From:
Sukie Crandall
Date: 2005-11-23 16:15:34 UTC
Subject: [ferrethealth] metanalysis of melatonin for a range of solid malignancies (and also some studies on its potential use for lympho, ADV, etc.)
To: ferrethealth@smartgroups.com
A press release in Eurekalert points to something on which the U.S.
veterinary community was faster on the uptake than the U.S. medical
community, though it has not be applied as widely as perhaps it can be.
In a metanalysis of multiple studies found a 34% reduction in death
rate at one year among the humans with a range of solid tumors when
large doses of melatonin were used.
I wonder what other tumors in ferrets besides adrenal ones may work
out better with melatonin as part of the treatment?
Melatonin is a natural product which the pineal gland produces in
response to darkness. Light exposure decreases melatonin production,
even a night light. In fact, I recall reading a while back of a
study starting on whether NOT using night lights would improve
survival for human childhood leukemia patients, but have not run into
anything on that, yet, but in looking for that I found some
potentially intriguing studies that are mentioned under the J. Pineal
Res. article.
START QUOTE
Journal of Pineal Research
Volume 39 Issue 4 Page 360 - November 2005
doi:10.1111/j.1600-079X.2005.00258.x
Melatonin in the treatment of cancer: a systematic review of
randomized controlled trials and meta-analysis
Edward Mills1, Ping Wu2,3, Dugald Seely3,4 and Gordon Guyatt1
Abstract: Most observational studies show an association between
melatonin and cancer in humans. We conducted a systematic review of
randomized controlled trials (RCTs) of melatonin in solid tumor
cancer patients and its effect on survival at 1 yr. With the aid of
an information specialist, we searched 10 electronic databases from
inception to October 2004. We included trials using melatonin as
either sole treatment or as adjunct treatment. Prespecified criteria
guided our assessment of trial quality. We conducted a meta-analysis
using a random effects model. We included 10 RCTs published between
1992 and 2003 and included 643 patients. All trials included solid
tumor cancers. All trials were conducted at the same hospital
network, and were unblinded. Melatonin reduced the risk of death at 1
yr (relative risk: 0.66, 95% confidence interval: 0.59Ð0.73, I2 = 0%,
heterogeneity P ² 0.56). Effects were consistent across melatonin
dose, and type of cancer. No severe adverse events were reported. The
substantial reduction in risk of death, low adverse events reported
and low costs related to this intervention suggest great potential
for melatonin in treating cancer. Confirming the efficacy and safety
of melatonin in cancer treatment will require completion of blinded,
independently conducted RCTs.
END QUOTE
Press release:
http://www.eurekalert.org/pub_releases/2005-11/mudo-ttr112205.php
MORE (There are others so I will need to make time to read more
widely if I can, BUT NOTE THE GENERAL STATEMENT BELOW since it should
also have veterinary implications):
START QUOTE
Med Hypotheses. 2005;64(4):864-71.
Related Articles, Links
Could visible light contribute to the development of leukaemia and
other cancers in children?
Erren TC.
Institute and Policlinic for Occupational and Social Medicine, School
of Medicine and Dentistry, University of Cologne, Joseph-Stelzmann-
Str. 9, 50924 Koln, Lindenthal, Germany. tim.erren@uni-koeln.de
This paper suggests to rigorously test the hypothesis that there are
causal links between visible light and the development of leukaemia
and other cancers in children. Light can be considered as a candidate
risk factor because it suppresses melatonin biosynthesis which may
play a role in a series of anticancer defences. Indeed, melatonin may
offer some protection against all "hallmarks of cancer" [i.e., self-
sufficiency in growth signals; insensitivity to growth-inhibitory
signals; evasion of programmed cell death (apoptosis); limitless
replicative potential; sustained angiogenesis; tissue invasion and
metastasis] recently suggested by Hanahan and Weinberg. Already
ongoing investigations into the possible nexus of light, endocrine
systems and the development of cancers will be further fueled by
recent insights into photoreception and -- transduction, including
the discovery of "novel" photoreceptors in the eye. Among a variety
of different photosensory tasks, these receptors constitute crucial
gates for light information from the environment which is employed
for the temporal organization of our physiology and it has been
proposed that chronodisruption, i.e., a significant disturbance of
the coordination and thus order of biological rhythms, could
contribute to the development of cancers. With regard to public
health, the pervasive exposures to light -- at work and in homes --
imply that visible radiation could be a strong risk factor defined
epidemiologically as a causal contributor to disease in a large
proportion of cases. Importantly, if light were to be corroborated as
a contributor to cancers in children, it would be amenable to
manipulations with the perspective of reducing inherent risks
significantly. In fact, it could be much easier -- and much more
effective -- to reevaluate and modify lighting systems than to
manipulate other possible determinants of the chronic processes of
cancer such as genetic, nutritional or lifestyle factors.
This article in PubMed may be of use to some, too, because of an
interesting possible mechanism discussed (abstract available at PubMed):
START QUOTE
Henshaw DL, Reiter RJ.
Do magnetic fields cause increased risk of childhood leukemia via
melatonin disruption?
Bioelectromagnetics. 2005;Suppl 7:S86-97.
PMID: 16059923 [PubMed - in process]
END QUOTE
This is a veterinary study of melatonin reducing the impact of some
viral diseases in animals. Note the ADV mention and more. Also,
remember that some malignancies can have disease triggers:
START QUOTE
J Pineal Res. 2004 Mar;36(2):73-9.
Related Articles, Links
Melatonin and viral infections.
Bonilla E, Valero N, Chacin-Bonilla L, Medina-Leendertz S.
Instituto de Investigaciones Clinicas 'Dr. Americo Negrette',
Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.
ebonillaro@yahoo.com
The therapeutic effects of melatonin against viral infections, with
emphasis on the Venezuelan equine encephalomyelitis (VEE), are
reviewed. Melatonin has been shown to prevent paralysis and death in
mice infected with the encephalomyocarditis virus and to decrease
viremia. Melatonin also postpones the onset of the disease produced
by Semliki Forest virus inoculation and reduces the mortality of West
Nile virus-infected mice stressed by either isolation or
dexamethasone injection. An increase in the host resistance to the
virus via a peripheral immunostimulatory activity is considered
responsible for these effects. It has also been demonstrated that
melatonin protects some strains of mink against Aleutian disease, and
prevents the reduction of B- and T-cells as well as Th1 cytokine
secretion in mice infected with leukemia retrovirus. In VEE-infected
mice, melatonin postpones the onset of the disease and death for
several days and reduces the mortality rate. This protective effect
seems to be due to the increase in the production of
interleukin-1beta (IL-1beta), as 100% of the infected mice treated
with melatonin die when IL-1beta is blocked with antimurine IL-1beta
antibodies. Although melatonin administration raises serum levels of
tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-
gamma), the mortality observed in neutralization experiments with the
corresponding anticytokine antibodies, suggests that neither TNF-
alpha nor IFN-gamma are essential for the protective effect of
melatonin on murine VEE virus infection. Melatonin treatment also
enhances the efficiency of immunization against the VEE virus.
Reactive oxygen species have been implicated in the dissemination of
this virus, and their deleterious effects may be diminished by
melatonin. This indole inhibits nitric oxide synthetase activity and
it is a potent scavenger of nitric oxide, which also plays an
important role in the spread of the VEE virus. In conclusion, the
immunomodulatory, antioxidant, and neuroprotective effects of
melatonin suggest that this indole must be considered as an
additional therapeutic alternative to fight viral diseases.
END QUOTE
BTW, it has recently been found in humans that lymphoid cells also
produce melatonin and that this plays a part in immune system
regulation. (Found in this abstract which indicates that it may be
useful when lymphoma is present):
START QUOTE
J Pineal Res. 2005 Nov;39(4):425-31.
Related Articles, Links
Melatonin provokes cell death in human B-lymphoma cells by
mitochondrial-dependent apoptotic pathway activation.
Trubiani O, Recchioni R, Moroni F, Pizzicannella J, Caputi S, Di
Primio R.
Dipartimento di Scienze Odontostomatologiche, Universita di Chieti-
Pescara, Via dei Vestini, Chieti, Italy. trubiani@unich.it
Apoptosis is an important cell suicide programme involved in
physiological and pathological processes. Apoptosis can be induced in
different ways depending on cell type and acquired signal. Melatonin,
the major secretory product of the pineal gland, participates in many
important physiological functions and displays a remarkable
functional versatility exhibiting antioxidant, oncostatic, anti-
aging, and immunomodulatory properties. Recently, it has been shown
that, in addition to pineal gland, human lymphoid cells are an
important physiological source of melatonin and that may be involved
in the regulation of the immune system. In this work, we examine the
effect of melatonin on RAMOS-1 human leukaemic cells. Cell growth and
viability, DNA fragmentation and JC-1, and annexin V expression have
been determined. To elucidate the mechanism of action of melatonin,
Western blot analyses for Bcl-2 and caspase-3 expression, and
cytochrome c release were carried out. The results suggest that the
apoptotic effect of melatonin is associated with cell-cycle arrest,
downregulation of Bcl-2, mitochondrial membrane depolarization,
cytochrome c release and activation of caspase-3. The intrinsic
(mitochondrial dependent) pathway of caspase activation is the 'point
of no return' commitment to cell death. Taken together, our study
indicates that melatonin may play a role as potential therapeutic
drug in specific lymphoproliferative diseases.
END QUOTE
There also was a recent discovery that it is found in large amounts
in marrow [pers. com. Dr. Jerry Murray]
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