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Onco boards 2024 > Principles of cancer part II AB > Flashcards

Principles of cancer part II AB Flashcards

1
Q

CD 45

A

All Leukocytes
- not expressed on erythroid leukemias
- CD45- INDOLENT LSA

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2
Q

CD1

A

MHC class 1 proteins A-E

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3
Q

CD3

A

T cell receptor complex
- T cell LSA
- epsilon, delta, gamme component
- epsilon is where Ab sticks
- positive in chickens with Maricks

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4
Q

CD4

A

T helper cells binds to MHC II
- T cell LSA

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5
Q

CD8

A

cytotoxic T cells bind MHC class I
- T cell LSA

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6
Q

CD11

A

one chain of a/b heterodimeric B2 integral that helps leukocytes binds to cells
- 4 types A-d

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7
Q

CD11d

A
  • T cell subset (splenic), Macs, histiocytes
    HS, LGL
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8
Q

CD14

A

Monocytes
- LPS macrophages
- monocytes leukemia

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9
Q

CD18

A

common beta chain on all leukocytes
- can distinguish HS from STS
- cannot distinguish HS from LSA

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10
Q

CD20

A

mature B cell
- NOT on plasma cells
- rituximab tagets

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11
Q

CD21

A

mature B cell
- NOT on plasma cells

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12
Q

CD25

A

alpha chain of IL-2 receptor on activated T cells and Tregs
- used for Tregs most commonly

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13
Q

CD31

A

platelet Endothelial cells adhesion molecule 1 (pecam1)
- HSA, pCam1

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14
Q

CD79a

A

B cell receptor
- ON PLASMA CELLS
- pro B cell through plasma cells

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15
Q

CD204

A

class A scavenger for Macs
- on 50% HS

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16
Q

CD34

A

hematopeotic stem cells

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17
Q

CD11b

A

granulocytes, monocytes
- myelomonocytic myeloid leukemias

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18
Q

CD11d+ and CD8+ cell

A

LGL morphology

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19
Q

myeloperoxidase

A

myeloid lineage leukemias

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20
Q

CD11c

A

dendritic cells

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21
Q

CD1a

A

dendritic cells, cortical thymocytes
- immature t cells

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22
Q

Mediastinal mass CD5+ CD4+ CD8+

A

thymoma = dog
LSA = cat

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23
Q

CD5

A

T cells and some B cells
- TZL

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24
Q

MHC II

A

mature B cell
- B cell LSA

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25
CD 117
KIT immunolabeling - MCT, T cell LSA, various
26
Surface IgM
immature B cell - B cell LSA
27
Surface IgG
Mature B cell - B cell LSA
28
Node CD45-, CD5+, CD21+
TZL
29
Increased JAK/STAT signaling associated with which tumors?
MCT, HSA, thyroid carcinoma, AGASCA - pSTAT3 correlated with metastasis for MCT - increased JAK1 survival for MCT and HSA
30
PD-1/PD-L1 expression found on what cells?
- activated T cell and peripheral blood mononuclear cells in canine - production of IFN-y secreting T cells increased significantly with anti-PD-1 Ab alone in in vitro
31
Preconditioning of canine adipose tissue derived mesenchymal stem cells with deferoxamine can reprogram to which TAM phenotype?
M2 to aid in anit-inflammatory effects
32
PDL1 membranous labeling on which tumor types?
Melanoma 100% Renal cell carcinoma 24% SCC 18% Pulmonary carcinoma 10% Mammary carcinoma 3% - NONE on GI carcinoma
33
Which cancer have been found to have high infiltrates of tregs?
OMM, oSCC, pulmonary adenocarcinoma and mammary carcinoma - OST sig shorter for high tregs vs low tregs in OMM, oSCC, and PA
34
IBA1
pan macrophage maker - ionized calcium binding adapter molecue
35
DOG1
interstitial cells of Cajal - GIST
36
Actin
smooth/skeletal m
37
E-cadherin
adhering junction of epithelial cells (carcinomas) - specific to Langerhans cells over other types of macs
38
Calponin
polypeptide that modulates atpase during smooth m contraction
39
CD10
renal promiximal tubular epithelium and lymphoid progenitor cells Ag - renal carcinomas, ALL
40
CD90
aka thy-1 - thyme t cell
41
Chromogranin A
neuroendocrine tumors
42
Claudin 7, CK7
hepatocellular vs biliary carcinoma in bile duct epithelial cells
43
CNPase
oligodendrogliomas
44
cytokeratin
skin
45
desmin
musle - leiomyomas/sarcomas, rhabdos
46
factor VIII related Ag
vWF, endothelial differentiation - HSA, lymphangiosaercomas - diff HSA from telangiectatic OSA
47
Glucagon
pancreatic islet alpha cells - glucagonomas
48
Glypican 3
HCC - not in chloangio, cirrhotic, or normal liver - more sn than heppar1
49
hepatocyte parafin 1
specific for HCC
50
inhibin alpha
gonadal sex cord stromal tumors, adenrocortical tumors
51
Insulin
pancreatic beta cells - insulinoma
52
Melan A
specific for melnoma also on Sertoli and leydig tumors
53
mesothelin
mesothelial and epithelial cells
54
mullerian inhibiting substance
Sertoli cells NOT leydig
55
MUM1
plasma cells
56
MyoD1
rhabdos
57
myoglobin
skeletal muscles
58
napsinA
pulmonary adenocarcinoma not SCC or mesothelioma
59
NXK 3..1
may be able to distinguish prostatic from UC
60
olig-2
oligodendrocyte
61
p63
myoepithelial cells of ductular-lobular epithelial - distinguishes invasive vs non invasive carcinomas
62
PAX 5
pre B cell marker - B cell LSA - positive for avian leukosis
63
pax 8
renal and thyroid epithelium
64
periaxin
Schwann cells, transmissible facial tumors in devils
65
PNL2
monoclonal AB for melanoma - more specific than melan A in dogs - 100% + in horse melanoma where melan A is not
66
synaptophysin
neural tissue, neuroendocrine cells
67
BLA 35
Hodgkins LSA in cats
68
Ki67
- all phases of M phase, absent in non cell cycling - melanoma and MCT primarily
69
AgNOR
- expressed during high transcription activity - MCT
70
Intratumoral micro vessel desnsity
angiogenesis, MCT
71
cyclins CDK
cell check points
72
Prox-1
lymphatic epithelium
73
RACK1
melanoma
74
S-100
neuronal tissue - distinguish schwannomas from neurofibromas and fibro
75
somatostatin
pancreatic endocrine cells
76
surfactant protein A SP-A
alveolar type II cells and Clara cells - pulm carcinomas with TTF1 or napsin
77
Thyroglobulin
follicular carcinomas with TTF1
78
Uroplakin III
transitional epithelium - UC - fibroblast activation marker of CAFS
79
Villin
colorectal and pulmonary caricnoms
80
Vimetin
intermediate filament - distinguish between epithelial and mesenchymal tumors - can use with cyokeratin for mesothelioma (cytokeratin +, vimentin +)
81
a-SMA
fibroblast activation marker of CAFS
82
What do cancer associated fibroblasts (CAFs) arise from? How they activated?
- bone marrow-derived cells or transdifferentiation from epithelial/endothelial cells - TGFb
83
How do CAFs contribute to cancer?
- GF signaling: HGF, FGF - survival: IGF - ECM remodeling: intigrens, MMP and ADAM proteinase expression - chemokines: SDF-1, CXCL12, IL2, CXCL8 - angiogenesis: VEGF - mice deficient in CAFs have reduced metastasis/tumor growth --> CAFs = poor prognosis
84
Markers of CAFs
a-SMA, FSP-1. FAP, neuron-glial antigen2, PDGFGb
85
What is meant by intraturmoral vs intertumoral heterogeneity?
cancer cells within an individual are as diverse as the same cancer amongst various individuals
86
What are the coexisting theories of tumor heterogeneity?
- EMT: cells transdifferentiate to more motile mesenchymal phenotype via TGFb, Wnt, PDGF - CSCs: a minority of cancer cells have the potential to self renew, proliferate, and differentiate (variations in types, long vs short term). - role in chemo/RT resistance, responsible for recurrence when control appears complete - Phenotypic plasticity: cell populations are in dynamic equilibrium controlled by epigenetics, cells can switch btw diff. phenotypes in response to microenvironmental stimuli. - Cells are the periphery are different than cells in the core
87
CSC markers?
- High ALDH and ABCB1 - high CD44, low CD24 - CD133 = brain/colon - CD34 = myeloid - ESA = colon
88
How does tumor heterogeneity impact clinical practice?
precision medicine: - tumor genome sequencing for individual draggable targets - liquid biopsy for mutation (V600E used in humans ctDNA) for diagnosis/monitoring - CTCs act as a surrogate for presence/absence of some tumors
89
What is a barrier to precision medicine (sequencing individual tumor)?
- intratumoral heterogeneity - resistant sub clones outcompete tumor clones - may be able to overcome with combinations therapy e.g. MEK and BRAF targeting
90
What is differentiation therapy? Example?
strategy to overcome tumor heterogeneity by using agents that cause EMT/CSC differentiation to make them more susceptible to therapy - check point inhibitors
91
What is the concept of adaptive therapy?
use of patient specific tumor dynamics to make decisions about when to treat and not to treat with the same effective tx in the individual goal: suppress proliferation of treatment resistant cell while extending the duration of therapy while lowering drug exposure
92
How do CSC contribute to tumor resistance?
- remain quiescent making them less responsive to therapy --> activity later in disease --> prog/mets - high levels of ABC transporters - multiple DNA repair mechanisms - interact w/ TME (CAFs, Tregs) to make a more favorable environment for survival - CSCs can give rise to non-CSC progeny that may be more sensitive to therapy, but the presence of CSCs ensures the continued survival and regeneration - interaction with signaling pathways: HH, wnt, NOTCH, tgfb
93
How can you reverse CTX resistance in stem cells?
PARP inhibitor
94
How do stem cells contribute to RT AE?
Help repair acutely damaged tissues = high a/b
95
Increased SHH signaling causes?
Proliferation, invasion, mets - embryogenesis, angiogenesis, and activation of CSC
96
Result of CSC upregulation of B-catenin?
longer telomeres
97
CSCs and radiation
- CSCs can regenerate tumors after tx - their radio sensitivity is crucial to control - knowing the radiation sensitivity and # of CSC would allow prediction of survival following in RT tx - dose of RT to control a tumor depends on # of CSC - difficult to predict due to various phenotypes, TME, etc
98
CD133 and Oct-4 expressing cells are radio resistant vs adherent?
radio resistant - these are CSCs sphere forming cells - CSC resistance may depend on reaction of DNA dsbreak after RT
99
Lymphoma cells resistant to CHOP have upregualation of?
CD133, ALDH, and readily formed spheres = CSC
100
Carcinogenesis: initiation, promotion, & progression
initiation: process by which carcinogenic event interacts with DNA to prove damage that cannot be repaired --> error prone DNA replication --> fixed mutation in genome promotion: clinical expansion of an initiated cell as a result of altered gene expression progression: lesions acquire the ability for further growth, invade adjacent tissues, and met (may occur slowly and/or never manifest in life)
101
Which stage of carcinogenesis is reversible?
promotion
102
Are most carcinogens direct acting or do they require activation?
most require activation to electrophilic state to induce DNA damage
103
Define/explain how the promotion step of carcinogenesis manifests clinically?
Promotion = expand cell proliferation results in survival and proliferation of cells and clinically many pre-neoplastic lesions (e.g. polyps, nodules, papillomas)
104
How do chemicals contribute to the carcinogenic process?
DNA damage producing somatic mutations
105
Shared characteristics of genotoxic chemicals
directly elecrtrophilic (e- seeking), capable of conversion to electrophiles typically via P450 to electrophilic metabolic --> interact with neucleophilic (electron rich) groups on intracellular molecules (DNA, proteins) to form covalent adducts or oxidative damage
106
Chemical factors associated with carcinogenesis
- tobacco smoke - Pest, herb, insecticides (specifically 2,4,-dichlorophenoxyacetic acid [2,4-D]) - cyclophosphamide - UC in people and dogs via acrolein - pollutants
107
Physical factors associated with carcinogenesis
- UV exposure (SCC) - trauma/chronic inflammation - magnetic fields - RT - SX implants - asbestos
108
Which tumors have an increased risk of development following castration?
- cardiac tumors - OSA (purebred, Rottweilers <1 yr of age at castration) - Prostatic epithelial tumors (including UC) - UC - LSA (Goldens <1 yr at castration)
109
Which tumors have a decreased risk after castration?
testicular
110
Which tumors have an increased risk of development after spay?
- cardiac (esp HSA) - OSA (purebred, rotties <1yr at spay) - splenic HSA (esp viszlas, godens <1 yr spay) - MCT (esp viszlas, goldens) - LSA
111
Which tumors have a decreased risk after spay?
- Ovarian - Uterin - mammary (spay b4 3rd estrus; feline and canine)
112
Mareck virus type/class, animal, tumor?
- DNA/herpes - Chickens - lymphoid with bursa
113
Papilloma virus type/class, animal, tumor?
-non enveloped DNA - dogs, cats, cattle, horses - papillomas, Bowen's dz in cats, sarcoids in horses
114
Woodchuck virus type/class, animal, tumor?
- dsDNA/orthohepadnavir - Woodchuck - HCC
115
Feline sarcoma virus, virus type/class, animal, tumor?
- RNA/acute trans - Cat - fibrosarcoma
116
Reticuloendotheliosis virus type/class, animal, tumor?
- RNA/ acute = chicken, lymphoid without bursa - RNA/chronic = Fowl, B or T cell LSA
117
Avian leukosis virus type/class, animal, tumor?
- RNA/chronic - chicken - B cell LSA
118
Rous sarcoma virus type/class, animal, tumor?
- RNA/chrnoic - chicken - sarcoma
119
lymphoproliferative dz virus type/class, animal, tumor?
-RNA/chronic - turkey - marbled spleen
120
FIV virus type/class, animal, tumor?
- RNA/ chronic/ lenti - cats - lymphoid, SCC, myeloproliferative dz
121
FeLV virus type/class, animal, tumor?
- RNA/chrnoic/oncovirinae - cat - lymphoid
122
Bovine leukemia virus virus type/class, animal, tumor?
- RNA/chronic - cow - LSA
123
Which are DNA viruses?
- hepatitis B = HCC - adenovirus - papilloma virus - polyomavirus - Epstein Barr - Burkitts LSA - HHV8 = capos sarcoma, endothelial tumors, NHL
124
Which are retroviruses?
Human T lymphocytic virus type 1, hepatitis C, HIV
125
RNA viruses associated with cancer?
Hep C, human T lymphocytic virus type1, FeLV, Feline sarcoma, FIV
126
Which is true about FeLV?
type c: <1% of cats, early erythroid precursors affected die within 1-2 mo
127
FeLV vaccines protect against ?
1 variant of subgroup A - FeLV A occurs in all infected cats and causes immunosuppression, associated with natural transmission - FeLV B occurs in 50% of all infected cats and causes neoplasia more than A alone - Subgroups A and B – recombine w proto-oncogenes MYC or TCR - FeLV C causes severe anemia in <1% of ctas
128
What is the function of the E6 and E7 HPV proteins?
E6- targets p53 for degradation via ubiquitin pathways E7- binds/inhibits Rb
129
Risk of developing LSA in FeLV + cats?
6.2x higher
130
Tumor types associated with obesity?
- UC in Scottish Terries - OSA - mammary
131
Tumor types associated with diet?
- mammary - red meat intake, fat, and table food - vegetable intake reduces risk of UC
132
Tumor types associated with environmental pollutants?
- anthracosis - pulmonary cancer - urban area - LSA - kerosene/coal exposure - nasal carcinoma
133
Tumor types associated with pesticide exposure?
- LSA - UC - flea tick products too
134
Tumor types associated with tobacco smoke?
- nasal carcinoma in dolichocephalic breeds - LSA - SCC
135
Carcinoma: molecular markers & localization/expression?
- cytokeratin+, vimentin - - both cytoplasmic - coexpression can occur in mesotheliomas and may reflect EMT in carcinomas
136
GIST: molecular markers & localization/expression?
- *KIT (CD117)+/- = PM and cyto - SMA+/- = cyto - Desmin- = cyto - s100- = N & cyto - *dog1+ = PM and cyto
137
HSA/lymphangiosarcoma: molecular markers & localization/expression?
- Factor VIII-RAg/vWF+ = cyto - CD31/PECAM1+ = PM & cyto
138
HS: molecular markers & localization/expression?
- CD18+ = PM - CD3- = PM - CD79a- = PM - Pax5- = N - IBA1+ = cyto - lysozyme +/- = cyto
139
Leiomyosarcoma: molecular markers & localization/expression?
- KIT/CD117- = PM & cyto - SMA+ = cyto - Desmin +/- = cyto - s100- = N and cyto - Dog1- = PM & cyto desmin confirms myosin origin but does not differentiate between smooth, striated, or cardiac m
140
B cell LSA: molecular markers & localization/expression?
- CD18 +/- = PM - CD3- = PM - CD79a+ =PM - PAx5+ = N - CD20+ = PM
141
T cell LSA: molecular markers & localization/expression?
- CD18+/- =PM - CD3+ = PM - CD79a- = PM - PAX5- = N
142
Null cell LSA: molecular markers & localization/expression?
- CD18- - CD3- - CD79a- - PAX5- all PM except PAX5 N
143
MCT: molecular markers & localization/expression?
- Tryptase+ = cyto - KIT/CD117+ = PM and/or cyto (type I-III expression pattern)
144
Melanocytic: molecular markers & localization/expression?
- Melan-A +/- = cyto - PNL2 +/- = cyto - Tyrosinase +/- = cyto - TRP1 or 2 +/- = cyto - Vimentin + = cyto - s100+ = N & cyto
145
Mesothelioma: molecular markers & localization/expression?
- cytokeratin +/- - vimentin +/- - both cyto - coexpression for most mesotheliomas
146
Neural astrocytic tumor
- GFAP+ = cyto - s100+/- = N & cyto - Olig2+/- = N
147
Neuroendocrine: molecular markers & localization/expression?
- Chromogranin A +/- = cyto - Synaptophysin +/- = cyto - NSE+ = cyto
148
Plasma cell tumor: molecular markers & localization/expression?
- MUM1/IRF4+ = N - CD18 +/- = PM - CD3- = PM - CD79a +/- = PM - PAX5- = N
149
Rhabdo: molecular markers & localization/expression?
- Vimentin + cyto - Desmin + = cyto - Myoglobulin +/- = cyto - SMA- (MyoD1 +/-, myogenein +/-) = N - myoglobulin typically late stage marker which may be negative in poorly differentiated tumors - MyoD1 and myogenin can be useful if undifferentiated - PTAH may highlight cross striations in skeletal m
150
Sarcoma: molecular markers & localization/expression?
- Vimentin + - Cytokeratin - - both cyto
151
Synovial cell sarcoma: molecular markers & localization/expression?
- Vimentin + = cyto - cytokeratin +/- = cyto - CD18- = PM
152
Thyroid tumors (follicular epithelial origin): molecular markers & localization/expression?
- Thyroglobulin + = cyto - TTF1+ = N - Calcitonin- = cyto - Chromagranin A- - Synaptophysin _ - NSE -
153
Thyroid tumors (C-cell/parafollicular cell origin - medullary): molecular markers & localization/expression?
- Thyroglobulin - = cyto - TTF1+ = N - Calcitonin+ - ChromograninA+ - Syntaptophysin+ - NSE+

Onco boards 2024 (17 decks)

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