The
information in this column is intended for informational
purposes only, and does not constitute medical advice or
recommendations by the author. Please consult with your
physician before making any lifestyle or medication changes, or if you
have any other concerns regarding your health.
BONE
MARROW STEM CELLS
& LIVER FAILURE
The liver is an
extraordinarily complex organ, and is responsible for, literally,
hundreds of
critical metabolic processes in the body.
While the liver is the only organ that is capable of
regeneration in
adults, this regenerative capability has its limits, making progressive
liver
failure a very serious health condition.
When advanced liver failure occurs (most commonly from
chronic hepatitis
and cirrhosis), a liver transplant is generally the only hope for
long-term survival. Unfortunately,
there are far too few donor
livers available to go around, and most patients with advanced liver
failure
will die before a liver transplant becomes available to them (liver
failure is currently
the 12th most common cause of death in the United States).
As
in other areas
of medicine, the emerging field of stem cell therapy has caught the
attention
of physicians who manage patients with liver failure.
Due to the ongoing ethical debate over the
use of embryonic stem cells, which are removed from aborted fetuses, a
great
deal of research has been done on harvesting a patient’s own stem cells
from
the bone marrow, and using these cells to repair or replace failing
organs. In what has
been widely hailed as a
breakthrough in stem cell research, scientists at several different
institutions
have recently shown that specialized cells for many different organs
can be
produced from bone marrow stem cells, including the liver. While bone marrow stem
cell research is still
in its infancy, the fervent hope of researchers in this field is that
failing
organs, like the liver, might someday be revived by growing bone marrow
stem
cells under laboratory conditions that induce them to grow into the
cells and,
ultimately, the tissues specific to those failing organs. A new laboratory research
study in the
journal Gastroenterology, from
researchers in Taiwan,
and at
Emory University,
in Atlanta,
has
now demonstrated that, at least in mice, failing livers can indeed be
rejuvenated and rescued with replacement liver cells grown from bone
marrow
stem cells.
In
this
innovative study, laboratory mice were treated to induce complete liver
failure, which is a uniformly lethal condition.
The researchers then injected liver cells derived from
bone marrow stem
cells into the mice, as well as bone marrow stem cells themselves
(i.e.,
without first transforming them into liver cells).
These cells were injected into the blood of
some of the mice, while other mice received injections of these
specialized
cells directly into the spleen. Amazingly,
both the stem cells that had been transformed into liver cells and the non-transformed stem cells were
subsequently found to be growing in the livers of these mice when they
were euthanized
at the end of the research experiment, and both types of cells were
found to
have developed into functional, mature liver cells within the animals’
previously
damaged livers. Even
more amazing was
the finding that these bone marrow stem cells, whether transformed into
liver
cells outside of the recipient animals or not, were able to induce
liver
regeneration and function in mice who had suffered otherwise lethal
damage to
their livers. In
particular, the mice
that had received stem cell injections directly into a vein had more
impressive
liver regeneration, and return of liver function, than the animals that
had
received their stem cell injections into the spleen.
In
this striking
experiment, mice with mortally damaged livers were, effectively,
rescued by
injecting them with bone marrow stem cells.
These stem cells, including stem cells that were not
deliberately
transformed into liver cells in the laboratory, then made their way to
the
animals’ damaged livers, and began to grow and function as normal liver
cells,
regenerating the animals’ severely damaged livers in the process. Currently, there are a
handful of human
clinical trials underway that are working to replicate the dramatic
results
obtained in this mouse study. If
stem
cell therapy, using stem cells taken from a patient’s own bone marrow,
can be
shown to repopulate failing livers with healthy, functional new liver
cells,
this would represent an enormous step forward in the management of
end-stage
liver failure and might, someday, eliminate the need for liver
transplants in
the majority of liver failure cases.
Similarly, the successful use of stem cells and genetic
engineering to,
someday, recreate other failing organs (like the heart, kidneys and
pancreas,
for example) would transform the field of regenerative medicine from
something
resembling the pages of science fiction books and futuristic movies
into a
mature technology suited for routine clinical use.
Studies such as this are laying the essential
groundwork for a coming revolution in the management of critical organ
failure
in humans.
VITAMIN
D &
COLORECTAL CANCER SURVIVAL
Colorectal
cancer
is the third most common cancer in the US,
and the third most common cause
of death due to cancer. I
have
previously reviewed other studies that have suggested that high levels
of
Vitamin D in the blood may reduce the risk of developing colorectal
cancer
(please see my recent Archives for my reviews of several such studies). Although not all studies
have confirmed a
protective effect of Vitamin D on the risk of developing colorectal
cancer,
many studies suggest a modest but significant reduction in the
incidence of
this disease among patients with higher levels of this important
vitamin in
their blood. A
logical question to ask,
then, is whether or not higher levels of Vitamin D in the blood might
also be
beneficial to patients who have already been diagnosed with colorectal
cancer. A newly
reported study, in the Journal of Clinical
Oncology, from
researchers at Harvard
University
and the University
of South Carolina,
may provide an answer to this important
question.
In
this study,
304 adults participating in the very large Nurses’ Health Study and the
Health
Professionals Follow-Up Study were diagnosed with colorectal cancer
between
1991 and 2002. As
with other
participants in these two large public health studies, the patients who
were
diagnosed with colorectal cancer while participating in the study
underwent
extensive testing upon entering into the study, including the
measurement of blood
levels of Vitamin D. When
the
researchers compared patient outcomes (i.e., long-term survival versus
death),
they found that the patients with the highest Vitamin D levels were
only half
as likely to die, of any cause, during the course of these studies when
compared to patients who had the lowest Vitamin D levels. When comparing the
incidence of death
specifically due to colorectal cancer according to Vitamin D levels in
the
blood, this study revealed a trend towards improved survival with
higher blood
levels of Vitamin D, although this trend did not quite reach
statistical
significance.
This
study adds
to prior studies that have suggested a potentially beneficial role for
Vitamin
D in reducing both the incidence and mortality of colorectal cancer. Whether these benefits, if
they truly exist,
result directly from the effects of Vitamin D itself, or whether a high
level
of Vitamin D in the blood is simply a marker of other factors that are
providing these benefits, is unknown at this time.
(For this reason, taking significant doses of
Vitamin D supplements cannot be recommended for colorectal cancer
prevention or
treatment at this time.)
Vitamin
D
supplementation is beginning to find its way into clinical research
trials
looking at colorectal polyp and colorectal cancer formation, but it
will
probably be at least 5 to 10 years before definitive, prospective
clinical
research data becomes available regarding Vitamin D’s true role, if
any, in
preventing or treating colorectal cancer.
For now, I can only recommend that readers ensure a
sufficient intake of
Vitamin D, including modest sun exposure (5 to 10 minutes at a time, 2
to 3
times per week, although dark-skinned people may require longer and
more
frequent sun exposure in order to generate adequate levels of Vitamin
D); and
moderate intake of foods rich in Vitamin D, including fish (and salmon,
in
particular), Vitamin D-fortified dairy products and, if you are an
aficionado
of organ meats, an occasional slice of liver.
At the same time, remember that taking large amounts of
Vitamin D
supplements may cause very high levels of Vitamin D to accumulate in
the blood,
which can be toxic and harmful to your health.
GREEN
TEA &
COLORECTAL CANCER
The
antioxidant
effects of the active compounds in green tea are the focus of
tremendous
clinical research in the areas of cardiovascular disease and cancer
prevention
(please see my Archives for my reviews of several important recent
studies in
this area). Numerous
studies of the
“catechins” derived from green tea have suggested that, at least in
laboratory
animals, green tea catechin supplementation appears to reduce the risk
of some
types of cancer, including precancerous polyps and cancers of the colon
and
rectum. An
interesting new study from
Columbia University, Cornell University, and Gifu University in Japan,
and just
now published in the journal Carcinogenesis,
extends our understanding of at least one possible mechanism whereby
green tea
catechins might reduce the risk of developing colorectal cancers, and
might
even potentially improve survival once colorectal cancer has been
diagnosed.
One
important
mechanism whereby colorectal cancer cells grow and divide is through a
molecule
found on the surface of such cells, the epidermal growth factor
receptor
(EGFR). When EGFR
encounters certain
other circulating proteins, including the epithelial growth factor
(EGF), the
receptor and its growth factor bind together and set off a chemical
chain
reaction that, ultimately, results in increased tumor cell growth and
reproduction. Indeed,
newer
“molecularly-targeted” drugs have recently been developed that
interrupt EGFR
binding to its stimulatory proteins (also known as ligands).
Recent
research
has shown that the predominant catechin in green tea, epigallocatechin
gallate,
appears to inhibit EGF binding to the EGFR in Petri dish cultures of
human
colon cancer cells. Researchers
in this
study, therefore, sought to better understand the effects of
epigallocatechin
gallate on EGFR function, as the EGFR-EGF pathway is an important
mechanism
whereby cancers of the colon and rectum, and other cancers as well,
reproduce
themselves and grow.
In
this study,
researchers treated cultures of human colon cancer cells with
epigallocatechin
gallate. They found
that even tiny
concentrations of this green tea extract resulted in markedly reduced
numbers
of EGFR on the surface of colon cancer cells, and with as little as 30
minutes
of treatment time. However,
this
presumably beneficial reduction in EGFR levels on the surface of the
cancer
cells only lasted 1-2 hours, following 30 minutes of treatment with the
green
tea extract, before the cells were able to begin restoring the prior
number of
surface EGFR molecules.
This
study is an
important advance in our understanding of how green tea might exert its
possible anti-cancer effects at the cellular and molecular levels. While other potential
anti-cancer mechanisms
have also been described for green tea and its active components, this
particular study focuses on the EGFR-EGF pathway, which is known to be
very
important for many cancer cells, including colorectal cancer cells, in
terms of
their survival and progression. Other
studies have also suggested, as this study does, that the effects of
individual
doses of green tea extracts only persists for a couple of hours,
implying that
frequent doses of green tea, or its active components, may be required
for
sustained effect around the clock (alternatively, longer-acting
synthetic
analogues of these active green tea compounds will have to be
synthesized).
While
this
particular study offers no proof that green tea might be clinically
useful in
patients with colorectal cancer, it does very elegantly reveal at least
one
potential mechanism whereby green tea catechins might be able to exert
significant alterations in cancer cell physiology that, in turn, might
result
in clinically significant benefits for patients diagnosed with
colorectal
cancer.
Disclaimer:
As always, my advice to readers is to seek the advice of your physician
before making any significant changes in
medications, diet, or level of physical activity.
