The newest dr. Antoine Sayegh declarations on the cancer treatments and for the aids also

The newest dr. Antoine Sayegh declarations on the cancer treatments and for the aids also :
http://sayeghresearches.wetpaint.com/
http://antsay.webs.com/sayeghresearches.htm

My great dear:
please contact me on these E-mails in the same time to confirm your sending of your e-mails to me
E-mails:
antsay@aloola.sy
dr.antoine7sayegh@dcemail.com
dr.antoine7sayegh@yahoo.com
dr.antsay@gmail.com
the websites :
https://www.facebook.com/people/Antoine-Sayegh/100002063614016
http//:sayeghresearches.wetpaint.com
http//:antsay.webs.com
with the best regards from the dr. Antoine Sayegh
http://antsay.webs.com/apps/photos
http://sayeghresearches.wetpaint.com/photo/11223556/internatinal+certificate
http://www.iainternalmeds.com/certificate.6128612.html
The newest dr. Antoine Sayegh declarations on the cancer treatments and aids also :
I call all the cancer research centers of the world to concentrate on my new suggestions in their trials on cancer and on aids also :
We must use the combinations from many drugs which act on the ( Myristate , farensyl ,glucosylphosphatidylinositol ) in the same time in the protection from cancers which promise us for the new the treatments for the aids and the cancer also.
The membrane-attached proteins divided into three groups:
1.group A : bound to the cytosolic face of the plasma membrane by myristate as v-Src is a kind of non-receptor protein tyrosine kinase involved in cell signaling:
1.we must get more benefits from the properties of the Dihydropyridine-type calcium-channel antagonists (DTCCA) which plays an important roles in many diseases , because they decrease vasospastic propensity. These drugs are suspected to have anti-oxidant properties in other diseases as in the systemic sclerosis . that nifedipine and nicardipine decrease circulating markers of oxidative stress damage in patients.. the effects of nifedipine on O2•- release from human monocytes, on protein phosphorylation with phorbol myristate acetate (PMA) as stimulator and on protein kinase C (PKC) activity, This beneficial property of nifedipine seems to be mediated by its cellular action and by the inhibition of PKC activity,so we can use this drugs against the diseases which associate with the oxidative harms. ( Paris V University, Cochin Hospital, Cochin Institute,france)
2.we must get more benefits also from the relations from the Phorbol 12-Myristate 13-acetate (PMA) and angiotensin II (Ang II)which increased both the percentage of scavenger receptors Scr-positive cells and the Scr mean fluorescence intensity. PMA and Ang II also increased Scr mRNA and promoter activity in a time- and dose-responsive manner. Protein kinase C and calmodulin transduction pathways were involved in Scr up-regulation induced by PMA and Ang II. Additionally, a serine/threonine kinase was involved in PMA stimulation. Functional analysis showed that both AP-1 and ets motifs were specific response elements to PMA stimulation in HMCLs ,so the drugs which change the relations between the PMA and the ANGII which inhibits the actions of the ANGII can breaks down the transduction pathways (Center for Nephrology, Royal Free and University College Medical School, Royal Free Campus, London, England, United Kingdom)
2. group B:bound to the cytosolic face of the plasma membrane by farnesyl as Ras protein which also plays a key role in cell signaling:
From my participation with Webinar on the antitumor effects of the biophosphonate in breast cancer
1. The gene on the chromosome 1 and the location q22 encodes an enzyme that catalyzes the production of geranyl pyrophosphate and farnesyl pyrophosphate from isopentenyl pyrophosphate and dimethylallyl pyrophosphate. The resulting product, farnesyl pyrophosphate, a substrate for protein farnesylation and geranylgeranylation, Drugs Zoledronic acid is an amino-bisphosphonate that inhibit this enzyme FPP [farnesyl diphosphate] synthase prevent the post-translational modifications of small GTPases and have been used to treat diseases related to bone resorption. Multiple pseudogenes have been found on chromosomes 1, 7, 14, 15, 21 and X. Multiple transcript variants encoding different isoforms have been found for this gene .so we can can the Bisphosphonates as clodronate and zoledronic acid to inhibit also the other isoforms .
2.the second point to avoid the the harm effects on the normal cells from the uses of the Bisphosphonates as clodronate and zoledronic acid , we can use the antibodies against the FPP [farnesyl diphosphate] synthase as in my theoretic researches for temporary periods instead of the biophosphonates
Please visit the all researches I and all researches II on my website
http://sayeghresearches.wetpaint.com/
http://sayeghresearches.wetpaint.com/forum
3.from the effects of the uses of the biophosphonates on the relation the FPP [farnesyl diphosphate] synthase as a molecular partner for p13(II) and G4 accessory proteins which opens new prospects for treatment of retrovirus-induced leukemia HTLV1 p13(II) not on cancer but on the retroviruses also
4, the HMG-CoA reductase inhibitors (statins) as an anticancer drugs: from the international researches we found : ( University of Mainz, Germany )
Apart from their lipid lowering activity, HMG-CoA reductase inhibitors (statins) impair numerous cellular functions associated with metastasis, e.g. gene expression, angiogenesis, cell adhesion, cell motility and invasiveness. Furthermore, statins have impact on apoptotic cell death and modulate cellular susceptibility to cell killing by anticancer drugs and ionizing radiation. Part of the effects provoked by statins are due to the inhibition of the prenylation of low molecular weight GTPases, in particular Ras and Rho, which play key roles in signaling evoked by stimulation of cell surface receptors. C-terminal lipid modification of Ras/Rho GTPases is essential for their correct intracellular localization and function. By depletion of the cellular pool of isoprene precursor molecules, statins reduce the level of membrane-bound active Ras/Rho proteins, thereby impairing corresponding functions. Since broad clinical experience already exists for statins, their incorporation into established tumor-therapeutic regimens would be realizable in a rather short period of time. Here, data available at present arguing for the usefulness of statins in anticancer therapy are summarized and discussed.
3. group C: bound to the extracelluar face of the plasma membrane by glycosylphosphatidylinositol;(dr. Antoine Sayegh clinic Aleppo ,Syria)
1.the amlodipine acts as Calcium channels blockers (CCB) which inhibits for the CA++ to enter intracellular from many mechanisms by the blocking the voltage channels dependent for the CA++ or from the acting on the receptor channels dependent for CA++ ,and from the other actions of the CCB on the relations between the CA++ and the IP3 which plays an important roles on its formation from the PIP2 to IP3 + DAG and on its receptors ( ip3)also from the effects of the CA++ on the ubiquitin proteasome pathway ,so from the last roles of the CCB which inhibits the actions of the CA++ on the relations between the CA++ and the IP3 and on the also IP3 receptors So we can we use the CCB for the treatment for the cancers ,because the IP3 and the CA++ with the relation with the calcineurin and the active NFAT help for the genes transcription , so ,we must study the patients which treated from the CCB and we must evaluate the ratios of the cancers in these groups of the patients ( the ratios in this group very very low ) ,also from the roles of the multiple kinase as the(calcium/calmodulin-dependent protein kinase (CaMK),with the other proteinkinase as protein kinase D (PKD), microtubule affinity-regulating kinase (MARK), salt-inducible kinase (SIK), checkpoint kinase-1 (CHK1) and other kinases) mediate specific phosphorylation of human histone deacetylase-4 (HDAC4) on three 14-3-3-binding sites. Myosin phosphatase-targeting subunit-1 (MYPT1)–protein phosphatase-1 (PP1) and PP2A can also act on these sites. The association of 14-3-3 proteins with HDAC4 retains it in the cytoplasm and prevents its interaction with transcription factors such as myocyte enhancer factor-2 (MEF2), thereby releasing these transcription factors for transcriptional activation. So when we inhibits the (calcium/calmodulin-dependent protein kinase (CaMK)which acts with other mechanisms in the signaling of the CA++ for the translations and for the transductions or transcription on the genes by the STAT or SMAD4 pathways
2. we use the angiotensin converting enzyme inhibitors (ACEI) with the CCB so to get the most important synergistic effects from their combination , and because the ACEI inhibits the actions of the Ang II ,and from the relation from the Ang II on the ATII receptor and on the ATI receptor especially also ( angiotensin I receptor) which excite the formation of the IP3 also from the PLC which acts to form the IP3 and the DAG from the PIP2,so the IP3+ the CA++ and the DAG activates the PKC which play as the vasoconstrictive roles in the hypertension ( HT) , so when we use the combination from the ACEI +CCB we get the best effects on the HT from the vasodilatation roles and from the indirect effects on the IP3 formation, so we can use the ACEI + CCB in the treatment of the cancer in the futures also .
3.the most important notices for the treatments for the cancer from two new ways : a. the neprilysin path ways :(from the mechanism of degradation ) which convert the GTP to c GMP with the CA++ which act as vasodilatation:
1.the first way: the neprilysin(nep) activate( degradation )the ANP which convert the GTP to c GMP .
2.the second way :the nep acts ( degradation) on the BK to BK2and the BK2 NOS convert the L Arg to NO (nitrous oxide ) which also convert the GTP to c GMP with the CA++ to dilate the vessels. So the drugs which activate the neprilysin pathways cause the vasodilatation with the important roles of the NO on the genes
2. the effects of the :
a. angiotensin converting enzyme inhibitors (ACEI)which decrease the breakdown of the bradykinin.
b. the calcium channels blockers (CCB ) which increase the synthesis of the bradykinin . the bradykinin which binds to the b2 kinin receptors which acts as:
1. on the coronary epithelium activate the intracellular NO synthase and to release the endothelium derived NO.
2.on the myocardium : diffuses of the NO in the myocytes and regulates the mitochondrial respiration .
But the NO in the tissues plays an important roles in the cancers because the macrophages :these cells activated by the cytokines or by the TNF which produces the nitric oxide ( NO ) which kills the organisms ( for the aids viruses also) and the malignant cells ( cancers )and the macrophages which aid and which did not aid also by the antibodies .
So the most important uses of the combination from the ACEI with the CCB in the future to treat the different cancers and for the different organisms like the aids also .
4. can we use the combination also for the treatment for HT as before between the ACEI plus angiotensin II receptor blockers( ARB) to get more synergistic effects when we face the genetic mutations on the ANG gene, Ang I and Ang I receptor genes ,or on the ADDI ( adducin gene )??? . Please answer me as fast as you can
The newest relations between the Calcium channels blockers (CCB) and the angiotensin converting enzyme inhibitors (ACEI) with the transcription factor nuclear factor E2-related factor 2 (Nrf2) directly or indirectly as anti oxidant or anti cancer
The proofs :
1. Nrf2 is a protein messenger contained in every cell of the body that sends information to the cell’s DNA, When this protein messenger called Nrf2 is activated, it enters the nucleus of every cell and it turns on several hundred of the DNA genes. And the genes that it turns on, or turns up, are known collectively as “survival genes.” These genes enable cells to survive in the face of several different kinds of stress, especially oxidative stress which is due to the over production of free radicals and other oxidants. many researches confirm my declaration of the link :
WikiGenes - NFE2L2 - nuclear factor (erythroid-derived 2)-like 2.mht
2. Flunarizine induces Nrf2-mediated transcriptional activation of heme oxygenase-1 in protection of auditory cells from cisplatin
H-S So, H-J Kim, J-H Lee, J-H Lee, S-Y Park, C Park, Y-H Kim, J-K Kim, K-M Lee, K-S Kim, S-Y Chung, W-C Jang, S-K Moon, H-T Chung and R-K Par
Pretreatment with flunarizine predominantly induced the transcriptional expression of HO-1 among other Nrf2-regulated genes in cisplatin-treated cells. (a) Cells were treated with 20 M cisplatin for the indicated periods in the presence or absence of 10 M flunarizine. Then, total RNA was isolated by RNAzol and cDNA was synthesized by reverse transcriptase. The Nrf2-related genes, including HO-1, NQO1, GCLC, GCLM, GST-1, and GSTA4, were amplified with specific primer sets, respectively. Also, cells were treated with 20 M cisplatin, 10 M flunaizine and various doses of SnPPIX for 36 h and used to measure the cell viability (b), to determine the enzymatic activity of HO-1 at 20 h (c), or to test the expression level of HO-1 protein by Western blotting (d). # P<0.01, ** P<0.01 by one-way ANOVA, compared with only cisplatin treated group (#) or flunarizine/cisplatin-cotreated group (*, **). (e) To examine the effect of calcium channel blockers on the HO-1 induction, cells were treated with various calcium channel blockers for 24 h. Cell lysates were separated on 12% SDS-PAGE to probe for HO-1 and -actin by Western blot. Nicardipine, 10 M; nifedipine, 12.5 M; ditiazem, 10 M; pimozide, 2.5 M
3. Nitric oxide activation of Keap1/Nrf2 signaling in human colon carcinoma cells
Chun-Qi Li Min Young Kim Luiz C. Godoy Apinya Thiantanawat Laura J. Trudel Gerald N. Wogan
The transcription factor NF-E2-related nuclear factor 2 (Nrf2) regulates expression of genes that protect cells from oxidative damage. Here, we characterized nitric oxide (•NO)-induced Nrf2–Kelch-like ECH-associated protein 1 (Keap1) signaling and its role in counteracting •NO-induced apoptosis of human colon cancer HCT116 cells. Nrf2 was localized in the cytoplasm in control cells; •NO triggered its rapid nuclear accumulation, transcriptional activation, and up-regulation of HO-1, NQO1, and GCL, but not GST A4 and P1 subunits. Nrf2 accumulation in the nucleus was also associated with enhanced transcription and posttranscriptional modifications. (S)-nitrosation of Keap1 may contribute to nuclear accumulation of Nrf2 by facilitating its dissociation from Keap1, thus initiating •NO-mediated Nrf2–Keap1 signaling. •NO-mediated induction of ARE-dependent genes occurred well before apoptosis, as judged by caspase 3 activation. Collectively, these results show that the Nrf2–Keap1 signaling pathway mediates protective cellular responses to mitigate •NO-induced damage and may contribute to the relative resistance of HCT116 to •NO-induced cytotoxicity.

4.the researches from
iHOP - Information Hyperlinked over Proteins [ NPPA ].mht
a. To verify the hypothesis that the angiotensin converting enzyme (ACE) level may affect the metabolism of circulating atrial natriuretic factor (ANF), the acute and chronic effects of benazepril on plasma ANF levels were studied in hypertensive patients under basal conditions and in response to acute volume expansion

b. Atrial natriuretic peptide (ANP ), C-type natriuretic peptide, and C-ANP-(4-23), a ligand for the natriuretic peptide clearance receptor, equipotently inhibited production of VEGF by as much as 88% and inhibited ET- or hypoxia-stimulated VEGF transcription
c. Atrial natriuretic peptide (ANP) has been shown to reduce tumor necrosis factor-alpha (TNF-alpha)-induced activation of endothelial cells via inhibition of p38 mitogen-activated protein kinase (MAPK ) and nuclear factor (NF)-kappaB pathways.
d. Atrial natriuretic factor 1-28 (ANF) and C-type natriuretic factor-22 (CNP) reduced angiotensin II (Ang II)- and platelet-derived growth factor-stimulated PAI-1 mRNA expression in rat aortic smooth muscle cells by 50% to 70%, with corresponding reductions in PAI-1 protein release
e. Arial natriuretic factor ANP evoked production of superoxide was found to activate c-Jun N-terminal kinase (JNK).

f. Atrial natriuretic peptide (ANP)-C receptor activation has been shown to inhibit adenylyl cyclase (AC) activity as well as to stimulate phospholipase C (PLC) signaling pathways.

5.researches from :

WikiGenes - Evolutionary Knowledge.mht
1. NFE2L2 - nuclear factor (erythroid-derived 2)-like 2
Gene: induction via Nrf2 activation in hepatoma cells. Early effects( only 1 h of exposure) of Disease relevance of NFE2L2 Human prx1 gene is a target of Nrf2 and is up- regulated by hypoxia/ reoxygenation: implication to tumor biology. Neuroblastoma cells were stably transfected with DN- Nrf2, which/ Synonyms: NRF2

2. MAPKAP1 - mitogen-activated protein kinase...
Gene: Physical interactions of MAPKAP1 Transfection of PC12 cells with dominant- negative Nrf2 abolished the SIN- 1- induced increase in Nrf2- ARE binding and subsequent upregulation of HO- 1 expression, leading neuroblastoma cells( TAM- 67 cells) to apoptosis induced by the nitric oxide( NO)

3. Hmox1 - heme oxygenase (decycling) 1
Gene: stress induced the nuclear import of Nrf2 and the binding of Nrf2 to the HO- 1 antioxidant and inducible nitric oxide synthase( iNOS) expression in the aortas of ovariectomized rats, and the regulatory heme oxygenase( HO) and calcium- dependent nitric oxide synthase( cNOS) activities were increased

With the best regards from the dr. Antoine Sayegh

The new dr. Antoine Sayegh methods for treatments from the stem cells:
http://sayeghresearches.wetpaint.com/page/The+new+dr.+Antoine+Sayegh+methods+for+treatments+from+the+stem+cells%3A
http://antsay.webs.com/
the aims for the treatments :
1.to use the new methods for the treatments of the chronic and for the fatal diseases also.
2.for the new hopes in the treatments for the different cancers from the killer cells( K cells ,LAK cells ), in the bone marrow suppressions ,and for the aids also from the new created of the CD4 cells .
3.to replace the harmed cells in the different tissues from the infective diseases .
4.to open the new treatments in the future for the hereditary diseases.
The sources of the stem cells
1. from placenta.
2. from the adults bone marrow and from the adipose tissues .
3. from the cloning from the somatic cell nucleus transfer to the unucleated ovum as a new totipotent cells which form the blastocyte which gave us the new stem cells .
4.the methods of the dr. James Thompson : to get the pluripotent cells from the blostocyte.
5. the methods of the dr. John Gearhart :to get the stem cells from the embryonic germ cells .
The methods which isolate and purify human of the different stem cells from the bone marrow or from the adipose tissues or from other sources, which use different materials for the isolation and for the culture for these cells in the different steps
1. for the processing of the bone marrow mononuclear (adipose , placental) cells.
2. for the magnetic activated cell sorting and for the fluorescence activated cells sorting also.
3.for the culture of the human monoclonal bone marrow cells.
These methods use many harmful materials for the stem cells which weak its metabolic vitalities and can change its normal properties or qualities to shortening its ages and help for the deviation toward the oncogene positions ( as carcinogenic cells in the recipient tissues ) .
The new dr. Antoine Sayegh methods as below:
The first step
:the preparing of the isolated and purified stem cells from the bone marrow:
a. we take the bone marrow from the iliac crest from the human being .
b. we divide the specimen into two parts :
1. we inject the first part in the blood of the animal to form against every component the antibodies the IGM and the IGG to use them later .
2. we incubate the second part (of the bone marrow ) with the animal antibodies which we got it from the first step ( the serum of the animal ) ,and in the same times we incubate the second part with the anti anti bodies the hyper variable part prepared against the anti bodies for the target cells which we need for the isolation like the CD34 or the CD38( from the known isolated cells ) to destroy all the unneeded cells and to protect the target cells .
*****The preparation of the hyper variable part of the anti –antibodies from the ( known isolated target cells like CD34 ,CD38, or for ES embryonic stem cells):
a. we get the antibodies against the markers proteins ( against the known makers proteins of the target cell from any person as the SSEA-3 (Stage-specific embryonic antigen) ,SEA-4,TRA-1-60(Tumor rejection antigen-1) ,TRA-1-81 or the markers of the CD34 ,CD38 )
b. we incubate part of these antibodies with the pepsin to get the Fab(ab)2 the binding antigen sites ,and the other part with the papain to get the fab(ab)1 and the fragment c (FC)to get different types of the FAB parts with the different types of the FC also in the same times ..
c. we incubate the bone marrow of the patient with the different types of the antibodies residues (held on latex) with the different suitable complements proteins to form heavy immune complexes ,we centrifuge the complexes to get from the layer of the latex the target cells .
d. we isolate the target cells from the complexes from the cooling or heating , or from the changes of the ph ,so we get the weakened target cells to use them later to form from them only the anti antibodies.
e. we can use instead of the latex ,the red blood cells held on its surfaces the hyper variable part of the antibodies against the different types of the FABs which act as the target antigens to form with the bone marrow of the patients with different FABs residue with complements proteins also the agglutinations forms of the immune response to collect between its nets the weakened target cells .
3. we incubate and culture the residues of the second part to get more of the target cells with its high vital activities while the other cells weakened and destroyed from the different antibodies from the uses of the STAT 3 factor and Oct-4 transcription factor which activate the LIF receptor to activate LIF –STAT 3 Signaling pathway which promotes Embryonic Stem cell self-renewal . .
4. we isolate the residues from the low speeds by the centrifuge to avoid the harms for the target cells to get the pure target cells because when these cells were cultured it gained very huge masses which precipitate it easily to the bottom of the tube.
5. we wash the cultured cells from the saline or from not harmful fluids (buffers) many times to clean it from the other ineffective attached cells.
The second step:
1. we inject the patients from the vaccine( under the skin) which composed from the anti antibodies( the hyper variable parts of the antibodies ) against the target cells ( CD34,CD38 ,other cells like Embryonic Stem Cells) before many days of the uses of the stem cells ,to destroy every anti bodies against the target cells from the immune response of the uses of the stem cells..
2. we inject the patients from the new purified stem cells with the low numbers ( not millions but hundreds thousands ) to decrease the cost( money payments) of the treatments .
3.we help the recipient tissues to receive the new stem cells with the low numbers ( hundreds thousands ) and to elongate its ages and to embrace into the defected tissues as a new normal cells from:
the next third step : to confirm the new actions of the injected stem cells :
a. by the injection of the angiogenesis factors into the blood of the patients , as FGFs , FGF1( the potent factors for angiogenesis ) and as FGF2 , VEGF factors also and from the TGF beta to help the stem cells to invade the recipient tissues .
b. we inject into the blood of the patients also the helper the HGF and the MET which activates the proliferations of the stem cells with the E-cadherine, or from the uses of the ET-1 ( endotheline-1) which help the stem cells to be accepted from the target tissues .
so the new treatments from the new methods of the isolated stem cells promise us for the best treatments for the fatal diseases in the future which act near the normal cells mechanisms to re repair the defected ( failed ) tissues or organs .
My new E-mails:
antsay@aloola.sy
dr.antoinesayegh@gmail.com
dr.antoine7sayegh@dcemail.com
dr.antoine7sayegh@yahoo.com
dr.antsay@gmail.com
dr.antoinesayegh@mail.com
the websites :
http//:sayeghresearches.wetpaint.com
http//:antsay.webs.com
https://www.facebook.com/people/Antoine-Sayegh/100002063614016

with the best regards from the dr. Antoine Sayegh