Oncology (NAVDF 2023 LaPorte) Flashcards
Which proteins work by phosphorylating (activating) downstream tumor suppressor proteins.
Cyclins, cyclin-dependent kinases
Regulate the cell cycle
On which phase of the cell cycle do most chemotherapies work?
S phase (DNA replication)
(Can be M phase or signal transduction to start cell cycle)
In which phase of the cell cycle are cells most resistant to radiation
S phase
What are intrinsic causes of cancer development
Inherited gene, gene product abnormality
What are extrinsic causes of cancer development
Environmental factors
(UV, virus, ROS, chronic inflammation, trauma, chemicals, implants, radiation, magnetic field, hormones)
How does UV light cause cancer
Forms thymidine dimers
Nucleotide excision repair fails to fix them –> Cancer
Function of proto-oncogenes
Proto-oncogenes stimulate cell division, inhibit cell differentiation, inhibit cell death –> help make new cells, stay alive
When mutated to oncogene: Gas pedal stuck down!
Examples of oncogenes
- c-KIT
-Encodes tyrosine kinase protein; best known on mast cells tumors!
*c-myc
-Encodes TF that regulates cell cycle
Ligand for c-kit
c-kit binds stem cell factor (SCF) to increase signals for cell survival differentiation, proliferation
Function of tumor suppressor proteins
Slow down cell division. Induce apoptosis
TSP = Brake of the car
What is the most mutated protein in human cancer
p53– TSP
Name 2 tumor suppressor proteins
p53
pRB (E7 on papillomavirus binds, inhibits pRb –> uncontrolled cell cycling and cancer)
Function of DNA repair genes
Fix DNA mistakes around cell division. If can’t fix it -> trigger cell death
DNA repair gene = car mechanic
Steps of the metastatic cascade (4)
1) Invasion and migration
-Break through BMZ
2) Angiogenesis and intravasation
3) Survival in circulation and Attachment to endothelium
4) Extravasation and Colonization
What is the difference between pre-cancerous neoplasia and malignant cancer
Invasion through the BMZ in malignant cancer
This the the “differentiating step”
How can immunosuppresive drugs cause cancer
Immune system can no longer surveil for cancer growth, so easier for neoplastic growth to occur
Cyclosporine inhibits which cell that is crucial for cancer immunosurveillance
CD8 T cells
How could Apoquel potentially be associated with increased risk of cancer
Suppresses JAK1 –> inhibits IL-2, IL-4 –> reduces stimulation of innate tumor immunosurveillance (gamma delta T cells, NK cells)
T or F: it is likely that higher doses of oclactinib and cyclosporine are more likely pro-neoplastic
True
Metastatic pathway of Sarcomas
Sarcoma to Lungs via BLOOD
CXR
Metastatic pathway of Carcinomas
Carcinoma to REGIONAL LN -> lungs, liver spleen via BLOOD AND LYMPHATICS
Regional FNA, CXR, AUS
Metastatic pathway of Round cell tumors
Tumor -> Regional LN -> liver, spleen via LYMPHATICS
Regional FNA, AUS
Neoplastic consequences of Feline papillomavirus
1) BISC
2) SCC
3) Feline sarcoid (BPV14)
4) Viral plaqu
How do papillomaviruses cause malignant transformation
Destabilize TSP p53 by E6
Inhibit pRb by E7
Cancers associated with Feline Skin Fragility Syndrome
Adrenal carcinoma
Abdominal carcinomas
Multicentric lymphoma
Cancer associated with Bilateral Ischemic Necrosis of the HIndpaws
Multicentric follicular lymphoma
IHC marker for T cells
CD3
IHC markers for B cells
CD20, CD79a, PAX5
IHC marker for epithelial cells
Cytokeratin
IHC marker for Mesenchymal cells
Vimentin
IHC marker for melanocyes
Melan A
Origin of melanocytic tumors
Mesenchymal. But can look like epithelial or round cell on cytology
Stains for mast cell granules (2)
Toludine blue
Giemsa
Stain for melanoma (melanin vs hemosiderin)
Fontana Masson
IHC marker for plasma cell tumor
MUM1
IHC marker for Mast cell tumor
C-Kit
CD117
IHC marker for histiocytoma
CD18, CD204, E cadherin, IBA1
NEGATIVE for CD4, CD90
(reactive histiocytoma is negative for E cadherin; positive for CD4, CD90)
IHC marker for hemangiosarcoma
Factor VIII related antigen
Claudin 5
CD31 (endothelial origin)
IHC for melanoma
Melan-A
PNL2
TRP-1
TRP-2
+/- S100
IHC for smooth muscle
Smooth muscle actin
Desmin
IHC for skeletal muscle
Myogenin D
Sarcomeric actin
Desmin
IHC for neuroendocrine tumor
Chromogranin A
Synaptophysin
Definition of sentinel lymph node
First lymph node to which cancers would spread from a primary tumor
Chemotherapeutic effect of imiquimod
SCC
Activates TLR7, secrete cytokines (IFNa, IL6, TNF-alpha)
activate LCs to go to LN and activate adaptive immunotherapy
Chemotherapeutic effect of prednisone
Inhibits DNA synthesis
Induces apoptosis
Mechanism not know
Acute AEs of radiation
Mucositis, erythema, alopecia, desquamation, lymphedema, changes in pigmentation
Usually SELF RESOLVING, RAPID RECOVERY
Severe Late AEs of radiation
Fibrosis, necrosis
RARE
Radiation recall
Return of acute radiation side effects once an animal receives chemo later on
Are dogs or cats more likely to have MALIGNANT skin tumors
Cats
Most common skin tumor in dogs
1) MCT
2) Lipoma
3) Histiocytoma
Most common skin tumor in cats
1) Basal cell tumor
-Basal cell carcinoma
-Basal cell epithelioima
-Trichoblastoma
-Solid-cystic ductular sweat gland adeno(carcino)mas
2) MCT
3) Fibrosarcoma
4) SCC
*Collectively, account of 70% of all feline skin tumors
Which species develops cutaneous plasmacytosis
Dogs only
Which cancer should you may particular attention to iCa and Renal Function
Plasma cell tumors –> Multiple myeloma
IHC for plasma cell tumors
MUM1/Interferon regulatory factor4
T or F: Cutaneous plasmacytosis has a high metastatic rate
TRUE
Staging is important. Multiple myeloma also has high metastatic rate
Where on the body are you most likely to find a plasmacytoma
Head (ears), limbs
Breeds predisposed to plasmacytoma
Airedale terrier
Boxer
Cocker Spaniel
GSD
WHWT
Yorkshire terrier
Treatment plasmacytoma dogs
Surgery is usually curative. Normal lifespan
Local recurrence 5%
In cats with plasmacytoma, what should you monitor for
Progression to systemic myeloma-related illness
May be benign though! Just monitor