Molecular Basis of Neoplasia

Question 1

Define neoplasia

Answer 1

Disordered cell growth that is triggered by mutations acquired by a single cell or a whole progeny of cells.

Question 2

Is neoplasia always acquired change? Are there any environmental or genetic factors associated with it?

Answer 2

Yes. Even though it has environmental and genetics factors associated with it but it is an acquired change.

Question 3

What are the 2 main characteristics of neoplasia

Answer 3

It is autonomous, cells get free from restrainment of cell proliferation

Question 4

What are some of the systemic effects of cancer

Answer 4

1. Cachexia
2. Bleeding and secondary infections
3. Local invasion
4. Infarction and rupture

Cancers of endocrine glands can have a wide variety of secondary effects

Question 5

Explain the biochemical basis of cachexia

Answer 5

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.

Question 6

Define paraneoplastic syndromes

Answer 6

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

Question 7

What is cancer grading

Answer 7

Determine to what extent is it differentiated

Question 8

What is the criteria employed for cancer staging? What are the characteristics that are looked at

Answer 8

TNM
T - characteristic of primary tumor, like size and extent of invasion
N - involvement of regional lymph node
M - distance to metastasis

Question 9

What is the idea of trasnformation

Answer 9

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.

Question 10

Further notes on trasnformation

Answer 10

Multiple genetic changes are needed to cause cancer:

1. 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.
2. Vast majority of mutations are somatic, so cancer happens later in life
3. 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.

Question 11

BCL2 is associated with

Answer 11

Follicular lymphoma

Question 12

What is chromothrypsis

Answer 12

Extensive breakage and rejoining of chromosomes. Associated with osteosarcoma and glioma

Question 13

What happens in evasion of senescence

Answer 13

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

Question 14

What is always required for cancer activation stage

Answer 14

Telomerase activity is always required before cancer activation phase

Question 15

At what size is when tumor angiogenesis needed

Answer 15

When the tumor gets to 1 to 2 mm in size

Question 16

What is needed for metastasis

Answer 16

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

Question 17

How does PET scan work

Answer 17

Increase glucose uptake by cancer cells is the basis for PET scan

Question 18

What does tumor cells do to increase ATP production for rapid growth

Answer 18

They undergo metabolic reprogramming induced by upregulated pathways facilitated by oncogenes and these same pathways were previously inhibited by tumor suppressor genes

Question 19

What cells fight the tumor cells

Answer 19

Cytotoxic T cell
Macrophages
Natural killer T cells

Question 20

How does tumor cell avoid the immune system of the body

Answer 20

1. Selective outgrowth of antigen-negative variants
2. 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.
3. Some cancer cells secrete immunosuppressants that decreases the rigor of the immune system
4. Induction of T cells

Question 21

What is induction of T cells

Answer 21

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

Question 22

Explain the concept of one hit and two hit in terms of moving forward function and blocking function

Answer 22

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

Question 23

By that concept reactivation of telomerase, would that need one hit or two hits

Answer 23

One hit