets covering the whole Texas challenge...Remember all Taxpayers are coming together in this. The story of this organization will be talked about by historians for years to come! New leaders are being put into place, let's give them a chance to shine and amaze us! Take us to the cure of cancer!
We cannot tell when.
There has been complete silence from the Organization.
Activities and news about CPRIT have focused on the lack of actual oversight by the District Attorney Greg Abott who had appointed someone who missed a third of CPRIT critical meetings. DA Abott is now runing for the governorship in Texas!
CPRIT has 595 Millions in its coffers to give to mostly University projects. So we will hear sooner or later about this organization before the year ends. Based on its past performance, we expect that close to half of the money will go to 3 universities. We refuse to comment on the rest. There is no official news at CPRIT but you know the grapevine is still hard at work. We refuse to add to speculations. But we should mention that El Paso did not get its fair share the first time around with less than 1% of CPRIT grant attribution gone to the 4th City in Texas! And don't say we did not try to apply! CRBCM alone submitted 7 grant applications, none met somehow the political muscle requirements for funding! Now we are thinking we have a better chance with Deutche Krebshiffe, the Swiss Federal Government and Bundes Ministerium fur Bildung und Forschung than from CPRIT! In fact we got a UK funding for our genetic research being completed with UTEP help! The same project kindly declined by CPRIT!
How the new CPRIT will meet its expected many " raisons d'etre" is still to be seen. Abandoning its mission to Universities was the first achievement of the first dance...and we know what it led us to...let's wait and see the 2nd round...lets see how it meets the disparity challenge, and how it meets covering the whole Texas challenge...Remember all Taxpayers are coming together in this. The story of this organization will be talked about by historians for years to come! New leaders are being put into place, let's give them a chance to shine and amaze us! Take us to the cure of cancer!
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