Vitamins
Steph
reported in the journal "Breast Cancer Research and Treatment", which shows
that high-dose vitamin therapy may in fact be harmful for some cancer
patients.
Before the loonies start up with the conspiracy theories, please note that a
co-author on this study is Dr Abram Hoffer, an "orthomolecular physician"
beloved of the alternative community.
You can read a short precis at http://www.canada.com/vancouver/ but here is
an extract:
Breast cancer study hints at harmful effects of vitamins: Caution advised in
taking mega-doses during treatment
The Vancouver Sun
Wed 04 Dec 2002
Page: A1
Section: News
Byline: Pamela Fayerman
Source: Vancouver Sun
Breast cancer patients who took vitamin supplements during treatment were
not only more likely to relapse, but also to die, according to a B.C. study.
"It's surprising, because a lot of people take vitamins in the hopes and
belief it will improve outcomes, but the study shows that there may even be
a harmful effect," said Dr. Ivo Olivotto, a study co-author and leader of
radiation oncology at the B.C. Cancer Agency, Vancouver Island Centre.
Other authors of the study, published in the current volume of the
international journal Breast Cancer Research and Treatment, included Mary
Lesperance, a statistician with the University of Victoria department of
math and statistics, and Dr. Abram Hoffer, a Victoria physician who
practises orthomolecular medicine, in which illness is treated and prevented
with nutritional supplements.
"This study dispels the myths about vitamins, at least in my mind," Olivotto
said, adding that he won't try to talk his patients out of using vitamins if
they are committed to them, but "for those who are wavering, we can tell
them about the findings in this study."
To conduct the study, funded with a $70,000 grant from the Lotte and John
Hecht charitable foundation, which often sponsors research on alternative
medicine therapies, investigators looked at survival and breast cancer
recurrence outcomes for 90 breast cancer patients diagnosed between 1989 and
1998. The supplements were recommended by Hoffer in the hope that they would
enhance immune systems, boost the efficiency of radiation and chemotherapy
and decrease the toxicity of the conventional therapy, among other things.
(Both the control group and vitamin group received conventional cancer
therapy.)
Hoffer has treated about 1,000 cancer patients with large doses of vitamins
and minerals, including 271 with breast cancer.
The vitamins and minerals included vitamin C, vitamin B3, selenium, zinc,
beta carotene and co-enzyme Q10. Supplements were prescribed in various
dosages that generally ranged from three to 300 times the recommended daily
allowance for such nutrients, as set by the food and nutrition centre of the
U.S. department of agriculture.
The vitamin-treated group was compared to a similar demographic of case
controls consisting of 180 breast cancer patients who did not take
supplements. Both groups of women had cancer in one breast that had not
spread at the time of diagnosis to any other part of the body.
The study found that overall survival at five years was 81 per cent for the
control (non-vitamin) group but only 72 per cent for the mega-vitamin
patients. Investigators calculated the hazard ratios -- the relative risk of
dying -- and found the vitamin group were 1.75 times more likely to die than
the control group and 1.55 times more likely to suffer a cancer relapse.
Lesperance said that of the 180 women in the control group, there were 35
deaths (19.4 per cent) from breast cancer and 44 relapses (24.4 per cent).
In the vitamin group, which was half the size, with 90 women, there were 23
deaths (25 per cent) from breast cancer and 30 relapses (33 per cent.)
"Breast cancer specific survival and disease-free survival times were not
improved for the vitamin/mineral treated group compared to controls," she
said.
The investigators do not know exactly why large doses of vitamins may not be
beneficial and in fact may be harmful. They state:
"Some oncologists believe that antioxidants could interfere with the actions
of some chemotherapy agents, however, the scientific debate on this subject
is still ongoing. In the meantime this study suggests caution in the use of
mega-doses of vitamins and minerals in patients with operable breast cancer
who are being treated with curative intent."
Olivotto said it is common for cancer patients to use alternative or
complementary therapies . Seventy per cent do, but it is not known how many
of those go to naturopathic doctors or doctors like Hoffer who believe in
the benefits of vitamins and minerals.
Hoffer could not be reached for comment.
Olivotto said the statistical outcomes had to be viewed with some caution
because the study group was relatively small: "The sample size may be too
small for us to absolutely say that there is a true statistical difference,
but I think we can conclude at this point that there is no evidence that
megadose vitamins are beneficial, and if anything, there is a hint of a
harmful effect."
He added that he hopes more research, involving larger groups of subjects,
will be done on the same subject. It is unclear what the implications are
for the relationship between vitamins and the prevention of cancer.
Kristofer D. Dale
> The proponents of high doses of vitamins may wish to look at a recent study
> reported in the journal "Breast Cancer Research and Treatment", which shows
> that high-dose vitamin therapy may in fact be harmful for some cancer
> patients.
Key phrase, "high dose". Before assuming that a nutritional approach is
undesirable, check this out:
http://www.vitaleTherapeutics.org/vtlwhatr.htm
--
_o Kristofer Dale,
_ \<,_ ragged individualist,
_____( )/ ( )_____ statistic at large...
p.s. Learn and live, http://www.vitaletherapeutics.org
Steph
"Kristofer D. Dale" <bare...@plato.nmia.com> wrote in message
news:o5WH9.5$K5.0@fe01...
> In sci.med.diseases.cancer Steph <st...@vancouver.island> wrote:
> > The proponents of high doses of vitamins may wish to look at a recent
study
> > reported in the journal "Breast Cancer Research and Treatment", which
shows
> > that high-dose vitamin therapy may in fact be harmful for some cancer
> > patients.
>
Get a grip
Kristofer D. Dale
> Get a grip
A grip on your pathetic fantasy that nutrition is bad for us? ;^]
Steph
> In sci.med.diseases.cancer Steph <st...@vancouver.island> wrote:
>
> > Get a grip
>
> A grip on your pathetic fantasy that nutrition is bad for us? ;^]
>
You are the one in a fantasy if you think that "good nutrition" is the same
as "high-dose vitamins", Dale.
doe
>From: "Kristofer D. Dale" bare...@plato.nmia.com
>Date: 12/7/2002 6:24 PM Mountain Standard Time
>Message-id: <dbxI9.4277$K5.3230@fe01>
>
>In sci.med.diseases.cancer Steph <st...@vancouver.island> wrote:
>
>> Get a grip
>
>A grip on your pathetic fantasy that nutrition is bad for us? ;^]
>
You are really wasting your time with ..
Steph..
Seeing that he professes to be a medical professional .. and in the next breath
states all the work the NIH is funding in regards to chelators of iron in
cancer is money 'misspent' .. and all the regression of cancer that is being
seen WITH the inclusion of chelators is simply .. placebo ..?
The 'man' has a screw loose ..most likely due to watching his patients
continuously .. die ..
Oh yeah .. especially since the drugs he has been using for years happen to BE
.. iron chelators ..
Nuts .. and THAT is NOT .. 'a good thing' .. when it comes to your doctor.. it
is a 'bad' .. thing.
The ONLY thing that protects us from the likes of 'Steph' is a little thing
called 'standard of care' in which the medical profession FORCES doctors to use
'approved methods' of treatment and in the case of doxorubicin .. is the
inclusion of iron chelators to PREVENT the 'likes of Steph' .. from killing us
with his/her .. stupidity.
Vet Pathol 2000 Jan;37(1):86-8
Anthracycline cardiotoxicity in a black rhinoceros (Diceros bicornis): evidence
for impaired antioxidant capacity compounded by iron overload.
Paglia DE, Radcliffe RW
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los
Angeles, CA 90095-1732, USA. dpa...@pathology.medsch.ucla.edu
Two weeks before dying of congestive heart failure, a juvenile black rhinoceros
(Diceros bicornis minor) received a single low dose of doxorubicin as part of
combination chemotherapy for acute lymphoblastic leukemia. Diffuse
hemosiderosis was present at necropsy in a pattern indicative of dietary iron
overload, but unique iron-positive degenerative lesions were found in isolated
myocardiocytes. Serum analyses revealed hyperferremia, 87% transferrin
saturation, and 5- to 10-fold elevations in ferritin concentration, reflecting
markedly increased tissue iron stores. Since both toxic and therapeutic effects
of anthracyclines are mediated by formation of reactive free radicals via
iron-catalyzed reactions, these observations suggest that iron overload may
have enhanced myocardial susceptibility to cardiotoxic effects of doxorubicin.
Impairments in other myocardial antioxidant defenses, such as deficiencies in
catalase and glutathione S-transferase that are known to exist in rhinoceros
erythrocytes, may have been underlying factors contributing to an inherent
sensitivity of rhinoceros tissues to oxidant-induced injury.
PMID: 10643986, UI: 20106802
--------------------------------------------------------------------------
------
Who loves ya.
Tom
Jesus was a vegetarian!
http://jesuswasavegetarian.7h.com
Jesus was a vegetarian! http://www.nucleus.com/watchman
Moses was a mystic! http://www.nucleus.com/watchman/light.html
Steph
"doe" <ironj...@aol.comdoe> wrote in message
news:20021208093116...@mb-mv.aol.com...
> >Subject: Re: Vitamins
> >From: "Kristofer D. Dale" bare...@plato.nmia.com
> >Date: 12/7/2002 6:24 PM Mountain Standard Time
> >Message-id: <dbxI9.4277$K5.3230@fe01>
> >
> >In sci.med.diseases.cancer Steph <st...@vancouver.island> wrote:
> >
> >> Get a grip
> >
> >A grip on your pathetic fantasy that nutrition is bad for us? ;^]
> >
>
> You are really wasting your time with ..
> Steph..
> Seeing that he professes to be a medical professional .. and in the next
breath
> states all the work the NIH is funding in regards to chelators of iron in
> cancer is money 'misspent' .. and all the regression of cancer that is
being
> seen WITH the inclusion of chelators is simply .. placebo ..?
>
Making it up again, Tom? When did I post either of those things?
> The 'man' has a screw loose ..most likely due to watching his patients
> continuously .. die ..
>
> Oh yeah .. especially since the drugs he has been using for years happen
to BE
> .. iron chelators ..
>
> Nuts .. and THAT is NOT .. 'a good thing' .. when it comes to your
doctor.. it
> is a 'bad' .. thing.
>
> The ONLY thing that protects us from the likes of 'Steph' is a little
thing
> called 'standard of care' in which the medical profession FORCES doctors
to use
> 'approved methods' of treatment and in the case of doxorubicin .. is the
> inclusion of iron chelators to PREVENT the 'likes of Steph' .. from
killing us
> with his/her .. stupidity.
>
You are a complete nutter
doe
>From: "Steph" st...@vancouver.island
>Date: 12/8/2002 11:19 AM Mountain Standard Time
>Message-id: <C2MI9.53844$Qr.12...@news3.calgary.shaw.ca>
>
>
>"doe" <ironj...@aol.comdoe> wrote in message
>news:20021208093116...@mb-mv.aol.com...
>> >Subject: Re: Vitamins
>> >From: "Kristofer D. Dale" bare...@plato.nmia.com
>> >Date: 12/7/2002 6:24 PM Mountain Standard Time
>> >Message-id: <dbxI9.4277$K5.3230@fe01>
>> >
>> >In sci.med.diseases.cancer Steph <st...@vancouver.island> wrote:
>> >
>> >> Get a grip
>> >
>> >A grip on your pathetic fantasy that nutrition is bad for us? ;^]
>> >
>>
>> You are really wasting your time with ..
>> Steph..
>> Seeing that he professes to be a medical professional .. and in the next
>breath
>> states all the work the NIH is funding in regards to chelators of iron in
>> cancer is money 'misspent' .. and all the regression of cancer that is
>being
>> seen WITH the inclusion of chelators is simply .. placebo ..?
>>
>
>Making it up again, Tom? When did I post either of those things?
It is called deduction there .. 'Steph' .. something that comes in handy when
one actually attempts to do research and since you obviously have NO idea what
research actually IS .. it is 'putting two and two together' .. and coming to a
possible conclusion / hypothesis.
You have repeatedly downplayed iron chelator use in cancer .. and HAVE gone so
far as to call them useless .. therefore .. deduction leads on to believe
EITHER you do not follow research OR if you do .. you have made the CONSCIOUS
decision to disregard these findings / research DUE TO your .. knowledge.
Therefore .. any regression of cancer with the use of chelators would be a
placebo effect .. or .. you simply ARE .. nuts ..
Now which conclusion do you prefer ..
Placebo .. or .. nuts .. ?
Actually I think I 'may' have to retract my statement of .. placebo effect ..
and settle for just plain .. nuts.. upon review of your statements in regards
to iron chelators in cancer.
-----------------------------------------------------------
Carcinogenesis 2001 Oct;22(10):1607-14
p53-independent apoptosis mediated by tachpyridine, an anti-cancer iron
chelator.
'Steph' replies ..
> charlatans/cancer
-----------------------------------------------------------
I believe the above .. spoken in a conference just might provoke one of the
researchers into crackin' ya right in the head ..
But .. no chance of that happening on a ng .. eh .. 'Steph' ..
Steph
"doe" <ironj...@aol.comdoe> wrote in message
>
> It is called deduction there .. 'Steph' .. something that comes in handy
when
> one actually attempts to do research and since you obviously have NO idea
what
> research actually IS .. it is 'putting two and two together' .. and coming
to a
> possible conclusion / hypothesis.
>
Tom, a rational deduction drawn from facts requires two things: rationality
and facts.
Since both concepts are alien to you, when you put two and two together, it
is clear that the answer is rarely four, and if it is, it is only so by
chance.
There are loonies, and there are the uneducated. Some loonies realise they
are loonies, some uneducated people realise they are uneducated. And some
uneducated loonies like you lack the insight necessary to realise what they
are.
doe
>From: "Steph" st...@vancouver.island
>Message-id: <vXNI9.179684$ka.41...@news1.calgary.shaw.ca>
>There are loonies, and there are the uneducated. Some loonies realise they
>are loonies, some uneducated people realise they are uneducated. And some
>uneducated loonies like you lack the insight necessary to realise what they
>are.
From the above I will 'dedeuce' you consider yourself to be a member of the ..
educated .. and thusly .. I say again .. the world needs more loonies ..
I say again . You disagree?
Again . YOU .. would.
Steph
"doe" <ironj...@aol.comdoe> wrote in message
> >Subject: Re: Vitamins
> >From: "Steph" st...@vancouver.island
> >Date: 12/8/2002 1:28 PM Mountain Standard Time
> >Message-id: <vXNI9.179684$ka.41...@news1.calgary.shaw.ca>
>
> >There are loonies, and there are the uneducated. Some loonies realise
they
> >are loonies, some uneducated people realise they are uneducated. And some
> >uneducated loonies like you lack the insight necessary to realise what
they
> >are.
>
> From the above I will 'dedeuce' you consider yourself to be a member of
the ..
> educated .. and thusly .. I say again .. the world needs more loonies ..
>
"dedeuce" what you like Tom
mike
>"Some oncologists believe that antioxidants could interfere with the actions
>of some chemotherapy agents, however, the scientific debate on this subject
>is still ongoing.
Steph,what do you think of amifostine? Amifostine just "happens" to
be a sulfhydryl antioxidant.Pubmed search yields 975 studies,many of
these do demonstrate amifostine to protect noncancerous cells and some
show potentiation with other agents against cancerous ones.
Chem Biol Interact 2002 Apr 20;140(1):1-18 Related Articles, Links
Genotoxicity of idarubicin and its modulation by vitamins C and E and
amifostine.
Blasiak J, Gloc E, Wozniak K, Mlynarski W, Stolarska M, Skorski T,
Majsterek I.
Department of Molecular Genetics, University of Lodz, Banacha 12/16,
Poland. jan...@biol.uni.lodz.pl
Idarubicin is an anthracycline anticancer drug used in haematological
malignancies. The main side effect of idarubicin is free-radicals based
cardiotoxicity. Using the comet assay we showed that the drug at
concentrations from the range 0.001 to 10 microM induced DNA damage in
normal human lymphocytes, measured as the increase in percentage of DNA in
the tail (% tail DNA). The effect was dose-dependent. Treated cells were
able to recover within a 120-min incubation. Recognised cell protector,
amifostine at 14 mM decreased the mean % tail DNA of the cells exposed to
idarubicin at all tested concentrations of the drug. So did vitamin C at
10 microM, but vitamin E (alpha-tocopherol) at 50 microM increased the %
tail DNA. Lymphocytes exposed to idarubicin and treated with endonuclease
III, formamidopyrimidine-DNA glycosylase and 3-methyladenine-DNA
glycosylase II, enzymes recognizing oxidized and alkylated bases,
displayed greater extent of DNA damage than those not treated with these
enzymes. Pretreatment of lymphocytes with nitrone spin traps,
N-tert-butyl-alpha-phenylnitrone and
alpha-(4-pyridil-1-oxide)-N-tert-butylnitrone decreased the extent of DNA
damage evoked by idarubicin. To discuss the influence of vitamins and
amifostine in cancer cells we used also murine pro-B lymphoid BaF3
transformed with BCR/ABL oncogene. These cells can be treated as model
cells of human acute myelogenous leukemia. The response of these cells to
vitamin E was quantitatively the same as human lymphocytes. However,
vitamin C did not exert any effect on DNA damage and amifostine, in spite
to normal lymphocytes, potentiated this effect. The results obtained
suggest that reactive oxygen species, including free radicals, may be
involved in the formation of DNA lesions induced by idarubicin. The drug
can also methylate DNA bases. Our results indicate that not only
cardiotoxicity but also genotoxicity and in consequence induction of
secondary malignancies should be taken into account as diverse side
effects of idarubicin.
* Amifostine may potentate DNA-damage effect of idarubicin in cancer cells
and decrease this effect in normal cells. *
Vitamin C can be considered as protective agents against DNA damage in
normal cells in persons receiving idarubicin-based chemotherapy, but the
use of vitamin E cannot be recommended and at least needs further
research.
PMID: 12044557 [PubMed - indexed for MEDLINE]
mike
>"Steph" <st...@vancouver.island> wrote:
>
>>"Some oncologists believe that antioxidants could interfere with the actions
>>of some chemotherapy agents, however, the scientific debate on this subject
>>is still ongoing.
Another good article on amifostine:
Anticancer Res 1998 May-Jun;18(3C):2203-10 Related Articles, Links
Chemoprotection in anticancer therapy: the emerging role of amifostine
(WR-2721).
Kurbacher CM, Mallmann PK.
Department of Gynecology and Obstetrics, University of Cologne Medical
Center, Germany.
Amifostine (WR-2721, Ethyol),
S-2[3-aminopropylamino]-ethyl-phosphorothioic acid, was selected as a
clinically usable radioprotector from more than 4,400 compounds in the
1950s. A considerable amount of preclinical work suggested that
amifostine, or its activated thiol WR-1065, protected normal cells
effectively against the adverse effects of irradiation and several
anticancer drugs without exhibiting tumor protection. In non-randomized
and randomized trials in malignant melanoma, colorectal cancer, head and
neck cancer, non-small cell lung cancer, and epithelial ovarian carcinoma,
amifostine significantly reduced the hematological and non-hematological
toxicity of DNA-damaging agents such as alkylators, platinum compounds, or
mitomycin C. In more recent studies, the drug also protected patients from
side effects produced by taxanes or topoisomerase I inhibitors and is thus
likely to allow higher cytostatic doses to be administered.
*Currently, there is no evidence that amifostine compromises the
antineoplastic effect of the drugs studied.
Otherwise, W/R-2721 may even improve the therapeutic efficacy of agents
like cisplatin, carboplatin, or paclitaxel.*
Moreover, amifostine appears to produce growth-factor like properties
resulting in growth-promoting effects on primitive blood progenitor cells
ex vivo. Amifostine offers a rational approach to protect patients against
chemotherapy-specific and often dose-limiting effects and is thus likely
to improve therapeutic outcome significantly. Future studies should be
focused on both new indications like childhood cancer, myelodysplastic
syndromes, dose-intensified or high- dose chemotherapy, and multimodality
approaches and optimization of amifostine dosage in order to reduce
dose-limiting side effects. Then, the drug may play a major role in more
specific and individualized oncologic strategies.
Publication Types:
Review
Review, Tutorial
Steph
"mike" <emka...@dodgenet.com> wrote in message
news:at1her$33f$1...@ins22.netins.net...
> "Steph" <st...@vancouver.island> wrote:
>
> >"Some oncologists believe that antioxidants could interfere with the
actions
> >of some chemotherapy agents, however, the scientific debate on this
subject
> >is still ongoing.
>
> Steph,what do you think of amifostine? Amifostine just "happens" to
> be a sulfhydryl antioxidant.Pubmed search yields 975 studies,many of
> these do demonstrate amifostine to protect noncancerous cells and some
> show potentiation with other agents against cancerous ones.
>
We use amifiostine as a salivary gland protector in some patients.
The ideal radioprotector would completely protect normal tissues, and offer
no protection to the cancer.
The ideal doesn't exist
mike
it protect normal tissues(not perfectly,but some),while still(according
to many pubmed studies),potentiate chemo or radiotherapy? According,to
the study you just gave this shouldnt be theoretically possible.
Would it be all that far-fetched to assume vitamins *could* do the same
thing;given adequate *effective* doses? Vitamins taken orally dont
probably achieve adequate AUC levels for very long.Given vitamins or
synthetic antioxidants such as amifostine with much longer half-lives,this
could be a much different story.
Steph
Most radioprotectors are sulfhydryls. Sulfhydryls soak up hydroxyl radicals,
which are reponsible for about 90% of the DNA damage done by radiation. They
don't really potentiate radiation or chemo, but they improve the therapeutic
ratio by protecting normal tissues more than cancers. The rreason they do
this are complex and often poorly understood, but at least in part, it is
because cancers have a poor blood supply, so drugs like amifostine don't get
to the cancer as well as they get to normal tissues.
The Holy Grail of radiation oncologists is to find one drug which is the
perfect radioprotector of normal tissues, and a second drug which is the
perfect radiosensitiser of cancers.
doe
>From: "Steph" st...@vancouver.island
>The Holy Grail of radiation oncologists is to find one drug which is the
>perfect radioprotector of normal tissues, and a second drug which is the
>perfect radiosensitiser of cancers.
So this is why IP6 would be working so well?
Iron chelator .. compared to other iron chelators .. used in trials to judge
the efficacy between chelators .. which have been shown to be BOTH radio
sensitiser and radioprotective?
Logic?
Radiat Res 2001 Aug;156(2):205-9
Redox metal chelation ameliorates radiation-induced bone marrow toxicity in a
mouse model.
Nagler RM, Eichen Y, Nagler A
Department of Oral and Maxillofacial Surgery and Oral Biochemistry Laboratory,
Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of
Technology, Haifa, Israel.
Since zinc desferrioxamine (Zn-DFO) has been shown to be a very potent
protector against injuries induced by redox-active metal ions, we examined its
protective effect against radiation-induced toxicity. We found that treatment
with Zn-DFO given before TBI increased the survival of mice irradiated with 7.5
and 8.5 Gy. Zn-DFO also protected against radiation-induced myelosuppression
and body weight loss, while soluble Il6 levels in serum were normalized in mice
pretreated with Zn-DFO. We concluded that administration of Zn-DFO prior to TBI
protected BALB/c mice from radiation-induced toxicity, increasing survival
rates by up to 75%. The biological effect of Zn-DFO is known to result from its
effect on the production of intracellular hydroxyl free radicals mediated by
redox-active metal ions, and both metal chelation and zinc delivery appear to
be equally likely mechanisms for this outcome. We suggest that
radiation-induced toxicity is caused by the deleterious effect of redox-active
metal ions, and that compounds which modulate this redox activity may act as
radioprotectors.
PMID: 11448242, UI: 21342546
--------------------------------------------------------------------------
------
CANCERLIT®
AUTHOR: Cook J
TITLE: Radiation sensitization of mammalian cells by metal chelators.
SOURCE: Radiat Res; 155(2):304-10 2001 UI: 21107885
ABSTRACT: The cell cycle effects, alteration in radiation response,
and inherent cytotoxicity of the metal chelators mimosine,
desferrioxamine (DFO),
N,N'-bis(o-hydroxybenzyl)-ethylenediamine-N,N'-diacetic acid (HBED),
and deferiprone (L1) were studied in exponentially growing Chinese
hamster V79 cells. Incubation of cells with 200-1000 microM mimosine
for 12 h reduced clonogenic survival to 50-60%, while incubation for
24 h reduced survival further to 0.5%. Mimosine treatment resulted in
cell cycle blocks at the G(1)/S-phase border and in S phase. Pulse
labeling with 5-bromodeoxyuridine indicated that the S-phase cells
ceased to actively replicate DNA after only 2 h of mimosine treatment
and were unable to replicate DNA for extended periods. Treatment of
V79 cells with 600 microM mimosine for 12 h resulted in
radiosensitization, yielding a sensitizer enhancement ratio (SER) of
2.7 +/- 0.3 at the 10% survival level. To study the kinetics of the
sensitization, V79 cells were incubated with mimosine for various
times up to 12 h and irradiated with a single 10-Gy dose of X rays. It
was found that the radiosensitization increased continually up to 8 h
(from a 3- to a 100-fold difference in survival) and then reached a
plateau after 8 h. Mimosine also equally radiosensitized human lung
cancer cells having either a normal or mutated TP53 gene, suggesting a
TP53-independent mechanism. To test whether iron binding by mimosine
was responsible for the observed radiosensitization, additional
experiments were performed using the iron chelators DFO, HBED and L1.
V79 cells treated with 500 microM of these agents for 8 h followed by
various doses of X rays gave SERs similar to that for mimosine
(2.0-2.7). These studies indicate that metal chelators are potent
radiosensitizers in V79 and human cells. Importantly, when the DFO was
preloaded together with Fe(3+) [Fe(III)-DFO], the radiosensitizing
effect was lost. These preliminary findings warrant further studies
for the possible application of metal chelators as radiation
sensitizers in radiation oncology.
MESH TERMS: Animal
Cell Cycle/Drug Effects
Chelating Agents/*Pharmacology
Colony-Forming Units Assay
Comparative Study
Cricetulus
DNA Replication/Drug Effects
Deferoxamine/*Pharmacology
Edetic Acid/Analogs and Derivatives/*Pharmacology
Fibroblasts/*Drug Effects/Radiation Effects
Genes, p53
Hamsters
Human
Iron Chelating Agents/Pharmacology
Lung/Cytology/Radiation Effects
Lung Neoplasms/Genetics/Pathology
Mimosine/*Pharmacology/Toxicity
Pyridones/*Pharmacology
Radiation-Sensitizing Agents/*Pharmacology
S Phase/Drug Effects
Tumor Cells, Cultured/Drug Effects/Radiation Effects
LANGUAGE: ENG
PUBLICATION TYPE: JOURNAL ARTICLE
TITLE ABBREVIATION: Radiat Res
YEAR: 2001
ADDRESS: Cellular Biochemistry and Human Genetics, Schools of Medicine
and Dentistry, Hebrew University, Jerusalem 91120, Israel.
ENTRY MONTH: 200104
CAS NO.: 0 (Chelating Agents)
0 (Iron Chelating Agents)
0 (Pyridones)
0 (Radiation-Sensitizing Agents)
30652-11-0 (1,2-dimethyl-3-hydroxypyrid-4-one)
35998-29-9 (N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic
acid)
500-44-7 (Mimosine)
60-00-4 (Edetic Acid)
70-51-9 (Deferoxamine)
_________________________________________________________________
National Cancer Institute
Steph
Tom,
read my post in the ["doe" and more truth] thread, take some more
phenothiazines and try to get back onto planet earth.
That's my advice. I'm really trying to help you.
_PT_
>Steph,please comment on the antioxidant properties of amifostine.How can
>it protect normal tissues(not perfectly,but some),while still(according
>to many pubmed studies),potentiate chemo or radiotherapy? According,to
>the study you just gave this shouldnt be theoretically possible.
Some cancer cells have altered enzimatic content reletively to normal
cells and these kind of compounds use that to do the trick. The
administration only gives a "window of time" of protection, so the use
is very limited. Most toxic drugs require very long time infusions and
so do no benefict from this. Also the protectors have their own
toxicities themselves...
>Would it be all that far-fetched to assume vitamins *could* do the same
>thing;given adequate *effective* doses? Vitamins taken orally dont
>probably achieve adequate AUC levels for very long.Given vitamins or
>synthetic antioxidants such as amifostine with much longer half-lives,this
>could be a much different story.
Amifostine discovery is from the 60's... It was kept by the USA as a
military secret for many years. The interest was protecting your
soldiers from chemical weapons you would use on the enemies...
A lot of effort and money and time was put into that research so it's
naive to think you could have an idea now that wasn't fully tested
back then.
Being VERY simplistic the main idea is:
The interest of chemo and radio is to be toxic.
Normal healthy cells survive, sick cancer cells die.
Vitamins, healthy food, etc can help both normal and cancer cells to
survive. We don't want that.
Citotoxic drugs used to cure cancer have the power to induce cancer as
well. This isn't a perfect world...
Some citotoxic drugs are vitamin derived, like the all-trans-retinoic
acid used to cure M3 leukemia.
Some vitamins interfere with some citotoxic drugs like folinates and
MTX.
The future of cancer treatment is geneticaly oriented molecular
therapy. Till then we have to use these barbaric methods of
intoxicating and amputating people because we have nothing else.
And we (the patient himself is a big part of this we) succeed most of
the times!
John Moulder
Zpaul...@mad.scientist.com wrote:
> Amifostine discovery is from the 60's... It was kept by the USA as a
> military secret for many years...
Not true (the kept military secret part). Studies with amifostine (then
called WR-2721) were published in the open literature in the late 1960's.
The earlist reference I have on hand is (and not necessarily the first):
Yuhas, J. M. and Storer, J. B. Differential chemoprotection of normal and
malignant tissues. Journal of the National Cancer Institute. 1969;
42:331-335.
I had access to the compound more than 25 years ago:
Moulder, J. E.; Lo, P. S., and Fischer, J. J. Effect of the
radioprotectors MEA, DMSO and WR2721 on tumor control and skin tolerance
in the rat. Cancer Treatment Reports. 1977; 61:825-833.
It (WR-2721, amifostime, ethyol) has not proven very useful in cancer
therapy because:
1) In some schedules it protects tumors as well as normal tissues.
2) It has bad acute "side effects" including nausea, vomiting and hypotension
mike
>
>Most radioprotectors are sulfhydryls. Sulfhydryls soak up hydroxyl radicals,
>which are reponsible for about 90% of the DNA damage done by radiation. They
>don't really potentiate radiation or chemo, but they improve the therapeutic
>ratio by protecting normal tissues more than cancers. The rreason they do
>this are complex and often poorly understood, but at least in part, it is
>because cancers have a poor blood supply, so drugs like amifostine don't get
>to the cancer as well as they get to normal tissues.
>
And, if amifostine *does* get to the cancer cell it could act
synergistically with either the chemo or radiation.Some studies show no
effect on the cancer cell which is ok also.The first
study I gave was done in vitro,so we cant argue that the amifostine didnt
reach the cancer cells.Their comments:
"Amifostine may potentate DNA-damage effect of idarubicin in cancer cells
and decrease this effect in normal cells.
Vitamin C can be considered as protective agents against DNA damage in
normal cells in persons receiving idarubicin-based chemotherapy, but the
use of vitamin E cannot be recommended and at least needs further
research."
Some other in vitro studies done with amifostine(or other antioxidants) on
cancer cells:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11699416&dopt=Abstract
Leuk Lymphoma 2001 Jul;42(3):507-10 Related Articles, Links
Amifostine does not protect malignant lymphoma cell lines from the
cytotoxic effects of various chemotherapeutics in vitro.
Kuittinen O, Ruokolainen H, Turpeenniemi-Hujanen T.
Department of Oncology and Radiotherapy, Oulu University Hospital,
University of Oulu, Finland.
Amifostine didnt interfere with chemo drugs:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10525371&dopt=Abstract
Gynecol Oncol 1999 Nov;75(2):194-7 Related Articles, Links
The effect of amifostine on the in vitro cytotoxicity of chemotherapeutic
agents in three epithelial ovarian carcinoma cell lines.
Ng TY, Ngan HY, Cheng DK, Wong LC.
Department of Obstetrics and Gynecology, The University of Hong Kong, Hong
Kong SAR, China.
Again doesnt interfere with chemotherapy:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=9389935&dopt=Abstract
Eur J Cancer 1997 Sep;33(10):1693-8 Related Articles, Links
Amifostine protects normal tissues from paclitaxel toxicity while
cytotoxicity against tumour cells is maintained.
Taylor CW, Wang LM, List AF, Fernandes D, Paine-Murrieta GD, Johnson CS,
Capizzi RL.
Department of Medicine, Arizona Cancer Center, University of Arizona
College of Medicine, Tucson 85724, USA.
Comments from below:"A second hypothesis is that antioxidants may
interfere with the efficacy of radiation therapy and chemotherapy. This
hypothesis is based on the concept that antioxidants will destroy free
radicals that are generated during therapy, thereby protecting cancer
cells against death. *None* of the published data on the effect of
antioxidants in combination with radiation or chemotherapeutic agents on
tumor cells supports the second hypothesis."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11603656&dopt=Abstract
: J Am Coll Nutr 2001 Oct;20(5 Suppl):450S-463S; discussion 473S-475S
Related Articles, Links
Scientific rationale for using high-dose multiple micronutrients as an
adjunct to standard and experimental cancer therapies.
Prasad KN, Cole WC, Kumar B, Prasad KC.
Center for Vitamins and Cancer Research, Department of Radiology, School
of Medicine, University of Colorado Health Sciences Center, Denver 80262,
USA. Kedar....@UCHSC.edu
Another antioxidant beside amifostine accomplishes same thing:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11350909&dopt=Abstract
Clin Cancer Res 2001 May;7(5):1378-84 Related Articles, Links
Frederine, a new and promising protector against doxorubicin-induced
cardiotoxicity.
van Acker FA, Boven E, Kramer K, Haenen GR, Bast A, van der Vijgh WJ.
Department of Medical Oncology, University Hospital Vrije Universiteit,
1081 HV Amsterdam, The Netherlands. f.van...@azvu.nl
I dunno,do you think there is at least a *chance* antioxidants have
utility in treating cancer? At a bare minimum,they protect normal tissues
and some show synergism with the main treatment.If there was such a thing
as a win-win proposition with cancer this would have to be it!
Steph
>
> I dunno,do you think there is at least a *chance* antioxidants have
> utility in treating cancer? At a bare minimum,they protect normal tissues
> and some show synergism with the main treatment.If there was such a thing
> as a win-win proposition with cancer this would have to be it!
>
There is plenty of evidence (icluding clinical trial evidence in humans)
that hyperbaric oxygen improves local control rates for some cancers.
Therefore antioxidants which get to normal tissues but not cancers MAY well
be useful. But that is theory, not tested fact. And if antioxidants get into
the tumour as well, they will be at best useless, and at worst,
counterproductive.
mike
Steph,I am baffled by your comment.:) I'll post this for others to read..
and then I'll let it go.
Ann N Y Acad Sci 2002 May;957:260-70 Related Articles, Links
Cellular protection with proanthocyanidins derived from grape seeds.
Bagchi D, Bagchi M, Stohs S, Ray SD, Sen CK, Preuss HG.
Department of Pharmacy Services, Creighton University School of Pharmacy &
Allied Health Professions, Omaha, Nebraska 68178, USA.
deb...@creighton.edu
Grape seed proanthocyanidins have been reported to possess a broad
spectrum of pharmacological and medicinal properties against oxidative
stress. We have demonstrated that IH636 proanthocyanidin extract (GSPE)
provides excellent protection against free radicals in both in vitro and
in vivo models.
GSPE had significantly better free radical scavenging ability than
vitamins C, E and beta-carotene and demonstrated significant cytotoxicity
towards human breast, lung and gastric adenocarcinoma cells, while
enhancing the growth and viability of normal cells.
GSPE protected against tobacco-induced apoptotic cell death in human oral
keratinocytes and provided protection against cancer chemotherapeutic
drug-induced cytotoxicity in human liver cells by modulating cell
cycle/apoptosis regulatory genes such as bcl2, p53 and c-myc.
Recently, the bioavailability and mechanistic pathways of cytoprotection
by GSPE were examined on acetaminophen-induced hepatotoxicity and
nephrotoxicity, amiodarone-induced pulmonary toxicity, doxorubicin-induced
cardiotoxicity, DMN-induced immunotoxicity and MOCAP-induced neurotoxicity
in mice. Serum chemistry changes, integrity of genomic DNA and
histopathology were assessed. GSPE pre-exposure provided near complete
protection in terms of serum chemistry changes and DNA damage, as well as
abolished apoptotic and necrotic cell death in all tissues.
Histopathological examination reconfirmed these findings. GSPE
demonstrated concentration-/dose-dependent inhibitory effects on the drug
metabolizing enzyme cytochrome P450 2E1, and this may be a major pathway
for the anti-toxic potential exerted by GSPE. Furthermore, GSPE treatment
significantly decreased TNFalpha-induced adherence of T-cells to HUVEC by
inhibiting VCAM-1 expression.
These results demonstrate that GSPE is highly bioavailable and may serve
as a potential therapeutic tool in protecting multiple target organs from
structurally diverse drug- and chemical-induced toxicity.
Publication Types:
Review
Review, Tutorial
PMID: 12074978 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------
------
Steph
> "Steph" <st...@vancouver.island> wrote:
> >
> >"mike" <emka...@dodgenet.com> wrote in message
> >news:at6lsg$e23$1...@ins22.netins.net...
> >>
> >> I dunno,do you think there is at least a *chance* antioxidants have
> >> utility in treating cancer? At a bare minimum,they protect normal
tissues
> >> and some show synergism with the main treatment.If there was such a
thing
> >> as a win-win proposition with cancer this would have to be it!
> >>
> >
> >There is plenty of evidence (icluding clinical trial evidence in humans)
> >that hyperbaric oxygen improves local control rates for some cancers.
> >Therefore antioxidants which get to normal tissues but not cancers MAY
well
> >be useful. But that is theory, not tested fact. And if antioxidants get
into
> >the tumour as well, they will be at best useless, and at worst,
> >counterproductive.
>
> Steph,I am baffled by your comment.:) I'll post this for others to read..
> and then I'll let it go.
>
I'm sorry you are baffled.
It seems quite straightforward to me.........
mike
But are you looking in the rearview mirror? :)
doe
>From: "Steph" st...@vancouver.island
>Message-id: <J6BJ9.142445$ea.27...@news2.calgary.shaw.ca>
>
>There is plenty of evidence (icluding clinical trial evidence in humans)
>that hyperbaric oxygen improves local control rates for some cancers.
And this is .. because?
It boosts the production of .. ferritin .. the iron chelating protein in the
body which sequesters iron away .. removing it from the process .. the same as
the modern day 'drugs' .. the iron chelators which are being developed and used
in cancer today.
Who loves ya.
Tom
>Therefore antioxidants which get to normal tissues but not cancers MAY well
>be useful. But that is theory, not tested fact. And if antioxidants get into
>the tumour as well, they will be at best useless, and at worst,
>counterproductive.
Steph
"doe" <ironj...@aol.comdoe> wrote in message
> >Subject: Re: Vitamins
> >From: "Steph" st...@vancouver.island
> >Date: 12/10/2002 11:41 PM Mountain Standard Time
> >Message-id: <J6BJ9.142445$ea.27...@news2.calgary.shaw.ca>
> >
> >
> >"mike" <emka...@dodgenet.com> wrote in message
> >news:at6lsg$e23$1...@ins22.netins.net...
> >>
>
> >
> >There is plenty of evidence (icluding clinical trial evidence in humans)
> >that hyperbaric oxygen improves local control rates for some cancers.
>
> And this is .. because?
>
It is beloved of space-aliens?
_PT_
>In article <2fecvu45ahdnfptsi...@4ax.com>,
>Zpaul...@mad.scientist.com wrote:
>
>> Amifostine discovery is from the 60's... It was kept by the USA as a
>> military secret for many years...
>
>Not true (the kept military secret part). Studies with amifostine (then
>called WR-2721) were published in the open literature in the late 1960's.
>
>I had access to the compound more than 25 years ago:
I guess the chemical formula was included in the open literature in
the 60's
It became comercial available in the late 90's.
The only conclusion is that you were part of the system...
Funny that it's so good for Nitrogen mustard (a close relative to the
well known war gas) and so bad for the majority of other drugs...
Sadam is a bad guy, you are one of the good guys, and all the
usefullness of Amifostine in recent medical literature is a lie.
John Moulder
<Zpaul...@mad.scientist.com> wrote:
> jmou...@mcw.edu (John Moulder) wrote:
>
> >In article <2fecvu45ahdnfptsi...@4ax.com>,
> >Zpaul...@mad.scientist.com wrote:
> >
> >> Amifostine discovery is from the 60's... It was kept by the USA as a
> >> military secret for many years...
> >
> >Not true (the kept military secret part). Studies with amifostine (then
> >called WR-2721) were published in the open literature in the late 1960's.
> >
> >I had access to the compound more than 25 years ago:
>
> I guess the chemical formula was included in the open literature in
> the 60's
>
> It became comercial available in the late 90's.
> The only conclusion is that you were part of the system...
It may not have been commercially available for clincial use till the
late 90's but it was widley available to lab researchers in the US (and
in the UK) by about 1970 and was in controlled clinical trial in the US
by the mid-80's.
If you look in medline you will find close to 400 papers on WR-2721
(aka amifostine and ethyol) in the 80's.
John Moulder
<st...@vancouver.island> wrote:
It is because many tumors have chronically or transiently hypoxic areas
(largely because they outgrow their blood supply and/or have
disorganized blood supplies), and hypoxia confers resistance to
ionizing radiation.
Kristofer D. Dale
> You are the one in a fantasy if you think that "good nutrition" is the same
> as "high-dose vitamins", Dale.
Non non, mon sewer. "High-dose" is a different matter entirely. If you
are out of power steering fluid, giving your engine more oil and gas
won't make it any easier to navigate sharp curves. I am pointing out
that a study on high-dose supplementation does not prove that nutrition
is ineffective, for those who might be confused by "Steph's" attempt
at misdirection...
--
_o Kristofer Dale,
_ \<,_ ragged individualist,
_____( )/ ( )_____ statistic at large...
p.s. Learn and live, http://www.vitaletherapeutics.org