Stress Is The Primary Driver Of Tumor Spread, By Promoting Inflammation

haidut

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Ray has written so much of the effects of stress on health and specifically on how chronic stress promotes energetic dysfunction and tumor formation/growth/spread. However, up until a year ago there was very little "official" research to back up his views. This study does just that, and it shows that the chronic overactivation of the sympathetic nervous system drives up expression of VEGF, which increase angiogenesis in lymphatic vessels and thus promotes tumor growth and spread. Blocking sympathetic activation (using drugs like propranolol) or inhibiting VEGF increase (using COX inhibitors like aspirin) blocked tumor spread. Instead of propranolol, which has quite a few side effects, drugs like clonidine may be more suitable for blocking the adrenergic systemic effects of chronic stress.

Science says stress really does spread cancer in the body
Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination : Nature Communications : Nature Publishing Group

"...Norepinephrine is released from parenchymal nerve fibres in response to stress, and binds β-adrenoceptors to modulate cell function1. β-adrenoceptors are present on tumour cells and stromal cell populations in the tumour microenvironment37, 38, including inflammatory cells6. Accumulating evidence from preclinical studies suggests that chronic stress promotes cancer progression through β-adrenoceptor activation3, 4, 6, 26, 39. To investigate if β-adrenergic signalling is required for the effects of stress on intratumoural LVD, we treated mice with propranolol, a non-selective β-adrenoceptor antagonist (beta-blocker; BB) that is used clinically for the treatment of hypertension. Treatment with propranolol during MDA-MB-231 tumour development blocked chronic stress from increasing tumour LYVE-1+ LVD and reduced metastasis to lymph nodes, suggesting that reduced LVD had functional effects on tumour cell dissemination (Fig. 3a and Supplementary Table 1). Conversely, systemic activation of β-adrenoceptors with the β-adrenoceptor agonist isoproterenol was sufficient to increase intratumoural LVD and increase lymph node metastasis (Fig. 3b and Supplementary Fig. 3A) without affecting primary tumour growth (Supplementary Fig. 3B). These findings demonstrate that β-adrenoceptor signalling is sufficient to promote intratumoural LVD and is necessary for the adverse effects of stress on lymphatic vascular remodelling.

"...While chronic stress increased tumour cell VEGFC expression in primary mammary tumours in vivo (Fig. 4a), direct treatment of cultured tumour cells with the β-adrenoceptor agonist isoproterenol was insufficient to drive VEGFC expression in vitro (Fig. 4f), suggesting that a mediating factor is required for the effect of stress on tumour cell VEGFC expression in vivo. As inflammation promotes VEGFC expression and drives lymphatic remodelling15, we investigated if inflammatory pathways are linked to stress regulation of lymphatic vasculature in vivo. We first looked at expression of the inflammatory marker cyclooxygenase-2 (COX2, or PTGS2). While tumour COX2 levels were low in control mice, stress or isoproterenol elevated COX2 mRNA transcript levels (Fig. 5a and Supplementary Fig. 5A), which were strongly associated with VEGFC mRNA levels (Fig. 5b and Supplementary Fig. 5B). This is consistent with findings in other solid cancers49, 50, 51, 52, and extends observations that inflammation is linked with lymph vessel formation by identifying stress signalling as a potential driver of this relationship. To determine if inflammation is necessary for stress to modulate lymphatic architecture and lymphogenous spread, we treated control and stressed mice bearing MDA-MB-231 mammary tumours with the COX2 inhibitor celecoxib. Inhibition of COX2 activity blocked the effect of stress on tumour LYVE-1+ LVD (Fig. 5c,d) and prevented metastasis to lymph node and distant organs (Fig. 5c,d and Supplementary Fig. 5C), demonstrating a functional consequence of limiting lymphatic remodelling."
 

Tenacity

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Screen Shot 2018-04-26 at 18.31.46.png Screen Shot 2018-04-26 at 18.29.06.png
Some good examples of the derangement of modern treatment. Note the interesting wording on that first one. It's 'healing' that makes cancer spread.
 

haidut

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