The document discusses the role of vascular endothelial growth factor (VEGF) and angiogenesis in cancer progression. It notes that VEGF promotes angiogenesis, which is critical for tumor growth and metastasis. Several studies have shown that VEGF expression is elevated in skin tumors compared to normal skin tissue, and promotes skin carcinogenesis and angiogenesis. Inhibiting VEGF, such as with antibodies, compounds the formation of blood vessels in tumors and reduces tumor growth in animal models.
you can find out all types of VEGF in this ppt and it is about physiological and path-physiological significance of VEGF and its possible targeting manoeuvering
angiogenesis, anti angiogenic agents, angiogenic mechanism, types of angiogenesis, wound healing, disorders of angiogenesis, tumour angiogenesis, factors of angiogenesis, theurepeutic angiogenesis, father of tumour angiogenesis, terminology of angiogenesis, angiogenesis in health and disease, diabetic retinopathy, retinopathy of prematurity, macular degeneration, rheumatoid arthritis, arteriogenesis, intussusceptive agiogenesis, angioblasts, angiogenesis inhibitors, william harvey, judah folkman, interferon, thromospondin,sprouting angiogenesis, VEGF,FGF, PDGF, matrix metalloproteinases ,
Watch the slideshow: https://youtu.be/TP7iP1HEVps
Learn key concepts:
Hallmarks of cancer, Angiogenic switch, Tumor Angiogenesis
VEGF family i.e ligand and receptors, Effect of VEGF
VEGF Inhibitors or angiogenic
Bevacizumab, Ramucirumab, Ziv-Aflibercept
you can find out all types of VEGF in this ppt and it is about physiological and path-physiological significance of VEGF and its possible targeting manoeuvering
angiogenesis, anti angiogenic agents, angiogenic mechanism, types of angiogenesis, wound healing, disorders of angiogenesis, tumour angiogenesis, factors of angiogenesis, theurepeutic angiogenesis, father of tumour angiogenesis, terminology of angiogenesis, angiogenesis in health and disease, diabetic retinopathy, retinopathy of prematurity, macular degeneration, rheumatoid arthritis, arteriogenesis, intussusceptive agiogenesis, angioblasts, angiogenesis inhibitors, william harvey, judah folkman, interferon, thromospondin,sprouting angiogenesis, VEGF,FGF, PDGF, matrix metalloproteinases ,
Watch the slideshow: https://youtu.be/TP7iP1HEVps
Learn key concepts:
Hallmarks of cancer, Angiogenic switch, Tumor Angiogenesis
VEGF family i.e ligand and receptors, Effect of VEGF
VEGF Inhibitors or angiogenic
Bevacizumab, Ramucirumab, Ziv-Aflibercept
The Wnt cascade has emerged as a critical regulator of stem cells. In many tissues, activation of Wnt signaling has also been found to be associated with cancer. Understanding the regulation by Wnt signaling may serve as a paradigm for understanding the dual nature of self-renewal signals.
Angiogenesis is the growth of blood vessels from the existing vasculature. It occurs throughout life in both health and disease, beginning in utero and continuing on through old age.
Anti VEGF cause regression of neovascularization.
There is no effect on the basic pathology responsible for neovascularization (hypoxia).
It’s the disease that is to be cured to prevent hypoxia and its effects.
They are a valuable ammunition in our armamentarium but alone are not curative of the condition.
They give us time & VALUABLE breathing space during which we can plan our course of further action.
The Wnt cascade has emerged as a critical regulator of stem cells. In many tissues, activation of Wnt signaling has also been found to be associated with cancer. Understanding the regulation by Wnt signaling may serve as a paradigm for understanding the dual nature of self-renewal signals.
Angiogenesis is the growth of blood vessels from the existing vasculature. It occurs throughout life in both health and disease, beginning in utero and continuing on through old age.
Anti VEGF cause regression of neovascularization.
There is no effect on the basic pathology responsible for neovascularization (hypoxia).
It’s the disease that is to be cured to prevent hypoxia and its effects.
They are a valuable ammunition in our armamentarium but alone are not curative of the condition.
They give us time & VALUABLE breathing space during which we can plan our course of further action.
The term angiogenesis is generally applied to the growth of .docxssusera34210
The term angiogenesis is generally applied
to the growth of microvessel sprouts the size
of capillary blood vessels, a process that is
orchestrated by a range of angiogenic factors
and inhibitors (FIG.1). Although proliferating
endothelial cells undergoing DNA synthesis
are a common hallmark of angiogenic
microvascular sprouts, extensive sprouts
can grow for periods of time, mainly by the
migration of endothelial cells1. Physiological
angiogenesis is distinct from arteriogen-
esis and lymphangiogenesis and occurs in
reproduction, development and wound
repair. It is usually focal, such as in blood
coagulation in a wound, and self-limited
in time, taking days (ovulation), weeks
(wound healing) or months (placentation).
By contrast, pathological angiogenesis can
persist for years. Pathological angiogenesis is
necessary for tumours and their metastases
to grow beyond a microscopic size and it can
give rise to bleeding, vascular leakage and
tissue destruction. These consequences of
pathological angiogenesis can be responsible,
directly or indirectly, for the symptoms, inca-
pacitation or death associated with a broad
range of ‘angiogenesis-dependent diseases’2.
Examples of such diseases include cancer,
autoimmune diseases, age-related macular
degeneration and atherosclerosis (TABLE 1).
The concept of angiogenesis-dependent
diseases originated in 1972 with the recogni-
tion that certain non-neoplastic diseases, such
as the chronic inflammatory disease psoriasis,
depend on chronic neovascularization to
provide a conduit for the continual delivery
of inflammatory cells to the inflammatory
site3–5. Subsequently, other non-neoplastic
diseases were recognized to be in part angio-
genesis dependent, for example, infantile
haemangiomas6, peptic ulcers7, ocular
neovascularization8, rheumatoid arthritis9 and
atherosclerosis3,10,11. This led to a more general
understanding that the process of angiogen-
esis itself could be considered as an ‘organ-
izing principle’. Organizing principles are
common in the physical sciences, and are now
starting to be recognized in biology — other
examples might be inflammation or apopto-
sis, which are also aspects of many otherwise
unrelated diseases. The heuristic value of
such a principle is that it permits connections
between seemingly unrelated phenomena.
For example, the discovery of a molecular
mechanism for one phenomenon might be
more rapidly demonstrated for a second
phenomenon if one understands a priori that
the two are connected. Furthermore, when
the mechanisms underlying different diseases
can be related in this way, the development
of therapeutics for one disease could aid
the development of therapeutics for others.
Although it remains to be determined to what
extent treating pathological angiogenesis in
different angiogenesis-dependent diseases will
be successful, the recent approval of ranibi-
zumab (Lucentis; Genentech) — an antibody
fragment bas ...
Vascular Endothelial Growth Factor (VEGF) is a key player in the complex dance of blood vessel creation, highlighting its importance in the body's physiological and pathological functions.
Creative Bioarray's SuperQuick® angiogenesis assay kit provides a robust method to determine angiogenesis (in vitro) in less than 18 hrs. This assay kit provides a simple, easy to perform, semi-quantitative tool for assessing angiogenesis.
https://www.creative-bioarray.com/superquick-angiogenesis-assay-kit-item-csk-xa001-5627.htm
SIGNALING MECHANISM DRIVING ANGIOGENESIS IN HYPOXIC TUMOR MICRO-ENVIRONMENTMinali Singh
Cancer and stromal cells often have restricted access to nutrients and oxygen during tumor development and progression. Most solid tumors have regions permanently or transitorily subjected to hypoxia because of deviant vascularization and a poor blood supply. To meet oxygen demands, hypoxic cancer cells activate transcriptional, post-transcriptional and translational mechanism that leads to the generation of new blood vessels from pre-existing ones (angiogenesis) which is a prerequisite not only for Oxygen delivery, but also for tumor growth and metastasis.
The angiogenesis process, the factors regulating it, different assays for it, a little about tumour angiogenesis, the drugs and new therapeutic approaches towards inhibiting or augmenting the process.
Similar to Vascular endothelial growth factor signaling pathwys in cancer (20)
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Vascular endothelial growth factor signaling pathwys in cancer
1. Department of Biochemistry
Subject
Vascular Endothelial Growth Factor
Signaling Pathway in Cancer
Supervisor
Prof.Dr: Amal EL-giar
By/
Ahmed abdallah hamed Ibrahim.:91
Ahmed abd-elnaby Ibrahim elmogazy.:92
93: Ahmed abd-rabelnaby Ahmed farag.
94:Ahmed abd-dlrahman ahmed el-mekkawy
95:Ahmed Attia Ibrahim El-khateeb
2. Vascular endothelial growth factor:
A peptide released from vascular endothelial cells and other cells in
response to hypoxia, ischemia, or hypoglycemia. VEGF promotes
angiogenesis. Interaction of VEGF with VEGF-2 receptor induces the full
spectrum of VEGF biologic responses in endothelial cells, including
permeability enhancement, cellular proliferation, and migration. VEGF is
released continuously to maintain the survival of the microvasculature of
a tissue. Inhibition of VEGF production by hyperoxia results in
regression of surplus micro vascular elements.
The vascular endothelial growth factor (VEGF)/VEGF
receptor system
Angiogenesis, the formation and maintenance of blood vessel structures,
is essential for the physiological functions of tissues and is important for
the progression of diseases such as cancer and inflammation. In recent
decades, a variety of signaling molecules, such as VEGF-VEGFRs.
Among these, vascular endothelial growth factors (VEGFRs) and
receptors (VEGFRs) regulate both vasculogenesis, the development of
blood vessels from precursor cells during early embryogenesis, and
angiogenesis, the formation of blood vessels from pre-existing vessels at
a later stage (Fig. 1). The VEGF family of genes contains at least 7
members, including the viral genome–derived VEGF-E, whereas the
VEGFR family of genes has 3 to 4 members depending on the vertebrate
species VEGF-A and its receptors VEGFR-1 and VEGFR-2 play major
roles in physiological as well as pathological angiogenesis, including
tumor angiogenesis. VEGF-C/D and their receptor VEGFR-3 can
regulate angiogenesis at early embryogenesis but mostly function as
critical regulators of lymph angiogenesis.
3. Structure and Function of the VEGF Family
The VEGF family includes VEGF-A, VEGF-B, VEGF-C, VEGF-D,
PlGF (placental growth factor), and VEGF- and Trimeresurus flavoviridis
svVEGF. With the exception of the latter 2 members, 5 genes of the
VEGF family exist in mammalian genomes, including humans.
VEGF-A: is a protein with vascular permeability activity that was
originally purified from a fluid secreted by a tumor.VEGF-A binds to and
activates both VEGFR-1 and VEGFR-2, promoting angiogenesis,
vascular permeability, cell migration, and gene expression In addition.
Showed that an autocrine loop of VEGF-A and its receptor system exist
within vascular endothelial cells, contributing to endothelial functions.PlGF
and VEGF-B: These molecules bind to and activate only VEGFR-1. As
will be described later, VEGFR-1 has the ability to bind tightly to its
ligands but has a weak tyrosine kinase activity, generating signals weaker
than VEGFR-2. VEGF-C and VEGF-D: These 2 members of the VEGF
family are produced as premature forms and are cleaved by proteases
such as furin in both the amino- and carboxyl-terminal portions. After
processing, these molecules develop a higher affinity for VEGFR-3,
which is expressed on lymphatic endothelial cells and stimulates the
receptor for lymph angiogenesis. VEGF-E, an Angiogenic Protein
Encoded in the Pro-Angiogenic Orf Virus Genome: The Orf virus, a
parapoxvirus infecting sheep, goats, and sometimes humans, is known to
induce angiogenesis at sites of infection on the skin.
The VEGF (vascular endothelial growth factor) family and its receptors
are essential regulators of angiogenesis and vascular permeability.
VEGF-A binds to and activates two tyrosine kinase receptors, VEGFR
(VEGF receptor)-1 and VEGFR-2. VEGFR-2 mediates most of the
endothelial growth and survival signals, but VEGFR-1-mediated
4. signaling plays important roles in pathological conditions such as cancer,
ischemia and inflammation. In solid tumors, VEGF-A and its receptor are
involved in carcinogenesis, invasion and distant metastasis as well as
tumor angiogenesis. VEGF-A also has a neuroprotective effect on
hypoxic motor neurons, and is a modifier of ALS (amyotrophic lateral
sclerosis). Recent progress in the molecular and biological understanding
of the VEGF/VEGFR system provides us with novel and promising
therapeutic strategies and target proteins for overcoming a variety of
diseases.
What is angiogenesis?
Angiogenesis is the formation of new blood vessels. This process
involves the migration, growth, and differentiation of endothelial cells,
which line the inside wall of blood vessels.
The process of angiogenesis is controlled by chemical signals in the
body. These signals can stimulate both the repair of damaged blood
vessels and the formation of new blood vessels. Other chemical signals,
called angiogenesis inhibitors, interfere with blood vessel formation.
Normally, the stimulating and inhibiting effects of these chemical signals
are balanced so that blood vessels form only when and where they are
needed.
Why is angiogenesis important in cancer?
Angiogenesis plays a critical role in the growth and spread of cancer. A
blood supply is necessary for tumors to grow beyond a few millimeters in
size. Tumors can cause this blood supply to form by giving off chemical
signals that stimulate angiogenesis. Tumors can also stimulate nearby
normal cells to produce angiogenesis signaling molecules. The resulting
new blood vessels “feed” growing tumors with oxygen and nutrients,
allowing the cancer cells to invade nearby tissue, to move throughout the
body, and to form new colonies of cancer cells, called metastases.
Because tumors cannot grow beyond a certain size or spread without a
blood supply, scientists are trying to find ways to block tumor
angiogenesis. They are studying natural and synthetic angiogenesis
inhibitors, also called antiangiogenic agents, with the idea that these
molecules will prevent or slow the growth of cancer.
5. How do angiogenesis inhibitors work?
Angiogenesis requires the binding of signaling molecules, such as
vascular endothelial growth factor (VEGF), to receptors on the surface of
normal endothelial cells. When VEGF and other endothelial growth
factors bind to their receptors on endothelial cells, signals within these
cells are initiated that promote the growth and survival of new blood
vessels.
Angiogenesis inhibitors interfere with various steps in this process. For
example, bevacizumab (Avastin®) is a monoclonal antibody that
specifically recognizes and binds to VEGF (1). When VEGF is attached
to bevacizumab, it is unable to activate the VEGF receptor. Other
angiogenesis inhibitors, including sorafenib and sunitinib, bind to
receptors on the surface of endothelial cells or to other proteins in the
downstream signaling pathways, blocking their activities (2).
Are any angiogenesis inhibitors currently being used to
treat cancer in humans?
Yes. The U.S. Food and Drug Administration (FDA) has approved
bevacizumab to be used alone for glioblastoma that has not improved
with other treatments and to be used in combination with other drugs to
treat metastatic colorectal cancer, some non-small cell lung cancers, and
metastatic renal cell cancer. Bevacizumab was the first angiogenesis
inhibitor that was shown to slow tumor growth and, more important, to
extend the lives of patients with some cancers.
how are angiogenesis inhibitors different from conventional
anticancer drugs?
Angiogenesis inhibitors are unique cancer-fighting agents because they
tend to inhibit the growth of blood vessels rather than tumor cells. In
some cancers, angiogenesis inhibitors are most effective when combined
with additional therapies, especially chemotherapy. It has been
hypothesized that these drugs help normalize the blood vessels that
supply the tumor, facilitating the delivery of other anticancer agents, but
this possibility is still being investigated.
Angiogenesis inhibitor therapy does not necessarily kill tumors but
instead may prevent tumors from growing. Therefore, this type of therapy
may need to be administered over a long period
6. Do angiogenesis inhibitors have side effects?
Initially, it was thought that angiogenesis inhibitors would have mild side
effects, but more recent studies have revealed the potential for
complications that reflect the importance of angiogenesis in many normal
body processes, such as wound healing, heart and kidney function, fetal
development, and reproduction. Side effects of treatment with
angiogenesis inhibitors can include problems with bleeding; clots in the
arteries (with resultant stroke or heart attack), hypertension, and protein
in the urine .Gastrointestinal perforation and fistulas also appear to be
rare side effects of some angiogenesis inhibitors. Animal studies have
revealed the potential for birth defects, although there is no clinical
evidence for such effects in humans.
What is the ongoing research on angiogenesis inhibitors?
In addition to the angiogenesis inhibitors that have already been approved
by the FDA, others that target VEGF or other angiogenesis pathways are
currently being tested in clinical trials (research studies involving
patients). If these angiogenesis inhibitors prove to be both safe and
effective in treating human cancer, they may be approved by the FDA
and made available for widespread use.
The list below includes cancers that are being studied using angiogenesis
inhibitors.
Types of Cancer of Angiogenesis Inhibitors:
• Breast cancer
• Colorectal cancer
• Esophageal cancer
• Gastrointestinal stromal tumor (GIST)
• Kidney (renal cell) cancer
• Liver (adult primary) cancer
• Lymphoma
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Ovarian epithelial cancer
• Pancreatic cancer
• Prostate cancer
• Stomach (gastric) cancer
7. Kidney cancer:
Sometimes surgical treatment alone is not sufficient for kidney cancer. If
you had metastatic disease (cancer that has spread to other organs) when
you were diagnosed, or if you have developed metastatic cancer since
your nephrectomy, your doctor will most likely recommend additional
treatment. The most commonly used treatments for kidney cancer are
various forms of “targeted therapies” or immunotherapy. Targeted
therapies — so-called because they “target” cancer at the cellular level —
have expanded the options for the treatment of kidney cancer.
In 2005 and 2006, the U.S. Food and Drug Administration (FDA)
approved the first new medications to treat kidney cancer in more than a
decade: sorafenib tosylate and sunitinib malate. Both of these new drugs
disrupt the angiogenesis process. Known as tyrosine kinase inhibitors,
they interfere with the proteins inside cancer cells, thus interfering with
certain cell functions.
Medications
Nexavar® (sorafenib tosylate) is a medication that targets the blood
supply of a tumor, depriving it of the oxygen and nutrients it needs for
growth. By blocking the vascular endothelial growth factor (VEGF) and
platelet-derived growth factor (PDGF), Nexavar can interfere with the
tumor cell’s ability to increase its blood supply.
Sutent® (sunitinib malate) also deprives tumor cells of the blood and
nutrients needed to grow by interfering with VEGF and PDGF signaling
pathways. Sutent was approved by the FDA in 2006 for kidney cancer
patients because of its ability to reduce the size of tumors.
Avastin® (Bevacizumab), FDA-approved for kidney cancer in August,
2009, is a biologic antibody designed to specifically bind to a protein
called vascular endothelial growth factor (VEGF) that plays an important
role throughout the lifecycle of the tumor to develop and maintain blood
vessels, a process known as angiogenesis. Avastin is designed to interfere
with the blood supply to a tumor by directly binding to the VEGF protein
to prevent interactions with receptors on blood vessel cells. Avastin does
not bind to receptors on normal or cancer cells. The tumor blood supply is
thought to be critical to a tumor's ability to grow and spread in the body
(metastasize.(
8. Introduction of Non-melanoma skin cancer:
Non-melanoma skin cancer (NMSC) is the most commonly diagnosed
type of cancer. Over 2 million patients are treated for these cancers each
year in the USA alone resulting in nearly $1.5 billion total direct costs
annually. Unlike many other types of cancer, the rates of Non-melanoma
skin cancer continue to rise indicating the need to increase research and
identify new, more effective therapies. Non-melanoma skin cancer are
primarily caused by chronic exposure to ultraviolet (UV) light from the
sun, although chemical exposure, chronic wounds, and viral infection can
be risk factors as well. There are two main types of Non-melanoma skin
cancer: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
Basal cell carcinoma account for about 80% of skin cancers and although
these tumors are rarely metastatic, patients have a high risk of developing
additional tumors within 5 years of diagnosis. Squamous cell carcinoma
make up roughly 16% of all skin cancers and are typically more
aggressive than basal cell carcinoma, posing a higher risk for metastasis
and leading to approximately 2,500 deaths annually. The risk of
developing skin cancer is very high in the general population, as one in
five people will develop skin cancer in their lifetimes however; certain
populations such as transplant patients are at an even greater risk.
Angiogenesis, the growth and expansion of the vasculature, is an
important process in the growth and metastasis of many cancers,
including Non-melanoma skin cancer. Vascular endothelial growth factor
(VEGF) is a potent pro-Angiogenic factor and several studies have
established a critical role for vascular endothelial growth factor in skin
cancer. Vascular endothelial growth factor promotes skin carcinogenesis
through the induction of angiogenesis. Additionally, several recent
studies have now uncovered direct effects of vascular endothelial growth
factor on keratinocytes and skin tumor cells.
9. VEGF and Angiogenesis in Skin Tumors:
Strong evidence has demonstrated that VEGF plays an important role in
skin carcinogenesis. In human skin, VEGF is expressed at low levels in
normal epidermis, with more differentiated epidermal cell layers
generally expressing more VEGF than less differentiated epidermal cells.
Several studies have confirmed that VEGF levels are elevated in tumor
cells compared to normal epidermal cells using immunohistochemistry
and hybridization techniques. Tumor cells of human BCCs tend to show
weak VEGF expression with positive tumor cells predominantly localized
to the invading margin. In contrast, SCCs, which are typically more
10. aggressive than BCCs, display more intense and widespread staining,
with higher expression in tumor cells localized near infiltrating
inflammatory cells. Furthermore, VEGF expression is elevated in poorly
differentiated SCCs compared to well differentiate tumors. Vessel density
is also high in SCCs, especially in late-stage SCCs, compared to normal
skin, actinic keratoses, BCCs, or early-stage SCCs.
In mice, acute exposure to tumor promoters such as TPA or UV light
causes up regulation of VEGF and induction of angiogenesis in the skin.
What is observed in human tumors. VEGF is low in murine skin and
increases stepwise during tumor genesis. A functional role for VEGF in
skin tumor angiogenesis has been demonstrated through the use of
transgenic. Both K6-VEGF and K14-VEGF transgenic mice which over
express VEGF in epidermal keratinocytes show elevated blood vessel
density in the skin and in skin tumors. K14-VEGF mice develop
chemically-induced tumors more rapidly and also have a dramatically
higher incidence of metastasis. Conversely, conditional K14-VEGF mice
have reduced blood vessel density in tumors and are much more resistant
to chemical carcinogenesis.
VEGF also plays a role in UV-induced skin carcinogenesis. UV exposure
increases VEGF levels and neovascularization in the skin. Inhibition of
VEGF in the skin with compounds such as epigallocatechin-3-gallate
(ECGC) and myricetin leads to a decrease in angiogenesis and a
reduction in the number of UV-induced skin tumors .
SCC-13 cells transfected with VEGF when injected subcutaneously or
intradermally into nude mice .Furthermore, treatment with VEGFR-2
blocking antibodies reduces endothelial cell proliferation and vessel
density in tumors.
Conclusion:
Transfected cells were injected subcutaneously into mice .VEGF-driven
tumors were larger, more vascular, more invasive, and had higher
numbers of infiltrating M2 macrophages compared to control tumors.
Depletion of macrophages reversed the effects of VEGF over expression,
indicating that VEGF was influencing tumor development by affecting
macrophages. In this model, VEGF stimulated the recruitment of
macrophages to the tumors. These studies indicate that in addition to
12. Each of us wants and needs to believe that
we will be helped and “cured” by whatever
therapy is used. The information you
receive may cause disappointment. It is
important not to let disappointment rob
you of your determination or will to live.
Simply learn from your experience and go
on.