Module 2.1: Physiology Review
● Introduction to Cancer
○ Second leading cause of death in the United States.
○ Statistics (2018 estimates): Deaths, New Diagnoses.
○ Improved death rates and 5-year survival rates since 1990s.
○ Can affect all ages and almost any organ.
○ Most common types by diagnosis (overall, men, women).
○ Highest mortality rate (men and women).
○ Topics covered in module: Cell cycle, proliferation, differentiation, terminology,
characteristics, etiology, diagnostics, treatments.
● Defining Neoplasia and Neoplasms
Cancer Cause - caused by genetic mutations. Different organs are prone to different types of
mutations.
○ Cancer: Unregulated growth of abnormal cells.
1. Often shows patterns of altered cell differentiation and growth. ○
Neoplasia: "New growth" process.
○ Neoplasm: The new growth itself. Lacks coordination and control of typical
proliferation and differentiation. Can be benign or malignant.
1. Benign (slow growth, well differentiated not as likely to undergo
mitosis, resemble tissue or origin, stay contained, don't invade or spread)
2. Malignant - invade and destroy nearby tissue, grow rapidly, metastasis
through blood system or lymphatic system
○ Lack normal regulatory controls (unlike hypertrophy/hyperplasia).
○ Serve no purpose, don't respond to stimuli, grow at host's expense. ●
Normal Tissue Renewal and Repair
○ Requires:
1. Proliferation: Cell division for replacement or additional cells.
■ In neoplasms: excessive, uncontrolled, unregulated proliferation due
to genetic abnormalities.
2. Differentiation: Cells become specialized with mitotic division.
■ Cell goes down a path to become more specialised and less likely to
proliferate
3. Apoptosis: Controlled cell death to eliminate old, damaged, or unwanted
cells.
● Regulation of Cell Lifecycle
○ Carefully regulated at beginning (proliferation) and end (apoptosis).
, ○ Proto-oncogenes: Encode proteins that signal for cell proliferation (tightly
regulated). Cause cells to divide.
1. Growth factors, transcription factors, cytokines, etc
○ Tumor suppressor genes: Encode proteins that inhibit cell growth and signal for
apoptosis when necessary (e.g., if unregulated growth could lead to tumor
formation).
1. Detect DNA damage, mutations, stop cell from proliferating
2. Some can fix.repair, if they cannot they stop cell from dividing, or if
damage is so great, they trigger apoptosis to prevent those cells from
passing on to next generation
○ Dysregulation in either (proto-oncogenes or tumor suppressor genes) can lead to
unregulated growths and cancer.
○ Cancer → oncogenes are overexpressed, tumor suppressors lost or reduced,
silenced or stopped.
● The Cell Cycle [5, 6, 7 (Figure 2.1)]
○ 2 major phases - interphase and mitosis
1. During interphase busy growing, and doing their particular job to keep up
and maintain a tissue/organ.
■ If cell is going to be highly differentiated think of muscle cell or
neuron, they can leave interphase and enter G0 - growth zero -
live out their life and never proliferate and die
■ If in tissue that generates often- then goes from interphase to
mitosis where it can actively divide
■ For somatic cells (non gametes, or eggs, or sperm) in interphase
DNA is going to be replicated
○ Process: Cell duplicates genetic information and divides into two identical
daughter cells.
○ Phases:
1. INTERPHASE G1 (gap 1): DNA synthesis stops; cell enlarges;
RNA/protein synthesis begins.
■ Doubles organelles, increases proteins, and cytoskeletal
components to make sure that daughter cells to come will have
enough
■ At the end it stops at G1 S checkpoint to make sure it has
everything needed
○ Right components have been duplicated, nothing detrimental
to stop cell going forward
○ If everything is okay here, the cell enters the S phase.
2. INTERPHASE S phase: DNA synthesis occurs (produces two sets of
chromosomes).
3. INTERPHASE G2 (gap 2): DNA synthesis stops; RNA/protein synthesis
continues.
Interphase: G1, S, and G2 phases.
, 4. M phase: Mitosis (dividing DNA) and cytoplasmic division.
○ Cell Cycle Checkpoints: Molecular surveillance at end of G1, S, G2.
1. Ensures readiness for next phase, halts cycle for replication completion or
DNA repair.
○ G0 (resting state): Occurs when nutrients/growth factors unavailable or for
highly specialized cells leaving cell cycle.
1. Cells can re-enter when conditions are favorable.
2. Highly specialized/terminally differentiated cells (e.g., neurons)
may permanently stay in G0. ● Cell Proliferation
○ Process of increasing cell numbers by mitotic cell division.
○ Normal tissues: New cells produced = cells dying/shed; tissue structure/function
maintained.
○ Cancer: Equilibrium unregulated and unbalanced.
○ Human cell categories:
1. Gametes: Ovum and sperm; haploid (one set of chromosomes); for
sexual fusion.
2. Somatic cells: Non-reproductive; diploid (both sets of chromosomes);
form rest of body.
○ Three groups of proliferating cells:
1. Well-differentiated neurons, skeletal/cardiac muscles (rarely divide).
2. Progenitor/parent cells (continue to divide, e.g., blood, skin, liver).
3. Undifferentiated stem cells (can enter cell cycle, produce progenitor cells
if needed).
○ Varying reproduction rates (e.g., WBCs, GI lining cells).
○ Increased reproduction during injury/loss (e.g., blood loss stimulating bone
marrow).
● Cell Differentiation
○ Process by which cells become more specialized in structure and function.
○ Resulting adult cell has specific characteristics (composition, function, lifespan).
○ Origin: Fertilized ovum.
○ Factors influencing differentiation: Specific genes, gene expression patterns,
chemical/environmental stimuli.
○ Precise control in prenatal/postnatal life is crucial for proper numbers and types of
cells.
○ As differentiation progresses, cells lose ability to develop characteristics of other
cell types (maintains organ integrity).
● Progenitor Cells vs. Stem Cells [11, 12, 13, 14, (Figure 2.2)]
○ Progenitor (parent) cells: Partially differentiated cells of a lineage, still able to
divide to produce daughter cells of same lineage.
○ Stem cells: Incompletely differentiated and dormant until needed.