History Of Cancer

Front 1

Hippocrate

Back 1

Cancerous growth=moving crabs

Front 2

Galen

Back 2

Sarcoma

Front 3

Necrosis

Back 3

Oribaslus

Front 4

Lanfran

Back 4

Benign and Malignant tumors

Front 5

Bonetti Terms: Pappilomatosis

Back 5

skin elevation

Front 6

carcinomatosis

Back 6

metastasis

Front 7

milliary spread

Back 7

distant metastasis

Front 8

carcinoma dropsy

Back 8

malignant ascites

Front 9

strumatosia

Back 9

lymphoma

Front 10

carcinoids

Back 10

small carcinoma.

Front 11

Recaimer

Back 11

coined metastasis

Front 12

Home

Back 12

Characterized leukemia

Front 13

Lebert

Back 13

characterized myeloid tumors

Front 14

Henry bench jones

Back 14

Characterized myeloma

Front 15

Boveri:

Back 15

Did sea urchin experiments

Chromosome affect cancer.

Front 16

• Cell cycle checkpoint

Back 16

o Cells somehow defective o Reacts differently to its surroundings.

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TSG

Back 17

o Chromosome that inhibits cell division

Front 18

Oncogene

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o Chromosome that causes proliferation

Front 19

malignant progression

Back 19

o Benign tumors can progress to malignant tumors

Front 20

• Clonogenicity

Back 20

cancers arise from a single cell

Front 21

warburg effect

Back 21

changes in metabolism

Front 22

inflammation

Back 22

may lead to cancer.

Front 23

neoplasm

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new growth

Front 24

hyperplasia

Back 24

increase in size of an organ (physiological, compensatory, pathological)

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metaplasia

Back 25

adaptive subsititution of one type of adult tissues for another

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desmoplasia

Back 26

formation and proliferation of connective tissue

Front 27

dysplasia

Back 27

abnorma cellular proliferation, loss of nomrla architechture and orientation

Front 28

anaplasia

Back 28

dedifferentiation of cells.

Front 29

TGFB

Back 29

signals to halt cell cycle, inhibit proliferation, differnetiate, and if needed apoptosis.

Front 30

matrigel

Back 30

see if the cells form tight structures or break off

Front 31

boyden chamber

Back 31

measure chemotactic movement

migrate across membrane

Front 32

VEGF FGF measurement

Back 32

angiogenic factors, used to detect angiogenesis.

Front 33

Angiogenic Assays

Back 33

Clonogenic assay (measure cell survival)

Caspase assay (detects presence of caspase by looking for products of its protease cleavage)

DNA fragmentation (tunel reagent binds to broken up DNA, fluoreseces, like in DNA from apoptosis)

Annexin V (high conserved protein, only on inside due to phosphatidly serine, it flips during apoptosis due to PS switching to the outisde of the membrane)

Front 34

3 components of epidemiology

Back 34

Uncover new etiological lead

Efficacy of preventative measures

Investigate survival predictors

Front 35

GWAS

Back 35

Genome wide association study: looks at tons of markers in the genome to find certain varients that trend to cancer.

Front 36

5 criteria for cuase effect relationship

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Timing

Strength

Interaction with other factors

prevelance (multiple populations)

Plausability

Front 37

HSC Cell surface markers

Back 37

CD34+

CD38-

CD59+

CD90+

CD117/Ckit+

lin-

Front 38

How to characterize leukemia cells

Back 38

Morphology

Histochemical stains

Clel surface markers for flow cytometry

Gene expression profiles

Karyotype (quantitative and qualitative)

Front 39

Causes of ALL

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Hyper/hypodiploidy (best, mainly kids)

BRC-Abl (bad, main one in adults)

MLL rearrangements (bad)

Front 40

Risk factors of ALL

Back 40

Gender (1.3x more male)

Younger

Higher socioeconomeit

In utero radiation

Genetic sydrome (like Downs)

Front 41

Greaves hypothesis

Back 41

• Greaves hypothesis, two mutations required. o One in utero, one out of utero.

Patents who don't go to daycare are more likely to get disease.

Front 42

AML1 ETO

Back 42

C8-C21 translocation

Silences AML1 gene. Which is needed for differentiation

needs proliferation mutation too to cause leukemia

Front 43

Gleevac

Back 43

Used to treat CML (ablbcr fusion)

pauses cancer, does not kill it.

small fraction of genetic mutation wont respond to first gen gleevac, need second gen gleevac.

Front 44

3 types of developments

Back 44

Observational (hey these people get cancer)

empirical (hey this causes cancer in labs)

epidemiolocial (hey this population tends to have this disease)

Front 45

Miller hypothesis

Back 45

most if not all chem carcinogens consiste of or can become an electrophile, which reacts with a nucleic acid or protein.

Front 46

Non miller carcinogens

Back 46

nongenotoxic carcinogens.

Front 47

Friedwald and rous

Back 47

Painted mice with 3MC got cancer, initiated cells. added turpentine (chloroplastic agent) or wounding, lead to tumor development.

Front 48

Murine two stage carcinogenesis protocol

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stage one: put carcinogen dose on back. wait, nothing happens. put a promoter on (continually treat for a while) get papillomas, sometimes get SSC.

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Initiator

Back 49

genotoxic

initiation creates the genotoxic changes needed for cancer to form. Promotion merely activates those changes. Promotion alone wont cause cancer. Needs to be on initiated cells.

Front 50

promoter

Back 50

nongenotoxic

Nongenotoxic Epigenetic Affect gene regulation, not the genes themselves

They don’t have to be carcinogens on their own. Don’t necessarily cause cancer Complete carcinogens do have promoting activity. Do both promotion and initiation

Front 51

3 types of common skin cancer in US

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SCC

BCC

Melanoma

Front 52

Dosage of carcinogen

Back 52

greater dose, more likely cancer.

Front 53

are carcingens =

Back 53

no!

Front 54

Procarcinogens

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Pro carcinogens are carcinogens that haven’t yet been activated/put into a carcinogen form. P450 and phase 1 phase 2 molecules are used to catabolize molecules in the cell. Lots of factors: location of cells, individual person. Lots of variety.

Front 55

Phase I and Phase II molecules:

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Phase II enzymes mask the functional group. Conjugate Phase I modify

Front 56

term that causes differntial sensitivity to things within a species/different species

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polymorphism

Front 57

why stem cells?

Back 57

Live for a long time and are phenotypically vauge. Normally rarely divide.

Front 58

Protooncogenes, TSG and two stage model

Back 58

Protooncogenes and tumor suppressor genes both need to be effected in order for cancer to occur. Need to accumulate a lot of mutations in these both.

Front 59

Screening and cancer

Back 59

Doesn't always save lives, can cause mental stress, detect cancer that isn't fatal, detect cancer early that wouldve been detected later and could have been treated fine.

Front 60

Tumor cell targets:

Back 60

o Growth factors

Extracellular matrix

Angiogenic pathways o Cell survival pathways • mTor o signaling pathways • Ras, MAPK o Tumor associated antigens • Targets for drugs. o Proteasome

Front 61

5FU

Back 61

block dTMP synthesis by blocking thymidine synthase. dUMP analogue, deletes enzyme activty and can kill stop dna replication.

Front 62

Bevacizumab

Back 62

Binds to VEGF, inhibits it. prevents angiogensies

Front 63

axtinib

Back 63

RTK

Binds further down RTK, affet angiogenic growth factors

antitumor due to lack of blood vessels and tumor necrosis.

Front 64

Oxygen and cancer

Back 64

Too much or too little. hypoxic areas don't allow drug in. tumor is dormant there. radiation and other drugs need oxygen to work.

radiation can kill some cells, which relieves oncotic pressure, and decreases cell tumor size.

blood flow can be viewed by DCE MRI (dynamic contrast mri)

Front 65

function of protein interactions

Back 65

amongst others, leads to transcription

Front 66

protooncogenes

Back 66

normally promote normal growth

mutated, become oncogenes

Front 67

Vertical Transfer

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MMTV

Front 68

No oncogene in the virus, but activates an oncogene

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MMTV, Leukemia Viruses

Front 69

acute transforming tumor retrovisures

Back 69

rare, capture genes with oncogenes, need helper virus to replicated, cellular genes might prmote growth of transduced cells

Front 70

HIV

Back 70

increases cancer by reducing immune system

Front 71

RNA viruses

Back 71

Leukemia viruses I and II

HIVI

Front 72

Oncogene types

Back 72

viral and cellular

Front 73

Mutation leading to RAS oncogene

Back 73

GTPase activity inhibition, constituitively bound GTP

Front 74

CMyc

Back 74

• Oncogene • Burkitts lymphoma: csome translocations activate it. • Insertion of retrovirus LTR causes c-myc overexpression • C-myc isn’t altered though, just its expression i.s

Front 75

Example oncogenes

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Cmyc, Csrc, RAS, BCLT

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viral oncogenes

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• Oncogene of viral origins • Vsrc o Viral, can be inserted into cell o Rous sarcoma virus in chicken o Oncogene (not proto) o Related to Csrc, but without activation section.

Front 77

cellular oncogenes

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• Cellular orgins • C-src. o Protooncogenes. o Can be mutated to be overexpressed or have increased activity.

Front 78

Somatic mutations

Back 78

o Consistent observations, changes in somatic cells. o Burkitts lymphoma • Translocation which activates oncogene o Ras oncogene, put in mic fibroblasts, cause tumors • Causes cancer in humans o Follilculatr lymphomas, • BCL2 oncogene always defregulated by trasnlocations on the gene o Activated human oncogenes cause corresponding tumors in transgenic mice. • Genes mutate in human cancer, make transgenic mice, causes cancer.

Front 79

Oncogenes

Back 79

o Promote proliferation o Dominant, highly conserved o Types • Viral • Cellular

Front 80

TF

Back 80

trasncription facotr: regulate genes, increase/decrease expression, incresae and decrease oncogene transcription

Front 81

Chromatin remodelers

Back 81

move chromatin, effect expression epigenetically

Front 82

growth factors

Back 82

• Auto and paracrine • Too much growth factor, increases growth. • Changes in receptors that are responsible for carrying signals. • Change in receptor, change in signaling

Front 83

cell cycle regulators

Back 83

regulate cell cycle! haha

Front 84

apoptosis regulators

Back 84

cell s must die, if disrupted they wont, if they survive they can become cancerous.

Front 85

TSG Concept

Back 85

• Brief concept: o Can go over full lecture, possibly add something: we’ll summarize later in the lecture. • A type of gene that makes a protein called tumor suppressor protein that helps control cell growth. Mutations (changes in DNA) in tumor suppressor genes may lead to cancer. o AKA anti-oncogene.

Front 86

TSG examples

Back 86

Rb, P53, APC, BRCA1/2, (read notes on all)

Front 87

Mechanisms of TSGs

Back 87

And what TSG does what

Front 88

Supression of cell division

Back 88

APC, Rb, P53, P21

Front 89

Induction of apoptosis

Back 89

APC, P53, FasR, pTen

Front 90

DNA damage repair

Back 90

FA/BRCA, P53

Front 91

Inhibition of metastasis

Back 91

metastatin