liver cancer - Apr 2011

Chemotherpay for Liver met, complementary alternative treatment
- Q

Heather BoydRoberts

Message 1 of 4 , Apr 30, 2011[-- Image: Frame1 --]



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My mother has colon cancer with liver mets.  She already had
surgery and they removed 18 inches of her colon.  She has been
receiving IV therapy from a Dr Dobbs in the Toronto area.  He
has been giving her a basic IV with water soluble vitamins
including Mg, B's and vitamin C.  During the IVs her mets
increased in size over a 2 month period.  She is about to start
chemotherapy.  The surgeon verbally told her he was going to
start with the big guns because she was so strong and healthy.
 I listed the drugs they will be using below.  I need input
from all u docs who treat cancer.  The more the merrier.  What
therapies do u use?  What will help her during chemo?

 Secondly and more urgently I need to know if anyone knows what
will interfere with the chemo working?  I was going to send her
the following:  Resveratrol, AHCC (active hexose correlated
compound), ECGC,  Coriolus, oligo Se, turmeric, and pectasol
(modified citrus pectin).  Are any of the going to interfere
with her chemo.  Also, Dr Guniot had a chemo protocol to use to
help deal with the chemo and I can't find it.  I thought he used
junipers plus others. Any ideas?  One final question can she
take antioxidants up to 3 days before her chemo and then start
them again right after?  Her oncologist doesn't want her taking
any antioxidants at all.  Her ND said it doesn't matter, and I
don't think this is right.  I haven't yet delved into treating
cancer so any advice you can provide would be highly
appreciated.



Her Chemotherapy drugs

  SFU (Fluorouracil) injection

  Leucovorin (vitamin- according to my mothers oncologist)

  Irinotecan

  Bevacizimab (Avastin)

  SFU infusion x 46 hours



Her doc has also prescribed:



Anti-Nausea Medications

  Ondansetron (can cause temporary constipation}

  Dexamethasone (steroid)

  Prochlorperazine (also called stemetil)

Anti - Diarrheal medication

  Lomotil

Thank you for you help!

Heather Boyd Roberts, ND
Vancouver WA

jacob

Message 2 of 4 , May 1 4:54 PM[-- Image: Frame2 --]



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Heather,

There are several general rules of practice that may have been
neglected in your medical training that most MDs take for
granted. I don't know whether they just forgot to teach us
these things in naturopathic school or like so many other
little details that seemed to escape me, I was either dosing
off during class or thinking about something else during the
lecture.

The first is, doctors should not treat their own family members.
Hippocrates did not say this that I know but it seems all MDs
know this. When dealing with our own family members, something
about the dynamics can easily throw off the objectivity needed.
Forming a workable doctor patient relationship can be difficult
if not impossible with family members.

The second is to refer patients to someone who has experience
treating something you don't have experience with. You should
not use patients as your own personal guinea pigs, well outside
of the school clinics. [Whoops probably shouldn't write that]

Third, Even if this patient under discussion wasn't your mother
and you were highly experienced working with cancer patients,
we should whenever possible see our patients in person. There
are of course exceptions when necessity may force us to do
phone consults, Skype or email, but trying to treat someone a
continent away, where you can't do a PE or even see how much
they wince on palpation or how pale or queasy they look, it
just seems inappropriate. This is why we refer.

Fourth, I an all your colleagues are always eager to volunteer
information and answer specific questions, but you've just
asked for a huge amount of education. Neil McKiney has just
published a new volume on naturopathic oncology that only half
begins to answer the many questions you have laid out. Where to
begin with all of your questions? I would suggest making sure
your mom is seeing a competent and experienced naturopathic
doctor in her area. YOur job in this situation may be to be her
daughter and not her doctor.

Jacob Schor
[who once had a mother with cancer]

Denver CO

Heather BoydRoberts

Message 3 of 4 , May 2 12:39 AM[-- Image: Frame3 --]



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Jacob I did not ask for your counsel.  I am not treating my
mother, I have referred her to a physician, but the one I know
is too far for her to travel.  I do not live near her and don't
know the physicians in her area.  She chose to go to someone who
supposedly specializes in cancer therapy.  Yes I do live across
an entire continent and yes I do not know a lot about treating
cancer because I chose not to travel that route.  However, now
my mother, whom I love dearly, is receiving care that I believe
is not GOOD ENOUGH!  So, unless you have had multiple very close
family members die, and can relate to such a loss I would
suggest you hold your strong opinions about a personal
situation that you know nothing about to yourself.  I rarely
become angry, but your accusations were uncalled for.

Heather Boyd Roberts, ND
Vancouver, WA

jacob

Message 4 of 4 , May 2 3:03 PM[-- Image: Frame4 --]



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Heather,



I am sorry you took offense in my prior post, though I sort of
suspected it would not be well received as I wrote it.  You say
you are mad and I suspect you have good reason to be.  This kind
of experience with family members who are seriously ill cannot
help but to generate intense emotions.  It is because we care
so deeply about those in our family that our common sense may
wobble.



It sounds as if your mother may live in the Toronto area.  There
is a naturopathic school in Toronto, home of Dugald Seely, Paul
Saunders, Andre Seine and others.  Someone among them should
supervise your mother's care.



The school runs an adjunctive cancer care clinic:

http://www.ccnm.edu/cancercare



I would also suggest looking at the Ontario naturopathic
associations website.

Here is the sublink to their Find an ND for the central Ontario
region:

http://oand.org/index.php?page=central



Also look at oncanp's website for Ontario NDs who specialize in
oncology:

http://www.oncanp.org/find_state.html#ontario



There are numerous `calls' one must make in choosing stuff to
use in conjunction with chemotherapy and at this point there is
no definitive list.



Let's look at the list you posted and start with resveratrol as
an example.



There is an active debate about resveratrol use, aside from the
fact that there are doubts on whether adequate amounts are even
absorbed.  How resveratrol interacts with bevacizumab is
something else.

Bharat Aggarwal touches on this briefly in his book on
resveratrol and hints that the two might go well together:

 http://books.google.com/books?id=Bv-qdbs4cdwC&pg=PA159&lpg=PA159&dq=Bevacizumab+and+resveratrol&source=bl&ots=7HgfNJRKS1&sig=5S6VrV_kSELhJyIfYqkc1k1xG50&hl=en&ei=xbq-TYOaFJDqgQeP58TsBg&sa=X&oi=book_result&ct=result&resnum=2&ved=0CCMQ6AEwAQ#v=onepage&q=Bevacizumab%20and%20resveratrol&f=false



That's because resveratrol  acts as an angiogenesis inhibitor
the way bevacizumab also does.



Srivastava's 2009 paper also touches on this and suggests that
the two may play well together:

http://www.springerlink.com/content/063246828m755565/



Definitive trials combining these two, resveratrol and
bevacizumab, together are not leaping out of pubmed so the idea
of using the two together is still rather theoretical and hardly
well substantiated.



Put this uncertainty in the context of a number of  papers
suggesting that resveratrol may interfere with a certain
specific chemo drugs.

For example:

Mao 2010 "Resveratrol confers resistance against taxol via
induction of cell cycle arrest in human cancer cell lines." [i]

Rigolio 2005 "Resveratrol interference with the cell cycle
protects human neuroblastoma SH-SY5Y cell from
paclitaxel-induced apoptosis." [ii]

Nicolini 2003 "Effect of trans-resveratrol on signal
transduction pathways involved in paclitaxel-induced apoptosis
in human neuroblastoma SH-SY5Y cells." [iii]

Nicolini 2001 "Anti-apoptotic effect of trans-resveratrol on
paclitaxel-induced apoptosis in the human neuroblastoma SH-SY5Y
cell line." [iv]





 And add to  this  the recent concern published last month that
resveratrol may not 'play well' with proteasome inhibitors such
as Bortezomab ["Resveratrol protects leukemic cells against
cytotoxicity induced by proteasome inhibitors via induction of
FOXO1 and p27Kip1." [v]]



And also add to this last year's cancellation of a significant
clinical trial using resveratrol in treating multiple
myeloma. [vi]



At this point we have a sum total that is unclear,  lots of data
both for and against using resveratrol.  Data that seems to
shift with each new publication



What the bottom line really is remains the subject of an ongoing
debate.  Do we observe Hippocratic caution or do we proceed
based on clinical experience and the claims of some who think
they  have seen  benefit?



I'm not writing to take a position or suggest whether your
mother should or shouldn't take resveratrol.  I am using this
as an example of how complex your question really is.



 In the end, this, like many other questions,  ends up being a
judgment call for the treating naturopathic doctor to
make.  One has to weigh the evidence, hopefully being free of
prejudice, in an objective manner.  This isn't easy for any of
us to do and has to be more difficult when dealing with those
close to us.



You also mention using B vitamins along with IV vitamin
C.  Davis Lamson has expressed strong reservations against
this practice because, "Many B-vitamins quench superoxide or
hydrogen peroxide…."



Although this may be a common practice, I for one take any
mutterings from Davis quite seriously and would suggest not
continuing to mix B vitamins with IV-C.



I am not writing to tell you what to do but trying to once again
suggest that your mother would be better served by finding
someone other than yourself taking the responsibility to
prescribe supplements to her during her ongoing
treatment.  There are decent, capable and experienced
practitioners in the Toronto area and your efforts might be
better rewarded by having your mother see one of them rather
than your trying to prescribe for her.



I would prefer you not to be mad at me over this but your anger
does not change my basic premise, doctors should not treat
their family members, especially in serious situations, but
should refer to other practitioners.



Jacob Schor

Denver CO









Resveratrol, AHCC (active hexose correlated compound), ECGC,

>  Coriolus, oligo Se, turmeric, and pectasol (modified citrus
pectin).

>  Are any of the going to interfere with her chemo.



SFU

> (Fluorouracil) injection

>

>   Leucovorin

> (vitamin- according to my mothers oncologist)

>

>   Irinotecan

>

>   Bevacizimab

> (Avastin)

>

>   SFU

> infusion x 46 hours

[i] Mol Nutr Food Res. 2010 Nov;54(11):1574-84.

Resveratrol confers resistance against taxol via induction of
cell cycle arrest in human cancer cell lines.

Mao QQ, Bai Y, Lin YW, Zheng XY, Qin J, Yang K, Xie LP.

Department of Urology, The First Affiliated Hospital, School of
Medicine, Zhejiang University, Hangzhou, Zhejiang Province, PR
China.

Abstract

Resveratrol, which is highly concentrated in the skin of grapes
and is abundant in red wine, has been demonstrated to account
for several beneficial properties, including antioxidant,
anticoagulant, anti-inflammatory and anticancer effects. Taxol
is a microtubule-stabilizing drug that has been extensively
used as effective chemotherapeutic agents in the treatment of
solid tumors. Here, we investigated whether the combination of
the two compounds would yield increased antitumor efficacy in
human cancer cells. Unexpectedly, resveratrol effectively
prevented tumor cell death induced by taxol in 5637 bladder
cancer cells. This pronounced antagonistic function of
resveratrol against taxol was associated with changes in
multiple signal transduction pathways, but not with tubulin
polymerization. Importantly, cell cycle analysis showed that
resveratrol prevented the cells from entering into mitosis, the
phase in which taxol exerts its action. Furthermore, resveratrol
blocked the cytotoxic effects of vinblastine but not cisplatin
in 5637 cells. Interestingly, resveratrol pre-treatment
followed by taxol resulted in synergistic cytotoxicity.
Finally, we extended our studies to various human cancer cell
lines. Taken together, our results indicate that resveratrol
may have the potential to negate the therapeutic efficacy of
taxol and suggest that consumption of resveratrol-related
products may be contraindicated during cancer therapy with
taxol.

PMID: 20521268 [PubMed - indexed for MEDLINE]



[ii] Neurochem Int. 2005 Feb;46(3):205-11. Epub 2004 Dec 31.

Resveratrol interference with the cell cycle protects human
neuroblastoma SH-SY5Y cell from paclitaxel-induced apoptosis.

Rigolio R, Miloso M, Nicolini G, Villa D, Scuteri A, Simone
M, Tredici G.

Dipartimento di Neuroscienze e Tecnologie Biomediche, Università
degli Studi di Milano-Bicocca, Via Cadore 48, 20052 Monza,
Italy.

Abstract

In previous studies we demonstrated that resveratrol acts in an
antiapoptotic manner on the paclitaxel-treated human
neuroblastoma (HN) SH-SY5Y cell line inhibiting the apoptotic
pathways induced by the antineoplastic drug. In the present
study we evaluated the antiapoptotic effect of resveratrol,
studying its activity on cell cycle progression. We determined
the mitotic index of cultures exposed to resveratrol and
paclitaxel alone or in combination, the cell cycle distribution
by flow cytometric analysis (FACS), and the modulation of some
relevant cell cycle regulatory proteins. Resveratrol is able to
induce S-phase cell arrest and this interference with the cell
cycle is associated with an increase of cyclin E and cyclin A,
a downregulation of cyclin D1, and no alteration in cyclin B1
and cdk 1 activation. The resveratrol-induced S-phase block
prevents SH-SY5Y from entering into mitosis, the phase of the
cell cycle in which paclitaxel exerts its activity, explaining
the antiapoptotic effect of resveratrol.

PMID: 15670636





[iii]

Neurochem Int. 2003 Apr;42(5):419-29.

Effect of trans-resveratrol on signal transduction pathways
involved in paclitaxel-induced apoptosis in human neuroblastoma
SH-SY5Y cells.

Nicolini G, Rigolio R, Scuteri A, Miloso M, Saccomanno
D, Cavaletti G, Tredici G.

Dipartimento di Neuroscienze e Tecnologie Biomediche, Facoltá di
Medicina e Chirurgia, Via Cadore 48, Università degli Studi di
Milano-Bicocca, 20052 Monza, Italy.

Abstract
--------

trans-Resveratrol (3,4',5-trihydroxystilbene) is able to
significantly reduce paclitaxel-induced apoptosis in the human
neuroblastoma (HN) SH-SY5Y cell line, acting on several
cellular signaling pathways that are involved in
paclitaxel-induced apoptosis. trans-Resveratrol reverses
phosphorylation of Bcl-2 induced by paclitaxel and
concomitantly blocks Raf-1 phosphorylation, also observed after
paclitaxel exposure, thus suggesting that Bcl-2 inactivation may
be dependent on the activation of the Raf/Ras cascade.
trans-Resveratrol also reverses the sustained phosphorylation
of JNK/SAPK, which specifically occurs after paclitaxel
exposure.Overall, our observations demonstrate that (a) the
toxic action of paclitaxel on neuronal-like cells is not only
related to the effect of the drug on tubulin, but also to its
capacity to activate several intracellular pathways leading to
inactivation of Bcl-2, thus causing cells to die by apoptosis,
(b) trans-resveratrol significantly reduces paclitaxel-induced
apoptosis by modulating the cellular signaling pathways which
commit the cell to apoptosis.

PMID: 12510025 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/12510025





[iv]

Neurosci Lett. 2001 Apr 13;302(1):41-4.

Anti-apoptotic effect of trans-resveratrol on paclitaxel-induced
apoptosis in the human neuroblastoma SH-SY5Y cell line.

Nicolini G, Rigolio R, Miloso M, Bertelli AA, Tredici G.

Dipartimento di Neuroscienze e Tecnologie Biomediche, Università
degli Studi di Milano-Bicocca, Via Cadore, 48, 20052, Monza,
Italy.

Abstract
--------

Paclitaxel, an anticancer drug, induces apoptosis in human
neuroblastoma cell line SH-SY5Y. The addition of
trans-resveratrol, a natural antioxidant present in grapes and
red wine, to SH-SY5Y cultures exposed to paclitaxel
significantly reduces cellular death. The neuroprotective
action of trans-resveratrol is due neither to its antioxidant
capacity nor to interference with the polymerization of tubulin
induced by paclitaxel. However, trans-resveratrol is able to
inhibit the activation of caspase 7 and degradation of
poly-(ADP-ribose)-polymerase which occur in SH-SY5Y exposed to
paclitaxel. Resveratrol, therefore, exerts its anti-apoptotic
effect by modulating the signal pathways that commit these
neuronal-like cells to apoptosis.

PMID: 11278107 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/11278107





[v] BMC Cancer. 2011 Mar 19;11:99.

Resveratrol protects leukemic cells against cytotoxicity induced
by proteasome inhibitors via induction of FOXO1 and p27Kip1.

Niu XF, Liu BQ, Du ZX, Gao YY, Li C, Li N, Guan Y, Wang HQ.

Department of Biochemistry & Molecular Biology, China Medical
University, Shenyang 110001, PR China. wanghq_doctor@....

Abstract

ABSTRACT:

BACKGROUND: It was reported recently that resveratrol could
sensitize a number of cancer cells to the antitumoral effects
of some conventional chemotherapy drugs. The current study was
designed to investigate whether resveratrol could sensitize
leukemic cells to proteasome inhibitors.

METHODS: Leukemic cells were treated with MG132 alone or in
combination with resveratrol. Cell viability was investigated
using MTT assay, and induction of apoptosis and cell cycle
distribution was measured using flow cytometry. Western blot
and real-time RT-PCR were used to investigate the expression of
FOXO1 and p27Kip1. CHIP was performed to investigate the binding
of FOXO1 to the p27 Kip1 promoter.

RESULTS: Resveratrol strongly reduced cytotoxic activities of
proteasome inhibitors against leukemic cells. MG132 in
combination with resveratrol caused cell cycle blockade at G1/S
transition via p27Kip1 accumulation. Knockdown of p27Kip1 using
siRNA dramatically attenuated the protective effects of
resveratrol on cytotoxic actions of proteasome inhibitors
against leukemic cells. Resveratrol induced FOXO1 expression at
the transcriptional level, while MG132 increased nuclear
distribution of FOXO1. MG132 in combination with resveratrol
caused synergistic induction of p27Kip1 through increased
recruitment of FOXO1 on the p27Kip1 promoter.

CONCLUSIONS: Resveratrol may have the potential to negate the
cytotoxic effects of proteasome inhibitors via regulation of
FOXO1 transcriptional activity and accumulation of p27Kip1.

PMID: 21418583 [PubMed - in process]PMCID: PMC3066124Free PMC
Article





[vi] Resveratrol Trial In Multiple Myeloma Suspended Due To
Safety Concerns
2 Comments By The Myeloma Beacon Staff
Published: May 3, 2010 6:15 pm; Updated: May 5, 2010 9:45 am
Resveratrol Trial In Multiple Myeloma Suspended Due To Safety
Concerns

A clinical trial of a proprietary form of resveratrol has been
suspended due to
safety concerns. The resveratrol-based drug, SRT501, was being
studied in a
Phase 2 trial with multiple myeloma patients. Phase 2 trials
usually are the
first clinical trials that look in detail at a drug's potential
effectiveness.

SRT501, which is not yet approved by the Food & Drug
Administration, is being
developed by Sirtris Pharmaceuticals, a Cambridge,
Massachusetts, biotech
company. Sirtris was founded in 2004 and acquired in 2008 by the
British
pharmaceutical company GlaxoSmithKline.

Sirtris describes SRT501 as a "proprietary formulation of
resveratrol" with an
improved ability to deliver the drug where it is needed in a
patient's body. In
the halted clinical trial, SRT501 was to be administered orally
once daily.
Some of the multiple myeloma patients in the trial were to take
SRT501 while
also receiving treatment with Velcade (bortezomib). Others were
to take only
SRT501.

The status of the SRT501 myeloma trial is currently described by
trial
organizers as "suspended" due to "unexpected safety events."
There is no
further information as to the exact nature of the safety events
or which
patients were affected by the safety issues.

The information about the trial is viewable at the
ClinicalTrials.Gov website,
which is maintained by the United States National Institutes of
Health.

The suspended trial appears to be the first SRT501 trial carried
out with
multiple myeloma patients. Earlier trials, which were completed
without any
reports of safety issues, involved either healthy participants,
patients
suffering from diabetes, or patients with colorectal cancer.

Representatives from GlaxoSmithKline did not respond to email
requests from The
Myeloma Beacon for further clarification of the issues that led
to the SRT501
trial being halted. [See update below.]

News of the SRT501 trial's suspension was first reported at the
blog "In the
Pipeline." For further information on resveratrol's potential as
a multiple
myeloma treatment, see the Beacon's resource article on the
subject.

Update (May 4, 2010; 11:30 a.m.): In response to a Beacon
inquiry regarding the
suspension of the SRT501 trial, representatives from
GlaxoSmithKline provided
the following information:

The study in question was being conducted in patients with
advanced multiple
myeloma. A number of patients developed a complication generally
associated with
myeloma while on study. New patient enrollment into the study
was put on hold
while we analyze the data collected to date.

Investigators and regulators in the U.K. and Denmark, where the
study was being
conducted, were appropriately notified of the decision to
temporarily hold
further enrollment while determining next steps for this
particular trial.

Update (May 5, 2010; 9:45 a.m.): Reports indicate that the
SRT501 trial was
halted after 24 patients had enrolled in the trial. Of the 24
patients, five
developed a kidney condition called cast nephropathy. Cast
nephropathy is so
commonly associated with multiple myeloma that it is often
called "myeloma
kidney." It also is one of the main contributors to kidney
failure in myeloma
patients.