Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Causal relationships among stress, immune suppression, and enhanced tumor development have often been suggested, but direct evidence is scant. We studied stress effects in Fischer 344 rats using a tumor model in which lung metastases of a syngeneic mammary tumor (MADB106) are controlled by natural killer (NK) cells. Animals exposed to acute stress showed a substantial decrease in NK cell cytotoxicity against this tumor in an in vitro assay and, when intravenously injected with this tumor, showed a twofold increase in surface lung metastases. The critical period during which stress increases metastases appears to be the same as that during which this tumor is known to be controlled by NK cells. These findings support the hypothesis that stress can facilitate the metastatic process via suppression of the immune system.
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PMID:Stress increases metastatic spread of a mammary tumor in rats: evidence for mediation by the immune system. 165 66

Hormones of the hypothalamic-pituitary-adrenal system were studied in 31 patients with early stage breast cancer and patients with metastatic breast cancer. Both groups received tamoxifen as first-line treatment. As a control group 15 age-matched healthy women participated in the study. The results showed that breast cancer patients had significant elevations in basal cortisol levels compared to controls. Metastatic breast cancer patients had higher cortisol levels than early stage breast cancer patients. No significant differences between breast cancer patients and controls were found in basal plasma ACTH and prolactin levels. These data provide evidence that breast cancer is associated with a hyperactive adrenal gland, which may be due to the physiological stress associated with the presence of (micro)metastases or tumor cells in the circulation, in combination with administration of tamoxifen. In response to a behavioral challenge increases were observed in plasma ACTH and prolactin. Metastatic breast cancer patients had a faster prolactin response to acute stress than healthy women. However, metastatic breast cancer patients showed a blunted ACTH response compared to healthy women. Stress-induced ACTH responses and basal cortisol levels were negatively correlated in the metastatic group only. Thus, the blunted ACTH response to the behavioral challenge might be related to hypercortisolemia suggesting that the pituitary corticotroph cell in metastatic cancer is appropriately restrained possibly by the negative feedback effects of chronic cortisol elevations. Interestingly, the behavioral challenge induced decreases in cortisol levels in all three groups. However, metastatic breast cancer patients had a faster cortisol decline compared to healthy women. We hypothesize that this is caused by increased metabolic clearance of cortisol due to increased utilization of metabolic substrates often observed in the presence of a tumor.
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PMID:Elevated basal cortisol levels and attenuated ACTH and cortisol responses to a behavioral challenge in women with metastatic breast cancer. 884 75

This study explores by means of statistical modeling the relations between adrenocorticotrophin hormone (ACTH) and cortisol levels and distribution and function of peripheral blood cells in response to an acute stressor consisting of a standardized speech task in breast cancer patients with axillary lymph node metastases and distant metastases. As a control group age-matched women participated in this study. The preliminary findings show that the effect of ACTH on immunoreactivity is related to the health of the doctor. In node-positive breast cancer patients and healthy women, ACTH has a modest positive effect on T lymphocyte percentages and on pokeweed-induced proliferation at baseline and in response to the speech task. In contrast, in breast cancer patients with distant metastases, ACTH has a negative effect on T lymphocyte and function at baseline and in response to the stressor. Interestingly, neither ACTH nor cortisol levels were related to natural killer (NK) cell percentages and natural killer cell activity (NKCA). In addition, it appeared that cortisol had a positive effect on CD3 cell percentages when the health of the donor was taken into account. This effect was most distinct on CD3 cells measured at baseline. If replicated on a larger scale, these findings may indicate that the hypothalamic pituitary adrenal axis plays a role in the adaptation of the host defenses in reaction to acute stress, particularly those involving T lymphocytes. Moreover, these findings may suggest that the health of the donor may be an important effect modification factor in the relations between neuroendocrines and immunoreactivity.
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PMID:Relations of plasma ACTH and cortisol levels with the distribution and function of peripheral blood cells in response to a behavioral challenge in breast cancer: an empirical exploration by means of statistical modeling. 1625 Jul 36

Commonly used dermatologic eponyms and characteristic skin signs are enormously helpful in guiding a diagnosis, even though they may not be pathonemonic. They include, on the nails, Aldrich-Mees' lines (syn.: Mees' lines), Beau's lines, Muehrcke's lines, Terry's nails, and half and half nails, often associated, respectively, with arsenic poisoning, acute stress or systemic illness, severe hypertension, liver disease and uremia, and, around the nails, Braverman's sign, associated with collagen-vascular disease. Elsewhere, one may see the Asboe-Hansen and Nikolsky's signs, indicative of the pemphigus group of diseases, Auspitz's sign, a classic finding in psoriasis, Borsieri's and Pasita's signs, seen in early scarlet fever, the butterfly rash, indicative of systemic lupus erythematosus, and the buffalo hump, seen in Cushing's disease and also in the more common corticosteroid toxicity. Gottron's papules and the heliotrope rash are signs of dermatomyositis. Janeway's lesions and Osler's nodes are seen in bacterial endocarditis. A Dennie-Morgan fold under the eye is seen in association with atopic disease. Koplik's spots are an early sign of rubeola. Fitzpatrick's sign is indicative of a benign lesion (dermatofibroma), whereas Hutchinson's sign is indicative of a malignant one (subungual melanoma). Petechiae are seen in many diseases, including fat embolization, particularly from a large bone fracture following trauma. Palpable purpura is indicative of leukocytoclastic vasculitis, and is an early, critical sign in Rickettsial diseases, including Rocky Mountain Spotted Fever, which must be diagnosed and treated early. Hyperpigmentation of areolae and scars is seen in Addison's disease. Acanthosis nigricans may indicate internal cancer, especially stomach cancer, whereas Bazex's syndrome occurs in synchrony with primary, usually squamous cancer, in the upper aerodigestive tract or metastatic cancer in cervical lymph nodes. Perioral pigmented macules or one or more cutaneous sebaceous neoplasms may be a sign of the Peutz-Jeghers or Muir-Torre syndrome, respectively, both associated also with intestinal polyps that have a malignant potential. Telangiectasiae in the perioral region may be associated with similar lesions internally in Osler-Weber-Rendu disease. Kerr's sign is indicative of spinal cord injury and Darier's sign of mastocytosis. Post proctoscopic periobital purpura (PPPP) is a phenomenon observed in some patients with systemic amyloidosis. Koebner's isomorphic response refers to the tendency of an established dermatosis, such as psoriasis, to arise in (a) site(s) of trauma, whereas Wolf's isotrophic response refers to a new dermatosis, such as tinea, not yet seen in the patient, arising in (a) site(s) of a former but different dermatosis, such as zoster.
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PMID:Cutaneous signs of systemic disease. 2185 27

The effect of a depression-like status formed by chronic stress on development of Lewis lung carcinoma metastases in C57Bl/6J mice was investigated. Two types of acute stress (restraint and social stress) were used for comparison. The depression-like status was induced by eight-week exposure to repeated but unpredictable stressors (chronic mild stress model) and was assessed in the forced swim test. Tumor cells were inoculated an hour after the onset of social stressor or immediately after physical or chronic stressor impacts. The number of metastases was counted 17 days after the inoculation. The results indicate that chronic mild stress provokes the development of a depression-like state in mice and causes a twofold increase in the number of metastases in the lungs, while both types of acute stress have no such effects. Thus, a depression-like psychoemotional status of animals enhances the metastasis of Lewis lung carcinoma.
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PMID:[The effect of psychoemotional state on Lewis lung carcinoma metastasis]. 2264 51

The use of TLR agonists as an anti-cancer treatment is gaining momentum given their capacity to activate various host cellular responses through the secretion of inflammatory cytokines and type-I interferons. It is now also recognized that the perioperative period is a window of opportunity for various interventions aiming at reducing the risk of cancer metastases-the major cause of cancer related death. However, immune-stimulatory approach has not been used perioperatively given several contraindications to surgery. To overcome these obstacles, in this study, we used the newly introduced, fully synthetic TLR-4 agonist, Glucopyranosyl Lipid-A (GLA-SE), in various models of cancer metastases, and in the context of acute stress or surgery. Without exerting evident adverse effects, a single systemic administration of GLA-SE rapidly and dose dependently elevated both innate and adaptive immunity in the circulation, lungs and the lymphatic system. Importantly, GLA-SE treatment led to reduced metastatic development of a mammary adenocarcinoma and a colon carcinoma by approximately 40-75% in F344 rats and BALB/c mice, respectively, at least partly through elevating marginating-pulmonary NK cell cytotoxicity. GLA-SE is safe and well tolerated in humans, and currently is used as an adjuvant in phase-II clinical trials. Given that the TLR-4 receptor and its signaling cascade is highly conserved throughout evolution, our current results suggest that GLA-SE may be a promising immune stimulatory agent in the context of oncological surgeries, aiming to reduce long-term cancer recurrence.
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PMID:Perioperative treatment with the new synthetic TLR-4 agonist GLA-SE reduces cancer metastasis without adverse effects. 2645 48