Biology of Cancer Flashcards
Define Cancer
a group of diseases characterised by unregulated cell growth followed by the invasion and spread of cells from the site of origin to other sites in the body.
What % of Cancers arise in Epithelial Cells? Why
85%
it is a site of constant proliferation
What is a Cancer of Epithelial Origin Called?
Carcinoma
What is a Cancer of Mesodermal Tissues Called?
Sarcomas
What is a Cancer of Glandular Tissues Called?
Adenocarcinomas
Define Senescent
cell no longer replicates
At what point do Cells become Senescent
- at the end of each chromosome = telomere
a telomere is a repeated sequence of DNA - telomere shortens with every round of replication
- cell stops dividing when telomere reaches a certain length
What are the 6 Hallmarks of Cancer? Add 2 Extra Hallmarks
- Sustaining Proliferative Signalling
- Evading Growth Suppressors
- Activate Invasion and Metasis
- Enabling Replicative Immortality
- Induing Angiogenesis
- Resisting Cell Death
- Deregulating Cellular Energetics
- Avoiding Immune Destruction
Give 2 Enabling Characterstics of Cancer which Enhances the Hallmarks
- Genome Instability and Mutation
- by causing dna to be faulty, it causes genome instability, passes down onto daughter cells - Tumour Promoting Inflammation
- all malignant cells contain inflammatory cells
- can release reactive species, growth factors and enzymes
Give 6 Environmental Factors Causing Cancer
smoking
obesity
radiation
diet
alcohol use
chemicals
How is the Epidemiology of Nutrition and Cancer Found?
the links between cancer, nutrition and migration
- someone moves from low risk to high risk areas
- new local diets are adopted
What 7 Cancers can Unhealthy Diets Lead to?
Oral and Upper Throat
Larynx
Oesophagus
Lung
Stomach
Bowel
What are the 3 Dietary Cancer Causative Factors?
- Genotoxic agents in food - dietary carcinogenics
- Lack of specific nutrients
- Public health Issues - alcohol and obesity
Give 3 Genotoxic Contaminants and Where they are found in Food
Aflatoxin and Fumonsin B
- mold growing on poorly stored food
Heterocyclic Amines
- high heat cooked meats like BBQ
Polychlorinated Biphenols
- occur in farmed salmons
- in a process called biomagnification, goes through the food chain
Which Deficient Nutrient Increases the Risk for Colorectal Cancer
Vitamin B9 (Folate)
How does Folate Deficiency Increase risk for Cancer? (6)
- hypomethylation of DNA
- inhibits production of dTMP
(deoxyythymidine monophosphate)
= imbalance of nucleotide availability
- Uracil incorporated into DNA due to no Thymine
- DNA repair to remove u and place with T but makes DNA breaks
= increased frequency of mutations
What 4 Cancers are Alcohol a Risk Factor?
oral, breast, colon and liver
How does Alcohol Increase the Risk for Cancer?
Ethanol is metabolised into Acetylaldehyde by endogenous alcohol dehydrogenase
- binds to DNA
= DNA adducts - have a cancer chemical bound to it - causes mutations
After Drinking Alcohol, How much more Acetylaldehyde is Present in the Saliva?
100x
What are the 6 Common Cancer Tissues from Which Obesity Has a High Risk association
- breast
- colorectal
- endometrium
- oesophagus
- kidney
- liver
- multiple myeloma
What are the Proposed Mechanisms for How Obesity Leads to Cancer?
1) endocrine organ, secretes hormones like oestrogen = links to breast cancer
2) adipose increases storage for carcinogens
3) induces a chronic inflam response, more IL6 and TNFa
4) shift in gut microbiome, increased production of deoxycholic acid bacterial metabolism, reaches liver, DNA damage
What are Antioxidants?
compounds that significantly inhibit or delay the damaging action of ROS, may have a protective effect against cancer
Give 4 Phytochemical Antioxidants
Vitamin C
Isoprenoids
Flavonoids
Organosulfur Compounds
= plant derived
What is Isothiocynate?
a micronutrient from vegetables that can affect gene expression
What Cancers does Increased Consumption of Red and Processed Meat Link to?
Gastroesophageal groups
Why does Increased Consumption of Red/Processed Meat Link to Cancer?
- high levels of haem in red meat
- high levels of nitrate/nitrite preservatives in processed
can be converted into carcinogenic chemicals
- N-nitroso compounds (NOCs)
What are the 2 Major Types of Mutated Genes Contributing to Carcinogenesis?
Oncogenes
Tumour Suppressor Genes
Define an Oncogene
product of the mutated gene that is increased in high quantities, therefore acts in a dominant fashion, a positive factor
What are Unmutated Forms of Oncogenes?
proto-oncogenes
What is the Function of a Tumour Suppressor Gene?
inhibiting growth and tumour formation
mutation = loss of function, allows growth
usually recessive, a negative factor
What are Germline mutations?
inherited cancer genes
What are Somatic Mutations?
spontaneous cancer genes
What are 4 Common Protoco-Oncogenes?
growth factors
components of signal transduction cascades
nuclear DNA binding
DNA repair
How is Cell Division Initiated?
- signalling molecule binds to signal receptor
- signal passed through the cell via signal cascade
- protein are phosphorylated and activated by protein kinase
- phosphorylated proteins activate transcription factor
How can Mutation Affect Proto-oncogenes?
- increased growth factors
- increased signal receptors
- increased protein kinases
- increased transcription factors
==== more division
What is a Tyrosine Kinase Receptor and how does it work?
a receptor on the extracellular surface of the cell
- substrate binds to receptor in its inactive form
- kinase activity is stimulated
- tyrosines on the in the cystol are phosphorylated
- intracellular proteine bind to phospho-tyrosin docking sites
What are 2 Examples of Mutated TKRs, linked to Cancer?
FGFR - Fibroblast growth factor receptor
ERBB2
What Gene Helps Control Cell Division?
CDK4, a cyclin dependent kinase
What Happens to a Mutated CDK4?
altered CDK4 protein
= abnormally overreactive
= fast division, tumour
Name a Mutated Transcription Factor
myc gene
How does p53 Mutate and then Link to Cancer?
- mutations on chromosome 17
- loss of heterozygosity at the short arm
- tumour of lung, colon and breast
- mutations on p53 locus
- cancers of lung, colon, breast and liver
What can p53 be Activated by?
Telomere shortening
DNA damage
hypoxia
hyper proliferative signals
What 3 things can p53 lead to?
Senescene
Apoptosis
Cell-Cycle Arrest
How does DNA Damage Activate p53, and lead to cell death?
- phosphorylated p53 can no longer bind to protein Mdm2
- not sent to the proteasome for next steps
- begins to accumulate
- induces transcription of several genes
- activation of p21 gene
- transcription and translation of p21 protein
- p21 binds and inhibits cyclin-dependent kinases
- cells dont progress to s phase of cell cycle
- doesn’t complete cell cycle = apoptosis
Which 4 Processes allow a Proto-oncogene Form an Oncogene?
- Translocation
- Gene Amplification
- Point Mutation within control element
= excess growth stimulating protein - Point mutation within the gene
= hyperactive or degradation resistant protein
What are 3 Functions of Macrophages in Inflammation?
release pro inflam cytokines
ROS and RNS release
suppression of anti-tumour immune response
How do Pro Inflam Cytokines Link to Gene Regulation?
pro inflam cytokines induced NF-kB
- NF-kB regulates genes
- drive cell cycle
- cell survival
- anti-apoptotic
What are the 2 Types of Tumour Viruses?
DNA Genome
RNA Genome (retrovirus)
Describe the Features on How Cancer Develops in the Benign Stage NAHAKATAPCI
Hyperproliferation
Small to Larger Polyps
- normal epithelial
- loss of APC
- hyper plastic epithelium
- early adenoma
- activation of K-ras
- intermediate adenoma
- loss of 18q TSG
- late adenoma
Describe the Development of Cancer in the Malignant Stage NAHAKATAPCI
Abnormal cell growth and severe dsyplasia
Adenocarcinoma
Cancer
- late adenoma
- loss of p53
- carcinoma
- invasion and metastasis
Describe the Steps for Metastasis
- primary tumour formation
- localised invasion
- intravasation - interaction with blood components
- transport through blood circulation
- arrest in micro vessels of various organisms
- extravasation
- formation of micro metastasis
- colonisation - formation of macrometasasis
