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Prof Trevor Marshall
Foundation Staff
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Posted: Fri Dec 18th, 2009 06:02 |
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http://bit.ly/8Lfj5y"The renin-angiotensin pathway plays an important role in promoting cancer growth, explained Dr. Chae on December 11. The AT1 receptor is functionally expressed in several tumor types, including ovarian cancer. Prior retrospective studies have documented lower cancer incidence among users of ACE inhibitors/ARBs compared with nonusers, and 1 randomised trial showed a protective effect of these agents on the development of major skin cancers, he said. No studies, however, have looked at the relationship between ACE inhibitors/ARBs and cancer recurrence. For the study, Dr. Chae and colleagues reviewed the medical records of female patients diagnosed with stage II/III breast cancer at Albert Einstein between 1999 and 2005, and who later reached no evident disease (NED) after curative therapy. A user of ACE inhibitors/ARBs was defined as a patient who took the medication in the NED stage for at least 6 months. The mean follow-up period was 4.4 years and the maximum follow-up was 9.8 years. About one-fourth (23.3%) of the patients, overall, were prescribed an ACE inhibitor or ARB, including 49.0% of the 164 patients with hypertension. Fourteen percent (23/164) of the women who took either an ACE inhibitor or ARB developed a tumour recurrence, compared with 23.3% (125/541) of nonusers ([P = .01).
The 5-year disease-free survival was 0.85 in the ACE inhibitor/ARB users and 0.756 in the nonusers (P < .01)"
75 to 85% survival rate at 5 years. Interesting data in and of itself.
One of the problems with studies like this is that they clump all the drugs into one class - for example - 'ARBs' - without realizing that each of the ARB drugs is a little bit different. They also assume that ACEI have a similar mechanism of action - a sad commentary on the lack of precision in modern medicine.
Still - this is confirmation that Benicar should not increase the rate of relapse with cancers, even if it doesn't yet have the (study) strength to back up my suspicions as to why the MP has essentially wiped out metastasis in our cohort...
http://www.youtube.com/watch?v=y8AfUg3aJVk
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Freddie Ash
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Posted: Fri Dec 18th, 2009 09:19 |
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HI ALL
This is Fred in WV . I just got my email from the Doctor's Guide today and that is the main story in it. Thanks for posting that for all to see. Another reason to take Benicar.
Remember, we are all in this together and I am pulling for us.
Your friend in Sarcoidosis
Freddie
____________________
Freddie: dx-sarc 2/82 lymph; skin, eyes, joints, esophagus, intestines, spleen, heart,lungs-25D-7; 125-D43
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Bane
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Posted: Fri Dec 18th, 2009 12:59 |
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Impact of angiotensin I converting enzyme inhibitors and angiotensin II type 1 receptor blockers on survival in patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy.
http://www.ncbi.nlm.nih.gov/pubmed/19399518
Application of angiotensin II receptor blocker in prostate cancer
http://www.ncbi.nlm.nih.gov/pubmed/19348246
Ets-1 and hypoxia inducible factor-1alpha inhibition by angiotensin II type-1 receptor blockade in hormone-refractory prostate cancer.
http://www.ncbi.nlm.nih.gov/pubmed/19760626
Angiotensin II Type 1 Receptor Antagonist as an Angiogenic Inhibitor in Urogenital Cancer.
http://www.ncbi.nlm.nih.gov/pubmed/19463103
Synergistic inhibitory effect of gemcitabine and angiotensin type-1 receptor blocker, losartan, on murine pancreatic tumor growth via anti-angiogenic activities.
http://www.ncbi.nlm.nih.gov/pubmed/19578777
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Ruth Goold
Health Professional
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Posted: Fri Dec 18th, 2009 14:06 |
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And here is some info on (one of the) ways in which olmesartan (Benicar) mediates it's anticancer effects:
The Host Defense Peptide Cathelicidin Is Required for NK Cell-Mediated Suppression of Tumor Growth
http://www.ncbi.nlm.nih.gov/pubmed/19949065
And from the same issue of the Journal of Immunology, yet another study outlining a clever way in which intracelluar pathogens compromise the immune response (albeit, in mice in this case):
Dissemination of Mycobacteria to the Thymus Renders Newly Generated T Cells Tolerant to the Invading Pathogen
http://www.ncbi.nlm.nih.gov/pubmed/19949112
Happy Holidays,
Ruth
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03/02/07 Ph 1 MP; 2001: Pulmonary sarc; 01/04/07: 125 D=110pmol/L(45.8 pg/ml)| 25D=20.8 ng/ml: 04/07 19.2: 07/07 11?: 09/07 16.5: 11/07 <10.0: 01/08 <10.0: 05/08 10 ng/ml. Ca. Elocom (ears). diphenhydramine 25 mg. Adidas EE glasses outside. NoIRs
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Prof Trevor Marshall
Foundation Staff
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Posted: Fri Dec 18th, 2009 14:31 |
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Ah yes, the Thymus - so they can pervert the function of AIRE
Great find Ruth - I just hadn't put two and two together...
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ChrisMavo
Member
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Posted: Fri Dec 18th, 2009 15:16 |
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Great STUFF!
So not only can we cure ourselves from chronic Th1 diseases... but we can protect ourselves from the Big C too....
Great stuff INDEED!!!
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PLS/ALS, speech difficulty, dizziness, leg weakness, overly emotional, Ph1Aug2609,11/2012 25D-12, 11/11: 25D-10, 04/11: 25D-11, 07/10: 25D-13, 05/10: 25D-15, 11/09: 25D-20, 9/09: 25D-27, 7/09: 25D-38, 1,25D-46, Mod Ph2Oct09, 100mg Mino
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Phil Schoner
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Posted: Sun Dec 20th, 2009 06:07 |
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Trevor,
You state "the MP has essentially wiped out metastasis in our cohort..."
Epidemiologically speaking, have we developed the percentages of expected cancer metastasis in the cohert versus the (nearly?) zero percent experienced?
Phil
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Phil Schoner, MP Support Spouse, no symptoms, 1,25D 74 5/08, 25D 16 12/08, 25D 16 7/09, 25D 15 2/10, ph1 11/08, ph2 12/08, ph3 7/09, started discontinuance of Benicar 12/28/11. NoIR's, sunscreen Went off MP 1/11/2012
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Prof Trevor Marshall
Foundation Staff
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Posted: Sun Dec 20th, 2009 06:41 |
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Phil,
Different sources have different expectations. The one that seems to be most reliable is an expectation of 10 % to 30% of autoimmune disease patients will die from cancer within a decade. This is also in line with the overall cancer death-rate in CFS patients.
I break this down to a year-by year average expectation of 1% to 3%. For our current reporting cohort size of 700+ this would lead to an expectation of 7 to 21 cases a year.
We are well below that Whether total cancers or just metastasizing cancers (the ones which lead to death) are considered in the total...
One of the biggest problems this cohort faces is that they are pushed (by oncologists) to accept treatments for a non-metastasizing tumor regardless of whether those treatments will exacerbate their underlying inflammatory disease, and thus eventually fuel the metastasis. We need to work on getting together enough case histories so that MP cohort members don't panic when Doc considers a potential "cancer" diagnosis.
We have been walking around for decades without the probing and testing and imaging that Doc has available these days. We should not be surprised if all this new technology finds tumors, some of which may have been there for years... The key is to focus on whether they present a future danger of spreading (metastasis)...
..Trevor..
Last edited on Sun Dec 20th, 2009 09:43 by Prof Trevor Marshall
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Bane
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Posted: Sun Dec 20th, 2009 07:44 |
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http://www.ncbi.nlm.nih.gov/pubmed/18677709
http://www3.interscience.wiley.com/cgi-bin/fulltext/121359256/PDFSTART
Last edited on Sun Dec 20th, 2009 09:40 by Bane
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Joyful
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Posted: Sun Dec 20th, 2009 09:37 |
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Bane, your link is to a pay-to-view article. 
Would you care to summarize here?
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Bane
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Posted: Sun Dec 20th, 2009 09:57 |
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Joyful wrote: Bane, your link is to a pay-to-view article.
Would you care to summarize here?
"To investigate the effect of Ang-III on human prostate cancer cells, we applied it in LNCaP (androgen-dependent) and DU145 (androgen-independent) cells. As shown in Figure 2A,B, Ang-III treatment increased both prostate cancer cells in a dose-dependent manner. Because earlier reports indicated that Ang-III can bind to theAT1 receptor,which is predominantly for Ang-II (Fig. 1) [16], we investigated the effect of an AT1 receptor blocker on cell proliferation induced by Ang-III. Olmesartan is a selective blocker of the AT1 receptor and is widely used as anti-hypertensive agent. As shown in Figure 2A,B, olmesartan significantly suppressed the cell growth induced by Ang-III treatment in prostate cancer cells."
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jrfoutin
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Posted: Sun Dec 20th, 2009 14:09 |
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"75 to 85% survival rate at 5 years. Interesting data in and of itself.
"One of the problems with studies like this is that they clump all the drugs into one class - for example - 'ARBs' - without realizing that each of the ARB drugs is a little bit different.."
Along with lumping ARBs together, there is no discussion of atypical dose for any ARB. The study assumption for the full ARB set they lump is standard ARB dose, right?
The MP cohort daily ARB intake has always been on the line. With a void annual 7-21 cohort cancer record to date, might it be appropriate already--specific to study strength--to state more Benicar (typical MP dose levels with extra when needed) is simply not leading to cancer?
Thank you Dr Marshall and others for excellent discussion and links--Janet
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Sarcoidosis 125D61, MP10/05 ModP2 12/05 Ph2 6/06 Ph3 10/06, NoIRs limited outings covered, 2/08 25D6.2, 10/08 25D6.9, 7/20 25D<7 1,25D 23.8
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Bane
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Posted: Fri Dec 25th, 2009 10:08 |
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Dr Trevor Marshall wrote: Phil,
Different sources have different expectations. The one that seems to be most reliable is an expectation of 10 % to 30% of autoimmune disease patients will die from cancer within a decade. This is also in line with the overall cancer death-rate in CFS patients.
I break this down to a year-by year average expectation of 1% to 3%. For our current reporting cohort size of 700+ this would lead to an expectation of 7 to 21 cases a year.
We are well below that Whether total cancers or just metastasizing cancers (the ones which lead to death) are considered in the total...
One of the biggest problems this cohort faces is that they are pushed (by oncologists) to accept treatments for a non-metastasizing tumor regardless of whether those treatments will exacerbate their underlying inflammatory disease, and thus eventually fuel the metastasis. We need to work on getting together enough case histories so that MP cohort members don't panic when Doc considers a potential "cancer" diagnosis.
We have been walking around for decades without the probing and testing and imaging that Doc has available these days. We should not be surprised if all this new technology finds tumors, some of which may have been there for years... The key is to focus on whether they present a future danger of spreading (metastasis)...
..Trevor..
Immunological Similarities between Cancer and Chronic Fatigue Syndrome: The Common Link to Fatigue?
http://www.ncbi.nlm.nih.gov/pubmed/20032425
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Bane
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Posted: Mon Feb 8th, 2010 07:13 |
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Blocking Angiotensin II Type 1 Receptor Triggers Apoptotic Cell Death in Human Pancreatic Cancer Cells.
http://www.ncbi.nlm.nih.gov/pubmed/20118823
Angiotensin II regulates the expression of monocyte chemoattractant protein-1 in pancreatic cancer cells.
http://www.ncbi.nlm.nih.gov/pubmed/19816747
Inhibition of angiotensin II receptor 1 limits tumor-associated angiogenesis and attenuates growth of murine melanoma.
http://www.ncbi.nlm.nih.gov/pubmed/19771429
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Bane
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Posted: Sun Feb 28th, 2010 13:30 |
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Association of ACE inhibitors and angiotensin receptor blockers with keratinocyte cancer prevention in the randomized VATTC trial.
http://jnci.oxfordjournals.org/cgi/content/full/100/17/1223
"Among a high-risk group of veterans, users of ACE inhibitors or ARBs had a lower incidence of keratinocyte cancers than nonusers. The more pronounced reduction among those who initiated use during the study may indicate an immediate effect."
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Bane
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Posted: Fri Apr 2nd, 2010 08:01 |
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Angiotensin II regulates the expression of monocyte chemoattractant protein-1 in pancreatic cancer cells.
http://www.ncbi.nlm.nih.gov/pubmed/19816747
In this study, we investigated the potential proinflammatory role of AngII in PDA through studying its effect on MCP-1. AngII significantly increased the expression of MCP-1 mRNA and protein in PDA cells and induced its promoter activity. Constitutive and AngII-induced MCP-1 transcription was inhibited by an AngII type 1 receptor (AT1R) blocker, but was unchanged by an AT2R blocker. AngII activated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, but not p38 or c-Jun NH2-terminal mitogen-activated protein kinases. Inhibition of ERK1/2 activation reduced the AngII-induced MCP-1 synthesis. AngII induced the activation and nuclear translocation of nuclear factor-kappaB (NF-kappaB), an effect that was inhibited by AT1R blockade. Inhibition of NF-kappaB by pyrrolidine dithiocarbamate decreased the AngII-mediated increase in MCP-1 mRNA. Our data provide a novel insight into an AngII-initiated signal transduction pathway that regulates MCP-1 as a possible inflammatory mechanism in PDA and suggest that AngII blockade may regulate chemokine-induced signal transduction to prevent or reduce inflammation in PDA.
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Phillyguy
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Posted: Fri Apr 2nd, 2010 10:45 |
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With respect to NFKB, I have a question that has been troubling me for some time. While we know that inhibition of this transcription factor blocks the expression of various inflammatory cytokines, I believe the pathway is also required for Toll like receptor and NOD signalling.
For example, if the VDR is activated, the intracellular pathogen recognition receptor NOD2 will be expressed. However, if NOD2 senses bacteria, then it is unable to signal for the expression of human beta defensin 2 as this requires NFKB. My unerstanding is that TLR2 also signals in a NFKB dependent manner.
That being said, I've read that the cathelecidin promoter has 3 VDREs and no NFKB sites. Many viruses also rely upon NFKB signalling so blockade of this factor is probably beneficial in viral infection.
I wonder if one of the reasons that less frequent dosing is more painful for us (in addition to increased inflammatory cytokines) is due to heightened PRR signalling via a relaxed NFKB blockade.
So my question is if there is any concern about knocking out the TLRs and NODs via NFKB blockade?
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Prof Trevor Marshall
Foundation Staff
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Posted: Fri Apr 2nd, 2010 11:14 |
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We don't 'blockade' NuclearFactor-kappaB, we just suppress its expression A body on Olmesartan can still mount a robust defense, if attacked by acute pathogens
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Phillyguy
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Posted: Fri Apr 2nd, 2010 11:19 |
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| Fair enough!
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Bane
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Posted: Fri Apr 2nd, 2010 12:43 |
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Role of renin-angiotensin system in prostate cancer
http://www.ncbi.nlm.nih.gov/pubmed/19692759
Although a low prevalence of cancer in hypertensive patients receiving angiotensin converting enzyme inhibitors was reported, the molecular mechanisms have not been elucidated.
Angiotensin II up-regulates PAX2 oncogene expression and activity in prostate cancer via the angiotensin II type I receptor.
http://www.ncbi.nlm.nih.gov/pubmed/19517575
CONCLUSIONS: Therefore, PAX2 may be a novel therapeutic target for the treatment of carcinomas such as prostate cancer via the down-regulation of its expression by targeting the AT1R signaling pathways.
AGTR1 overexpression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689309/
In addition to prioritizing ERBB2, we found AGTR1, the angiotensin II receptor type I, to be markedly overexpressed in 10-20% of breast cancer cases across multiple independent patient cohorts. Validation experiments confirmed that AGTR1 is highly overexpressed, in several cases more than 100-fold. AGTR1 overexpression was restricted to estrogen receptor-positive tumors and was mutually exclusive with ERBB2 overexpression across all samples. Ectopic overexpression of AGTR1 in primary mammary epithelial cells, combined with angiotensin II stimulation, led to a highly invasive phenotype that was attenuated by the AGTR1 antagonist losartan. Similarly, losartan reduced tumor growth by 30% in AGTR1-positive breast cancer xenografts. Taken together, these observations indicate that marked AGTR1 overexpression defines a subpopulation of ER-positive, ERBB2-negative breast cancer that may benefit from targeted therapy with AGTR1 antagonists, such as losartan.
Local angiotensin II-generation in human gastric cancer: correlation with tumor progression through the activation of ERK1/2, NF-kappaB and survivin.
http://www.ncbi.nlm.nih.gov/pubmed/19424575
Angiotensin II stimulates the cell proliferation in the AT1 receptor-positive OCUM2MD3 gastric cancer cell line and this proliferative effect of angiotensin II was inhibited by a specific AT1 receptor antagonist, candesartan.
Blockade of an angiotensin type I receptor enhances effects of radiation on tumor growth and tumor-associated angiogenesis by reducing vascular endothelial growth factor expression.
http://www.ncbi.nlm.nih.gov/pubmed/18691848
These results suggest that combination of radiation with AT1-R blockade markedly reduced the LLC growth rate, and that this was due to reduction of neovascularization by reducing VEGF levels. Combination therapy consisting of radiation and AT1R blockade may become an effective novel strategy for cancer treatment.
Potential role of Renin-Angiotensin-system for tumor angiogenesis in receptor negative breast cancer.
http://www.ncbi.nlm.nih.gov/pubmed/18395779
In conclusion, it is hypothesized that Angiotensin II may be involved in regulation of tumor angiogenesis especially in receptor negative breast cancer by regulation of angiogenesis associated genes via At(1)R. These findings are the first evidence for targeting tumor angiogenesis by inhibition of At(1)R in receptor negative human breast cancer cells and may lead to new therapeutical anticancer strategies based upon inhibition of At(1)R.
Angiotensin II induces oxidative stress in prostate cancer.
http://www.ncbi.nlm.nih.gov/pubmed/18314486
The hypothesis that angiotensin II has the potential to induce oxidative stress, which may be implicated in carcinogenesis of the prostate gland through long-term exposure to chronic inflammation is proposed.Last edited on Fri Apr 2nd, 2010 12:51 by Bane
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