Malignant disease 17/10/22 Flashcards
What is the cell cycle?
There are four phases in the eukaryotic cell cycle, G1, S, G2, and M.
Interphase - G1, S, G2
G0 - cell exists and doesn’t divide.
G1 - cell plans to divide and grows in size. The end of G1 produces proteins, such as geminin that turn off the DNA replication system. Cells in G1 may exit from the cell cycle and enter G0 instead.
S phase - nuclear DNA is replicated (S = synthesis).
G2 - organelles are replicated. Towards the end chromatin fibres of the interphase nucleus begin to condense.
M - cell enters mitosis.
What are the cell cycle checkpoints?
The G 1–S boundary - cell must receive a signal to continue into next phases, of not then it enters G0.
The G 2 –M boundary - cell checks all DNA is properly replicated.
Multiple DNA damage checkpoints - this occurs through all cell cycle phases.
The M-phase checkpoint - ensures the mitotic spindle checkpoint which ensures that mitosis cannot progress until the spindle is fully organized and all the chromosomes are attached to it.
What is mitosis
Prophase - individual chromosomes can be observed as discrete structures under the microscopy. Each duplicated chromosome appears as two identical sister chromatids joined at
their centromeres. The two centrosomes move towards the opposite poles of the cell. Mitotic spindle (microtubules/asters) extends from each centrosome. Nucleoli disappears and chromosomes become condensed.
Metaphase - chromosomes are aligned at the metaphase plate.
Anaphase - cohesion proteins holding the two sister chromatids of each
chromosome pair together are cleaved so the chromatids can be pulled apart. Chromosomes move centromeres first toward the opposite poles of the cell, this is anaphase A movements. Anaphase is complete when the two poles of the cell have received a complete set of chromosomes.
Telophase - the cell divides and the nucleus reappear in each one. The spindle disappears and nuclear envelopes form.
Cytokinesis - the cytoplasm of the parent cell divides, this is known as cleavage. This slowly divides the cells and pinches them off, this process happens in late anaphase to end of telophase.
What is meiosis?
Meiosis happens in two phases, Meiosis I and meiosis II.
Meiosis I is just mitosis, however, crossing over of genetic material also occur (recombination) so that you produce 4 genetically different haploid gametes at the end.
Meiosis II during prophase II, the two daughter cells prepare for the second division and form a new spindle.
Metaphase II, the chromosomes move to the equator of the spindle and the chromatids are oriented to face opposite poles.
Anaphase II, the chromatids separate from each other and move to opposite poles of the cell.
Telophase II, each cell divides to form two daughter cells that have only
haploid numbers of chromosomes. Thus, the parental cell has produced four haploid daughter cells.
What regulates the cell?
External regulation is proteins or large peptides called growth factors control the cell growth, mitosis, and meiosis.
Internal regulation is cyclin-dependent kinases (CDKs), cyclins, and CDK inhibitory proteins.
What is apoptosis?
Programmed cell death.
What is necrosis?
Accidental cell death resultant from chemical or physical assault to the cell or tissue.
What is cancer?
Uncontrolled growth of abnormal cells in any tissue or organ.
What is neoplasia?
Uncontrolled growth of abnormal cells or tissue. Can be benign or malignant.
For example, carcinoma and fibroids in uterus.
What is anaplasia?
Lack of differentiated neoplastic cells. Cells become more primitive.
For example, leiomyosarcoma (malignant smooth muscle tumour) and leiomyoma (benign smooth muscle tumour).
What is hyperplasia?
An increase in the number of cells in an organ or tissue.
For example, Cushing’s syndrome (adrenal cortical hyperplasia) and breast growth in puberty.
What is metaplasia?
One differentiated somatic cell differentiates into another differentiated somatic cell.
For example, fibrous tissue into bone tissue.
What is dysplasia?
Abnormal cells (size, shape, organisation) within a tissue or organ.
For example, atypical mole (melanoma).
What is hypertrophy?
An increase in the size of a cell without increase in numbers. Results in large tissue or organ.
For example, prostatic hypertrophy and muscle gain.
What is atrophy?
A decrease in cell size and/or cell number.
For example, muscle wasting and thymic atrophy.
What are the causes of atrophy?
Decreased functional demand
Loss of hormone stimulation
Decreased physical exercise
Loss of blood supply
Injury to blood vessel
Decreased flow of blood (atheromatous occlusion)
Transection of nerve fibres
Infective/inflammatory disorders
What’s the difference between physiological and pathological?
Physiological is normal development and pathological is diseased or not normal development.
What are the characteristics of malignant cells?
Loss of growth control
Resistance to apoptosis
Immortal (telomerase)
Sustained angiogenesis
Invade the surrounding tissue
Colonise and survive in an ectopic environment (metastasis)
Anchorage-independent growth
Loss of contact-inhibition
What is anchorage-independent growth?
Cancer cells are able to survive without anchoring to an extracellular matrix or neighboring cells. They can proliferate alone in a Petri dish.
What is contact inhibition?
Process of stopping cell growth. Cancer cells lose sensitivity to contact inhibition leading to proliferation.
What are the characteristics of benign cells?
Slow growth
Resemble tissue of origin
Lack of invasion
Absence of metastases
What is the growth factor signaling cascade?
1) Growth factor binds to a growth factor receptor (ligand-independent signaling).
2) Signal transducers and transcription factors lead to a cell proliferation, apoptosis, and differentiation.
What is a telomere?
It is a structure found at the ends of our chromosomes. They consist of the same short DNA sequence repeated over and over again. This protects the DNA from degradation over time as each replication causes the loss 25-200 bases.
What role do telomeres play in disease?
In cancer there is a higher activity of telomerase and alternative lengthening of telomeres which means the DNA is not as easily damaged and cells can become immortal.
What is angiogenesis?
Angiogenesis is how the body forms new blood vessels. This is a normal part of growth and healing.
What is the angiogenesis switch?
1) Cancer cells need oxygen and nutrients to grow.
2) Tumours will send signals (pro-angiogenic factors such as VEGF/FGF) that exceed the anti-angiogenic factors.
3) This results in the angiogenic process proceeding which means more blood vessels develop around the tumour to sustain growth.
What is metastasis?
The spread of cancer cells from the place where they first formed to another part of the body.
What are the 6 routes is cancer spread by?
1) Direct
2) Lymphatic
3) Venous
4) Transcoelomic
5) Cerebrospinal fluid
6) Arterial routes
Direct - tumour grows into structures and tissues surround it.
For example, mediastinal tumour surrounding and compressing the superior vena cava.
Lymphatics - tumours spread through the lymphatic system.
For example, carcinoma of breast first spreads to the local axillary lymph nodes.
Venous - tumours spread through the veins. For example, sarcomas commonly spread this way and some tumours can grow in a vein causing its obstruction (renal cell carcinoma).
Arteries - spread of tumours through arteries. This is not common as they are difficult to penetrate but can occur in later stages of metasistic spread.
Transcoelomic - spread of a tumour through a body cavity.
For example, gastric carcinoma cells seeding through the peritoneal cavity to cause ovarian cancer.
CSF - spread of a tumour through the CFS fluid in the nervous system. This can cause brain cancer.
What is the mechanism behind metastasis?
1) The cancer will grow at the primary site and infiltrate the surrounding connective tissue; this may necessitate breaking through a basement membrane and the connective tissues nearby. It may also have to overcome inhibitor substances to the enzymes that it produces to break down these connective tissue proteins.
2) It is only then that it can reach the lymphatic and blood vascular channels, which are an important route for dissemination. The vessel wall is traversed and the tumour cells must detach to float in the blood or lymph and hope to evade any immune cells that might destroy them.
3) They must lodge in the capillaries at their destination, attach to the endothelium again, and penetrate the vessel wall to enter the perivascular connective tissue where they finally proliferate to produce a tumour deposit and angiogenesis can occur. Even here, the local environment is important in dictating whether the cells will grow.
What is the gross appearance of a malignant tumour?
The tumour edge is irregular, due to infiltrative growth.
The cut surface is variegated, due to haemorrhage and necrosis within tumour.
Evidence of secondary spread in the draining of lymph nodes or adjacent structures may obviously be infiltrated.
