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Angiogenesis
By
Eng. Nashat M. Dahiyat
Seminar Title : Angiogenesis
 Objectives
 Introduction “ understanding of angiogenesis “
 The Angiogenic Process
 Growth Factors & Inhibitors & Anti –Angiogenesis
 Angiogenesis in Disease 
 Tumor Angiogenesis
 Therapeutic Angiogenesis
  Diet, Lifestyle & Angiogenesis
 Conclusion
 Recommendation
 References
summary
Understanding  Angiogenesis
o  Angiogenesis is defined as the 
growth of blood vessels and is an 
important natural process used by 
the body for reproduction and for 
healing injured tissues 
o  Blood vessels bring oxygen and  
           nutrients via the circulation 
to nourish all tissues in the body 
o  The cells comprising blood 
vessels  are called endothelial cells 
o  The endothelial cells of a blood 
vessel also produce molecules that 
support the growth of tissues 
o  Cancer cells take over the 
body's control of angiogenesis in 
order to recruit their own private 
blood supply 
vascular endothelial growth factor. J Biol 
Chem 272, 24203-24209 (1997
Angiogenesis and
Vascular Endothelial Cells
Vascular
endothelial
cells
Blood
vessel
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
Metastasis Requires
Angiogenesis
Angiogenesis
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.
I.  The endothelial cells begin to divide (proliferate) and migrate 
out through the dissolved holes of the existing vessel towards 
the diseased tissue (tumor). 
II. Specialized molecules called adhesion molecules called 
integrins (avb3, avb5) serve as grappling hooks to help pull 
the sprouting new blood vessel sprout forward. 
III. Additional enzymes (matrix metalloproteinases, or MMP) are 
produced to dissolve the tissue in front of the sprouting vessel 
tip in order to accommodate it. As the vessel extends, the 
tissue is remolded around the vessel. 
IV. Sprouting endothelial cells roll up to form a blood vessel tube. 
V. Individual blood vessel tubes connect to form blood vessel 
loops that can circulate blood. 
VI. Finally, newly formed blood vessel tubes are stabilized by 
specialized muscle cells (smooth muscle cells) that provide 
structural support. Blood flow then begins. 
The Angiogenesis Process continued
Folkman J, D’Amore PA. Blood vessel formation: what is 
its molecular basis? Cell 1996;87:1153-1155.
The Angiogenesis Process continued
 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.
 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.
 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.
Angiogenic growth
FActors
 Basic fibroblast growth
factor (bFGF)
 Acidic fibroblast growth
factor (aFGF)
 Angiogenin
 Angiotropin
 Insulin-like growth
factor
 Interleukin-8
 Platelet activating
factor (PAF)
 Platelet-derived growth
factor (PDGF)
 Proliferin
 Transforming growth
factor-
 Transforming growth
factor-
 Tumor necrosis factor-
 Vascular endothelial
growth factor (VEGF)
J. Battegay: J. Mol Med; 1995
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(
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
What Is Tumor
Angiogenesis?
Small localized tumor Tumor that can grow and spread
Angiogenesis
Signaling
molecule
Blood vessel
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
Angiogenesis
Definition of Angiogenic Therapy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.
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.
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).
Angiogenesis
Anti-Angiogenic Drugs in Clinical Trial for Cancer
A6
Alpha5Beta1 Integrin
Antibody
ABT-510
Actimid
Angiocol
Angiostatin
Angiozyme
Aplidine
Aptosyn
ATN-161
Avastin (bevacizumab)
AVE8062A
Benefin
BMS275291
Carboxymidotriazole
CC4047
CC7085
CDC801
Celebrex (Celecoxib)
CEP-7055
CGP-41251/PKC412
Cilengitide
Combretastatin A4P
CP-547, 632
CP-564, 959
Dexrazoxane
Didemnin B
DMXAA
EMD 121974
Endostatin
Flavopiridol
GBC-100
Genistein Concentrated
Polysaccharide
Green Tea Extract
Interleukin-12
INGN 201
Interferon alfa
Iressa
LY317615
Mab huJ591-DOTA-90 Yttrium
(90Y)
Medi-522
Metaret (suramin)
Metastat (Col-3)
Neovastat
NM-3
NPe6
Octreotide
Oltipraz
Paclitaxel
Panzem (2ME2)
Penicillamine
PI-88
PSK
Revimid
Ro317453
Squalamine
SU11248
SU6668
Temptostatin
Tetrathiomol
Thalidomide
UCN-01
VEGF Trap
ZD6126
rate Proc. Natl. Acad. Sci.USA 95, 8875-8800 (1998)
Thalidomide
 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.
 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.  
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
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
references
1. O’Reilly, M.S., et al., Cell, 79, 315 (1994). Folkman, J., Nat. Med., 1, 27 (1995). Wu, Z., et
al., Biochem. Biophys. Res. Commun., 236, 651 (1997).
2. Boehm, T. Folkman, J. Browder, T. & M. O’Reilly : Anti-angiogenic therapy of experimental
cancer does not induce acquired drug resistance. Nature 390, 404-407 (1997)
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. &
L.E. Smith: Suppression of retinal neovascularization in vivo by inhibition of vascular
endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl
Acad Sci USA 92, 10457-10461 (1995)
5. Jonca, F. Ortéga, N. Gleizes, P.E. Bertrand, N. & J. Plouët: Cell release of bioactive fibroblast
growth factor by exon 6 encoded sequence of vascular endothelial growth factor. J Biol Chem
272, 24203-24209 (1997)
6. M. Tsujii, S. Kawano, S. Tsuji, H. Sawaoka, M. Hori, R.N. DuBois, Cyclooxygenase regulates
angiogenesis induced by colon cancer cells [published erratum appears in Cell 1998 Jul
24;94(2):following 271], Cell 93 (1998) 705-716.
7. P. Pradono, R. Tazawa, M. Maemondo, M. Tanaka, K. Usui, Y. Saijo, K. Hagiwara, T. Nukiwa,
Gene transfer of thromboxane A(2) synthase and prostaglandin I(2) synthase antithetically
altered tumor angiogenesis and tumor growth, Cancer Res. 62 (2002) 63-66.
8. Y. Takahashi, F. Kawahara, M. Noguchi, K. Miwa, H. Sato, M. Seiki, H. Inoue, T. Tanabe, T.
Yoshimoto, Activation of matrix metalloproteinase-2 in human breast cancer cells
overexpressing cyclooxygenase-1 or -2, FEBS Lett. 460 (1999) 145-148.
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.
Thank you for attending
For inquiries
Ndhayyat@aseza.jo
Nashatdhiat@yahoo.com

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Angiogenesis

  • 2. Seminar Title : Angiogenesis  Objectives  Introduction “ understanding of angiogenesis “  The Angiogenic Process  Growth Factors & Inhibitors & Anti –Angiogenesis  Angiogenesis in Disease   Tumor Angiogenesis  Therapeutic Angiogenesis   Diet, Lifestyle & Angiogenesis  Conclusion  Recommendation  References summary
  • 4. Angiogenesis and Vascular Endothelial Cells Vascular endothelial cells Blood vessel
  • 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.
  • 8. I.  The endothelial cells begin to divide (proliferate) and migrate  out through the dissolved holes of the existing vessel towards  the diseased tissue (tumor).  II. Specialized molecules called adhesion molecules called  integrins (avb3, avb5) serve as grappling hooks to help pull  the sprouting new blood vessel sprout forward.  III. Additional enzymes (matrix metalloproteinases, or MMP) are  produced to dissolve the tissue in front of the sprouting vessel  tip in order to accommodate it. As the vessel extends, the  tissue is remolded around the vessel.  IV. Sprouting endothelial cells roll up to form a blood vessel tube.  V. Individual blood vessel tubes connect to form blood vessel  loops that can circulate blood.  VI. Finally, newly formed blood vessel tubes are stabilized by  specialized muscle cells (smooth muscle cells) that provide  structural support. Blood flow then begins.  The Angiogenesis Process continued 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.
  • 13. Angiogenic growth FActors  Basic fibroblast growth factor (bFGF)  Acidic fibroblast growth factor (aFGF)  Angiogenin  Angiotropin  Insulin-like growth factor  Interleukin-8  Platelet activating factor (PAF)  Platelet-derived growth factor (PDGF)  Proliferin  Transforming growth factor-  Transforming growth factor-  Tumor necrosis factor-  Vascular endothelial growth factor (VEGF) J. Battegay: J. Mol Med; 1995
  • 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
  • 16. What Is Tumor Angiogenesis? Small localized tumor Tumor that can grow and spread Angiogenesis Signaling molecule Blood vessel
  • 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 Therapy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. 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).
  • 22. Anti-Angiogenic Drugs in Clinical Trial for Cancer A6 Alpha5Beta1 Integrin Antibody ABT-510 Actimid Angiocol Angiostatin Angiozyme Aplidine Aptosyn ATN-161 Avastin (bevacizumab) AVE8062A Benefin BMS275291 Carboxymidotriazole CC4047 CC7085 CDC801 Celebrex (Celecoxib) CEP-7055 CGP-41251/PKC412 Cilengitide Combretastatin A4P CP-547, 632 CP-564, 959 Dexrazoxane Didemnin B DMXAA EMD 121974 Endostatin Flavopiridol GBC-100 Genistein Concentrated Polysaccharide Green Tea Extract Interleukin-12 INGN 201 Interferon alfa Iressa LY317615 Mab huJ591-DOTA-90 Yttrium (90Y) Medi-522 Metaret (suramin) Metastat (Col-3) Neovastat NM-3 NPe6 Octreotide Oltipraz Paclitaxel Panzem (2ME2) Penicillamine PI-88 PSK Revimid Ro317453 Squalamine SU11248 SU6668 Temptostatin Tetrathiomol Thalidomide UCN-01 VEGF Trap ZD6126 rate Proc. Natl. Acad. Sci.USA 95, 8875-8800 (1998)
  • 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 1. O’Reilly, M.S., et al., Cell, 79, 315 (1994). Folkman, J., Nat. Med., 1, 27 (1995). Wu, Z., et al., Biochem. Biophys. Res. Commun., 236, 651 (1997). 2. Boehm, T. Folkman, J. Browder, T. & M. O’Reilly : Anti-angiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390, 404-407 (1997) 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. & L.E. Smith: Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci USA 92, 10457-10461 (1995) 5. Jonca, F. Ortéga, N. Gleizes, P.E. Bertrand, N. & J. Plouët: Cell release of bioactive fibroblast growth factor by exon 6 encoded sequence of vascular endothelial growth factor. J Biol Chem 272, 24203-24209 (1997) 6. M. Tsujii, S. Kawano, S. Tsuji, H. Sawaoka, M. Hori, R.N. DuBois, Cyclooxygenase regulates angiogenesis induced by colon cancer cells [published erratum appears in Cell 1998 Jul 24;94(2):following 271], Cell 93 (1998) 705-716. 7. P. Pradono, R. Tazawa, M. Maemondo, M. Tanaka, K. Usui, Y. Saijo, K. Hagiwara, T. Nukiwa, Gene transfer of thromboxane A(2) synthase and prostaglandin I(2) synthase antithetically altered tumor angiogenesis and tumor growth, Cancer Res. 62 (2002) 63-66. 8. Y. Takahashi, F. Kawahara, M. Noguchi, K. Miwa, H. Sato, M. Seiki, H. Inoue, T. Tanabe, T. Yoshimoto, Activation of matrix metalloproteinase-2 in human breast cancer cells overexpressing cyclooxygenase-1 or -2, FEBS Lett. 460 (1999) 145-148. 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

  1. 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 .