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Author 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 Anisimov, V.N.; Vinogradova, I.A.; Panchenko, A.V.; Popovich, I.G.; Zabezhinskii, M.A.
Title Light-at-Night-Induced Circadian Disruption, Cancer and Aging Type Journal Article
Year 2012 Publication Current Aging Science Abbreviated Journal
Volume 5 Issue 3 Pages 170-177
Keywords Animals; Light-at-night; aging; cancer; cardiovascular diseases; circadian; circadian rhythm; diabetes; disruption; melatonin; shift-work
Abstract Light-at-night has become an increasing and essential part of the modern lifestyle and leads to a number of health problems, including excessive body mass index, cardiovascular diseases, diabetes, and cancer. The International Agency for Research on Cancer (IARC) Working Group concluded that “shift-work that involves circadian disruption is probably carcinogenic to humans” (Group 2A) [1]. According to the circadian disruption hypothesis, light-at-night might disrupt the endogenous circadian rhythm and specifically suppress nocturnal production of the pineal hormone melatonin and its secretion into the blood. We evaluated the effect of various light/dark regimens on the survival, life span, and spontaneous and chemical carcinogenesis in rodents. Exposure to constant illumination was followed by accelerated aging and enhanced spontaneous tumorigenesis in female CBA and transgenic HER-2/neu mice. In male and female rats maintained at various light/dark regimens (standard 12:12 light/dark [LD], the natural light [NL] of northwestern Russia, constant light [LL], and constant darkness [DD]) from the age of 25 days until natural death, it was found that exposure to NL and LL regimens accelerated age-related switch-off of the estrous function (in females), induced development of metabolic syndrome and spontaneous tumorigenesis, and shortened life span both in male and females rats compared to the standard LD regimen. Melatonin given in nocturnal drinking water prevented the adverse effect of the constant illumination (LL) and natural light (NL) regimens on the homeostasis, life span, and tumor development both in mice and rats. The exposure to the LL regimen accelerated colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in rats, whereas the treatment with melatonin alleviated the effects of LL. The maintenance of rats at the DD regimen inhibited DMH-induced carcinogenesis. The LL regimen accelerated, whereas the DD regimen inhibited both mammary carcinogenesis induced by N-nitrosomethylurea and transplacental carcinogenesis induced by N-nitrosoethylurea in rats. Treatment with melatonin prevented premature aging and tumorigenesis in rodents. The data found in the literature and our observations suggest that the use of melatonin would be effective for cancer prevention in humans at risk as a result of light pollution.
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 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number LoNNe @ christopher.kyba @ Serial 377
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Author Arendt, J.
Title Biological rhythms during residence in polar regions Type Journal Article
Year 2012 Publication Chronobiology International Abbreviated Journal Chronobiol Int
Volume 29 Issue 4 Pages 379-394
Keywords *Acclimatization; Activities of Daily Living; Affect; Antarctic Regions; Arctic Regions; *Biological Clocks; *Circadian Rhythm; *Cold Climate; *Cold Temperature; Energy Metabolism; Feeding Behavior; Humans; Melatonin/metabolism; Personnel Staffing and Scheduling; *Photoperiod; Seasonal Affective Disorder/physiopathology/prevention & control/psychology; *Seasons; Sleep; Sleep Disorders, Circadian Rhythm/etiology/physiopathology/*prevention & control/psychology; Time Factors; Workload; Workplace
Abstract At Arctic and Antarctic latitudes, personnel are deprived of natural sunlight in winter and have continuous daylight in summer: light of sufficient intensity and suitable spectral composition is the main factor that maintains the 24-h period of human circadian rhythms. Thus, the status of the circadian system is of interest. Moreover, the relatively controlled artificial light conditions in winter are conducive to experimentation with different types of light treatment. The hormone melatonin and/or its metabolite 6-sulfatoxymelatonin (aMT6s) provide probably the best index of circadian (and seasonal) timing. A frequent observation has been a delay of the circadian system in winter. A skeleton photoperiod (2 x 1-h, bright white light, morning and evening) can restore summer timing. A single 1-h pulse of light in the morning may be sufficient. A few people desynchronize from the 24-h day (free-run) and show their intrinsic circadian period, usually >24 h. With regard to general health in polar regions, intermittent reports describe abnormalities in various physiological processes from the point of view of daily and seasonal rhythms, but positive health outcomes are also published. True winter depression (SAD) appears to be rare, although subsyndromal SAD is reported. Probably of most concern are the numerous reports of sleep problems. These have prompted investigations of the underlying mechanisms and treatment interventions. A delay of the circadian system with “normal” working hours implies sleep is attempted at a suboptimal phase. Decrements in sleep efficiency, latency, duration, and quality are also seen in winter. Increasing the intensity of ambient light exposure throughout the day advanced circadian phase and was associated with benefits for sleep: blue-enriched light was slightly more effective than standard white light. Effects on performance remain to be fully investigated. At 75 degrees S, base personnel adapt the circadian system to night work within a week, in contrast to temperate zones where complete adaptation rarely occurs. A similar situation occurs on high-latitude North Sea oil installations, especially when working 18:00-06:00 h. Lack of conflicting light exposure (and “social obligations”) is the probable explanation. Many have problems returning to day work, showing circadian desynchrony. Timed light treatment again has helped to restore normal phase/sleep in a small number of people. Postprandial response to meals is compromised during periods of desynchrony with evidence of insulin resistance and elevated triglycerides, risk factors for heart disease. Only small numbers of subjects have been studied intensively in polar regions; however, these observations suggest that suboptimal light conditions are deleterious to health. They apply equally to people living in temperate zones with insufficient light exposure.
Address Centre for Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK. arendtjo@gmail.com
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 0742-0528 ISBN Medium
Area Expedition Conference
Notes PMID:22497433; PMCID:PMC3793275 Approved no
Call Number IDA @ john @ Serial 143
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Author Arendt, J.; Middleton, B.
Title Human seasonal and circadian studies in Antarctica (Halley, 75 degrees S) Type Journal Article
Year 2018 Publication General and Comparative Endocrinology Abbreviated Journal Gen Comp Endocrinol
Volume 258 Issue Pages 250-258
Keywords Human Activities; Acclimatization/*physiology; Actigraphy; Adult; Antarctic Regions; Behavior/*physiology; Circadian Rhythm/*physiology; Darkness; Female; Heart Rate/physiology; Humans; Libido; Light; Male; Melatonin/blood; Photoperiod; *Seasons; Sleep/physiology; Young Adult; *Antarctica; *Circadian; *Light; *Melatonin; *Seasonal
Abstract Living for extended periods in Antarctica exposes base personnel to extremes of daylength (photoperiod) and temperature. At the British Antarctic Survey base of Halley, 75 degrees S, the sun does not rise for 110 d in the winter and does not set for 100 d in summer. Photoperiod is the major time cue governing the timing of seasonal events such as reproduction in many species. The neuroendocrine signal providing photoperiodic information to body physiology is the duration of melatonin secretion which reflects the length of the night: longer in the short days of winter and shorter in summer. Light of sufficient intensity and spectral composition serves to suppress production of melatonin and to set the circadian timing and the duration of the rhythm. In humans early observations suggested that bright (>2000 lux) white light was needed to suppress melatonin completely. Shortly thereafter winter depression (Seasonal Affective Disorder or SAD) was described, and its successful treatment by an artificial summer photoperiod of bright white light, sufficient to shorten melatonin production. At Halley dim artificial light intensity during winter was measured, until 2003, at a maximum of approximately 500 lux in winter. Thus a strong seasonal and circadian time cue was absent. It seemed likely that winter depression would be common in the extended period of winter darkness and could be treated with an artificial summer photoperiod. These observations, and predictions, inspired a long series of studies regarding human seasonal and circadian status, and the effects of light treatment, in a small overwintering, isolated community, living in the same conditions for many months at Halley. We found little evidence of SAD, or change in duration of melatonin production with season. However the timing of the melatonin rhythm itself, and/or that of its metabolite 6-sulphatoxymelatonin (aMT6s), was used as a primary marker of seasonal, circadian and treatment changes. A substantial phase delay of melatonin in winter was advanced to summer phase by a two pulse 'skeleton' bright white light treatment. Subsequently a single morning pulse of bright white light was effective with regard to circadian phase and improved daytime performance. The circadian delay evidenced by melatonin was accompanied by delayed sleep (logs and actigraphy): poor sleep is a common complaint in Polar regions. Appropriate extra artificial light, both standard white, and blue enriched, present throughout the day, effectively countered delay in sleep timing and the aMT6s rhythm. The most important factor appeared to be the maximum light experienced. Another manifestation of the winter was a decline in self-rated libido (men only on base at this time). Women on the base showed lower aspects of physical and mental health compared to men. Free-running rhythms were seen in some subjects following night shift, but were rarely found at other times, probably because this base has strongly scheduled activity and leisure time. Complete circadian adaptation during a week of night shift, also seen in a similar situation on North Sea oil rigs, led to problems readapting back to day shift in winter, compared to summer. Here again timed light treatment was used to address the problem. Sleep, alertness and waking performance are critically dependent on optimum circadian phase. Circadian desynchrony is associated with increased risk of major disease in shift workers. These studies provide some groundwork for countering/avoiding circadian desynchrony in rather extreme conditions.
Address Biochemistry and Physiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK. Electronic address: b.middleton@surrey.ac.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 0016-6480 ISBN Medium
Area Expedition Conference
Notes PMID:28526480 Approved no
Call Number IDA @ john @ Serial 2248
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Author Asher, A.; Shabtay, A.; Brosh, A.; Eitam, H.; Agmon, R.; Cohen-Zinder, M.; Zubidat, A.E.; Haim, A.
Title “Chrono-functional milk”: The difference between melatonin concentrations in night-milk versus day-milk under different night illumination conditions Type Journal Article
Year 2015 Publication Chronobiology International Abbreviated Journal Chronobiol Int
Volume 32 Issue 10 Pages 1409-1416
Keywords Animals; Heart rate; illumination; melatonin; night-milk; chronobiology
Abstract Pineal melatonin (MLT) is produced at highest levels during the night, under dark conditions. We evaluated differences in MLT-concentration by comparing daytime versus night time milk samples, from two dairy farms with different night illumination conditions: (1) natural dark (Dark-Night); (2) short wavelength Artificial Light at Night (ALAN, Night-Illuminated). Samples were collected from 14 Israeli Holstein cows from each commercial dairy farm at 04:30 h (“Night-milk”) 12:30 h (“Day-milk”) and analyzed for MLT-concentration. In order to study the effects of night illumination conditions on cows circadian rhythms, Heart Rate (HR) daily rhythms were recorded. MLT-concentrations of Night-milk samples from the dark-night group were significantly (p < 0.001) higher than those of Night-illuminated conditions (30.70 +/- 1.79 and 17.81 +/- 0.33 pg/ml, respectively). Interestingly, night illumination conditions also affected melatonin concentrations at daytime where under Dark-Night conditions values are significantly (p < 0.001) higher than Night-Illuminated conditions, (5.36 +/- 0.33 and 3.30 +/- 0.18 pg/ml, respectively). There were no significant differences between the two treatments in the milk yield and milk composition except somatic cell count (SCC), which was significantly lower (p = 0.02) in the Dark-Night group compared with the Night-Illuminated group. Cows in both groups presented a significant (p < 0.01) HR daily rhythm, therefore we assume that in the night illuminated cows feeding and milking time are the “time keeper”, while in the Dark-night cows, HR rhythms were entrained by the light/dark cycle. The higher MLT-concentration in Dark-night cows with the lower SCC values calls upon farmers to avoid exposure of cows to ALAN. Therefore, under Dark-night conditions milk quality will improve by lowering SCC values where separation between night and day of such milk can produce chrono-functional milk, naturally rich with MLT.
Address b Department of Evolutionary and Environmental Biology , Faculty of Natural Sciences, The Israeli Center for Interdisciplinary Research in Chronobiology, University of Haifa , Mount Carmel , Haifa , Israel
Corporate Author Thesis
Publisher Taylor & Francis Place of Publication Editor
Language English Summary Language English Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0742-0528 ISBN Medium
Area Expedition Conference
Notes PMID:26588495 Approved no
Call Number IDA @ john @ Serial 1312
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