eBook Chapter 1 - Introduction

Question 1

Define a neoplasm

Answer 1

uncontrolled proliferation of an abnormal cell

• partially or completely independent of the factors which control normal cell growth
• growth persists even if the initiarint stimulus is withdrawn

Question 2

What are the two types of neoplasm?

Define them

Answer 2

Benign - not invasive, does not migrate
Malignant - invades and destroys the tissues in which it originates ands the potential to spread to other sites in the body via the blood and lymph

Question 3

What are the two basic components of all neoplasms?

Answer 3

parenchyma = distinguishing cells or tissue of a gland or organ, responsible for carrying out the specialised functions, where the primary tumour starts 
stroma = supporting, host derived, non-neoplastic component, composed of different cell types: epithelial cells, fibroblasts, immune cells and ECM

Question 4

Name the benign tumours of the following areas:

• fibrous tissue
• cartilagenous tissue
• smooth muscle
• fat tissue

Answer 4

• fibrous tissue = fibroma
• cartilagenous tissue = chrondroma
• smooth muscle = leiomyoma
• fat tissue = lipoma

Question 5

Naming epithelial cancers:
Define the following:
- adenoma 
- papilloma 
- polyp

Answer 5

• adenoma = benign epithelial neoplasm, may or may not produce glandular patterns
• papilloma = benign epithelial neoplasm which grows on any surface and produces fronds
• polyp = mass that projects above a mucosal surface to form a macroscopically visible structure

Question 6

Define adenocarcinoma

Answer 6

malignant neoplasm arising from glandular epithelium

Question 7

Define squamous cell carcinoma

Answer 7

malignant neoplasm arising from squamous epithelium

Question 8

Define the following non epithelial cancers:

• sarcoma
• leukaemia
• lymphoma
• neuroectodermal tumour
• glioma
• neuroblastoma

Answer 8

• sarcoma = malignant tumour of connective tissue of mesenchymal cells
• leukaemia = cell of origin is a haemoatopoetic cell in the bone marrow and the neoplastic cells are present in the blood
• lymphoma = cell of origin is in the lymph needs or a lymphoid organ, neoplasm may be present in the blood
• neuroectodermal tumour = cells of the central and peripheral nervous system
• glioma = tumours of the glial cells
• neuroblastoma = neuroendocrine tumour arising from any element of the sympathetic nervous system, most frequently from one of the adrenal glands

Question 9

Define microevolution

Answer 9

term that describes the process of accumulating 5-10 critical mutations that result in cancer
- requires many years and the mutations can occur in both germline and somatic cells

Question 10

Critical mutation occur in genes that normally control:
-
-
-
-
-

Answer 10

• growth
• passing on signals from outside the cell across the cytoplasm to the nucleus
• programme cell death (apoptosis)
• the cell cycle
• the integrity of the genome (DNA repair)

Question 11

Define and describe oncogenes

Give examples

Answer 11

• positive regulators of cell growth - they makes cells grow
• porto-oncogenes play important roles in normal cells, especially during development.
• their activity is strictly controlled in normal cells
• in cancer, control is lost due to mutations and they become constituently active
• oncogene deregulation only requires mutation in one of the alleles to cause cancer
  Examples
• c-myc
• EGFR
• Raf kinase
• Ras protein

Question 12

Define and describe tumour suppressor genes

Answer 12

• normally, TSGs are negative regulars of cell growth
• they oppose the action of oncogenes when activated, to prevent growth
• TSG deregulation requires a mutation in both alleles
  Examples
• p53, pRB, PTEN, APC (each gene codes for a protein of the same name)

Question 13

List the 6 original hallmarks of cancer

Answer 13

1. Sustained proliferative signalling
2. Evasion of growth suppressors
3. Resisting cell death/Evasion of apoptosis
4. Enabling replicative immortality
5. Inducing angiogenesis
6. Activating invasion and metastases

Question 14

Describe 1. Sustained Proliferative Signalling

Give an example

Answer 14

Sustained Proliferative Signalling
- ability of a tumour to proliferate without pro-growth factors
- normally GFs bind to cell receptor and cause downstream signalling which leads to cell growth, usually a receptor tyrosine kinase, proliferation occurs in response to the extracellular stimuli
- in cancer, three re at least three possible ways to overrule this, allowing growth in absence of signal
1. Tumour cells may secrete their own Bfs - autocrine
2. Receptor mutation making it constituently active
3. Key downstream signalling proteins mutated to sustain signalling
Example
- Ras oncogene –> initiates 3 major downstream signalling cascades
- Cause inhibition of apoptosis, cell growth, transcription

Question 15

Describe 2. Evasion of Growth Suppressors

Give an example

Answer 15

Evasion of Growth Suppressors

• growth suppressors are molecules that prevent the cell from progressing through the cell cycle, a cell will only respond to extracellular mitogens and inhibitory factor during discrete window of time between onset and end of G1 phase, designated by the restrictor point
• the product of TSG pRB, operates as central control node in the circuit
• loss or mutation of pRB leads to loss of control over progression from G1 to S phase, this means the cell will continue to proliferate

Question 16

Describe 3. Resisting Cell Death/Evasion of Apoptosis

Answer 16

Resisting Cell Death/Evasion of Apoptosis

• apoptosis is programmed cell death
• process is activates if a cell’s genomic integrity is complicated and non-repairable
• mediated by TSG p53
• transcription of this gene, and the resulting increase in TF p53 levels, is stimulated by cellular stress e.g. lack of nucleotides UV/ionising radiation, hypoxia, blockage of transcription
• p53 is able to induce cell cycle arrest and apoptosis if the problem cannot be solved
• p53 frequently lost or mutated in tumours, loss of p53 renders tumours less responsive to chemotherapy

Question 17

Describe 4: Enabling Replicative Immortality

Answer 17

Enabling Replicative Immortality

• cancer cells can circumvent senescence and crisis
• proliferation of cultured cells is usually limited by the number of telomeres on the ends of chromosomal DNA, but cancer cells can escape criss by expressing telomerase thereby regenerating their telomeres

Question 18

Describe 5: Inducing Angiogenesis

Answer 18

Inducing Angiogenesis

• since cancerous cell are highly proliferative, they require a sustained blood supply which provides them with nutrients and oxygen and removes metabolic wastes
• vasculature is also important for metastasis
• tumour-associated neovasculatrure is generated by a process of tumour-induced angiogenesis
• activators include VEGF, FGF1
• inhibitor include IFNalpha/beta and angiostatin
• in cancer cells, the balance is tipped in favour of the activators

Question 19

Describe 6: Activating Invasion and Metastasis

Answer 19

• metastasis is a multistep process leading to the spread of cancer to distant organs, it has important implication for prognosis
• to allow for metastases, there are changes in expression of adhesion receptors such as E-cadherin and integrins.
• there is also activation of extracellular proteases that degrade the ECM, allowing the cell to move
• cancer cells in tumours of epithelial origin frequently undergo a reversible programme called epithelial-mesenchymal transition. induced by activated of specific TFs (slug/snail) which leads to changes in expression levels of adhesion molecules, MMPs, proteins regulating actin polymerisation, signalling molecules etc. It also results in morphological changes when epithelial cells acquire a fibroblast like elongated shape.
• EMT allows migration of cancerous cells, therefore leading to invasion and metastasis