Cancer Flashcards
(106 cards)
1
Q
Define neoplasia
A
Abnormal mass of tissue, growth exceeds that of normal tissue, which persists in same excessive manner after the cessation of the stimulus which has evoked the change
2
Q
Describe hyperplasia
A
Abnormal increase in no of normal cells in normal arrangement of tissue/organ which stops growing when the stimulus is removed
3
Q
Define anaplasia/undifferentiation
A
Loss of differentiation of cells so cells of origin are unknown
4
Q
Define tumour differentiation
A
Description of how alike cancer cells are to normal cells- helpful in predicting how tumour will behave
Cells well diff and resemble tissue of organ- better prognosis
5
Q
Histogenesis
A
Identification by cell or tissue of origin
6
Q
Describe benign tumours
A
Don’t infiltrate other tissues
Not always harmless- brain- increase intra cranial pressure
7
Q
Describe malignant tumoura
A
Tumours can infiltrate and invade adjacent tissue and spread (via lymph and blood) to distant sites forming separate metastases-invasive and destructive behaviour
Potentially fatal
8
Q
Describe epithelial tumours
A
Epi tumours- common due to high turnover rate and exposure to outside environment- GI, resp tract cells
9
Q
Define adenomas
A
Tumour of glandular epithelium eg colonic/thyroid
10
Q
Define papillomas
A
Tumour of squamous and transitional epi eg
squamous cell, transitional cell
11
Q
List the main mesenchymal tissues
clue: suffix- osarcoma
A
Osteoma- bone Lipoma- adipose tissue Chondrosarcoma- cartilage Leiomyosarcoma- smooth muscle Rhabdomyosarcoma- striated muscle Fibroma- fibroblasts
12
Q
List tumours that don’t follow rules
A
Germ cell tumours- from germ cells in ovaries and testes Teratomas- from germ cells- 3 germ layers Lymphoma Glioma Melanoma- melanocytes Embryonal tumours Leukemia- haemopoeitic cells in bm Neuroendocrine tumours Hodgkin's Kaposi's Wilm's
13
Q
Define cellular pleomorphism
A
Variation in size/shape of tumour cell
14
Q
Define nuclear pleomorphism
A
Variation in size/shape of nuclei of tumour cells
15
Q
Define nuclear hyperchromatism
A
Dark staining nuclei due to an increase in nuclear DNA
16
Q
Define high mitotic count
A
Increase of no cells in mitosis, including abnormal mitotic forms
17
Q
Define dysplasia
A
Abnormal cell structure due to the above
18
Q
Define carcinoma in situ
A
Dysplasia in an epithelium without invasion across the epi basement membrane
19
Q
List 6 criteria of a malignant tumour
A
High mitotic count High nucleus to cytoplasm ratio Nuclear hyperchromatism nuclear/cellular pleomorphism Abnormal mitoses Diff varies
20
Q
Outline the role of dysplasia and carcinoma in situ in malignancy
A
Dysplasia in tumour cells- invasive behaviour
Dysplasia in epi without invasion- CIS
CIS assoc with hi grade dyplasia and many forms of invasive carcinoma originate from CIS
cancer precursor
21
Q
List the main routes of metastatic spread in malignant tumours
A
Blood stream
Lymphatics
Serosal surfaces
22
Q
Describe lymphatic spread of malignant tumours
A
MT invades lumen of lymph vessel, bits break off and pass to LN draining the area
Become trapped in subscapular sinus, tumours prolif until whole LN is replaced by tumour
23
Q
Describe the bloodstream spread of malignant tumours
A
Tumour invades wall of small vessel-caps and small veins
Clumps of tumour cells break off, move in circ until meet vessel too small to pass through
Grow- distant metastases
Common sites- liver, brain, CSF, lungs, adrenals and bone
ALSO SEROSAL SURFACES
24
Q
Bad effects of benign tumours
A
- bleeding eg gut, bladder
- pressure on adjacent vital structures eg in brain
- obstruction eg in brain, bronchus
- hormone secretion eg pituitary adenoma
- conversion to a malignant tumour
25
How do malignant tumours cause death
Non metastatic effects
| Cachexia
26
List the main techniques used in the investigation and diagnosis of tumours
S&S- clinical history, exam
Imaging- CT, MRI, Xray
Tumour markers- Substances liberated by tumours detected in body fluids
Biopsy- fix in Formalin- histology staining and immunucytochemistry
Glutaraldehyde- electron microscopy
Send fresh for cytogenetics or tumour genetics
Smear- diagnostic cytology, exam of cell in tissue fluid/exfoliated from surface
27
Define tumour stage
Description how much cancer has spread
takes into account size, degree of local penetration, regional lymphatics, spread by distant metastases
Important indicator of prognosis and treatment
28
Two clinical examples of tumour stage
Breast cancer- TMN- tumour, node metastases
Duke's staging for colorectal cancer
A- in muscles more than 90% survival for 5 years
B through muscles 70%
C nodes involved 30%
29
Define the tumour grade and outline how this is determined in practice
Degree of differentiation of tumour cells, relative to normal tissue of origin
Assessed by mitotic indiex and plemorphism
30
Give 3 examples of tumour markers
HCG- tumours with trophoblast elements
AFP- liver, cell tumours
PSA- prostate specific antigen- prostate carcinomas
31
List the main modes of therapy for tumours
Radiotherapy
Chemotherapy
Surgery
Multimodal therapy
32
Outline the main cellular targets for tumour therapy
EGF receptors
| Herceptin targets these receptors in breast cancer
33
Give examples of tumours with good prognosis
Thyroid
34
Give examples of tumours with moderate prognosis
Kidney, prostate, cervix, breast
35
Give examples of tumours with poor prognosis
Pancreas, brain, oesophagus
36
What is cancer?
Disease caused by uncontrollable division of abnormal cells in a part of the body
37
What sort of mutations cause cancer?
Somatic
38
What are familial syndromes?
Pts inherit predisposition to cancer
39
Describe the features that define a cancer cell
```
Proliferation- grow w/o signals
Immortality- avoid senescence/telomere shortening
Avoid cell death- apoptosis
Angiogenesis- must be fed
Metastasis- many activities needed
```
40
Describe the prinicipal of a multi hit, multi step cancer progression
Sequential mutations give cell clones a growth advantage
41
Define passenger and driver mutations
Passenger- not relevant to cancer
| Driver- reg prolif, apop etc
42
List cell cycle checkpoints
Regulate progression through cell cycle
1. Restriction point in G1
2. DNA damage checkpoints in G1 and 2
3. Metaphase checkpoint in M
43
Describe the phenomena of senescence and apoptosis
Limit no of times cell can divide
Senescence- cells in G0 don't prolif
Apoptosis- programmed cell death in response to DNA damage, cell damage, stress
Restrict tumour growth, overcome in cancer
44
Describe senescence
Metabolically active, irreversible inability to enter cell cycle
Normal cells reach Hayflick limit of proliferative capacity, stop dividing-- senescnece
Cancers avoid this
Telomeres undergo shortening
Cells bypass if p53 is inactivated
Telomeres lost, chromose instability, sis chromatids fuse, torn apart at anaphase
Cells undergo apoptosis
45
Describe TERT
In cancer, rare cell reactivates TERT to become cancerous
| Most cancers have activating mutations in the TERT gene promoter
46
Describe how cancer cells evade senescence
50 cell divisions, telomeres too short, p53 fails, continue shortening, chromosomes rearranged, TERT reactivated, cells continue to proliferate with severely damaged chromosomes
47
Describe apoptosis
Avoids inflam using caspases
Triggered by cell damage/DNA stress/oncogene activation
p53 and RB control prolif, sen and apop
48
Describe renewed angiogenesis
O2 and nutrients needed for survival
Tumours promote angiogenesis
- Hypoxia induced factor 1 alpha
- cancers produce VEGF- new vessel growth and endo precursor cells in bone marrow, travel to tumour
- Disorganised vasculature, imbalance of factors
- Leaky due to impaired cell/cell junctions
49
Describe the main stages of tumour metastasis
```
Cells grow as benign tumour in epi
Break through basal lamina
Invade capillary (1/1000 survive when travelling in bs)
Adhere to bv in liver
Escape from bv-extravasion
Proliferation-metastasis in liver
```
Invasion of leaky bv
Activated of endogenous metalloproteinases
50
What causes loss of adhesion?
E cadherin
51
List the two main ways that cell growth occurs
Individual level- change in mass/vol
| Proliferation- increased cell no (population) via clonal generation, exponential binary fission
52
List the main stages of the cell cycle
G1- increase in cell mass
S- 7.5 hours, semi conservative rep of DNA
G2- prolif- 3.5-4 hrs
Mitosis- 1 hour- genome sep into 2 groups for daughter cells
G1- continued prolif and decision to exit cell cycle- 10hrs
G0- quiescence, cell decides whether to go to cell cycle or not
53
Describe the M checkpoint
Cell monitors spindle formation and kinetochore attachment
54
Describe the G2/M checkpoint
Cell monitors size and correct copy of DNA
55
Why do cells enter G0?
To differentiate and specialise into non proliferative cell types eg skeletal, SM, cardiac
- If limited resources
exponential growth- no competition, unlimited resources
sigmoid curve- stabilised by available resources and competition
56
List the three stages of resuming the cell cycle
Competency
Re entry
Progression
57
Describe a cell's re entry back into the cell cycle
```
PDGF and FGF stimulate TFs c-cos c-jun and c-myc. These are all competency factors and immediate early genes. (G1a)
TFs transcribe proteins CYCLIN D and EZE which stimulate the cell to go into re entry.
(delayed response) (G1b)
progression factors (eg insulin) finally cause the cell to reenter G1
```
58
Which cyclins are expressed where in the cell cycle
DE in G1 cdk 6 and 4
A in S cdk2
B in M and G2 cdk1
59
What is the role of CDK1
| What does its activity depend on
Regulate entry into mitosis
Association with cyclin B
60
How is cdk1 destroyed?
By proteolysis (ubiquitination) during cell cycle, stops cell activity, allowing cell to exit mitosis and enter G1
61
How is cdk1 regulated
- By inhibitory phosphorylation of tyrosines 14 and 15 by wee1
- And by partial activatory phosphorylation by CAK
- Activity of CKI (cyclin dependent kinase inhibitors)
62
Define oncogenes
Promote tumour formation, +ve reg of cell cycle
Many needed for normal progression and are proto oncogenes when normal
When no longer need signal to become activated- become oncogenic
63
List some proto oncogenes and their viral version
c- Jun, c-myc, c-fos
| V-fos, v-jun, v-myc
64
What are the activators of oncogenes?
Mutation
Gene amplification
Translocation
65
Define tumour supressor genes
Negative regulators of cell cycle, prevent progression
| Usually TFs or regulators of TF eg pRB
66
Where was pRB first identified?
| What occurs to pRB in tumours?
Childhood cancer, initial changes occur in the retina- retinoblastoma
Mutated in nearly all cancers, inactivated/absent in more than half
67
list the three checkpoints where the integrity of the genome is monitored?
G2/M- p53 activated- arrest. G1/S- environment favourable?
Metaphase/Anaphase- are all chroms central and attached to spindle
Trigger anaphase and proceed to cytokinesis
68
Describe the meaning of proto oncogenes and tumour suppressor genes
Proto oncogenes- promote events leading to cancer reg prolif
| Tumour suppressor- inhibit events events leading to cancer, reg prolif, immortality, apoptosis
69
What type of mutations are associated with TS and PO?
TS- loss of function
| PO- gain of function
70
What are the main types of mutations associated with loss and gain of function?
Loss- point, deletion, frameshift, loss of allele
Gain- amplification, regulatory regions change
Point mutations, fusions, non silent changes in aa sequence
Fusions- telomere shortening- hybrid gene
71
Name three familial syndromes and describe one in detail
2 hit hypothesis
Retinoblastoma- rare childhood tumour, thickening of optic nerve due to tumour extension
Tumour arises in precursors of photoreceptors
Treat by radiotherapy and surgery
Colon cancer
Breast cancer
Phenotype of mutant Rb id dominant at level of whole organism
Recessive at cellular level
Characteristic of TS genes
72
Describe how TS genes are associated with loss of heterozygosity in tumours
Highly unlikely that both genes copies inactivated by two successive mutational events
2nd mutation- diff process with higher frequency
eg mitotic recombination
- LOH for region containing the Rb gene
- Cells lacking functional Rb, advantage
73
How do TS Rb and p53 act?
Rb- G1/S- require growth signals to pass
| p53- G1/S, G2/M
74
What is true about familial cancer and oncogene mutations?
Oncogone mutations rarely associated with familial cancer
Not tolerated in germ line- dominant
Disrupt normal embryonic development
75
List the two main causes of cancer
Carcinogens
| Infectious agents
76
List infectious agents and the cancers they cause
1. H Pylori- cure with antibiotics- stomach cancer
2. HepB virus- inflammation and genes- acute- hepatitis, chronic- liver cancer
3. HPV- oncogenes E6 and E7- cervical cancer
EBV- oncogene- glandular fever, nasopharyngeal cancer (with malaria)
4. HIV- immune suppression- Kaposi's sarcoma
77
Other mechanisms that cause cancer
Inflammation- viruses, asbestos
Immune suppression- HIV
Food, chemicals
Intrinsic causes- tissue growth- kids, hormones- breast, prostate
78
What is caused by a mutation in p53, breast cancer
p53- Li Faraumini syndrome
| BRCA1, BRCA2- breast cancer
79
List the current cancer screening programmes
- Breast- X ray based mammography- carcinogenic
- Cervical- pap smear, liquid based cytology
- Colon- faecal occult blood test- use colonscopy- detects 4-5 more polyps/virtual/sigmoidoscopy
80
List the main cancer treatment therapies
Surgery, radiotherapy, chemo
Targeted therapies
- Radio- hi energy radiation targets tumour- fractionated/brachytherapy
- Conformational radiotherapy- beams matched to same shape as tumour
81
Describe mitotic catastrophe
Dividing cells initially survive, continue to progress through cell cycle despite breaks in DNA
Genome more damaged until due
Free radicals gen during therapy can also damage other components eg cell membrane proteins- trigger apoptosis
82
Describe the use of chemotherapy
Target cancers you can't see
Mitomycin- streptomyces- cross link DNA
Bleomycin- streptomyces- break DNA strands
Etopside- Mayapple- topoisomerase inhibitor
Vincristine- bind tubulin subunit, block division
83
List some targeted therapies
- Antibodies- herceptin, EGFR, breast cancer
- Small mol inhibitors- Abl, leukemia, BRAF, melanomas
Synthetic lethality
Angiogenesis inhibitors
84
Describe cancer prevention
Immunisation- HPV/hepatitis
Lifestyle- smoking, UV, processed meat
Prenatal genetic diagnosis
85
How do tumours develops?
Imbalance between rate of cell division and cell death
| Growth control mechanisms regulate this
86
What are growth control mechanisms?
Levels of secreted growth factors/inhibitors
Environmental growth inhibitory factors
Intrinsic programme of diff/apoptosis
Tumour immune response
87
Give an example of increased growth factor secretion
IGF2 upreg in Wilm's tumour
88
Give an example of upreg of growth factor receptor
cErbB2 (EGFR fam) upreg in breast cancer
89
Give an example of activation of gf receptors
Mutation in TK domain of c-kit in GISTs
90
Give an example of upreg of anti apoptotic factors
Bcl2 upreg in follicular lymphomas
91
Give an example of loss of function of pro apoptotic factors
TP53 mutated in colorectal tumours
92
Give an example of down reg of pro apoptotic factors
Caspase 3 down reg in colorectal tumours
93
How can knowledge of these factors be used in clinical practice
- Identify mutations characteristic of tumour type, use in diagnostic test
- Identify genetic subgroups with a morphologically uniform group of tumours
- Identify new prognostic factors eg n-myc in neuroblastoma
- Identify mutations which predict response to specific treatments
- Identify therapeutic targets
94
Define chemical causatives and list 3
Chemicals grouped depending on mechanism by which they stimulate neoplasia
- Genotoxic
- Mitogenic
- Cytotoxic
95
Outline genotoxic causatives
Cause direct damage to DNA
Form adducts, abnormal segment of DNA bound to cancer causing chemicals- start carcinogenesis
Prone to damage in replication, some resistant to normal DNA repair mechanisms
96
Outline mitogenic causatives
Not direct damage to DNA
bind to receptors in/on cell, stim cell division
eg SKIN CARCINOGENESIS- agents bind to protein kinase C- sustained epidermal hyperplasia
97
Outline cytotoxic causatives
Produce tissue damage- hyperplasia, cycles of tissue regen and damage
Cytokines generated in response
98
Describe the difference between direct and indirect agents
Direct- directly cause neoplasia eg cyt p450
| Initiating agents- exposure doesn't directly cause neo,promoting agents cause increased cell division
99
Describe the role of the following in human tumours:
- Polycyclic hydrocarbons
- Aromatic amines
- Nitrosamines
- Alkylating agents
- Diet and exercise
- Infection
1- from tars, cig smoke-- lung cancer
2. from dyes/rubber--urothelial carcinoma
3. from dietary nitrates--stomach/GI tract cancer
4. from environ, chemo-- mutagenic
5. Viral- Slow/acute transforming- viral oncogene
100
List examples of pre-neoplasia
Endometrial hyperplasia/epi of breast lobules/ducts
Chronic gastritis/colonitis
Hepatic cirrhosis
Chronic autoimmune diseases
101
Define lymphoma and give a simple classification
Neoplastic proliferation of lymphoid cells of various types
- HL and non HL
102
List the types of Hodgkin's Lymphoma
Nodular lymphocyte- good prognosis
Lymphocyte rich Hodgkin’s (GOOD)
Mixed cellularity Hodgkin’s (IN BETWEEN)
Nodular sclerosing Hodgkin’s (IN BETWEEN)
Lymphocyte-depleted Hodgkin’s (BAD)
103
List features of Non Hodgkins Lymphoma
and define myeloma
Majority are malignant
B most common in adults- poor diff, high grade
T cell lymphomas affect skin
Tumour of mature plasma cells. Presents with bone tumours, osteolytic, painful
104
Name three glial cells and the one that most commonly gives rise tu tumours
ASTROCYTOMAS- malignant, don't metastasise
oligodendrocytes
ependymal ce;;s
105
Define embryonal tumours and give two examples
EMBRYONAL TUMOURS are derived from embryonic remnants of primitive “blast’ tissue.
Nephroblastoma-Wilm's of kidney
- Neuroblastoma- adrenal gland
106
Define teratoma and give 2 examples
are tumours derived from primitive germ cells which retain the capacity to differentiate along all 3 primitive embryological lines
- OVARY- young women- benign, cystic, cont keratin, skin hair, bronchial
- TESTIS- young men, swelling, MALIGNANT, spread early via bs, lung liver, chemo,
