merhaba,
bir sure once, 2004 yilina ait, kefir ve kanser iliskisi ile ilgili
bir yazi indirmistim, sayfanin adresini ne yazik ki bulamadim ama
makalenin yazarindan yola cikarak bulmak mumkun olabilir. ben yaziyi
asagiya kopyaliyorum.

iyi gunler,
esin

THE APPLICATION OF PROTEOLYTIC ENZYME AND ANNONACEOUS
ACETOGENEN THERAPIES FOR THE TREATMENT OF CANCER.
Prepared For Linda Jemmett
Biology 1220-012
By Karina Blatter
April 2, 2004


The recent development of treating cancer with the combination of
proteolytic enzyme therapy in addition to using Annonaceous
Acetogenins
instead of radiation and chemotherapy is a promising and less toxic
means
to treat cancer. These two separate therapies have been practiced
and
researched for almost a century, but only in the last decade have the
reasons for their success been understood.



Background
Some of the research that is currently under way is based
on the original work of the Scottish embryologist and research
biologist, Dr. John Beard. Observations made by Beard centered on
the placenta
and how its trophoblast cells have a microscopic similarity and
cellular behavior akin to cancer cells. These similarities include
the
following: Both placental and cancer cells are invasive. This means
that
they produce many different enzymes that help them to break down
tissue
barriers and spread through normal tissues. Both develop their own
blood
supply (known as angiogenesis), and both can grow with out restraint
or
inhibition. The only difference between the placental cells and
cancer
cells is that the placenta eventually stops growing. This halt in
placental growth directly correlates with the activation of the fetal
pancreas on approximately the 56th day of gestation, the same time
the fetal
pancreas becomes active (Beard, J., 1911).

The primary signaling factor for the placenta to become a
non-invasive growth was concluded to be the proteolytic enzymes
produced by the
pancreas of the fetus. Although the fetus has no digestive reasons
to
produce these enzymes before birth (these enzyme shouldn't be
necessary
until the ingestion of the child's first meal), they are produced
months
before they are otherwise needed. When this check is not in place,
choriocarcinoma (cancer of the placenta, where the placenta keeps
growing
and endangers life of fetus and the mother) occurs.

Upon further study, Beard came to the conclusion that
cancer cells were misplaced trophoblastic cells that that grew
unchecked by
insufficient amounts of proteolytic enzymes. Almost one hundred
years
later Beard's findings are being proven. First, it has been shown
that
mouse trophoblast cell lines, similar to those of human
choriocarcinomas, can form tumors when transplanted elsewhere in the
subject
(Erlebacher, A., Lukens, A., & Glimcher, L. 2002). Secondly,
research has also
shown that pregnant trophoblasts and cancer cells have the same
method
of gene expression (Hohn, H. P., Linke, M., Ugele, B., & Denker,
H.W.,
1998 and Acevedo, H. F., Tong, J. Y., & Hartsock, R. J., 1995)

Cancer studies during the past ten years have brought a greater
understanding as to how cancer cells develop, and how they work.
Armed with
this information, it is now easier to understand how such simple
methods
of treatments involving enzyme and acetogenin usage can have such a
huge impact on the lives of cancer patients.

What affects cancer growth?

Let's delve into what researchers have uncovered recently
regarding why cancer cells develop and how they work. There are
three
areas to be addressed here. The first is the mitochondria of tumor
(cancer) cells; second is the relationship between telomerase and TGF
(Tumor Growth Factor)-beta activity; and finally, the relationship
between
TGF-beta, and dendritic cells.

In a study utilizing MnSOD (magnesium superoxide
dismutase)
to slow down the growth of cancer, it was discovered how important
the
mitochondria are to the cancer cells (Zhao, Y., Oberley, T. D.,
Chaiswing, L., Lin, S., Epstein, C. J., Huang, T. T., & St. Clair, D.
2002).
As genes that were coded for MnSOD were inserted into cancer cells
found in mice, the metastasis of the tumors was blocked. This
suggests
that without proper mitochondria function, the cancer cells could be,
in
effect, shut down. Since the mitochondria of cancer cells requires a
much higher generation of ATP than normal cells (Aisenberg, A. 1961),
shutting down mitochondria function should effectively stop the
growth and
ends the life cycle of the cell.

There has been a flurry of research regarding telomerase
and TGF-beta activity. Telomerase is the enzyme that rebuilds the
chromosome ends (telomeres). With each cell division, the telomeres
of its
chromosomes shorten and the cell ages, eventually bringing about the
death of the cell. When telomerase is present, the chromosome no
longer
has a division limit, making the cell capable of replicating
endlessly
(Sharma, G. G., Gopta, A., Wang, H., Scherthan, H., Dhar, S., Gandi,
V.,
et al. 2003). These "immortal" cancer cells have a tendency to
create
an over production of TGF-beta.

The over production of TGF-beta prevents dendritic cells
from maturing, thus rendering them ineffective. Dendritic cells act
as
scouts that "show" the cancer cell's antigens to the immune system.
This warns the immune system that there are out of control cells that
need
to be killed off. If the dendritic cells have been rendered
incapable
of performing their duties, the immune system has been disarmed, and
the cancer cells continue to multiply, producing even more TGF-beta.
Should an immune cell (lymphocyte) come across a cancer cell, the TGF-
beta
that has already been produced penetrates the immune cell and shuts
off
its ability to kill the cancer cell. Between eliminating the
effectiveness of the dendritic cells and shutting off the remaining
lymphocytes,
TGF-beta production of the cancer cells has ensured its longevity.

These three areas of research directly factor in to how
and
why the use of proteolytic enzyme, and annonaceous acetogenin
therapies
are effective at getting to and shutting down cancer cells.


Proteolytic enzymes
So what exactly are proteolytic enzymes and why do they help keep
rogue
trophoblastic cells from growing uncontrollably throughout the body?
These enzymes, when produced by the body, come from the pancreas, in
the
form of pancreatin. Pancreatin is a mixture of different enzymes,
such
as protease (for the digestion of proteins), lipase (for the
digestion
of lipids, or fats), and amylase, for the digestion of carbohydrates,
or sugars (Wardlaw, G., Kessel, M., 2002). While all of these
enzymes
have a large part in the digestion of food, protease and amylase are
directly involved in the degradation of cancer cells (Tarutinove, V.,
Nosa, P. P., Ros, N. V., Galachin, K. A., & Slipilevega, S. I., 1999).

Cancer cells have a unique make up that makes it
difficult
for outside attack by immune cells. Their membranes are covered with
a
thick coat of fibrin (protein) that can stick to tissues. This
allows
them to relocate and begin to multiply. The fibrin coat also helps
the
cancer cells to hide their antigens that would otherwise make it
easier
for the immune system to recognize and attack (Wrba, H., & Pecher, O.
1993). Also, attached to this fibrin coat are hair-like strands that
are composed of carbohydrates (Currie, G. A. & Bagshawe, K. D.
1967).
These strands make it difficult for enzymes like trypsin and
chymotrypsin
to gain access to the outer proteins that protect the growing tumor.
Having extra amylase circulating in the blood (above that which is
needed
for day-to-day digestion) will provide the means to break down the
carbohydrate protrusions covering the fibrin coating of the cancer
cell
(Beard, 1911). As with amylase, if protein-digesting enzymes are in
high
enough supply, they will begin to break down the fibrin coating
(Maurer, H., 2001), exposing the antigens, as well as help transport
cancer
killing agents to enter the tumor and do their job (Tarutinove,
1999).

Along with the degradation of the cancer's outer
membranes,
proteolytic enzymes have another vital role, which affects dendritic
cells. When these enzymes are present, they activate a compound
called
alpha-two-macroglobulin (Dresser, L. L., Holmanova, D., Zavadova, E.,
Pavella, K., & Mohr, T., 2001). Alpha-two-macroglobulin binds to and
irreversibly renders TGF-beta inactive. With the TGF-beta levels back
in
balance, the previously immature dendritic cells are allowed to
mature
and perform their function in the immune system (Dresser, L. L.,
Sakalova, A., Zavadova, A., Holomanova, D., & Mohr, T., 1997). This,
in turn,
activates the immune system, which begins to attack the previously
shielded cancer cells.

A National Cancer Institute (NCI) funded study is
currently
being conducted by Columbia University's College of Physicians at
Columbia-Presbyterian Medical Center (National Cancer Institute at:
www.
Cancer.gov/clinical_trials). Under the Direction of Dr. Nicholas J.
Gonzalez, seventy to ninety patients with metastacised pancreatic
cancer
will take part in a study where one-half of the patients will receive
"state of the art" conventional chemotherapy (receiving gemcitabine),
and
the other half will undergo non-conventional treatment involving diet
modification, nutrient and proteolytic enzyme supplementation, and
regular detoxification. This five-year study began in 1999, and is
to be
completed this year.

The NCI funded study was approved only after Gonzalez's
preliminary study in 1995, involving 11 patients with pancreatic
cancer
(funded by Nestec), resulted in a one- year survival rate of 81%, a
two-year survival rate of 45%, a three-year survival rate of 36% and
a
four-year survival rate of 18%. Compared to the one-year survival of
18.6%
and two-year survival rate of 8.4%, a three-year survival rate of
5.3%
and a four-year survival rate of 4% for patients receiving standard
chemotherapy (SEER survival rates 1975-2000), Dr. Gonzalez's
protocol has
promise.



Annonaceous Acetogenins
In multiple studies at Purdue University, these derivatives of
long-chain fatty acids from the Annoncae (plant) family have been
proven to be
cytotoxic to six human solid tumor cell lines, particularly the lung,
colon, pancreatic (Zeng, L., Wu, F., Oberlies, N. H., McLaughlin, J.
L.,
& Sastrodihahdjo, S., 1996) and prostrate cell lines. In fact, these
compounds were ten to one hundred times as cytotoxic as adriamycin (a
chemotherapy medication) in the prostrate cell line, and about one
thousand times more potent than adriamycin in the pancreatic cell
line (Woo,
M.H., Chung, S. O., & Kim, D. H., 1999). How is this so?

As previously mentioned, cancer cells have a high need for ATP.
Annonaceous acetogenins have been found to be very effective
inhibitors of
Complex I activity in the mitochondria of mammals (Degli, E. M.,
Ghelli, A., Ratta, M., Cortes, D & Estornel, E., 1994). The
inhibition of
Complex I, in turn, prevents NADH oxidase of the plasma membranes of
tumor cells (Alali, F.Q., Liu, X. X., & McLaughlin, J. L., 1999).
This
depletes the amount of ATP that can be made available to the tumor
cells.
Without ATP to fuel its growth, the tumor cells die. However, if
acetogenins are used without tumors being present, the ATP depletion
will
occur in healthy cells. For this reason, annonaceous acetogenins
should
not be used as a preventative regime.

It has been noted that even in Multi-Drug Resistant (MDR) cancers,
acetogenins effectively shut down the mitochondria (Oberlies, N.H.,
Chang,
C., McLaughlin, J.L., 1997). This is possible because MDR cancer
cells
develop "pumps" (P-glycoprotein mediated pumps) that remove
anti-cancer agents out of the cell before the agents can kill it
(Alali 1999).
These pumps use a lot of energy (ATP) to remain functional, so if
their
ATP is shut off, they can no longer utilize their pump. The
previously
drug resistant cancer cells can now become an accessible target for
anti-cancer agents.



Putting it all together
When proteolytic enzymes are used in conjunction with annonaceous
acetogenins, the affects are increased exponentially. The enzymatic
effects
of breaking up the fibrin coat of the cancer cell, reducing the level
of TGF-Beta, and allowing the dendritic cells to mature, as well as
the
acetogenic effects of shutting down mitochondria activity in tumor
cells, creates a very effective means of eradicating cancer. One
should
also consider the fact that these preparations are not toxic to the
patient the way that standard radiation and chemotherapy treatments
are.
The most bothersome side effects of proteolytic enzyme and acetogenin
therapies tend to be gastrointestinal disturbances as the body breaks
down
and eliminates toxins produced by the degradation of the tumor cells
(Gonzalez 1999).

It has been noted that chemotherapy efficacy is limited by its
toxicity, and the same is true for radiation. What good is a
treatment if
just a little too much kills the patient? I look forward to the
results
of Dr. Gonzalez's study this year, and continue to delight in the new
path that traditional medicine is beginning to take: A path that
will
truly heal patients, rather than just relieve symptoms.



REFERENCE LIST
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Aisenberg, A. (1961). The glycolysis and respiration of tumors: A
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Aacetogenins from the
leaves of annona muricata. J Nat Prod, 59 (11), 1035-42.







--- In kefirtaneleri@yahoogroups.com, Murat Ozdemir <mro@q...> wrote:
> Selamlar -,
> Gerek Turkce, gerek Ingilizce hazirlanmis pek cok sitede pek cok
insan
> kefir'in faydali olduguna inaniyor. Bu cok guzel. Ancak hic bir
yerde son
> 20 sene icerisinde basilmis, kontrollu deney neticelerinin
yayinlandigi
> bir arastirmaya rastlayamadim. Benim gorebildiklerim sitelerdeki
bilgiler
> genel biyoloji/tip/beslenme prensipsiplerinden yapilan cikarimlar
gibi
> geldi. Bu da guzel birsey ama insan surekli tibbi bir dergide veya
bir
> biyoloji dergisinde yayinlanmis bilimsel bir makalede kontrollu
deney
> neticelerini okumak istiyor.
>
> Yukaridakileri yeterince arastirma yapmadigimin farkinda olarak
> soyluyorum. Eger bildigimiz bir bilimsel calisma neticesi varsa
bana
> bahsedebilir misiniz? Eger mumkunse URL'sini gonderebilir misiniz?
> (Hakemleri olan bir bilimsel dergide yayinlanmis olan yazi olmasi
veya FDA
> gibi otorite bir kurum tarafindan basilmis olmasi benim icin
onemli.)
>
> Tesekkurler,
> Murat.