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 ,
Angiogenesis is the formation of new blood vessels from pre-existing vessels. It involves sprouting, splitting, and remodeling of existing vessels. It supplies oxygen and nutrients and removes waste. Tumors stimulate angiogenesis to grow beyond 2mm3 by producing angiogenic factors like VEGF. Angiogenesis inhibitors like endostatin can restrict tumor growth. Anti-angiogenic therapies cut off the tumor blood supply, while vascular disrupting agents directly damage existing tumor vessels.
This document discusses angiogenesis, the process by which new blood vessels form from pre-existing vessels. It covers the positive and negative regulators of angiogenesis, as well as conditions of excessive and insufficient angiogenesis. The document also reviews several drugs that target angiogenesis, including inhibitors of endothelial cell activation, intracellular signaling, and extracellular matrix remodeling. These drugs show promise in treating diseases driven by abnormal angiogenesis like cancer and retinal diseases.
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.
1. Angiogenesis is the process of forming new blood vessels from pre-existing vessels.
2. In 1971, Dr. Judah Folkman hypothesized that tumor growth depends on angiogenesis and published this theory, which was initially rejected.
3. Since the 1970s, many important discoveries have been made regarding angiogenic factors like VEGF and angiogenesis inhibitors.
Angiogenesis is the growth of new blood vessels from pre-existing vessels. It is a normal process in growth and development as well as wound healing. It involves the breakdown of the basement membrane by proteolytic enzymes, migration and proliferation of endothelial cells stimulated by growth factors, and formation of new vessels. Key regulators of angiogenesis include vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and angiopoietins. A balance between activators and inhibitors normally keeps angiogenesis in check, but it can be stimulated under conditions like hypoxia.
Tumor growth requires angiogenesis to develop new blood vessels. This process is regulated by a balance of pro-angiogenic and anti-angiogenic factors. Tumors disrupt this balance by inducing hypoxia and secreting factors like VEGF, which activate the "angiogenic switch" and promote new vessel growth. This allows tumors to recruit blood vessels to supply nutrients and remove waste. Anti-angiogenic therapies aim to block this process by targeting VEGF and its receptors. Drugs like bevacizumab and sorafenib inhibit angiogenesis to limit tumor growth and progression.
Angiogenesis is the formation of new blood vessels from pre-existing vessels. It involves sprouting, splitting, and remodeling of existing vessels. It supplies oxygen and nutrients and removes waste. Tumors stimulate angiogenesis to grow beyond 2mm3 by producing angiogenic factors like VEGF. Angiogenesis inhibitors like endostatin can restrict tumor growth. Anti-angiogenic therapies cut off the tumor blood supply, while vascular disrupting agents directly damage existing tumor vessels.
This document discusses angiogenesis, the process by which new blood vessels form from pre-existing vessels. It covers the positive and negative regulators of angiogenesis, as well as conditions of excessive and insufficient angiogenesis. The document also reviews several drugs that target angiogenesis, including inhibitors of endothelial cell activation, intracellular signaling, and extracellular matrix remodeling. These drugs show promise in treating diseases driven by abnormal angiogenesis like cancer and retinal diseases.
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.
1. Angiogenesis is the process of forming new blood vessels from pre-existing vessels.
2. In 1971, Dr. Judah Folkman hypothesized that tumor growth depends on angiogenesis and published this theory, which was initially rejected.
3. Since the 1970s, many important discoveries have been made regarding angiogenic factors like VEGF and angiogenesis inhibitors.
Angiogenesis is the growth of new blood vessels from pre-existing vessels. It is a normal process in growth and development as well as wound healing. It involves the breakdown of the basement membrane by proteolytic enzymes, migration and proliferation of endothelial cells stimulated by growth factors, and formation of new vessels. Key regulators of angiogenesis include vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and angiopoietins. A balance between activators and inhibitors normally keeps angiogenesis in check, but it can be stimulated under conditions like hypoxia.
Tumor growth requires angiogenesis to develop new blood vessels. This process is regulated by a balance of pro-angiogenic and anti-angiogenic factors. Tumors disrupt this balance by inducing hypoxia and secreting factors like VEGF, which activate the "angiogenic switch" and promote new vessel growth. This allows tumors to recruit blood vessels to supply nutrients and remove waste. Anti-angiogenic therapies aim to block this process by targeting VEGF and its receptors. Drugs like bevacizumab and sorafenib inhibit angiogenesis to limit tumor growth and progression.
It starts with brief introduction about angiogenesis, history of angiogenesis, types and various stages of angiogenesis, followed by its clinical usage.
The document summarizes angiogenesis, which is the growth of new blood vessels from pre-existing vessels. It describes the multi-step process of angiogenesis including initiation, endothelial cell migration and proliferation, and maturation. Key growth factors that stimulate angiogenesis like VEGF and FGF are discussed as well as inhibitors like endostatin and angiostatin that regulate the process. Pathological angiogenesis and potential clinical applications of modulating angiogenesis to treat conditions like chronic wounds and ischemia are also mentioned.
This document discusses angiogenesis pathways. It begins by introducing angiogenesis and its role in tumor growth. It then provides an overview of angiogenesis, defining it as the formation of new blood vessels from pre-existing vessels in response to various stimuli. This enhances tumor survival and progression as tumors require new blood vessels to obtain oxygen and nutrients. The document then discusses several signaling pathways involved in angiogenesis, including the roles of ROS, calcium homeostasis, HIF1α, and VEGFR2. It concludes by discussing therapeutic angiogenesis and the need to understand molecular mechanisms of angiogenesis and arteriogenesis to treat tissue hypoxia.
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.
Comprehensive Notes on the Molecular Basis of Cancermeducationdotnet
This document summarizes key aspects of cancer growth and spread. It notes that most benign tumors grow slowly over months to years, while cancers generally grow faster and can metastasize. Cancer stem cells have been identified in some cancers and may sustain tumor growth. Cancers infiltrate and invade surrounding tissue, unlike benign tumors which develop capsules. Metastasis, the growth of secondary tumors in distant sites, is a hallmark of malignancy. Cancers can metastasize through seeding in body cavities, lymphatic spread, or hematogenous spread through the bloodstream.
1) Tumor suppressor genes normally apply brakes to cell proliferation through proteins that form checkpoints to prevent uncontrolled growth. Loss of function of these genes allows tumor development.
2) The proteins encoded by tumor suppressor genes regulate cell cycle control, apoptosis, and cell survival/growth through mechanisms like transcription factors, cell cycle inhibitors, and DNA damage response.
3) Famous tumor suppressor genes include RB, p53, APC, and WT1. Mutation of both copies is required for loss of function, leading to cancers like retinoblastoma, Li-Fraumeni syndrome, colon cancer, and Wilms tumor.
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
VEGF signaling plays an important role in angiogenesis and vasculogenesis. VEGF binds to VEGFR receptors and activates several key pathways involved in endothelial cell proliferation, survival, migration and permeability. This includes the Ras/MAPK, PI3K/Akt, eNOS and PKC pathways. VEGF signaling is tightly regulated during development and in response to hypoxia. Dysregulation of VEGF signaling can lead to various angiogenic diseases if there is either excess or deficiency of VEGF.
1) Tumors exist within a complex microenvironment consisting of various cell types that influence tumor growth, progression, and metastasis.
2) Chronic inflammation can promote tumor development by increasing genetic mutations while also stimulating angiogenesis and tumor cell proliferation.
3) The tumor microenvironment interacts bidirectionally with cancer cells to encourage processes like angiogenesis, immune suppression, invasion, and metastasis through factors such as TGF-β, VEGF, and cytokines.
4) Therapies targeting the tumor microenvironment can impact its composition and make cancer cells more invasive, highlighting the need for combination treatments.
Tumor angiogenesis refers to the formation of new blood vessels within tumors to supply nutrients and oxygen needed for growth. Cancer cells stimulate angiogenesis through release of pro-angiogenic factors like VEGF. This allows tumors to grow larger and metastasize by remodeling the extracellular matrix and sprouting new blood vessels from existing vasculature. The extent of angiogenesis correlates with worse cancer progression and outcomes, making it a promising therapeutic target for anti-angiogenic drugs aimed at inhibiting blood vessel formation within tumors.
This document discusses targeted cancer therapies, which work by interfering with specific molecular targets involved in cancer growth and progression, unlike traditional chemotherapy which acts on all rapidly dividing cells. It provides examples of molecular targets for small molecule drugs and monoclonal antibodies, including growth factor receptors and fusion proteins. The document also discusses methods of target identification, categories of targeted therapies, examples of FDA-approved targeted drugs, limitations and side effects of targeted therapies, and concludes by emphasizing the importance and promise of targeted therapies while noting challenges that remain.
Proto-oncogenes are normal cellular genes that encode proteins involved in cell proliferation. When mutated, they become oncogenes that encode constitutively active oncoproteins driving increased cell growth. Proto-oncogenes can encode growth factors, growth factor receptors, signal transducers, transcription factors, or cell cycle regulators. Common mutations include RAS mutations in pancreatic cancer, BRAF mutations in melanoma, PI3K mutations in breast cancer, and MYC translocations in Burkitt's lymphoma. These mutations result in constitutive activation of signaling pathways that drive uncontrolled cell proliferation.
The document summarizes the process of cancer metastasis through the invasion-metastasis cascade. It involves 6 key steps: 1) Localized invasion of primary tumor cells aided by loss of cell adhesion molecules and matrix metalloproteinases. 2) Intravasation of tumor cells into blood vessels assisted by tumor-associated macrophages. 3) Transport of circulating tumor cells protected by platelet emboli. 4) Extravasation of tumor cells from vessels into distant tissues. 5) Formation of dormant micrometastases. 6) Rare colonization of micrometastases into macroscopic tumors limited by the foreign tissue environment. Metastasis suppressor genes and strategies targeting multiple steps simultaneously show promise for preventing cancer spread.
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.
This document summarizes key concepts about neoplasms and cancer. It defines neoplasms as abnormal masses of tissue with uncontrolled growth. Oncology is the study of tumors. Tumors can be benign, meaning localized growth, or malignant (cancerous), meaning they can invade other tissues and metastasize. Cancers arise from genetic changes in cells that disrupt normal growth regulation. Key cancer genes include oncogenes that promote growth and tumor suppressor genes that inhibit growth. Evasion of apoptosis and unlimited replication are also critical to cancer development.
The document summarizes the hallmarks of cancer, which are the key capabilities that enable tumor growth and metastasis. The hallmarks include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, deregulating cellular energetics, and evading immune destruction. Genomic instability and mutation, and tumor-promoting inflammation also enable cancer's capabilities by altering DNA and creating an inflammatory microenvironment. Targeting these hallmark capabilities is important for cancer therapeutics.
Exosomes - Diagnostics and TherapeuticsSumedhaBobade
This document discusses exosomes, which are extracellular vesicles that originate inside cells and are released outside. It provides background on the discovery of exosomes and their structure. Exosomes are 40-150nm in size and have a phospholipid bilayer. They are secreted by various immune cells, epithelial cells, and are present in many body fluids. The document outlines their biogenesis pathway and composition. It discusses the many potential roles and applications of exosomes in diagnostics and therapeutics for diseases like cancer, neurological disorders, and infectious diseases. Exosomes show promise as novel biomarkers for diagnosis and as vehicles for drug delivery.
This document discusses cancer stem cells (CSCs), which are rare cells in tumors that have the ability to self-renew and differentiate into the diverse cells that comprise the tumor. CSCs were first hypothesized in the 1870s and experiments in the 1950s-60s provided early evidence for their existence. The concept of CSCs was revived in the 2000s, with the definition that they can recapitulate tumor growth. CSCs are identified experimentally by markers and assays. They are thought to originate from somatic or adult stem/progenitor cells and have properties of self-renewal, differentiation, immortality. CSCs may cause metastases, therapy resistance and recurrence. Targeting CSCs may improve cancer treatment and CSCs may serve
This document discusses various targeted cancer therapies including monoclonal antibodies, small molecule inhibitors, and other targeted agents. It describes key targets of these therapies such as protein kinases, growth factor receptors, angiogenesis pathways, and nuclear factors. Specific drugs are discussed that target ABL, EGFR, VEGFR, mTOR, MAPK pathways, and the proteasome. Resistance mechanisms and combination approaches are also mentioned.
Cancer Stem Cells (CSCs) have become a vital target for biologists and researchers.
The following presentation focuses on the treatment of cancer through targeting CSCs and its advantages.
Angiogenesis is the formation of new blood vessels from pre-existing vessels. There are two main types of angiogenesis: sprouting angiogenesis and intussusceptive angiogenesis. Sprouting angiogenesis involves the activation of endothelial cells by growth factors, degradation of the extracellular matrix, endothelial cell proliferation and migration, and formation of new loops and branches to form new vessels. Intussusceptive angiogenesis involves the extension of endothelial cell junctions into the vessel lumen to split existing vessels. Angiogenesis plays an important role in development, wound healing, and diseases like cancer by supplying tumors with nutrients and oxygen needed for growth.
1. Angiogenesis is the process of new blood vessel growth from pre-existing vessels. It occurs both in health and disease through a balance of pro-angiogenic and anti-angiogenic factors.
2. In health, angiogenesis is important for wound healing and reproduction. Diseases involving excessive angiogenesis include cancer, rheumatoid arthritis, and ocular diseases like diabetic retinopathy.
3. Diseases of insufficient angiogenesis include ischemic heart disease. Tumor angiogenesis provides nutrients and oxygen to support tumor growth and is a target for therapies like bevacizumab.
It starts with brief introduction about angiogenesis, history of angiogenesis, types and various stages of angiogenesis, followed by its clinical usage.
The document summarizes angiogenesis, which is the growth of new blood vessels from pre-existing vessels. It describes the multi-step process of angiogenesis including initiation, endothelial cell migration and proliferation, and maturation. Key growth factors that stimulate angiogenesis like VEGF and FGF are discussed as well as inhibitors like endostatin and angiostatin that regulate the process. Pathological angiogenesis and potential clinical applications of modulating angiogenesis to treat conditions like chronic wounds and ischemia are also mentioned.
This document discusses angiogenesis pathways. It begins by introducing angiogenesis and its role in tumor growth. It then provides an overview of angiogenesis, defining it as the formation of new blood vessels from pre-existing vessels in response to various stimuli. This enhances tumor survival and progression as tumors require new blood vessels to obtain oxygen and nutrients. The document then discusses several signaling pathways involved in angiogenesis, including the roles of ROS, calcium homeostasis, HIF1α, and VEGFR2. It concludes by discussing therapeutic angiogenesis and the need to understand molecular mechanisms of angiogenesis and arteriogenesis to treat tissue hypoxia.
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.
Comprehensive Notes on the Molecular Basis of Cancermeducationdotnet
This document summarizes key aspects of cancer growth and spread. It notes that most benign tumors grow slowly over months to years, while cancers generally grow faster and can metastasize. Cancer stem cells have been identified in some cancers and may sustain tumor growth. Cancers infiltrate and invade surrounding tissue, unlike benign tumors which develop capsules. Metastasis, the growth of secondary tumors in distant sites, is a hallmark of malignancy. Cancers can metastasize through seeding in body cavities, lymphatic spread, or hematogenous spread through the bloodstream.
1) Tumor suppressor genes normally apply brakes to cell proliferation through proteins that form checkpoints to prevent uncontrolled growth. Loss of function of these genes allows tumor development.
2) The proteins encoded by tumor suppressor genes regulate cell cycle control, apoptosis, and cell survival/growth through mechanisms like transcription factors, cell cycle inhibitors, and DNA damage response.
3) Famous tumor suppressor genes include RB, p53, APC, and WT1. Mutation of both copies is required for loss of function, leading to cancers like retinoblastoma, Li-Fraumeni syndrome, colon cancer, and Wilms tumor.
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
VEGF signaling plays an important role in angiogenesis and vasculogenesis. VEGF binds to VEGFR receptors and activates several key pathways involved in endothelial cell proliferation, survival, migration and permeability. This includes the Ras/MAPK, PI3K/Akt, eNOS and PKC pathways. VEGF signaling is tightly regulated during development and in response to hypoxia. Dysregulation of VEGF signaling can lead to various angiogenic diseases if there is either excess or deficiency of VEGF.
1) Tumors exist within a complex microenvironment consisting of various cell types that influence tumor growth, progression, and metastasis.
2) Chronic inflammation can promote tumor development by increasing genetic mutations while also stimulating angiogenesis and tumor cell proliferation.
3) The tumor microenvironment interacts bidirectionally with cancer cells to encourage processes like angiogenesis, immune suppression, invasion, and metastasis through factors such as TGF-β, VEGF, and cytokines.
4) Therapies targeting the tumor microenvironment can impact its composition and make cancer cells more invasive, highlighting the need for combination treatments.
Tumor angiogenesis refers to the formation of new blood vessels within tumors to supply nutrients and oxygen needed for growth. Cancer cells stimulate angiogenesis through release of pro-angiogenic factors like VEGF. This allows tumors to grow larger and metastasize by remodeling the extracellular matrix and sprouting new blood vessels from existing vasculature. The extent of angiogenesis correlates with worse cancer progression and outcomes, making it a promising therapeutic target for anti-angiogenic drugs aimed at inhibiting blood vessel formation within tumors.
This document discusses targeted cancer therapies, which work by interfering with specific molecular targets involved in cancer growth and progression, unlike traditional chemotherapy which acts on all rapidly dividing cells. It provides examples of molecular targets for small molecule drugs and monoclonal antibodies, including growth factor receptors and fusion proteins. The document also discusses methods of target identification, categories of targeted therapies, examples of FDA-approved targeted drugs, limitations and side effects of targeted therapies, and concludes by emphasizing the importance and promise of targeted therapies while noting challenges that remain.
Proto-oncogenes are normal cellular genes that encode proteins involved in cell proliferation. When mutated, they become oncogenes that encode constitutively active oncoproteins driving increased cell growth. Proto-oncogenes can encode growth factors, growth factor receptors, signal transducers, transcription factors, or cell cycle regulators. Common mutations include RAS mutations in pancreatic cancer, BRAF mutations in melanoma, PI3K mutations in breast cancer, and MYC translocations in Burkitt's lymphoma. These mutations result in constitutive activation of signaling pathways that drive uncontrolled cell proliferation.
The document summarizes the process of cancer metastasis through the invasion-metastasis cascade. It involves 6 key steps: 1) Localized invasion of primary tumor cells aided by loss of cell adhesion molecules and matrix metalloproteinases. 2) Intravasation of tumor cells into blood vessels assisted by tumor-associated macrophages. 3) Transport of circulating tumor cells protected by platelet emboli. 4) Extravasation of tumor cells from vessels into distant tissues. 5) Formation of dormant micrometastases. 6) Rare colonization of micrometastases into macroscopic tumors limited by the foreign tissue environment. Metastasis suppressor genes and strategies targeting multiple steps simultaneously show promise for preventing cancer spread.
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.
This document summarizes key concepts about neoplasms and cancer. It defines neoplasms as abnormal masses of tissue with uncontrolled growth. Oncology is the study of tumors. Tumors can be benign, meaning localized growth, or malignant (cancerous), meaning they can invade other tissues and metastasize. Cancers arise from genetic changes in cells that disrupt normal growth regulation. Key cancer genes include oncogenes that promote growth and tumor suppressor genes that inhibit growth. Evasion of apoptosis and unlimited replication are also critical to cancer development.
The document summarizes the hallmarks of cancer, which are the key capabilities that enable tumor growth and metastasis. The hallmarks include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, deregulating cellular energetics, and evading immune destruction. Genomic instability and mutation, and tumor-promoting inflammation also enable cancer's capabilities by altering DNA and creating an inflammatory microenvironment. Targeting these hallmark capabilities is important for cancer therapeutics.
Exosomes - Diagnostics and TherapeuticsSumedhaBobade
This document discusses exosomes, which are extracellular vesicles that originate inside cells and are released outside. It provides background on the discovery of exosomes and their structure. Exosomes are 40-150nm in size and have a phospholipid bilayer. They are secreted by various immune cells, epithelial cells, and are present in many body fluids. The document outlines their biogenesis pathway and composition. It discusses the many potential roles and applications of exosomes in diagnostics and therapeutics for diseases like cancer, neurological disorders, and infectious diseases. Exosomes show promise as novel biomarkers for diagnosis and as vehicles for drug delivery.
This document discusses cancer stem cells (CSCs), which are rare cells in tumors that have the ability to self-renew and differentiate into the diverse cells that comprise the tumor. CSCs were first hypothesized in the 1870s and experiments in the 1950s-60s provided early evidence for their existence. The concept of CSCs was revived in the 2000s, with the definition that they can recapitulate tumor growth. CSCs are identified experimentally by markers and assays. They are thought to originate from somatic or adult stem/progenitor cells and have properties of self-renewal, differentiation, immortality. CSCs may cause metastases, therapy resistance and recurrence. Targeting CSCs may improve cancer treatment and CSCs may serve
This document discusses various targeted cancer therapies including monoclonal antibodies, small molecule inhibitors, and other targeted agents. It describes key targets of these therapies such as protein kinases, growth factor receptors, angiogenesis pathways, and nuclear factors. Specific drugs are discussed that target ABL, EGFR, VEGFR, mTOR, MAPK pathways, and the proteasome. Resistance mechanisms and combination approaches are also mentioned.
Cancer Stem Cells (CSCs) have become a vital target for biologists and researchers.
The following presentation focuses on the treatment of cancer through targeting CSCs and its advantages.
Angiogenesis is the formation of new blood vessels from pre-existing vessels. There are two main types of angiogenesis: sprouting angiogenesis and intussusceptive angiogenesis. Sprouting angiogenesis involves the activation of endothelial cells by growth factors, degradation of the extracellular matrix, endothelial cell proliferation and migration, and formation of new loops and branches to form new vessels. Intussusceptive angiogenesis involves the extension of endothelial cell junctions into the vessel lumen to split existing vessels. Angiogenesis plays an important role in development, wound healing, and diseases like cancer by supplying tumors with nutrients and oxygen needed for growth.
1. Angiogenesis is the process of new blood vessel growth from pre-existing vessels. It occurs both in health and disease through a balance of pro-angiogenic and anti-angiogenic factors.
2. In health, angiogenesis is important for wound healing and reproduction. Diseases involving excessive angiogenesis include cancer, rheumatoid arthritis, and ocular diseases like diabetic retinopathy.
3. Diseases of insufficient angiogenesis include ischemic heart disease. Tumor angiogenesis provides nutrients and oxygen to support tumor growth and is a target for therapies like bevacizumab.
This document discusses the mechanisms of angiogenesis, or the formation of new blood vessels. It describes how the vascular endothelium growth factor (VEGF) signaling system is a key regulator of angiogenesis. VEGF stimulates endothelial cell growth and survival, and induces the formation of new blood vessels. The emergence of blood vessels during embryonic development and tumor growth both involve activation of the VEGF signaling pathway. The document outlines the different VEGF isoforms and receptors, and how they regulate angiogenesis. It also discusses how other signaling systems, like angiopoietins and PDGF, are involved in recruiting mural cells to stabilize and mature new blood vessels. Understanding the molecular mechanisms that control angiogenesis can help develop new drugs to inhibit unwanted angiogenesis or stimulate therapeutic angiogenesis
This document discusses angiogenesis, which is the growth of new blood vessels from pre-existing vessels. It occurs in both health and disease as a normal process to meet metabolic demands, but can also enable tumor growth and progression. The document outlines the history of angiogenesis research, mechanisms of healthy and pathological angiogenesis, roles in conditions like cancer and wound healing, therapeutic applications and limitations. Angiogenesis-targeting treatments like bevacizumab are FDA-approved but many clinical trials of other anti-angiogenic therapies have failed due to tumor complexity and resistance mechanisms. Combination therapies may be more effective approaches.
Angiogenesis, the formation of new blood vessels, plays a key role in tumor growth. Several growth factors and cytokines can promote angiogenesis, with vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) being especially important. VEGF expression is increased under hypoxic conditions via hypoxia-inducible factor-1 (HIF-1). PDGF stimulates cell proliferation and migration and is involved in wound healing and tissue remodeling. Both VEGF and PDGF signaling can be targeted by anti-angiogenic drugs, though clinical results have been mixed.
This document discusses tumor angiogenesis and stromagenesis. It describes 4 main mechanisms of tumor angiogenesis: 1) sprouting angiogenesis, 2) angioblast recruitment, 3) cooption of existing blood vessels, and 4) formation of mosaic vessels. It also outlines 10 steps in the process of tumor stromagenesis, including vascular hyperpermeability, fibrin deposition, new blood vessel formation, and eventual formation of dense connective tissue. Finally, it compares wound healing and tumor stroma formation, noting that VEGF and vascular permeability are transient in wound healing but persistent indefinitely in tumor stromagenesis.
The document discusses angiogenesis, the formation of new blood vessels. It describes the key processes of vasculogenesis, angiogenesis and arteriogenesis. It outlines the key regulators and mediators of angiogenesis including growth factors like VEGF, FGF, PDGF, inhibitors like thrombospondins. The role of angiogenesis in health and various diseases like cancer, retinopathy, arthritis is explained. Therapeutic strategies targeting angiogenesis are also mentioned.
This document discusses arteriogenesis and angiogenesis for treating peripheral arterial disease. It defines various types of neovascularization including vasculogenesis, arteriogenesis, and angiogenesis. Arteriogenesis involves growth and remodeling of preexisting collateral vessels, while angiogenesis is the formation of new capillaries from existing blood vessels in response to ischemia. Gene and protein therapies for promoting neovascularization have shown limited benefits, while cell-based therapies using endothelial progenitor cells and bone marrow mononuclear cells have demonstrated more promising results. The goals of therapy for critical limb ischemia are to relieve pain, heal ulcers, prevent amputation, and improve quality of life.
1. Venous pathophysiology involves a complex interplay between genetic, environmental, and acquired factors that can disrupt the normal balance between procoagulant and anticoagulant mechanisms in the veins.
2. The venous endothelium plays a critical role in homeostasis by maintaining an anticoagulant state, but this can be damaged by various disease processes, promoting thrombosis.
3. Abnormal venous biomechanics and valve incompetence, as seen in varicose veins and post-thrombotic syndrome, can lead to ambulatory venous hypertension from impaired flow and reflux of blood in the veins.
A systemic review on in vivo & in vitro models of angiogenesis & preliminary ...Abhijeet Mihir
This document provides a summary of 3 key points about angiogenesis:
1. Angiogenesis is the growth of new blood vessels from pre-existing vessels. It is a normal process in growth and wound healing but also plays a role in diseases where there is either too much or too little blood vessel growth.
2. There are multiple types of angiogenesis including sprouting, intussusception, and recruitment of endothelial progenitor cells. Sprouting is the main type where new vessels branch off existing ones.
3. Angiogenesis is controlled by a balance of pro-angiogenic and anti-angiogenic factors. Diseases occur when this balance is disrupted, leading to either excessive or insufficient new blood vessel formation
Vascular endothelial growth factor signaling pathwys in cancerKarim El-sayed
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.
The document summarizes anastomotic intimal hyperplasia (AIH), which is thickening of the intimal layer at vascular graft anastomoses. AIH occurs due to endothelial damage during anastomosis construction between a graft and blood vessel. This damage allows proliferation and migration of smooth muscle cells into the intima. Growth factors released by platelets and damaged cells promote this process. AIH develops mainly at the suture line and arterial floor opposite the graft hood. Techniques using venous material in a transverse orientation may help reduce AIH by creating a gradual transition between the graft and vessel properties.
Interaction of tumor cells and lymphatic vessels in cancerDragon Yott
1) Lymphatic vessels play an important role in cancer progression by allowing tumor cells to metastasize through the lymphatic system. Key mediators of lymphangiogenesis like VEGF-C and VEGFR-3 signaling are potential targets for inhibiting tumor lymphangiogenesis.
2) Lymphatic endothelial cells develop from blood vascular endothelium and differentiate under guidance of transcription factors like Prox-1 and VEGF-C/VEGFR-3 signaling.
3) Tumor lymphangiogenesis promotes progression of cancers like melanoma and breast cancer by allowing tumor cells access to lymphatic vessels for dissemination.
Slideshare biological actions of endothelium aj Anu Priya
The endothelium forms an interface between circulating blood and the vessel wall. It plays several important biological roles beyond just acting as a covering for blood vessels. Endothelial cells regulate vascular tone through the secretion of vasoactive substances like nitric oxide and endothelin. They also regulate coagulation, inflammation, cell growth, angiogenesis, and other processes. Dysfunction or damage of the endothelium is involved in the development of cardiovascular and other diseases.
This document discusses angiogenesis, invasion, and metastasis of tumors. It describes how angiogenesis allows tumors to grow beyond 1-2mm by developing new blood vessels. The metastatic cascade is explained as a two-step process involving invasion of the extracellular matrix and vascular dissemination. Key factors and genetic alterations that influence angiogenesis and the various steps of invasion and metastasis are also outlined.
The document summarizes the structure and functions of the vascular endothelium. It discusses how endothelial cells form a single layer lining the interior of blood vessels, acting as a permeability barrier and performing important roles in coagulation, immune response, angiogenesis, and regulation of vascular tone. Dysfunction of the endothelium is implicated in many vascular diseases such as atherosclerosis, hypertension, diabetes, and sepsis. The integrity of the endothelial layer is essential for organ health.
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
Tissue repair occurs through regeneration, replacing damaged cells with the same cell type, or fibrosis, replacing tissue with scar tissue. During fibrosis, blood vessels bleed and mast cells release histamine to promote vasodilation. A clot forms while macrophages remove damaged tissue. Fibroblasts migrate in and produce collagen, forming scar tissue through angiogenesis, fibroblast migration and proliferation, extracellular matrix deposition, and remodeling. Vascular endothelial growth factor is important for angiogenesis and permeability while transforming growth factor promotes fibroblast migration.
Thrombocytes and Thrombopoiesisand ThrombopoiesisAmany Elshamy
Megakaryocytes in bone marrow produce platelets through the process of megakaryopoiesis. Mature megakaryocytes extend proplatelets between endothelial cells and release platelets into circulation. Platelets have no nucleus and an average lifespan of 8-12 days. Their functions include maintaining vascular integrity by initiating repairs to damaged blood vessels and forming a primary hemostatic plug to stop bleeding through adhesion and aggregation. Platelets express membrane glycoproteins important for adhesion and aggregation and contain granules that release mediators promoting coagulation when activated.
This document provides an overview of hemostasis (blood clotting). It discusses:
- The mechanisms of primary hemostasis mediated by platelets, including platelet adhesion, activation, release of granule contents, and aggregation.
- The process of secondary hemostasis (blood coagulation) mediated by coagulation proteins generating thrombin which converts fibrinogen to fibrin.
- Methods of achieving hemostasis including mechanical methods, electrosurgery, pharmacological agents, and topical hemostatic products.
Congestive Heart failure is caused by low cardiac output and high sympathetic discharge. Diuretics reduce preload, ACE inhibitors lower afterload, beta blockers reduce sympathetic activity, and digitalis has inotropic effects. Newer medications target vasodilation and myosin activation to improve heart efficiency while lowering energy requirements. Combination therapy, following an assessment of cardiac function and volume status, is the most effective strategy to heart failure care.
STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7shruti jagirdar
Unit 4: MRA 103T Regulatory affairs
This guideline is directed principally toward new Molecular Entities that are
likely to have significant use in the elderly, either because the disease intended
to be treated is characteristically a disease of aging ( e.g., Alzheimer's disease) or
because the population to be treated is known to include substantial numbers of
geriatric patients (e.g., hypertension).
Can Traditional Chinese Medicine Treat Blocked Fallopian Tubes.pptxFFragrant
There are many traditional Chinese medicine therapies to treat blocked fallopian tubes. And herbal medicine Fuyan Pill is one of the more effective choices.
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
Storyboard on Acne-Innovative Learning-M. pharm. (2nd sem.) CosmeticsMuskanShingari
Acne is a common skin condition that occurs when hair follicles become clogged with oil and dead skin cells. It typically manifests as pimples, blackheads, or whiteheads, often on the face, chest, shoulders, or back. Acne can range from mild to severe and may cause emotional distress and scarring in some cases.
**Causes:**
1. **Excess Oil Production:** Hormonal changes during adolescence or certain times in adulthood can increase sebum (oil) production, leading to clogged pores.
2. **Clogged Pores:** When dead skin cells and oil block hair follicles, bacteria (usually Propionibacterium acnes) can thrive, causing inflammation and acne lesions.
3. **Hormonal Factors:** Fluctuations in hormone levels, such as during puberty, menstrual cycles, pregnancy, or certain medical conditions, can contribute to acne.
4. **Genetics:** A family history of acne can increase the likelihood of developing the condition.
**Types of Acne:**
- **Whiteheads:** Closed plugged pores.
- **Blackheads:** Open plugged pores with a dark surface.
- **Papules:** Small red, tender bumps.
- **Pustules:** Pimples with pus at their tips.
- **Nodules:** Large, solid, painful lumps beneath the surface.
- **Cysts:** Painful, pus-filled lumps beneath the surface that can cause scarring.
**Treatment:**
Treatment depends on the severity and type of acne but may include:
- **Topical Treatments:** Such as benzoyl peroxide, salicylic acid, or retinoids to reduce bacteria and unclog pores.
- **Oral Medications:** Antibiotics or oral contraceptives for hormonal acne.
- **Procedures:** Such as chemical peels, extraction of comedones, or light therapy for more severe cases.
**Prevention and Management:**
- **Cleanse:** Regularly wash skin with a gentle cleanser.
- **Moisturize:** Use non-comedogenic moisturizers to keep skin hydrated without clogging pores.
- **Avoid Irritants:** Such as harsh cosmetics or excessive scrubbing.
- **Sun Protection:** Use sunscreen to prevent exacerbation of acne scars and inflammation.
Acne treatment can take time, and consistency in skincare routines and treatments is crucial. Consulting a dermatologist can help tailor a treatment plan that suits individual needs and reduces the risk of scarring or long-term skin damage.
BBB and BCF
control the entry of compounds into the brain and
regulate brain homeostasis.
restricts access to brain cells of blood–borne compounds and
facilitates nutrients essential for normal metabolism to reach brain cells
“Environmental sanitation means the art and science of applying sanitary, biological and physical science principles and knowledge to improve and control the environment therein for the protection of the health and welfare of the public”.The overall importance of sanitation are to provide a healthy living environment for everyone, to protect the natural resources (such as surface water, groundwater, soil ), and to provide safety, security and dignity for people when they defecate or urinate .Sanitation refers to public health conditions such as drinking clean water, sewage treatment, etc. All the effective tools and actions that help in keeping the environment clean come under sanitation. Sanitation refers to public health conditions such as drinking clean water, sewage treatment. All the effective tools and actions that help in keeping the environment clean and promotes public health is the necessary in todays life.
CLASSIFICATION OF H1 ANTIHISTAMINICS-
FIRST GENERATION ANTIHISTAMINICS-
1)HIGHLY SEDATIVE-DIPHENHYDRAMINE,DIMENHYDRINATE,PROMETHAZINE,HYDROXYZINE 2)MODERATELY SEDATIVE- PHENARIMINE,CYPROHEPTADINE, MECLIZINE,CINNARIZINE
3)MILD SEDATIVE-CHLORPHENIRAMINE,DEXCHLORPHENIRAMINE
TRIPROLIDINE,CLEMASTINE
SECOND GENERATION ANTIHISTAMINICS-FEXOFENADINE,
LORATADINE,DESLORATADINE,CETIRIZINE,LEVOCETIRIZINE,
AZELASTINE,MIZOLASTINE,EBASTINE,RUPATADINE. Mechanism of action of 2nd generation antihistaminics-
These drugs competitively antagonize actions of
histamine at the H1 receptors.
Pharmacological actions-
Antagonism of histamine-The H1 antagonists effectively block histamine induced bronchoconstriction, contraction of intestinal and other smooth muscle and triple response especially wheal, flare and itch. Constriction of larger blood vessel by histamine is also antagonized.
2) Antiallergic actions-Many manifestations of immediate hypersensitivity (type I reactions)are suppressed. Urticaria, itching and angioedema are well controlled.3) CNS action-The older antihistamines produce variable degree of CNS depression.But in case of 2nd gen antihistaminics there is less CNS depressant property as these cross BBB to significantly lesser extent.
4) Anticholinergic action- many H1 blockers
in addition antagonize muscarinic actions of ACh. BUT IN 2ND gen histaminics there is Higher H1 selectivitiy : no anticholinergic side effects
The biomechanics of running involves the study of the mechanical principles underlying running movements. It includes the analysis of the running gait cycle, which consists of the stance phase (foot contact to push-off) and the swing phase (foot lift-off to next contact). Key aspects include kinematics (joint angles and movements, stride length and frequency) and kinetics (forces involved in running, including ground reaction and muscle forces). Understanding these factors helps in improving running performance, optimizing technique, and preventing injuries.
This presentation gives information on the pharmacology of Prostaglandins, Thromboxanes and Leukotrienes i.e. Eicosanoids. Eicosanoids are signaling molecules derived from polyunsaturated fatty acids like arachidonic acid. They are involved in complex control over inflammation, immunity, and the central nervous system. Eicosanoids are synthesized through the enzymatic oxidation of fatty acids by cyclooxygenase and lipoxygenase enzymes. They have short half-lives and act locally through autocrine and paracrine signaling.
Storyboard on Skin- Innovative Learning (M-pharm) 2nd sem. (Cosmetics)MuskanShingari
Skin is the largest organ of the human body, serving crucial functions that include protection, sensation, regulation, and synthesis. Structurally, it consists of three main layers: the epidermis, dermis, and hypodermis (subcutaneous layer).
1. **Epidermis**: The outermost layer primarily composed of epithelial cells called keratinocytes. It provides a protective barrier against environmental factors, pathogens, and UV radiation.
2. **Dermis**: Located beneath the epidermis, the dermis contains connective tissue, blood vessels, hair follicles, and sweat glands. It plays a vital role in supporting and nourishing the epidermis, regulating body temperature, and housing sensory receptors for touch, pressure, temperature, and pain.
3. **Hypodermis**: Also known as the subcutaneous layer, it consists of fat and connective tissue that anchors the skin to underlying structures like muscles and bones. It provides insulation, cushioning, and energy storage.
Skin performs essential functions such as regulating body temperature through sweat production and blood flow control, synthesizing vitamin D when exposed to sunlight, and serving as a sensory interface with the external environment.
Maintaining skin health is crucial for overall well-being, involving proper hygiene, hydration, protection from sun exposure, and avoiding harmful substances. Skin conditions and diseases range from minor irritations to chronic disorders, emphasizing the importance of regular care and medical attention when needed.
Allopurinol, a uric acid synthesis inhibitor acts by inhibiting Xanthine oxidase competitively as well as non- competitively, Whereas Oxypurinol is a non-competitive inhibitor of xanthine oxidase.
PGx Analysis in VarSeq: A User’s PerspectiveGolden Helix
Since our release of the PGx capabilities in VarSeq, we’ve had a few months to gather some insights from various use cases. Some users approach PGx workflows by means of array genotyping or what seems to be a growing trend of adding the star allele calling to the existing NGS pipeline for whole genome data. Luckily, both approaches are supported with the VarSeq software platform. The genotyping method being used will also dictate what the scope of the tertiary analysis will be. For example, are your PGx reports a standalone pipeline or would your lab’s goal be to handle a dual-purpose workflow and report on PGx + Diagnostic findings.
The purpose of this webcast is to:
Discuss and demonstrate the approaches with array and NGS genotyping methods for star allele calling to prep for downstream analysis.
Following genotyping, explore alternative tertiary workflow concepts in VarSeq to handle PGx reporting.
Moreover, we will include insights users will need to consider when validating their PGx workflow for all possible star alleles and options you have for automating your PGx analysis for large number of samples. Please join us for a session dedicated to the application of star allele genotyping and subsequent PGx workflows in our VarSeq software.
TEST BANK For Brunner and Suddarth's Textbook of Medical-Surgical Nursing, 14...Donc Test
TEST BANK For Brunner and Suddarth's Textbook of Medical-Surgical Nursing, 14th Edition (Hinkle, 2017) Verified Chapter's 1 - 73 Complete.pdf
TEST BANK For Brunner and Suddarth's Textbook of Medical-Surgical Nursing, 14th Edition (Hinkle, 2017) Verified Chapter's 1 - 73 Complete.pdf
TEST BANK For Brunner and Suddarth's Textbook of Medical-Surgical Nursing, 14th Edition (Hinkle, 2017) Verified Chapter's 1 - 73 Complete.pdf
6. ➤ Vasculogenesis: Formation of new vessels from EC
precursors
➤ Angiogenesis: Formation of new vessels from pre existing
Blood vessels by sprouting
➤ Arteriogenesis : Subsequent Stabilisation and maturation
➤ Collateralisation: Enlarging existing vessels as bridges
between networks
16. ➤ 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.
➤ Capillaries are needed in all tissues for diffusion and exchange of
nutrients and metabolites.
➤ Changes in metabolic activity lead to proportional changes in
angiogenesis and, hence, proportional changes in capillarity.
➤ Oxygen plays a pivotal role in this regulation.
19. SPROUTING ANGIOGENESIS
➤ Sprouting angiogenesis is characterized by sprouts composed
of endothelial cells
➤ They grow towards an angiogenic stimulus such as VEGF-A.
➤ It can add blood vessels to portions of tissues previously
devoid of blood vessels.
➤ It is initiated in poorly perfused tissues
24. INTUSSUSCEPTIVE ANGIOGENESIS
➤ Intussusceptive angiogenesis is also called splitting
angiogenesis
➤ The vessel wall extends into the lumen causing a single
vessel to split in two
➤ . This type of angiogenesis is thought to be fast and efficient
compared with sprouting angiogenesis:
1. Reorganization of existing endothelial cells
2. No immediate endothelial proliferation
3. Migration
25.
26. ➤ Occurs throughout life
➤ But plays a prominent role in vascular development in
embryos where growth is fast and resources are limited
➤ However, intussusception mainly causes new capillaries to
develop where capillaries already exist.
➤ Both types of angiogenesis are thought to occur in virtually all
tissues and organs
30. VEGF
VEGF-A VEGF -B VEGF C&D
After injury
Tumors
Embryonic vessel
development
Lymphangiogene
sis
31. ➤ VEGF is a survival factor for endothelial cells in vivo and in vitro
➤ It prevents apoptosis of endothelial cells caused by the lack of serum .
➤ It is also known to induce expression of antiapoptotic proteins Bcl- 2 in
endothelial cells
➤ It is also known as a factor regulating vascular permeability.
32. ➤ The ability of VEGF to enhance vascular permeability defines its important
role in inflammation and other pathological processes.
➤ The tumor vessels are characterized by enhanced permeability
➤ Also the ability of VEGF isoforms to bind to heparin,
defines whether the secreted protein will be accumulated in extracellular matrix
➤ or will be released and thus become accessible for interaction with other
cells.
33. VEGF RECEPTORS
➤ Growth factors of the VEGF family exert their biological effect via
interaction with receptors located on endothelial cell membranes.
➤ Three receptors have been identified that bind different VEGF
growth factors: VEGFR1 , VEGFR2 and VEGFR3
➤ These receptors belong to the superfamily of receptor tyrosine
kinases (RTK)
➤ They are transmembrane proteins with a single domain
44. INTEGRINS
➤ Angiogenic endothelium over expresses INTEGRIN family of
ECM binding proteins that mediate EC adhesion, migration,
survival
➤ αv
β3
, αv
β5
, α5
β1
➤ Mediates spreading and migration of EC’S
➤ αvβ3 forms cell surface complexes with matrix metalloproteinases that cleave ECM proteins
45. MATRIX METALLOPROTEINASE
➤ Major contributor to angiogenesis
➤ Zinc requiring proteases that cleave the extracellular matrix
proteins
➤ This proteolysis allows the endothelial cells to escape into the
interstitial matrix (as seen in sprouting angiogenesis)
47. ➤ The healthy body controls angiogenesis through a
series of on and off switches:
➤ On switches– angiogenesis stimulating growth factors
➤ Off switches- angiogenesis inhibiting growth factors
➤ The normal healthy body maintains a perfect balance
of angiogenesis modulators.
52. In females, angiogenesis also occurs
➤ During the monthly reproductive cycle -to rebuilt the
uterus lining
➤ To mature the egg during ovulation
➤ During pregnancy (to built the placenta)
55. ➤ 1945 Algire and Chalkley concluded that the growth of a solid
tumor is closely connected to the development of an intrinsic
vascular network.
➤ 1970s, the surgeon Folkman: hypothesized that targeting the
blood supply by inhibiting blood vessel formation will lead to
arrest of tumor growth or even tumor shrinkage.
➤ In 2004, the first antiangiogenic compound bevacizumab
(Avastin) was approved
56.
57. WHY TUMORS REQUIRE
ANGIOGENESIS➤ Tumors less than 1mm3 receive oxygen and nutrients by
diffusion from host vasculature
➤ Larger tumors require new vessel network.
➤ Tumor secretes angiogenic factors that stimulate migration,
proliferation, and neovessels formation by endothelial cells in
adjacent established vessels.
58. CHARACTERISTICS OF TUMOUR
VESSELS
Chaotic architecture and heterogeneous blood flow that leads to
abnormal growth
1. Excessively dilated blood vessels
2. Extreme corkscrew like tortuosities
3. Lack of pericyte support or abnormal pericytic function
4. Permeability strongly increased fenestrae
74. ORGAN DYFUNCTION MECHANISM
SKIN HAIR LOSS
Retarded hair growth by
angiogenesis inhibitors
REPRODUCTIVE
SYSTEM
PRE ECLAMPISA
Decreased VEGF
production
LUNG
NEONATAL
RESPIRATORY
DISTRESS
Insufficient lung
maturation due to
decreased HIF ,VEGF
NERVOUS SYSTEM
ALZHEIMERS
DISEASE
Vasoconstriction,
Microvascular
degeneration,
DISEASES DUE TO DECREASES
ANGIOGENESIS
76. ➤ Several studies show a correlation between production of
angiogenic factors and relapse, metastasis and poor
prognosis in human cancer patients.
➤ Renal cancer patients with high levels of the angiogenic factor
bFGF in their primary tumors have a poorer survival rate than
those patients with lower bFGF levels
➤ In breast cancer, VEGF production correlates with early
relapse .
77. ➤ Because the plasticity of the tumor cell population allows the
development of cells that produce other angiogenic factors and
thus the tumor may become resistant to treatment.
➤ But if the treatments directly target the endothelial compartment by
inhibiting components of the angiogenic process such as
1. Endothelial cell adhesion or
2. Migration
➤ This may generate tumor treatments that do not lead to the
78. THROMBOSPONDIN
➤ Thrombospondin is confirmed to be an inhibitor of:
1.Endothelial cell proliferation
2.Motility
3.Morphogenesis
➤ The initial correlation of thrombospondin production with tumor
suppression was reported that the tumor suppressor P53 could
repress angiogenesis by up-regulating the production of
thrombospondin
79. INTERFERON
➤ Interferon inhibits the migration of capillary endothelial cells, a
critical step in angiogenesis
➤ Interferon action may also block the production or efficacy of
angiogenic factors produced by tumor cells .
➤ Some vascular tumors are more sensitive to the inhibitory activity
of interferon.
80. METALLOPROTEINASES
➤ These are matrix metalloproteinases (MMPs) because of their ability to
degrade extracellular matrix
➤ These enzymes inhibit both angiogenesis and tumor metastasis .
➤ The mechanism whereby TIMPs inhibit angiogenesis and metastasis
1. Their ability to suppress matrix degradation
2. They also directly block proliferation and migration of both tumor cells and
endothelial cells
➤ The combined activities of this class of inhibitor make them potent anti-tumor
agents.
81. ANGIOSTATIN
➤ Angiostatin was the first molecule specifically isolated as a potential
tumor-derived angiogenesis inhibitor .
➤ Angiostatin itself is not produced by tumor cells but rather that certain
tumors can produce or activate proteases capable of generating
angiostatin from circulating plasminogen.
➤ Angiostatin has been reported to be an endothelial-specific inhibitor of
both endothelial cell proliferation and migration
➤ It can act as a circulating angiogenesis inhibitor that suppresses angio-
genesis at downstream sites distant from the tumor.
82. ENDOSTATIN
➤ Endostatin is reported to be a highly active endothelial-specific
inhibitor that inhibits microvascular endothelial cell proliferation
➤ Endostatin inhibits primary tumor growth as well as establishment
and growth of metastases.
83. CAI
➤ Carboxyamidotriazole (CAI) is a calcium channel inhibitor that blocks
tumor cell migration and proliferation and has antiangiogenic activity.
➤ CAI retards metastasis in experiment animals and has completed
phase I clinical trials in cancer patients.
➤ Published results from trials showed disease stabilization in 49% of
the patients who had disease progression before starting CAI
treatment
84. THALIDOMIDE
➤ In a recent finding, D’Amato and colleagues reported that the drug
thalidomide has potent antiangiogenic activity
➤ The antiangiogenic activity of thalidomide now provides a potential
mecha- nism for this teratogenic activity, as growing limbs are sensitive
to the vascular density
➤ Thalidomide is relatively nontoxic when taken by nonpregnant adults
It is now being tested in clinical trials as a
1. Potential anticancer agent
2. Treatment for vascular eye diseases
85. AGM1470
➤ It was observed that the fungal antibiotic fumagillin was a potent
angiogenesis inhibitor.
➤ This agent inhibits endothelial cell proliferation in vitro and
angiogenesis in vivo .
➤ The drug is being used both as a primary antitumor treatment and
also as a sequel to other treatments.
86. Can Total Tumor Regression be
Achieved by Administration of Angiogenic
Inhibitors?
87. ➤ Antiangiogenic treatment can reduce a tumor mass back to its
avascular size.
➤ It may not completely eliminate tumors that regress to sizes no
longer dependent on increased vascularity.
➤ The antiangiogenic agents may also be useful for prolonged
treatment to prevent regrowth of dormant micrometastases.
➤ There are, however, sporadic reports of tumors that have
been completely eliminated by antiangiogenic therapy alone.
92. 1. Robbins and Cotran- Pathological basis of diseases: 9th edition
2. Walter and Israel- General Pathology: 7th edition
3. Anderson’s Pathology: 10th Edition
4. Karamysheva AF. Mechanisms of angiogenesis. Biochemistry
(Moscow). 2008 Jul 1;73(7):751.
5. Eichhorn ME, Kleespies A, Angele MK, Jauch KW, Bruns CJ.
Angiogenesis in cancer: molecular mechanisms, clinical impact.
Langenbeck's archives of surgery. 2007 May 1;392(3):371-9.
6. Zetter BR. Angiogenesis and tumor metastasis. Annual review of
medicine. 1998 Feb;49(1):407-24.
7. Blood CH, Zetter BR. Tumor interactions with the vasculature:
angiogenesis and tumor metastasis. Biochimica et Biophysica Acta
(BBA)-Reviews on Cancer. 1990 Jun 1;1032(1):89-118.
8. Hart IR, Saini A. Biology of tumour metastasis. The lancet. 1992 Jun
13;339(8807):1453-7.
93. THANK YOU
Modulation of angiogenesis may
have an impact on diseases in the
21st century .
Similar to that which the discovery
of antibiotics had in the 20th century
Editor's Notes
The Scottish anatomist and surgeon John Hunter provided the first recorded scientific insights into the field of angiogenesis.
His observations suggested that proportionality between vascularity and metabolic requirements occurs in both health and disease.
This is the inside view of john hunter museum which is under the royal college of surgeons
weibel salade body is a unique cytoplasmic structure that contains VWF and a protein GP 140 which is exposed on the cell surface shortly after injury
Vasculogenesis is the de novo formation of blood vessels from angioblasts .
The cardiovascular system is the first organ system to develop in the embryo . The luminal surface of the circulatory system in contact with blood is a single layer of endothelial cells: these are derived from mesoderm. Hemangioblasts differentiate from mesodermal stem cells and give rise to hematopoietic stem cells and angioblasts. Angioblasts are a cell type with potency to differentiate into endothelial cells.
No metabolically active tissue in the body is more than a few hundred micrometers from a blood capillary, which is formed by the process of angiogenesis.
when oxygen sensing mechanisms detect a level of hypoxia that demands the formation of new blood vessels to satisfy the metabolic requirements of parenchymal cells
this shows sprouting of new blood vessels from the aorta. within the tube a single endothelial cell gets activated by the angiogenic stimulus. this forms the tip cell which develops into a capillary sprout. then there is formation of pinocytic vesicles which fuse and form a tube inside the capillary sprout. this leads to the formation of lumen.
The basic steps of sprouting angiogenesis include enzymatic degradation of capillary basement membrane, endothelial cell (EC) proliferation, directed migration of ECs, tubulogenesis (EC tube formation), vessel fusion, vessel pruning, and pericyte stabilization.
and this peculiarity contributes to tumor cell penetration into vascular networks and metastasis.
Under Normoxjmic conditions HiF levels are maintained low by proteasome mediated destruction
The ANGIOPOIETINS have recently joined the members of the VEGF family as the only known growth factors largely specific for vascular endothelium.
They include a naturally occurring agonist : ANGIOPOIETIN-1
A naturally occurring antagonist: ANGIOPOIETIN-2,
They act by means of the Tie2 receptor.
there are 3 phases of wound repair.
inflammatory phase is characterised by haemorrhage and plasma exudation in wound site. a fibrin clot forms as a result of coagulation cascade.then inflammatory cells enter the site and phagocytosize the bacteria.
The second phase is proliferative phase which is characterised by accumulation of proliferating fibroblasts, myofibroblasts and endothelial cells. these cells secrete many growth factors and promote development of immature vascular tissue which is known to have granular appearance called granulation tissue. new vessels sprout from existing blood vessels. these capillaries have poorly formed inter cellular attachments and are thus leaky leading to oedema and they bleed easily
Maturation phase is characterised by some level of restitution or restoration of prior tissue with replacement of that tissue by fibrous connective tissue or scar
by the Food and Drug Administration as first-line therapy in combination with 5-fluorouracil-based chemotherapy in patients with advanced colorectal cancer.
Newly vascularized tumor no longer relies solely on diffusion from host vasculature, facilitating progressive growth.
No functional lymphatics inside the tumour enlarged in surrounding,Increases metastasis
Once a neoplastic mutation has occurred, an avascular phase of tumor growth follows. Tumor cells are supplied by diffusion, and tumor growth is arrested at a size of 1– 2 mm3. The following stadium of ‘tumor dormancy’ can last up to years Today, the theory of an angiogenic switch, controlled by the balance between pro- and antiangiogenic molecules in the solid tumor microenvironment, is accepted
The switch clearly involves proangiogenic factors over- come the effect of angiostatic molecules, the tumor acquires an angiogenic phenotype that leads to the formation of new blood vessels.
Increased angiogenesis has been associated with various inflammatory disease states including rheumatoid arthritis (RA). Angiogenic mediators released by various types of cells within the synovium activate EC. ECs then proliferate and emigrate into the interstitial tissue. Hence externally administered organic or synthetic compounds may disrupt neovascularization. These agents are used to suppress angiogenesis in inflammatory
Two major retinal problems cause most of the diabetes related vision loss: diabetic macular edema and diabetic retinopathy.Diabetic retinopathy, a secondary microvascular complication of diabetes mellitus is the leading cause of blindness Secondary to angiogenesis, increased retinal blood flow is of pathogenic importance in the progression of diabetic retinopathy.Hypoxia is a key regulator of VEGF induced ocular neovascularization. Hence utilizing anti-VEGF treatments has proved to be a successful protocol in the treatment of proliferative diabetic retinopathy.
Retinopathy of prematurity (ROP), also called retrolental fibroplasia is a disease of the eye affecting prematurely born babies generally having received intensive neonatal care, in which oxygen therapy is used on them due to the premature development of their lungs. It is thought to be caused by disorganized growth of retinal blood vessels which may result in scarring and retinal detachment. ROP can be mild and may resolve spontaneously, but it may lead to blindness in serious cases.
Age-related macular degeneration (AMD) is one of
the most common irreversible causes of severe loss of
vision, including legal blindness, in the elderly population. it is of 2 types The exudative form is linked to choroidal neovascularization directed to the subretinal macular region, with subsequent bleeding and/or fluid leakage, which may result in a sudden loss of central vision; it is the most rapidly progressing form of AMD.
the role of angiogenesis in atherosclerosis is still controversial .bur Intimal angiogenesis has
been hitherto assumed to participate intimately in the promotion of atheroma growth
and intraplaque edema and hemorrhage, possibly resulting in plaque rupture. Attention
has recently refocused on intimal angiogenesis in atherosclerotic plaque.
Capillary hemangioma is the most common benign vascular tumor of infancy,It can affect almost any organ but by far the commonest location is the skin and soft tissues, especially in the head and neck area.
types: capillary hemangimos ,cavernous hemangioma,
epithelioid hemangioma ,deep hemangioma.
Cavernous hemangiomas consist of poorly circumscribed, irregularly dilated blood vessels lined by flat endothelium and with walls of varying thickness. Thrombosis, secondary dystrophic calcification, and mild inflammation are frequently found.
Although the cell of origin remains controversial, most evidence points towards endothelial cells, particularly lymphatic endothelium, as the principal cellular component
associated with hhv8
types classical endemic, AIDS related,immunosuprresive associated ,african ks
Cutaneous angiosarcoma always occurs in one of three different clinical settings: namely, idiopathic angiosarcoma of the head and neck, lymphedema- associated angiosarcoma, and post-irradiation angio- sarcoma
The typical case is an infiltrative dermal tumor, composed of numerous, irregular, anastomosing vascular spaces in a distinctive dissecting pattern between collagen bundles. The vascular channels are lined by variably pleomorphic, hyper- chromatic endothelial cells which frequently show multilayering and papillary formation
The expansion of the primary tumor and metastasis to distant organs depend critically on the formation of new blood vessels
Large solid tumors contain cells that release one or more angiogenic factors such as basic fibroblast growth factor and vascular endothelial growth factor.
Hence the best strategy for inhibiting angiogenesis is to repress the ability of the endothelial cell to participate in the angiogenic process rather than prevent tumor cells from producing one particular angiogenic factor,
Angiogenesis has been implicated in affecting outcomes in human cancer.
suggesting that increased angiogenesis due to bFGF production may lead to increased metastatic potential and con- sequently decreased survival
in addition, it appears that tumors that produce multiple angiogenic factors show increased rates of primary tumor expansion.
Angiogenesis inhibition can lead to tumor regression and, in some cases, to complete elimination of the tumor.
Hemangiomas, are tumors comprised predominantly of endothelial cells, are particularly sensitive to treatment with interferon. Treatment with interferon is one of the first clinically successful treat- ment protocols for patients with proliferating hemangiomas
Invasive events require both active cell migration and the ability to cause lim- ited degradation of the connective tissue in order to allow passage of the tumor cells through tissue. This is accomplished, in part, by the activity of metallo- proteinases that are sequestered on the tumor cell surface and concentrated at the leading edge of the tumor
all members of the TIMP family inhibit angiogenesis.
A serine protease that specifically cleaves angiostatin from plasminogen is pro duced by prostate cancer cells
Angiostatin treatment of tumor-bearing mice causes regression of the primary tumor and prevents vascularization and growth of metastatic colonies.
The finding that both angiostatin and endostatin are fragments of larger precursor forms that have no angiogenic effector activity themselves suggests that the natural control of angiogenesis is much like that of repair processes such as blood clotting in which latent precursors become activated by proteolysis only when needed.
endostatin is a fragment of a larger molecule, in this case collagen XVIII, a novel collagen frequently found near blood vessels
Originally used as a seda- tive, thalidomide’s use was discontinued when it was found to be a potent tera- togen, causing serious birth defects, especially affecting limb development.
diabetic retinopathy, blindness of pre- maturity, and macular degeneration.
gave rise to the testing of synthetic analogs of fumagillin for their relative antiangiogenic activty
Preliminary results suggest that long-term (>1 year) treatments are optimal and that the drug should not be stopped early if the tumor appears to progress, because the effects of the agent take some time to be translated into tumor stasis or regression.
It is therefore possible that strategies will emerge that use antiangiogenic therapies as the primary antitumor therapy, without the addition of cytotoxic agents.
Future clinical trials are necessary to see whether this is a viable strategy in human cancer patients.