Resources

Resources

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Obstructive Sleep Apnea Syndrome (OSA) and Cancer: Current Insights

"The obstructive sleep apnea syndrome (OSA) is an independent risk factor for atherosclerosis.  Chronic intermittent hypoxia (CHI) causes atherosclerosis in the occurrence of a pre-existing hyperlipidemia.  A new pathway, in animal models has been demonstrated that CIH significantly increased atherosclerotic lesion sizes, mRNA levels of Cox-1 and thromboxane synthase (TXBS).  Lesion size is correlated to COX-1 and TXBS mRNA levels.  COX-1 inhibition reduced lesion progression in intermittent hypoxia mice.  This study demonstrated for the first time, that the activation of the COX pathway exposed to CIH is associated with increased atherosclerotic lesions in mice, highlighting early atherosclerosis markers in OSA patients."

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Cyclooxygenase Pathway Activation in Sleep Apnea Syndrome

"Patients with obstructive sleep apnea syndrome (OSA) exhibit an early vascular remodelling and alterations of acid arachidonic pathway 2.  Thromboxane A2 (TXA2) is a cycloxygenase (COX)-derived metabolite of AA involved in vascular remodelling."

"Atherosclerosis is a chronic inflammatory disease characterized by the activation of some components of the cyclooxygenase pathway.  OSA is associated with activation of the thromboxane A(TXA2)-pathway, in which obesity seems to be a major confounding factor." 

"Urinary excretion of 11-dTXB2 did not differ between OSA patients free of cardiovascular complications and healthy volunteers but increased in OSA patients with cormobidities compared to OSA patients without 694.0 (425.9-1235.6) versus 616.0 (354.3-838.2) pg/mg creatinine respectively; p=0.007). Finally, urinary 11-dTXB2 was increased by 30% in OSA Patients with cartoid hypertrophy (IMT>compared to OSA patients without carotid hypertrophy (783.0 (582.8-938.0) versus 592.9 (278.9-782.5) pg/mg creatinine, respect p=0.02)."

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Curcumin May Help Lower Inflammation in metabolic syndrome

"Adding spice- in the form of curcumin supplements - to the daily diets of people with risk factors for heart disease may lower inflammation, a new study suggests."

"Inflammation is implicated in a wide range of illnesses, from heart disease to cancer and joint pain.  In the eight week trial, researchers found significant reductions in signs of inflammation, such as C-Reactive protein and other blood markers."

"Curcumin is the active ingredient of the famous spice turmeric and has a long history of culinary and medicinal use in the Asian countries," said the study's senior author Amirhossein Sahebkar."

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Prostaglandins & Other Lipid Mediators

"Urinary 11-dehydro-thromboxane B2 levels are associated with vascular inflammation and prognosis in atherosclerotic cardiovascular disease."

"Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality worldwide despite recent advances in its management and treatment. Inflammation is a key driver of the pathogenesis and progression of ASCVD in preclinical models and humans." 

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The role of aspirin in cancer prevention

“Recently published secondary analyses of cardiovascular trials provide the first randomized evidence that daily aspirin use may also reduce the incidence of all cancers combined, even at low doses (75-100 mg daily)”

“10% reduction in overall cancer incidence beginning during the first 10 years of treatment could tip the balance of benefits and risks favourably in average-risk populations.”

"This Review considers the general mechanism of action that defines aspirin and other non-steroidal anti inflammtory drugs (NSAIDs) as a class, the specific advantages of aspirin over other NSAIDs for prophylactic use, the current evidence concerning the main health outcomes affected by aspirin use, and the hypothesis that inhibition of platelet activiation may mediate both the cardioprotective and cancer preventive effects of low-dose aspirin."

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Platelet activation in patients with colorectal cancer

“Enhanced platelet activation occurs in colorectal cancer patients. Permanent inactivation of platelet COX-1 by low dose aspirin might restore anti tumor reactivity.”

"Thus we aimed to address whether enhanced platelet activation, as assessed by the measurement of the urinary excretion of 11-dehydro-TXB(2) (a major enzymatic metabolite of TXB(2), occurs in patients with colorectal cancer.  In 10 patients with colorectal cancer, the urinary excretion of 11-dehydro-TXB(2) was significantly higher than in 10 controls, matched for sex, age and cardiovascular risk factors"

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Role of platelets in inflammation and cancer; novel therapeutic strategies

“The results of clinical studies have shown that the antiplatelet drug aspirin reduces the incidence of vascular events and colorectal cancer.”

“Low-dose aspirin treatment (which is associated with a preferential inhibition of platelet COX-1) causes a 70-80% reduction of urinary 11-dehydro-TXB2  and 2,3-din-or-TXB2 excretion.”

"Moreover, the results of clinical studies have shown that the antiplatelet drug aspirin reduces the incidence of vascular events and colorectal cancer.  All these pieces of evidence support the notion that colorectal cancer and atherothrombosis may share a common mechanism of disease, that is, platelet activation in response to epithelial (in tumourigensis) and endothelial (in tumourgenesis and atherothrombosis) injury."

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Communicating clinical research to reduce cancer risk through diet: Walnuts as a case example

"The connection between diet and cancer has been well established, as affirmed by the considerable international consistency among dietary and lifestyle recommendations for reducing risk of cancer and other chronic diseases. The World Cancer Research Fund, American Institute for Cancer Research, and the American Cancer Society guidance each emphasize a plant-based diet, a physically active lifestyle, limited alcohol, and maintaining a healthy weight."

“Both the walnut and fish diets inhibited prostaglandin E metabolite (PGEM) and 11-dehydro thromboxane B2, but had no effect on IL-1β, IL-6, TNF-α, CRP, or the number of circulating lymphocyte subsets.”

“A plant-based diet is associated with decreased risk for cancer and other chronic diseases, due in part to reduced chronic inflammation.”

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The thromboxane synthase and receptor signaling pathway in cancer: an emerging paradigm in cancer progression and metastasis

“Increased cyclooxygenase (COX)-2 expression has been described in a variety of human cancers, which has focused attention on TXA2 as a downstream metabolite of the COX-2-derived PGH2.”

“It is a great importance to further determine whether and how prostanoids, such as TXA2, mediate the effects of COX-2 in cancer, potentially leading to a more targeted approach for cancer prevention and treatment."

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Molecular targets of dietary polyphenols with anti-inflammatory properties

"Inflammation is the immunological defense mechanism by which the body fights infection or injury from bacteria, viruses and other pathogens.  The defining clinical features of inflammation are known in Latin as rubor (redness), calor (warmth), tumor (swelling) and dolor (pain)."

"In the early 1970's, aspirin and other non-steroidal anti-inflammatory drugs were found to inhibit cyclooxygenase (COX), which produces prostaglandins (PG's), a class of physiological and pathophysiological inflammatory mediators.  Since then, the biosynthetic cascade of arachadonic acid (AA) has been the subject of intense research.  This is because AA, having been previously liberated from phospholipids using various stimuli, can be metabolized by the COX pathway into PG's and thromboxane A2, or by the lipoxygenase pathways to hydroperoxyeicosateraenoic acids, (HpETEs), hydroxyeicosateraenoic acids (HETEs), and leukotrienes (LTs).  These proteins play a vital role in inflammation by controlling the intensitry and duration of pain, as well as the occurrence of fever, swelling and heat of an affected area."

“Given that certain polyphenols are known to affect more than one protein, it is necessary consider the possibility that any single com- pound may affect multiple mechanisms.”

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