Path I - Midterm Mcneil

Front 1

why is adaptation necessary?

Back 1

cells and tissues must adapt or respond to changes in their environment or die

Front 2

what could cause alterations in the cell or tissue environment

Back 2

- physiological processes
- pathological processes

Front 3

what do adaptation responses depend on?

Back 3

- cell type
- capacity for divison

Front 4

what happens if the cell is unable to adapt to a mild stimulus?

Back 4

sub-lethal damage (ex: fatty change)

if stimulus increases can become irreversible damage (ex: necrosis)

Front 5

what happens if the cell is unable to adapt to a severe stimulus?

Back 5

irreversible damage (ex: necrosis)

Front 6

what are the 3 types of cells?

Back 6

- permanent
- stable
- labile

Front 7

describe permanent cells

Back 7

non-replicating and non replaceable

ex: neurons, cardiac muscle, skeletal muscle

Front 8

describe stable cells

Back 8

normally non-dividing but have the capacity for proliferation (conditionally dividing)

ex: hepatic and renal parenchymal cells (regeneration), fibroblasts (repair)

Front 9

describe labile cells

Back 9

constant cell renewal by a precisely orchestrated sequence of cell replication, differentiation and death

ex: cutaneous and intestinal epithelia

Front 10

list adaptive processes

Back 10

1- increased cellular activity
2- decreased cellular activity
3- change in cell type or position
4- increase in cell size (hypertrophy)
5- increase in cell numbers (hyperplasia)
6- decrease in cell size and/or in cell number (atrophy)
7- change of one adult cell type into another (metaplasia)
8- change of cell orientation (dysplasia)

Front 11

define hypoplasia

Back 11

usually restricted to the failure of an organ to attain full size during embryological development

Front 12

when do hypertrophy and hyperplasia occur

Back 12

as a response to increased functional demand

Front 13

when does atrophy occur?

Back 13

as a response to decreased functional demand

Front 14

when do metaplasia and dysplasia occur?

Back 14

can occur in response to chronic injury

Front 15

list the characteristics of hypertrophy

Back 15

- increased tissue/organ size due to increase in size of individual cells
- adaptive response to increased functional demand or hormonal stimulation
- simple form mainly seen in tissues composed of cells that do not readily divide (ex: striated muscles)
- in stable and labile cell populations, hypertrophy can occur together with hyperplasia (# of cells)

Front 16

types of hypertrophy

Back 16

- physiological hypertrophy
- pathological hypertrophy
- drug-induced hypertrophy

Front 17

when can physiological hypertrophy occur

Back 17

- response to workload (mechanical hypertrophy)
- response to hormones

Front 18

give examples of responses to workload

Back 18

- skeletal muscle in a weight lifter
- cardiac muscle in an athlete (horse, human...)

Front 19

give examples of responses to hormones

Back 19

- mammary gland during pregnancy/lactation
- uterus during pregnancy

Front 20

causes of pathological hypertrophy

Back 20

- increased workload
- excess hormones

Front 21

examples of increased workload causing pathological hypertrophy

Back 21

- cardiac hypertrophy due to valvular damage/distortion and altered blood flow
- thickening of bladder wall muscle due to urinary outflow obstruction
- remaining kidney after nephrectomy (compensatory hypertrophy)

Front 22

examples of excess hormones causing pathological hypertrophy

Back 22

hyperthyroidism in cats -> cardiac hypertrophy

Front 23

explain drug-induced hypertrophy (i.p. hepatomegaly)

Back 23

induction of enzymes and/or proliferation of various cell organelles leads to increased cell size

Front 24

list examples of drug-induced hypertrophy

Back 24

- induction of mixed oxidase systems in SER (smooth endoplasmic reticulum) of hepatocytes by phenobarbitol and alcohol
- proliferation of mitochondria in rat hepatocytes by methapyriline (an antihistamine)

Front 25

list the characteristics of hyperplasia

Back 25

- increased tissue/organ size due to increased numbers of individual cells
- occurs in response to increased functional demands or hormonal stimulation
- more common than hypertrophy
- may result in increased function
- controlled reversible process that occurs in response to a stimulus and stops when stimulus is removed
- regulated by cytokines, growth factors, protooncogenes and tumor suppressor genes

Front 26

list the types of hyperplasia

Back 26

- due to hormonal stimulation
- compensatory/reactive hyperplasia
- pathological hyperplasia
- feline multinodar thyroid hyperplasia
- canine cystic endometrial hyperplasia
- chronic proliferative cystitis (polypoid cystitis)

Front 27

give examples of hyperplasia due to hormonal stimulation

Back 27

- estrogen can cause hyperplasia of breast epithelium
* normal at puberty and during pregnancy
*pathological in males due to endogenous (sertoli cell tumour) or exogenous estrogens

- testosterone can cause prostatic hyperplasia
* common pathology of older individuals
* affects men and dogs

Front 28

when does compensatory/reactive hyperplasia occur

Back 28

occurs in response to loss of tissue

Front 29

list examples of compensatory/reactive hyperplasia

Back 29

- proliferation of basal layer of epidermis in response to skin abrasion
- proliferation of hepatocytes in response to loss/removal of part of the liver (regeneration to normal size within 2 weeks in rats following partial hepatectomy)
- proliferation of red blood cell precursors following severe blood loss

Front 30

what can pathological hyperplasia result in?

Back 30

diffuse or localised (nodular) enlargement of an organ

ex: thyroid hyperplasia

Front 31

describe thyroid hyperplasia (goitre)

Back 31

- deficiency of maternal iodine
- diffuse hyperplasia (and hypertrophy) of neonatal thyroid follicular epithelial cells
- symmetrical thyroid enlargement

Front 32

describe feline multinodular thyroid hyperplasia

Back 32

- common lesions in aged cats
- often functional and result in clinical hyperthyroidism
- atrophy of contralateral gland
- cause unknown: suggested may be due to wide variation in iodine intake over prolonged periods

Front 33

describe canine cystic endometrial hyperplasia

Back 33

- common uterine change in the bitch
- occurs mostly during diestrus (i.e. under the influence of progesterone after estrus)
- may provide suitable environment for bacteria or be secondary to uterine infection

Front 34

describe chronic proliferative cystitis

Back 34

- mucosal hyperplasia due to chronic irritation by bacterial infection or uroliths (calculi)
- seen mostly in the bitch

Front 35

list the characteristics of atrophy

Back 35

- decrease in tissue mass after achieving normal growth
- due to decreased cell number and/or decreased cell size
- regressive change usually due to gradual and continuous injury
- implies reduced function

Front 36

list the types of atrophy

Back 36

- physiological
- pathological
- nutritional
- due to other causes

Front 37

what is another name for physiological atrophy

Back 37

involution

Front 38

list the characteristics of physiological atrophy

Back 38

- reduced numbers of cells
- usually by apoptosis

Front 39

list examples of physiological atrophy

Back 39

- thymic involution following sexual maturity
- uterine involution following decrease in hormone levels at parturition
- mammary gland involution at the end of lactation

Front 40

list causes of pathological atrophy

Back 40

- disuse
- denervation
- pressure

Front 41

list an example of atrophy from disuse

Back 41

muscle atrophy in a fractured limb

Front 42

list an example of atrophy from denervation

Back 42

muscle fibre size decreases following loss of innervation

Front 43

list examples of atrophy from pressure

Back 43

prolonged pressure will compromise blood supply and lead to cell degeneration and necrosis
ex: pressure "bed" sores
mass lesions i.p. within skull

Front 44

list causes of nutritional atrophy

Back 44

- starvation
- cachexia

Front 45

give examples of problems resulting in starvation

Back 45

- malnutrition
- malabsorption
- parasitism
- mis-mothering

Front 46

define cachexia

Back 46

physical wasting caused by disease i.p. neoplasia

Front 47

list other causes of atrophy

Back 47

- loss of endocrine stimulation
- infection
- chronic inflammation
- post-inflammatory atrophy

Front 48

list examples of loss of endocrine stimulation

Back 48

- adrenal atrophy (zona fasciculata) following prolonged corticosteroid administration (negative feedback)
- involution of uterus after overioectomy

Front 49

list examples of infection

Back 49

- bacterial (atrophic rhinitis in pigs)
- viral (intestinal villous atrophy from parvovirus in dogs)

Front 50

what could be reasons for fat atrophy in necropsy

Back 50

- anorexia
- starvation
- cachexia

Front 51

list examples of serous atrophy of fat found in necropsy

Back 51

- atrophic lipocytes
- interstitial edema
- grey, gelatinous appearance grossly

Front 52

list an example of post-inflammatory atrophy

Back 52

testicular atrophy (bovine)

Front 53

list characteristics of metaplasia

Back 53

- usually affects epithelial cells
- altered differentiation results in replacement of a specialised epithelium by less specialised cells
- metaplasia is mostly beneficial but it may be preneoplastic

Front 54

give examples of metaplasia

Back 54

- respiratory (columnated ciliated) epithelium replaced by stratified squamous cells in cigarette smokers [partially protective (squamous cells are more resistant to injury) but protective mucus is lost]

- estrogen toxicity causes squamous metaplasia of prostatic epithelium

- transformation to squamous cell carcinoma in smokers

Front 55

describe metaplasia in connective tissue

Back 55

- one type of CT changes to another
- less clearly adaptive than epithelial metaplasia
- cells respond to changes in microenvironment i.p. oxygen tension

Front 56

list examples of metaplasia in CT

Back 56

- osseous metaplasia in injured soft tissue (like lung)
- bone or cartilage formation in the stroma of some tumours

Front 57

list characteristics of dysplasia

Back 57

- includes abnormal appearance of (usually epithelial) cells which may indicate precancerous change
- response to chronic irritation/infection/stimulation
- term is mostly used for abnormal formation during embryonic development
- in some texts dysgenesis vs dysplasia

Front 58

list examples of responses to chronic irritation/infection/stimulation

Back 58

- cervical dysplasia in women (HPV)
- esophageal dysplasia in cattle (BPV)
- epidermal dysplasia in sun-exposed skin (UV-light)

Front 59

list examples of abnormal embryonic development

Back 59

- retinal dysplasia
- hip dysplasia

Front 60

list examples of failure of normal growth/development (malformation & developmental anomalies)

Back 60

- aplasia
- atresia
- hypoplasia
- dysplasia
- dystrophy

Front 61

define dysplasia

Back 61

abnormal formation during development

Front 62

define dystrohpy

Back 62

abnormal growth due to insufficient nourishment

Front 63

list the characteristics of aplasia

Back 63

- failure of tissue/organ to develop during embryogenesis
- structure in adult may be absent or rudimentary (gonad, kidney, tail, limb)
- failure may be segmented (uterus, intestine)
- best examples in reproductive organs (ex: tail aplasia and malformation of caudal urogenital tract in neonatal fold: urine scalding)

Front 64

list the characteristics of atresia

Back 64

- absence of a normal opening
- may affect orifice or tubular structure
- can cause obstruction

Front 65

examples of organs that are affected by atresia

Back 65

- anus
- intestine
- bile duct

Front 66

list the characteristics of hypoplasia

Back 66

- failure of organ to obtain full size
- implies decreased function
- usually noticed in young animals
- may be congenital
- usually due to events occurring in mid or late gestation

Front 67

list examples of cerebellar hypoplasia due to in utero viral infections

Back 67

- calves: bovine virus diarrhoea virus (pestivirus)
- kittens: feline panleukemia virus (parvovirus)
- lambs: blue tongue virus (orbivirus)
- piglets: swine fever virus (pestivirus)

Front 68

list characteristics of cerebellar abiotrophy

Back 68

- cerebellar cortical degeneration
- due to spontaneous (premature) degeneration of neurons some time after birth
- cause often unknown

Front 69

list presumed caused of cerebellar abiotrophy

Back 69

- specific cytological defect
- genetic basis

Front 70

list an example of cerebellar abiotrophy

Back 70

"Daft Lamb Disease" in Border Leicesters
(previously recorded as cerebellar hypoplasia)

Front 71

list the characteristics of enamel hypoplasia

Back 71

- disruption in enamel formation
- reported in large and small animals
- various possible causes

Front 72

list possible causes of enamel hypoplasia

Back 72

- infection (distemper virus in dogs)
- toxicosis (flurocosis in cattle)
- trauma
- pyrexia
- malnutrition

Front 73

describe enamel hypoplasia in dogs from canaine distemper virus infection

Back 73

affected teeth are prone to plaque & tartar accumulation, bacterial penetration and formation of caries

Front 74

list causes of optic nerve hypoplasia

Back 74

- inherited (i.e. genetic)
- in utero viral infection
- nutritional

Front 75

which species are affected by inherited optic nerve hypoplasia?

Back 75

miniature poodle

Front 76

which species are affected by in utero viral infection causing optic nerve hypoplasia

Back 76

- kittens (FPV)
- calves (BVDM)

Front 77

which species are affected by nutritional optic nerve hypoplasia?

Back 77

calves (maternal avitaminosis A)

Front 78

what is a cause of exocrine pancreatic hypoplasia? which species are affected

Back 78

- idiopathic
- affects calves

Front 79

list characteristics of pancreatic acinar atrophy (PAA)

Back 79

- canine juvenile pancreatic atrophy
- thought to be hereditary (early reports stated hypoplasia rather than atrophy)
- more common in German Shepherd Dogs
- clinical syndrome in which the onset of PAA (and EPI) usually occurs from 6 months to 1 year

Front 80

how is a rudimentary (aplastic) structure differentiated from hypoplastic structure or dysplastic structure?

Back 80

- rudimentary structure lacks normal architecture
- hypoplastic structure has recognizable but incomplete normal architecture
- dysplastic structure has disordered architecture

Front 81

list the developmental anomalies of the kidney

Back 81

- aplasia
- hypoplasia
- dysplasia

Front 82

describe consequences of kidney aplasia

Back 82

- no recognisable renal tissue
- ureter may or may not be present

Front 83

describe kidney hypoplasia

Back 83

- incomplete development
- fewer nephrons than normal

Front 84

describe kidney dysplasia

Back 84

- altered structural organisation
- must be distinguished from contraction and distortion due to fibrosis

progressive juvenile nephropathy in dogs may be dysplasia (often familial, presumed genetic)

Front 85

list characteristics of dystrophy

Back 85

- degenerative disorder caused by inadequate or defective nutrition (ex: osteodystrophies)
- the term is also used for inherited disorders where the tissues degenerate and atrophy

Front 86

list examples of osteodystrophies

Back 86

- rickets
- osteomalacia
- renal fibrous

Front 87

list examples of inherited dystrophy

Back 87

- muscular dystrophies
- neuroaxonal dystrophies

Front 88

describe renal fibrous osteodystrophy in dogs

Back 88

- bone resorption and replacement with fibrous tissues
- hyperparathyroidism secondary to renal disease (response to low Ca)

Front 89

describe muscular dystrophy

Back 89

- progressive weakening and wasting
- may or may not be congenital
- variation in fibre size often the earliest histological indicator
- progressive degeneration -> increased fibrosis
- some forms have been linked to individual protein absence/abnormality

Front 90

define neoplasia

Back 90

uncontrolled new growth

Front 91

list characteristics of neoplasia

Back 91

- grow out with normal growth controls
- have no clear stimulus
- serve no useful function
- may or may not resemble cells of origin
- have no orderly structural arrangement
- may be benign or malignant
- malignant tumours may metastasise
- neoplasms can involve any tissue of the body and have many different forms in each body area
- most tumours are named for the type of cell or organ in which they start
- if a cancer metastasised the new secondary tumour (metastasis) bears the same name as the original primary tumour

Front 92

list types of non-neoplastic mass forming lesions

Back 92

- nodular hyperplasia
- hamartoma (ex: cutaneous)
- choristoma (ex: corneal)

Front 93

describe nodular hyperplasia

Back 93

non-neoplastic overgrowth of tissues in response to a stimulus (will regress if stimulus is removed)

Front 94

describe hamartoma

Back 94

non neoplastic overgrowth of mature tissues which normally occur in that site

Front 95

describe choristoma

Back 95

non neoplastic overgrowth of tissues that do not normally occur in that site
" aberrant rest", "heterotopic tissue"

Front 96

which animals are usually affected by non neoplastic mass forming lesions?

Back 96

common lesions in older animals

Front 97

what causes non neoplastic mass forming lesions

Back 97

usually idiopathic - cause unknown

Front 98

do all neoplasms form swellings?

Back 98

no

ex: invasive carcinoma in bovine hard palate

Front 99

list examples of carcinomas

Back 99

- squamous cell carcinoma in bovine eyelid
- infiltrating carcinoma in bovine oesophagus

Front 100

define carcinoma

Back 100

malignant epithelial tumour

Front 101

define cancer

Back 101

malignant tumour

Front 102

what can be seen on some malignant tumours?

Back 102

crab-like extensions

Front 103

define oncology

Back 103

the study of tumours

Front 104

list cancer facts

Back 104

- cancer is not one disease
- benign tumours are NOT cancer; malignant tumours are cancer
- the frequency of a particular cancer may depend on gender
- cancer frequency does not equate cancer mortality

Front 105

list examples of tumours that depend on gender

Back 105

- skin cancer is the most common type of malignancy for both men and women
- the second most common type in men is prostate cancer
- the second most common in women is breast cancer

Front 106

list examples of cancer frequency not equating mortality

Back 106

- skin cancers are often curable
- lung cancer is the leading cause of death from cancer for both men and women in the US

Front 107

list 2 cancer dogmas

Back 107

- cancer is NOT contagious, although the tendency to develop it may be (ex: papillomavirus infection)

- cancer is NOT hereditary, although the tendency to develop it may be (ex: inherited behaviours), BUT single gene mutations can increase risk
*breast cancer <60% lifetime risk
*colon cancer <100% lifetime risk

Front 108

which factors allow classification as benign or malignant

Back 108

- behaviour
- clinical effect
- gross appearance
- microscopic appearance

Front 109

list examples of benign and malignant liver tumours

Back 109

benign: hepatocellular adenoma (hepatoma)

malignant: hepatocellular adenocarcinoma (hepatic carcinoma)

Front 110

list examples of benign and malignant fibrocyte tumours

Back 110

benign:fibroma

malignant: fibrosarcoma

Front 111

list examples of benign and malignant fat cell tumours

Back 111

benign: lipoma

malignant: liposarcoma

Front 112

list examples of benign and malignant bone tumours

Back 112

benign: osteoma

malignant: osteosarcoma

Front 113

list examples of benign and malignant cartilage tumours

Back 113

benign: chondroma

malignant: chondrosarcoma

Front 114

list examples of benign and malignant muscle tumours

Back 114

benign: myoma

malignant: myosarcoma

Front 115

describe the appearance of fibroma

Back 115

gross: smooth, rounded structure
histo: no invasion of underlying muscle

Front 116

describe the appearance of fibrosarcoma

Back 116

gross: poorly defined, ulcerated mass
histo: irregularly arranged, spindle-shaped cells

can cause pathological fractures

Front 117

describe the appearance of a chondrosarcoma

Back 117

gross: can cause swelling and distortion of affected limb, multiple small nodules of secondary tumour

histo: granular, hyaline surface with haemorrhage. highly cellular, poorly formed cartilage

Front 118

describe the appearance of osteosarcoma

Back 118

gross: increased bone density due to neoplastic osteogenesis

histo: highly cellular mass with osteoid trabeculae

Front 119

tumours of glandular epithelium

Back 119

benign: adenoma
ex: bovine intestinal polyp

malignant: adenocarcinoma
ex: mammary gland bitch

Front 120

tumours of surface/protective epithelium

Back 120

benign: papilloma
ex: canine oral mucosa

malignant: carcinoma

Front 121

malignancy associated with squamous epithelium (ex: skin, oesophagus)

Back 121

squamous cell carcinoma

Front 122

malignancy associated with transition epithelium (ex: urinary bladder)

Back 122

transitional cell carcinoma

Front 123

describe the appearance of adenocarcinomas

Back 123

gross: ulcerated mass

histo: mucus producing cells invading submucosa

Front 124

describe squamous cell carcinoma

Back 124

gross: non-pigmented nodular ulcerated growth

histo: dense fibrous tissue surrounds squamous cell nets (scirrhous carcinoma)

Front 125

describe the appearance of transitional cell carcinoma

Back 125

gross: nodular growth covering surface

histo: abnormal transitional cells replace subepithelial CT

Front 126

list the germ layers epithelia & carcinomas can develop from

Back 126

- sweat gland carcinoma
- pancreatic carcinoma
- renal carcinoma
- ectoderm
- endoderm
- mesoderm

Front 127

what is exceptional about carcinoma development

Back 127

tumours may be composed of more than one cell type or derived from more than one germ layer

ex: mixed mammary tumour - epithelial & CT elements
teratoma (embryonic tumour, totipotential cells) - 3 germ layers

Front 128

describe appearance of a mixed mammary tumour

Back 128

gross: lobulated with cystic and hyaline areas

histo: cystic glandular elements, central bone, cartilage

Front 129

describe appearance of a teratoma

Back 129

gross: various tissue types include small mass of matted hairs

histo: hair follicles in nervous tissue

Front 130

list benign and malignant nomenclature for tumours in the following areas:
- lymphoid organs
- bone marrow (lymphocytes)
- melanocytes
- astroglia

Back 130

benign lymphoid = lymphoma
malignant lymphoid = lymphosarcoma

malignant bone marrow = leukaemia

benign melanocyte = melanoma
malignant melanocyte = malignant melanoma

malignant astroglia = astrocytoma (low grade or high grade)

Front 131

describe the appearance of lymphoid leukemia

Back 131

lymphoblasts seen in blood smear

Front 132

describe the appearance of lymphosarcoma

Back 132

enlarged mesenteric lymph nodes

Front 133

describe the appearance of melanomas

Back 133

gross: small pigmented plaque
histo: clusters of pigmented cells at base of epithelium

Front 134

describe the apearance of astrocytoma

Back 134

ill-defined mass (can distort & compress ventricles in brain)

Front 135

list the characteristics of benign tumours

Back 135

- good differentiation
- growth rate usually slow
- growth type expansion
- metastasis never occurs

Front 136

list the characteristics of malignant tumours

Back 136

- variable differentiation
- growth rate variable, often rapid
- growth type expansion and infiltration/invasion
- metastasis is common

Front 137

how are benign tumours differentiated from malignant

Back 137

no absolute criteria

histological indicators include:
- abnormal mitotic activity
- nuclear hyperchromasia
- poor/abnormal differentiation (dysplasia) absence of differentiation (anaplasia)
- loss of polarity (epithelia)
- invasive growth pattern

Front 138

what is the spectrum of behaviour exhibited by naturally occuring tumours? give examples.

Back 138

- self- limiting (papilloma warts and canine hystiocytoma)
- benign (fibroma and perianal adenoma)
- intermediate (basal cell carcinoma & mast cell tumour)
- malignant (mammary carcinoma & haemangiosarcoma)

Front 139

list the main categories of tumour cell attributes

Back 139

- cell growth
- cell motility
- cell signaling & cell interaction
- cell products
- cell surface alterations
- structural changes

Front 140

elaborate on the cell growth of tumour cells

Back 140

- loss of normal growth control
- loss or reduction of contact
- growth to high density in vitro
- decreased requirements for growth factors

Front 141

elaborate on the cell motility of tumour cells

Back 141

- altered cell motility
- decreased anchorage dependence
- increased contact guidance

Front 142

elaborate on cell signaling & cell-cell interaction of tumour cells

Back 142

- altered adhesiveness
- altered intercellular communication
- changes in intracellular signaling activity

Front 143

elaborate on cell products of tumour cells

Back 143

- enzymes
- hormones
- autocrine secretion of GFs
- tumour antigens (TSAs, TAAs, TATAs)

Front 144

elaborate on cell surface alterations of tumour cells

Back 144

- altered glycoproteins & proteoglycans
- altered cell junctions
- decreased fibronectin
- altered surface charge

Front 145

elaborate on structural changes of tumour cells

Back 145

- altered ploidy
- chromosomal aberrations
- cytoskeletal alterations
- increased histological heterogeneity

Front 146

list the properties of tumour cells which facilitate metastasis

Back 146

- reduced adhesiveness
- increased motility
- increased contact guidance
- production of injurious substances
- translocation survival

Front 147

is there a universal property or marker to distinguish metastatic capability

Back 147

no

Front 148

describe tumour cell populations with regards to metastatic capability

Back 148

tumour cell population is heterogenous in relation to metastatic capability and this changes with time

Front 149

describe the steps of metastasis

Back 149

1- cell detachment
2- invasion of lymphatics and blood vessels
3- transportation
4- arrest
5- penetration
6- invasion and growth

Front 150

list the various routes of tumour spread

Back 150

- via the lymphatic system (epithelial tumours)
- via the blood vascular system (mesenchymal tumours)
- across serous cavities (transcoelomic)
- within epithelia
- along gland ducts
- via cerebrospinal fluid pathways

Front 151

list the factors included by the local effects of neoplasia produced by primary and secondary tumours

Back 151

- compression
- obstruction
- tissue destruction
- organ replacement

Front 152

list the signs included by the local effects of neoplasia produced by primary and secondary tumours

Back 152

- pain
- inflammation
- haemorrhage
- functional deficit
- death

Front 153

what are the systemic effects of neoplasia associated with and due to

Back 153

- mostly associated with malignant tumours
- due to aberrant/excessive cytokine production

Front 154

list the systemic effects of neoplasia

Back 154

- cachexia (wasting syndrome)
- anaemia (haemorrhagic and hypoplastic)
- immuno suppression (esp. lymphoid tumour, viral infection and therapy)

Front 155

which factors and mechanism are implicated in cachexia

Back 155

TNFalpha (cachectin) + other cytokines >> altered fat metabolism, loss of appetite and proteolysis

Front 156

which factors and mechanism are implicated in anaemia

Back 156

IL-1 impaires iron transport >> defect in iron re-utilisation

Front 157

which factors and mechanism are implicated in immunosuppression

Back 157

TGFbeta modulates cellular and humoral immune response; also IFNgamma synergises with TNFalpha

Front 158

describe the products of tumour cells

Back 158

may be:
- normal
- increased
- decreased
- new

Front 159

list the products of tumour cells

Back 159

- cytokines (ex: IL-1)
- growth factors (ex: TGFbeta)
- vasoactive amines (ex: histamine)
- hormones (indiginous and ectopic)

Front 160

list an example of an indiginous hormones

Back 160

insulin from pancreatic islet cells

Front 161

list an example of an ectopic hormone

Back 161

PTH-like peptides from non-parathyroid tissues

Front 162

what can the systemic effects of tumour products result in?

Back 162

paraneoplastic syndrome

Front 163

describe paraneoplastic syndrome

Back 163

- a constellation of clinical findings (physical signs and laboratory findings)
- due to the effect of tumour products (stimulatory & inhibitory)

Front 164

give examples of paraneoplastic syndromes from indigenous hormones

Back 164

- hypoglycaemia (insulin)
- Cushing's syndrome (cortisol)
- hypertension (adrenalin)
- feminisation (oestrogen)

Front 165

give an example of a tumour causing hypoglycaemia

Back 165

insulinoma

Front 166

give an example of a tumour causing Cushing's syndrome

Back 166

adrenocortical adenoma

Front 167

give an example of a tumour causing hypertension

Back 167

phaechromocytoma

Front 168

give an example of a tumour causing feminisation

Back 168

sertoli cell tumours

Front 169

in the case of insulinoma, what to the clinical signs of hypoglycaemia relate to

Back 169

- neuroglycopenia
- sympathoadrenal stimulation (counter-regulatory hormones)

Front 170

list characteristics of neuroglycopenia

Back 170

- lethargy, weakness
- altered behaviour
- syncope, collapse
- seizures, coma

Front 171

list characteristics of symphathoadrenal stimulation

Back 171

- muscle tremors
- nervousness
- restlessness

Front 172

list the characteristics of Cushing's syndrome

Back 172

- clinical syndrome reflecting functional disturbances in multiple organs
- due to hyperadrenocorticism

Front 173

list the characteristics of hyperadrenocosticism

Back 173

- due do endogenous cortisol excess
- or excess exogenous corticosteroids
* glyconeogenesis
* lipolysis
* protein catabolism
* anti-inflammatory

Front 174

list the characteristics of phaechromocytoma

Back 174

- catecholamine release
*adrenalin (epinephrine)
*noradrenalin (norepinephrine)

- sympathetic nervous system hyperactivity
* elevated heart rate (tachycardia)
* elevated blood P
* excessive sweating (diaphoresis)

Front 175

give an example of a paraneoplastic syndrome from an ectopic hormone

Back 175

hypercalcemia

Front 176

list examples of tumours that can cause hypercalcemia

Back 176

- adenoma: PTH-like peptides
- lymphosarcoma: osteoclast activating factor

Front 177

list other paraneoplastic syndromes

Back 177

- gastric ulceration (histamine)
- hypertrophic osteopathy (uncertain hormone)
- neurological disorders (antibody mediated)

Front 178

what can cause gastric ulcerations?

Back 178

indiginous/eutopic inflammatory mediator

ex: from mast cell tumour

Front 179

what can cause hypertrophic osteopathy?

Back 179

prolonged hypoxia?

ex: from pulmonary tumours

Front 180

what can cause neurological disorders?

Back 180

neural Ag expression from pulmonary ca.

Front 181

how can a mast cell tumour cause a peptic ulcer?

Back 181

mast cell tumours > histamine release > stimulation of H2 receptors > hypersecretion of gastric acid > peptic ulcer

Front 182

give the characteristics of hypertrophic pulmonary osteopathy

Back 182

- periosteal proliferation of long bones (begins in metacarpals, metatarsals and phalanges)
- pathogenesis unknown
- occurs secondary to intrathoracic disease (ex: neoplasia, chronic infection like S. lupi, heartworm etc.)

Front 183

how does the host respond to neoplasia?

Back 183

- inflammation
- immune response

Front 184

describe inflammation response to neoplasia

Back 184

- response of tissues to injury/irritation
- characterised by cardinal signs
- essentially a vascular response
- mediated by cytokines

Front 185

what are the cardinal signs of inflammation

Back 185

- redness
- swelling
- pain
- heat
- loss of function

Front 186

describe the immune response to neoplasia

Back 186

- directed against specific agents of injury (antigens)
- humoral response (antibody production)
- cell mediated response (T cells)
- mediated by cytokines

Front 187

list the antitumour effector mechanisms

Back 187

- inflammation (stimulated by tissue injury and non-specific)
- macrophages
- cytotoxic T cells (esp. against virus-associated neoplasms)
- NK cells
- humoral immunity (activation of complement and induction of ADCC by NK cells)

Front 188

elaborate on the role of macrophages as antitumour effector mechanisms

Back 188

- selective cytotoxicity in vitro
- can collaborate with cytotoxic T cells (T cell cytokine IFNgamma)
- secrete TNFalpha
- lytic for several tumour cells

Front 189

elaborate on the role of NK cells as antitumour effector mechanisms

Back 189

- after activation with IL2
- can lyse wide variety of tumours
- can participate in antibody dependent cell-mediated cytotoxicity (ADCC)

Front 190

list characteristics of tumour specific antigens (TSA)

Back 190

- esp. in chemically induced tumours of rodents
- individual tumours may possess unique antigens not shared by other histologically identical tumours, induced by the same chemical, even in the same animal
*may be derived from mutant forms of normal cell proteins > peptide-class 1 complex recognisable as non-self
*altered internal non-binding peptide may bind to MHC > display on cell surface
*generated by activation of normally silent genes ex: melanoma antigen (MAGE-1) in human melanoma and some carcinomas
*novel peptides derived from oncogenes and antioncogenes

Front 191

list tumours associated antigens (TAA)

Back 191

- tumour associated carbohydrate antigens
- oncofetal (embryonic antigens)
- differentiation specific antigens

Front 192

elaborate on tumour associated carbohydrate antigens

Back 192

- abnormal glycoproteins and glycolipids

ex: blood group antigens, epithelial mucins

Front 193

elaborate on oncofetal antigens

Back 193

- alpha-feto protein AFP
- carcinoembryonic antigen CEA

Front 194

elaborate on differentiation of specific antigens

Back 194

- related to the particular stage of differentiation at which the cancell cells are arrested

ex: CD10 in early B lymphocytes and in B cell leukemia/lymphoma

Front 195

list characteristics of prostate specific antigens (PSA)

Back 195

- produced by normal and neoplastic prostatic epithelial cells
- level in blood increases with age
- increased levels may reflect prostatic disease
- the higher the level the more likely it is to be cancer
- used as an aid to diagnose and to monitor therapy

Front 196

elaborate on potential immunosurveillance

Back 196

- increased occurrence of certain tumours in immunodeficient hosts
- but largely limited to :
~ B cell lymphomas (EBV)
~ papillomas (HPV)
~ Kaposi's sarcoma (KSHV)
(viral cofactors involved in tumour development)
- increased incidence of the most common forms of cancer might be anticipated in immunodeficiency but this does NOT occur

Front 197

list the mechanisms developed by tumour cells to escape or evade the host immune response

Back 197

- antigen negative variants
- reduced levels of HLA (MHC) class 1 molecules
- down regulation of other integrins
- tumour products may be immunosuppressive (ex: TGFalpha)

Front 198

list methods of immunotherapy

Back 198

- adoptive cellular therapy
- cytokine therapy
- antibody-based therapy ("magic bullets")

Front 199

list characteristics of adoptive cellular therapy

Back 199

- PBL (peripheral blood leukocytes) incubated with IL2 > LAK (lymphokine activated killer cells derived from NK cells)

- TIL (tumour infiltrating lymphocytes) incubated with IL2 > expanded/activated population
Can also be transfected with gene for TNFalpha
- incubated with

Front 200

what is adoptive cellular therapy used for

Back 200

used for therapy of renal carcinoma in humans (highly immunogenic)

has led to further studies ex: with dendritic cells, vaccines

Front 201

describe cytokine therapy

Back 201

- alone or in combination (ex: IL2, IFNalpha, IFNgamma, TNFalpha)
- IFNalpha
> activates NK cells
> increases expression of MHC molecules
> is directly cytotastic

Front 202

describe antibody-based therapy using "magic bullets"

Back 202

antibodies are used to deliver toxins (immunotoxin)

ex: mAb against B-cell lymphoma conjugated with ricin

Front 203

list traditional cancer treatment methods

Back 203

tumour removal or ablation via:
- surgery
- cryosurgery
- electrocautery
- radiotherapy

Front 204

describe chemotherapy

Back 204

interferes with DNA structure or replication via:
- antimetabolites
- alkylating agents, platinum compounds
- anthracyclines
- microtubule-targeting agents (alkaloids)
- topoisomerase inhibitors

Front 205

how do antimetabolites interfere with DNA structure/replication

Back 205

compete or interfere with normal purine/pyrimide synthesis

Front 206

how do alkylating agents/platinum compounds interfere with DNA structure/replication

Back 206

chemically modify DNA

Front 207

how do anthracyclines interfere with DNA structure/replication

Back 207

intercalating agents

Front 208

how do microtubule-targeting agents interfere with DNA structure/replication

Back 208

interfere with cell cycling (spindle poisons)

Front 209

how do topoisomerase inhibitors interfere with DNA structure/replication

Back 209

interfere with transcription and replication

Front 210

list novel cancer treatments

Back 210

- hormonal therapy
- immunotherapy

Front 211

list examples of hormonal therapy

Back 211

- corticosteroids > apoptosis
- anti-oestrogens, androgens

Front 212

describe how immunotherapy works and list examples

Back 212

antibody targeted to tumour-specific cell surface protein

- herceptin (transtuzumab) targets HER-2 which is overproduced in some breast cancers
- avastin (bevacizumab) targets VEGF which is required for new blood vessel formation

Front 213

what does HER-2 stand for?

Back 213

human epidermal GF receptor 2

Front 214

what does VEGF stand for

Back 214

vascular endothelial growth factor

Front 215

what cancer therapies are being developed?

Back 215

- gene therapy: successful treatment of metastatic melanoma
- virotherapy: experimental viral engineering & oncolytic viruses

Front 216

describe oncolytic viruses

Back 216

- able to infect and lyse cancer cells but leave normal cells unharmed
- adenovirus, herpes simplex, Newcastle disease virus

Front 217

define epidemiology

Back 217

study of disease in populations (patterns, causes, control)

Front 218

define epidemic/epizootic

Back 218

an outbreak of disease in a population/locality

Front 219

define endemic/enzootic

Back 219

disease always present to a greater or lesser extent in a particular population/locality

Front 220

define incidence

Back 220

number of new cases in population at risk over given period

Front 221

define prevalence

Back 221

number of existing cases in population at risk over given period

Front 222

list the epidemiology of cancer

Back 222

- incidence of most cancers increases with age
- incidence of different cancers varies between populations and geographical areas
- inherited predisposition has a major role in rare syndromes

Front 223

what information is provided by the fact that the incidence of most cancers increases with age?

Back 223

supports the theory that development of cancer requires a series of mutational changes (multistep carcinogenesis)

ex: peak incidence of canine lymphoma is at 10 years although disease may occur in young animals

ex: prior to widespread vaccination, peak incidence of feline lymphoma was in younger (2-6 yr) FeLV Ag+ve cats

Front 224

list the tumour type and carcinogen associated with the farmer/fishermen profession

Back 224

skin cancer from UV light

Front 225

list the tumour type and carcinogen associated with the radiologist profession

Back 225

skin cancer from soft radiation X rays

leukemia from hard radiation X rays

Front 226

list the tumour type and carcinogen associated with the asbestos miner profession

Back 226

mesothelioma from asbestos

Front 227

list the tumour type and carcinogen associated with the woodworker profession

Back 227

nasopharyngeal adenocarcinoma from wood dust

Front 228

list the tumour type and carcinogen associated with the rubber/dye worker professions

Back 228

bladder cancer from naphthylamine

Front 229

list the tumour type and carcinogen associated with the polymerisation-chamber cleaner profession

Back 229

liver angiosarcoma from vinyl chloride monomer

Front 230

list the timeline of Pott's tumour

Back 230

-1775 Percival Pott reports scrotal cancer in young chimney sweeps
- 1915 Yamagiwa & Ichikawa induce cancer in rabbits using coal tar
- 1932 Cook & others report first cancer induction by pure chemical
- 1940+ many compounds demonstrate carcinogenic activity

new era of research begins on structure-activity relationships and molecular biology of cancer

Front 231

list an example of a pollution associated tumour in small animals

Back 231

squamous cell carcinoma

Front 232

where do squamous cell carcinomas occur

Back 232

- tonsil (dog)
- tongue (cat)
- oesophagus (cat)

Front 233

the nasal cavity of which animal often gets various pollution associated tumours?

Back 233

dog

Front 234

list examples of cancer incidences that vary between geographical areas

Back 234

- cattle cancer from environmental carcinogens and papilloma viruses in Kenya and Brazil

- toxicity from bracken fern in alimentary cancer

Front 235

list the various etiologies of cancer

Back 235

- exogenous factors
> chemical
> physical
> biological

- genetically determined factors
- most cancers have a multifactorial causation

key factor is altered cellular DNA

Front 236

list chemical carcinogens

Back 236

- aromatic hydrocarbons
- aromatic amines (dyes)
- N-nitroso compounds (processed meats)
- epoxides (adhesives)
- organohalogen compounds (solvents, plastics)
- hydrazines (jet fuel)

Front 237

list the chemicals contained in aromatic hydrocarbons

Back 237

- benzene
- benzanthracene
- benzopyrene

Front 238

list the chemicals contained in aromatic amines

Back 238

- benzidine
- aniline
- o-Anisidine
- o-Toluidine

Front 239

list the chemical contained in N-Nitroso compounds

Back 239

N-nitrosodimethylamine

Front 240

list the chemicals contained in epoxides

Back 240

- ethylene oxide
- propylene oxide

Front 241

list the chemicals contained in organohalogens

Back 241

- vinyl chloride
- carbon tetrachloride
- chloroform
- hexachlorobenzene
- trichloroethylene

Front 242

list the chemicals contained in hydrazines

Back 242

- hydrazine (and salts)
- 1,2-dimethylhydrazine

Front 243

list carcinogens in plants

Back 243

- aspergillus (aflatoxin B)
- betel nut (various alkaloids)
- bracken fern (quercetin & ptaquiloside)
- tobacco (various alkaloids)

Front 244

list physical carcinogens

Back 244

- ionising radiation (X-ray)
- UV light

Front 245

describe the effects of X-ray radiation

Back 245

- depurination
- single, double strand breaks

Front 246

describe the effects of UV light

Back 246

- UVA: oxygen radicals > oxidative damage (esp. guanine)

- UVB: pyrimidine dimers (ex: in the p53 tumour suppressing gene)

Front 247

describe the various historical events relating radiation and cancer

Back 247

- early investigators exposed to X-rays/radionuclides died of cancer (Roentgen, Curie)
- survivors of atomic bomb (Hiroshima, Nagasaki) and nuclea reactor disasters (Chernobyl) display increased cancer incidence (CML, thyroid cancers)
- experimental exposure of rodents confirms carcinogenic potential of radiation
- UV light is an important cause of skin cancer (melanoma, squamous cell carcinoma)

Front 248

which animals get UV light associated skin tumours affecting the eyelids and cornea

Back 248

ox, horse, sheep

Front 249

which animals get UV light associated skin tumours affecting the vulva

Back 249

cow

Front 250

which animals get UV light associated skin tumours affecting the muzzle

Back 250

sheep, dog

Front 251

which animals get UV light associated skin tumours affecting the ear

Back 251

cat, sheep

Front 252

which animals get UV light associated skin tumours affecting the ventral abdomen

Back 252

dog

Front 253

what type of tumours are associated with UV light

Back 253

generally squamous cell carcinoma but also haemangioma and haemangiosarcoma (in man: basal cell carcinoma and melanoma)

Front 254

list carcinogenic biological agents

Back 254

- viral
- bacterial
- parasitic

Front 255

list examples of viral carcinogenic agents

Back 255

- FeLV
- BLV
- BPV
- HPV

Front 256

list examples of bacterial carcinogenic agents

Back 256

- helicobacter pylori
- lawsonia intracellulare

Front 257

list examples of parasitic carcinogenic agents

Back 257

- spinoverca lupi
- opisthorchis viverrini

Front 258

list the characteristics of viruses and cancer

Back 258

- viruses from several families can cause cancer
- viruses can be direct or indirect causes of cancer
- viruses are generally inefficient cancer agents

Front 259

list virus families that can cause cancers

Back 259

- retroviruses
- herpesviruses
- paova/papillomaviruses

Front 260

explain direct and indirect viral causes of cancer

Back 260

- directly oncogenic viruses induce a heritable change in the cancer cell
- indirect mechanisms include immune suppression (HIV)

Front 261

list retroviruses causing cancer in animals

Back 261

- birds (avian leukosis virus & Rous sarcoma virus)
- mice (mouse mammary tumour viruses & murine leukemia virus)
- cats (feline leukemia virus)
- monkeys (simian foamy virus, simian retrovirus type D)
- cattle (bovine leukemia virus)
- humans (human immunodeficiency virus and human T-lymphotropic virus)
- sheep (Maedi-Visna virus & Jaagsiekte sheep retrovirus)
- fish (walleye dermal sarcoma virus)

Front 262

list characteristics of bacteria & parasites as causes of cancer

Back 262

- carcinogenesis is indirect
- persistent infection/infestation will lead to chronic inflammation and release of immunosuppressive factors
- products of infectious agent or metabolism may be mitogenic or mutagenic or may disrupt cell-signaling pathways

Front 263

list characteristics of inflammation as a cause of neoplasia

Back 263

- clinical observations support the view that chronic inflammation can predispose an individual to the development of cancer
- developing tumours induce a local and/or systemic chronic inflammatory environment associated with enhanced tumour development and metastasis
- common denominator is immunosuppression

Front 264

list examples of clinical observations relating chronic inflammation to cancer development

Back 264

- subcutaneous silica deposits in rats
- vaccine/adjuvant related sarcoma in cats
- inflammatory bowel disease and colon cancer in humans

Front 265

list examples of immunosuppression from inflammation

Back 265

- TCR, down regulation
- impaired T-cell and NK cell function

Front 266

give an example of how inherited predisposition has a major role in rare cancer syndromes

Back 266

Knudson proposed simple genetic model for retinoblastoma
- sporadic retinoblastoma
> children genetically normal at birth
> require 2 somatic mutations for tumour development

- familial retinoblastoma
> children carry 1 (inherited) mutation from conception
> retinal cells "primed" for tumour development
> only 1 additional mutation required

(disease often occurs as multiple foci in both eyes)

Front 267

which genetic factors are analysed to improve cancer risk assessment

Back 267

- ras activation
- Kinase pathway
- Rb phosphorylation
- E2F release
- cell cycle progression
- apoptosis

Front 268

list inherited syndromes (hereditary DNA repair disorders) with increased cancer susceptibility

Back 268

- xeroderma pigmentosum
- ataxia telangiectasia
- bloom's syndrome

Front 269

list characteristics of xeroderma pigmentosum

Back 269

- sensitive to UV radiation
- early development of skin cancers in affected individuals
- inherited defect in nucleotide excision repair (NER)
- general mechanism of NER in humans has been based upon analyses of NER-defective individuals with XP

Front 270

explain nucleotide excision repair

Back 270

- NER is the major process for removal of structurally diverse lesions from DNA
- in human cells a major function is removal of UV induced DNA photoproducts causes by sunlight:
> photoproduct recognition
> assembly of the excision complex
> displacement of the excised fragment
>polymerization of the replacement patch

Front 271

list examples of DNA repair disorders

Back 271

- HNPCC
- BRCA1 and BRCA2 mutations"

Front 272

explain HNPCC

Back 272

"hereditary non-polyposis colorectal cancer

strongly associated with specific mutations in the DNA mismatch repair pathway

Front 273

explain implication of BRCA1 and BRCA2 mutations

Back 273

2 famous mutations conferring a hugely increased risk of breast cancer on carriers, associated with a large number of DNA repair pathways, especially non-homologous and joining (NHEJ) and homologous recombination

Front 274

list breed disposition to neoplasia and familial tumours

Back 274

- bull mastiff: lymphosarcoma
- Bernese mountain dog: malignant histiocytosis
- German Shepherd: haemangiosarcoma
- Boxer: various
- Giant breeds: osteosarcoma

Front 275

list the components of the cell cycle

Back 275

- G1: interval between mitosis and DNA replication - characterized by cell growth
- S phase: synthesis - replication of DNA
- G2: interval during which growth and preparation for cell division occurs
M phase: mitosis - production of 2 daughter cells

Front 276

list characteristics of the control of the cell cycle pRb

Back 276

- restriction point
- majority of cells exit to G0 at this point
- once past this point the cell is committed to the mitotic cycle
- progression depends on
>the presence of mitogens (ex: growth factors)
> inactivation of the retinoblastoma protein (pRb)
- controlled by inhibitiors of cyclin dependant kinases (CDKs)

Front 277

list characteristics of the control of the cell cycle p53

Back 277

- verify accurate completion of previous stage (i.e. monitor DNA integrity)
- consequences of DNA damage are:
> succesful DNA repaire
> programmed cell death (apoptosis)
- controlled by p53 and mediated by cell cycle inhibitors

Front 278

list the steps of cell proliferation

Back 278

1- GF binds to receptor
2- active receptor > active signal transducing proteins (NB transient)
3- signal transmission via second messengers
4- induction and activation of nuclear regulatory factors initiate DNA transcription > cell division

Front 279

list the theories about the molecular basis of cancer (nonlethal damage induces heritable change)

Back 279

- epigenetic theory: aberrant differentiation i.e. altered expression of normal genes, loss of controlling factors (no irreversible genetic change)
- genetic theory: mutation hypothesis, alterations in regulatory or structural genes
- unified theory (oncogene hypothesis): abnormal expression of cell growth control genes

Front 280

list characteristics of oncogenes

Back 280

- oncogenes are modified (i.e. mutant or over-expressed) versions of normal cellular genes (proto-oncogenes)
- oncogenes act dominantly to promote cancer development
- activated by
*point mutations
*chromosomal translocations
*gene amplification
*viruses
- directly responsible for neoplastic transformation of cells
- originally discovered in transforming viruses (v-onc)
- derived from normal regulatory genes of cells: proto-oncogenes
- cellular oncogenes subsequently discovered which are unrelated to viruses (c-onc)

Front 281

list characteristics of tumour-suppressor genes

Back 281

- act recessively to restrict tumour development
- are inactivated in cancer cells

ex: gatekeepers control aberrant proliferation (p53 & Rb)
ex: caretakers (DNA repair genes)

Front 282

cancer is a multi-step process

Back 282

- rate of increase in cancer incidence with age is complex: modelling suggests 6-7 "hits" for common cancers of solid tissue
- tumour karyotypes are often complex, with multiple chromosomal aberrations
- animal models display distinct phase of carcinogenesis: initiation, promotion, progression
- transgenic models display synergystic effects of mutation affecting oncogenes and tumour suppressor genes

Front 283

what happens when normal skin of rodent models is exposed to dimethyl benzanthrancene (DMBA) initiator

Back 283

papilloma

Front 284

what happens when a papilloma on a rodent model is exposed to phorbol ester (tumour promoter)

Back 284

carcinoma

Front 285

list the stages in chemical carcinogenesis (without detoxification or repair)

Back 285

1- metabolic activation of carcinogen
2- electrophilic intermediates
3- binding to DNA (adduct formation)
4- permanent DNA damage (= initiated cell)
5- cell proliferation
6- altered differentiation
7- neoplastic cell

Front 286

list the types of DNA damage produced depending on the type of mutagen

Back 286

- oxidative damage
- intercalation
- cross linking

Front 287

list characteristics of oxidative damage

Back 287

- ex: free radicals or hydrogen peroxide
- base modifications (esp. guanosine) and double-strand breaks
- estimated that in each human cell, about 500 bases are damaged per day
- the most dangerous lesions are double stranded breaks: difficult to repaire and can produce point mutations, insertions and deletions as well as chromosomal translocations

Front 288

list the characteristics of intercalation

Back 288

- intercalators are mostly aromatic and planar molecules (nexopyrene, accidines and aflatoxin)
- base pairs are separated, distorting DNA strands by unwinding the double helix. These structural changes inhibit transcription and DNA replication

Front 289

describe what causes cross-linking

Back 289

alkylating agents and high energy electromagnetic radiation

Front 290

list an example product, gene and mechanism of growth factors as a molecular basis of cancer

Back 290

- PDGFbeta
- sis
- overexpression

Front 291

list an example product, gene and mechanism of growth factor receptors as a molecular basis of cancer

Back 291

- EGF receptor
- erbB1
- over expression

Front 292

list an example product, gene and mechanism of signal transduction proteins as a molecular basis of cancer

Back 292

- GTP binding (guanosine di/tri phosphate)
- ras
- point mutation

Front 293

list an example product, gene and mechanism of nuclear regulator proteins as a molecular basis of cancer

Back 293

- transcriptional activators
- myc
- translocation (amplification)

Front 294

list characteristics of proto-oncogene c-ras (involved in signal transduction)

Back 294

- mutation of this gene is the most common abnormality of dominant oncogenes found in human tumours
- normal ras proteins have a flip "switch" function
- activation leads to GDP>GTP conversion
- plus intrinsic GTPase>>GTP>>GDP augmented by GTPase activator (GAP)
- failure of this "brake" leads to persistent mitogenic signalling

Front 295

list characteristics of proto-oncogene c-myc (nuclear regulator gene)

Back 295

- orchestrates DNA replication and cell division
- expressed in virtually all eukaryotic cells - an early growth response gene
- signale to divide >> rapid induction and transient increase in c-myc RNA
- c-myc protein rapidly transported to nucleus
*forms a complex (heterodimer) with max
*binds to specific DNA sequences
*activates transcription of growth related genes
- overexpression >> continuing signal for transcription

Front 296

list characteristics of tumour suppressor genes p53: a normal regulator/modulator of cell growth

Back 296

- "molecular policeman" "guardian of the genome"
- prevents propagation of genetically damaged cells
- accumulated p53 binds to DNA causing arrest in G1 phase of growth cycle
- allows time for DNA repair
- if repair fails apoptosis is triggered

c-myc: activation leads to apoptosis unless:
*sufficient growth factors are present
*bcl-2 "rescues" the cell

Front 297

list characteristics of p53 and lung cancer

Back 297

- primary carcinogens (initiating agents) are mutagenic
- 60% of human lung cancers contain mutations in the p53 tumour suppressor genes
- mutant p53 protein accumulates in tumours of the lung (as it does in other tumours)
- carcinogens in tobacco smoke product DNA adducts (addition products)
- the "target" has now been confirmed as the p53 gene
*preferential formation of benzopyrene adducts at lung cancer mutational hotspots in p53
*study provides a direct link between a defined cigarette smoke carcinogen and human cancer mutations

Front 298

list characteristics of DNA repair and cancer

Back 298

- DNA repair limits mutagenic damage
- DNA repair functions are encoded by multiple genes which encode components of multi-enzyme complexes
- DNA repair deficiencies predispose to cancer
* autosomal recessice
*"premature" aging syndromes

Front 299

list examples of premature aging syndromes

Back 299

- xeroderma pigmentosum
- ataxia telangiectasia - ALL/lymphoma (ATM gene)
- Bloom's syndrome - various cancers

Front 300

list examples of canine DNA repair genes

Back 300

- ERCC2 (nucleotide excision repair)
- MSH2 (mismatch repair)
- POLB (base excision repair)
- MRE11 (non-homologous end-joining)
- WRN (homologous recombinational repair)

Front 301

explain the functions of ERCC2

Back 301

- encodes CPD helicase
- essential for NER and p53-mediated apoptosis

Front 302

what roles does MRE11 have?

Back 302

- associated with ataxia telangiectasia in humans
- has a role in the maintenance of telomere length

Front 303

- list the attributes of tumour cells

Back 303

- abnormal cell growth
> activation of oncogenes
> inactivation of tumour suppressor genes

- abnormal differentiation
> altered gene expression

Front 304

list the cell functions affected by altered gene expression

Back 304

- cell motility
- cell signaling and cell-cell interaction
- cell products
- cell surface alterations
- structural changes

Front 305

list the role of inflammatory cells and angiogenesis in tumour progression

Back 305

- tumours often infiltrate by bone-marrow derived inflammatory cells
- some of these cells (monocytes/macrophages) are "educated" by the tumour cells to promote angiogenesis, lymphangiogenesis and tumour cell invasion
- the pro-inflammatory enzyme COX-2 is expressed by inflammatory cells and has a tumour-promoting function

Front 306

list molecular cancer diagnosis methods

Back 306

- immunostaining markers
> p53 accumulation
> telomerase
> replication markers ex: MCM2

- PCR
> markers of clonal identity
> chromosomal breakpoints
> TCR/Ig rearranging genes

- microarrays
> gene expression profiling

Front 307

list novel cancer therapies

Back 307

- gene therapy
- selective inhibitors of activated oncogenes
- oncolytic viruses

Front 308

give an example of gene therapy and explain how it works

Back 308

enzyme (ex: HSV-TK) delivered by viral vector
activates prodrug in tumour

Front 309

list examples of selective inhibitors of activated oncogenes

Back 309

- tyrosine kinase (Bcr-Abl) inhibitor (ex: ST1-571 in CML)
- protease inhibitors
- telomerase inhibitors

Front 310

list examples of oncolytic viruses

Back 310

- adenovirus (p53 nulls cells)
- herpes simplex virus mutant (replicating cells)

Front 311

explain the potential "anti-cancer" virus

Back 311

- mutant adenovirus lacks protein to shut down p53
- unable to infect healthy cells
- infects and destroys p53 defective cells (ex: cancer cells)

Front 312

list characteristics of DNA repair and cancer therapy

Back 312

- cancer therapy procedures such as chemotherapy and radiotherapy work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death
- cells that are most rapidly dividing (most typically cancer cells) are preferientially affected
- the side effect is that non-cancerous but rapidly dividing cells such as stem cells in the bone marrow are also affected
- modern cancer treatments attempt to localize the DNA damage to cells and tissues only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body)

Front 313

list characteristics of regulation of apoptosis and therapeutic implications

Back 313

- succesful tumour therapies depend largely on induction of endogenous apoptotic pathways
- bcl-2 family of proteins block apoptosis (including apoptosis resulting from radio or chemotherapy)
- restoration of wild-type p53 is predicted to restore ability of tumour cells to respond to therapy