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Sent: Saturday, November 1, 2008 8:18 PM
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Subject: Chemotherapy: Stem Cell Killer



HEALING THERAPIES NEWSLETTER

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This is the 39th email newsletter� associated with www.healingtherapies.info ,
the purpose of which is to expand the healing spectrum of people with physical
disabilities, especially spinal cord injury (SCI) and dysfunction.

This issue summarizes research indicating that chemotherapy(CT) is more toxic to
CNS stem cells than targeted cancer cells. SCI researcher Dr. Mark Noble and
colleagues have stated that the "prevalence of cancer in the world's populations
means that the total number of individuals for whom adverse neurological changes
are associated with cancer treatment is as great as for the more widely
recognized neurological syndromes." Basically, if you want to knock out
CNS-regenerative potential after SCI, CT is the way to do it. In addition,
chemotherapeutic agents are increasingly used to treat individuals with
autoimmune disease, including MS. It is thus essential to know whether CT has
adverse effects on patients with MS receiving such treatment.

Please support those who have made this newsletter possible. Specifically,
consider subscribing to PN/Paraplegia News (602-224-0500 or www.pn-magazine.com
) or donating to the Paralyzed Veterans of America's Research and Education
Program (www.pva.org ).

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ALTERNATIVE-MEDICINE BOOK

Check out Alternative Medicine and Spinal Cord Injury: Beyond the Banks of the
Mainstream either at http://www.demosmedpub.com/prod.aspx?prod_id=9781932603507
or Amazon.com. (rated 5 stars, highly informative). This is an informative book
for anyone, with or without disability.

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Learn more about divergent function-restoring therapies for spinal cord injury
at www.sci-therapies.info (or www.sci.is ).

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STUDY PARTICIPANTS SOUGHT WITH SENSORY OR MOBILITY IMPAIRMENTS

Interested in making some extra money?

If you have a sensory impairment or mobility impairment, you may be eligible to
participate in a new NIH-funded research project at Washington University (St.
Louis). This research aims to understand what people with sensory and/or
mobility impairments do in their daily life, how their environment affects their
community participation and what, if any, help they need to complete these
activities. This web-based assessment contains a set of two surveys and will
take approximately one hour to complete. If you are interested, click on the
following link (http://emc.wustl.edu/ncmrrstudyad.htm ).

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CHEMOTHERAPY: CNS STEM-CELL KILLER

(Adapted from a October 2008 PN/Paraplegia News article)

As discussed elsewhere, stem cells or cells derived from them will inevitably
play a key role in restoring function after spinal cord injury (SCI) Since
funding some of the first SCI-focused stem-cell research as PVA's research
director in the mid-1990's, I've been amazed how many programs have emerged
throughout the world which transplant stem cells from various sources into
individuals with SCI.

However, to fully appreciate their healing ability, understand that the
regenerative impact of these cells is not just from those externally
transplanted into the patient. From conception until death, they are the cells
of renewal and regeneration inherent within us all.

Stem and progenitor cells are found in most tissues, including the central
nervous system (i.e., brain & spinal cord). Sometimes, they are involved in
ongoing tissue maintenance, such as the bone-marrow's production of
blood-cell-replenishing stem cells; in other tissues, they are quiescent and
need to be coaxed into action by appropriate stimuli. In the case of SCI, injury
may mobilize dormant spinal-cord stem-cells into action.

The function of our endogenous stem cells can be positively or negatively
influenced by numerous therapies. For example, acupuncture and hyperbaric oxygen
therapy - both of which have been used to treat SCI - have been claimed to
stimulate their expression. In contrast, the focus of this article, chemotherapy
may be more toxic to CNS stem cells than the targeted cancer cells. As a result,
it can sabotage the much needed and desired CNS-regenerative potential in
individuals with SCI - even long after the chemotherapy.

In brief, stem and progenitor cells encompass a continuum of cell types that
transform into our end-product tissue. As our CNS develops, embryonic stem cells
generate more specialized tissue-specific neural stem cells. In turn, these
tissue-specific stem cells can differentiate into neuron- or glial-restricted
precursor cells, the former with the potential to generate neurons and the
latter into CNS support cells called oligodendrocytes and astrocytes. Especially
important for this discussion, oligodendrocytes generate the insulating myelin
sheaths that enwrap axons and are needed for signal transmission. These
distinctions between different cell types are important because chemotherapy is
more toxic to some of the precursor cell populations than others.

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CHEMOTHERAPY

More than half of cancer patients receive chemotherapy. Although the research
discussed below challenges the assumption, chemotherapeutic agents have been
generally thought to target rapidly growing, dividing cells, like cancer cells.

Because chemotherapy is administered systemically, it eradicates cancer cells
that have spread throughout the body, but, as a result, the whole body is
vulnerable to potential adverse side effects. Although the blood-brain barrier
may limit somewhat their infusion into the CNS, cancer drugs do, nevertheless,
cross this barrier, often producing persistent, long-term cognitive deficits. It
has been thought that chemotherapy especially affects brain areas associated
with learning and memory, such as the stem-cell-rich hippocampus, but there is
also substantial evidence of damage to myelinated regions of the brain (white
matter).

Many studies have documented chemotherapy's neurotoxicity, especially with
high-incidence cancers. For example, 50% of breast-cancer patients may have
cognitive impairments a year after chemotherapy was stopped. Even 3-6 years
later, breast-cancer survivors have more auditory-processing dysfunction than
age-matched controls.

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CHEMOTHERAPY & CNS STEM CELLS

Dr. Mark Noble and his University of Rochester (NY) colleagues have recently
carried out ground-breaking studies that help us understand more clearly
chemotherapy's neurotoxicity. These studies have evaluated the impact of various
commonly used cancer drugs on CNS progenitor cells grown in culture (in vitro)
and in mice (in vivo). The cell-culture studies indicated that clinically
relevant levels of commonly used drugs were more lethal to CNS-progenitor cells
than they were for a variety of cancer cell types.

The progenitor cells that evolved into myelin-producing oligodendrocytes (see
illustration) were especially sensitive to the toxic effects of chemotherapy. In
addition, non-dividing oligodendrocytes themselves were also particularly
vulnerable, a finding which challenges the widely held belief that chemotherapy
only targets dividing cells. Although less sensitive to chemotherapy than
oligodendrocytes, astrocytes (the other key glial support cell) were still as
susceptible as the targeted cancer cells.

Chemotherapy also changed the composition of surviving cells. Specifically, the
oligodendrocyte precursor cells would not renew themselves through cell division
but would differentiate into oligodendrocytes. The investigators stated "Such a
loss of dividing cells would compromise the ability of dividing progenitor cells
to contribute to repair processes, and could also contribute to long-term or
delayed toxicity reactions."

Confirming these results, progenitor cells and oligodendrocytes were compromised
in vivo when mice were systemically given these cancer drugs. Short-term
systemic administration of one of these drugs was shown to cause "both acute CNS
damage and .progressively worsening damage to myelinated tracts of the CNS."
Consistent with the observations in breast-cancer survivors, this damage
correlated with a delayed loss of function in the mice as measured by auditory
dysfunction.

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WHAT ABOUT RADIATION?

Although beyond the scope of this article, evidence also suggests that neural
precursor cells are extremely sensitive to radiation, the other twin pillar of
cancer treatment. Once again challenging the assumption that therapy
preferentially targets proliferating cells, radiation is especially lethal to
quiescent, non-dividing neural precursor cells.

CONCLUSION

Noble et al stated that the "prevalence of cancer in the world's populations
means that the total number of individuals for whom adverse neurological changes
are associated with cancer treatment is as great as for the more widely
recognized neurological syndromes." In other words, the leading cause of
neurological dysfunction may not be disease (e.g., MS) or injury (SCI or head
injury) but that brought about by medicine (i.e., iatrogenic).

Although chemotherapy's risk-benefit tradeoffs have always challenged the
physician's pledge to first do no harm, this is an especially sobering
assessment that underscores the need to develop new treatment options. In
addition, chemotherapeutic agents are increasingly used to treat individuals
with autoimmune disease, including MS. It is thus essential to know whether
chemotherapy has adverse effects on patients with MS receiving such treatment.

On the positive side, Noble's pioneering work provides invaluable insights on
how we can assess such options with respect to their ability to preserve the
body's neurological regenerative potential.

REFERENCES

1) Meyers CA. How chemotherapy damages the central nervous system. J Biol
2008; 7.

2) Dietrich J, et al. CNS progenitor cells and oligodendrocytes are targets
of chemotherapeutic agents in vitro and in vivo. J Biol 2006; 5.

3) Han R, et al. Systemic 5-flurouracil treatment causes a syndrome of
delayed myelin destruction in the central nervous system. J Biol 2008; 7.

4) Encinas, et al. Quiescent adult neural stem cells are exceptionally
sensitive to cosmic radiation. Exp Neurol 2008; 210.

5) Moss RW, Questioning Chemotherapy. Equinox Press, 2004.

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