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Flashcards in BMS379 Cancer Biology Deck (451)
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What are the main hallmarks of cancer?

-Sustaining proliferative signalling
- Evading growth suppressors
- Resisting cell death
- Activating invasion and metastasis
- Inducing angiogenesis
- Enabling replicative


What are the two elements that underpin cancer development?

Genome instability and mutation and Avoiding immune destruction are the two underpinning elements that allow the other cells to express the other hallmarks


How common is cancer?

- 50% of the population will be diagnosed with cancer
- 75% of 75 year olds who die from something that was not cancer is shown to have a tumour


What is the main risk factor of cancer?



Is cancer increasing?

Cancer incidence is increasing because life span is increasing


Give a study that shows that risks to certain types of cancers are due to environment

Migration studies
- On two occasions there are accounts of large amounts of migration from japan to US
- In japan have an increased risk of stomach cancer and a low risk of prostate and breast cancer
- Caucasian people in the US have a large risk of prostate and breast cancer but low risk of stomach cancer
- Japanese American people (who have lived in America) have profiles that resemble Caucasians, implying that a major factor for risks to types of cancer is based on the environment and not genetics


What is the relationship between the log of cancer incidence and the log of Age?



Why is the relationship between the log of cancer incidence and the log of Age linear?

- The probability of a change associated with cancer P(C1)
- The chance that the change will have happened goes up with age: P(C1) A
- Several changes needed (n) before a tumour (T) develops: P(T)=P(C1). P(C2). P(C2) ….P(Cn) x A^n
- This can be rearranged to LogP(T) = nLogA + Constant which is the equation of a straight line


How many mutations are required for a tumour to form?

Can use LogP(T) = nLogA + Constant to calculate the slope (n)
= 6


Give evidence for the genetic basis of cancer

- Some families are susceptive to some types of cancer e.g. retinoblastoma, Wilms Tumour
- This provides evidence for a genetic component e.g. the existence of tumour suppressor genes


What were the first experiments that showed an environmental component in cancer?

Percival Pott
- He undertook an examination of chimney sweeps and noticed that they were prone to scrotal cancer suggesting an environmental influence
- Lead to the Chimney Sweepers Act of 1788
John Hill
- Found that people who took snuff were prone to nasopharyngeal cancer


How did Richard Doll look find a link between smoking and cancer?

- Looked at data in relation to cancer and found that an increase in smoking in men and women resulted in an increase in counts of deaths due to lung cancer with a 20-year lag
- Lung cancer is a rare form of cancer unless a smoker
- Link between number of smokers in a country and lung cancer prevalence in men


Give the first experimental evidence for link between smoking and tumour formation

Katsusaburo Yamagiwa 1915
- His experiment was the first experimental method to induce cancer
- Took an extract from coal tar and treated the ears of rabbits, forming carcinomas. This proved that a substance found in cigarettes directly induced cancer


In the 1950s what origins of cancer had been identified?

- Benzopyrene is the substance found in coal tar
- Also found that x rays could induce cancer
- Chicken virus could cancer
- At the time, it was not clear what the relationships were between these things but it did eventually lead to the mutagenesis theory of cancer


What are the two types of mouse models used to model cancer?

- Genetically engineer mice where genetic changes are introduced
- This looks at endogenous cancers in that organism
Nude mice
- Xenograft model of human cancer
- Introduce human cells into the immuno-compromised mice
- These mice will develop tumours derived from the human cells


What are oncomice used for?

Useful for looking and understanding mouse cancer, as well as cancer development


What are nude mice used for?

This is useful when studying treatments for human cancers – essential before human clinical trials


What are the problems with oncomice?

- Charcateristics of mouse cancer
- Time of onset
- Nature and behaviour of primary and metastatic tumour


What are the problems with nude mice?

- Some characteristics of human cancer
- Time of onset
- Nature and behaviour of primary and metastatic tumour


What model of cancer dominated in the 1970s?

The viral model


What and when was the first tumour virus discovered?

In 1910, Peyton Rous discovered the first tumour virus: Rous Sarcoma Virus (RSV)


How did Peyton Rous shown that RSV induced cancer?

He removed the sarcoma from the muscle of the chicken and filtered through fine pore filter. Too small to bacteria so must be virus. He then injected this filtrate into chickens and they all developed sarcomas. This suggested that there was an infectious agent causing cancers


How did Howard Temin and Harry Rubin contribute to understanding of viral cancers?

- They found that RSV could continuously infect cells and have a productive lifecycle in cultured cells. Infected tissue culture cells displayed traits that were similar to cancerous cells
- Primary cells morphology changes if infected with RSV - increased thickness of cell layer, loss of contact inhibition and became rounded
- Anchorage independent growth - If suspend cells in a semi solid medium and infect them with RSV, they will grow in the medium unlike primary cells. Primary cells need to attach to something to grow.
- They took fibroblasts (primary cells) that were previously infected with RSV into immune compromised mouse (nude. This resulted in tumour formation


What kind of virus is RSV?



How many genes do retrovirus's have?

Three genes: gag, pol (polymerase), env


How many genes does RSV have?

RSV has an extra gene to other retrovirus's: src


Who gave the first theory to how an RNA virus can persist through successive cell growth cycles?

Temin first suggested that the viral genome could be reverse transcribed into a DNA intermediate


How was the theory of reverse transcription proved?

David Baltimore discovered the enzyme reverse transcriptase in 1970, proving this theory. This provides the basis for molecular biology


How does an RNA virus persist in the cell through successive cell growth cycles?

- The virus converts RNA into DNA using reverse transcriptase which is then integrated into the host genome. This DNA is then transcribed by the host cell machinery making lots of RNA copies of the virus
- This suggested away that mutations are caused by these viruses: potential explanation for causing cancer


Why did the viral theory of cancer dominate?

- Due to experiments where cells, that are treated with a nucleic analogue, were added into a culture medium. This resulted in the retroviral sequences, that were embedded in DNA, excising from DNA causing the virus to propagate, producing viral particles
- Theory was that these insults to nucleic acids would cause the nucleic acids reactivation in some way. This could induce viral production
- This might lead to an infectious and transforming virus under certain circumstances