Outline Of Cancer process Flashcards
How do cancer cells grow/divide?
Mitosis - increased!! But abnormal
Invade and spread
Heterogenous group of disease
Most are monoclonal - arise from a single cell
Loss of contact inhibition
Increase in GF secretion
Increase oncogene
TSG decrease
Poorly differentiated - abnormal heterogenous cells
Cancer cells
Oncogene rare
Presence of TSG
Some/ coordinated GF secretion
Few mitosis
Normal cells
Carcinogen > initiation > promotion > tumour growth > (Metastases )progression to clinical cancer
Multistage carcinogenesis
To rem the order Think initiation as interphase; promotion as prophase, tumour growth as telophase - these are pre clinical cancer
Diagnostic threshold of tumour growth
1cm
(10^9 cancer cells)
Host death around 10^12)
Causes: Chemical, physical, viral carcinogens
Causes of cancer initiation
Causes - GF, oncogenes
Cause of cancer promotion
Causes - metastasis
Progression
Not random
Arcade of limited sequential steps
Involves tumour host interactions
Survival of the fittest
Metastasis
Invasion and Metastasis
Where are these enzymes involved?
MMP
Plasmin
Cathepsin
In ECM
matrix metalloproteinases (MMP) To help rem: Plasma is a part of ECF - so =plasmin
Invasion and Metastasis
Where are these enzymes involved?
cahedrins (loss correlates with tumour invasion and metastasis)
Integrins
CD44
Cell adhesion
Remember by:cahedrins (adhere); Integrins (integrate); CD44( pair attach)
Cell carries receptor and secrete GF
Trigger response on it itself
Autocrine
GFs activity on a cell are produced locally by the cell or its immediate neighbours Short distance (adjacent cells)
Paracrine
Formation of new blood vessels
Angiogenesis
Key factor in the maintenance and progression of malignant tumours
Degradation of …. required for new blood vessel formation. And new blood vessels must form for a tumour mass to …… In diameter
ECM
Exceed 2 mm
Clinical correlation are seen between vessel density, tumour malignancy and metastasis.
invasion of cancer cells through the basal membrane into a blood or lymphatic vessel
Intravasation
One of the carcinogenic events that initiate the escape of cancerous cells from their primary sites
cancer cells exiting the capillaries and entering organs.
Extravasation (malignant cancer metastasis)
leakage of a fluid out of its container. In the case of inflammation, it refers to the movement of white blood cells from the capillaries to the tissues surrounding them (leukocyte extravasation), also known as diapedesis.
…binds VEGF. It prevents interaction with … And activation of downstream signalling pathways
Ultimately vascular regression and tumour….
Anti-VEGF antibody Avastin
receptors
Dormant
The therapy normalises vasculature / ovarian carcinoma and glioma
This helps the drug accompanied to be more effective too
But it is limited in other areas
Cancer
Mass
Tumour
Growth
Neoplasm
Carcinoma or disorderly growth of epithelial cells - invade adjacent tisc and spread by lymphatics and blood vessels to other parts of body
Most are monoclonal - arise from single cell
Only 20% originate in CT, MSK or nervous tisc
Stimulate formation of blood vessels
VEGF
In normal healing too
But disorganised in cancer
Why does our immune cells not recognise cancer cells
Cancer cells hide from T cells - programmed death receptor (PD1) on T lymphocytes cannot detect
PDL1 on tumour cell bind PD1 on T cells > suppression of T cell act
PD1 inhibitor (checkpoints) improve overall survival
Nivolumab (anti-PD1 Ab)
tested in melanoma and lung cancer
