Depression of serum melatonin in patients with primary breast cancer is not due to an increased peripheral metabolism

Article Abstract:

Melatonin is a hormone secreted by the pineal gland in the brains of most animals, including man. It is clear that the serum levels of melatonin follow a diurnal cycle, that is, vary with the time of day or night, and therefore many believe that melatonin may play a key role in sleep and waking cycles. Hard evidence is lacking, and the normal role of melatonin in human physiology is not understood. However, it is clear that melatonin levels are depressed in a number of different cancers, including breast cancer, colon cancer, stomach cancer, and prostate cancer. Since none of these cancers directly impinges upon the pineal gland, researchers suspect that finding the reason for the depression of melatonin levels might provide important clues about the physiology of cancer. The two most likely explanations for the depression of melatonin levels in the blood are that the pineal gland is making less, or that the pineal gland is making the normal amount but the liver is metabolizing it faster. To distinguish between these two possibilities, researchers examined the levels of melatonin and its major metabolite in nine patients with primary breast cancer. Eight patients with secondary breast cancer and four patients with benign breast disease served as controls. The rationale of the experiment suggests that if the pineal gland is producing the same amount of melatonin and the liver is destroying it faster, there should be an increase in the main metabolic product, 6-sulfatoxymelatonin. When the levels of melatonin and 6-sulfatoxymelatonin were measured, however, both were found to be depressed in the patients with primary breast cancer. Measurements made throughout a 24-hour period showed the depression of both was most noticeable during the hours after midnight, when the levels of melatonin are normally highest. The authors suggest that primary tumors secrete some factor that depresses melatonin production. It is unclear, however, why metastatic breast cancer does not exert the same effect on the pineal gland. The fact that patients with secondary breast cancer may have normal patterns of melatonin secretion does, however, indicate that whatever changes depress melatonin levels in primary breast cancer are reversible. (Consumer Summary produced by Reliance Medical Information, Inc.)

Melatonin

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Impaired production of tumor necrosis factor in breast cancer

Article Abstract:

Tumor necrosis factor is a lymphokine produced by a type of defense cell called macrophages when they are exposed to bacterial toxic products called endotoxins. Tumor necrosis factor has been shown to be active against tumors under experimental conditions and may be effective in the treatment of human cancers. The spontaneous and stimulated production of tumor necrosis factor by macrophages was assessed in patients with breast cancer. The spontaneous production of tumor necrosis factor by macrophages from breast cancer patients was similar to that of normal healthy subjects. However, the production of tumor necrosis factor by macrophages stimulated by lipopolysaccharide was lower in patients in remission or with widespread, advanced breast cancer than in normal, healthy subjects. The production of tumor necrosis factor was similar among all patients with breast cancer, regardless of whether they were in remission or had metastatic cancer. The impairment of lipopolysaccharide-stimulated production of tumor necrosis factor was not related to tumor characteristics or types of treatment. The production of interleukin-1 (IL-1) by macrophages was also studied. IL-1 is important in mediating the acute phase response, which is characterized by fever, the activation of immune responses, release of amino acids from muscle, and induction of slow-wave sleep. There were no differences in the production of IL-1 by macrophages between patients with breast cancer and normal subjects. These findings show that the lipopolysaccharide-stimulated production of tumor necrosis factors by macrophages is decreased in patients with breast cancer irrespective of the presence of metastatic disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Measurement, Tumor necrosis factor, Interleukin-1

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