By Teresa Conrick
In this series on xenobiotic chemicals, like mercury/thimerosal, and their connection to autism, cancer and neurodegeneration, there are indications that some companies and researchers are racing to the "cure" yet avoiding inconvenient truths. As a result, there is a continuation of denial about the environmental and pharmaceutical toxins -- both man made -- that have their fingerprints on many of these cases of regression into disease. Some would say the fingerprints are on both poison and "cure', as mercury, and especially Thimerosal, are shown to be guilty of causing damage that, for example, Riluzole, via clinical trials, is supposed to fix:
Poison "Within a eukaryotic cell there is careful regulation of the levels of phosphorylation which is controlled by the delicate balance between the activity of protein kinases and protein phosphatases......In this study we show that the thiol-reactive heavy metal HgCl2, known to contribute to the development of autoimmune disorders, induces a rapid and robust activation of tyrosine phosphorylation within human myelomonocytic cells."
Poison "Focal adhesion kinase (FAK) is a signaling molecule associated with cell survival. Previously, we showed that thimerosal, a reactive oxygen species (ROS) generator, can acutely induce FAK tyrosine phosphorylation (within minutes) and chronically induce apoptosis (within days)"
"Cure" The Neuroprotective Agent Riluzole Inhibits NMDA-Induced FAK 125 Tyrosine Kinase Phosphorylation in the Rat Hippocampus
Glutamate: a potential mediator of inorganic mercury neurotoxicity. "Exposure to mercury vapor (Hg0) produces neurotoxic effects which are for the most part subsequent to its biotransformation in brain to the mercuric cation (Hg2 +), which has an exceptionally strong affinity towards the SH groups in proteins. However, neurologic symptoms are often encountered in subjects in which Hg+ concentration in the brain remains in the SUBMICROMOLAR range, markedly below the anticipated threshold for direct inhibition of cerebral metabolism and function. In this report we review biochemical and morphological evidence obtained in this and other laboratories in tissue culture studies suggesting that in such instances mercury neurotoxicity may be mediated by excitotoxic activity of GLUTAMATE (GLU)."
David H. Gorski
Drug Discovery and Development
"The research interests of the Gorski laboratory fall into two broad categories. First, we are interested in the transcriptional regulation of vascular endothelial cell phenotype. Our second area of interest is the role of metabotropic glutamate receptors (mGluRs) in breast cancer. These receptors have traditionally been believed to be restricted to the central nervous system, but our collaborators at Rutgers University and Robert Wood Johnson University first serendipitously observed that mGluR-1 induces melanoma in transgenic mice.... we have noted that mGluR1 is expressed on vascular endothelial cells and have preliminary evidence that its inhibition is also antiangiogenic......"
More evidence based research:
Mercury induces inflammatory mediator release from human mast cells HgCl2 stimulates VEGF ( vascular endothelial growth factor ) and IL-6 release from human mast cells. This phenomenon could disrupt the blood-brain-barrier and permit brain inflammation. As a result, the findings of the present study provide a biological mechanism for how low levels of mercury may contribute to ASD pathogenesis......HgCl2 induced a 2-fold increase in β-hexosaminidase release, and also significant VEGF release....HgCl2 (1 μM) also induced release of significantly more VEGF (182 ± 57 pg/106 cells) from hCBMCs (n = 5, p < 0.05) compared to control cells
Riluzole Inhibits VEGF-Induced Endothelial Cell Proliferation In Vitro and Hyperoxia-Induced Abnormal Vessel Formation In Vivo "PURPOSE. The present study examined the effects of riluzole, a Food and Drug Administration–approved drug for amyotrophic lateral sclerosis, on VEGF-stimulated endothelial cell proliferation in culture, and on neovascularization in a rat model of retinopathy of prematurity (ROP).
RESULTS. Riluzole inhibited VEGF-stimulated PKC (protein kinase c ) ßII activation and cell proliferation in bovine retinal endothelial cell and human umbilical vein endothelial cell cultures. In addition, systemic administration of riluzole substantially ameliorated abnormal new vessel formation in the rat ROP model."
I think it's important to get some pertinent facts about Riluzole/Rilutek.
These are a sample from Sanofi but there are 37 pages to read for a complete picture: (Sanofi Aventis)
< 18 years of age): The safety and efficacy of RILUTEK in any neurodegenerative disease occurring in children or adolescents have not been established....Liver chemistries should be monitored in all patients on RILUTEK as the drug can increase serum aminotransferase, even in patients without a prior history of liver abnormality. Interstitial lung disease: Cases of interstitial lung disease have been reported in patients treated with RILUTEK, some of them were severe....The most commonly observed adverse events associated with the use of RILUTEK, more frequently than with placebo treatment were: asthenia, nausea, elevations in liver function tests,dizziness, decreased lung function, diarrhea, abdominal pain, pneumonia, vomiting, vertigo,circumoral paresthesia, anorexia and somnolence. ...the most commonly reported associated adverse events were nausea, abdominal pain, constipation and ALT elevations...Post-Market Adverse Drug Reactions -This section provides the adverse drug reactions not listed above which have been reported through post-market surveillance. Although a causal relationship with RILUTEK may be suspected, other causes can not be excluded.
: abdominal pain lower, abdominal pain upper, dysphagia,
gastrointestinal disorders, gastrointestinal dysplasia, illeus, illeus paralytic, intestinal functional
disorder, intestinal obstruction, mouth ulceration, oesophagitis, pancreatitis acute
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
: gastric cancer, lung
neoplasm malignant, non-Hodgkin's lymphoma
Nervous System Disorders
: cerebral hematoma, depressed level of consciousness, disturbance
in attention, dystonia, hypoaesthesia, intercostal neuralgia, intracranial pressure increased,
lethargy, loss of consciousness, motor neurone disease, myasthenia gravis, neuropathy
peripheral, poor quality sleep, radiculopathy, sedation, sensory disturbance, somnolence
: anxiety, completed suicide, depression, mental disorder, mental status
change, psychiatric symptom, psychiatric disorder, restlessness
Skin and Subcutaneous Tissue Disorders:
alopecia, drug eruption, hyperhidrosis, pemphigoid,
pruritus, rash, rash popular, skin discolouration, skin exfoliation, skin nodule
It may be helpful to look at a few other evidence-based studies that show positive results with glutamate/VEGF/tyrosine kinase issues (Dr. Gorski calls them "fairy dust") :
"In the present study, we investigated if thiol-reducing agents are capable of altering mercury (Hg2+), lead (Pb2+) and cadmium (Cd2+) effects on platelet glutamatergic system. The findings of the present investigation indicate that dithiol-reducing agents are capable of altering Hg2+, Pb2+ and Cd2+ effects on platelet glutamatergic system. In vitro data on chelating–metal interactions provide only an estimated guide to the treatment of heavy metal poisoning. Consequently, more studies in intoxicated patients are necessary to determine the precise use of the peripheral models and chelating agents."
"The antiangiogenic activity of Piper longum was studied using in vivo as well as in vitro models. In vivo, antiangiogenic activity was studied using B16F-10 melanoma cell-induced capillary formation in C57BL/6 mice. The extract of P. longum at non-toxic concentrations (10 microg/ml, 5 microg/ml, 1 microg/ml) inhibited the VEGF-induced vessel sprouting in rat aortic ring assay. Moreover, P. longum was able to inhibit the VEGF-induced proliferation, cell migration and capillary-like tube formation of primary cultured human endothelial cells. Hence, the observed antiangiogenic activity of the plant P. longum is related to the regulation of these cytokines and growth factors in angiogenesis-induced animals."
Curcumin suppresses breast tumor angiogenesis by abrogating osteopontin-induced VEGF expression Our results indicate that curcumin suppresses OPN-induced VEGF expression and tumor angiogenesis, and suggest that this study may aid in the development of a curcumin-based OPN-targeted therapeutic approach to the control of breast tumor angiogenesis.
"Dietary phytochemicals are known to exhibit a variety of anticarcinogenic properties. This study investigated the chemopreventive activity of blueberry extract in triple-negative breast cancer cell lines in vitro and in vivo.... Blueberry decreased cell proliferation in HCC38, HCC1937, and MDA-MB-231 cells with no effect on the nontumorigenic MCF-10A cell line.... These data illustrate the inhibitory effect of blueberry phytochemicals on the growth and metastatic potential of MDA-MB-231 cells through modulation of the PI3K/AKT/NFkappaB pathway."
"Recent studies indicate that receptor tyrosine kinases (RTKs), which play important roles in cell proliferation, are one of the possible targets of green tea catechins (GTCs) in cancer cell growth inhibition..... The present report reviews evidence indicating that GTCs exert anticancer and chemopreventive effects by inhibiting the activation of specific RTKs, especially EGFR, IGF-1R, and VEGFR2, and concludes that targeting RTKs and their related signaling pathways by using tea catechins could be a promising strategy for the prevention of human cancers."
"The present study examines the modulatory effects of dietary antioxidant vitamin C (VIT C), vitamin E (VIT E) and quercetin on MSG-induced oxidative damage in the liver, kidney and brain of rats.....Simultaneous administration of VIT C, VIT E and quercetin to MSG-treated rats significantly reduced this increase in MDA induced by MSG. VIT E reduced lipid peroxidation most in the liver followed by VIT C and then quercetin, while VIT C and quercetin showed a greater ability to protect the brain from membrane damage than VIT E....The results indicate that dietary antioxidants have protective potential against oxidative stress induced by MSG and, in addition, suggest that active oxygen species may play an important role in its genotoxicity."
"Luteolin, a flavonoid present in various vegetables including onion and broccoli, has been reported to possess anticarcinogenic effects. However, its chemopreventive effect on UV-induced skin cancer and its mechanism are not fully understood... Immunoblot and kinase assay data showed that luteolin attenuated protein kinase C(epsilon) (PKC(epsilon)) and Src kinase activities and subsequently inhibited UVB-induced phosphorylation of mitogen-activated protein kinases and the Akt signaling" pathway."
"Vitamin E (dl-alpha-tocopherol) has been found to inhibit in vitro brain protein kinase c with a half inhibitory concentration of 450 microM. The known plasma concentrations of vitamin E are one order of magnitude lower than the protein kinase c half-inhibitory concentration but it is also known that, at the membrane level where the active protein kinase c is located, the lipophilic vitamin E is more concentrated (Burton, G.W., Joyce, A. and Ingold, K.U. and Locke, S. (1983) Arch. Biochem. Biophys. 221, 281-290). It appears that vitamin E, in addition to its antioxidant function, may play a role in regulating the activity of protein kinase c"
Interesting that VIT E also protects against mercury-
Inhibitory effect of α-tocopherol (Vit E) on methylmercury-induced oxidative stress http://www.ncbi.nlm.nih.gov/pubmed/21432319
"Oxidative stress, especially lipid peroxidation, may play an important role in the cerebellar degeneration process during MeHg intoxication and Vit E may play a protective role against MeHg toxicity as an effective antioxidant."
More oxidative stress protection-
N-Acetylcysteine Protects Melanocytes against Oxidative Stress/Damage and Delays Onset of Ultraviolet-Induced Melanoma in Mice http://clincancerres.aacrjournals.org/content/13/19/5952.full
"Results: NAC (1-10 mmol/L) protected melan-a cells from several UV-induced oxidative sequelae, including production of intracellular peroxide, formation of the signature oxidative DNA lesion 8-oxoguanine, and depletion of free reduced thiols (primarily glutathione). .. Additionally, topical NAC reduced UV-mediated GSH depletion and peroxide induction in normal human skin (17). NAC also seems to have some anticancer effects independent of its role as an antioxidant. It has specifically been shown to decrease VEGF production in melanoma cells in vitro (18) and decrease matrix metalloproteinase activity in invasive tumor cells (19). Thus, in addition to its demonstrated safety record, NAC has the capacity to modulate both UV-induced oxidative stress and carcinogenesis in the skin."
Interesting that N-Acetylcysteine Protects Melanocytes against Oxidative Stress/Damage and Delays Onset of Ultraviolet-Induced Melanoma in Mice AND apparently has been researched for treating MERCURY toxicity:
N-acetylcysteine as an antidote in methylmercury poisoning.
"Methylmercury is a ubiquitous environmental pollutant and potent neurotoxin. Treatment of methylmercury poisoning relies almost exclusively on the use of chelating agents to accelerate excretion of the metal. The present study demonstrates that oral administration of N-acetylcysteine (NAC), a widely available and largely nontoxic amino acid derivative, produces a profound acceleration of urinary methylmercury excretion in mice.
I will continue researching with thoughts of Megan, who is the source of my energy and passion. Her health issues now have me looking at cancer and other neurodegenerative diseases. The implications of causation and treatments for each seem related in many ways. The "race for the cure" of these diseases seems paved with not enough good intentions and unfortunately, too many glutinous wallets. It is time to stop the corruption and revolving door of the Medical Industrial Complex and Government Agencies. Megan is but one of so very many who regressed after vaccinations -- injured, silenced, and left behind as the race to the cure folks count genes, new "cures" for xenobiotic-induced diseases, and money in their banks.
I need to conclude this series with a sobering fact -- we are not only looking at connections in common with autism and cancer - we are looking at autism BECOMING cancer:
"Autism is associated with high rates of genomic aberrations, including chromosomal rearrangements and de novo copy-number variations. These observations are reminiscent of cancer, a disease where genomic rearrangements also play a role. We undertook a correlative epidemiological study to explore the possibility that shared risk factors might exist for autism and specific types of cancer."
"These findings suggest that there may be an association between autism and specific forms of cancer."
More clues to that connection yet where is the CONCERN and OUTRAGE?
Epidermal Growth Factor Receptor (EGFR) Levels Significantly Elevated in Women Who Developed Breast Cancer
Increased Serum Levels of Epidermal Growth Factor in Children with Autism
If you care about the health of your family, your descendants, and Mankind, please join the growing Canary Party. - "It is time for an end to the corruption that is destroying the health of Americans."