Week 4 Breast Mass Flashcards
What are some Key structural features of the nucleus ?
Nuclear pores —> increased permeability
Double layer nuclear membrane continuous with ER
Nucleolus
Chromatin
What are some key functions of the nucleus ?
DNA transcription —> mRNA
Controls and regulates activities of the cell: metabolism and growth
Main functions of the ER
Ca2+ storage
Protein and lipid synthesis
Protein folding, modification and transport
What are the important functions of the golgi ?
Protein maturation
Vesicle transport and packaging
Production and secretion of mucus
What are the important structural features of the golgi ?
Consists of cisternae
Has cis and trans face
What are the main functions of the mitochondria ?
Produce ATP
Structure of mitochondria
Inner and outer membrane with transmembrane space between
Contains own genome
Cristae
Inner membrane responsible for ATP synthesis and respiration
Briefly outline protein targeting and translocation into the ER
- Signal sequence of growing peptide
- Binding of SRP to signal peptide —> pause in translation
- SRP binds to SRP receptor in rough ER membrane and protein translocator is present
- Translation continues and translocation begins, SRP is released and will be recycled
- Protein is released into ER lumen
What happens to ubiquitin tagged protein ?
Bound for degradation
What is the function of chaperones
Help with protein folding and prevent accumulation of protein aggregates
CTFR gene mutation mechanism and effect
Protein misfolding and degradation —> CF
B-glucoside mutation and effect
Decrease lysosome enzyme —> decreased degradation of lipids —. Gaucher’s disease
Proteosome (ubiquitin) resistance mechanism and effect
Evasion of apoptosis —> multiple myeloma
Cell polarity definition
Positional asymmetry within and between cells
Describe what is seen in hyperplasia
Increased proliferation
Lumens still present
Describe what is seen with LCIS
Increased dysplasia
Epithelial polarity disturbed
Lumens are lost
Describe what is seen with ILC
Loss of epithelial polarity
Cells invade basement membrane
What are microfilaments composed of
Globular actin
important functions of microfilaments
Cell adhesion
Generation of contractile force
Cell shape
Surface projections
Important functions of intermediate filaments
Tensile strength
Architectural scaffold
Markers of specific tissues
What is the importance of motors that move along microtubules ?
Critical for binding cargo and moving it around the cell
What do cell surface receptors bind to ?
Other receptors on neighbouring cells
ECM proteins outside cell
Describe structure and function of linker proteins
Peripheral membrane scaffolding proteins in the cytoplasm
Bind to cytoplasmic tails of cell surface receptors
Link complex to cytoskeleton inside cell
Adherens junctions function
Initiate cell-cell adhesion on lateral aspect of cells
Adherens junction receptors
Cadherins
Function of Cadherins
Bind same Cadherin on adjacent cell
—> tissue segregation
Adherens junction linker proteins
Catenins
Functions of catenins
Link cadherins to cytoskeletal elements
Proliferative signal transduction
What is the cytoskeletal element of adherens junctions
Actin
Function of tight junctions
Regulate the movement of macromolecules between cells
Located near apical surface —> delineate apical and basolateral membrane domains
Desmosomes structure
Spots
Linked to stable intermediate filaments
Function of desmosomes
Link cells together
What is the function of gap junctions ?
Allow for passage of small molecules and ions between cells
Communicating junctions
Hemidesmosomes function
Anchor cells to ECM
What is the function of focal adhesions ?
Critical for cell migration
What is needed for cell to pass through restriction point in G1 ?
Mitogens (ex. Estrogen)
What do tumour suppressors do ?
Halt cell cycle at multiple checkpoints when damaged DNA is recognized
What are two mutations that can lead to bypass of restriction point ?
Rb, p53
How is cancer classified at the cellular level ?
Excessive cellular proliferation
Uncontrolled growth
Tissue infiltration
How is cancer classified at the molecular level ?
Genes that regulate growth are disordered
What happens during G1 gap phase ?
Cell increases in size
New proteins and organelles synthesized
What happens during S phase
Chromosomes replicated
DNA synthesis
What happens during G2 phase ?
Organelles and molecules required for cell division are produced
What 3 factors cause cells to go into G0 ?
Cell-cell contact
Cell differentiation
Anti-mitogenic factors
4 hallmarks of cancer
Genomic instability
Inappropriate cell proliferation, evasion of cell death
Angiogenesis
Invasion and metastasis
What do oncogenes do ?
Code for proteins and factors involved in cell growth
What happens when oncogenes are mutated
Increase in cell division
Tumour suppressor genes usually need ____ allele(s) to be affected to develop cancer and oncogenes need ___ allele(s) to be affected
Both, one
What is the most commonly mutated gene in cancer ?
P53
What do BRCA 1 and BRCA 2 genes do when functional ?
Code for proteins that allow for DNA repair using a mechanism called homologous recombination
Sporadic cancer cause
Mutation in somatic cell leading to cancer (various causes)
What is inherited cancer ?
Mutation in germ line of a tumour supressor gene
What is the significance of the PDL1-ligand in cancer ?
Inhibitory ligand produced by tumour cells
Like an invisibility cloak
What types of tissues are most prone to neoplasm ?
Proliferating tissues or tissues that are more undifferentiated
(Skin, lung, gut)
Hormonally regulated tissues (breast, prostate)
Positive regulators for angiogenic switch
Vascular endothelial growth factor (VEGF)
Basic fibroblastic growth factor (bFGF)
Negative regulators for angiogenic switch
Thrombospondin-1
- regulated by p53 tumour supressor gene
Why are alterations in CAMs important in cancer invasion
Allow detachment in cancer cells and enhance cell mobility
what is growth fraction ?
Percent of cells in cycle
what is cell death fraction ?
Percent of new daughter cells that die
What is the number of cancer cells at diagnostic threshold
10^9
What is a neoplasm (tumour)?
Abnormal mass of tissue in which the growth exceeds and is uncoordinated with that of the adjacent normal tissue
Persists even after cause if removed
what is dysplasia ?
A pre-malignant change in cells characterized by disordered growth and morphologic changes in the cell nucleus.
What is the main difference between high grade dysplasia (carcinoma-in-situ) and cancer cells ?
Not yet invasive and therefore cannot metastasize
What is the difference between benign and metastatic neoplasms?
Malignant, benign :
Rapid growth, slow growth
Poorly circumscribed, usually circumscribed
Infiltrates and destroys adjacent tissue, pushes adjacent tissue aside
Can metastasize, do not metastasize
May poorly resemble tissue of origin, resemble tissue of origin
4 common ways for malignant neoplasms to spread
Direct: nearby tissue
Lymphatic
Blood vessels —> lungs or liver
Serosal surfaces —> may spread across pleura, paracardium or peritoneum
What does differentiation refer to ?
Degree to which cells of neoplasm resemble normal cells both morphologically and functionally
Major categories of neoplasms (6)
Epithelial CT (bone and soft tissue) Lymphoid and hematopoetic CNS tumours (gliomas) Germ cell Tumours Melanoma
Benign epithelial neoplasm nomenclature in general
Papilloma
Adenoma
Nevus* (skin)
Malignant epithelial neoplasm general nomenclature
Carcinoma
Melanoma*
Malignant mesenchymal neoplasm general nomenclature
Sarcoma suffix
Malignant neoplasms of lymphocytes (2)
Hodgkin’s and Non-Hodgkin’s lymphoma
Malignant neoplasm of granulocytes
Myeloid leukaemia
Malignant neoplasm of marrow lymphocytes
Lymphatic lymphoma
Malignant neoplasm of plasma cells
Multiple myeloma
What is the estimated time for an adenoma to become malignant ?
At least 5 years
What does tumour staging take into account ?
Size
Extent of spread
Metastases
Mutations in BRCA 1 and BRCA 2 genes are associated with which cancers
Breast cancer
Ovarian cancer
What gene mutations are associated with Lynch syndrome ?
MLH1
MSH2
MSH6
PMS2
Benefits of oncologist led genetic testing
Improved efficiency
More effective working relationships with oncology team
Positive feedback all around
What is sensitivity ?
True positive/total cases
What is specificity
True negative / total well people
What is the positive predictive value
Positive cases with condition / total positive cases
3 important steps for diagnosing carcinoma-in-situ and invasive cancer
History
Exam
Blood tests
What is the importance of doing a biopsy to diagnose cancer ?
Malignant vs benign
Type of cancer: site of origin
What is done in staging of cancer ?
Imaging
Additional biopsies
TNM staging system
T: primary tumour characteristics - size and depth of invasion N: nodal status - involved ?, #, size M: metastasis - yes or no? Extent ?
Who came up with the seeds and soil hypothesis for breast cancer metastasis ?
Stephen Paget
What is the meaning of palliative intent
Treatment being given does not have curative intent
Radiotherapy mechanism of action
Damages DNA in tumour and normal cells
Chemotherapy mechanism of action
Kills rapidly diving cells
Cancer, bone marrow, digestive tract and hair follicles
Targeted therapy mechanism of action
Disruption of tumour cell proliferation and/or survival factors
Immunotherapy mechanism of action
Mark tumour cells for destruction
Remove signals that is suppressing the immune response
What is neoadjuvant treatment ?
Treatment given prior to the primary therapy
Shrink tumour to allow for safe removal
Radiotherapy common side effects
Local effects such as skin irritation, organ hypofunction
Common side effects of chemotherapy
Bone marrow, GI tract, constitutional
