Molecular Basis of Neoplasia Flashcards
Define neoplasia
Disordered cell growth that is triggered by mutations acquired by a single cell or a whole progeny of cells.
Is neoplasia always acquired change? Are there any environmental or genetic factors associated with it?
Yes. Even though it has environmental and genetics factors associated with it but it is an acquired change.
What are the 2 main characteristics of neoplasia
It is autonomous, cells get free from restrainment of cell proliferation
What are some of the systemic effects of cancer
- Cachexia
- Bleeding and secondary infections
- Local invasion
- Infarction and rupture
Cancers of endocrine glands can have a wide variety of secondary effects
Explain the biochemical basis of cachexia
It is caused by later stages of cancer, these cancer cells release cytokines which causes the body to be in a hyper metabolic state that leads to weakness, fatigue, wasting of lean mass, weakness and severe weight loss.
Define paraneoplastic syndromes
Some of the diseases can be associated with cancers since cancer cells produce excess of hormones or other proteins that are the first symptoms that an individual experiences regarding its cancer. For example small cell carcinoma can lead to Cushing’s syndrome whereas squamous cell carcinoma of the lung can lead to hypercalcemia
What is cancer grading
Determine to what extent is it differentiated
What is the criteria employed for cancer staging? What are the characteristics that are looked at
TNM
T - characteristic of primary tumor, like size and extent of invasion
N - involvement of regional lymph node
M - distance to metastasis
What is the idea of trasnformation
When a cell acquires a mutation to become a cancer cell with the progress of time there is a process called transformation that happens in the cell which leads to further mutations in the cell that gives it added survival advantage and impairs apoptotic pathways and eventually the cancer becomes malignant. Also with time this leads to the development of metastatic cancer.
Further notes on trasnformation
Multiple genetic changes are needed to cause cancer:
- Only a small number of genes have the ability to acquire mutation and lead to the development of cancer. Mutations in most of the other genes causes cell to undergo apoptosis.
- Vast majority of mutations are somatic, so cancer happens later in life
- Only small number of mutations are constitutional (meaning that they are always present in a cell. These are important as they can be passed on to individuals and predisposes a person to cancer.
BCL2 is associated with
Follicular lymphoma
What is chromothrypsis
Extensive breakage and rejoining of chromosomes. Associated with osteosarcoma and glioma
What happens in evasion of senescence
p53 and p16 regulate senescence. Mutation in the genes for these 2 proteins leads to tumor development.
Usually when telomere is lost, this is sensed as DNA damage and the cell undergoes apoptosis. Telomerase doesn’t let this happen as it can make telomeres and add it to the ends of the DNA
What is always required for cancer activation stage
Telomerase activity is always required before cancer activation phase
At what size is when tumor angiogenesis needed
When the tumor gets to 1 to 2 mm in size
What is needed for metastasis
A lot of genes have to get active before the cell can metastasise. This is achieved through diversity in the neoplastic colony where cancer cells literally evolve by undergoing further mutations
How does PET scan work
Increase glucose uptake by cancer cells is the basis for PET scan
What does tumor cells do to increase ATP production for rapid growth
They undergo metabolic reprogramming induced by upregulated pathways facilitated by oncogenes and these same pathways were previously inhibited by tumor suppressor genes
What cells fight the tumor cells
Cytotoxic T cell
Macrophages
Natural killer T cells
How does tumor cell avoid the immune system of the body
- Selective outgrowth of antigen-negative variants
- Some cells make MHC (major histocompatibility complex), which is made from HLA gene (Human Leukocyte Antigen). So these cancer cells are not identified as foreign by the body.
- Some cancer cells secrete immunosuppressants that decreases the rigor of the immune system
- Induction of T cells
What is induction of T cells
I think what he is trying to say here is that cancer cells express PD-1 or either they secrete PD1 ligand that inhibits immune response by increasing apoptosis of T cells and reducing the apoptosis of help T cells that are involved in immune suppression
Explain the concept of one hit and two hit in terms of moving forward function and blocking function
One hit mutation is needed by moving forward functions such as oncogenes as they have gain of function whereas blocking function needs two hits in order to allow development of cancer
By that concept reactivation of telomerase, would that need one hit or two hits
One hit
