1."NO INSURANCE STATUS" KILLING YOUNG PEOPLE WITH CANCER IN EL PASO.
Young people holding small jobs can barely afford life on their own and one of the sacrifice they make is health insurance. In El Paso, a border town of the great State of Texas at least 30% of working young families do not have health insurance. You can get by with a headache, Tylenol is available without prescription. But when you have cancer, young people are waiting for death in silence. Many have found their qualification for MEDICAID which these days means a government certificate of "no insurance". Not only its payments are meaningless but it is very hard to come by! Therefore most physicians do not take patients with it. At Medicare and Medicaid, the government uses its time to imagine new ways (Red tape) to cut or escape payment all together. The new latest method is to claim "we have a new computer system". "your claim was entered incorrectly or in the old system" we could not pay you because we could not find your claim in the new system". Who is responsible for entering data in the system in the first place or why is it the physician responsibility when a government personnel did not do its work. Rather than dealing with this mess physicians and some hospitals are turning away patients. And the best way to turn patient away is NO FOLLOW-UP APPOINTMENT ONCE CANCER DIAGNOSIS IS MADE. You can't show up at the ER for cancer, cancer does not cause a pressing symptom while it is spreading. So we have a walking dead situation where a normal looking individual is living of the knowledge of having cancer but with no treatment!
In this border town, Mexico is the answer for many! There they get treated as far as their money can take them...they comeback to die in their home fully disconnected for the American Health system most of the time having missed to the latest treatment available in the US.
WHILE ALL THIS IS HAPPENING, POLITICIANS AND LOCAL JOURNALISTS TURN THEIR BACK!
2.SHE CAME TO DIE IN MY ARMS!
May 8th, 2013, I was waiting for a new patient when I ended up with such case. A desperate mother seeing her daughter dying, brought her to my clinic hours before her death which she escaped after IV fluid was given in a reluctant ER where I was forced to take the patient urgently!
A 25 year old American woman, mother of 3 kids, was reportedly sick without health insurance, she sought treatment in Mexico, she was reported to have an aggressive form of Leukemia (ALL). She received chemotherapy reportedly for a full year. With her money exhausted she could no longer afford to go back and follow-up could not be accomplished. The last bone marrow obtained just 6 weeks ago showed no leukemia but the marrow beaten by chemotherapy is failing to make cell blood cell as it should. Over the last few weeks she has been home weakening by the time she was brought to the office in wheelchair, she had not walk for over a week, going in and out of consciousness, she dry and Anemic...the ER gave her fluid but no blood and discharged her with NO FOLLOW-UP APPOINTMENT. Contacted by the family, I referred the patient for transfusion to the only hospital still helping the poor, for how long your guess is as good as mine? The woman should now be evaluated for transplant but now she is free of cancer but mostly dying for lack of follow-up!
IF YOU CAN HELP IN ANYWAY, CONTACT OUR OFFICE !
THIS NOT THE ONLY CASE
Thursday, May 9, 2013
Wednesday, May 8, 2013
TREATING RESISTANCE TO HER-2 TARGETED THERAPY HAS NOW BEEN CLEARLY DEFINED.
In all evidence, the receptor resistance can be induced by change in shape, change in molecular content, and and change in molecular nature of product with which it interacts. As it pertains to the Human Epidermal Growth factor Receptor or HER-2 Receptor, downstream interaction is with the PI3K/AKT/MTOR.
We now take it for granted as a truth that when,in a pathway, some thing clog the action, we target downstream steps. If you can't stop the enemy in the street, or gate, try stop him at your doorstep.
So instead of stopping the Her-2 Receptor, inhibit the MTOR, mammalian target of Rapamycin!
So now inhibiting the MTOR is a strategy to stop resistance or add to the effect of target therapy aimed at HER-2.
and guess what, it works! Proof of concept did materialize in clinical trials!
Scientist now are also taking the Her-2 Receptor targeting molecule, attach it to a powerful chemotherapy molecule and send the whole thing into the cell (concept of T-DM1).
Trastuzumab emtansine (INN;[1][2] in the United States, ado-trastuzumab emtansine, trade name Kadcyla) is an antibody-drug conjugate consisting of the monoclonal antibody trastuzumab (Herceptin) linked to the cytotoxic agent mertansine (DM1).[3][4][5][6] Trastuzumab alone stops growth of cancer cells by binding to the HER2/neu receptor, whereas mertansine enters cells and destroys them by binding to tubulin.[7]
Because the monoclonal antibody targets HER2, and HER2 is only
over-expressed in cancer cells, the conjugate delivers the toxin
specifically to tumor cells.[8]
In the EMILIA clinical trial of women with advanced HER2 positive breast cancer who were already resistant to trastuzumab alone, it improved survival by 5.8 months compared to the combination of lapatinib and capecitabine.[8] Based on that trial, the U.S. Food and Drug Administration (FDA) approved marketing on February 22, 2013.[9][10][11]
Trastuzumab emtansine was developed by Genentech. The planned cost is expected to be $9,800 a month, or $94,000 for a typical course of treatment.[10] wikipidea.
ANOTHER STRATEGY CREATED BY SCIENTIST!
The structure of HER2 and pertuzumab
Pertuzumab (also called 2C4, trade name Perjeta) is a monoclonal antibody. The first of its class in a line of agents called "HER dimerization inhibitors". By binding to HER2, it inhibits the dimerization of HER2 with other HER receptors, which is hypothesized to result in slowed tumor growth.[1] Pertuzumab received US FDA approval for the treatment of HER2-positive metastatic breast cancer on June 8, 2012.[2] Pertuzumab was developed at Genentech and is now owned by Roche which acquired Genentech in 2009.
In all evidence, the receptor resistance can be induced by change in shape, change in molecular content, and and change in molecular nature of product with which it interacts. As it pertains to the Human Epidermal Growth factor Receptor or HER-2 Receptor, downstream interaction is with the PI3K/AKT/MTOR.
We now take it for granted as a truth that when,in a pathway, some thing clog the action, we target downstream steps. If you can't stop the enemy in the street, or gate, try stop him at your doorstep.
So instead of stopping the Her-2 Receptor, inhibit the MTOR, mammalian target of Rapamycin!
So now inhibiting the MTOR is a strategy to stop resistance or add to the effect of target therapy aimed at HER-2.
and guess what, it works! Proof of concept did materialize in clinical trials!
Scientist now are also taking the Her-2 Receptor targeting molecule, attach it to a powerful chemotherapy molecule and send the whole thing into the cell (concept of T-DM1).
Trastuzumab emtansine
From Wikipedia, the free encyclopedia
 |
|
|---|---|
| Monoclonal antibody | |
| Type | Whole antibody |
| Source | Humanized (from mouse) |
| Clinical data | |
| Trade names | Kadcyla |
| Pregnancy cat. | D (US) |
| Legal status | ℞-only (US) |
| Routes | Intravenous infusion |
| Pharmacokinetic data | |
| Bioavailability | N/A |
| Protein binding | 93% (in vitro) |
| Metabolism | Hepatic (CYP3A4/3A5-mediated) |
| Half-life | 4 days |
| Identifiers | |
| CAS number | 1018448-65-1  |
| ATC code | None |
| UNII | SE2KH7T06F |
| KEGG | D09980 |
| Chemical data | |
| Formula | C6448H9948N1720O2012S44·(C47H62ClN4O13S)n |
| Mol. mass | 148.5 kDa |
 (what is this?) (verify) |
|
In the EMILIA clinical trial of women with advanced HER2 positive breast cancer who were already resistant to trastuzumab alone, it improved survival by 5.8 months compared to the combination of lapatinib and capecitabine.[8] Based on that trial, the U.S. Food and Drug Administration (FDA) approved marketing on February 22, 2013.[9][10][11]
Trastuzumab emtansine was developed by Genentech. The planned cost is expected to be $9,800 a month, or $94,000 for a typical course of treatment.[10] wikipidea.
ANOTHER STRATEGY CREATED BY SCIENTIST!
Pertuzumab
From Wikipedia, the free encyclopedia
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized (from mouse) |
| Target | HER2 |
| Clinical data | |
| Trade names | Perjeta; Omnitarg |
| Licence data | US FDA:link |
| Pregnancy cat. | D (US) |
| Legal status | ℞-only (US) |
| Routes | Intravenous |
| Identifiers | |
| CAS number | 380610-27-5 |
| ATC code | L01XC13 |
| UNII | K16AIQ8CTM  |
| KEGG | D05446 |
| ChEMBL | CHEMBL2007641 |
| Chemical data | |
| Formula | ? |
| (what is this?) (verify) |
|
Tuesday, May 7, 2013
DON'T BEAT YOURSELF, THE WORK HAS BEEN DONE BY VON HOFF ET AL!
TARGET TESTED BY IHC DRUG PROPOSED AS INTERACTING WITH TARGET
1.EGFR..................................................CETUXIMAB,ERLOTINIB,GEFITINIB
2.SPARC................................................ABRAXANE
3.c-KIT...................................................IMATINIB,SUNITINIB,SORAFENIB
4.ER........................................................TAMOXIFEN,AROMATASE INHIBITOR,TOREMIFENE,
................................................................PROGESTATIONAL AGENT
5.PR........................................................(SAME AS ER) ADD GOSERELIN
6.ANDROGEN RECEPTOR..................FLUTAMIDE,ABARELIX,BICALUTAMIDE,LEUPROLIDE,
................................................................GOSERELIN
7.PGP......................................................DOXORUBICIN,ETOPOSIDE,DOCETAXEL,VINORELBINE
................................................................PLEASE AVOID NATURAL PRODUCT
8.HER-2/NEU.........................................TRASTUZUMAB
9.PDGFR.................................................SUTENT,GLEEVEC,SORAFENIB (NEXAVAR)
10. CD52.................................................ALEMTUZUMAB
11.CD25..................................................DENILEUKIN DIFTITOX
12.HSP90................................................GELDANAMYCIN, CNF2024
13.TOP2A...............................................DOXORUBICIN, EPIRUBICIN, ETOPOSIDE
THIS WAS PUBLISHED THROUGH ASCO
Comments
We can now go wild testing gene on our specimen. Basically after failure of standard of care, re-biopsy and adjust the attack using these agents!
Geldanamycin is a benzoquinone ansamycin antibiotic that binds to Hsp90 (Heat Shock Protein 90) and inhibits its function. HSP90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis.
Geldanamycin induces the degradation of proteins that are mutated in tumor cells such as v-Src, Bcr-Abl and p53 preferentially over their normal cellular counterparts. This effect is mediated via HSP90. Despite its potent antitumor potential, geldanamycin presents several major drawbacks as a drug candidate (namely, hepatotoxicity) that have led to the development of geldanamycin analogues, in particular analogues containing a derivatisation at the 17 position: (wikipedia)
Conceptually, this drug should be tested in triple negative breast cancer where receptors will fail stressing the cell to amplify HSP90. As a matter of facts, this drug should most likely be used widely given the importance of cellular stress in Neoplasia (including leukemia).
Invivo gene reports:
"Hsp90 is a ubiquitous molecular chaperone critical for the folding, assembly and activity of multiple mutated and overexpressed signaling proteins that promote the growth and/or survival of tumor cells. Hsp90 client proteins include mutated p53, Raf-1, Akt, ErbB2 and hypoxia-inducible factor 1a (HIF-1a) [1]. Binding of GA to Hsp90 causes the destabilization and degradation of its client proteins [2]." So disease where mutations of HSP90 "clients appear to be a driver mutation, should have Geldamycin theoritically !
"However due to poor aqueous solubility and liver toxicity, GA has not moved forward in clinical trials. To overcome these undesirable properties, numerous GA analogs have been synthesized which differ only in their 17-substituent. These include 17-allylamino-demethoxygeldamycin (17-AAG) and 17-dimethylamino- geldanamycin (17-DMAG) that have completed phase I and are currently entering phase II clinical trials."
TARGET TESTED BY IHC DRUG PROPOSED AS INTERACTING WITH TARGET
1.EGFR..................................................CETUXIMAB,ERLOTINIB,GEFITINIB
2.SPARC................................................ABRAXANE
3.c-KIT...................................................IMATINIB,SUNITINIB,SORAFENIB
4.ER........................................................TAMOXIFEN,AROMATASE INHIBITOR,TOREMIFENE,
................................................................PROGESTATIONAL AGENT
5.PR........................................................(SAME AS ER) ADD GOSERELIN
6.ANDROGEN RECEPTOR..................FLUTAMIDE,ABARELIX,BICALUTAMIDE,LEUPROLIDE,
................................................................GOSERELIN
7.PGP......................................................DOXORUBICIN,ETOPOSIDE,DOCETAXEL,VINORELBINE
................................................................PLEASE AVOID NATURAL PRODUCT
8.HER-2/NEU.........................................TRASTUZUMAB
9.PDGFR.................................................SUTENT,GLEEVEC,SORAFENIB (NEXAVAR)
10. CD52.................................................ALEMTUZUMAB
11.CD25..................................................DENILEUKIN DIFTITOX
12.HSP90................................................GELDANAMYCIN, CNF2024
13.TOP2A...............................................DOXORUBICIN, EPIRUBICIN, ETOPOSIDE
THIS WAS PUBLISHED THROUGH ASCO
Comments
We can now go wild testing gene on our specimen. Basically after failure of standard of care, re-biopsy and adjust the attack using these agents!
Geldanamycin is a benzoquinone ansamycin antibiotic that binds to Hsp90 (Heat Shock Protein 90) and inhibits its function. HSP90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis.
Geldanamycin induces the degradation of proteins that are mutated in tumor cells such as v-Src, Bcr-Abl and p53 preferentially over their normal cellular counterparts. This effect is mediated via HSP90. Despite its potent antitumor potential, geldanamycin presents several major drawbacks as a drug candidate (namely, hepatotoxicity) that have led to the development of geldanamycin analogues, in particular analogues containing a derivatisation at the 17 position: (wikipedia)
Conceptually, this drug should be tested in triple negative breast cancer where receptors will fail stressing the cell to amplify HSP90. As a matter of facts, this drug should most likely be used widely given the importance of cellular stress in Neoplasia (including leukemia).
Invivo gene reports:
"Hsp90 is a ubiquitous molecular chaperone critical for the folding, assembly and activity of multiple mutated and overexpressed signaling proteins that promote the growth and/or survival of tumor cells. Hsp90 client proteins include mutated p53, Raf-1, Akt, ErbB2 and hypoxia-inducible factor 1a (HIF-1a) [1]. Binding of GA to Hsp90 causes the destabilization and degradation of its client proteins [2]." So disease where mutations of HSP90 "clients appear to be a driver mutation, should have Geldamycin theoritically !
"However due to poor aqueous solubility and liver toxicity, GA has not moved forward in clinical trials. To overcome these undesirable properties, numerous GA analogs have been synthesized which differ only in their 17-substituent. These include 17-allylamino-demethoxygeldamycin (17-AAG) and 17-dimethylamino- geldanamycin (17-DMAG) that have completed phase I and are currently entering phase II clinical trials."
Monday, May 6, 2013
RESEARCH AT CRBCM
==================
We, the CRBCM, would like to thank one more time MDHonors from London UK for allowing us to kick start the lung cancer Biomarker early detection project. The project is unique because it will help detect early lung cancer in heavy smoker. Hopefully it will help find lung cancer at a still resectable level where we can make a difference in prognosis. It will strengthen the hand of the surgeon in small lesions where currently observation may be deemed dangerous if the lesion being observed is indeed a cancer which may metastasize if given more time. We have worked hard and set up collaboration with the statistics lab at UTEP, and Biomedical labs at UTEP and Texas Tech through the pathology lab. We were just waiting for the funding to initiate the project.
This one research project will be completed in 4 phases:
*1st phase will be to obtain tissue through Banks: The tissues will be from patients with lung cancer in order to determine the prevalence of these genetic abnormalities in cancer tissues. This part is critical because it will also ascertain our detection methods in patients with the cancer!
*The second phase will be the recruitment of Heavy smoker candidates, 2-3 pack/day for greater than 30-40 years who will be willing to sign a consent for participation and agree to let us collect samples of blood and sputum. And apply those testing techniques learned in the first phase!
*Conclusions and publications of our results will follow in the 3rd phase.
*4th phase is the development of an early lung cancer detection kit for by using our findings.
We thank MDHonors for their trust and funding!
At the CRBCM, we work hard to always deliver on our promises.
==================
We, the CRBCM, would like to thank one more time MDHonors from London UK for allowing us to kick start the lung cancer Biomarker early detection project. The project is unique because it will help detect early lung cancer in heavy smoker. Hopefully it will help find lung cancer at a still resectable level where we can make a difference in prognosis. It will strengthen the hand of the surgeon in small lesions where currently observation may be deemed dangerous if the lesion being observed is indeed a cancer which may metastasize if given more time. We have worked hard and set up collaboration with the statistics lab at UTEP, and Biomedical labs at UTEP and Texas Tech through the pathology lab. We were just waiting for the funding to initiate the project.
This one research project will be completed in 4 phases:
*1st phase will be to obtain tissue through Banks: The tissues will be from patients with lung cancer in order to determine the prevalence of these genetic abnormalities in cancer tissues. This part is critical because it will also ascertain our detection methods in patients with the cancer!
*The second phase will be the recruitment of Heavy smoker candidates, 2-3 pack/day for greater than 30-40 years who will be willing to sign a consent for participation and agree to let us collect samples of blood and sputum. And apply those testing techniques learned in the first phase!
*Conclusions and publications of our results will follow in the 3rd phase.
*4th phase is the development of an early lung cancer detection kit for by using our findings.
We thank MDHonors for their trust and funding!
At the CRBCM, we work hard to always deliver on our promises.
| May 6, 2013 Dear Dr. Kankonde,
This is the most exciting, momentous time in the history of medicine. For the first time, we can rapidly and affordably sequence a human genome. We have sensors that can remotely track virtually any physiologic metric, from vital signs to glucose to intraocular pressure. We can add a lab-on-a-chip to a smartphone to assay almost any routine chemistry and digitize pills to ensure adherence. Or use a smartphone to conduct all the components of the physical examination. This is superimposed and convergent with a remarkable digital infrastructure that includes ever-increasing bandwidth, pervasive connectivity, cloud- and supercomputing, enormous social networks, and those little mobile devices that we cannot put down. Medicine is thus poised for its biggest shakeup ever as it transforms to a more precise, individualized, and democratized model. My charge at Medscape is to help capture this excitement, the changes and opportunities, along with the challenges and the need for validation. Medscape will be expanding its breadth of coverage in areas that will be rebooting, which include not only diagnostics, imaging, and medical devices but also the operational aspects of office visits, hospitals, and medical informatics. We have an outstanding team of experts across all medical disciplines, and we'll provide you with timely and insightful commentary on the most important topics in medicine. We intend to take Medscape to the next level, one that embraces the need for change and zooms in on the ways to get there -- the ways to provide better, more efficient care for your patients. We are all connected, with only a few electrons that separate us. I welcome your ideas and feedback about Medscape, so please direct emails to etopol@medscape.net or follow me on Twitter at @EricTopol. Sincerely, Eric J. Topol, MD Editor-in-Chief of Medscape |
PHENOMENA SUGGESTING EVOLUTION OF GENETIC AND METABOLIC PROCESSES!
*It is now suggested that as receptor fail, there is a secondary increase of its specific growth factors which lead to stimulation of other susceptible receptors including MUC gene. What trigger the neoplastic transformation is fuzzy. However we know that the quantity of stimulation, the persistence of the stimulation, the stress induced at the failing receptor, stress which induces the NF-kB, c-JUN and eventually c-Fos and c-MYC the gene global amplifier, methylation of genes and reversal of mesenchymal transformation at MEK most likely, with its impact on EGFR. And through the RAS/MAPK, which interacts with PTEN, by now repressed! Neoplastic transformation is bound to happen. Particularly on a background of genetic Heterogenity, something unpredictable is bound to happen!
*The closeness of VEGF and Hypoxic stress/ phenomena is now legendary! Hypoxia is disturbing at cellular membrane but principally in the Mitochondria where the respiratory system of the cell is located.
It leads to formation of (Reactive oxygen species) superoxide and oxygen free radicals that need dampen by natural anti-oxidants which by the way include Uric Acid. Because of lack of these anti-oxidant (Asian "obsession" with veggies, in a subset of Asians, we hypothesize that insufficient anti-Oxidant and certain genetic susceptibility factor, ultimately lead to a number of Mutations including EGFR Mutation. Effects on other genes including the MUC2 gene will lead to respiratory system failure, in other words, occurrence of lung cancer (Adenocarcinoma) in these women. Sex/Steroid receptors in female patients may be involved in the susceptibility. The story does not stop here however since the Mitochondria takes the full effect of MTOR, the preserver of survival, As the process evolve, the MTOR will take the brunt of the changes and therefore will be increasingly important suggesting MTOR are more important after failure of Anti-VEGF! It is not surprising that combination of the 2 agents failed. VEGF effect seems to depend on MTOR preservation at some level but once the VEGF is incapacitated (resitant disease) MTOR inhibition is a logical step!
*It is now suggested that as receptor fail, there is a secondary increase of its specific growth factors which lead to stimulation of other susceptible receptors including MUC gene. What trigger the neoplastic transformation is fuzzy. However we know that the quantity of stimulation, the persistence of the stimulation, the stress induced at the failing receptor, stress which induces the NF-kB, c-JUN and eventually c-Fos and c-MYC the gene global amplifier, methylation of genes and reversal of mesenchymal transformation at MEK most likely, with its impact on EGFR. And through the RAS/MAPK, which interacts with PTEN, by now repressed! Neoplastic transformation is bound to happen. Particularly on a background of genetic Heterogenity, something unpredictable is bound to happen!
*The closeness of VEGF and Hypoxic stress/ phenomena is now legendary! Hypoxia is disturbing at cellular membrane but principally in the Mitochondria where the respiratory system of the cell is located.
It leads to formation of (Reactive oxygen species) superoxide and oxygen free radicals that need dampen by natural anti-oxidants which by the way include Uric Acid. Because of lack of these anti-oxidant (Asian "obsession" with veggies, in a subset of Asians, we hypothesize that insufficient anti-Oxidant and certain genetic susceptibility factor, ultimately lead to a number of Mutations including EGFR Mutation. Effects on other genes including the MUC2 gene will lead to respiratory system failure, in other words, occurrence of lung cancer (Adenocarcinoma) in these women. Sex/Steroid receptors in female patients may be involved in the susceptibility. The story does not stop here however since the Mitochondria takes the full effect of MTOR, the preserver of survival, As the process evolve, the MTOR will take the brunt of the changes and therefore will be increasingly important suggesting MTOR are more important after failure of Anti-VEGF! It is not surprising that combination of the 2 agents failed. VEGF effect seems to depend on MTOR preservation at some level but once the VEGF is incapacitated (resitant disease) MTOR inhibition is a logical step!
Reelin
From Wikipedia, the free encyclopedia
| Reelin | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 Crystallographic structure of the third reelin repeat domain.[1] |
|||||||||||
|
|||||||||||
| Identifiers | |||||||||||
| Symbols | RELN; LIS2; PRO1598; RL | ||||||||||
| External IDs | OMIM: 600514 MGI: 103022 HomoloGene: 3699 GeneCards: RELN Gene | ||||||||||
| EC number | 3.4.21.- | ||||||||||
|
|||||||||||
| RNA expression pattern | |||||||||||
 |
|||||||||||
| More reference expression data | |||||||||||
| Orthologs | |||||||||||
| Species | Human | Mouse | |||||||||
| Entrez | 5649 | 19699 | |||||||||
| Ensembl | ENSG00000189056 | ENSMUSG00000042453 | |||||||||
| UniProt | P78509 | Q60841 | |||||||||
| RefSeq (mRNA) | NM_005045 | NM_011261 | |||||||||
| RefSeq (protein) | NP_005036 | NP_035391 | |||||||||
| Location (UCSC) | Chr 7: 103.11 – 103.63 Mb |
Chr 5: 21.88 – 22.34 Mb |
|||||||||
| PubMed search | [1] | [2] | |||||||||
Reelin has been suggested to be implicated in pathogenesis of several brain diseases. The expression of the protein has been found to be significantly lower in schizophrenia and psychotic bipolar disorder, but the cause of this observation remains uncertain as studies show that psychotropic medication itself affects reelin expression. Moreover, the epigenetic hypothesis aimed at explaining the changed levels[6] has received some contradictory evidence.[7][8] Total lack of reelin causes a form of lissencephaly. Reelin may also play a role in Alzheimer's disease, temporal lobe epilepsy and autism.
Reelin's name comes from the abnormal reeling gait of reeler mice,[9] which were later found to have a deficiency of this brain protein and were homozygous for mutation of the RELN gene. The primary phenotype associated with loss of reelin function is a failure of neuronal positioning throughout the developing central nervous system (CNS). The mice heterozygous for the reelin gene, while having little neuroanatomical defects, display the endophenotypic traits linked to psychotic disorders.[10]WIKIPEDIA
======================================================================
NEXT INTEREST AT CRBCM
Crizotinib (trade name Xalkori,[1] Pfizer), is an anti-cancer drug acting as an ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) inhibitor, approved for treatment of some non-small cell lung carcinoma (NSCLC) in the US and some other countries, and undergoing clinical trials testing its safety and efficacy in anaplastic large cell lymphoma, neuroblastoma, and other advanced solid tumors in both adults and children.[2]WIKIPEDIA
CONCEPTUALLY, THROUGH ITS PTPN6 ACTIVITY, THIS DRUG SHOULD HAVE SIGNIFICANT JAK-2 ACTIVITY AND SHOULD THEREFORE HAVE A ROLE IN MYELOPROLIFERATIVE DISORDERS THAT HAVE JAK-2 POSITIVITY, AND IN FACT THROUGH THE SAME, IT HAS EFFECT ON THE ERYTHROPOIETIN RECEPTOR!
CONCEPTUALLY, THROUGH ITS PTPN6 ACTIVITY, THIS DRUG SHOULD HAVE SIGNIFICANT JAK-2 ACTIVITY AND SHOULD THEREFORE HAVE A ROLE IN MYELOPROLIFERATIVE DISORDERS THAT HAVE JAK-2 POSITIVITY, AND IN FACT THROUGH THE SAME, IT HAS EFFECT ON THE ERYTHROPOIETIN RECEPTOR!
VARIOUS NEWS
*FOR patients on chronic Doxil, watch for
-Renal failure
-squamous cell cancer of the tongue and oral cavity as a secondary malignancy
-and of course the hand foot syndrome
prolonged exposure to Anti-topoisomerase II (doxo,epirubicin)
leads to APL,AML and MDS.In children, various pediatric malignancies have been reported.
*Adding Pertuzumab to Trastuzumab plus Taxotere did not add to cardiac toxicity in Cleopatra!
*ixabepilone may induce radiation recall and decreased wound healing.
*10-20% of patients treated develop grade 3 Hypertension side effect, and development of Hypertension is not predictive of response to therapy!
*In cancer of the Salivary duct, the Her-2 status may be important since use of Herceptin can impact survival!
*Up to 95% of patients treated with Vemurafenib (used in BRAF positive Melanoma) will develop a dermatologic side effect to be treated supportively. Dose interruptions or modification occurs in less than 10% of cases only!
*Breast implant can be associated with the development of a CD30 Anaplastic ALK negative large cell lymphoma (ALCL).
*FOR patients on chronic Doxil, watch for
-Renal failure
-squamous cell cancer of the tongue and oral cavity as a secondary malignancy
-and of course the hand foot syndrome
prolonged exposure to Anti-topoisomerase II (doxo,epirubicin)
leads to APL,AML and MDS.In children, various pediatric malignancies have been reported.
*Adding Pertuzumab to Trastuzumab plus Taxotere did not add to cardiac toxicity in Cleopatra!
*ixabepilone may induce radiation recall and decreased wound healing.
*10-20% of patients treated develop grade 3 Hypertension side effect, and development of Hypertension is not predictive of response to therapy!
*In cancer of the Salivary duct, the Her-2 status may be important since use of Herceptin can impact survival!
*Up to 95% of patients treated with Vemurafenib (used in BRAF positive Melanoma) will develop a dermatologic side effect to be treated supportively. Dose interruptions or modification occurs in less than 10% of cases only!
*Breast implant can be associated with the development of a CD30 Anaplastic ALK negative large cell lymphoma (ALCL).
Sunday, May 5, 2013
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| Supported by an independent educational grant from Genentech. | |||||||||||||||||||
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JAMA Updates
*JAMA
"In the United States, there was a substantial decrease in mortality rates over time among children and adolescents initiating ESKD treatment with dialysis between 1990 and 2010. Further research is needed to determine the specific factors responsible for this decrease."
*Antiplatelet agents reduce myocardial infarction but increase major bleeding. Risks may outweigh benefits among people with low annual risks of cardiovascular events, including those with early stages of CKD who do not have clinically-evident occlusive cardiovascular disease. (PALMER ET AL)
*Although antioxidant therapy does not reduce the risk of cardiovascular and all-cause death or major cardiovascular events in people with CKD, it is possible that some benefit may be present, particularly in those on dialysis. However, the small size and generally suboptimal quality of the included studies highlighted the need for sufficiently powered studies to confirm this possibility. Current evidence suggests that antioxidant therapy in predialysis CKD patients may prevent progression to ESKD; this finding was however based on a very small number of events. Further studies with longer follow-up are needed for confirmation. Appropriately powered studies are needed to reliably assess the effects of antioxidant therapy in people with CKD. JUN ET AL
*Pigeon heart mitochondria produce H(2)O(2) at a maximal rate of about 20nmol/min per mg of protein. BOVERIS ET AL
* Food restriction (FR) is a well-recognized method of extending mean and maximum longevity of rodents, but the mode of its action remains to be uncovered. This article reviews the effect of FR on the physical-chemical properties and lipid peroxidizability of cellular membranes. FR prevents the age-dependent increase in microviscosity and peroxidizability of cellular membranes. It has been suggested that a decrease in the body temperature occurring in undernourished animals may play a fundamental role in the process. Indeed, the lowering of average body temperature occurring in FR animals may induce a modification in membrane lipid composition, stimulating the cells to counteract the rigidifying effect of lower temperature. Thus, membranes are maintained in a proper functional state by a mechanism similar to that found in poikilotherm animals. AGE ET AL
*All cellular membranes are especially vulnerable to oxidation due to their high concentration of polyunsaturated fatty acids. These processes combine to produce changes in the biophysical properties of membranes that can have profound effects on the activity of membrane-bound proteins. This review deals with aspects for lipid peroxidation of biological membranes in general, but with some emphasis on changes of polyunsaturated fatty acids, which arise most prominently in membranes and have been studied extensively in our laboratory. The article provides current information on the effect of melatonin on biological membranes, changes in fluidity, fatty acid composition and lipid-protein modifications during the lipid peroxidation process of photoreceptor membranes and modulation of gene expression by the hormone and its preventive effects on adriamycin-induced lipid peroxidation
"In the United States, there was a substantial decrease in mortality rates over time among children and adolescents initiating ESKD treatment with dialysis between 1990 and 2010. Further research is needed to determine the specific factors responsible for this decrease."
*Antiplatelet agents reduce myocardial infarction but increase major bleeding. Risks may outweigh benefits among people with low annual risks of cardiovascular events, including those with early stages of CKD who do not have clinically-evident occlusive cardiovascular disease. (PALMER ET AL)
*Although antioxidant therapy does not reduce the risk of cardiovascular and all-cause death or major cardiovascular events in people with CKD, it is possible that some benefit may be present, particularly in those on dialysis. However, the small size and generally suboptimal quality of the included studies highlighted the need for sufficiently powered studies to confirm this possibility. Current evidence suggests that antioxidant therapy in predialysis CKD patients may prevent progression to ESKD; this finding was however based on a very small number of events. Further studies with longer follow-up are needed for confirmation. Appropriately powered studies are needed to reliably assess the effects of antioxidant therapy in people with CKD. JUN ET AL
*Pigeon heart mitochondria produce H(2)O(2) at a maximal rate of about 20nmol/min per mg of protein. BOVERIS ET AL
* Food restriction (FR) is a well-recognized method of extending mean and maximum longevity of rodents, but the mode of its action remains to be uncovered. This article reviews the effect of FR on the physical-chemical properties and lipid peroxidizability of cellular membranes. FR prevents the age-dependent increase in microviscosity and peroxidizability of cellular membranes. It has been suggested that a decrease in the body temperature occurring in undernourished animals may play a fundamental role in the process. Indeed, the lowering of average body temperature occurring in FR animals may induce a modification in membrane lipid composition, stimulating the cells to counteract the rigidifying effect of lower temperature. Thus, membranes are maintained in a proper functional state by a mechanism similar to that found in poikilotherm animals. AGE ET AL
*All cellular membranes are especially vulnerable to oxidation due to their high concentration of polyunsaturated fatty acids. These processes combine to produce changes in the biophysical properties of membranes that can have profound effects on the activity of membrane-bound proteins. This review deals with aspects for lipid peroxidation of biological membranes in general, but with some emphasis on changes of polyunsaturated fatty acids, which arise most prominently in membranes and have been studied extensively in our laboratory. The article provides current information on the effect of melatonin on biological membranes, changes in fluidity, fatty acid composition and lipid-protein modifications during the lipid peroxidation process of photoreceptor membranes and modulation of gene expression by the hormone and its preventive effects on adriamycin-induced lipid peroxidation
The ability of melatonin to counteract lipid peroxidation in biological membranes.
Reactive oxygen species (ROS)
This is scary stuff that makes you think free radical build up is the cause of strokes, coronary artery disease and dementia! with uric acid one of our best defense, it makes you wonder if too much use of diuretics inducing low uric acid is contributing to these events. Makes you want to take coQ10 and vitamin C quickly! and reenforce the notion that one apple a day will keep the doctor away!
COULD ROS EXPLAIN LUNG CANCER OCCURRENCE IN ASIAN WOMEN WHO DEVELOP ADENOCARCINOMA? AND IF SO coQ, VITAMIN C COULD PREVENT THESE CANCERS?
Asian women nonsmokers with NSCLC have a high rate of EGFR + mutations and they have a better prognosis also. Could ROS be the underlying deficiency?
Zhang et al!
"Once thought of as toxic by-products of cellular metabolism, reactive oxygen species (ROS) have been implicated in a large variety of cell-signaling processes. Several enzymatic systems contribute to ROS production in vascular endothelial cells, including NA(D)PH oxidase, xanthine oxidase, uncoupled endothelial nitric oxide synthase, and the mitochondrial electron transport chain. The respiratory chain is the major source of ROS in most mammalian cells, but the role of mitochondria-derived ROS in vascular cell signaling has received little attention. A new paradigm has evolved in recent years postulating that, in addition to producing ATP, mitochondria also play a key role in cell signaling and regulate a variety of cellular functions. This review focuses on the emerging role of mitochondrial ROS as signaling molecules in vascular endothelial cells. Specifically, we discuss some recent findings that indicate that mitochondrial ROS regulate vascular endothelial function, focusing on major sites of ROS production in endothelial mitochondria, factors modulating mitochondrial ROS production, the physiological and clinical implications of endothelial mitochondrial ROS, and methodological considerations in the study of mitochondrial contribution to vascular ROS generation."
WIKIPEDIA!
" Normally, cells defend themselves against ROS damage with enzymes such as alpha-1-microglobulin, superoxide dismutases, catalases, lactoperoxidases, glutathione peroxidases and peroxiredoxins. Small molecule antioxidants such as ascorbic acid (vitamin C), tocopherol (vitamin E), uric acid, and glutathione also play important roles as cellular antioxidants. In a similar manner, polyphenol antioxidants assist in preventing ROS damage by scavenging free radicals. In contrast, the antioxidant ability of the extracellular space is less - e.g., the most important plasma antioxidant in humans is uric acid."
WHAT IS THE AFFECTED WOMEN'S LEVEL OF URIC ACID?
ARE THESE WOMEN TAKING A URICOSURIC?
=============================================================
UNDER HYPOXIC CONDITIONS, LACK OF ATP AND DECREASED coQ, A DANGER START GROWING IN THE MITOCHONDRIA, SUPEROXIDE ARE BUILDING UP AND UNLESS CONDITIONS CHANGE OR UNLESS THE ABOVE ENZYMES INTERVENE TO DILUTE THE SITUATION, THE OXIDE FREE RADICAL WILL SPILL OVER THE CYTOSOL (CYTOCHROME B WILL ALSO BE INVOLVED) WHERE THEY WILL OXYDIZE VARIOUS MOLECULES AND INDUCE INFLAMMATORY AND POTENTIALLY NEOPLASTIC PROCESSES!
" In general, harmful effects of reactive oxygen species on the cell are most often:[4]
- damage of DNA
- oxidations of polyunsaturated fatty acids in lipids (lipid peroxidation)
- oxidations of amino acids in proteins
- oxidatively inactivate specific enzymes by oxidation of co-factors"
Metabolic adaptation in tumours balances the cells' need for energy with equally important need for macromolecular building blocks and tighter control of redox balance. As a result, production of NADPH is greatly enhanced, which functions as a cofactor to provide reducing power in many enzymatic reactions for macromolecular biosynthesis and at the same time rescuing the cells from excessive ROS produced during rapid proliferation. Cells counterbalance the detrimental effects of ROS by producing antioxidant molecules, such as reduced glutathione (GSH) and thioredoxin (TRX), which rely on the reducing power of NADPH to maintain their activities.[19]
Most risk factors associated with cancer interact with cells through the generation of ROS. ROS then activate various transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein-1 (AP-1), hypoxia-inducible factor-1α and signal transducer and activtor of transcription 3 (STAT3), leading to expression of proteins that control inflammation; cellular transformation; tumor cell survival; tumor cell proliferation; and invasion, agiogenesis as well as metastasis. And ROS also control the expression of various tumor supressor genes such as p53, retinoblastoma gene (Rb), and phosphatase and tensin homolog (PTEN).[20]"
HOW THESE DRAMATIC EVENTS IMPACT THE MUC GENES FAMILY AND EGFR HAS NOT BEEN DESCRIBED FULLY AND COULD EXPLAIN HOW IN THE LUNG, AN ADENOCARCINOMA COULD RESULT. THE GOOD RESPONSE TO ANTI EGFR POINT TO A SINGLE CAUSAL EVENT THAT IS REVERSED OR ATTENUATED BY INITIATION OF TARCEVA AND RELATED MOLECULES. BEING MITOCHONDRIAL, IT MAY BE A CLUE TO MTOR INHIBITOR ACTIVITY AFTER FAILURE OF EGFR (SECOND LINE AS DISCUSSED PREVIOULSY)
*THE FDA AND MORE SPECIFICALLY ODAC SAYS NO TO TIVOZANIB IN METASTATIC RENAL CELL CANCER. TIVOZANIB, a second generation anti-VEGF kinase was being tested against Nexavar. The panel was not convinced enough to let it win approval. 17 studies were globally reviewed to arrive to this conclusion which will not let the drug moving forward!
*from Medscape
"New guidelines on prostate cancer screening, issued today by the American Urological Association (AUA), are supportive of routine use of the prostate-specific antigen (PSA) test in healthy men, but only for a specified age group, and only after discussion between a man and his physician.
Specifically, the new guidelines state that men 55 to 69 years of age who are at average risk and asymptomatic can consider PSA screening. They should speak to the their physician about the benefits and harms of testing to determine the best course of action." go to full article.
*from Medscape
"New guidelines on prostate cancer screening, issued today by the American Urological Association (AUA), are supportive of routine use of the prostate-specific antigen (PSA) test in healthy men, but only for a specified age group, and only after discussion between a man and his physician.
Specifically, the new guidelines state that men 55 to 69 years of age who are at average risk and asymptomatic can consider PSA screening. They should speak to the their physician about the benefits and harms of testing to determine the best course of action." go to full article.
Saturday, May 4, 2013
Case study
A 65 year old man came to our clinic with weakness
he was found with mild pancytopenia
the marrow was hypercellular and the cytogenic findings on the bone Marrow suggested del 5q
RAEB-1 was the comment of the pathologist based on blast count
and the rate of Erythrpoietin was below 500.
standard recommendation per the Atlas of Genetics
==========================================================
BASED ON ONLY ONE FINDING
5q deletion
most oncologists will propose REVLIMID to this patient
that is the power of Genetic findings!
and indeed if a complex Cytogenetic finding was present and no 5q minus, Azacytidine would have been the choice in the UNITED STATES....
==========so what is 5q minus?
AZACYTIDINE
generally given at 75mg/m2 SC 7 days per months
achieves 7% complete response and 16% partial remission with most response reached after 3 to 4 months of therapy. It also decreases the AML transformation and improves survival (11 Vs 18 months)
A 65 year old man came to our clinic with weakness
he was found with mild pancytopenia
the marrow was hypercellular and the cytogenic findings on the bone Marrow suggested del 5q
RAEB-1 was the comment of the pathologist based on blast count
and the rate of Erythrpoietin was below 500.
standard recommendation per the Atlas of Genetics
| Treatment ofthis condition in the elderly patient is largely supportive, including blood transfusion in patients with symptomatic anemia. Anemic patients with low serum erythropoietin (EPO) levels may benefit of the administration of rHu-EPO. Low dose cytarabine can be used to reduce the burden of blasts. Myeloablative regimens including anthracyclines and cytarabine in conventional or high doses can be used in high-risk patients under 60 years. Allogeneic bone marrow transplantation may offer a chance of cure in young patients. | ||
| Evolution | This is an
oligoblastic leukemia, carrying a 20-40% probability of evolving into
leukemia. In a study approximately 25% of the patient developed acute myeloid leukemia (AML) within 18 months. The probability of RAEB to transform into AML is lower in the RAEB-1 group (approximately 50% of the patients develop acute leukemia within 6 years) than in the RAEB-2 group (approximately 50% at 18 months with overt leukemia). | |
| Prognosis | Median survival of RAEB falls in the 1-2 year range. The best outcome is usually observed in RAEB-1. Chromosomal abnormalities have independent prognostic significance and are to be included in risk assessment at diagnosis. Favourable cytogenetic features are normal karyotype, 5q- or 20q- isolated; unfavourable features are complex karyotype (i.e. 3 or more clonal anomalies) and abnormalities of chromosome 7q; other abnormalities identify patients in the intermediate cytogenetic-risk group. |
==========================================================
BASED ON ONLY ONE FINDING
5q deletion
most oncologists will propose REVLIMID to this patient
that is the power of Genetic findings!
and indeed if a complex Cytogenetic finding was present and no 5q minus, Azacytidine would have been the choice in the UNITED STATES....
==========so what is 5q minus?
AZACYTIDINE
generally given at 75mg/m2 SC 7 days per months
achieves 7% complete response and 16% partial remission with most response reached after 3 to 4 months of therapy. It also decreases the AML transformation and improves survival (11 Vs 18 months)
Friday, May 3, 2013
CLINICAL RESEARCH QUESTIONS:
1. COULD ANTIBODY TO MBD3 (AND OR MTA2) BLOCK OR SLOW METASTASIS?
2.IS ANTI-NuRD A POWERFUL INHIBITOR OF HISTONE DEACETYLASE? AND WHAT COULD BE ITS ROLE IN LEUKEMIAS!
LET'S GO TO WORK, PEOPLE!
CRBCM, AN INTERNATIONAL AWARD WINNER ! WE ARE STEADILY ADVANCING!
2.IS ANTI-NuRD A POWERFUL INHIBITOR OF HISTONE DEACETYLASE? AND WHAT COULD BE ITS ROLE IN LEUKEMIAS!
LET'S GO TO WORK, PEOPLE!
CRBCM, AN INTERNATIONAL AWARD WINNER ! WE ARE STEADILY ADVANCING!
DISRUPTION AT BRCA IS TRULY BAD FOR OUR PATIENTS!
Before we start this discussion, let's remind ourselves what we know about the BRCAs by taking the example of BRCA-1
"
BRCA1 is expressed in the cells of breast and other tissue, where it helps repair damaged DNA, or destroy cells if DNA cannot be repaired. If BRCA1 itself is damaged, damaged DNA is not repaired properly and this increases risks for cancers (see BRCA mutation).[7][8]
The protein encoded by the BRCA1 gene combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC).[9] The BRCA1 protein associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. Thus, this protein plays a role in transcription, DNA repair of double-stranded breaks[8] ubiquitination, transcriptional regulation as well as other functions.[10]"wikipedia
This statement is a global description of many bad thing this BRCA does to people who have it.
And until this is re-emphasized, one may not know the full extent of the danger lurking in BRCA positive patients!
BRCA is not just a mere a DNA repair gene. And cells have all kind of gene repair genes, BRCA is also primarily a tumor suppression gene, in its wilde type it is attached to COBRA1, a true COBRA with its eyes on several bad genes that encode proteins which the cell wanted to keep in check. These molecules are known as NEGATIVE ELONGATIONS PROTEINS. And there is a number of them, and each once uncontrolled due to mutation of the BRCA gene will go to induce unduly other deleterious consequences...
Let's take the COBRA-1 itself, once unable to tie itself to the mutated BRCA, it will unnecessarily stimulate the Estrogen receptor alpha, and will reach at this area even the stress pathway c-JUN, and c-fos triggering manufacturing of unnecssary cyclins and growth factors, or the stuff that worsen cancers!
But we can choose to look at ARAF, another elongation proteins which, by being part of the RAF, will amplify the MAPK kinase pathway, this effect is seen even into the Mitochondria (waking the MTOR up )
if you pick the RDBP elongation factor, it will do what negative elongation factor generally do which is to amplify RNA polymerase and ready it to induce DNA polymerase for cell proliferation by DNA multiplicaton
the TH1L, will impact the DSIF and exacerbate RDBP actions!
You see that a good wild BRCA suppresses all these activities by elongation proteins, while repairing DNA mistakes.
I SHOULD EMPHASIZE THAT THE MOST IMPORTANT TARGET IN THIS TRACK IS THE RNA POLYMERASE THAT EVERY SINGLE NEGATIVE ELONGATION MOLECULE WANTS SO BADLY TO AMPLIFY! IT HAS DOMINION OVER DNA POLYMERASE IN THIS CASE!
Before we start this discussion, let's remind ourselves what we know about the BRCAs by taking the example of BRCA-1
"
BRCA1 is expressed in the cells of breast and other tissue, where it helps repair damaged DNA, or destroy cells if DNA cannot be repaired. If BRCA1 itself is damaged, damaged DNA is not repaired properly and this increases risks for cancers (see BRCA mutation).[7][8]
The protein encoded by the BRCA1 gene combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC).[9] The BRCA1 protein associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. Thus, this protein plays a role in transcription, DNA repair of double-stranded breaks[8] ubiquitination, transcriptional regulation as well as other functions.[10]"wikipedia
This statement is a global description of many bad thing this BRCA does to people who have it.
And until this is re-emphasized, one may not know the full extent of the danger lurking in BRCA positive patients!
BRCA is not just a mere a DNA repair gene. And cells have all kind of gene repair genes, BRCA is also primarily a tumor suppression gene, in its wilde type it is attached to COBRA1, a true COBRA with its eyes on several bad genes that encode proteins which the cell wanted to keep in check. These molecules are known as NEGATIVE ELONGATIONS PROTEINS. And there is a number of them, and each once uncontrolled due to mutation of the BRCA gene will go to induce unduly other deleterious consequences...
Let's take the COBRA-1 itself, once unable to tie itself to the mutated BRCA, it will unnecessarily stimulate the Estrogen receptor alpha, and will reach at this area even the stress pathway c-JUN, and c-fos triggering manufacturing of unnecssary cyclins and growth factors, or the stuff that worsen cancers!
But we can choose to look at ARAF, another elongation proteins which, by being part of the RAF, will amplify the MAPK kinase pathway, this effect is seen even into the Mitochondria (waking the MTOR up )
if you pick the RDBP elongation factor, it will do what negative elongation factor generally do which is to amplify RNA polymerase and ready it to induce DNA polymerase for cell proliferation by DNA multiplicaton
the TH1L, will impact the DSIF and exacerbate RDBP actions!
You see that a good wild BRCA suppresses all these activities by elongation proteins, while repairing DNA mistakes.
I SHOULD EMPHASIZE THAT THE MOST IMPORTANT TARGET IN THIS TRACK IS THE RNA POLYMERASE THAT EVERY SINGLE NEGATIVE ELONGATION MOLECULE WANTS SO BADLY TO AMPLIFY! IT HAS DOMINION OVER DNA POLYMERASE IN THIS CASE!
DID YOU KNOW?
An investigational antibody designed to
target the programmed death-1 (PD-1) pathway in patients with advanced
melanoma received a Breakthrough Therapy designation from the FDA.
Lambrolizumab demonstrated benefit from a small single-arm study.
Lambrolizumab, developed by Merck and formerly known as MK-3475, is a humanized monoclonal IgG4 antibody that acts against PD-1. In the results of a phase I trial that were presented at the American Society of Clinical Oncology (ASCO) annual meeting in 2012, the antibody was studied in nine patients with a variety of tumor types, including two patients with melanoma. The drug was well-tolerated and generated antitumor activity in three different doses.
Interim results from a phase IB study reported in November revealed data from 85 of 132 patients enrolled in the single-arm study. Merck reported that 43 patients (51%) showed an objective anti-tumor response and 8 patients (9%) showed a complete response at or after an assessment performed at 12 weeks. Further, 11 of 27 patients (41%) who had been previously treated with ipilimumab monotherapy for late-stage melanoma showed an objective antitumor response.
In general, MK-3475 was well-tolerated, with the most common adverse events including fatigue, rash, diarrhea, nausea, cough, joint pain, fever, and itching. Seven grade 3/4 events were reported as potentially immune-related."
go TO FULL ARTICLE
DON'T SLEEP AT THE WHEEL,
THE WORLD IS MOVING A BIT FASTER!
"FDA Grants Breakthrough Therapy Designation For PD-1 Targeted Antibody Lambrolizumab
Lambrolizumab, developed by Merck and formerly known as MK-3475, is a humanized monoclonal IgG4 antibody that acts against PD-1. In the results of a phase I trial that were presented at the American Society of Clinical Oncology (ASCO) annual meeting in 2012, the antibody was studied in nine patients with a variety of tumor types, including two patients with melanoma. The drug was well-tolerated and generated antitumor activity in three different doses.
Interim results from a phase IB study reported in November revealed data from 85 of 132 patients enrolled in the single-arm study. Merck reported that 43 patients (51%) showed an objective anti-tumor response and 8 patients (9%) showed a complete response at or after an assessment performed at 12 weeks. Further, 11 of 27 patients (41%) who had been previously treated with ipilimumab monotherapy for late-stage melanoma showed an objective antitumor response.
In general, MK-3475 was well-tolerated, with the most common adverse events including fatigue, rash, diarrhea, nausea, cough, joint pain, fever, and itching. Seven grade 3/4 events were reported as potentially immune-related."
go TO FULL ARTICLE
DON'T SLEEP AT THE WHEEL,
THE WORLD IS MOVING A BIT FASTER!
SAN ANTONIO, Texas — Omalizumab (Xolair, Roche, Genentech,
Novartis) appears to be safe and effective in the treatment of chronic
idiopathic urticaria that is refractory to antihistamines, according to
new phase 3 clinical trial results.(from Medscape)
Safety Of Triclosan, Antibacterial Soap Ingredient, Being Reviewed By FDA
It's a chemical that's been in U.S. households for more than 40 years, from the body wash in your bathroom shower to the knives on your kitchen counter to the bedding in your baby's bassinet... The agency's review comes amid growing pressure from lawmakers, consumer advocates and others who are concerned about the safety of Triclosan. Recent studies of Triclosan in animals have led scientists to worry that it could increase the risk of infertility, early puberty and other hormone-related problems in humans. By MATTHEW PERRONE
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