Sıra | DOSYA ADI | Format | Bağlantı |
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01. | Developed Increase Anisimov Tumor | pptx | Sunumu İndir |
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В. АнисимовLight desynchronosis, aging and cancer:Epidemiological and experimental data Vladimir N. AnisimovN.N.Petrov Research Institute of Oncologyaging@mail.ru “J. Gerontol. & Geriatr. Res.
Pineal gland, aging and cancer Night peak of melatonin inhibited by: Living at North Shift work Jet lag Light-at-night Insomnia Circadian genes KO Pinealectomy Peak of melatonin increased by: Hybernation Darkness at a day Blindness Melatonin Epitalon
XXXXXNeuro regulation of pineal function:Targets for interventions Constant illuminationLight deprivationSympathectomyPinealectomyEnucleationSCN damageClock genes KOJet lagInsomniaHybernationeye SCN
Survival of hamsters bearing tau-mutation in the circadian oscillator of hypothalamic SCNВозраст, мес.Hurd M.W., Ralph M.R., 1998
Cancer risk in air crewBreast cancer Prostatic cancerChronic jetlag increases cancer riskStewardesses Pilots
Light regimen and risk of diseases • Cardiovascular diseases + 51% Kawachi et al., Circulation, 1995; 92: 3178• Obesity and metabolic syndrome + 56% Karlsson et al., Occup. Environ. Med. 2001; 58:747• Stomach and duodenum ulcer – 3.9 times Pietroiusti et al., Occup. Environ. Med. 2006; 63:773• Breast and colon cancer + 36% Schernhammer et al., J.Natl.Cancer Inst., 2001, 2003Mean urinary 6-SOMT level was 43% lower in night workers compared to day workers. Papantoniou et al., 2014
Increase in breast cancer risk depends on the exposure to light at night Life style Breast cancer risk_____________________________________Insomnia Once a week 1.14 (1.01 - 1.28) 3 times a week 1.4 (1.0 - 2.0) > 4 times a week 2.3 (1.2 - 4.2) Bright light in bedroom 1.4 (0.8 - 2.6)Shift work 1.6 (1.0 -2.5)Davis S. et al., 2001
Relative risk of breast cancer in shift-worker nursesOccupation, years Breast carcinoma, RR____________________________________ 1 - 14 years 1.08 (0.99 - 1.18)15 - 29 years 1.08 (0.90 - 1.30) 30+ years 1.36 (1.04 - 1.78)Schernhammer E. et al., 2001Every 5 year increase of exposure to night shift work correspondingly enhance the risk of breast cancer in female by 3%. The increase in 500-night shifts would result in a 13% increase in breast cancer risk.Wang F. et al., 2013
Light deprivation and breast cancer risk in femalesVisual lesion RR of Authors(blindness) Breast cancer_________________________________________ Complete 0.82 (0.47-1.34) Feychting, 1998Partial 1.06 (0.92-1.21)________________________________________________Complete 0.47 (0.01-2.63) Verkasalo, 1999Significant 0.66 (0.24-1.44)Moderate 1.05 (1.05-1.30)________________________________________________Complete 0.57 (0.35-0.92) Hahn, 1991
Breast cancer mortality in inuites of Alaska increased 3 times since 1969 due to unknown reason. Kelly et al., 2006Energy consumption, kWh/ personNS
Сancer in Five Continents, vols.VI -IX Lyon: IARC, 1985 - 2007BreastEndometriumCervixStomachNSSNSNNSS Breast and colon cancer risk increased at NorthBorisenkov, Anisimov, 2011
Earth at nightBreast and prostatic cancer risk highest at more illuminated places. Kloog et al., 2008, 2009, 2010
Mutations in clock genes: main effects Per2-/-: life span reduction, premature switch-off reproduction function, increases cancer riskClock/Clock: obesity, metabolic syndrome, anovulation, tumorigenesis Bmal1-/-: life span reduction, lipid peroxidation, cataract, sarcopenia Cry1-/-Cry2-/-: no effect on life span and cancerE-box Per1, Per2, Per3, Cry1, Cry2, Rev-erbα, RorαCLOCK/NPAS2BMAL1REV-ERBαs RORsRORE Bmal1PERs CRYsCK1ε/δPPМетаболическийтранскрипционныйфакторМеханизм внутренних молекулярных часов клетки
Suppression of clock genes in human tumorsgene Cancer AuthorsPer1 Breast cancer Chen et al., 2005;Gery et al., 2006Lung cancer Gery et al., 2006Endometrial cancer Yeh et al., 2005Pancreatic cancer Pogue-Geile et al., 2006Per2 Acute myeloid leukemia Gery et al., 2005Breast cancer Chen et al., 2005Per3 Breast cancer Chen et al., 2005;Zhu et al., 2005
Effect of light regimen onlife span and spontaneous tumorigenesis in ratsVinogradova, Anisimov, 2009Rats NaturalNL(300 rats)ConstantLL(300 rats)Standard LD(300 ratz)DarknessDD(100 rats)controlMLTEpitaloncontrolMLTEpitaloncontrolMLTEpitaloncontrol
Effect of light regimen on puberty and ovulatory function in female rats*P<0.02LL and NL accelerated both switch-on and switch-off of estrus functionVinogradova et al., 2009020406080100120дни%LDNLLLDD01020304050607080903 5 8 11 14 17 20 23месяцы, возраст%* * * ** ******** **
LD – 12 h. : 12 h. ; NL – natural lighting at PetrozavodskLL – constant illumination; DD – light deprivation
Metabolic syndrome in rats exposed to constant or natural illumination Obesity and abdominal fat excess Hypercholesterolemia Beta-lipoproteinemia Hyperglycemia and glucosuria Increase in C-peptide level premature switching-off of reproductive function increase in spontaneous tumor incidence____________________________________________Overnight treatment with melatonin prevents metabolic syndrome, slows down reproductive aging and spontaneoustumor development in а female ratsVinogradova, Anisimov, 2013
Effect of light regimen on NMU-induced mammary carcinogenesis in ratsAnisimov et al., Adv. Pineal Res., 1994LAN promotes whereas darkness inhibits mammary carcinogenesis01020304050607080901000 50 100 150 200 250 300 350light:lightlight:darkdark:dark
Effect of light regime on NEU-induced transplacental carcinogenesis in rats Beniashvili & Anisimov, Cancer Lett., 2004 %Light at night promotes whereas darkness inhibits tumorigenesis in nervous system and kidney01020304050607080TotaltumorsNervoussystemKidneyLDLLDD
HemangiomaSarcomaLAN increases body weight and temperature, accelerates switching-off of estrous cycle, decreases tumor latency and life span.З
Effect of constant illumination and melatonin on mammary carcinogenesis in transgenic HER-2/neu miceGroup N No of Tumor No of TBM size, MAC/ cm mouse _________________________________________LD 30 23 (77%) 1,9 3,3LL-300 лк 28 20 (71%) 1,8 5,2*LL-2500 лк 38 19 (96%) 2,9* 4,8*LL + MLT 22 13 (59%) 1,3* 3.5* * P < 0.05 Anisimov et al., Int. J. Cancer, 2004M SalineSalMelMel1114900692501404320242190147124bp
Effect of light regime on 1,2-dimethylhydrazine-induced colon carcinogenesis in rats % * p<0,05***Panchenko et al., 2006Descended colon PCNAECLight at night promotes whereas darkness inhibits colon carcinogenesis024681012LDLLLL+MLTDD0100200300400500600LDLLL+MLTDD020406080100LDLLL+MLTDD
Melatonin inhibits 1,2-dimethylhydrazine-induced colon carcinogenenesis in rats (Anisimov et al., Carcinogenesis, 1987) Tumor incidence***p<0.05MI AI**Ascendent colon Descendent colon- C - Mel
Effect of melatonin on urethan-induced lung carcinogenesis in miceadenomaadenocarcinomaМДАVesnushkin et al.2007
Effect of melatonin on benzo(a)pyrene-induced skin carcinogenesis in miceMitotic indexMDAVesnushkin et al;. 20071,060,630,6900,20,40,60,811,2БП-контроль БП+мелатонин20 мг/лБП+мелатонин2 мг/л
Melatonin inhibits B(a)P-induced sarcomogenesis in miceMitotic index MDA in serum and in tumorsVesnushkin et al., 2007
Melatonin, aging and cancerMelatonin inhibits tumorigenesis in rodents: mammary gland*• endometrium• cervix and vagina*• colon*• skin*• soft tissues*• liver• lungs* * Anisimov et al.,Если эпифиз уподобить биологическим часам, то мелатонин можно уподобить маятнику, который обеспечиваетход этих часов и снижение амплитуды которого приводит к их остановке.Мыши-самки СВАStomach cancerMeta-analysis of 10 randomized trials showed dercrease in one-year mortality up to 0.66 (95% CI = 0.59-0.73) in solid tumor patients Mills et al., J.Pineal Res,2005SurvivorsErmachenkov et al, 2013
Effect of melatonin on life span, spontaneous tumorigenesis and gene expression in miceAnisimov et al., J. Gerontol. Biol.Med., 2001 Exp. Gerontol., 2003MLT and gene expression:Total clones : 15 247Effect of MLT: 233 (1,53%) Stimulation (>2 times): 164 Suppression (> 2 timrs): 69 Genes: Cell cycle Cell proliferation Adhesion Membrane transport Leukenia Mitochondrial genesСВАSHR
Effect of melatonin on life span of miceStrain % Authors______________Balb/c + 18% Pierpaoli & Regelson, 1994NZB + 40% Pierpaoli et al., 2001C57BL/6J + 20% Pierpaoli & Maestroni, 1987C3H + 20% Oxenkrug et al., 2001CBA + 7% Anisimov et al., 2001HER-2/neu + 13% Anisimov et al., 2002NOD + 17% Conti & Maestroni, 1998SAMP-8 + 35% Rodriguez et al., 2007
Decrease in melatonin productionTelomere lesionTelomere shorteningCellsenescence ApoptosisDNArepairp53, pRb p53AgingGenomic instabilityCancerConstant illumination: molecular mechanismsOxydative stressIGF-1Metabolicsyndrome
On the basis of ‘limited evidence in humans for the carcinogenicity of shift-work that involves nightwork”, and “sufficient evidence in experimental animals for the carcinogenicity of light during the daily dark period (biological night)” the Working Group concluded that “shift-work that involves circadian disruption is probably carcinogenic to humans” (Group 2A). Straif K. et al. Lancet Oncol. 2007; 8: 1065WHO International Agency for Research on Cancer, Lyon, France
Pineal, aging & cancer: ConclusionsPeak of melatonin increased by: Hybernation Darkness at a day Blindness Melatonin Epitalon Inhibition of nocturnal melatonin: Living at North Shift work Jet lag Light-at-night Insomnia Circadian genes KO Pinealectomy Premature aging and cancerSlow down of aging and cancer prevention
Journal of Gerontology& Geriatric Research Related Journals Aging Science Alzheimer's Disease & Parkinsonism Depression and Anxiety Emergency Mental Health Palliative Care & Medicinei il i ' i i ir i i tr t l ltlli ti i i
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