牙科公共衛生學 Prevention & detection of oral cancer 口腔癌之預防與偵測 陳玉昆副教授 : 高雄醫學大學 口腔病理科 07-3121101~2755 [email protected].

牙科公共衛生學

Prevention & detection of oral cancer

口腔癌之預防與偵測

陳玉昆副教授 : 高雄醫學大學 口腔病理科 07-3121101~2755 [email protected]

參 考 書 目1. Gibbs WW. Untangling the roots of cancer. Sci Am 2003;289:56-65.2. What you need to know about cancer. Sci Am 1996 ;289:28-119.3. Hannen EJM, Riediger D. The quantification of angiogenesis in relation to metastasis in oral cancer: a review. Int. J

Oral Maxillofac Surg 2004;33:2-7.4. Shieh et al. Role of angiogenic and non-angiogenic mechanisms in oral squamous cell carcinoma: correlation with

histologic differentiation and tumor progression. J Oral Pathol Med 2004;33:601-6.5. Sharma DC. Betel quid and areca nut are carcinogenic without tobacco. Lancet Oncol 2003;4:587.6. Sharma DC. Indian betel quid more carcinogenic than anticipated. Lancet Oncol 2001;2:464.7. Braakhuis BJM et al. A genetic progression model of oral cancer: current evidence and clinical implications. J Oral

Pathol Med 2004;33:317-22.8. Braakhuis BJM et al. A Genetic explanation of slaughter’s concept of field cancerization: evidence and clinical

implications. Cancer Res 2003;63:1727-30.9. Loktionov A. Common gene polymorphisms, cancer progression and prognosis. Cancer Letters 2004;208 :1-33.10. Desmaze C et al. Telomere-driven genomic instability in cancer cells. Cancer Letters 2003;194:173-82.11. Hiyama E & Hiyama K. Telomerase as tumor marker. Cancer Letters 2003;194:221-33.12. Kaohsiung Medical University, Oral Pathology Department13. Huang AH et al. Isolation and characterization of normal hamster buccal pouch stem/stromal cells – a potential oral

cancer stem/stem-like cell model. Oral Oncol 2009;45: e189-e195.14. Umezawa & Gorham. Dueling models in head and neck tumor formation. Lab Investig 2010; 90:1546-8.15. Spillane JB, Henderson MA. Cancer stem cells: a review. ANZ J Surg 2007;77:464-8.16. Zhou ZT, Jiang WW. Cancer stem cell model in oral squamous cell carcinoma. Curr Stem Cell Res Ther 2008;3:17–20.17. Harper LJ et al. Stem cell patterns in cell lines derived from head and neck squamous cell carcinoma. J Oral Pathol Med

2007;36:594-603.18. Lim YC et al. Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas.

Oral Oncol 2011;47:83-91.

1. Gibbs WW. Untangling the roots of cancer. Sci Am 2003;289:56-65.2. What you need to know about cancer. Sci Am 1996 ;289:28-119.3. Hannen EJM, Riediger D. The quantification of angiogenesis in relation to metastasis in oral cancer: a review. Int. J

Oral Maxillofac Surg 2004;33:2-7.4. Shieh et al. Role of angiogenic and non-angiogenic mechanisms in oral squamous cell carcinoma: correlation with

histologic differentiation and tumor progression. J Oral Pathol Med 2004;33:601-6.5. Sharma DC. Betel quid and areca nut are carcinogenic without tobacco. Lancet Oncol 2003;4:587.6. Sharma DC. Indian betel quid more carcinogenic than anticipated. Lancet Oncol 2001;2:464.7. Braakhuis BJM et al. A genetic progression model of oral cancer: current evidence and clinical implications. J Oral

Pathol Med 2004;33:317-22.8. Braakhuis BJM et al. A Genetic explanation of slaughter’s concept of field cancerization: evidence and clinical

implications. Cancer Res 2003;63:1727-30.9. Loktionov A. Common gene polymorphisms, cancer progression and prognosis. Cancer Letters 2004;208 :1-33.10. Desmaze C et al. Telomere-driven genomic instability in cancer cells. Cancer Letters 2003;194:173-82.11. Hiyama E & Hiyama K. Telomerase as tumor marker. Cancer Letters 2003;194:221-33.12. Kaohsiung Medical University, Oral Pathology Department13. Huang AH et al. Isolation and characterization of normal hamster buccal pouch stem/stromal cells – a potential oral

cancer stem/stem-like cell model. Oral Oncol 2009;45: e189-e195.14. Umezawa & Gorham. Dueling models in head and neck tumor formation. Lab Investig 2010; 90:1546-8.15. Spillane JB, Henderson MA. Cancer stem cells: a review. ANZ J Surg 2007;77:464-8.16. Zhou ZT, Jiang WW. Cancer stem cell model in oral squamous cell carcinoma. Curr Stem Cell Res Ther 2008;3:17–20.17. Harper LJ et al. Stem cell patterns in cell lines derived from head and neck squamous cell carcinoma. J Oral Pathol Med

2007;36:594-603.18. Lim YC et al. Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas.

Oral Oncol 2011;47:83-91.

探索癌症之旅

始 點How cancerarise

Stages of carcinogenesis

癌化的標準教條

四種癌化理論

Field cancerization

癌細胞的六種超能力

癌症的預防

學 習 目 標

終 點11

22

3344

55

66

77

In this model, clonal variants, including stromal cells derived from tumor cells, generate a microenvironment (niche) for tumor cells, and support tumor progression after tumor cells undergo clonal evolution.

Stochastic Clonal Evolution Model

第一站： How Cancer Arises

Ref. 14

Stochastic clonal evolution model Interaction between tumor cellsand stromal cells

Tumor cell

Stem cells create an exact copy of themselves and an EP cell when they divide. The EP cell then progresses to a late progenitor cell and then to the definitive cell line

Asymmetrical Division

Definitive Tissue Line

Early Progenitor

Late Progenitor

Stem Cell

Ref. 15

(a) The traditional model of tumor formation. A series of mutations affect a mature cell, causing it to become malignant. Any cell has the potential to form a tumor

Traditional Model ofTumor Formation

MatureDefinitiveTissueCell

TumorTumor

Mutation

Mutation

Mutation

Mutation Onlyat the Stem Cell

(b) Mutation only at the stem cell or progenitor cell level. The cancer stem cell replicates forming an exact copy of itself as well as a continuous supply of heterogeneous tumor cells

Tumor

Stem CellMutation

Ref. 15

Cancer Stem Cell Model

mutation

mutationSelf-renewingstem cell

Progenitorcell

Mature cell

Cancer cell

Self-renewingcancer stem cell

Ref. 15

In the stem cell model, only the stem cells or their progenitor cells have the ability to form tumors. Tumor characteristics vary depending on which cell undergoes the malignant transformation

Comparison of Somatic and Cancer Stem Cells

Somatic Stem Cell Cancer Stem Cell

Self renew, highly regulated

Self-renew, poorly regulated

Differentiate, produces mature tissue

Differentiate, produces tumor

Migrate to distant tissuesMetastasize to distant sites

Long lifespan Long lifespan

Resistant to apoptosisResistant to apoptosis

Ref. 15

• The hierarchical stem cell structure present in human oral epithelia indicates that stem cells are the only long-time residents of oral epithelia and, consequently, the only cells able to accumulate the necessary number of genetic changes for malignancy to develop

Stem cell - Oral Epithelia

• According to the progression model, the development of most of OSCC takes months or years.

• As normal human oral epithelia have a rate of renewal estimated to be about 14-24 days, most epithelial cells do not exist long enough to accumulate the genetic changes necessary for the development of an OSCC.

1, CSC might come from epithelial SC or progenitor within basal layer with genetic alterations; 2, muscle-derived SCs; 3, fibroblast-derived SCs; 4, vessel wall-derived SCs; 5, blood-derived SCs; and 6, adipose derived SCs.

A Schematic Diagram Showing Sites of Origins of Putative CSCs in OSCC

Ep

ith

eliu

mC

on

nec

tive

tis

sue

Ref. 16

Putative Cell Surface Markers of Presumptive CSC

SP-C+CCA+

Tumor Type Surface Markers

Ref. 16

CD44+CD24- Lineage negative

CD44+CD24-

CD44+CD24-Tumor formed

New tumor formed

Ref. 16

A minority population of CD44+ cancer cells (<3%/<10% of the cells in head and neck SCC cell line), but not the CD44- cancer cells, generate new tumors in vivo

Potential Mechanisms of CSC Formation

CSC

MUTATIONA

Progenitors

Self renewal

Self renewal

Stem/progenitor cellsDifferentiated cells

Ref. 16

CSC

MULTIPLE GENETIC HITSB

Stem/progenitor cells

Potential Mechanisms of CSC Formation

Ref. 16

CSC

FUSIOND

Cancer cell

Stem/progenitor cells

Potential Mechanisms of CSC Formation

Ref. 16

CSC

MULTISTEP DEDIFFERENTIATIONC

Cancer cell

DMBA-Induced Hamster Buccal Pouch Model

14-wk

Normal

Carcinogen: DMBA

• Hamster buccal-pouch mucosa provides one of the most widely-accepted experimental models for oral carcinogenesis

Ref. 12

DMBA-Induced Hamster Buccal Pouch Model• Despite anatomical and histological differences

between (hamster) pouch mucosa and human buccal tissue, experimental carcinogenesis protocols for the former induce premalignant changes and carcinomas that are similar to the development of premalignancy and malignancy in human oral mucosa.

AnimalAnimal StudyStudy

HumanHuman StudyStudy

Ref. 12

A B

Isolation and Characterization of Stem Cells from Normal Hamster Buccal Pouch (HBPSC)

Representative sample of the normal hamster buccal pouch tissues revealed no obvious grossly (A; inset) and histological (B, Hematoxylin & eosin stain, 200) changes.

Ref. 13

Minimal Criteria of Stem Cell Capacity

• Self-renewal---Colony forming unit (CFU)---Proliferation

• One or more lineages differentiation---Adipogenic differentiation---Osteogenic differentiation---Chondrogenic differentiation---Neurogenic differentiation

Representative sample of the HBPSCs obtained from the normal hamster buccal pouch tissues were spindle-shaped in morphology (200).

Ref. 13

A

B

Representative sample of the HBPSCs obtained from the normal hamster buccal pouch tissues were able to form colonies, stained with crystal violet (A; B, 100).

Ref. 13

A B

Cytoplasmic keratin (A, 200) and vimentin (B, 200) stainings were noted for the representative sample of the HBPSCs obtained from the normal hamster buccal pouch tissues.

Ref. 13

Prol

ifera

tion

rate

(# o

f fol

ds)

Pouch 2 Pouch 3

Proliferation rates for the HBPSCs obtained from the three normal hamster buccal pouch tissues (p: passage).

Ref. 13

A

NM GAPDH PPAR

B

50

100

150

200250300350400

bp

(A) Representative sample of the HBPSCs obtained from the normal hamster buccal pouch tissues were able to differentiate towards adipogenic lineage (×200). (B) Expression of PPARγ mRNA (401-bp) upon RT-PCR also indicates adipogenic lineage of HBPSCs obtained from normal hamster buccal pouch tissues; GAPDH (135-bp) was the positive control; H2O was the negative control (N); M: molecular weight marker.

Ref. 13

Representative sample of the HBPSCs obtained from the normal hamster buccal pouch tissues were able to differentiate towards chondrogenic lineage (×200); inset: a yellowish chondroid pellet (~3mm in diameter).

Ref. 13

Representative sample of the HBPSCs obtained from the normal hamster buccal pouch tissues were able to differentiate towards osteogenic lineage (×200).

Representative sample of the HBPSCs obtained from the normal hamster buccal pouch tissues expressed the differentiation markers (Osteonectin: 323-bp & Nestin: 416-bp) and stem cell markers (Nanog: 364-bp, Rex-1: 232-bp & Oct-4: 717-bp) upon RT-PCR. GAPDH (135-bp) was the positive control; H2O was the negative control (N); M: molecular weight marker.

M N GA

PD

H

Ost

eon

ecti

n

Ne

sti

n

Oc

t-4

Na

no

g

Re

x-1

100

200

300

400500600700

bp

Ref. 13

Representative sample of the HBPSCs obtained from the normal hamster buccal pouch tissues showed high expression for surface markers: CD29, CD90, and CD105 but very low expression for CD14, CD34, and CD45 (Black/blue line: isotype control, Red line: marker of interest; Max: maximum).

0.9

CD14

% o

f M

ax

100

CD 29

% o

f M

ax

93.6

100

CD 34

% o

f M

ax

100

1.7

CD 45

1.5

% o

f M

ax

100

CD 90

85.8

% o

f M

ax

100

51.3

CD 105

100

% o

f M

ax

100

Ref. 13

Isolation of normal HBPSC, we may follow in vitro the sequential changes of the normal HBPSCs during multistep oral carcinogenesis or the alternations of these cells upon irradiation treatment and/or chemotherapy. Hence, the isolated normal HBPSCs, would provide a potential avenue for the future study of CSCs of buccal SCCs.

DMBA-Induced Hamster Buccal Pouch Model

A colony with holoclone characteristics of circular outline and tightly packed cobblestone’ cells (h) is surrounded by cells with a spaced and fusiform paraclone morphology (p). A small colony (m) perhaps corresponds to a meroclone.

Comparison of Morphology Between Our Isolated

Cells & Literature ResultsOur isolated cells from DMBA-induced cancer pouch tissue

Refs. 13, 17

Self-renewal, stem cell marker expression, aberrant differentiation, and tumor-initiating potential

OSCC-driven squamospheres demonstrated:(1)A number of stem cell markers, such as CK5, OCT4, SOX2, nestin, and CD44, Bmi-1, CD133, ALDH1(2) Single-dissociated squamosphere cells were able to form new squamospheres within 1 week of reseeding(3) Serum treatment led HNSCC-driven squamospheres to be non-tumorigenic differentiated cancer cells(4) Injection of as few as 100 undifferentiated squamosphere cells in nude mice gave rise to tumor formation

Hallmarks of CSCs (1)

CSCs is known to be significantly resistant to various chemotherapeutic agents (cisplatin, 5-fluorouracil (FU), paclitaxel, and doxetaxel)

Hallmarks of CSCs (2)

Ref. 18

Genticallyaltered cell

HyperlasiaDysplasia

Tumor developmentoccurs in stages

Geneticallyalteredcell (CSC) Hyperplasia

Dysplasia

Oral premalignant lesionsLeukoplakia, Erythroplakia, Oral submucous fibrosis, Verrucous hyperplasia, Erosive lichen planus

基底層完整

基底層完整

Initiated cell起始細胞

第二站 : Stages of Carcinogenesis

Ref. 1

In situ cancer

Invasive cancer

Blood vessel/lymphatic vessel

Ref. 1

How Cancer Spreads

Primary tumor

Normal epithelial cell

Basement membrane

Invasive tumor cellBlood vessel/lymphatic channel

How Cancer Spreads

Ref. 1

Endothelial/lymphaticlining

Basement membrane

Metastatic cellin circulation

Secondary tumor site

Tumor celladheringto capillary

Ref. 1

How Cancer Spreads

Initiation Phase (Early) 第二站 : Further look on stages of carcinogenesis

去毒

Ref. 9

Initiation Phase (Late) Ref. 9

Promotion Phase (Early) Mutant clone establishment & appearance

of phenotypically transformed cells

Ref. 9

Promotion Phase (Late) Establishment of phenotypically

transformed cell population (dysplasia)

Ref. 9

Progression Phase (Early)

Malignisation

Ref. 9

Progression Phase (Middle)

Microinvasion

Ref. 9

Progression Phase (Late) Advanced invasion and metastasis

ChemotherapyRef. 9

NormalCell CycleCell enlargesand makesnew proteins

Beginningof cycleCell

divides(mitosis)

Cell preparesto divide

Cell replicatesas DNA

Cell rests

Restriction point:celldecides whetherto commit itself tothe complete cycle

崗 哨

第三站 : 癌化理論的標準教條

G1 arrest

Ref. 2

InhibitorypathwaysNormal Cell

Inhibitoryabnormality

Stimulatoryabnormality

Stimulatorypathways

標準教條

致癌基因 抑癌基因

Ref. 2

Activation ofoncogene

Inactivation of tumor suppressor gene

Cell Cycle

失 控失 控

下 坡

下 坡

下 坡 煞 車 失 靈

油 門 全 開

Aberrant cell cycle — accelerated cars without brake Ref. 2

Oncogene (1) Genes for growth factors or their receptors

PDGF Codes for platelet-derived growth factorInvolved in glioma (a brain cancer)

erb-B Codes for the receptor for epidermal growth factorInvolved in glioblastoma (a brain cancer) and breast cancer

erb-B2 Also called HER-2 or neu. Codes for a growth factor receptor Involved in breast, salivary gland and ovarian cancers

RET Codes for a growth factor receptorInvolved in thyroid cancer

Genes for growth factors or their receptors

Ki-ras Involved in lung, ovarian, colon and pancreatic cancers

N-ras Involved in leukemia

Ref. 2

Oncogene (2) Genes for growth factors or their receptors

c-myc Involved in leukemia and breast, stomach and lung cancers

N-myc Involved in neuroblastoma (a nerve cell cancer) and glioblastoma

L-myc Involved in lung cancer

Genes for growth factors or their receptors

Bcl-2 Codes for a protein that normally blocks cell suicide.Involved in follicular B cell lymphoma

Bcl-1 Also called PRAD1. Codes for cyclin D1, a stimulatory component of the cell cycle clock.Involved in breast, head and neck cancers

MDM2 Codes for an antagonist of the p53 tumor suppressor protein. Involved in sarcomas and other cancers

Ref. 2

Tumor Suppressor GeneGenes for proteins in the cytoplasm

APC Involved in colon and stomach cancers

DPC4 Codes for a relay molecule in a signaling pathway that inhibits cell division.Involved in pancreatic cancer

NF-1 Codes for a protein that inhibits a stimulatory (Ras) protein.Involved in neurofibroma and pheochromocytoma (cancers of the peripheral nervous system) and myeloid leukemia

NF-2 Involved in meningioma and ependymoma (brain cancers) and schwannoma (affecting the wrapping around peripheral nerves)

Ref. 2

Tumor Suppressor Gene

Genes for proteins whose cellular locations is not yet clear

BRCA1 Involved in breast and ovarian cancers

BRCA2 Involved in breast cancer

VHL Involved in renal cell cancer

Genes for proteins in the nucleus

MTS1 Codes for the p16 protein, a braking component of the cell cycle clock. Involved in a wide range of cancers

RB Codes for the pRB protein, a master brake of the cell cycle. Involved in retinoblastoma and bone, bladder, small cell lung and breast cancer

p53 Codes for p53 protein, which can halt cell division and induce abnormal cells to kill themselves. Involved in a wide range of cancers

WT1 Involved in Wilms’ tumor of the kidney

Ref. 2

基因突變地圖在各種癌症中發現超過百種以上的突變基因癌化理論 → 標準教條：細胞循環中，正常促進細胞形成基因 o 過度活化 ，變成致癌基因；而抑制細胞形成基因 o 發生突變，失去功能 X ，成為抑癌基因

A Subway Map for Cancer Pathways

Ref. 2

標準教條

第四站癌化的四個理論

Ref. 2

修 正 教 條

修 正 教 條 在癌化前期的細胞基因組當中，累積的隨機突變有顯著的增加，終於影響到癌症相關基因

Ref. 2

早期不穩定理論

早期不穩定理論 其餘兩個理論專注在非整倍體所扮演的角色，也就是染色體上大規模的變異

早期不穩定理論認為細胞分裂的主控基因受致癌物質影響而關閉，造成子代細胞染色體數目異常

Ref. 2

全盤非整倍體理論：非整倍體細胞的基因組非常不穩定，使得癌症基因極易發生突變而形成腫瘤

Ref. 2

癌症是一種基因的疾病然而癌症的複雜情況，卻不能用簡單的「基因突變」來描述。最近理論認為，染色體的異常可能才是細胞邁向癌症之路的第一步。

隨染色體起舞Ref. 2

正常 癌 症

Ref. 2Normal & Cancer Chromosomes

Field Cancerization (1)

Patch phase

Precursor lesionsdevelop within field

Carcinoma excised,field and precursorlesion remains

Expandingfield phase

Field

Second field tumordevelops fromprecursor lesion

Precursor lesionsbecomes carcinomaand new precursorbecomes develop

Epithelium

Connective tissue Basal layer withstem cells

第五站 :

Genetic altered

Ref. 7

Carcinoma

11q

Field Cancerization (2)

FieldPatch

Histological Proof

Chromosomal Proof

p armq arm

centromere

Normal

17p 3p, 9p, 8p, 18q

Ref. 8

癌細胞的第一種魔鬼能力第六站 : 癌細胞的六種魔鬼能力 Ref. 2

癌細胞的第二種魔鬼能力第六站 : 癌細胞的六種魔鬼能力 Ref. 2

癌細胞的第三種魔鬼能力第六站 : 癌細胞的六種魔鬼能力 Ref. 2

癌細胞的第四種魔鬼能力第六站 : 癌細胞的六種魔鬼能力 Ref. 2

Angiogenesis Factors (1)

Tumor island

Ref. 3

Angiogenesis Factors (2)

Newly-formedvessels

Tumor cellsNormal vessels

Ref. 4

Angiogenesis Factors (3)

Normal epithelium Dysplasia

Early localizedtumor

Advanced invasive

tumor

Normal vesselNewly-formed vesselTumor-lined vessel

Ref. 4

癌細胞的第五種魔鬼能力第六站 : 癌細胞的六種魔鬼能力

藍

p armq arm

centromere

Ref. 2

Consequences of teleomere lossin tumor cells

Teleomere( 末端粒腺體 )Normal

Mutant

Chromosomeinstability Chromosome

imbalances

Geneamplification

Tel

eom

ere

Fusions breakages

Duplicationof 16q: iso16qTrisomy 16qMonosomy 16q

Ref. 10

Regulation of Teleomeres –Alterative Length of Teleomere

(ALT), Teleomerase or BothGrowth Massive Apoptosis Immortalization

Teleomeresshorten

Teleomeresare critically short

Repeated cell divisions

Gen

om

ic I

nst

abil

ity

3. Teleomerase & ALT ?

2. Telomerase

Teleomeresare regulated

by1. ALT

Ref. 10

Immunohistochemical Staining of Teleomerase Reverse Transcriptase (h-TERT)

Brown colorstained dots

Cancertissues

Ref. 11

癌細胞的第六種魔鬼能力第六站 : 癌細胞的六種魔鬼能力

Ref. 2

Causesand Prevention

第七站

What Causes Cancer?

Chemical-environment

Virus

The top two causes - tobacco and diet-account for almost two thirds of all cancerdeaths and are amongst most correctable

PAPILLOMA VIRUS is asignificant cause of cancer

Ref. 1

Most Oral Carcinoma in Taiwan is Associated with Betel Quid

Ref. 12

Lancet Oncology 2001; August

印度檳榔包裝

Ref. 6

Lancet Oncology 2003; October

印度的檳榔攤

Ref. 5

Carcinogens in Work Place (1)

砷

石棉

Ref. 1

Carcinogens in Work Place (2) Ref. 1

Genes and Cancer Risk

基因警察

DNA修補基因

Ref. 1

Food

Strategiesfor MinimizingCancer Risk

Causes of currentcancer mortalityRealistic population goals for reduced cancer mortality

Risk factors

Estimated number of deaths in US (thousands per year)

100,000 to 125,000 current deaths

Simple, realistic preventive measurescould save hundreds of thousands of livesevery year in developed countries alone

Realistic Goals for Reducing Cancer Mortality Ref. 1

Chemopreventionof CancerSomeday people should be able toavoid cancer or delay its onset by takingspecially formulated pills or foods

Ref. 1

Chemoprevention 的原理

Healthy cell

Differentiation cell

Genetic mutationsthat can lead

to cancer

Processes that leadto excessive proliferation genetically damaged cells

Cancer cellDamaged cell(precancer

cell)

Programmed deathof altered cells(Apoptosis)

Ref. 1

BRCA1

Chromosome 17

A family search for BRCA1 mutation

Earlier Detection Earlier DetectionAdvances inCancer DetectionTests to look for the presence of a tumor before any symptoms appear may save more lives than new drug therapies do

Ref. 1

Some Family Causing Syndromes

Syndrome Cancers GeneDNA Testing cost

Ref. 1

Slide is prepared from Humphrey’s urine sample taken in 1967

Section of cancer is taken from Humphrey’s bladder surgically removed in 1967

Copies of DNA aremade from PCR

Mutant DNAprobe

Probe bind to mutant DNA

Probe for the mutation is constructed

DNA is purifed and p53 gene is sequenced

Gel showsmutation (red arrow) in p53 gene

Normal DNA

Mutant DNA

DNA is placed on nylon membrane

生物晶片

美國副總統—韓福瑞Diagnosing Hubert H. Humphrey

27 Years Later (2004)

Ref. 1Example of Early Detection

Mammograms CT scan

Liver

Hepatoma

Breast

Advances inTumor Imaging

Advances inTumor Imaging

New tools yield a three-dimensional viewinside the body and automated adviceon interpreting the anatomical landscape

Ref. 1

Advances inTumor Imaging

Advances inTumor Imaging

Positron Emission Tomography

Ref. 1

Immunotherapy/Stem Cell Therapyfor Cancer

Immunotherapy/Stem Cell Therapyfor Cancer

Orange: Stroma Green: Colon cancer cell

Antibodies recognizes specific cells and can be used to find and selectively destroy tumor cells

Ref. 1

Fighting Cancer by Attacking Its Blood Supply

Inhibition of NOS enzymes by NOS inhibitor

Relatively lower level of NO produced by SCC facilitates angiogenesis & tumor dissemination

NO

NOS inhibitor

NO

Before therapyBefore therapy After therapyAfter therapy

NOS inhibitor

NOS inhibitor

NO: nitric oxide NOS: nitric oxide synthase

Ref. 1

Summaries瞭解以下各點：1. How cancer arise2. Stages of carcinogenesis3. 癌化的標準教條4. 四種癌化理論5. Field cancerization6. 癌細胞的六種超能力7. 癌症的預防