Flashcards in T8 Deck (52)
What two heritable properties define cancers?
1. Reproduction in defiance of normal cell growth/reproduction
2. Colonization/invasion of territories normally reserved for other cells
Differ between malignant and benign tumours.
Malignant tumours spread (metastasize) into the territory of other cells whilst benign tumours are contained within territory of source tissue.
What are the two general categories of cancers and what two cancer types don't fit in either category?
Carcinomas arise from epithelial tissue, sarcomas from muscle/connetive tissue. Cancers of hemopoietic cells, in addition to cancers of nervous system.
Is a cancer necessarily a result of change in DNA sequence?
No, an epigenetic change may change gene expression leading to neoplasia. These include affecting heteromerization and gene silencing through methylation of cysteine.
What defines progression of cancer from on aberrant cell to a tumour?
Gradual development of degree of mutation, so that the parent cell may have had a few mutations whilst advanced daughter cells have aquired further mutations, changing the nature of the growth.
How can a cancer be likened to a species evolving?
Both follow the same rules for a successful proliferation:
1. mutation rate
2. number of reproducing individuals
3. rate of reproduction
4. selective advantage
What does genetic instability infer on cancerous cells?
That the DNA maintenance genes may be mutated in a way that increases incidence of further mutation in the cancer cell genome. This may or may not increase the malignancy of the cancer, depending on how much the DNA changes (approaches the optimum level of mutation/aquired properties).
Name two normally occurring cellular functions that if disturbed (up/down-regulated) can lead to neoplasia.
Cell division and apoptosis
How can cells with inactivated DNA-damage response mechanisms develop into cancers when the completion of their cell cycles sigbificantly slow down?
Accumulation over time of mutated cells eventually form a high-number basis, the division of which can be detected. This explains in part why cancers develop over many years before being detected.
How are replicative cell senescence mechanisms modulated in cancer cells?
Checkpoint mechanism, for example mediated by p53, is disabled through mutation of p53-gene so that replication continues despite de-capping of telomeres. Another modulation is the maintenance of telomerase activity, even when the activity would normally have been discontinued.
How is the cancer cell population maintained and enlarged?
Through divison of cancer stem cells into cancer strm cells or transit amplifying cells. These progress through mutations and epigenetic changes into malignant cancer stem cells.
Outline the steps leading to metastasis formation.
1. Cancers cells manage to escape into the blood through the 'leaky' blood vessles supplying the tumour, or a lymph vessle.
2. Cancer cells adhere to endothelium, penetrating it and forming a micrometastasis.
3. Parenchym is infiltrated and a full metastasis, cancer colony, is formed.
How does tumour angiogenesis lead to evolving of aggressive cancers?
The vessles formed are leaky and partyl malformed, leading to areas of hypoxia in the tumour. This makes for selection of cells that better withstand these hardh conditions. Metastasizing of these cells is more effective as they survive better in harsh conditions.
What is HIF-1α and what is its role in tumours?
Hypoxia inducible factor-1α, mediates tumour angiogenesis in hypoxic conditions.
What is the role of thre stroma for the tumour?
Throug extracellular signaling the stroma and tumour work together. The stroma induces tumour growth and the tumour excretes protein signal and proteases to modify the ECM.
List 9 properties that contribute to cancerous growth.
1. Self-sufficiency, no need fot survival sigbals
2. Insesitive to anti-proliferation signals
3. Less prone to apoptosis
4. Defective intracellular control mechanisms that respond to stress or DNA damage
5. Induction of help from normal stromal cells
6. Induction of angiogenesis
8. Genetic instability
9. Recruit ways of stabilizing telomeres
Are all carcinogens chemicals?
No. Ex. radiation is classified as carcinogenic.
Name a commo, rapid, test for mutagens.
The Ames test.
How come most carcinogenic chemicals are relatively inert as such?
They are converted enzymatically, ex. by liver cytochrome P-450, into more potent forms that induce mutation.
What combinations of tumour initiator and promotor exposure can lead to cancer?
1. One initiator and immediate rapid succession of multiple promoters
2. One initiator and delayed rapid succession of multiple promoters
3. Multiple, far spaced, initiator exposures
What are common tumour promoters?
Phorbol esters such as TPA (tetradecanoylphorbol acetate which activate PKC and phosphatidylinositol signaling pathway.
What is the first sign of initiator + promoter exposure in skin cancer?
Formation of a papilloma.
Are infections, for example by viruses, directly responsible for cancers?
Usually no. They mostly promote cancer formation. Ex. HIV virus weakens the immune response, making it easy for herpes virus HHV-8 to infect and directly cause Kaposi's sarcoma. Hepatitis B and C cause inflammation in the liver, increasing the chance of cancer formation. Also parasite may promote cancer formation.
What is a suggested most potent carcinogen?
Define cancer-critical genes.
Genes who alteration of which frequently leads to cancer.
What classes can cancer-critical genes be divided into?
1. Proto-oncogenes (overexpressed mutant form called oncogenes)
2. Tumour supressor genes(loss-of-function genes)
3. DNA maintenance genes (mutation results in genomic instability)
How do proto-oncogenes and tumour supressing genes differ in their activation into carcinogenic form?
Proto-oncogene mutation usually results in a dominant oncogene, whilst the mutation of a tumour supressor gene is usually recessive and need to by homozygous for it to take effect.
Why is Ras an oncogene in many cancer cells?
The mutation of Ras makes it unable to hydrolize GTP to GDP causing chronic activation and subsequent cancer.
What's so special about Rb gene and protein in oncology?
The Rb gene is commonly missing not only in retinobladtoma but aldo in many other forms of cancers. It is a tumour supressing gene.