Which of the following is a neoplastic condition in which malignant cells have not invaded across the cellular basement membrane?
Carcinoma in situ (CIS) is a flat, non-invasive neoplastic condition in which the cancerous cells have not invaded through the basement membrane of the cell. The basement membrane of a cell provides structural support and forms a selective barrier between the cell and the surrounding tissue. Once the cancer cells reach beyond the basement membrane, an invasive neoplasia is formed. In most cancers, CIS is pre-malignant; however, in bladder CIS it is considered to be a pre-invasive papillary cancer in which there is a greater than 50% chance of progression into invasive disease.
At which point of the cell cycle is p53 partially responsible for detecting genetic damage?
DNA damage causes a number of protein-protein interactions that alter protein phosphorylation. Initial sensing of damage is picked up by ATM and ATR proteins. These send signals to phosphorylate CHK2, CHK1, p53, MDM2 and BRCA1, which in turn arrest the cell cycle at checkpoints until DNA damage is repaired. The phosphorylation of p53 proteins causes altered activity in the CDK-inhibitor p21 WAF, which results in G1/S checkpoint arrest. S phase arrest results from phosphorylation of NBS1 and SMC1 directly via ATM. G2/mitosis arrest results from phosphorylation of CDC25C via CHK2 and CHK1.
Which of the following represents a premalignant process where abnormal cytological and architectural changes lead to disordered growth and maturation of a cell?
Dysplasia is a pre-malignant condition where there is abnormal cell growth, cellular atypia and abnormal differentiation. It can be a reversible process in its early stage but once it becomes severe it can progress to neoplasia. Metaplasia a process where one type of differentiated cell transforms into another differentiated cell type. This process is reversible. It is an adaptive response of a tissue to changes in the environment so that the tissue can withstand these changes.
Which of the following is NOT classically related to the effect of radiation therapy on tumour tissue?
The factors that influence the response of tumour and normal tissue to radiation are known as the 5 R’s: radiosensitivity, repair, repopulation, redistribution and reoxygenation. Tumours contain heterogenous cell populations, which vary in their response to radiation. The radiosensitivity, put simply, is the cell kill effect of radiation on a particular type of tissue. The cells ability to repair DNA damage caused by radiation will impact its ability to survive. After or during therapy surviving cells will have the ability to proliferate there by effecting response. A tumour with poor oxygen supply due to inadequate blood supply will be resistant to radiation. After a treatment the tumour blood supply may improve and hence reoxygenation occurs and this improves cell kill effect of further radiation doses. Radiation has differing cell kill effect depending on the cells position within the cell cycle. Radiation results in some synchrony of surviving cells, which then redistribute around the cell cycle. Hybridisation is the fusion of two somatic cells to form a single cell. It can also mean the binding of complimentary sequences of DNA or RNA. This is not classically involved in radiation effect on tumour tissues.
Which one of the following is FALSE regarding apoptosis?
Apoptosis or type 1 cell death is a type of programmed cell death, which is highly regulated and controlled. It is characterised by a sequence of molecular events that lead to particular morphological appearances. These include cellular shrinkage, breakdown of organelles, condensation of DNA into chromatin and blebbing. Autophagic cell death or type 2 cell death is a process where a cell digests itself.
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