Cellular Basis of Cancer

Question 1

neoplasia
oncology
benign
malignant
anaplasia

Answer 1

neoplasia= new growth

oncology= study of tumors or neoplasms

benign= localised growth that will not spread to other sites

malignant tumors= destroy surrounding tissue structures and spreads to other sites. grows rapidly, uncapsulated, consists of different types of cells.

anaplasia- lack of differentiation

Question 2

benign vs malignant tumours and their potential to spread

Answer 2

benign tumours grow and compress on local structures but do not spread to distant sites

malignant tumours can invade and destroy adjacent structures and spread to distant sites

Question 3

how might tumours spread?

Answer 3

lymphatic spread- sentinel node is the first node in the regional lymphatic basin that receives lymph flow from the primary tumour

tumours can spread with direct seeding of body cavities.

Question 4

what are some examples ofcarcinogens

Answer 4

environmental factors
infectious agents
smoking
alcohol consumptions
diet 
obesity
environmental carcinogens
age
acquired predisposing conditions
chronic inflammation and cancer
precursor lesions and cancer (Barretts oesophagus)
immunodeficiency states

Question 5

what are some example of microbial carcinogenesis?

Answer 5

oncogenic RNA viruses (human T cell leukaemia virus type 1)
oncogenic DNA (HPV)
Epstein Barr Virus (Burkitt lymphoma)

Question 6

hallmarks of cancer

Answer 6

1. sustaining proliferative signalling
2. evade growth suppressors
3. activating invasion and metastasis
4. enable replicative immortality
5. inducing angiogenesis
6. resisting cell death
7. sustaining proliferative signalling

Question 7

what are oncogenes?

Answer 7

oncogenes promote autonomous cell growth in cancer cells

(stuck on acceleration)

proto oncogenes are unmutated cellular counterparts.

Question 8

tumor supressor genes

Answer 8

tumour suppressor genes usually apply breaks to cell proliferation. abnormalities in these lead to failure of growth inhibition

• two-hit hypothesis (RB)
• p53 central monitor of stress in cell

p53- Li Fraumeni syndrome

Question 9

two hit hypothesis

Answer 9

two mutations involving both alleles of a tumour suppressor gene (RB) = retinoblastoma

familial- inherit one defective copy (first hit) and the other copy is normal.

sporadic cases- both normal RB alleles. undergo somatic mutations

Question 10

Lynch syndrome

Answer 10

linked with colon cancer and endometrial cancers

mismatch repair defect leads to a microsatellite instability (tandem repeats)

Question 11

staging cancer

Answer 11

tumor size
the extent of spread to regional lymph nodes
presence of absence of blood-borne metastasis

Question 12

diagnosis of cancer

Answer 12

clinical data
radiological images
cytology / FNA
histology: tissue scretions processed and sustained with haemotoxyline and eosin

immunohistochemistry
categorisation of undifferentiated malignant tumors
site of origin
flow cytometry
hereditary predisposition (BRcA1)

Question 13

cancer definition

Answer 13

uncontrolled proliferation of cells that arise from virtually any cell type in the body

Question 14

normal cell cycle

Answer 14

G0 phase= quiescent phase

G1 phase= growth phase. organelles duplicate
*G1 checkpoint

S phase= synthesis of DNA

G2 = growth and prepares for M phase
*G2 checkpoint

M phase= mitosis. the cell divides into 2 identical daughter cells.

can re-enter or go into G0

Question 15

cyclins and CKDS

Answer 15

these drive the cell cycle.

in G1, CKD 4 and 6 are produced. cyclin binds to CDK which causes a reaction of E2F and Rb spitting. this allows progression to the S phase.

S phase produces another CDK1/2 and cyclinA

G2 CDK 1 and Cyclin B

• too low cyclin= does not progress
• too much cyclin= continuous growth/proliferation

Question 16

cancer mutations

Answer 16

1. point mutation (single change in nucleotide)
2. DNA amplification. (a certain gene is amplified many times)
3. chromosomal rearrangement
4. epigenetic modifications (silence / more active DNA genes)
   * ACTIVATION OF ONCOGENES (RAS, MYC gene)
   * INACTIVATION OF TUMOR SUPPRESSOR GENE (p53, BRACA1/2)

Question 17

Oncogene activation

RAS

Answer 17

cell normally contains the RAS gene which makes the RAS protein

next to it is a growth factor receptor.

growth factor stimulates growth factor receptor which activates the RAS protein.

RAS protein causes a cascade of intracellular phosphorylation
this activates a transcription factor which will read the DNA gene to make proteins for cell growth (cyclin and CDK)

*if there is a mutation in the RAS gene you make genes that are always active= cascade of phosphorylation = overproduction. stuck on acceleration.

Question 18

oncogene activation

MYC gene

Answer 18

MYC gene is important for cell growth and cell survival.

mutation= more of this.

Question 19

Tumour suppressor gene

p53

Answer 19

if there is damaged DNA the cells make p53 for cell arrest like p21.

p21 usually causes cell arrest by inhibiting the CDK and cyclins (inhibits the drivers of the cell cycle)

p53 makes cells for apoptosis

***if there is inactivation of tumour suppressor gene then there is no surveillance of abnormal cells. no cell arrest or cell repair or apoptosis.

Question 20

immunological surveillance

Answer 20

natural physiological function to recognise and destroy transformed cells before they grow into tumors.

Tumors can inhibit t cell recognition, t cell function

central tolerance: newly formed T cells udnergo screening in the thymus. self peptides are removed. prevents attacking self.

however tumor cells are seen as ‘self’ so it’s not good for attacking/detecting these.

Question 21

peripheral tolerance

Answer 21

Anergy - renderedanergic(unresponsive)
May have the potential for self-reactivity

Activation Induced Cell Death (AICD) - Presentation of common proteins such as haemoglobin by APC leading to deletion

Immunological ignorance - Auto-reactive T cells may never come in contact with their auto-antigen

Sequestration - Prevention of antigen contact
(across a blood-brain barrier) eg. myelin

Question 22

HPV caccine

Answer 22

cervarix type 16,18

gardasil type 6 , 11, 16, 18

offered to girls 12-13 y/o
immunise before sexually active