癌症生物学课件3(国外)
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癌生物学(biology+of+cancer)
The cells are picking up additional mutations as they divide, accounting for the phenotypic differences
2b:Molecular Biology of Cancer 癌分子生物學
Oncogenes Tumor suppressor genes
2-naphthylamine causes bladder cancer, but only does so after several years. The point is that exposure to a carcinogen and the development of cancer can be years apart, pointing out how difficult it is to attach causation to cancers.
Note that cancer results ONLY if the cell is exposed to a tumor promoter repeatedly AFTER an initiator. Note also that multiple initiators may result in cancer (bottom timeline)
Neoplastic proteins/Oncogenes (致癌基因)
Growth factors and related hormones serving as ligands for their receptors (EGF, TGF-β, PDGF, etc.) Growth factor receptors (TK receptors, Glinked receptors, Smad receptors, etc.) Intracellular transducers (G- proteins, SH2SH3 proteins, etc.) Intracellular receptors/transcription factors that realize the ultimate result of the signal Cell-cycle control proteins
癌症英文版ppt课件
An adult human body has about 30 trillion cells — 30,000,000,000,00 0!
WHY CANCER IS DANGEROUS?
HOW DOCTORS TREAT CANCER?
The best weapon
to detect it early before spread
癌症英文版
Cancer — a scary word, a scary disease, a callous killer
马三立 （膀胱癌）
陈晓旭 （ breast cancer ）
李钰 （淋巴癌）
Patrick Swayze （胰腺癌）
luciano Pavarotti （胰腺癌）
good news：
•Millions of people with cancer still alive •Technology for cancer treating
Kylie Ann Minogue (breast cancer)
WHAT ISa single disease •includes more than 100 different diseases
WAYS TO PREVENT CANCER?
Don’t smoke! Keep healthy diet. Avoid too much sun.
Getting plenty of sleep and exercise and eating the right foods can help keep you healthy.
•Removed by surgery •Radiation, such as X rays
癌症科普知识课件PPT30页(最全)
04
预防癌症小知识
01.
癌症和肿瘤
癌症和肿瘤
ONE
TWO
THREE
FOUR
癌症是隐藏在我们周围的一个 “超级杀手”！
癌症和肿瘤
ONE
TWO
THREE
FOUR
什么是癌细胞？
机体内有的细胞受到致癌因子的作用，细胞 中遗传物质发生变化，就变成不受机体控制 的、连续进行分裂的恶性增殖细胞。
癌细胞的特征
+1
Science of cancer
ONE
TWO
THREE
FOUR
关于 癌症的科普
Popularscience on cancer
医学癌症
cancer
Science
+1
Science of cancer
ONE
TWO
THREE
FOUR
Contents
癌症和肿瘤 01
03
癌症治疗方法
癌症的原因、发展和分类 02
01
从癌症病人身上 分离免疫T细胞。
02
利用基因工程技术给T 细胞加入一个能识别 肿瘤细胞，并且同时 激活T细胞杀死肿瘤细 胞的嵌合抗体，T细胞 立马华丽变身为高大 上的CAR-T细胞。
03
体外培养，大量扩 增CAR-T细胞，一 般一个病人需要几 十亿，乃至上百亿 个CAR-T细胞（体 型越大，需要细胞 越多）。
经常接触放射线者，易诱发肺癌与白血病； 经常接触沥青者，易诱发皮肤癌； 经常接触煤焦油者，易患皮肤癌； 长期使用化学性染发剂可诱发淋巴癌； 经常在太阳下曝晒，可诱发皮肤癌。
预防癌症小知识
ONE
TWO
THREE
FOUR
癌症生物学(英文版)
2
The Hallmarks of Cancer
• 1. Sustaining proliferative signaling • 2. Evading growth suppressors • 3. Resisting cell death • 4. Enabling replicative immortality • 5. Inducing angiogenesis • 6. Activating invasion and metastasis • 7. Deregulating cellular energetics • 8. Avoiding immune destruction
factor • 5. Constitutive activation of signaling proteins downstream from the
receptor
2. Evading growth suppressors
• Cancer cells must overcome programs that negatively regulate cell proliferation
• Hallmarks of Cancer are eight, acquired, functional capabilities that allow cancer cells to survive, proliferate and disseminate
• First proposed by Hanahan and Weinberg in 2000 • Updated and expanded by Hanahan and Weinberg (Cell, 2011)
3
1. Sustaining proliferative signaling
The Hallmarks of Cancer
• 1. Sustaining proliferative signaling • 2. Evading growth suppressors • 3. Resisting cell death • 4. Enabling replicative immortality • 5. Inducing angiogenesis • 6. Activating invasion and metastasis • 7. Deregulating cellular energetics • 8. Avoiding immune destruction
factor • 5. Constitutive activation of signaling proteins downstream from the
receptor
2. Evading growth suppressors
• Cancer cells must overcome programs that negatively regulate cell proliferation
• Hallmarks of Cancer are eight, acquired, functional capabilities that allow cancer cells to survive, proliferate and disseminate
• First proposed by Hanahan and Weinberg in 2000 • Updated and expanded by Hanahan and Weinberg (Cell, 2011)
3
1. Sustaining proliferative signaling
英文版癌症介绍课件
Overview of Cancer
ቤተ መጻሕፍቲ ባይዱ
Basic definition
Cancer is a group of diseases characterized by the uncontrolled growth of cells in the body These cells form a mass called a tutor, which can invade and destroy normal issues
English version of cancer introduction courseware
目录
CONTENTS
Overview of CancerSymptoms and Diagnosis of CancerTreatment methods for cancerPrevention and control of cancerRehabilitation and numbering of cancerResearch progress and future prospects of cancer
要点一
要点二
Rehabilitation programs
Design rehabilitation programs to help patients register physical functions, including physical therapy, occupational therapy, and speech therapy
Rehabilitation and numbering of cancer
Psychological support
Provide emotional support and counseling to help patients scope with the emotional impact of cancer diagnosis and treatment
ቤተ መጻሕፍቲ ባይዱ
Basic definition
Cancer is a group of diseases characterized by the uncontrolled growth of cells in the body These cells form a mass called a tutor, which can invade and destroy normal issues
English version of cancer introduction courseware
目录
CONTENTS
Overview of CancerSymptoms and Diagnosis of CancerTreatment methods for cancerPrevention and control of cancerRehabilitation and numbering of cancerResearch progress and future prospects of cancer
要点一
要点二
Rehabilitation programs
Design rehabilitation programs to help patients register physical functions, including physical therapy, occupational therapy, and speech therapy
Rehabilitation and numbering of cancer
Psychological support
Provide emotional support and counseling to help patients scope with the emotional impact of cancer diagnosis and treatment
癌症遗传学课件
年代的统计数 字显示，该地
5死7C亡个年癌h龄i症n都患a在者，，24/10000
域的食管癌、 胃癌发病率为
50岁到60岁之
全国平均发病
间。
率的20多倍。
Both of genetic factor and environment factor
contribute to tumorigenesis.
•非整倍体（aneuploid）：X/23≠整数； •超二倍体(hyperdiploid)：比46多一条或几条染色体； •亚二倍体(hypodiploid)：比46少一条或几条染色体； •亚三倍体(hypotriploid)：比69少一条或几条染色体； •亚四倍体(hypotetraploid) ：比92少一条或几条染色体； •多倍体（polyploid）：染色体数目在三倍体以上者。 肿瘤由单克隆起源，但在生长过程中演变为多克隆，出现异 质性（heterogeneity)。其中占主导数目的克隆称为肿瘤的干 系（stem line）;占非主导数目的克隆称为旁系（side line）; 干系肿瘤细胞的染色体数目称为众数（modal number）。
Green-breast cancer; Yellow- glioblastoma; Purple- lukemia; Blue- lung cancer; Orange-pancreatic carcinoma; Red- sarcoma; Brown-Wilms tumor
Cancer and Genetics diseases
(造血和淋巴系统恶性肿瘤)
Lymphoma
(Lymphoid) Leukimia
②Sacoma (肉瘤)
(Hematopoietic)
(Mesenchymal tissue) 2%
癌症生物学课件(国外)
What is the evidence that cell cycle progression requires induction of new gene expression?
Smith and Stiles (1981)
No stimulus + PDGF
3 hrs wash away PDGF
The complex is formed by the 'Leucine zipper' Motif Structural motif that dimerises two alpha helical DNA binding regions of proteins
AP-1 and the TRE
Immediate early - within minutes
Delayed early - within hours Late - around onset of S phase
Induction and repression of genes is transient
DNA Array Experiment
Indeed the fibroblast response to serum induces many genes associated with wound healing or inflammation pathways.
Late Genes
After the R point up to the onset of the S -1 complex is regulated at multiple levels: Expression, Phosphorylation, Dimerisation
NF-κB transcription factor complex
癌的生物学(英文)
Secrete enzymes that digest these proteins Secrete a protease called plasminogen activator (plasminogen converted to plasmin) digestion of basal lamina
ASSOCIATION WITH HUMAN CANCERS
1. Growth Factor Receptor Increased numbers in 20 percent of breast cancers
2. Ras Protein Activated by mutations in 20 to 30 percent of cancers 3. Abl Kinase Activated by abnormal chromosomes in chronic myelogenous leukemia
Cancer: Benign
• Benign: localized and of small size • Cells that closely resemble, and may function, like normal cells • May be delineated by a fibrous (Basal lamina) capsule • Become problems due to sheer bulk or due to secretions (e.g. hormones)
Secrete factors that stimulate angiogenesis bFGF, TGF, VEGF (vascular endothelial growth factor)
Therapy: inhibit antiogenesis: endostatin. Question: how proliferative are blood vesssels in adults?
ASSOCIATION WITH HUMAN CANCERS
1. Growth Factor Receptor Increased numbers in 20 percent of breast cancers
2. Ras Protein Activated by mutations in 20 to 30 percent of cancers 3. Abl Kinase Activated by abnormal chromosomes in chronic myelogenous leukemia
Cancer: Benign
• Benign: localized and of small size • Cells that closely resemble, and may function, like normal cells • May be delineated by a fibrous (Basal lamina) capsule • Become problems due to sheer bulk or due to secretions (e.g. hormones)
Secrete factors that stimulate angiogenesis bFGF, TGF, VEGF (vascular endothelial growth factor)
Therapy: inhibit antiogenesis: endostatin. Question: how proliferative are blood vesssels in adults?
生物必修一苏教版 第三节 关注癌症(共26张PPT)
2、癌细胞具有什么特征（ ） A、无限增殖 B、形态结构变化 C、易分散转移 D、A、B、C都是
陈雅梅（版权所有）
原癌基因和抑癌基因( ) A．普遍存在于人和动物的染色体上 B．仅存在于健康人的染色体上 C．仅存在于被致癌病毒感染但尚未发 病者的染色体上 D．仅存在于癌症患者的染色体上
陈雅梅（版权所有）
物理
2.居里夫人在研究工作中长期被放射线损伤，导致 白血病。
物理
3.近几年肺癌的发生率日趋增加，可能与吸入烟草 燃烧的烟雾、工厂的煤烟、汽车尾气等有关。
化学
4.EB病毒是一种疱疹病毒，能使儿童患淋巴癌和成 人患鼻咽癌。
病毒
陈雅梅（版权所有）
细胞癌变的内因：
原癌基因：其很多的产物都负责调节 细胞周期，控制细胞生长 和分裂的进程。
•
10、阅读一切好书如同和过去最杰出 的人谈 话。202 1/8/14 2021/8/ 142021 /8/148 /14/202 1 2:01:08 AM
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11、一个好的教师，是一个懂得心理 学和教 育学的 人。202 1/8/14 2021/8/ 142021 /8/14A ug-211 4-Aug-2 1
•
14、谁要是自己还没有发展培养和教 育好， 他就不 能发展 培养和 教育别 人。202 1年8月 14日星 期六20 21/8/1 42021/ 8/14202 1/8/14
•
15、一年之计，莫如树谷；十年之计 ，莫如 树木； 终身之 计，莫 如树人 。2021 年8月20 21/8/1 42021/ 8/14202 1/8/14 8/14/20 21
• 2、Our destiny offers not only the cup of despair, but the chalice of opportunity. (Richard Nixon, American President )命运给予我们的不是失望之酒，而是机会之杯。二〇二一年六月十七日2021年6月17日星期四 • 3、Patience is bitter, but its fruit is sweet. (Jean Jacques Rousseau , French thinker)忍耐是痛苦的，但它的果实是甜蜜的。10:516.17.202110:516.17.202110:5110:51:196.17.202110:516.17.2021 • 4、All that you do, do with your might; things done by halves are never done right. ----R.H. Stoddard, American poet做一切事都应尽力而为，半途而废永远不行6.17.20216.17.202110:5110:5110:51:1910:51:19 • 5、You have to believe in yourself. That's the secret of success. ----Charles Chaplin人必须相信自己，这是成功的秘诀。-Thursday, June 17, 2021June 21Thursday, June 17, 20216/17/2021
分子生物学--癌症课件
etc.)
2020/3/30
④ 细胞从G1进入S
非磷酸化的RB 阻断细胞周期
• 正常细胞：通过RB 被磷 酸化来解除对细胞增殖的 抑制
肿瘤抗原（如SV40 T抗原） 与RB结合，使RB不能与 E2F结合，细胞周期可以自 由地进入S 期
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Example 2：
p53
Molecule of the year 1993
• 病毒癌基因（viral oncogene, v-onc）：病毒所携带 的致癌基因
• 细胞癌基因（ cellular oncogene, c-onc ）或原癌基 因（proto-oncogene）：细胞中与病毒癌基因同源的
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(二)细胞癌基因（ cellular oncogene, c-onc ）或 原癌基因（proto-oncogene）
肿瘤细胞中原癌基因表达的特点
• 某些原癌基因具有高水平的表达或过度表达 • 原癌基因的表达程度和次序发生紊乱
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effects of mutations
in oncogenes
原癌基因是显性的 !!
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Protooncogenes
become oncogenes,
how ?
• 是一类广泛存在生物体中，高度保守的基因， 其产物具有调控细胞增生的重要功能，当其受 某些因素的影响，能发生突变（活化）成为癌 基因，导致细胞恶性转化。
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原癌基因的特点
• （1）广泛存在于生物体。是未激活的癌基因，是人 或动物细胞中的一类固有的正常基因。
• （2）高度保守，功能相似。 • （3）产物有重要功能。促进正常细胞生长、增殖、
癌生物学第二章----英文原版图片
Figure 2.24 The Biology of Cancer (© Garland Science 2007)
Figure 2.25 The Biology of Cancer (© Garland Science 2007)
Table 2.8 The Biology of Cancer (© Garland Science 2007)
Table 2.1 The Biology of Cancer (© Garland Science 2007)
Figure 2.6a The Biology of Cancer (© Garland Science 2007)
Figure 2.6b The Biology of Cancer (© Garland Science 2007)
Figure 2.8a The Biology of Cancer (© Garland Science 2007)
Figure 2.8b The Biology of Cancer (© Garland Science 2007)
Figure 2.8c The Biology of Cancer (© Garland Science 2007)
Figure 2.16a The Biology of Cancer (© Garland Science 2007)
Figure 2.16b The Biology of Cancer (© Garland Science 2007)
Figure 2.17 The Biology of Cancer (© Garland Science 2007)
Figure 2.2c The Biology of Cancer (© Garland Science 2007)
癌症英文版ppt课件
Don’t smoke! Keep healthy diet. Avoid too much sun.
Getting plenty of sleep and exercise and eating the right foods can help keep you healthy.
Cancer—it’s scary word, and a scary disease. Cancer kills a lot of people all over the world. But there’s good news too. Millions of people who have had cancer are still alive. Doctors have learned a great deal about treating and preventing cancer. WHAT IS CANCER? Cancer is not a single disease. It includes more than 100 different diseases. They may affect any part of the body. But they have one thing in common. They are all caused by cells that are out of control. All living things are made up of cells. An adult human body has about 30 trillion cells—that’s 30,000,000,000,000! Cells reproduce (make more cells) by dividing in half. In an adult body, about 25 million cells divide every second. That’s how the body heals itself. Sometimes a cell goes out of control and divides over and over. And that’s what cancer is— unhealthy cells, growing and reproducing out of control. These cells are said to be cancerous. WHY CANCER IS DANGEROUS When cancerous cells multiply, they form tumors. Tumors can interfere with important body processes. Cancer of the lungs, for instance, interferes with breathing. Cancer of the stomach interferes with digesting food. Cancerous cells can also spread to other parts of the body. Then new tumors form. Cancer that has metastasized is the most dangerous. When cancer attacks several parts of the body, it is hard to stop. HOW DOCTORS TREAT CANCER The best weapon against cancer is detecting it at an early stage before it grows very much. Regular checkups by a doctor can detect cancer before it grows and spreads. People whose cancers are discovered early usually survive. Some cancerous tumors can be removed by surgery. Doctors must remove some surrounding healthy cells, too, to be sure they get all the caions of people with cancer still alive •Technology for cancer treating
Getting plenty of sleep and exercise and eating the right foods can help keep you healthy.
Cancer—it’s scary word, and a scary disease. Cancer kills a lot of people all over the world. But there’s good news too. Millions of people who have had cancer are still alive. Doctors have learned a great deal about treating and preventing cancer. WHAT IS CANCER? Cancer is not a single disease. It includes more than 100 different diseases. They may affect any part of the body. But they have one thing in common. They are all caused by cells that are out of control. All living things are made up of cells. An adult human body has about 30 trillion cells—that’s 30,000,000,000,000! Cells reproduce (make more cells) by dividing in half. In an adult body, about 25 million cells divide every second. That’s how the body heals itself. Sometimes a cell goes out of control and divides over and over. And that’s what cancer is— unhealthy cells, growing and reproducing out of control. These cells are said to be cancerous. WHY CANCER IS DANGEROUS When cancerous cells multiply, they form tumors. Tumors can interfere with important body processes. Cancer of the lungs, for instance, interferes with breathing. Cancer of the stomach interferes with digesting food. Cancerous cells can also spread to other parts of the body. Then new tumors form. Cancer that has metastasized is the most dangerous. When cancer attacks several parts of the body, it is hard to stop. HOW DOCTORS TREAT CANCER The best weapon against cancer is detecting it at an early stage before it grows very much. Regular checkups by a doctor can detect cancer before it grows and spreads. People whose cancers are discovered early usually survive. Some cancerous tumors can be removed by surgery. Doctors must remove some surrounding healthy cells, too, to be sure they get all the caions of people with cancer still alive •Technology for cancer treating
癌症课件
癌症的三级预防
• 一级预防：病因预防
• 二级预防：早发现、早诊断、早治疗
• 三级预防：提高治愈率、生存率和生存质 量，疼痛管理
肿瘤的三级预防
• １／３癌症是可以预防的
• １／３癌症通过早发现、早诊断、早治疗是可
以治愈的
• １／３癌症通过适当治疗可以延长生存时间，
提高生活质量
肿瘤的一级预防
• 病因预防 通过行政命令和法律条文严格规定， 以保护个人和社会免遭致病因素的危害， 普及癌症防治知识，建立安全健康的生活 方式。
1、反复发热和牙龈出血、皮下出血、贫血。 2、反复干咳、痰中带血、胸闷、胸痛。 3、肝脏肿大的速度较快，伴有肝区疼痛。 4、中年以上妇女不规则引导出血，或听更年期后 又来月经，白带明显增多。 5、不伴腹痛的明显加深的黄疸和上腹包块。 6、身体任何部位出现逐渐增大的肿块。 7、不明原因的无痛性血尿。 8、皮肤溃烂长久不愈合。 9、反复出现的不明原因的高热
饮用池溏蓄积雨水
林县的启示
• 林县以他20％的人死于食管癌的悲痛历史 告诉我们： 癌症，不是来自贫困，不是来 自落后，而是来自环境，来自文化，来自 人类本身。 如果在你的饮食中注意一些十 分简单的问题，或者作一些简单的改变， 就可以大大降低好多种癌症的发病率。
不合理膳食有哪些？
• 1．腌制与霉变食物
二、生物物理因素
• 中国医学科学院肿瘤医院 调查：有约10%~15%的 癌症是遗传造成的。在流 行病学调查中，的确存在 关于家族性癌症的记载。 • 19世纪60年代，法国有一 位医生报告，他家族中的 24个女性共有15人死于癌 症，其中10人死于乳腺癌； 这个家族的第二代的5个 子女中，有4人死于癌症。 而拿破仑一家，其父、祖 父、3个姐妹和4个兄弟， 以及拿破仑本人都死于胃 癌。
癌症生物学课程课件
基因突变
某些基因突变会增加个体患癌症的风险，如 BRCA1和BRCA2基因突变与乳腺癌的发生有关。
生活方式
不健康的生活方式，如缺乏运动、饮酒和暴露 于阳光下，可能导致癌症的发生。
环境因素
一些环境因素，如烟草使用、饮食习惯和暴露 于致癌物质，也会增加患上癌症的风险。
遗传因素
遗传因素在癌症的发生中起着重要的作用，有 些癌症可能会在家族中遗传。
除了传统治疗方法外，还有许多创新的癌症治疗方法正在研究和发展中，如基因治疗和靶向治疗等。
癌症药物的研发与临床试验
研发新的癌症药物需要经过严格的临床试验来评估其疗效和安全性，以确保 有效治疗癌症。
癌症生物学课程课件
欢迎参加本次癌症生物学课程！本课程将带领您深入了解癌症的各个方面， 包括癌症的定义、病因、生物学特征、治疗方法以及预防和早期诊断等内容人体组织中异常细胞的不受控制的生长和扩 散。了解癌症的发生机制对于预防和治疗至关重要。
癌症病因及风险因素
癌症与遗传
遗传因素在癌症的发生中扮演重要角色。了解基因突变与癌症之间的关系有助于早期发现和治疗。
癌症的治疗方法
1
化疗
使用化学药物杀死癌细胞或阻断其生长。
放疗
2
使用高能射线杀死癌细胞或控制其生长。
3
手术治疗
通过手术切除肿瘤及相关组织进行治疗。
免疫治疗
4
通过激活免疫系统来抑制癌细胞的生长 和扩散。
其他新型治疗方法
癌症的生物学特征
异常细胞增殖
癌症细胞具有无限增殖的能力， 而正常细胞则受到严格的调控。
肿瘤血管生成
迁移和转移
癌症细胞能够诱导新的血管生成， 为肿瘤提供充足的营养和氧气。
癌症细胞可以通过迁移和侵袭周 围组织，并通过血液或淋巴系统 转移到其他部位。
癌生物学简介英文版 PPT课件
Benign vs. Malignant Tumors
Benign Grow slowly Well-defined capsule Not invasive Well differentiated Low mitotic index Do not metastasize
Mosby items and derived items © 2006 by Mosby, Inc.
6
Mosby items and derived items © 2006 by Mosby, Inc.
Classification and Nomenclature
7
Mosby items and derived items © 2006 by Mosby, Inc.
Classification and Nomenclature
8
Mosby items and derived items © 2006 by Mosby, Inc.
Cancer Cells
Transformation
Cancer cell’s independence from normal cellular controls Anchorage independent Immortal Anaplasia
Stem cells are multipotent
10
Mosby items and derived items © 2006 by Mosby, Inc.
Cancer Stem Cells
11
Mosby items and derived items © 2006 by Mosby, Inc.
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• VEGF inhibitors can decrease tumour vascularisation and cause tumour regression
– Drugs that prevent VEGF from binding receptor
cell
VEGFR
VEGF
Treating cancer by stopping angiogenesis
• Initially thought that angiogenesis inhibitors would have mild side effects • Increasing evidence that this is not the case • Side effects can include bleeding, clots in the arteries (with resultant stroke or heart attack), hypertension • Do slow tumour growth • Several angiogenesis inhibitors approved by FDA; several more in clinical trials
Avastin (Bevacizumab)
• Humanised monoclonal antibody against VEGF-A • Approved by FDA in 2004
– First anti-angiogenesis treatment approved
• Made by Genentech (Roche) • Used in combination with chemotherapy (e.g. 5-fluorouracil) to treat metastatic colorectal or renal cell cancer and NSCLC
Angiogenesis
BIO387 – Cancer Biology
Dr Debbie Cunningham d.cunningham@
''Judah is going to cure cancer in two years''
Dr. James Watson
''Judah is going to cure cancer in two years''
Angiogenesis
Angiogenesis
• (A) A synthetic pellet containing a purified angiogenic factor is implanted into a rabbit cornea • (B) 10 to 12 days later, new blood vessels have grown ~2.0 mm from the edge of the cornea • There is no inflammation, the cornea remains clear and transparent, and the rabbits do not notice any irritation. • After pellet removal, the vessels undergo complete regression. (from Folkman, J Ped Surg 2007)
Angiogenesis
• Not to be confused with vasculogenesis, which is the formation of blood vessels from progenitors during development
Cardiovascular physiology
Angiogenesis
• Stimulated by:
– Increased tissue mass – Reduced oxygen levels (hypoxia) – Inflammation
Angiogenesis
1. Angiogenic factors bind to receptors on the surface of endothelial cells 2. Endothelial cells at sprout site proliferate 3. Endothelial cells migrate towards source of angiogenic factors 4. New vessel lumen is formed
• Why do we need blood?
– Delivery of oxygen and nutrients – Removal of CO2 and waste products – Acid/base balance
capillaries
de-oxygenated venous blood oxygenated arterial blood tissue
• VEGF is secreted by ~60% of solid tumours
Hypoxia-induced VEGF expression
Rahimi N Mol Cancer Ther 2012;11:538-548
VEGF and tumour growth
/gene/research/images/angiogenesis.jpg
Nature Medicine 9, 713 - 725 (2003)
Angiogenesis
• Situations where angiogenesis occurs:
– Development – Wound healing – Bone fractures – Menstrual cycle – Pregnancy
Treating cancer by stopping angiogenesis
• VEGF inhibitors can decrease tumour vascularisation and cause tumour regression
cell
VEGFR
VEGF
Treating cancer by stopping angiogenesis
What does angiogenesis have to do with cancer?
• Situations where angiogenesis occurs:
– Wound healing – Bone fractures – Menstrual cycle – Pregnancy – Development – Tumour Growth
Angiogenesis, cancer and VEGF movie
/watch?v=7YgwJeVEgvU
Treating cancer by stopping angiogenesis
• • • Largely a developmental process, inhibition should not cause side effects Inhibiting tumour angiogenesis - major therapeutic goal in the treatment of cancer Endothelial cells are easily accessible site for drug action
Tumour Angiogenesis
Normal vasculature Tumour vasculature
Nature Medicine 9, 713 - 725 (2003)
Tumour Angiogenesis
High levels of pro-angiogenic factors e.g. VEGF: Tumour vasculature
• Disorganised
• Lack of hierarchy • Leaky • Uneven delivery of O2 and nutrients
• Lack of/loose association with
pericytes
Nature Medicine 9, 713 - 725 (2003)
Dr. Judah Folkman
What is Angiogenesis?
• The growth of new blood vessels from existing vasculature
endothelial cell
vessel lumen
/2006/051906/images/angiogenesis_web.jpngiogenesis
Activated endothelial cells release proteases which digest extracellular matrix, permitting cells to move away from parent vessel
proteases
Treating cancer by stopping angiogenesis
• VEGF inhibitors can decrease tumour vascularisation and cause tumour regression
/gene/research/images/angiogenesis.jpg
• VEGF inhibitors can decrease tumour vascularisation and cause tumour regression
– Drugs that bind up all available VEGF
VEGF
Treating cancer by stopping angiogenesis
– Drugs that prevent VEGF from binding receptor
cell
VEGFR
VEGF
Treating cancer by stopping angiogenesis
• Initially thought that angiogenesis inhibitors would have mild side effects • Increasing evidence that this is not the case • Side effects can include bleeding, clots in the arteries (with resultant stroke or heart attack), hypertension • Do slow tumour growth • Several angiogenesis inhibitors approved by FDA; several more in clinical trials
Avastin (Bevacizumab)
• Humanised monoclonal antibody against VEGF-A • Approved by FDA in 2004
– First anti-angiogenesis treatment approved
• Made by Genentech (Roche) • Used in combination with chemotherapy (e.g. 5-fluorouracil) to treat metastatic colorectal or renal cell cancer and NSCLC
Angiogenesis
BIO387 – Cancer Biology
Dr Debbie Cunningham d.cunningham@
''Judah is going to cure cancer in two years''
Dr. James Watson
''Judah is going to cure cancer in two years''
Angiogenesis
Angiogenesis
• (A) A synthetic pellet containing a purified angiogenic factor is implanted into a rabbit cornea • (B) 10 to 12 days later, new blood vessels have grown ~2.0 mm from the edge of the cornea • There is no inflammation, the cornea remains clear and transparent, and the rabbits do not notice any irritation. • After pellet removal, the vessels undergo complete regression. (from Folkman, J Ped Surg 2007)
Angiogenesis
• Not to be confused with vasculogenesis, which is the formation of blood vessels from progenitors during development
Cardiovascular physiology
Angiogenesis
• Stimulated by:
– Increased tissue mass – Reduced oxygen levels (hypoxia) – Inflammation
Angiogenesis
1. Angiogenic factors bind to receptors on the surface of endothelial cells 2. Endothelial cells at sprout site proliferate 3. Endothelial cells migrate towards source of angiogenic factors 4. New vessel lumen is formed
• Why do we need blood?
– Delivery of oxygen and nutrients – Removal of CO2 and waste products – Acid/base balance
capillaries
de-oxygenated venous blood oxygenated arterial blood tissue
• VEGF is secreted by ~60% of solid tumours
Hypoxia-induced VEGF expression
Rahimi N Mol Cancer Ther 2012;11:538-548
VEGF and tumour growth
/gene/research/images/angiogenesis.jpg
Nature Medicine 9, 713 - 725 (2003)
Angiogenesis
• Situations where angiogenesis occurs:
– Development – Wound healing – Bone fractures – Menstrual cycle – Pregnancy
Treating cancer by stopping angiogenesis
• VEGF inhibitors can decrease tumour vascularisation and cause tumour regression
cell
VEGFR
VEGF
Treating cancer by stopping angiogenesis
What does angiogenesis have to do with cancer?
• Situations where angiogenesis occurs:
– Wound healing – Bone fractures – Menstrual cycle – Pregnancy – Development – Tumour Growth
Angiogenesis, cancer and VEGF movie
/watch?v=7YgwJeVEgvU
Treating cancer by stopping angiogenesis
• • • Largely a developmental process, inhibition should not cause side effects Inhibiting tumour angiogenesis - major therapeutic goal in the treatment of cancer Endothelial cells are easily accessible site for drug action
Tumour Angiogenesis
Normal vasculature Tumour vasculature
Nature Medicine 9, 713 - 725 (2003)
Tumour Angiogenesis
High levels of pro-angiogenic factors e.g. VEGF: Tumour vasculature
• Disorganised
• Lack of hierarchy • Leaky • Uneven delivery of O2 and nutrients
• Lack of/loose association with
pericytes
Nature Medicine 9, 713 - 725 (2003)
Dr. Judah Folkman
What is Angiogenesis?
• The growth of new blood vessels from existing vasculature
endothelial cell
vessel lumen
/2006/051906/images/angiogenesis_web.jpngiogenesis
Activated endothelial cells release proteases which digest extracellular matrix, permitting cells to move away from parent vessel
proteases
Treating cancer by stopping angiogenesis
• VEGF inhibitors can decrease tumour vascularisation and cause tumour regression
/gene/research/images/angiogenesis.jpg
• VEGF inhibitors can decrease tumour vascularisation and cause tumour regression
– Drugs that bind up all available VEGF
VEGF
Treating cancer by stopping angiogenesis