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Author (up) Anbalagan, M.; Dauchy, R.; Xiang, S.; Robling, A.; Blask, D.; Rowan, B.; Hill, S.
Title SAT-337 Disruption Of The Circadian Melatonin Signal By Dim Light At Night Promotes Bone-lytic Breast Cancer Metastases Type Journal Article
Year 2019 Publication Journal of the Endocrine Society Abbreviated Journal
Volume 3 Issue Supplement_1 Pages
Keywords Human Health; Cancer; Breast cancer; melatonin; shift work; mouse models
Abstract Breast cancer metastasis to bone is a major source of morbidity and mortality in women with advanced metastatic breast cancer. Morbidity from metastasis to bone is compounded by the fact that they cannot be surgically removed and can only be treated with chemotherapy and/or radiation therapy. Thus, there is critical need to develop new treatment strategies that kill bone metastatic tumors and reduce osteolytic lesions to improve patient quality of life and extend patient survival. Circadian rhythms are daily cycles of ~24 h that control many if not most physiologic processes and their disruption by exposure to light at night (LAN) or jet lag has been shown to be strongly associated with the development of cancer, particularly breast cancer. We have found that disruption of the anti-cancer circadian hormone melatonin (MLT) by light at night can significantly enhance the metastatic potential in breast cancer cells. Our work supports the report of the International Agency for Research on Cancer that shift work is a “probable human carcinogen” and highlights the association between exposure to light at night and invasive breast cancer. We recently reported that human breast tumor xenografts grown in athymic nude female rats housed in a photoperiod of 12h light at day: 12h dim light at night (dLAN, 0.2 lux – blocks the nighttime circadian MLT signal), display resistance to doxorubicin (Dox). More importantly, tumor growth and drug resistance could be blocked by the administration of Dox in circadian alignment with nocturnal MLT during dLAN. Our recent preliminary studies show that poorly invasive ERα positive MCF-7 breast cancer cells, when injected into the tibia (to mimic bone metastatic disease) of Foxn1nu athymic nude mice (which produce a strong circadian nighttime melatonin signal) housed in a dLAN photoperiod (suppressed nocturnal MLT production) developed full blown breast cancer tumors in bone (P<0.05) that are highly osteolytic (P<0.05). Moreover, patients with metastatic breast cancer are routinely treated with doxorubicin, which itself can promote bone damage. Our studies demonstrate that MLT slows the growth of metastatic breast cancer in bone but that the chrono-therapeutic use of doxorubicin in circadian alignment with melatonin in Foxn1nu mice with tibial breast tumors, reduced tumor growth in bone, reduced bone erosion, and promoted the formation of new bone. Successful use of this chronotherapeutic use of Dox and MLT in clinical trials increasing efficacy in preventing or suppressing breast cancer metastasis to bone while decreasing toxic side effects of doxorubicin would provide a revolutionary advancement in the treatment of bone metastatic breast cancer and decrease the morbidity and mortality associated with breast cancer metastasis to bone.
Address Tulane University School of Medicine, New Orleans, LA, United States
Corporate Author Thesis
Publisher Oxford Academic Place of Publication Editor
Language English Summary Language English Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2472-1972 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number GFZ @ kyba @ Serial 2433
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Author (up) Cherrie, J.W.
Title Shedding Light on the Association between Night Work and Breast Cancer Type Journal Article
Year 2019 Publication Annals of Work Exposures and Health Abbreviated Journal Ann Work Expo Health
Volume 63 Issue 6 Pages 608–611
Keywords Commentary; Human Health; Cancer; Breast cancer; shift work
Abstract Shift work that involves circadian disruption has been classified as probably carcinogenic to humans by the International Agency for Research on Cancer, although more recent epidemiological evidence is not consistent. Several mechanisms have been postulated to explain an association between night work and female breast cancer, but the most likely is suppression of the hormone melatonin by light exposure at night. Three articles recently published in this journal describe aspects of exposure to light during night work. These articles and other evidence suggest that nighttime light levels may not always be sufficient to affect melatonin production, which could in part explain the inconsistencies in the epidemiological data. There is need to improve the specificity and reliability of exposure assessments in future epidemiological studies of night shift workers.
Address Institute of Occupational Medicine, Research Avenue North, Edinburgh, UK
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2398-7308 ISBN Medium
Area Expedition Conference
Notes PMID:31175355 Approved no
Call Number GFZ @ kyba @ Serial 2530
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Author (up) Cho, Y.M.; Ryu, S.-H.; Lee, B.R.; Kim, K.H.; Lee, E.; Choi, J.
Title Effects of artificial light at night on human health: A literature review of observational and experimental studies applied to exposure assessment Type Journal Article
Year 2015 Publication Chronobiology International Abbreviated Journal Chronobiol. Int.
Volume 32 Issue 9 Pages 1294-1310
Keywords Artificial light at night; breast cancer; circadian rhythm; light exposure; light pollution
Abstract It has frequently been reported that exposure to artificial light at night (ALAN) may cause negative health effects, such as breast cancer, circadian phase disruption and sleep disorders. Here, we reviewed the literature assessing the effects of human exposure to ALAN in order to list the health effects of various aspects of ALAN. Several electronic databases were searched for articles, published through August 2014, related to assessing the effects of exposure to ALAN on human health; these also included the details of experiments on such exposure. A total of 85 articles were included in the review. Several observational studies showed that outdoor ALAN levels are a risk factor for breast cancer and reported that indoor light intensity and individual lighting habits were relevant to this risk. Exposure to artificial bright light during the nighttime suppresses melatonin secretion, increases sleep onset latency (SOL) and increases alertness. Circadian misalignment caused by chronic ALAN exposure may have negative effects on the psychological, cardiovascular and/or metabolic functions. ALAN also causes circadian phase disruption, which increases with longer duration of exposure and with exposure later in the evening. It has also been reported that shorter wavelengths of light preferentially disturb melatonin secretion and cause circadian phase shifts, even if the light is not bright. This literature review may be helpful to understand the health effects of ALAN exposure and suggests that it is necessary to consider various characteristics of artificial light, beyond mere intensity.
Address b Department of Preventive Medicine , College of Medicine, Korea University , Seoul , Republic of Korea
Corporate Author Thesis
Publisher Taylor & Francis Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0742-0528 ISBN Medium
Area Expedition Conference
Notes PMID:26375320 Approved no
Call Number IDA @ john @ Serial 1269
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Author (up) Dauchy, R.T.; Xiang, S.; Mao, L.; Brimer, S.; Wren, M.A.; Yuan, L.; Anbalagan, M.; Hauch, A.; Frasch, T.; Rowan, B.G.; Blask, D.E.; Hill, S.M.
Title Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer Type Journal Article
Year 2014 Publication Cancer Research Abbreviated Journal Cancer Res
Volume 74 Issue 15 Pages 4099-4110
Keywords *Cancer; breast cancer; melatonin; endocrinology; tamoxifen; *Circadian Rhythm; circadian disruption; human health; epidemiology
Abstract Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to antiestrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. In this study, we used a rat model of estrogen receptor (ERalpha(+)) MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speed the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characteristics were not observed in animals in which the circadian melatonin rhythm was not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to tamoxifen and tumor regression. Together, our findings show how dLEN-mediated disturbances in nocturnal melatonin production can render tumors insensitive to tamoxifen. Cancer Res; 74(15); 4099-110. (c)2014 AACR.
Address Departments of Structural and Cellular Biology and Tulane Cancer Center and Louisiana Cancer Research Consortium; Tulane Circadian Cancer Biology Group; and
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0008-5472 ISBN Medium
Area Expedition Conference
Notes PMID:25062775; PMCID:PMC4119539 Approved no
Call Number IDA @ john @ Serial 355
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Author (up) Davis, S.; Mirick, D.K.; Stevens, R.G.
Title Night Shift Work, Light at Night, and Risk of Breast Cancer Type Journal Article
Year 2001 Publication JNCI Journal of the National Cancer Institute Abbreviated Journal JNCI Journal of the National Cancer Institute
Volume 93 Issue 20 Pages 1557-1562
Keywords light at night; oncogenesis; melatonin; shiftwork; breast cancer; *Cancer
Abstract Exposure to light at night may increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin by the pineal gland, which, in turn, could increase the release of estrogen by the ovaries. This study investigated whether such exposure is associated with an increased risk of breast cancer in women. Methods: Case patients (n = 813), aged 20–74 years, were diagnosed from November 1992 through March 1995; control subjects (n = 793) were identified by random-digit dialing and were frequency matched according to 5-year age groups. An in-person interview was used to gather information on sleep habits and bedroom lighting environment in the 10 years before diagnosis and lifetime occupational history. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression, with adjustment for other potential risk factors. Results: Breast cancer risk was increased among subjects who frequently did not sleep during the period of the night when melatonin levels are typically at their highest (OR = 1.14 for each night per week; 95% CI = 1.01 to 1.28). Risk did not increase with interrupted sleep accompanied by turning on a light. There was an indication of increased risk among subjects with the brightest bedrooms. Graveyard shiftwork was associated with increased breast cancer risk (OR = 1.6; 95% CI = 1.0 to 2.5), with a trend of increased risk with increasing years and with more hours per week of graveyard shiftwork (P = .02, Wald chi-squared test). Conclusion: The results of this study provide evidence that indicators of exposure to light at night may be associated with the risk of developing breast cancer.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0027-8874 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number IDA @ john @ Serial 164
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