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RO General Section > Withrow Part 1 > Flashcards

Withrow Part 1 Flashcards

0
Q

Definitions of IPP cancer model:

A

Initiation: growth advantage, replicative potential
Promotion: expansion into tumor
Progression: malignant potential - invasion, tissue destruction, mets

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1
Q

Nodular dermatofibrosis of GSDs is associated w what neoplasms?
What canine chromosome?
What similar human syndrome?

A

Renal cystadenomas and uterine leiomyomas
CFA-5 (exon 7)
Birt-Hogg-Dube syndrome

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2
Q

CML in dogs is related to what translocation error? humans?

A

BCR-ABL
Dog: chromosomes 26 & 9 - Raleigh chromosome
Human: chromosomes 22 & 9 - Philadelphia chromosome

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3
Q

Compare the Cancer Stem Cell theory & the Stochastic model:

A

CSC: cells retain/acquire ability of self renewal, initiate & maintain the tumor
Stochastic: all cells in tumor have equal capacity for self-renewal, process of cancer is driven by environmental selection of favorable mutations

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4
Q

Cancer stem cells have been identified in what tumors?

A

HSA
OSA
brain tumors
LSA

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5
Q

What is the difference in mechanisms regarding MOA of DNA vs RNA viruses?

A

DNA virus: inhibits tumor suppressor genes

RNA virus: dysregulates signal transduction

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6
Q

What is ezrin?

What does it predict in dogs?

A

a membrane cytoskeleton protein connecting actin cytoskeleton to cell membrane.
Predicts a more aggressive course of disease in canine OSA - defined by pulmonary mets.

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7
Q

Name 3 types of invasion regarding intravasation of tumors.

A

Mesenchymal Invasion - enzymatic degredation (MMPs)
Ameboid Invasion - slip between fibers of ECM - not enzymatic
Collective Invasion - en masse regional extension into surround tissues

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8
Q

Name the 3 transcription factors involved in EMT (epithelial-to-mesenchymal transition) and the collective result in their activation.

A

involved factors are twist, snail, slug

activation of these results in: loss of polarity, loss of cell to cell contact, cell motility, invasion

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9
Q

Arrest in distant sites by circulating tumor cells occurs by what two mechanisms?

A
  1. Size-dependent trapping of tumor cells within the lumen of small vessels.
  2. Receptor-mediated interaction involving tumor cells and host vasculature
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10
Q

What is the survival rate of cancer cells in a new environment and what factors affect survival?

A

0.1 % survival within a few days
Success determined by:
1. interaction between tumor cells & ECM
2. adhesion molecules (CD44 - receptor for hyulronic acid)

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11
Q

What is a premetastatic niche?

A

The primary tumor modulates microenvironment of a secondary site before arrival of metastatic cells. Involves mobilization and recruitment of specific bone-derived cells

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12
Q

What is the significance of increased microvascular density?

A

It is associated with increased metastatic behavior.

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13
Q

What is the main cause of metastatic inefficiency?

A

Decrease survival of cancer cells at the distant site. <1% survive

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14
Q

What is PARR?

A
  1. determines clonality of lymphocytes
  2. PCR primers amplify variable regions, which are then separated by size. If single PCR size = neoplastic
  3. detects approx 1:100 neoplastic cells
  4. may determine lineage (T vs B)
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15
Q

What is flow cytometry?

A
  1. analyzes single cell suspensions
  2. uses lasers to indetify char. of cells - size, complexity, cell surfac proteins
  3. gives more info than IHC
  4. can tell T-cell vs. B-cell
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16
Q

What % of canine MCTs have duplication mutations?

What are the specific mutations?

A

14-20%

Internal tandem duplications of exons 8 and 11

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17
Q

What is real-time PCR (Q-PCR)?

A
  1. Quantitatively measures DNA using genes or RNA that has been reversed transcribed to cDNA
  2. DNA is amplified using primers and fluorescene relative to amount of PCR product is quantified
  3. uses SYBR green
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18
Q

Regarding surgical oncology list six positive prognostic factors

A 
Slow growth rate
Mobility
First surgical attempt
Discrete tumor borders
Small tumor size
Low-grade
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19
Q

What should a surgeon do early to prevent release of emboli into systemic circulation?

A

Ligate veins early in the procedure

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20
Q

Regarding surgical oncology, prophylactic lymph node removal:

A

Is not beneficial and may be harmful

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21
Q

What percentage of dogs with gross MCT have elevated histamine concentrations?
What percentage have G.I. signs?
How is it treated?

A
  1. 75%
  2. 30%
  3. Treat with proton pump inhibitor’s, H2 blockers, misoprostol, sucralfate, IV fluids
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22
Q

Hypercalcemia is seen in what tumors most commonly?

What mechanism causes this phenomenon?

A
  1. LSA, ASAC. Also thyroid CA, MM, thymoma, OSA, SCC, melanoma, mammary gland ACA
  2. due to ectopic production of PTH or PTHrp by the tumor
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23
Q

Primary clinical manifestations of hypercalcemia are due to impairment of what system?
List 4 things related to impairment of that system.

A

Renal system
1. Decreased ability to concentrate urine due to decreased responsiveness to ADH at distal tubule
2 decreased renal bloodflow & decrease GFR due to severe vasoconstriction
3. Urinary epithelium may undergo degeneration
4. PU/PD

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24
Q

In dogs with hypercalcemia of malignancy, what are the PTH and PTHrp concentrations? (i.e. low, high, or normal)

A

PTH low

PTHrp high

25
Q

What are the treatments for hypercalcemia of malignancy?

A 
0.9% NaCl
furosemide & pred to inhibit Ca++ resorption
calcitonin
biphosphonates
gallium nitrate
26
Q

Coagulopathies are most commonly caused by what tumor and what is the mechanism?

A

MCTs

increased heparin, which can cause bleeding post-op

27
Q

DIC is most commonly associated w what neoplasm?

28
Q

Myasthenia gravis is associated w what neoplasm?
Clinical signs?
Tx?

A
  1. thymoma
  2. muscle weakness, dysphagia, megaesophagus
  3. pred
29
Q

Diencephalic Syndrome is associated w what tumor?

A

Astrocytoma
Only 1 case reported in dog. In humans, excessive GH production by tumor in diencephalic region causes emaciation despite normal or increased caloric intake.

30
Q

Name two neoplasms that can cause cutaneous flushing

A
  1. pheochromocytoma - various shades of red due to changes in vasodilation
  2. MCT
31
Q

HO causes?

Degrees of periosteal rxn on rads???

A

lung tumors/pulmonary mets
bladder rhabdomyosarcoma
90º

32
Q

What are the 3 phases of immune surveilance/immunoediting?

A
  1. Elimination - of immunogenic tumor cells
  2. Equilibrium - tumor growth & destruction equal
  3. Escape - decrease immunogenicity results in rapid tumor cell growth
33
Q

List 5 mechanisms of immune evasion by tumors:

A
  1. Myeloid-derived supressor cells (monos, granulos, TAMs)
  2. Regulatory T-cells (T-regs)
  3. Impairment of DCs
  4. Immunosuprressive cytokines (IL-10, TGFß, TNF∂)
  5. Dowmodulate MHC surface expression to escape recognition by T-cells
34
Q

List 4 ways myeloid-derived supressor cells aid in immune evasion by tumors?

A
  1. Recruited to tumor microenviron & actively suppress local antitumor immune response
  2. promote tumor invasion & mets
  3. suppress T-cells, NK cells, and dendritic cells
  4. produce TGFß & IL-10 which stimulates Tregs & TAMs
35
Q

What markers do Tregs express?
What cells to they directly suppress?
What is their relationship w px?

A
  1. CD4, CD25, foxp3
  2. CD4&8 T cells, NK cells
  3. Increased Tregs correlate w poor px
36
Q

How do tumors impair DC function?

A

Fewer circulating myeloid DCs & increase in immature DCs decreases Ag presentation & T-cell stimulation….induces T-cell tolerance rather than activating them.

37
Q

What do each of the following cytokines do to suppress antitumor T-cell response and DC inhibition:
IL-10?
TGFß?
TNF∂?

A

IL-10 promotes Treg production & function
TGFß potentiates Treg proliferation & function
TNF∂ induces antiapoptotic proteins & promotes tumor angiongenesis

38
Q

In downmodulation of MHC Ag expression by tumor cells, which MHC(s) is/are affected?

A

Both MHC I and MHC II

39
Q

Using immune activation, name the tumors affected by the following agents:

  1. BCG
  2. Cornyebacterium parvuum
A
  1. TCC & MCTs

2. melanoma

40
Q

Using superantigens, such as those of Staph. aureus, to stimulate T-cel proliferation & TH1 production results in what ORR in:

  1. oral melanomas & STS
  2. STS
A
  1. 16%

2. 25 %

41
Q

How does L-MTP-PE work? Uses?

A

Activates monos & MØ to make ILs 1,6,7,8,12 and TNF∂

Used as adjunct in OSA, HSA, & melanoma

42
Q

Give 4 facts about IL-2

A

released by activated T-cells
induces clonal expansion of T-cells, activates DCs, MØ, & B-cells
stimulates NK cells

43
Q

Give 3 facts about IL-12

A
  1. produced by Ag-stimulated DCs, MØ, & B-cells
  2. stimulates growth & function of T-cells
  3. enhances cytolytic activity of T-cells & NK cells
44
Q

Two facts about IL-15:

A
  1. Stimulates NK cells & promotes proliferation of T-cells

2. vs. IL-2, does not cause activation-induced cell death of CD4+ T-cells

45
Q

What do the following RTks do regarding angiogenesis:

  1. VEGFR
  2. PDGRF
  3. FGFR
  4. Tie-1/Tie-2
A
  1. drives endothelial cell migration & proliferation
  2. expressed on stroma & pericytes, critical for maintenance of newly formed blood vessels
  3. expressed on endothelium, works w VEGFR to promote VEGF secretion
  4. expressed on blood vessels in tumors & recruits pericytes & smooth muscle cells
46
Q

ITD mutations of KIT are found in what % of grade II/III MCTs?

A

25-30%

also found in GISTs

47
Q

An autocrine loop is when a tumor expresses both the RTK & the GF.
Name two tumors, the RTK, and the ligand in which they have been documented.

A

OSA: MET & its ligand HGF
HSA: KIT & its ligand CSF

48
Q

What does the small molecule inhibitor crizotinib (Xalkori) inhibit?

49
Q

What does the small molecule inhibitor vemurafenib (Zelboraf) inhibit?

50
Q

Name 3 drugs that inhibit mTOR

A

Rapamycin
Temsirolimus
Everolimus

51
Q

Palladia general information:

  1. ORR?
  2. Biological response %?
  3. approved for use in…?
  4. Response w vs. w/o KIT mutation?
  5. Other neoplasms responsive?
A
  1. 42.8%
  2. 60%
  3. recurrent or metastatic Gr II/III MCTs
  4. 69% w; 37% w/o
  5. ASAC, thyroid CA, SCC, nasal CA, OSA
52
Q

Kinnavet vs. placebo?

A

40% alive at 2 yr vs. 15%

53
Q

Response to Gleevec in dogs and cats?

A

yes - documented in MCTs in both species

54
Q

Sorafenib (NexaVar) target?

55
Q

What are 2 mechanisms of anti-angiogenic therapy?

A
  1. Vascular collapse, resulting in impaired oxygen delivery and leading to decreased nutrition, hypoxia, death
  2. Vascular normalization results when smaller, torturous, leaky vessels are selectively destroyed resulting improved delivery of oxygen, nutrients, and drugs
56
Q

Metronomic chemotherapy results in changes in levels of what 3 things (in STS)?

A
  1. incr TSP-1
  2. decr VEGF
  3. decr Tregs
57
Q

Metronomic chemotherapy targets what cells?

A

Genetically stable endothelial cells

58
Q

What can be used to predict response to metronomic chemo?

A

low baseline VEGF

59
Q

Adverse events related to metronomic chemo?

A

metastatic condition by altering host microenvironment, resulting in incr invasion & mets w antiangiogenic drug tx

RO General Section (17 decks)

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