CANCER 1 Flashcards
VIRCHOWS LAW??
Why do tumours form?
Virchows law states that every cell is derived from another cell
Tumours are created by cells that have lost the ability to assemble and create tissues of normal form and function
THE PLASIAS
the overall trend in tumour progression?
Hyperplasia – tissue growth containing an excessive number of cells
Metaplasia – tissue growth containing displaced but otherwise normal cells (e.g. Barrett’s oesophageal cancer)
Dysplasia – tissue growth where cells first appear abnormal
Neoplasia – invasive abnormal tissue growth (often a mixture of all the other plasias)
Overall trend in tumour progression
Hyperplasia → Metaplasia → Dysplasia → Neoplasia
A pre cursor product relationship forms?
The trend in tumour progression - as trend progresses, suggest that cells actually become precursors for cancer cells.
Age and cancer?
Age and different cancers?
risk and age?
Older you are – higher the risk of cancers
The age/incidence profile varies with different cancers
Risk doesn’t always increase with age
NATURE VS NURTURE
% of death with tumours?
normal biological processes involved?
risk per population / nurture?
80% patients that die of other factors will show a tumour growing in them
Normal biological process (cell division and differentiation)
Risk of cancer isn’t the same in all human populations (nurture element)
Major disease risk is environment
Enabled by factors external to the body
MIGRANT STUDIES - Japanese Hawaiians
Japanese in Hawaii/California
Colon and prostate cancer incidence increased in Japanese migrants settling in Hawaii
Liver and stomach cancer incidence decreased in Japanese migrants settling in Hawaii
Migrants acquire cancer spectrum depending on where they live (environmental) NOT their GENETIC HERITAGE
Japanese Hawaiians inherit the Caucasian Hawaiian cancer profile
—-> Cancer risk affected by assignable ENVIRONMENTAL INFLUENCES?
RICHARD DOLL - link of the risk of cancer and smoking?
Induction of genetic instability in men?
Linked carcinoma of the lung to smoking
Correlation of the number of cigarettes smoked to the incidence of lung cancers
Identified the lag phase – time taken for the induction of genetic instability ?
20 years in men
The familial genetic basis of cancer?
What are cancers where familial predisposition is prevalent?
Familial pre-diposition to : retinoblastoma, wilms tumour, adenomatous polyposis coli hereditary breast cancer
Such occurrences imply the existence of GENES regulating CANCER INCIDENCE
A SINGLE MUTATION is NOT ENOUGH to cause cancer
LOGARHYTM FOR FAMILIAL INCIDENCE?
How is it derived
what does it mean
P(Cn) x An
P = probability of tumour
C = change in cells associated with tumour
n = number of changes in cells
A = age
the probability of all relevant changes is the product of the probability of each change multiplied by age.
Can produce a logarhytm:
Log P(T) = nLogA + constant
The slope on a graph - n is approximated to 6 –> is this the number of mutations needed for cancer?
Cyclin activity
Activated Cdks transfer phosphate groups from ATP to serine and threonine side chains on target proteins
Inactive Cdks have their active site occluded by the T loop (part of the cdk)
Cyclin binding to Cdk pulls the T loop away from the active site and exposes the bound ATP. The ATP can then access target proteins
IS CYCLIN ESSENTIAL? WHY?
Cdk can only phosphorylate target proteins when it is in a cyclin-Cdk complex
Cdk-activating kinase is required for full activation of Cdk
This kinase adds a phosphate group to a crucial threonine in the T loop
Enabling Cdk to bind to and phosphorylate its target proteins
CDK INHIBITOR PROTEINS? How do they work? why do we need them?
Cdk inhibitor proteins (CKIs) help regulate the rise and fall of cyclin-Cdk activity
Some inhibitors bind directly at the kinase active site and block kinase activity by interfering with ATP binding
