Cancer Flashcards
Which factors contribute to cancer development?
Factors that contribute to cancer development:
* Exposure to cancer causing chemicals (carcinogens. e.g. smoking, environment)
* Viruses (HPV)
* Lifestyle
* Genetics (Mutations in: BRCA1, BRCA2 (breast cancer). TP53, PALB2, PTEN)
Cancer definition
Definition of cancer:
* uncontrolled cell division of abnormal cells
Characteristics of cancer cells
Characteristics of cancer cells
*
What are the 3 most common forms of cancer in the UK?
3 most common cancers in the UK:
* Lung
* Colorectal
* Breast
Eating ___g processed meat/day increased colorectal cancer risk by 18%
Eating **50g ** processed meat/day increased colorectal cancer risk by 18%
Red meat consumption increased cancer risk by what percentage?
Red meat consumption increased cancer risk by 6%
50g of unprocessed red meat eaten once a day increases cancer risk by how much?
50g of unprocessed red meat eaten once a day increases cancer risk by 20%
What can the haem in red meat do?
The haem in red meat can alkylate DNA
What is a carcinogen?
A carcinogen is a substance that can cause cancer
What are the two types of carcinogens?
Two types of carcinogens: Gentoxic and Epigenetic carcinogens
Genotoxic carcinogens
Genotoxic carcinogens:
* Damage or modify DNA
* E.g: Radiation, Alkylating agents (CH2CH2 double bond), Asbestos, Arsenic, Dimethylnitrosamine
Epigenetic carcinogens
Epigentetic carcinogens:
* Indirect mechanisms e.g. immunosuppression, hormonal imbalance, alter gene expression.
* May alter the rate of cell growth
* Doesn’t damage DNA
* Takes longer to develop
* Creates a favourable environment for cancer development
* E.g: Saccharin, Oestrogen, Bile acids
What are the 3 main types of malignancies?
3 main types of malignancies:
* Carcinomas (90 %, most common)
* Sarcomas (2%)
* Leukaemias (8%)
Do most cancers come from self renewing, essentially non-renewing or conditionally renewing cells?
Most cancers form from self-renewing and conditionally renewing cells.
What is tissue classification based on?
Tissue classification is based on the ability to replace cells.
3 types of tissue renewability REC
3 types of tissue renewability
R: Rapidly self-renewing tissues
E: Essentially non-renewing tissues
C: Conditionally renewing tissues
Rapidly self-renewing tissues
Rapidly self-renewing tissues
* Skin
* Intestinal epithelium
* Haematopoietic system (blood)
* Balance between damaged/aged cells and cell replacement required
Conditionally renewing tissues
Conditionally renewing tissues
* Little or no replacement under normal circumstance
* Regeneration can occur after damage. disease or hormonal influence
* E.g.: Liver, breast, prostate, uterus
Essentially non-renewing tissues
Essentially non-renewing tissues
* Have no capacity to replace cells
* E.g. ovum, Central Nervous System
Which type of tissue doesn’t usually have cancer formation?
Most cancers don’t form from essentially non-renewing tissues.
Where do cancers arise from?
Cancers arise from stem cells
What can pluripotent stem cells differentiate into?
Pluripotent stem cells can differentiate into lymphoid stem cells or myeloid stem cells.
Cancer is a ______ disease
Cancer is a clonal disease
How many forms do fibroids express in?
Fibroids only express in one form
Explain Carcinogenesis
Carcinogenesis
* Process of a normal cell transforming into a cancerous cell
* Takes time to occur (hence relation to age)
* Results in GENETIC ALTERATIONS (mutations)
50% of cancers are caused by a mutation in which gene?
50% of cancers are caused by P53 gene mutation
What is hyperplasia?
Hyperplasia:
Increase in number of cells (cell proliferation)
What is adenomatous polyposis coli protein (APC)?
Adenomatous polyposis coli protein (APC):
tumor suppressor gene
If genes are mutated, what happens to hyperplasia cells?
If genes are mutated, hyperplasia cells develop into carcinoma
Is cancer a genetic disease?
Yes, cancer is a genetic disease.
What is Kirsten rat sarcoma viral oncogene (K-ras)?
Kirsten rat sarcoma viral oncogene (K-ras):
* a gene that provides instructions for making a protein called K-Ras
* The protein relays signals from outside the cell to the cell’s nucleus. These signals instruct the cell to grow and divide or to mature and take on specialized functions
As we age what happens to DNA?
As we age, there is more damage done to DNA
Describe carcinogenesis
- Carcinogenesis is the transformation of a normal cell to a cancerous cell.
- Normal cell> hyperplasia>carcinoma> metastasis (potentially)
- It occurs due to mutations in tumour suppressor genes or oncogenes (mutated proto onco genes)
- The mutation of these tumour suppressor genes may cause cancer: K-Ras, SMAD, APC, P53.
- It occurs under specific conditions (may be triggered by damage)
- DNA damage accumulation promotes cancer development
Why is there a correlation between cancer formation and age?
There is a correlation between cancer development and age because damage accumulation of DNA takes time
Carcinoma ______ respond to signalling to stop proliferating
Carcinoma don’t respond to signalling to stop proliferating
Define hyperplasia
Hyperplasia:
* Increase in number of cells (cell proliferation)
Define oncogene
Oncogene:
* Mutated protooncogene
* product is produced in higher quantity or has higher activity
* Instructs cell to divide
* drives carcinogenesis at a molecular level
* Synthesize growth factors that act as signals for uncontrolled proliferation which leads to cancer formation
* if highly expressed, cancer is formed
* maintains the cell cycle
What is P53?
p53:
* Tumour suppresor gene
* Prevents excessive proliferation (increase in cell number)
* May cause: cell cycle arrest, apoptosis, DNA repair, inhibition of angiogenesis
* Induced by radiation, drug induced DNA damage, oncogenic and hypoxia
What do tumour suppressor genes do?
Tumour suppressor genes code for proteins that can STOP the cell cycle
What might P53 cause?
P53 may cause: cell cycle arrest, apoptosis, DNA repair, inhibition of angiogenesis
What are CDKs?
- CDKs are cyclin dependent kinases.
- Enzymes that add phosphate groups.
- They play a role in cell cycle regulation.
Growth _______ and cyclins _________ cell growth
Growth factors and cyclins stimulate cell growth.
What does P53 do to CDK?
P53 stops CDK (cyclin dependent kinase) from binding to cyclin via competitive inhibition by promotion of p21.
Which p? does P53 promote to prevent CDK?
p53 promotes p21 to prevent CDK
Oncogenes: Action?
Oncogenes:
* Initiate cell division
* Increase rate of transformation from a normal cell to a cancer cell
Tumour-suppresor genes: Action?
Tumour-suppressor genes:
* Prevent excessive growth of a cell
* By controlling cell proliferation
OR
* By control of DNA repair rate
DNA repair genes: Action?
DNA repair genes:
* Repair damaged DNA
* Work in different ways to repair damaged DNA e.g. correct mismatched bases, correct copying erros that distort the structure of DNA.
Apoptosis genes: Action?
Apoptosis genes:
Control the cell’s self-destructive process
What is lipid peroxidation?
Lipid peroxidation:
- Free radicals steal electrons from lipids in cell membranes leading to cell damage
- Chain of events that can lead to reactive oxygen species formation and oxidative stress
What happens if apoptosis genes are switched off?
If apoptosis genes are switched off cancer development may be promoted
What are free radicals?
Free radicals are highly reactive molecules with unbound electrons. They are dangerous.
How can free radicals cause damage?
Free radicals can cause damage by attempt of stabilization by taking electrons from nearby molecules, causing cellular damage.
How can the cell generate free radicals?
The cell can generate free radicals in the following ways:
* Absorption of energy (e.g. UV light, x-rays can hydrolyse H20 to OH- and H)
* Metabolisms of chemicals or drugs, ( e.g., CCL4 (carbon tetrachloride) to CCL3.)
* Transition metals e.g., Fe & Cu catalyse free radical formation reactions.
* Nitric oxide can be converted to highly reactive species e.g., peroxynitrite anion (NO3-).
What can nitric oxide cause?
Nitric oxide can cause vasodilation of the blood vessels
What do free radicals target?
Free radicals target various cellular components including lipids, proteins and DNA.
Which areas have lipid bilayers?
The nucleus, mitochondria, and cell membrane have lipid bilayers.
What is lipid peroxidation?
Lipid peroxidation:
* Breakage of a lipid by a free radical
* Free radical is generated (initiation), free radical attacks the lipid, lipid broken down into two forms, another free radical is generated.
* Two stages: initiation and propagation
What are the cell injuries which can be caused by free radicals?
The cell injuries which can be caused by free radicals:
* Lipid bilayer
* Nucleus: DNA fragmentation
* Lysosomes (content can be released into cell), Nucleus, Mitochondria : Membrane lipid peroxidation
* Protein cross linking and fragmentation
What mechanisms are there to try and reduce free radical cell injury?
Mechanisms to reduce free radical injury:
* Antioxidants: block initiation of free radical formation or inactivate them (E.g.: Vitamin E, Ascorbic acid, glutathione)
* Iron (ferritin= iron storage form)and copper bound to storage/transport proteins> minimize OH formation.
* Enzyme free radical scavengers. E.g. superoxide dismutases, catalase, glutathione peroxidase
What creates oxidative stress?
Oxidative stress summary:
* Imbalance between production and removal of free radicals
* Cellular reactions may generate partially reduced reactive oxygen species (ROS) e.g.,
Alkoxyl radical from alcohol
Peroxynitrite (NO3-) from nitrite + H2O2
O-2 [superoxide] and H2O2,
All create: Oxidative Stress if not countered by antioxidants
What happens if oxidative stress isn’t countered by antioxidants?
If oxidative stress isn’t countered by antioxidants:
* Cellular components may be damaged
* Cancer, diabetes, neurodegeneration, kidney disease, and CVDs may materialize
Why is the ratio of reduced glutathione to oxidized glutathione important?
The reduced (GSH)-to-oxidized (GSSG) glutathione ratio represents a dynamic balance between oxidants and antioxidants.
It gives an indication of oxidative stress
Why is the link between diet and cancer complex?
The link between diet and cancer is complex because our diet is made of lots of different foods and nutrients.
What type of diet is likely to reduce the carcinogenic process?
A balanced diet is thought to reduce the carcinogenic process via:
* Maintaining high levels of antioxidants (fruit & veg)
* Healthy immune system
* Higher levels of fibre,
* Low red meat, salt and sugar
