G&D- Cancer Flashcards
1
Q
NAME 4 Types of (tissue) disorders: (can be developmental or due to a response from a certain stimulus)
A
- Too much (e.g. tissue)?
- Too little
- Wrong type
- Wrong place
2
Q
How might cell stress lead to cell death?
A
Cell stress (with high dose intensity and cell vulnerability) -> Injury-> Irreversible injury -> DEATH
Dividing cells are more vulnerable to radiation! Cells can metabolically or structurally adapt in response to chronic stress. But cell may not be able to cope… resulting in injury and eventually death.
3
Q
How might a cell adapt to stress in normal conditions (3)
A
Atrophy
Hypertrophy
Hyperplasia
Not normal: metaplasia…
4
Q
What is atrophy?
A
- Decrease in cell size
- Decrease in cell number
5
Q
What is hypertrophy?
A
Increase in cell size
6
Q
What is hyperplasia?
A
Increase in cell number
7
Q
Name 3 types of cells (relating to their diving qualities)
A
1- Labile
2- Permanent
3- Stable
8
Q
What are labile cells?
- Examples?
- What happens with cell stress?
A
continually dividing
Epidermal/ endothelial, GI tract lining, bone marrow, Immune
Stress in these cells results in INCREASED rate of cell division as they have the capacity to divide -> Hyperplasia
9
Q
What are permanent cells?
- Examples?
- What happens with cell stress?
A
(In an adult) No longer have capacity to divide:
Cardiac, Neurones
Stress may be high BP, Heart has to pump harder-> Hypertrophy occurs)
Heart attack-> Death of Myocytes-> No real way of regenerating
10
Q
What are stable cells?
A
Ceased cell division but retained the capacity to divide:
Liver (Hepatocytes)
If half of liver removed, can regrow!
11
Q
What is the cell cycle?
A
controlled way in which cells copy the nucleic acid and divide
12
Q
Name a developmental condition where there is Too much tissue
A
Hamartoma
13
Q
What is a Hamartoma?
A
Tumour-like overgrowth
Grows in patient’s growth period (child) but stops growing when they reach adulthood.
Tissues are normal for site but excessive.
14
Q
Give 3 examples of hamartomas
A
- Pigmented naevi (moles)- patch of naevi melanocytes (lots of melanin pigment)
- Haemangioma- blood vessels, can be big or small, knots of BVs (too much) – can cause problems with bleeding (common in older px as their mucosa thins and it becomes more apparent)
- Odontomes- teeth abnormalities, extra tooth or disorganised dental hard tissue
15
Q
Name a reactive/adaptive condition where there is Too much tissue
A
Hyperplasia.
Hypertrophy.
16
Q
What is hyperplasia?
A
increase in cell numbers
Response to stimulus, Regression once stimulus removed!
Increase in size and function of a tissue.
17
Q
Give some examples when hyperplasia occurs-
A
Endocrine (Physiological)- normal growth and devleopment, puberty, pregnancy
Endocorine, Pathological: parathyroids and thyroid
- Chronic irritation/ inflammation
- Bone marrow, lymphoid tissue
- Thyroid hyperplasia with iron deficiencies- Fe+ needed to make thyroid hormone! Will feed back to thyroid gland and cause cells to divide!
- Gingival hyperplasia- long term chronic inflammation stimulates division of epithelial and fibroblast cells; improve with OHI? Can be caused by medication
- Hyperplasia of the tonsils- immune response
18
Q
What is hypertrophy?
A
increase in cell size
Often occurs with hyperplasia.
19
Q
Name some Pure hypertrophy examples:
A
- Muscle- mechanical stimulus
- Skeletal- exercise
- Smooth- pregnancy
- Cardiac- LVH in hypertension- High BP, resistance to which heart is pumping has increased, increase power of pump!
20
Q
What is neoplasia?
A
growth which is uncontrolled and does not stop. Persists after the stimulus is removed!
21
Q
Name 3 developmental condition where there is Too little tissue
A
- Agenesis
- Aplasia
- Hypoplasia
22
Q
What is agenesis?
A
does not develop at all (Missing tooth?)
23
Q
What is Aplasia?
A
Present but fails to develop normal structure (e.g. major bodily organs, 2 kidneys but changed structure)
24
Q
What is hypoplasia?
A
: Present, normal structure but Less tissue formed (smaller)
Achondroplasia- problem with development of the long bones
Enamel hypoplasia
Amelogenesis Imperfecta
Hypoplastic mandible and malocclusion
25
Name a reactive/response condition where there is Too little tissue
Atropy
- Localised
- Generalised
26
What is atrophy?
decrease in size/number after growth... Can be physiological (embryology)
Mechanisms: Imbalance of cell loss/production
* Reduced proliferation
* Apoptosis rather than necrosis (mostly)
* Reduction in structural components of the cell, esp proteins
27
What is generalised atrophy?
Nutritional deficiency(starvation)- shiny tongue= iron deficiency
Senile (when people age)
Endocrine (physiological hypoplasia e.g. oestrogen, sexual hormones)
Bone- osteoporosis, reduction in bone mass/ density as trabecular structure becomes less compact (tendency in older females due to oestrogen levels and menopause)
28
What is localised atrophy?
Ischaemic (heart)- due to reduction in blood supply!
Pressure
Disuse (similar to below) – stop working out= lose muscle mass
Neuropathic/ denervation- nerve damage by trauma, atrophy of muscle
Immune mediated (autoimmune)
Idiopathic- Unknown reason
29
What is an Atrophic mandible?
bone resorption as tooth absent (rate varies between Px)
Important factor in denture retention
30
3 Examples of atrophy
- atrophic mandible
- Alzheimer's (white/grey matter)
- Romberg's disease- hemifacial
31
Name 2 conditions where tissue is the wrong type
- Metaplasia
| - Dysplasia
32
What is metaplasia?
Abnormal differentiation
- Change from one differentiated tissue to another (within the same germinal layer)
- Result from changes in environmental demands.
- Epithelium: mucous, squamous, mesenchymal
33
Give an example of metaplsia in smokers
(may be first step on the route to cancer)
* Squamous metaplasia in bronchi of smokers ( epithelium undergoes squamous metaplasia changes from respiratory type of epithelium to squamous)
* Px can get cancer
34
Give an example of metaplsia in px with acid reflux
* Gastric metaplasia in oesophagus of patients with acid reflux
* Squamous-> Gastrix type of epithelium
35
What is dysplasia?
- abnormal growth and differentiation in a tissue, with abnormal cells and tissue architecture.
- May be premalignant
36
Name the condition where tissue is in the wrong place
Ectopia- Developmental abnormality; Normal tissue but abnormal site!
e.g. Left kidney in wrong place or Max canines angled in the wrong direction!
37
What causes cancer?
* Cancer (neoplasia) is caused by abnormal cell growth
* This results from changes in the levels or function of proteins regulating proliferation, differentiation and survival of cells
* This is caused by mutations in genes
* These mutations may be genetic, environmental or viral
* A number of mutations are required to cause cancer
38
Why might a mutation not lead to cancer?
- Doesn’t necessarily change protein sequence
- Cells are usually good at noticing changes in bases
- DNA in a cell is huge and a lot of DNA doesn’t actually code for proteins
39
What is DNA transcription?
involves mRNA, leaves nucleus to cytoplasm, tRNA bring an amino acid which is complementary to the base sequence.
40
Name 3 Types of mutations:
1) Point mutations
a. Change in amino acid
b. Frameshift
c. Introduce STOP codon
d. Change splicing
2) Gene amplifications
3) Chromosomal translocations
41
What is a chromosome translocation?
a chromosome abnormality caused by rearrangement of parts between non-homologous chromosomes. A gene fusion may be created when the translocation joins two otherwise-separated genes. It is detected on cytogenetics or a karyotype of affected cells (may be able to see this by staining the chromosomes.
42
What is amplification?
increases the number of copies of a gene without a proportional increase in other genes.
This can result from duplication of a region of DNA that contains a gene through errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements.
43
What is a somatic mutation?
Somatic- occur in a single body cell and cannot be inherited (only tissues derived from mutated cell are affected)
- Somatic mutation occurs in non-germline tissues
- Non-heritable
e. g. breast cancer
44
What is a germ-line mutation?
occur in gametes and can be passed onto offspring (every cell in the entire organism will be affected)
- Mutation present in egg/sperm
- ARE heritable
- Cause cancer family syndrome
- All cells affected in offspring
45
NAme some Characteristics of cancer cells (7)
| mutations of genes that regulate the below processes are seen in all cancers!
* Excess proliferation without external stimuli
* loss of control mechanisms
* Loss of apoptosis
* Defects in DNA
* Irreversible, limitless change
* Acquisition of a blood supply - angiogenesis
* Invasion of surrounding structures
46
Name 4 genes involved in cancer
1) Oncogenes (accelerate cancer!)
2) Tumour suppressor genes (Prevent cancer!)
3) Apoptosis genes
4) Mismatch repair genes
47
What are oncogenes?
* Apply the accelerator to autonomous cell growth and proliferation (normal function...)
* Code for growth factors and their receptors, signal transducers and cell cycle components
* Increased expression (activation) in malignancy
48
What is a proto-oncogene
A normal gene which, when altered by mutation, becomes an oncogene that can contribute to cancer.
Proto-oncogenes may have many different functions in the cell. Some proto-oncogenes provide signals that lead to cell division. Other proto-oncogenes regulate programmed cell death (apoptosis).
49
What are tumour suppressor genes?
* Apply the brakes to cell proliferation
* Code for factors which control the cell cycle, regulate apoptosis, transcription or cell interactions
* Normal function in suppressing cell proliferation and maintaining tissue integrity
• Loss of expression (gene deletion) or function (mutations) in malignancy
50
What are apoptosis genes?
* Genes that regulate normal cell death
* May see Increased activity of a gene which inhibits apoptosis, eg. bcl-2, myc
* May see reduced activity of genes which promote apoptosis, eg. p53
* BCL-2 is overexpressed in lymphomas
51
What are mis-match repair genes?
• Code for enzymes important for the repair of damaged DNA
52
How might mis-match repair genes lead to cancer?
* DNA damage is common due to environmental carcinogens
* Loss of expression (deletion) or function (mutation) in malignancy
• Loss of repair mechanisms increases risk of mutations and activation or loss of oncogenes and tumour suppressor genes.
53
Name 4 factors that affect carcinogenesis
1- Genetic
2- environmental
3- chemical
4- viruses
54
Name 2 genetic factors that affect carcinogenesis
- Inherited mutations/deletions: p53, Rb, APC
| - Somatic mutations: Sporadic
55
Name 2 environmental factors that affect carcinogenesis
- Sunlight: Lip and skin cancer
| - Irradiation: Skin cancer
56
Name 2 chemical factors that affect carcinogenesis
- Nitrosamines (tobacco): Oral and lung cancer
| - Aniline dyes: Bladder cancer
57
Name 4 viruses that may lead to cancer
- EBV: Burkitts
- HBV: Liver
- HPV: Cervix, oral
- HTLV: Leukaemia
58
What is a neoplasm?
an abnormal mass of tissue from excessive growth
- Unco-ordinated with that of normal tissues
- Persists after the provoking stimulus is removed
59
What is invasion (cancer)?
unconfined growth into connective tissue, the defining feature of malignant tumours
60
What is a metastasis?
spread distant from the primary tumour
61
What is cytology?
features of individual cells, often very abnormal
62
Name 4 features of a neoplastic microenvironment
- Blood supply
- Fibroblasts
- Immune cells
- Nerves
63
Name the 2 ways of classifying cancers
1- By clinical behaviour
(benign, malignant)
2- by histology/ tissue of origin
( epithelial, mesenchymal)
64
Name some features of a benign tumour
Growth pattern: expands, encapsulated, localised.
Slow growth rate.
Cells resemble tissue of origin, are uniform shape and size.
Few mitoses (histology).
65
Clinical effects of benign tumours
Localised
Local pressure
Excision cures it!
66
Name some features on malignant tumours
Growth pattern: invasion, no capsule, metastasis.
Rapid growth- variable!
There is variable resemblance to tissue of origin... can have cellular/nuclear pleomorphism
- Many mitoses
67
Clinical effects of malignant tumours
Infiltration and spread.
- Local pressure
- Excision may not cure!
68
name 3 Components of a benign tumour
* Tumour cells
* Stroma (supporting connective tissue)- BVs, immune cells etc.
* Capsule (most but not all tumour, may be incomplete)
69
name 3 Effects of benign tumours: (varies by site and tumour, effect is not always benign)
- Pressure (on other structures like BVs, ducts??) – benign brain tumours will have an effect!
- Obstruction
- Function (esp hormone secretion)- it may do the same things the tissue it arose from did… e.g. parathyroid benign tumour will produce parathyroid hormone
70
name 2 Components of a malignant tumour
| No clear boundary between neoplasm and normal tissue
• Tumour cells: invade underlying tissues (and destroying)
- Cytologically abnormal
- Differentiation varies: well, moderate, poor
- Anaplasia
• Stroma: Fibroblasts, BVs, immune response
- Angiogenesis
- Immune response
71
What might there be an ulcerated surface in malignant tumours?
Some parts of tissue may undergo necrosis if tumour grows so fast and away from blood supply.
72
Name an example for a malignant tumour
squamous cell carcinoma of tongue and larynx
73
Name an example for a benign tumour
pleomorphic adenoma in parotid gland. Large, well-defined neoplasm.
74
Classification 2- By histology: Tissue of origin
Epithelial-lining or glandular
(GI tract, salivary glands)
Mesenchymal- various types (depends on exactly which cell)
75
What % of cancers are epithelial
90%
76
How to classify/name benign and malignant epithelial cancers:
Benign:
Lining= papilloma (e.g. squamous cell papilloma)
Glandular= adenoma
Malignant:
Lining= Carcinoma
Glandular= (Adeno)carcinoma
77
How to classify/name benign and malignant mesenchymal cancers:
Benign: depends on tissue
e.g. fibroma, osteoma, lipoma, myoma, chondroma
Malignant:
Sarcoma
e.g. osteosarcoma, leiomyosarcoma
78
Name 4 Oddities to naming cancers
* Melanoma: melanocytes- all malignant, no benign ones
* Lymphoma- lymphoid cells, lymphocytes
* Leukaemia: bone marrow precursors
* Teratoma: germ cell tumours, most in testes, most malignant (ovarian tend to be benign), can mimic any tissue; cells in ovary/testes can differentiate into anything!
79
Name of a benign lining epithelial cancer
Papilloma
80
Name of a malignant epithelial cancer
Carcinoma
81
Name of a benign mesenchymal cancer
Depends on the tissue
| Lipoma, fibroma, osteoma, myoma, chondroma
82
Name of a malignant mesenchymal cancer
Sarcoma
83
Name of a benign glandular epithelial cancer
Adenoma
84
Inherited factors of carcinogenesis
- Single mutant genes, often tumour suppressor genes
- Retinoblastoma- can lead to many types of tumours
- Some colon cancers
- 10% of breast/ ovarian cancers are hereditary
- BRCA1 or BRCA2 gene for breast cancer
85
What are familial cancers?
- Family clusters
- Gene(s) and pattern of inheritance not clear
- Breast, ovary, colon
86
What is Chemical carcinogenesis – DNA damage!?
What are the 2 stages
1) Initiation- permanent DNA damage, primes a cell
2) Promotion- may be reversible, promotes proliferation- might not be DNA damaging but may pushed primed cell to become cancerous
87
What is the latent period
time from promotion to clinical tumour
88
What is a pre-carcinogen?
- Pre-carcinogen often metabolised to ultimate -> carcinogen
89
What is a co-carcinogen?
- Co-carcinogens are not carcinogenic but when combined with carcinogen can help/aid it/potency!
90
What's the difference between direct chemical carcinogenesis and indirect chemical carcinogenesis?
Direct= Tumour arises at site of carcinogen application. E.g. smoking and lung cancer
Indirect= Tumour arises at different site from carcinogen application. E.g. aromatic amines- industrial exposure, Initial contact with lungs but cancer occurs someowhere else.
91
Name 4 chemical carcinogens
- Smoking: polycyclic, hydrocarbons, including tars
- Diet: burnt hydrocarbons
- Asbestos (from construction work): fibrous silicates, inhaled fibrosis, mesothelioma
- Synergy in smokers
92
Name some physical carcinogens
Ionising radiation/ X-rays
Radioactive metals and gases:
Radium- bone and bone marrow tumours
Radon- lung cancer
Atomic bomb
93
Most to least sensitive list of tissues (cells are rapidly dividing/renewed= more sensitive)
1. Embryonic tissues
2. Haematopoietic organs (spleen, bone marrow)
3. The gonads
4. The epidermis
5. The Intestinal mucous membranes (variable)
6. Connective tissue
7. Muscle tissue and nerve tissue
94
How might ultraviolet light cause cancer?
- Damages DNA (causes DNA crosslinks- we have a way of dealing with these)
- Skin: Squamous cell carcinoma, basal cell carcinoma (most common cancer), malignant melanoma
- Xeroderma pigmentosum- this condition, px inherits abnormality in ability to repair lesions caused by UV light
95
Name some viruses and the cancers they cause
Epstein- Barr virus (EBV) -> Burkitt's lymphoma/ nasopharyngeal carcinoma
Hep B/C -> Hepatocellular carcinoma
Human papillomavirus -> Cervical carcinoma
96
What does HPV do?
- Sexually transmitted
- Some genotypes cause cervical cancer and oro-pharyngeal cancer.
- Viral protein binds to and inactivates the tumour-suppressor p53 gene.
97
Name some influencers (promoters) of cancer
Hormones
Drugs
Inflammation
98
2 Examples of how hormones can affect cancer
o Breast cancer: hormonal dependence e.g. oestrogen (ovary, adrenal)
o Prostate cancer: testosterone
99
How can inflammation affect cancer?
cancers can arise more easily where chronic inflammation is present e.g. leukoplasias
100
% of deaths that are cancer?
20%
2nd most frequent cause
- Higher in elderly
90% carcinoma, 10% lymphoma or sarcoma
101
3 ways a cancer develops-
1- de novo (nothing preceding it)
2- Via a benign tumour - polyps?
3- via a premalignant lesion
102
What is premalignancy?
There are some changes in cells and tissue architecture that are seen before invasion occurs...
- Dysplasia
Premalignancy is the basis of cancer screening...
103
Non-metastatic effects of cancer
25% will die from cancer-related cachexia (whole-body metabolic effects, systemic/immune etc)
104
How does Invasion occur: local spread
- Path of least resistance
- Tissue destruction
- Perineural spread
105
How does Metastasis occur: lymphatic spread
- Invasion of vessels; embolism or permeation
- Spread to draining lymph node(s)
- Primary tumour-> distant site
- No 2 people have the same lymphatic drainage
106
How does Metastasis occur: haematogenous spread
- Invasion: mainly veins
| - Organs: liver, lung, bone and brain
107
How does Metastasis occur: transcoelomic spread
- Scoelomic- potential spaces in the body, have fluid and spaces for transmission
- Spread across serous cavities
E.g. abdominal cavity
108
What do tumour cells do that help them spread
```
Motility is enhanced
Alter adhesion molecules
Make poor basement membrane
Increase protease production or reduce inhibitors
Alter ECM
```
109
Patterns of spread for
- Carcinomas
- Sarcomas
Carcinomas
- Lymphatic
- Blood (often later)
Sarcomas
- Blood (lymphatic spread is very rare)
110
Predictable patterns of spread for:
- Lungs
- Tongue
- Lung to local nodes, liver, bone and brain
| - Tongue to neck nodes, later lung and spine
111
Effects of tumour spread
* Pressure and obstruction
* Destruction
* Haemorrhage
* Infection
* Pain
* Anaemia
* Starvation and cachexia
112
Non-metastatic effects, or ‘paraneoplastic syndrome’
- caused by biochemical substances released by tumour cells e.g. TNF-alpha
Fever, anorexia and weight loss/cachexia
Endocrine syndromes- cushings syndrome, metabolic effects e.g. hypocalcaemia
Neurological problems e.g. neuropathy
Haematological syndromes e.g. erythrocytosis
113
2 systems used to predict how tumours will behave-
1- Grading of tumours
| 2- Staging of tumours
114
How are tumours graded?
* Histological assessment
* Often related to differentiation
* Linked to prognosis
* Various methods: numerical, Low/intermediate/ high
115
How are tumours staged?
* Clinical extent of tumour
* TNM system
* T= tumour
* N= nodes (regional)
* M= metastases- distant
* Specific staging systems for tissue/ tumour
116
How is cancer diagnosed? )4)
* Biopsy
* Cytology (FNA)- fine needle aspiration
* Imaging- CT and MR scanning (cannot rely solely on MRI scans)
* Molecular analysis, genetic tests
117
Treatments for cancer
```
Surgery
Radiotherapy
Chemotherapy
Immunotherapy
Palliative care- supportive...
```
118
What is palliative care?
some circumstances where aggressive treatments are too hard to withstand- too ill or disease is too extensive to be cured.
119
what is radiotherapy
causes DNA damage in dividing cells and kills them. It is not very specific- head and neck has lots of different tissues that should not be irradiated!
120
Side effects of radiotherapy
- Tiredness
- Feeling sick
- Difficulty eating and drinking
- Skin reaction
- Hair loss
- Haematological changes- bone marrow affect
121
Clinical relevance to radiotherapy of oral cancer
radiotherapy can cause a horribly dry mouth- irradiation applied to (salivary) parotid gland when tongue tumour…
122
Possible side effects of chemotherapy-
```
Mucositis
Alopecia
Nausea/vomiting
Diarrhoea
Cystisis
Sterility
Neuropathy
Myalgia
Pulmonary fibrosis
Renal failure
```
123
What are cancer biomarkers?
- diagnostic tool
- optimal dose for drug therapy
- what type of cancer
- optimal drug?
- recurrence?
124
Oral problems in cancer management
- Oral mucosal disease
- Dental disease
- Discomfort
- Social embarrassment
Dry mouth, immuno-compromised, difficulting maintaining OH
