Lecture 7 Flashcards
What is a neoplasm?
This is a new growth or an abnormal mass of cells
What are the two main groups of neoplasms?
- benign
2. Malignant
What are the behavioral and histological hallmarks of benign neoplasms?
Behavior:
- local growth only
- often in a capsule
Histology:
- resembles cell of origin
- few mitoses
- normal or slight increase in ratio of nucleus to cytoplasm
- cells are uniform throughout the tumor
What are the behavioral and histological hallmarks of malignant neoplasms?
Behavior:
- Invasive growth
- does not have a capsule around it
Histology:
- may show failure or cellular differentiation
- many mitoses, some are abnormal forms
- high nuclear to cytoplasmic ratio
- cells vary in shape and size
Define carcinoma?
This is a malignant tumor growing from epithelial tissue
many carcinomas affect glands that are involved with secretion
Define sarcoma?
A malignant tumor growing from connective tissues
Ex: cartilage, fat, muscle, tendons, and bones
leukemia?
Cancer of the blood or bone marrow
Melanoma?
malignant tumor of the melanocytes in the skin
Describe metastasis and how it occurs?
distant spread of tumor cells into other tissues:
Vascular:
- cells grow as a benign tumor in epithelium
- the cells break through the basal lamina
- cells invade the capillary
lymphatic
transcoelomic
Ex: peritoneal or pleural cavities
What are the two theories of tumor formation?
- clonal evolution
Develops through repeated rounds of mutations and proliferation
These damaged cells have a growth advantage - Stem cell
Tumors contain cancer stem cells
indefinite proliferate growth
linked, at first, with leukemia’s
What are the two mechanisms of cell death?
- necrosis- principle outcome of injury
2. apoptosis- regulated cell death
Describe the characteristics of necrosis?
- cell swelling
- damage to PM
- random DNA degradation
- inflammation
- surrounding tissue damage
- cell contents released
What are the features of apoptosis?
- cell shrinkage
- PM blebbing
- aggregation of chromatin
- fragmentation of the nucleus
- DNA fragmentation
- caspase cascade activation
- no inflammation
- no tissue damage
Why would a cell die by necrosis?
- pathological reasons
- acute cell injury
- unable to maintain homeostasis
- loss of PM integrity
Why would a cell die by apoptosis?
- physiological reasons
- genetic reasons
- programmed cell death
How can I assess necrosis in a morphological way?
- Propidium iodide staining
- H&E staining
- TEM
PI staining and necrosis?
live cell imaging
PI labels DNA
PI + = leaky/discontinuous PM (necrosis)
How H&E staining determine necrosis?
Increased eosinophilia:
loss of cytoplasmic DNA
increased denatured proteins
variable nuclear staining:
typical loss of basophilia and loss of nuclear staining
How does TEM help determine necrosis?
Discontinuous plasma and organelle membranes
How can I biochemically determine necrosis?
Random DNA degradation
increased levels lactate dehydrogenase (LDH)
How can I tell a cell is going through apoptosis?
- Membrane phosphatidylserine moves from the inner leaflet to the outer leaflet
- The membrane blebs
- condensed chromatin is found in the nucleus
- Cytochrome C is released from the mito
Apoptosis and the immune system?
- phosphatidylserine is exposed on the surface of apoptotic cells
- The apoptotic cell is engulfed or phagocytosed by a macrophage
- the engulfed apoptotic cell is internalized then degraded
- The macrophage releases cytokines IL-10 and TGF-beta to inhibit inflammation
When is apoptosis normal?
The development of digits during embryological development
normal tissue homeostasis
billions of cells undergo apoptosis daily, but they are all replaced
When is apoptosis abnormal?
Loss of cells due to apoptosis
losing irreplaceable cells
accumulation of cells due to the failure of apoptosis
What are the two main pathways of apoptosis?
- intrinsic
2. extrinsic
How are intrinsic and extrinsic the same and different?
Differ in introduction and regulation
Both result in activation of initiator and executioner caspases
Describe the intrinsic pathway of apoptosis?
- Apoptotic stimulus
- The release of cytochrome C
- Activation of Apaf1
- assembly of apoptosome
- Recruitment and activation of procaspase-9
- Activation of executioner procaspases
- caspase cascade leads to apoptosis
Describe the extrinsic pathway of apoptosis?
- Binding of the fas ligand to the death receptor
- recruitment of death domain adaptor protiens FADD and TRADD
- the formation of the death inducing signaling complex (DISC)
- caspase cascade
activation of initiator caspases (caspase 8)
activation of effector (executioner) caspases (caspase 3)
What are caspases and what do they do?
They are a family of enzymes that break down proteins
they are synthesized as inactive precursor- procaspases
activated by proteolytic cleavage
What is the Bcl-2 family?
They are intracellular regulators of apoptosis
Two classes
What are the two classes of Bcl-2?
- pro-apoptotic
Bid….. links extrinsic and intrinsic pathways
Bax and Bak…….. permeabilization of mitochondrial outer membrane
- anti-apoptotic
Bcl-2
Pro survival proteins (bcl-2)?
bcl-2 and bcl-xL
pro death proteins (bcl-2)?
Bax
Bak
Bid
Bcl-2 family pathway?
- death receptor signaling results in the activation of caspase 8
- caspase 8 cleaves Bid and tBid
- Bak and Bax can now enter the mito membrane
- cytochrome C is released from the mito
- caspases are activated and induce apoptosis
Assessment of apoptosis?
- Caspase activity
- Annexin 5- binds to phosphatidylserine
- DNA laddering
- TUNEL- detects DNA fragmentation
