A new form of cancer treatment using drugs called 'angiogenesis inhibitors' that specifically halt new blood vessel growth and starve a tumor by cutting off its blood supply.
Many healthy foods contain bioactive compounds – specific substances that affect the body in certain ways, such as lowering blood pressure or cholesterol or inhibiting angiogenesis.
5. What Is Metastasis?
Blood
vessel
2.Cancer cells
are transported
by the circulatory
system to distant sites
3.Cancer cells
reinvade and
grow at new
location
1.Cancer cells
invade
surrounding
tissues and
vessels
7. The Angiogenesis Process
The Angiogenesis Process: How Do New Blood Vessels
Grow?
The process of angiogenesis occurs as an orderly series of events :
I. Diseased or injured tissues produce and release angiogenic growth
factors (proteins) that diffuse into the nearby tissues.
II. The angiogenic growth factors bind to specific receptors located on
the endothelial cells (EC) of nearby preexisting blood vessels.
III.Once growth factors bind to their receptors, the endothelial cells
become activated. Signals are sent from the cell's surface to the
nucleus.
IV. The endothelial cell's machinery begins to produce new molecules
including enzymes. These enzymes dissolve tiny holes in the
sheath-like covering (basement membrane) surrounding all existing
blood vessels.
Folkman J, D’Amore PA. Blood vessel formation: what is its
molecular basis? Cell 1996;87:1153-1155.
10. Blood vessels are comprised of cells called endothelial cells.
The total surface area covered by these cells in an adult is
1000 m2 -- roughly the size of a tennis court.
If all the blood vessels in the body were lined up end-to-end,
they would form a line that could circle the earth twice.
Blood vessel cells do not normally grow in the healthy adult
they are normally inactive, or quiescent.
There are at least 20 different known angiogenic growth
factors.
Five angiogenic growth factors are being tested in humans for
growing new blood vessels to heal wounds and to restore blood
flow to the heart, limbs, and brain.
Angiogenic gene therapy is also being developed as a method
to deliver angiogenic growth factors to the heart, limbs, and
wounds.
There are at least 30 known natural angiogenesis inhibitors
found in the body.
11. The first angiogenesis inhibitor molecule was discovered in 1975
by Dr. Judah Folkman and Dr. Henry Brem in a study of cartilage.
Angiogenesis inhibitors have been discovered from natural
sources, including tree bark, fungi, shark muscle and cartilage,
sea coral, green tea, and herbs (licorice, ginseng, cumin, garlic).
In total, more than 300 angiogenesis inhibitors have been
discovered to date.
At least 184 million patients in Western nations could benefit
from some form of antiangiogenic therapy.
At least 314 million patients in Western nations would benefit
from some form of angiogenesis-stimulating (pro-angiogenic)
therapy.
The first successful treatment of an angiogenesis-dependent
disease occurred in 1989, when the drug interferon alfa2a, an
angiogenesis inhibitor, was used to regress the abnormal blood
vessels growing in the lungs of a boy with a benign disease called
pulmonary hemangiomatosis.
12. Some cancer patients have experienced dramatic regression of their
tumors from antiangiogenic therapy; others have experienced
stabilization of their disease.
More than 2,000 patients with heart disease have received some form
of experimental angiogenic therapy.
The first FDA-approved device to stimulate new blood vessels to grow
in diseased hearts is a laser used in a technique called Direct
Myocardial Revascularization, or DMR (sometimes called
transmyocardial revascularization, TMR).
The first FDA-approved blood vessel therapy for eye disease is a type of
photodynamic therapy called Visudyne (QLT Therapeutics/CibaVision),
which has shown effectiveness for treating macular degeneration.
The first angiogenesis-stimulating medicine is a prescription gel called
Regranex (recombinant human platelet-derived growth factor-BB,
Ortho-McNeil Pharmaceuticals) that became FDA-approved to heal
diabetic foot ulcers in December 1997.
More than $4 billion has been invested in the research and
development angiogenesis-based medicines, making this one of the
most heavily funded areas of medical research in human history.
14. Angiogenesis Inhibitors
have been found in nature - in
green tea, soy products, fungi,
mushrooms, Chinese cabbage,
tree bark, shark tissues, snake
venom, red wine, and many
other substances.
Still other angiogenesis
inhibitors have been
manufactured synthetically in
the laboratory.
Some FDA-approved medicines
have also been "re-discovered"
to have anti-angiogenic
Inhibition of vascular vo. Nature 362, 841-844 (1993(
15. To date more than 300 angiogenesis inhibitor molecules have been discovered:
Some angiogenesis inhibitors are naturally present in the human body because healthy
tissues appear to resist cancer growth by containing these anti-angiogenic compounds.
List of 32 Known Angiogenesis Inhibitors in the Body
Angiostatin (plasminogen fragment) Metalloproteinase inhibitors (TIMPs)
Anti-angiogenic antithrombin III (aaATIII) Pigment epithelial-derived factor (PEDF)
Canstatin Placental ribonuclease inhibitor
Cartilage-derived inhibitor (CDI) Plasminogen activator inhibitor
CD59 complement fragment Platelet factor-4 (PF4)
Endostatin (collagen XVIII fragment) Prolactin 16kD fragment
Fibronectin fragment Proliferin-related protein
Gro-beta Retinoids
Heparinases Tetrahydroco
Heparin hexasaccharide fragment rtisol-S
Human chorionic gonadotropin (hCG) Thrombospondin-1
Interferon alpha/beta/gamma Transforming growth factor-beta
Interferon inducible protein (IP-10) Tumistatin
Interleukin-12 (IL-12) Vasculostatin
Kringle 5 (plasminogen fragment) Vasostatin (calreticulin fragment)
2-Methoxyestradiol (2-d) Angioarrestin
17. Without Angiogenesis,
Tumor Growth Stops
Injected cancer
cells stop
growing as mass
reaches
1–2 mm in
diameter
Isolated organ
(e.g., thyroid gland(
Infuse nutrient solution
19. Definition of Angiogenic TherapyA new form of cancer treatment using
drugs called 'angiogenesis inhibitors'
that specifically halt new blood vessel
growth and starve a tumor by cutting
off its blood supply.
A substance in the body called
Vascular Endothelial Growth Factor
(VEGF) is responsible for the growth of
new blood vessels. It promotes this
growth by stimulating the endothelial
cells, which form the walls of the
vessels and transport nutrients and
oxygen to the tissues.
Anti-Angiogenic drugs prevent the
VEGF from binding with the receptors
on the surface of the endothelial cells.
20. Three Major Types of Anti-
angiogenic Therapies for Cancer
1. Drugs that stop new blood
vessels from sprouting (true
angiogenesis inhibitors)
2. Drugs that attack a tumor's
established blood supply
(vascular targeting agents)
3. Drugs that attack both the cancer
cells as well as blood vessel cells
(the double-barreled approach).
24. Anti-angiogenesis, the starving of cancers by cutting off its
blood supply . Many healthy foods contain bioactive
compounds – specific substances that affect the body in
certain ways, such as lowering blood pressure or
cholesterol or inhibiting angiogenesis.
some other good examples of cancer fighting, anti-
angiogenesis foods include :
Green tea
Strawberries
Red Meeker raspberries
Soybeans
Chocolate
Cinnamon
Lavender
Olive Oil
Nutmeg
Artichokes
Sea Cucumber
Tuna
Parsleay
Garlic
Tomatoes
Grape See Oil
We now know that all
fruits and vegetables are
not created equal –
some are much more
potent than others,
based on their anti-
angiogenesis profiles.
25. Eat to Defeat: A New Way to Fight Cancer
At the Angiogenesis Foundation, we are launching an ambitious new
initiative, called Eat to Defeat Cancer, to help people take advantage
of foods that fight cancer. Using published data and the Foundation’s
own anti-angiogenesis food research, we are identifying and telling
the world about the most potent cancer-fighting foods.
26. Diet, Lifestyle & Angiogenesis
How You Can Eat (and Drink) to Defeat Cancer
Eating to defeat cancer can be accomplished simply by adding a few anti-angiogenic
foods to your meals each day, like those listed above. Like life itself, one’s diet is all
about making choices. Since we all eat every day, why not choose foods that can
reduce your risk of disease? Listed below are some food facts, supported by
scientific research, to help you get the most cancer fighting benefits from your diet.
Be picky. Red Delicious and Granny Smith apples have twice as many cancer
fighters as Fuji or Golden Delicious apples. The San Marzano tomato contains more
cancer fighters than any other variety. Wine grapes grown in cooler climates have
more cancer fighters than grapes grown in warmer climates.
Eat Your Sprouts. Broccoli sprouts can contain more cancer-fighting properties
than regular broccoli.
Dunk Your Teabag. Dunking a tea bag up and down releases more cancer-fighting
molecules than letting the bag just sit in the cup.
Cook Your Vegetables. Raw tomatoes are good, but cooking them in olive oil is
better.
Chew Your Greens. Chewing leafy greens helps to release enzymes that activate
cancer-fighting molecules embedded deep in the leaves.
Go Soy. Fermented soy, like the kind used in miso soup, contains four times more
cancer fighters than regular soybeans.
Choose one cancer fighting food for each meal. At 3 meals each day, that adds
up to more than a thousand of cancer fighting food choices each year
27. Summary
blood vessels. It promotes this growth by
stimulating the endothelial cells, which form
the walls of the vessels and transport
nutrients and oxygen to the tissues.
Angiogenesis inhibitors prevent the VEGF
from binding with the receptors on the
surface of the endothelial cells.
There are 3 major types of anti-angiogenic
therapies
Angiogenesis is the growth of blood
vessels and is an important natural process
used by the body for reproduction and for
healing injured tissues
28. references
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al., Biochem. Biophys. Res. Commun., 236, 651 (1997).
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3. Kim, K.J. Li, B. Winer, J. Armanini, M. Gillett, N. Phillips, H.S. & N. Ferrara : Inhibition of
vascular endothelial growth factor-induced angiogenesis suppresses ttumor growth in vivo.
Nature 362, 841-844 (1993)
4. Aiello, L.P. Pierce, E.A. Foley, E.D. Takagi, H. Chen, H. Riddle, L. Ferrara, N. King, G.L. &
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9. ^ Perhaps an inhibitor of angiogenesis: Sheppard D (October 2002). "Endothelial integrins
and angiogenesis: not so simple anymore". The Journal of Clinical Investigation 110 (7):
913–4. doi:10.1172/JCI16713. PMC 151161. PMID 12370267.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=151161.
Retrieved 2009-06-18.
29. Thank you for attending
For inquiries
Ndhayyat@aseza.jo
Nashatdhiat@yahoo.com
Notas del editor
National Cancer Institute Understanding Cancer and Related Topics Understanding Angiogenesis NCI Web site: http://cancer.gov/cancertopics/understandingcancer In early experiments, researchers asked whether cancer growth requires angiogenesis. Scientists removed a cancerous tumor from a laboratory animal and injected some of the cancer cells into a normal organ removed from the same strain of animal. The organ was then placed in a glass chamber and a nutrient solution was pumped into the organ to keep it alive for a week or two. Scientists found that the cancer cells grew into tiny tumors but failed to link up to the organ’s blood vessels. As a result, tumor growth stopped at a diameter of about 1-2mm. Without angiogenesis, tumor growth stopped .