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Melatonin, Circadian rythmn and cancer


john

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There is an interesting article in the Washingonian. It is a DC area magazine so it might be hard to find unless you are in near DC.

It was about melatonin and its cancer fighting properties and also sleeping and breast cancer.

Basically, it showed evidence that women whose sleep pattern was disrupted (night shift nurses) and a higher incidence of breast cancer.

It also showed some eveidence of melantonins ability to increase survival when given with chemo.

I have not read the whole article throughly but it looked interesting

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  • 5 weeks later...

Interesting tidbits from the article. Most of the info was about breast cancer but there was some stuff that seemed relavent to lc. I found links to similar information

http://www.mayoclinic.com/health/melato ... -melatonin

Off topic but Tamoxifen and melatonin may work better in treating breast cancer.

Someone mentioned chemothreapy and timing. The article talked about how certain chemos are best given at certain times of the day. Hrushesky is a leader in this research - circadian cancer therapy

http://www.annieappleseedproject.org/cirtimofcanc.html

http://www.jco.org/cgi/content/abstract/11/7/1403

drugs development based on circadian rhythm

http://www.sciencemag.org/cgi/content/a ... 28/4695/73

developing drugs using circadian rhythm

http://www.sciencedaily.com/releases/20 ... 080646.htm

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John,

Melatonin is one of the supplements that I have taken from the beginning. I now take 20mg before bed every night. I have read that it was used at this dose and had some good results with side effects as well as treating cancer. I take so many things so I can’t say what each one does. I just pray combined they will help.

Stay positive, :)

Ernie

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John,

Here is a list of studies, some showing some positive results, from the Sloan Ketering web site: Go to this site and go to melatonin for link to these studies.

http://www.mskcc.org/mskcc/html/11570.cfm?tab=HC

References

1. Sack RL, Lewy AJ, Hughes RJ. Use of melatonin for sleep and circadian rhythm disorders. Ann Med 1998;30:115-21.

2. Avery D, Lenz M, Landis C. Guidelines for prescribing melatonin. Ann Med 1998:30:122-30.

3. Brzezinski A. Melatonin in humans. N Engl J Med 1997;336:186-95.

4. Xi SC, et al. Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo by melatonin: association of antiproliferative action of the pineal hormone with mt1 receptor protein expression. Prostate 2001;46:52-61.

5. Cos S, Garcia-Bolado A, Sanchez-Barcelo EJ. Direct antiproliferative effects of melatonin on two metastatic cell sublines of mouse melanoma (B18BL6 and PG19). Melanoma Res 2001;11:197-201.

6. Blask E, Wilson ST, Zalatan F. Physiological melatonin inhibition of human breast cancer cell growth in vitro: evidence for a glutathione-mediated pathway. Cancer Res 1997;57:1909-14.

7. Karbownik M, Reiter RJ. Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation. Proc Soc Exp Biol Med 2000;225:9-22.

8. Reppert SM, Weaver DR. Melatonin Madness. Cell 1995;83:1059-62.

9. Lusordi P, Piazza E, Fogari R. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin Pharmacol 2000;49:423.

10. Hartter S, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.

11. Von Bahr C, et al. Fluvoxamine but not citalopram increases serum melatonin in healthy subjects - an indication that cytochrome P450 CYP1A2 and CYP2C19 hydroxylate melatonin. Eur J Clin Pharmacol 2000;56:123-7.

12. DeMuro RL, et al. The absolute bioavailability of oral melatonin. J Clin Pharmacol 2000;40:781-4.

13. Zhdanova IV, Wurtman RJ, Regan MM, et al. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab 2001;86:4727-30.

14. Leone M, et al. Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia 1996;16:494-6.

15. Shamir E, et al. Melatonin treatment for tardive dyskinesia: A double-blind, placebo-controlled, crossover study. Arch Gen Psychiatry 2001;58:1049-52.

16. Garfinkel D, et al. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med 1999;159:2456-60.

17. Wolfler A, et al. Questionable benefit of melatonin for antioxidant pharmacologic therapy. J Clin Oncol 2002;20:4127-9.

18. Ghielmini M, et al. Double-blind randomized study on the myeloprotective effect of melatonin in combination with carboplatin and etoposide in advanced lung cancer. Br J Cancer 1999;80:1058-61.

19. Lissoni P, et al. A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients. Br J Cancer 1996:74:1466-8.

20. Lissoni P, et al. A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer 1994;73:699-701.

21. Lissoni P, Chilelli M, Villa S, Cerizza L, Tancini G. Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial. J Pineal Res. 2003 Aug;35(1):12-5.

22. Peres MF, et al. Melatonin, 3 mg, is effective for migraine prevention. Neurology. 2004 Aug 24;63(4):757.

23. Buscemi N, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta analysis. BMJ 2006; 332: 385-88.

Stay positive, :)

Ernie

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John

I read a lot about it

you could goggle

Night workers and breast cancer

and get many studies about

Melantonin.

I have breast cancer so I

know about it

Jackie

here is a study

Night shifts 'increase breast cancer risk'

Night work may alter the body's chemical balance

Scientists have produced more evidence that night work can damage health.

An analysis of data from Denmark suggests women who work at night may be at an increased risk of developing breast cancer.

The study follows research which suggests working at night increases the risk of heart disease.

This study is big enough not to be swept under the carpet

Professor Gordon McVie, Cancer Research Campaign

Dr Johnni Hansen, of the Institute of Cancer Epidemiology in Copenhagen, studied the medical and employment records of 7,035 women between the ages of 30 and 54 who had been diagnosed with breast cancer.

He found that women whose work involved night shifts were 1.5 times more likely than daytime workers to be diagnosed with breast cancer.

Dr Hansen found that the longer a woman regularly worked at night, the higher her risk of developing the disease.

The reason for the link is unclear.

But some studies have suggested night workers are more likely to consume alcohol, a known risk factor for breast cancer.

Artificial light

Another theory is that the risk is increased by exposure to artificial light.

It is thought artificial light acts to suppress production of a hormone called melatonin, which is normally produced in the body at night.

Research has suggested low levels of melatonin may either stimulate the growth of cancerous cells in the breast, or encourage the production of the female sex hormone oestrogen, which has been widely linked to breast cancer.

Dr Hansen argues that the experience of blind women provides evidence to back this theory up.

Blind women have approximately a 50% smaller risk of developing breast cancer than other women.

As these women cannot sense light visually, it has no impact on their melatonin production.

Professor Gordon McVie, director general of the Cancer Research Campaign, said: "This study is completely inconclusive, and the increased risk is not enormous.

"But it is a big enough study not to be swept under the carpet."

Prof McVie said the fact that people who live in the Mediterranean area do not suffer higher rates of breast cancer suggested the melatonin theory may not be correct.

He said several other hormones could equally be implicated in any possible link between night work and breast cancer

The research is published in the journal Epidemiology.

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John

Here is one and lung cancer

is mentioned.

Melatonin as Cancer Treatment

Although it is not usually considered a standard antioxidant, melatonin, the hormone secreted by the pineal gland in response to cycles of light and dark, has exhibited potent free radical-scavenging properties against hydroxyl and peroxyl radicals.108

Melatonin has also been found to have some interesting anti-tumor properties in vitro. It increases p53 expression in breast cancer cells, and therefore significantly reduces cell proliferation.8 Impaired p53 expression is associated with many human cancers.109 Melatonin is also known to modify many cytokines, including TNF, IL1, IL-2, IL-6, and gamma-interferon, in ways consistent with increased host defense against cancers.110 Melatonin, perhaps through reduction of TNF secretion, has been shown to reduce cachexia in patients with metastatic solid tumors.

Patients taking melatonin (20 mg/day) were found to have significantly less weight loss (3 kg vs. 16 kg) and disease progression (53% vs. 90%) than those treated with supportive care alone.111

In another study, 63 patients with non-small cell lung cancer refractory to cisplatin therapy were randomized to receive either 10 mg/day of melatonin or supportive care alone. Patients receiving melatonin lived longer on average than those receiving supportive care alone (6 vs. 3 months) and were more likely to survive for one year (8/31 survivors vs. 2/32).

No drug-related toxicity was noted by the authors.112 Treatment with melatonin (20 mg/day) was also associated with greater one-year survival than supportive care alone in patients with brain metastases.113 Other studies have noted increased survival in malignant melanoma114 and patients with metastatic disease.115

The latter study stressed that based in its effects on the immune system, melatonin could be tested in association with other anti-tumor treatments.115 The DiBella multitherapy of cancer, of which melatonin is a part (along with many other agents), was found not to have sufficient efficacy against advanced cancer to warrant further investigation.116 Animal experiments suggest doses as high as 250 mg/kg are non-toxic.117

Melatonin with Radiation

In a randomized trial including 30 patients with glioblastoma, the effect of radiotherapy plus 20 mg/day of melatonin was compared to that of radiotherapy alone. At the end of one year, six of the 14 patients receiving melatonin were still living, compared to one of the 16 undergoing radiotherapy alone. The authors also noted fewer side effects from radiotherapy in patients taking melatonin.118

Melatonin with Chemotherapy

Melatonin has been studied a number of times as an adjunct to standard chemotherapy in humans. A phase II study used tamoxifen plus melatonin (20 mg/day) in the treatment of metastatic breast cancer which had progressed under treatment with tamoxifen alone. Four of the 14 patients tested had partial response to this combination, with a median of eight months before disease progression. Treatment was well-tolerated and relief of anxiety or depression was noted by many patients.19

A similar study was conducted using the same combination of treatments in patients with metastatic solid tumors other than breast cancer which had not responded to previous chemotherapies. Partial response or stable disease was seen in 16/25 patients. One year survival was seen in 7/25 patients.119

In another phase II study, melatonin (20 mg/day) led to a normalization of platelet counts in nine of twelve breast cancer patients who acquired thrombocytopenia during epirubicin therapy. Objective tumor regression was noted in five of the 12 patients.120 A randomized trial investigated the difference between melatonin (20 mg/day), cisplatin, and etoposide, and treatment with cisplatin and etoposide alone in advanced non-small cell lung cancer.

One-year survival was significantly higher in patients receiving adjunctive melatonin compared to standard chemotherapy alone (15 of 34 vs. 7 of 36). There was a non-significant trend toward greater tumor response in melatonin-treated patients as well (11 of 34 vs. 6 of 36). Myelosuppression, neuropathy, and cachexia were noted less frequently in patients receiving melatonin than in those that were receiving only chemotherapy.121

A double-blind trial was unable to replicate this protective effect of melatonin on the myelosuppression mediated by carboplatin and etoposide. This may reflect the effect higher doses of chemotherapeutic agents given in the second trial. The authors concluded that potentiation of the effect of chemotherapy by melatonin was unlikely.122 Concomitant therapy with melatonin (40 mg/day) has been found to increase the effect of interleukin-2 against a variety of solid cancers.123 The combination of melatonin (40 mg/day) and interleukin-2 has been found to be a more effective treatment than cisplatin and etoposide in non-small cell lung cancer.124

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I read if you have to get up during the night, never put or leave a light on! If you must, use a red light.

Boy that sounds like we'll be in the "red light district" Maybe they knew something we don't, to preserve their job security.

Donna G

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Donna,

We have to get back to the

stone age, I think it is the

stimulus with the light, more

than only the light that may

cause it.

I know that a study was done

after many nurses in the same

hospital were dx with cancer,

they were on the night shift.

No word about people looking

at TV all night long or out

in clubs all night.

For myself I read very late

at night and always did it,

still reading.

Jackie

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