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Onc Boards > Withrow > Flashcards

Withrow Flashcards

1
Q

Only one heritable cancer syndrome has been identified in dogs. What is it?

A

germ line mutation of the BHD gene encoding follicular. Found in a family of GSDs, shows susceptibility to a syndrome of renal cystadenoma and nodular dermatofibrosis

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2
Q

What is Peto’s paradox

A

At the species level, the incidence of cancer does not appear to correlate with number of cells in an organism

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3
Q

Elephants have enhanced activity of __ (tumor suppressor gene) which confers protection against cancer

A

TP53 gene

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4
Q

What are the 10 hallmarks of cancer

A

(1) sustain proliferative signaling
(2) evade growth suppressors
(3) resist cell death
(4) enable replicative immortality
(5)induce angiogenesis
(6) activate invasion and metastasis

The updated hallmarks of cancer added two “enabling” characteristics
(7) genome instability and mutation
(8) tumor-promoting inflammation

And two “emerging” hallmarks
(9) deregulating cellular energetics
(10) avoiding immune destruction

The important concepts that were clarified included these: no single gene is universally responsible for transformation; five or six critical (driver) mutations are the minimum theoretical number required to endow the cancer phenotype (an observation that has since been confirmed experimentally); each step in the path toward transformation and cancer progression is regulated by multiple interactive biochemical pathways, and thus, mutations of different genes along a pathway can result in equivalent phenotypes and, conversely, mutations of the same gene can result in different cancers with distinct biology; tumors behave as tissues; and the interactions between the tumor and its microenvironment are major drivers of cancer behavior.

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5
Q

What is the Hayflick limit

A

Limitation of the number of times a cell can replicate by the genetic program

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6
Q

VEGF expression is upregulated by

A

Hypoxia and inflammation

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7
Q

What transcription factor is a major regulator of VEGF expression

A

HIF-1alpha

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8
Q

What tumor suppressor gene is involved HIF-1alpha in the VEGF regulation pathway

A

von Hippel-Lindau (VHL) tumor suppressor gene

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9
Q

Under conditions of __, the VHL protein targets HIF for degradation; under __ conditions, hif increases as VHL-mediated degradation is reduced, allowing for upregulation of VEGF

A

Normal oxygen tension ; low oxygen conditions

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10
Q

How does PDGF-beta contribute to angiogenesis

A

Recruitment of pericytes and maturation of new capillaries

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11
Q

Canine HSAs show elevated production of what proangiogenic drivers

A

VEGF
IL-8
sphingosine-1 phosphate (S1P) and its receptor (S1P1)

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12
Q

Magnitude of angiogenic drive in canine hemangiosarcoma is associated with somatic mutations of

A

Angiopoietin
VEGF
PI3K signaling pathways

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13
Q

___ is upregulated recurrently in canine HSA and OSA where it is presumed to promote invasion and migration upon binding CXCL12

A

CXCR4

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14
Q

Upregulation of what glucose transporter is seen in virtually all cancer cells

A

GLUT-1

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15
Q

PET mots commonly uses what molecule as a reporter

A

18F-fluorodeoxyglucose (18F-FDG)

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16
Q

The BCR gene is located on what chromosome number in humans vs dogs

A

Humans = chromosome 22
Dogs = chromosome 26

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17
Q

The ABL gene is located on what chromosome number in humans and dogs

A

Chromosome 9 in both

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18
Q

The Philadelphia chromosome is called the __ chromosome in dogs

A

Raleigh

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19
Q

What five viruses are known human carcinogens

A

Epistein-Barr virus
HIV type 1
Human T-cell lymphotrophic virus type 1
Kaposi sarcoma-associated herpesvirus
Merkel cell polyomavirus

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20
Q

Secondhand smoke exposure in dogs is associated with development of what cancer

A

Nasal cancer (especially in dolichocephalic breeds)

NOT LUNG CANCER in dogs

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21
Q

A case control study of 80 cats with malignant lymphoma showed a __x risk of lymphoma in cats with environmental tobacco smoke

A

2.4x

Risk of lymphoma increased with increases in duration of quantity of exposure

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22
Q

Exposure to environmental tobacco smoke was associated with a __ (but statistically insignificant) increased risk of oral SCC in cats in one study (by Bertone et al)

A

Twofold

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23
Q

A positive association between the lawn care chemical __ and lymphoma in dogs has been suggested but not definitively confirmed

A

2,4-dichlorophenoxyacetic acid (2,4-D)

The study was called into question and subsequent studies have not been able to confirm a correlation

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24
Q

Scottish terriers exposed to lawn and garden care products containing phenoxy herbicides, including what three compounds, have an increased risk of developing TCC

A

2,4-D,4-chloro-2-methylphenoxy acetic acid (MCPA)

2-(4-chloro-2-methylphenoxyl) propionic acid (MCPP)

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25
Q

Significantly increased risk of oral SCC was seen in cats
that wore

A

Flea collars

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26
Q

In humans, daily use of what chemo drug has an increased risk of bladder cancer

A

Cyclophosphamide

**In dogs treated with metronomic chemotherapy occurrence of hemorrhagic cystitis appears to be higher than in dogs receiving maximally tolerated dose cyclophosphamide. Development of TCC after cyclophosphamide in dogs is rare but reported

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27
Q

What portion of the UV spectrum is most likely to be responsible for non-melanotic skin lesions and people and animals

A

UV B (280-320nm)

Light skin pigmentation and chronic sun exposure are associated with the development of facial, aural, and nasal planum SCC in white or partially white cats and may play a similar role in some cutaneous SCC lesions in dogs.

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28
Q

In human oncology most tumors occurring in heavily irradiated treatment fields are __, rather than epithelial, in
origin

A

Mesenchymal

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29
Q

T/F: there incidence of plate associated OSA is high

A

False - rare

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30
Q

60% to 88% of all cases of human mesothelioma are attributable to

A

asbestos exposure

Similar association has been found for dogs whose
owners have an asbestos-related occupation or hobby

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31
Q

What is the most common neoplasm of female intact dogs

A

Mammary tumors

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32
Q

The risk of developing mammary tumors rises what percent for dogs spayed after their second estrus?

A

26%

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33
Q

T/F: In dogs spayed at the time of mammary tumor excision, significantly fewer dogs subsequently developed
nonmalignant tumors than if they were not spayed at the same time (hazard ratio 0.47).

A

True

Dogs with intermediate grade and estrogen receptor positive tumors especially benefit from spay

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34
Q

Use of what products to prevent estrus or to treat
pseudopregnancy has been linked to an increased incidence of mammary tumor development in dogs

A

medroxyprogesterone acetate products (progestin and estrogen combination)

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35
Q

In one study, cats ovariectomized at 6 months of age had an approximate __ reduction in risk of mammary tumor development
compared with intact cats.

A

Sevenfold

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36
Q

Overley et al’s study of 308 cats with biopsy-proven mammary carcinoma diagnosed between 2000 and 2001 and a control population of 400 female cats not diagnosed with mammary tumors reported a ___% reduction in risk for those spayed before 6 months
of age and an ___% reduction in risk for those spayed before 1 year of age, compared with intact cats.

A

91 ; 86

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37
Q

T/F: non–Hodgkin lymphoma
is approximately 50% more common among women than men

A

FALSE - more common among men than women

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38
Q

Two breed-specific studies have evaluated gonad status
and lymphoma development. Both studies concluded that
spaying increases the risk of lymphoma in what breeds

A

golden retrievers and
Vizslas

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39
Q

In one study, female golden retrievers spayed after 1 year of age were diagnosed with HSA __ times more frequently than intact female dogs, or dogs spayed “early.”

A

Four

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40
Q

In one study Spayed Vizsla dogs were __ times more likely than intact females to develop HSA

A

Nine

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41
Q

is a benign neoplasm that is androgen dependent and occurs primarily in intact male dogs

A

Perianal adenoma - most resolve after castration

perianal adenocarcinoma occurs in both intact and castrated males

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42
Q

canine papillomaviruses are what kind of viruses

A

naked (e.g. non-enveloped)
DNA viruses

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43
Q

What virus is thought to be responsible for feline sarcoid

A

Bovine papillomavirus BPV-14

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44
Q

FeLV is what kind of virus

A

RNA virus

Oncoronavirinae

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45
Q

What are the two clinically important envelope proteins of FeLV?

A

P15E - mediates immunosuppression

GP70

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46
Q

What core protein of FeLV is detected in immunofluorescent assay tests (IFAs) and enzyme linked immuno sorbent assays (ELISAs)

A

P27

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47
Q

Cats infected with subgroups _ and _ of FeLV often develop thymic lymphoma
and myeloproliferative disease

A

A and B

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48
Q

Cats carrying FeLV-_ have developed severe erythroid hypoplasia and anemia and usually die within 1 to 2 months

A

C

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49
Q

What percentage of cats infected with FeLV develop lymphoid cancer

A

20%

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50
Q

__% of cats with nonlymphoid hematopoietic neoplasia (myeloproliferative disease) test positive for FeLV

A

70% to 90%

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51
Q

The relative risk of developing lymphoma is __ times higher in FeLV-positive cats

A

62

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52
Q

T/F: cats that are FeLV negative but that have had previous exposure to FeLV have a fortyfold increase in the risk of developing lymphoma.

A

TRUE

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53
Q

Most spontaneous lymphomas of cats that test positive for FeLV arise from __ cells, whereas FeLV-negative
lymphoma frequently is of alimentary or __-cell origin

A

T ; B

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54
Q

Cats that have felines sarcoma virus always test positive for what

A

FeLV

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55
Q

Sarcoma virus induced tumors are most frequently found in what age group

A

Young cats

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56
Q

Metastasis to the lungs or other organs occurs with approximately __% of virally induced fibrosarcomas in cats

A

30

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57
Q

How would you differentiate a feline virally induced fibrosarcoma from an injection sites sarcoma

A

Wally induced fibrosarcoma are always FeLV positive

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58
Q

Prognosis for cats with multicentric feline sarcoma virus induce tumors

A

Very poor

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59
Q

FIV is what kind of virus

A

enveloped, single-stranded RNA virus

Lentivirus

RNA is copied into the DNA in the infected host by RT in the virus

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60
Q

T/F: prevalence of neoplasms in FIV-positive cats ranges from 1% to 62%

A

TRUE

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61
Q

One study found that cats infected with FIV and
FeLV are __ times more likely to develop lymphoma or leukemia than if they had been infected with either virus alone

A

5.6

Cats with combined infections had a 77% greater likelihood of developing lymphoma or leukemia than noninfected cats

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62
Q

In contrast to FeLV-associated lymphomas, FIV-associated lymphomas most often develop in __ sites and occur in older cats (mean age, 8.7 years).

A

Extranodal

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63
Q

FIV-positive cats with lymphoma have extremely low CD_ lymphocyte counts

A

4

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64
Q

Progression through the cell cycle lasts approximately how many hours?

A

12-24

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65
Q

Phosphorylation of CDK/cyclin complexes at what residues suppresses their activity

A

Serine and threonine

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66
Q

CDK inhibitors can block G1/S progression by binding CDKs/cyclin complexes and can be classified into what two groups

A

INK4A family (p15INK4b, p16INK4a, p18INK4c, and p19INK4d)

CIP/KIP family (p21Cip1, p27Kip1, and p57Kip2)

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67
Q

INK4A CDKIs act primarily on what CDKs

A

CDK4 and CDK6 complexes and prevent the association with cyclin D

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68
Q

T/F: CIP/KIP family CDKIs are more specific than INK4As

A

FALSE - These are less specific and can inactivate various cyclin/CDK complexes

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69
Q

G1-phase cyclin–CDK complexes commit the cell to cell cycle entry at the G1/S transition through phosphorylation of __, causing release of the __ transcriptional factor and therefore an ability to overcome the restriction point R and move into the S
phase.

A

Rb ; E2F

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70
Q

Cell cycle checkpoints occur in the G1 phase in response to

A

DNA damage

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71
Q

Cell cycle checkpoints occur in S phase to

A

monitor the quality of DNA replication and the occurrence of DNA damage

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72
Q

Cell cycle checkpoints occur during the G2/M phase to

A

examine the status of the spindle

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73
Q

What are the two sensor kinases

A

ATM
ATR

If DNA is damaged during the cell cycle, there is activation of ATM and ATR and subsequent phosphorylation of downstream targets involved in cell cycle progression, repair, and cell death.

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74
Q

The p53 response to stress is largely mediated through the__ kinase

A

ATM

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75
Q

Phosphorylated p53 can function as a transcriptional regulator binding to specific DNA regulatory sequences and transactivating a number of genes, including __ which has a high affinity for G1 CDK/cyclin complexes and acts as a CDKI inhibiting kinase activity, thereby arresting cells in G1.

A

p21

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76
Q

Cellular levels of p53 protein are regulated by the product of what gene

A

mouse double minute 2 oncogene (MDM2)

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77
Q

How does MDM2 regulate p53 activity

A

1 - targets it for ubiquitylation leading to degradation

2 - suppresses p53 transcriptional activity

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78
Q

What are nutlins

A

cis-imidazoline analogs which inhibit the interaction between mdm2 and tumor suppressor p53

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79
Q

necrosis is characterized by __, apoptosis is marked by __

A

swelling of the cell and lysis

cellular and nuclear shrinkage followed by fragmentation and subsequent phagocytosis

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80
Q

Describe the difference between activation of a proton-oncogene versus a tumor suppressor gene

A

The conversion of a proto-oncogene to an oncogene is a result of somatic events in the genetic material of the target tissue. The activated allele of the oncogene dominates the wild-type allele and results in a dominant gain of function. This means that only one allele needs to be affected to obtain phenotypic change; this is in contrast to TS genes, in which both alleles have to be lost for phenotypic change.

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81
Q

the __ gene, which is frequently activated in feline T-cell lymphomas

A

myc

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82
Q

Inheritance of retinoblastoma is

A

Autosomal dominant with incomplete penetrance

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83
Q

Rb function can be
abrogated by point mutations, deletions, or complex formation with viral oncoproteins, such as

A

SV40 large T antigen and adenoviral E1a protein

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84
Q

What areare two prominent signaling molecules in the formation of blood vessels in tumors

A

VEGF and basic fibroblast growth factor

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85
Q

The degree of __ expression in the primary tumor of dogs with osteosarcoma (OSA) was shown to predict a more aggressive course of disease, defined by metastasis to the lung.

A

Ezrin

Ezrin is a membrane-cytoskeleton linker protein that functionally and physically connects the actin cytoskeleton to the cell membrane.

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86
Q

Steps in metastatic cascade

A

Intravasation —> circulation and resistance of anoikis —> immune evasion —> arrest/localization —> adherence —> extravasation —> survival/proliferation/angiogenesis —> metastasis

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87
Q

specific mechanisms used by cancer cells
to invade and intravasate

A

1 - mesenchymal invasion = enzymatic degradation of the ECM

2 - amoeboid invasion = cancer cells individually slip between fibers of the ECM without evidence or a need for enzymatic degradation

3 - collective invasion = en masse regional extension of a tumor into
surrounding tissues

collective invasion is observed clinically in dogs with oral SCC and biologically high-grade/histologically low-grade fibrosarcoma

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88
Q

The activity of what proteins associated with the mesenchymal invasion model of metastasis is correlated with grade and metastatic propensity of canine OSA and mast cell tumors

A

Matrix metalloproteases

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89
Q

What transcription factors are important for EMT

A

twist, snail, slug

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90
Q

__ is a loss of differentiation or atypical differentiation and is a feature of many, but not all, malignancies.

A

Anaplasia

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91
Q

Benign tumors of both epithelial and mesenchymal origin typi-
cally are associated with the suffix

A

-oma

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92
Q

Malignant tumors of epithelial origin are typically

A

carcinoma

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93
Q

Malignant tumors of mesenchymal origin are

A

Sarcomas

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94
Q

Round cell tumors

A

MCT
Lymphoma
Histiocytic sarcoma
Melanoma
TVT

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95
Q

Important mediators of tumoral neoangiogenesis

A

VEGF
Thrombospondin-1
Hypoxia-inducible factor-1alpha (HIF-1alpha)

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96
Q

Internal tandem duplications in exon __ of the c-kit proto-oncogene have been linked to tumor grade, survival, and response of TKI therapy

A

11

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97
Q

Describe WHO TNM tumor grading system

A

T = tumor size and/or invasion
N = nodal involvement
M = metastasis

Varies for each tumor type

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98
Q

Masson trichrome stain recognizes

A

Collagen / fibrocytic tumors

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99
Q

Alcian blue stain recognizes

A

Proteoglycans / myxoma, myxosarcoma

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100
Q

Congo red recognizes

A

Amyloid / plasma cell tumors, amyloid producing odontogenic tumors

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101
Q

AgNOR staining has prognostic value in what canine tumor types

A

Lymphoma
MCTs
Mammary tumors

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102
Q

Process of IHC staining

A

Can be performed on frozen or formalin fixed tissues

Tissue sections are incubated with primary antibodies to a specific cell protein (antigen)

Sections bound with primary antibody are then exposed to secondary antibodies directed against the primary antibody

Secondary antibodies are linked to peroidase or avoiding-biotin peroxidase complexes that catalyze a reaction in the presence of dye that precipitates at the site of the complex and is visible under the microscope

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103
Q

Periodic acid-Schiff (PAS) stain is used for what tumor type

A

Granular cell tumors

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104
Q

Oil Red-O or Sudan stains are used for what tumors

A

Liposarcomas / lipid-rich neoplasms

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105
Q

Stains used for MCTs

A

Toluidine blue
Giemsa
PAS

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106
Q

Special stain used for melanoma

A

Fontana-Masson

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107
Q

Silver stains can be used for what tumors

A

Neuroendocrine tumors

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108
Q

Phosphotungstic acid-hematoxylin is used for what tumors

A

Rhabdomyosarcoma

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109
Q

Number of newly diagnosed cancer cases divided by total population at risk over a specified period of time

A

Incidence

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110
Q

Number of total cancer cases divided by the number of dogs in the population at risk at one point in time

A

Prevalence

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111
Q

Proportional morbidity ratio

A

(Number of tumor type in breed / number of total tumors in breed) / (number of tumor type in all other breeds / number of total tumors in all other breeds)

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112
Q

Risk ratio formula

A

Incidence among exposed subjects / incidence among unexposed subjects

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113
Q

Odds ratio formula

A

(Number of exposed cases / number of unexposed cases) / (number of exposed controls / number of unexposed controls)

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114
Q

For risk ratio and odds ratio, a value greater than __ indicates the exposure is positively associated with disease (increases risk)

A

1.0

Value <1.0 indicates exposure is inversely associated with disease (decreases risk)

Value = 1.0 means no association between exposure and disease

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115
Q

If the 95% confidence interval includes 1.0, the RR or OR are considered __

A

Statistically nonsignificant

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116
Q

Environmental tobacco smoke exposure in dogs is linked to increased risk of what tumors

A

Lymphoma and sinonasal cancers

3.4-fold increased risk of

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117
Q

What cytokines interfere with normal balance of anorexigenic and orexigenic signals, thus contributing to cancer cachexia

A

IL-1
IL-6
TNF-alpha

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118
Q

Cytokines release in cancer cachexia results from

A

Activation of NF-kappaB signaling

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119
Q

TNF-alpha, via NF-kappaB signaling, upregulates the __ pathway as well as __, a member of the TGF-beta superfamily that negatively regulates muscle mass

A

Ubiquitin proteasome
Myostatin

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120
Q

Ways TNF-alpha contributes to cachexia

A

1 - activation of NF-kB leading to ubiquitin proteasome pathway activation

2 - activation of NF-kB signaling which upregulates myostatin

3 - interference with anabolic effects of growth hormone and IGF-1

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121
Q

What percentage of weight loss in people is considered consistent with cancer cachexia

A

30-70%

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122
Q

In a study of cancer cachexia in cats, what factors were identified as negative prognostic indicators

A

Low body weight
Low BCS

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123
Q

__ are the most common cause of paraneoplastic GI ulceration

A

Mast cell tumors

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124
Q

What is the driver of MCT related GI ulceration

A

Hyperhistaminemia

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125
Q

What other tumor type is associated with paraneoplastic gastroduodenal ulceration

A

Gastrinoma

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126
Q

What percentage of dogs vs cats with hypercalcemia are diagnosed with cancer?

A

Dogs - 60%
Cats - 30%

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127
Q

What percentage of dogs with T cell lymphoma develop hypercalcemia of malignancy

A

35-55%

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128
Q

What percentage of dogs with AGASACA develop hypercalcemia of malignancy

A

25%

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129
Q

What tumor types in cats are most commonly associated with hypercalcemia of malignancy

A

Lymphoma, squamous cell carcinoma, multiple myeloma

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130
Q

Primary hyperparathyroidism is usually caused by what tumor types

A

Parathyroid adenoma or adenomatous hyperplasia

131
Q

What are some mediators of hypercalcemia of malignancy

A

PTHrP - most common
IL-1
IL-6
TNF
Calcitriol

132
Q

T/F: Hypercalcemia of malignancy can be caused by osteoblasts when tumors invade or metastasize to bone

A

True

133
Q

Symptoms of hypercalcemia in dogs

A

Polyuria
Polydipsia
Anorexia
Vomiting
Muscle weakness or twitching

134
Q

Signs of hypercalcemia in cats

A

Anorexia and vomiting most common
PU/PD is much less common

135
Q

What is the mechanism of PU/PD from hypercalcemia

A

Impaired action of antidiuretic hormone (ADH) on tubular cells of the collecting duct

136
Q

Serum phosphate should be __ in dogs and cats with hypercalcemia of malignancy that are euhydrated and not azotemic

A

low to low-normal

137
Q

Serum PTH should be __ in hypercalcemia of malignancy, and serum PTHrP is usually __

A

Serum PTH should be low
Serum PTHrP is usually elevated but can be normal

(Serum calcitriol typically is normal but can be increased or decreased)

138
Q

When should supportive care for hypercalcemia be considered

A

Serum calcium concentration >16mg/dL
Calcium (mg/dL) x Phosphate (mg/dL) product >60
Patients that are clinically ill or azotemic
Patients with cancers that cannot be surgically removed or are unlikely to respond to chemotherapy/other therapy

139
Q

What IV fluid is recommended for correcting dehydration in hypercalcemia of malignancy patients

A

0.9% NaCl

The high sodium content competes with calcium for renal tubular absorption which enhances calciuresis

140
Q

What diuretic can be added to continued saline diuretics to further promote urinary calcium loss in hypercalcemia of malignancy

A

Furosemide

141
Q

If IV diuresis is unsuccessful what other therapies can be used to treat hypercalcemia of malignancy

A

Bisphosphonates (pamidronate 1.0-2.0mg/kg IV; zoledronate 0.1-0.25mg/kg IV)

Salmon calcitonin (4-8IU/kg SQ q8-12h) - expensive, can get rapid resistance to its effect within days

Steroids - NEED DIAGNOSIS FIRST; also can cause chemo resistance

142
Q

T/F: In humans, zoledronate is more effective at inducing normocalcemia and maintains normocalcemia for longer duration compared to pamidronate

A

True

143
Q

The most common cause of paraneoplastic hypoglycemia in dogs is __

A

Insulinoma

144
Q

What is the mechanism of hypoglycemia in dogs with insulinoma

A

Produce excessive amounts of insulin

Rarely can also release IGF-1 or IGF-2

145
Q

What are the most common non-islet cell tumors associated with paraneoplastic hypoglycemia

A

Liver tumors (HCC and hepatocellular adenomas)

Smooth muscle tumors (leiomyosarcoma and leiomyoma, especially hepatic and GI ones)

146
Q

What is the most common mechanism of paraneoplastic hypoglycemia in non-islet cell tumors

A

Tumor cell production of IGF-2

Other mechanisms include production of IGF-1 or somatomedins, hypermetabolism of glucose, production of substances stimulating insulin release, production of hepatic glucose inhibitor, insulin binding by monoclonal immunoglobulin (plasma cell tumors), insulin receptor proliferation, and rarely ectopic insulin production

147
Q

How are insulinomas usually diagnosed

A

Hypoglycemia with inappropriately elevated serum insulin

(Usually not visible on AUS)

148
Q

What tumor is most commonly associated with hyperestrongenism

A

Sertoli cell tumors

149
Q

What % of dogs with Sertoli cell tumors will display clinical signs of hyperestrogenism

A

25-50%

150
Q

Dogs with Sertoli cell tumors have significantly higher plasma __ levels compared with healthy controls

A

Estradiol-17beta

151
Q

Clinical signs of hyperestrogenism

A

Bilaterally symmetric alopecia
Cutaneous hyperpigmentation
Epidermal thinning
Gynecomastia
Galactorrhea
Pendulous prepuce
Penile atrophy
Atrophy of the contralateral testicle
Prostatic atrophy OR prostatomegaly
Attraction of other males

152
Q

Bone marrow toxicity with hyperestrogenism is characterized by

A

Transient increase in granulocytopoiesis and neutrophilic leukocytosis, followed by progressive bone marrow hypoplasia or aphasia leading to aplastic anemia (nonregenerative anemia, thrombocytopenia, and leukopenia)

153
Q

T/F: Clinical signs of hyperestrogenism do not resolve with surgical removal of the Sertoli cell tumor

A

False - they do, can take several months

Mortality rate for dogs with severe myelotoxicosis and pancytopenia is high

154
Q

Feline acromegaly is caused by

A

Hypersomatropism - excessive growth hormone secretion by a functional pituitary adenoma rising from somatotroph cells

155
Q

Canine acromegaly most commonly results from

A

Progestin-induced growth hormone secretion by mammary ductal epithelium

There are case reports of two GH-producing mammary tumors and one GH-producing pituitary tumor in dogs

156
Q

Signs of acromegaly in cats

A

Diabetes mellitus
Broad facial features
Prognathica inferior
Diffuse thickening of the oropharyngeal tissues
Hepatomegaly
Renomegaly
Adrenomegaly
Hypertrophic cardiomyopathy
Clubbing of paws and distal extremities
Degenerative arthropathy

157
Q

Measurement of __ in blood is the most practical way to confirm acromegaly

A

IGF-1

158
Q

3-5% of people with small cell lung cancer develop

A

Hyperadrenocorticism

due to ectopic production of ACTH or ACTH-like substances

159
Q

Expression of the __ gene, which contains ACTH, is responsible for hyperadrenocorticism in human small cell lung cancer

A

Proopiomelanocortin gene

Gene contains ACTH but also melanocyte-stimulating hormone, lipoprotein, endorphins, and enkephalins

160
Q

Clinical signs of ectopic ACTH production

A

Cushing’s signs
Hyperpigmentation

161
Q

How is ectopic ACTH diagnosed in people

A

Urine cortisol
Dex suppression test
Elevated plasma levels of ACTH or ACTH precursors

162
Q

Myeloma related disorders tumor cells typically produce an overabundance of a single type or component of immunoglobulin, which is referred to as the __ component.

A

M

163
Q

M components can interfere with coagulation primarily by

A

coating platelets

inhibiting platelet aggregation to damaged endothelial surfaces

release of platelet factor 3

164
Q

Bence jones proteinuria results from

A

Excessive free light chain due to an imbalance of production of heavy and light chains by plasma cells

165
Q

T/F: Bence Jones proteinuria can be detected on a urine dipstick

A

FALSE - need to do urine electrophoresis

166
Q

Bence jones proteins can cause renal tubular casts, leading to

A

Interstitial nephritis and possibly renal failure

167
Q

Hyperviscosity syndrome is associated with what conditions

A

Myeloma related disorders
Polycythemia Vera
Paraneoplastic erythrocytosis

168
Q

In patients with myeloma related disorders, hyperviscosity syndrome occurs most frequently in patients with __ macroglobulinemia

A

IgM - because IgM typically forms a high molecular weight pentamer

When it occurs in patients with multiple myeloma, the M component is more commonly IgA than IgG b/c IgA exists as a dimmer and occasional will polymerize (IgG is a monomer)

169
Q

What are some clinical signs of hyperviscosity syndrome

A

Neuro signs (stuporous mentation, ataxia, seizures)
Ocular abnormalities (torturous retinal vessels, retinal hemorrhage, retinal detachment w/acute onset blindness)
Bleeding distressing
Hypertrophic cardiomyopathy
CHF

170
Q

If hyperviscosity syndrome is caused by serum proteins, __ should be performed as emergency treatment if presentation is severe

A

Plasmapheresis

(If due to erythrocytosis, phlebotomy and IV fluids)

171
Q

What percentage of dogs with lymphoma present with anemia

A

30-43%

172
Q

What percentage of cats with lymphoma present with anemia

A

43-58%

173
Q

T/F: Anemia at diagnosis is a negative prognostic factor for both dogs and cats with lymphoma

A

True

174
Q

Anemia secondary to hemorrhage is NONREGENERATIVE/REGENERATIVE

A

Regenerative

175
Q

How long after hemorrhage can it take for reticulocytosis to manifest

A

2-3 days

176
Q

Iron deficiency anemia can develop with

A

GI ulceration (any chronic external hemorrhage)

177
Q

CBC findings with iron deficiency anemia

A

Microcytosis
Hypochromasia
Anemia

also get low serum iron and low saturation of transferrin

178
Q

CBC findings with immune mediated hemolytic anemia

A

Regenerative anemia (usually but not always)
Spherocytes
Autoagglutination

Hemoglobinemia and/or hyperbilirubinemia are also commonly seen

May have positive Coombs test

179
Q

IMHA is most commonly __ in dogs and __ in cats

A

Idiopathic in dogs

Secondary to FeLV in cats

180
Q

What cancers are most frequently associated with IMHA

A

Lymphomas and leukemias

181
Q

Non-immune mediated hemolytic anemia can arise secondary to what

A

Microangiopathy
Tumor cell erythrophagocytosis
Oxidative damage to erythrocytes

182
Q

Microangiopathic hemolytic anemia (MAHA) is caused by

A

Endothelial cell injury and fibrin deposition

Most commonly seen in patients with DIC, and by inherent abnormalities in tumor vasculature (think HSA)

183
Q

Clinically significant tumor cell erythrophagocytosis is seen most commonly with

A

Histiocytic sarcoma especially the hemophagocytic variant

184
Q

Clinicopathologic abnormalities of non-immune mediated hemolytic anemia

A

Markedly regenerative anemia
Negative direct agglutination test
Thrombocytopenia
Hypoalbuminemia
Hypocholesterolemia

185
Q

CBC findings with anemia of inflammatory disease/anemia of chronic disease

A

Mild to moderate nonregenerative normocytic, normochromic anemia

186
Q

What inflammatory cytokines reduce production of endogenous erythropoietin in the face of hypothermia and suppress the erythroid progenitor response to erythropoietin

A

TNF-alpha
IFN-gamma
IL-1
IL-6
IL-10

187
Q

__ increases production of hepcidin by the liver

A

IL-6

End result is sequestration of iron resulting in hypoferremia and decreased availability of iron for erythropoiesis

188
Q

__ is an acute phase protein that causes increased cellular internalization and degradation of ferroportin

A

Hepcidin

189
Q

__ is a membrane bound protein that exports iron from macrophages, hepatocytes, and duodenal enterocytes into peripheral blood

A

Ferroportin

190
Q

Paraneoplastic erythrocytosis has been reported in dogs with what tumor types

A

Various renal tumors
Nasal fibrosarcoma
Cecal leiomyosarcoma
Spinal cord schwannoma

191
Q

Paraneoplastic erythrocytosis is associated with increased serum

A

EPO

192
Q

What causes increased EPO in paraneoplastic erythrocytosis

A

Production by tumor cells
Impaired renal blood flow causing local tissue hypoxia

In humans, paraneoplastic erythrocytosis also results from tumor cells producing androgenic hormones and prostaglandins that enhance effects of EPO

193
Q

Primary absolute erythrocytosis is

A

Polycythemia Vera

194
Q

Causes of secondary absolute erythrocytosis

A

Chronic respiratory disease
Heart disease causing L to R shunting
Nonneoplastic renal disease

195
Q

Extremes neutrophilic leukocytosis also known as leukemoid response (> or =70k cells/uL), often with a left shift, monocytosis, and eosinophllia, has been reported in dogs with what tumor types

A

Pulmonary carcinoma
Renal tumors
Intestinal T cell lymphoma
Metastatic fibrosarcoma
Adenomatous rectal polyps

In cats: pulmonary SCC and dermal tubular adenocarcinomas

Thought to be due to tumor production of G-CSF and/or GM-CSF

196
Q

Eosinophilia is uncommon in dogs and cats but is seen most commonly with what tumor types

A

MCT
Lymphoma (especially T cell)

197
Q

Mast cells produce what eosinophilic cytokine

A

IL-5

(Human T cell lymphomas have been documented to produce this too)

198
Q

Cancer-associated immune mediated thrombocytopenia is most commonly associated with what tumor types

A

Lymphoma
Multiple myeloma
Histiocytic sarcoma

199
Q

The most common clotting factor dysfunction seen in veterinary cancer patients results from the release of __ by MCT

A

Heparin

200
Q

Heparin acts as a cofactor for what coagulation protein

A

Antithrombin III

Antithrombin III inactivates clotting factors XII, XI, X, IX

201
Q

Hyper or hypocoagulability is more common in cancer patients

A

Hypercoagulability

202
Q

In some studies, TEG documented hypercoagulability in __% of dogs with lymphoma and __% of dogs with various other cancers

A

56% of dogs with lymphoma
50% of dogs with various other cancers

203
Q

What tumor types have the most common incidence of DIC

A

HSA
Mammary adenocarcinoma (especially inflammatory form)
Pulmonary adenocarcinoma

204
Q

__, expressed on monocytes and endothelial cells dur-
ing inflammation and on some cancer cells, complexes with factor
VIIa to activate the extrinsic clotting cascade

A

Tissue factor

205
Q

__ is a paraneoplastic syndrome characterized by multiple slowly growing cutaneous collagenous nodules in association with bilateral renal cystadenocarcinomas or cystadenomas

A

Nodular fibrosis

206
Q

What breed of dog is most commonly (almost always) reported in cases of nodular dermatofibrosis

A

GSDs

Pedigree analysis strongly indicates autosomal dominant inheritance

207
Q

The nodular dermatofibrosis-associated mutation was mapped to the __ gene on chromosome __ that encodes __

A

BHD gene on chromosome 5 that encodes folliculin

208
Q

The BHD gene is the causative gene for what human renal cancer syndrome that is similar to renal cystadenocarcinoma/nodular dermatofibrosis in dogs

A

Birt-Hogg-Dube syndrome

209
Q

Female dogs affected with nodular dermatofibrosis almost always have what concurrent tumor

A

Uterine leiomyomas

210
Q

Superficial necrolytic dermatitis is seen most commonly in dogs with

A

Hepatic disease (it’s also known as hepatocutaneous syndrome)

Also reported in dogs and cats with glucagon-secreting tumors of the pancreas and liver

211
Q

Major dermatological findings of superficial necrolytic dermatitis

A

Erosions and ulcerations, with alopecia, exudation, and adherent crusts (Usually on the feet, pressure points, flank, perineal area, muzzle, facial mucocutaneous junctions, and/or oral cavity)

**Hyperkeratosis and fissuring of foot pads occurs in all affected animals

212
Q

Feline paraneoplastic alopecia has been reported in cats with what tumor types

A

Pancreatic carcinoma
Biliary carcinoma

213
Q

Paraneoplastic exfoliative dermatitis has been reported in cats with what tumor type

A

Thymomas

214
Q

Paraneoplastic myasthenia gravis is reported most commonly in dogs and cats with what tumor type

A

Thymoma

215
Q

T/F: in recent studies both myasthenia gravis and megaesophagus affected prognosis in dogs and cats with thymoma

A

FALSE: neither affected prognosis

216
Q

What tumor types were associated with paraneoplastic neuropathies in one study

A

Bronchogenic carcinoma
Mammary adenocarcinoma
Melanoma
Insulinoma
Osteosarcoma

217
Q

__ is a generalized osteoproductive disorder of periosteum that affects the long bones of the extremities, typically beginning on the digits and then progressing proximally

A

Hypertrophic osteopathy

218
Q

Paraneoplastic hypertrophic osteopathy is most commonly associated with what tumor types

A

Primary one tumors or tumors that have metastasized to the lungs

Two studies reported the majority of dogs with paraneoplastic HO presented with pulmonary metastasis, and the most common tumor type was osteosarcoma

219
Q

What nonneoplastic diseases have been associated with HO

A

Infectious/inflammatory lung disease
Dirofilaria immitis infection
Bacterial endocarditis
PDA with R to L shunting
Spirocera lupi esophageal granulomas
Esophageal foreign body
Congenital megaesophagus

220
Q

Radiographic findings of HO

A

Symmetric periosteal new bone formation that appears nodular or speculated, classically radiating 90 degrees from the long axis of the affected bones

Often evidence of adjacent soft tissue swelling and edema

221
Q

Fever is mediated primarily by what things

A

TNF-alpha
IL-1
IL-6
Hypothalamus

222
Q

Cytokines that mediate fever (TNF-alpha, IL-1, IL-6) activate the __ cascade, producing __ which acts on the thermoregulatory center of the hypothalamus

A

Activate the arachidonic acid cascade producing prostaglandin E2

223
Q

CT can detect pulmonary nodules as small as __mm in diameter whereas radiographs are limited to those at least __mm in diameter

A

CT: 1mm
X-ray: 7-9mm

224
Q

Pure ground-glass lesions __mm have a high probability of malignancy, whereas those __ are considered benign

A

> 8mm have high probability of malignancy

<4mm are considered benign

225
Q

Fluid is brighter on what sequence MRI

A

T2

226
Q

What hepatocyte specific MR contrast agent can potentially allow for differentiation between benign and malignant liver nodules

A

Gadoxetate disodium (Gd-EOB-DTPA)

227
Q

T/F: Scintigraphy can detect between benign inflammatory lesions and malignant lesions

A

FALSE - lacks specificity, cannot do this

228
Q

What compound is used in thyroid scintigraphy

A

99m-technetium pertechnetate (99mTcO4− There is a superscript negative sign beside the O and over the 4.)

229
Q

What is the most commonly used radiopharmaceutical for PET imaging

A

2-deoxy-2-18F-fluorodeoxy-glucose (FDG) bound to the positron emitter fluorine-18 (F-18)

230
Q

T/F: both tumors and inflammation result in increased glucose metabolism; therefore detection of a hypermetabolic lesion on PET is not definitively indicative of neoplasia

A

True

231
Q

PET agents other than FDG and their mechanism

A

F-18 labeled sodium fluoride (NaF) - bone specific

Tc99m-methyldiphosphonate - bone imaging with single-photon emission CT (SPECT)

F-18 labeled FLT (3’-deoxy-3’[18F]fluorothymidine) - reflects DNA synthesis, images proliferating tissues

Copper(II)-diacetyl-bis(N4-methylthiosemicarbazone) aka Cu-ATSM - radiation boost planning

232
Q

The standardized uptake value (SUV) is a semiquantitative measure of FDG uptake that is directly proportional to the metabolic activity. In human medicine an SUVmax __ is predictive of malignancy in patients with solitary pulmonary nodules.

A

> 2.5

No specific cut-offs established in vet med

233
Q

F-18 FDG was shown to correlate with grade of what tumor in a study of a small group of dogs

A

MCTs

234
Q

Special cytochemical stains for cytoplasmic/nuclear structures

A

Prussian blue = iron
Periodic acid–Schiff (PAS) v carbohydrates
Alkaline phosphatase = identifying osteoblasts

wide variety of leukocyte markers:
Sudan black B, peroxidase, chloracetate esterase, and nonspecific esterases

235
Q

Immunocytochemical staining - Common antibodies used in veterinary oncology

A

CD3 (T cells)
CD79a and CD20 (B cells)
cytokeratin (epithelial cells)
vimentin (mesenchymal cells)
Melan A (melanocytes)

236
Q

Cellular and cytoplasmic criteria of malignancy

A

variation in cell size (anisocytosis)
abnormal cellular arrangement (3D clusters instead of a monolayer)
cells that are smaller or larger than their normal counterpart
variable nuclear-to-cytoplasmic (N:C) ratios or N:C ratios that differ from what is expected for the cell type
intensely basophilic cytoplasm (hyperchromasia)
abnormal vacuolation or granulation
aberrant phagocytic activity

237
Q

Nuclear criteria of malignancy

A

variation in nuclear size (anisokaryosis)
unusual nuclear shape
multinuclearity
variation in nuclear size within the same multinucleated cell
nuclear fragments
multiple nucleoli that vary in size and shape within the same nucleus or among cells
increased mitoses
nonsymmetric mitoses

238
Q

In people, leukemia/small cell lymphoma (CLL/SCL) and mantle cell lymphoma (MCL) are both neoplasms of mature B cells, with a similar (but not identical) immunophenotype. However, MCL almost always
has a rearrangement between the immunoglobulin heavy chain locus (IgH) and the __ gene (encoding cyclinD1), whereas this rearrangement is very rare in CLL/SCL.

A

CCND1

239
Q

Canine mast cell tumors typically have internal tandem duplications of what exons

A

8 and 11

240
Q

What percentage of canine mass cell tumors have a duplication in either exon 8 or exon 11

A

14-20%

Dogs with tumors that carry the ITDs consistently have been shown to have a worse outcome than dogs with a wild-type c-kit gene

241
Q

What percentage of canine TCC have a single nucleotide change in the BRAF gene

A

80%

V595E mutation

This is the V600E mutation in people present in a variety of cancers, particularly melanoma

242
Q

droplet digital PCR (ddPCR). ddPCR can detect the V595E mutation when it is present in
as little as __% of the DNA

A

.01%

243
Q

In one study of 19 dogs with cutaneous mast cell tumors, the sentinel lymph node was different from the regional anatomic LN in __% of these dogs

A

42% (8 dogs)

244
Q

In a recent study, indirect lymphography was successful at identifying the sentinel lymph node in __% of veterinary patients with solid tumors of various histologies.

A

96.6%

245
Q

What chemo drugs are typically used in electrochemotherapy

A

Bleomycin
Cisplatin

246
Q

ratio between the toxic dose and the therapeutic dose for that drug

A

Therapeutic index

247
Q

empirically derived
value that represents the highest dose of a given drug that can
be administered with few patients experiencing unacceptable or
irreversible adverse effects

A

Maximum tolerated dose

248
Q

measured response at a putative target or surrogate that is related
to the mechanism of action of the agent

A

Biologically effective dose

249
Q

measure of dose
per unit of time; allows comparisons between protracted
and compacted dosing schedules

A

Dose intensity

250
Q

evaluated
when combining two drugs or a drug with radiation therapy, and
quantitatively describes any improved tumor response relative to
increased normal tissue toxicity when agents are used in a planned
schedule

A

Therapeutic gain

The basis for a positive therapeutic gain is the additive or
synergistic tumor effects that exceed any summative toxicity pat-
terns in normal tissues accomplished with combination therapy.

251
Q

used most commonly with hematopoietic cancers

the reintensification of therapy after remission is
attained to further reduce the likelihood of relapse.

A

Consolidation therapy

252
Q

also used after remission is attained but involves low-
intensity therapy given over a protracted period of time

A

Maintenance therapy

253
Q

enhancement of cytotoxicity when irradiation and chemotherapeutic agents are combined such that a therapeutic gain
is obtained

A

Radiosensitization

254
Q

basis for chemotherapeutic exposure leading to
enhanced radiosensitivity can be multifaceted and involve

A

(1) the
enrichment of the tumor cell population in a more sensitive phase
of the cell cycle, (2) increased tumor oxygenation through cytore-
duction or alterations in tumor vascularization, and (3) selective
killing of inherently radioresistant hypoxic cell fractions

255
Q

Chemosensitivity depends on a number of factors, including

A

drug uptake into the cell, interaction with a cellular target, genera-
tion of lethal damage to important cellular macromolecules, repair
of potentially lethal damage, and the cell’s response to generated
damage

256
Q

__ is actively transported
into cells by two amino acid transporters,5 and blocking transport
with amino acid substrates or analogs can significantly affect cyto-
toxicity

A

Melphalan

257
Q

__ levels can play a role in the sen-
sitivity of tumor cells to doxorubicin (DOX)

A

topoisomerase IIα

258
Q

increased levels of __ correlate with a decrease in sensitivity to 5-FU

A

thymidylate synthetase

259
Q

Induction of __ has been shown to be a mechanism by which tumor
cells can acquire resistance to nitrogen mustards.

A

glutathione-S-transferases

260
Q

sensitivity of tumor cells to
5-FU is inversely correlated with the expression of __, the enzyme predominantly responsible
for the metabolism of 5-FU to the inactive 5-FUH2 metabolite

A

dihydropyrimidine dehydrogenase

261
Q

gemcitabine must be phosphorylated to
the di- and triphosphate forms before eliciting an inhibitory effect
on DNA synthesis. The enzyme responsible for this metabolic
activation is __

A

deoxycytidine kinase

262
Q

T/F: in dogs with appendicular osteosarcoma (OSA), adjuvant
treatment with combinations of platinum and DOX empirically
does show any improvement in disease-free interval or survival over those treated with single-agent DOX or platinum protocol

A

FALSE: does NOT

263
Q

T/F: Alcohol will deactivate chemotherapy drugs

A

FALSE - Alcohol will not deactivate chemotherapy drugs and can spread contamination.

264
Q

BSA formula

A

m2 = [A x (weight in grams)^2/3] / 10,000

A for dogs = 10.1
A for cats = 10.0

265
Q

What excipient (drug carrier) in earlier paclitaxel formulations was the cause of hypersensitivity reactions in dogs

A

Cremaphor-EL

Newer formulations use water-soluble micellar formulations of paclitaxel but are not yet commercially available

266
Q

MOA of alylators

A

Covalent binding of alkyl groups to DNA to form monofunctional or bifunctional adducts that generate inter- or intrastrand cross-links

267
Q

Classes of alylators

A

Nitrogen mustards (mustargen, melphalan, cyclophosphamide, ifosfamide, chlorambucil)

Nitrosureas (CCNU, streptozotocin)

Others - dacarbazine and procarbazine

268
Q

MOA of antitumor antibiotics

A

Diverse - specific to each drug in the class

269
Q

Drugs classified as antitumor antibiotics

A

Doxorubicin
Mitoxantrone
Actinomycin D (Dactinomycin)

270
Q

MOA of antimetabolites

A

Inhibit use of cellular metabolites in the course of cell growth and division

Usually analogs of compounds used in the normal course of metabolism/anabolic processes associated with DNA replication

271
Q

Drugs classified as antimetabolites

A

Cytosine arabinoside (cytarabine, Ara-C)
Methotrexate
Gemcitabine 5-FU
Rabacfosadine (Tanovea)

272
Q

MOA of antimicrotubule agents

A

Interference with the polymerization or depolymerization of the microtubule

273
Q

Classes of antimicrotubule agents

A

Taxanes - paclitaxel, docetaxel
Vinca alkaloids - vinblastine, vincristine, vindesine, vinorelbine

274
Q

MOA of topoisomerase inhibitors

A

Inhibit either type I or type II topoisomerase enzymes that are involved in the unlinking or unwinding of the DNA strand for replication and transcription

275
Q

Classes of topoisomerase II inhibitors

A

Anthracyclines
Epipodophyllotoxins - etoposide, teniposide

276
Q

Major class of topoisomerase I inhibitors

A

Camptothecins - little to no use in vet med, more common in people

277
Q

MOA of platinum agents

A

Covalent binding to DNA through displacement reactions, resulting in bifunctional lesions and inter- or intrastrand cross-links

Intrastrand adducts account for the majority of platinum-DNA damage and are highly correlated with drug-induced cell killing

278
Q

Major intrastrand adducts of platinum agents

A

N7-d(GpG)
N7-d(ApG)

279
Q

MOA of hydroxyurea

A

Inhibitor of ribonucleotide reductive —> results in depletion of deoxyribonucleotide pools

280
Q

MOA of L-asparaginase

A

Hydrolysis of L-asparagine to L-aspartic acid —> depletion of circulating L-asparagine —> inhibition of protein synthesis in tumor cells lacking L-asparagine synthetase —> induction of apoptosis

281
Q

Mechlorethamine undergoes spontaneous hydrolysis to __ and __, yielding nucleophilic reactive centers capable of forming DNA cross-links

A

2-hydroxyethyl-2-chloroethylmethylamine and bis-2-hydroxyethylmethylamine

282
Q

What are the dose limiting toxicities of mechlorethamine-containing protocols

A

GI toxicity
Bone marrow toxicity

283
Q

Mechlorethamine is a strong vesicant - how should extravasation be treated?

A

Sodium thiosulfate (0.17mmol/L, or 2.5%) administered through the catheter before removal, or injected directly into affected site after catheter has been removed

Volume injected should be equal to that of the intended mechlorethamine dose

284
Q

Uptake of melphalan into tumor cells by anime acid transporters can be blocked by what amino acid

A

Leucine

285
Q

T/F: Melphalan requires activation prior to exerting alkylating activity

A

FALSE - has direct alkylating activity, doesn’t require metabolic activation

286
Q

What is the oral bioavailability of melphalan

A

30%

287
Q

T/F: Cyclophosphamide and ifosfamide are prodrugs that require metabolic activation by
microsomal mixed function oxidases

A

TRUE

288
Q

How is cyclophosphamide activated

A

Activation occurs via microsomal mixed function oxidases predominantly in the liver

ring oxidation to 4-hydroxycyclophosphamide (4-OHCP) —> spontaneous and
reversible ring opening to the amino aldehyde aldophosphamide —> irreversible breakdown of aldophosphamide to phosphoramide mustard and acrolein

289
Q

Most active CP metabolite; it is capable of bifunctional alkylation and cross-linking

A

Phosphoramide mustard

290
Q

DLT of cyclophosphamide

A

Neutropenia

291
Q

T/F: incidence of sterile hemorrhagic cystitis is higher with chronic oral dosing, and a cumulative dose is a risk factor.

A

True

292
Q

Substitute for patients that get sterile hemorrhagic cystitis

A

Chlorambucil

293
Q

Treatment for sterile hemorrhagic cystitis

A

symptomatic

nonsteroidal antiinflammatory drugs (NSAIDs)
oxybutynin (0.2–0.3 mg/kg PO q8–12 h)
pentosan polysulfate sodium (20 mg/kg PO twice weekly for 5 weeks, then once weekly for 12 weeks)

In extreme cases, intravesicular dimethyl sulfoxide (DMSO) or
dilute formalin, or surgery can be considered

294
Q

__ accounts for up to 25% of the metabolism of ifosfamide

A

dechloroethylation

295
Q

neurotoxic metabolite that develops after ifosfamide dosing

A

chloracetaldehyde

296
Q

DLT for ifosfamide

A

Dose related myelosuppression

nephrotoxicity and damage
to the bladder epithelium are not uncommon

297
Q

__, a urinary
epithelial protectant, must be administered with ifosfamide to avoid severe cystitis

Also given in people who get high dose cytoxan

A

sodium 2-mercaptoethane sulfonate

Aka mesna

298
Q

primary metabolite of chlorambucil that is presumably responsible for much of the clinical activity

A

phenylacetic acid

299
Q

DLT of chlorambucil

A

Myelosuppression

300
Q

CCNU can cross the blood brain barrier because it is highly

A

Lipophilic

301
Q

Metabolism of CCNU

A

extensive hepatic metabolism, predominantly by hydroxylation of the cyclohexyl ring, to metabolites with at least equivalent alkylating activity that
presumably play an important role in the cytotoxic activity.

This extensive hepatic metabolism is presumably responsible for the lack of oral bioavailability of the parent compound but rapid appearance of metabolites after oral dosing.

302
Q

DLT for CCNU

A

myelosuppression with acute neutropenia followed by cumulative and potentially irreversible thrombocytopenia

303
Q

For cats that receive CCNU, when does the neutrophil nadir occur

A

anywhere from 1 to 4 weeks post-
treatment

304
Q

MOA of denamarin

A

Increases glutathione levels and acts as an antioxidant

305
Q

What side effect of CCNU has been rarely reported in cats

A

Pulmonary fibrosis

306
Q

Cat dose of CCNU

A

40-60mg/m2

Dogs 70-90mg/m2

307
Q

Cellular uptake of streptozotocin is dependent on the __ transporter and

A

GLUT2

expression of this transporter determines sensitivity of both
insulinoma and pancreatic beta cells

308
Q

T/F: Streptozotocin can induce diabetes in animals

A

True

309
Q

Dacarbazine is a prodrug that requires metabolic activation by the ___ system

A

Hepatic cytochrome P450 system

310
Q

Activation of dacarbazine results in what

A

5-aminoimidazole carboxamide and the active methylating intermediate methyldiazonium ion

Resulting DNA methylation products are 3-methyl adenine, 7-methyl guanine, and O6-methyl guanine

311
Q

Use of dacarbazine is not recommended in cats because

A

Lack of info regarding ability to convert it to the active form

312
Q

DLT of dacarbazine

A

GI toxicity

Severe myelosuppression can be observed

313
Q

T/F: Procarbazine is a prodrug

A

True - requires activation to active metabolites

314
Q

Route of administration for procarbazine

A

Oral

IV has been tested in people but caused neurotoxicity

315
Q

MOAs of doxorubicin

A
  • DNA intercalation and inhibition of RNA and DNA polymerases and topoisomerase II
  • alkylation of DNA
  • ROS generation
  • perturbation of calcium homeostasis
  • inhibition of thioredoxin reductase
  • interaction with plasma membrane components
316
Q

Elimination of doxorubicin occurs through

A

Renal and biliary elimination

Also is metabolized to doxorubicinol and the 7-hydroxy a glycine

317
Q

Rapid administration of doxorubicin can cause

A

Anaphylactoid-like reactions

Administer over 15-30mins to avoid this

318
Q

Doxorubicin is a VESICANT/IRRITANT; in the event of extravasation, __ should be applied

A

Vesicant
Cold compress

319
Q

__ has been shown to substantially reduce the extent of tissue damage and should be given IV immediately after extravasation and ideally again 24 and 48h later

A

Dexrazoxane (Zinecard)

10mg per 1mg of doxorubicin given

Given in different vein from site of extravasation

320
Q

Acute DLTs with doxorubicin

A

Myelosuppression and GI toxicity

321
Q

Acute cardiotoxicity from doxorubicin manifests as

A

Transient arrhythmias associated with transient increases in circulating histamine and catecholamines

ACUTE is usually of little clinical significance

322
Q

Cytosine arabinoside is phosphorylated in cells to generate __ which acts as a competitive inhibitor of __

A

Arabinosylcytosine triphosphate (ara-CTP)

DNA polymerase alpha

323
Q

MOA of cytarabine

A

Ara-CTP is incorporated into DNA and cannot be excised —> inhibitors both the function of the DNA template and subsequent synthesis

324
Q

primary targets of toceranib

A

KIT (stem cell factor receptor, CD117),
vascular endothelial growth factor receptor 2 (VEGFR2)
platelet-derived growth factor receptor β (PDGFRβ)
FMS-like tyrosine kinase-3 (Flt-3)

Onc Boards (4 decks)

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