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Breast cancer is the most common cancer diagnosed in women. It is associated with multiple symptoms in both patients and caregivers, such as stress, anxiety, depression, sleep disturbance, and fatigue. Stress appears to promote cancer progression via activation of the sympathetic nervous system releasing epinephrine and norepinephrine as well as activation of hypothalamic-pituitary-adrenal axis releasing cortisol. These stress hormones have been shown to promote the proliferation of cancer cells. This review focuses on stress-reducing strategies which may decrease cancer progression by abrogating these pathways, with a main focus on the β-adrenergic signaling pathway. Patients utilize both non-pharmacologic and pharmacologic strategies to reduce stress. Non-pharmacologic stress-reduction strategies include complementary and alternative medicine techniques, such as meditation, yoga, acupuncture, exercise, use of natural products, support groups and psychology counseling, herbal compounds, and multivitamins. Pharmacologic strategies include abrogating the β2-adrenergic receptor signaling pathway to antagonize epinephrine and norepinephrine action on tumor and immune cells. β-Blocker drugs may play a role in weakening the pro-migratory and pro-metastatic effects induced by stress hormones in cancer and strengthening the anti-tumor immune response. Preclinical models have shown that non-selective β1/2-blocker use is associated with a decrease in tumor growth and metastases and clinical studies have suggested their positive impact on decreasing breast cancer recurrence and mortality. Thus, non-pharmacological approaches, along with pharmacological therapies part of clinical trials are available to cancer patients to reduce stress, and have promise to break the cycle of cancer and stress.
Breast cancer is the most common cancer diagnosed in women. It is associated with multiple symptoms in both patients and caregivers, such as stress, anxiety, depression, sleep disturbance, and fatigue. Stress appears to promote cancer progression via activation of the sympathetic nervous system releasing epinephrine and norepinephrine as well as activation of hypothalamic-pituitary-adrenal axis releasing cortisol. These stress hormones have been shown to promote the proliferation of cancer cells. This review focuses on stress-reducing strategies which may decrease cancer progression by abrogating these pathways, with a main focus on the β-adrenergic signaling pathway. Patients utilize both non-pharmacologic and pharmacologic strategies to reduce stress. Non-pharmacologic stress-reduction strategies include complementary and alternative medicine techniques, such as meditation, yoga, acupuncture, exercise, use of natural products, support groups and psychology counseling, herbal compounds, and multivitamins. Pharmacologic strategies include abrogating the β2-adrenergic receptor signaling pathway to antagonize epinephrine and norepinephrine action on tumor and immune cells. β-Blocker drugs may play a role in weakening the pro-migratory and pro-metastatic effects induced by stress hormones in cancer and strengthening the anti-tumor immune response. Preclinical models have shown that non-selective β1/2-blocker use is associated with a decrease in tumor growth and metastases and clinical studies have suggested their positive impact on decreasing breast cancer recurrence and mortality. Thus, non-pharmacological approaches, along with pharmacological therapies part of clinical trials are available to cancer patients to reduce stress, and have promise to break the cycle of cancer and stress.
The effect of norepinephrine administration on pulmonary blood flow during the neonatal period is unclear. Therefore, norepinephrine responses were studied in isolated pulmonary arteries, pulmonary veins, and femoral arteries taken from normal pigs from birth to adulthood and from pigs subjected to chronic hypoxia either from birth for 3 days or from 3 to 14 days of age. Normally, the contractile response of pulmonary arteries and veins to norepinephrine decreased after birth (p < 0.01), and alpha2-adrenoceptor-mediated relaxation increased in pulmonary arteries and veins and in femoral arteries. Hypoxic exposure from birth prevented the normal postnatal reduction in pulmonary arterial contractile response, nor was there a postnatal increase in pulmonary arterial adrenoceptor-mediated relaxation. When hypoxic exposure followed a period of normal adaptation, the pulmonary arterial contractile response was not enhanced, but relaxation was significantly impaired. The response of pulmonary veins and femoral arteries was not affected by hypoxic exposure. The contractile effect of norepinephrine was 15- to 60-fold greater in isolated systemic arteries than in pulmonary arteries taken from both normal and pulmonary hypertensive piglets at all ages. This suggests that use of norepinephrine to manage systemic hypotension in infants and children will not compromise the pulmonary vasculature.
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