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
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
3
Q
Elephants have enhanced activity of __ (tumor suppressor gene) which confers protection against cancer
A
TP53 gene
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.
5
Q
What is the Hayflick limit
A
Limitation of the number of times a cell can replicate by the genetic program
6
Q
VEGF expression is upregulated by
A
Hypoxia and inflammation
7
Q
What transcription factor is a major regulator of VEGF expression
A
HIF-1alpha
8
Q
What tumor suppressor gene is involved HIF-1alpha in the VEGF regulation pathway
A
von Hippel-Lindau (VHL) tumor suppressor gene
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
10
Q
How does PDGF-beta contribute to angiogenesis
A
Recruitment of pericytes and maturation of new capillaries
11
Q
Canine HSAs show elevated production of what proangiogenic drivers
A
VEGF
IL-8
sphingosine-1 phosphate (S1P) and its receptor (S1P1)
12
Q
Magnitude of angiogenic drive in canine hemangiosarcoma is associated with somatic mutations of
A
Angiopoietin
VEGF
PI3K signaling pathways
13
Q
___ is upregulated recurrently in canine HSA and OSA where it is presumed to promote invasion and migration upon binding CXCL12
A
CXCR4
14
Q
Upregulation of what glucose transporter is seen in virtually all cancer cells
A
GLUT-1
15
Q
PET mots commonly uses what molecule as a reporter
A
18F-fluorodeoxyglucose (18F-FDG)
16
Q
The BCR gene is located on what chromosome number in humans vs dogs
A
Humans = chromosome 22
Dogs = chromosome 26
17
Q
The ABL gene is located on what chromosome number in humans and dogs
A
Chromosome 9 in both
18
Q
The Philadelphia chromosome is called the __ chromosome in dogs
A
Raleigh
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
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
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
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
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
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)
25
Significantly increased risk of oral SCC was seen in cats
that wore
Flea collars
26
In humans, daily use of what chemo drug has an increased risk of bladder cancer
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
27
What portion of the UV spectrum is most likely to be responsible for non-melanotic skin lesions and people and animals
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.
28
In human oncology most tumors occurring in heavily irradiated treatment fields are __, rather than epithelial, in
origin
Mesenchymal
29
T/F: there incidence of plate associated OSA is high
False - rare
30
60% to 88% of all cases of human mesothelioma are attributable to
asbestos exposure
Similar association has been found for dogs whose
owners have an asbestos-related occupation or hobby
31
What is the most common neoplasm of female intact dogs
Mammary tumors
32
The risk of developing mammary tumors rises what percent for dogs spayed after their second estrus?
26%
33
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).
True
Dogs with intermediate grade and estrogen receptor positive tumors especially benefit from spay
34
Use of what products to prevent estrus or to treat
pseudopregnancy has been linked to an increased incidence of mammary tumor development in dogs
medroxyprogesterone acetate products (progestin and estrogen combination)
35
In one study, cats ovariectomized at 6 months of age had an approximate __ reduction in risk of mammary tumor development
compared with intact cats.
Sevenfold
36
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.
91 ; 86
37
T/F: non–Hodgkin lymphoma
is approximately 50% more common among women than men
FALSE - more common among men than women
38
Two breed-specific studies have evaluated gonad status
and lymphoma development. Both studies concluded that
spaying increases the risk of lymphoma in what breeds
golden retrievers and
Vizslas
39
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.”
Four
40
In one study Spayed Vizsla dogs were __ times more likely than intact females to develop HSA
Nine
41
is a benign neoplasm that is androgen dependent and occurs primarily in intact male dogs
Perianal adenoma - most resolve after castration
perianal adenocarcinoma occurs in both intact and castrated males
42
canine papillomaviruses are what kind of viruses
naked (e.g. non-enveloped)
DNA viruses
43
What virus is thought to be responsible for feline sarcoid
Bovine papillomavirus BPV-14
44
FeLV is what kind of virus
RNA virus
Oncoronavirinae
45
What are the two clinically important envelope proteins of FeLV?
P15E - mediates immunosuppression
GP70
46
What core protein of FeLV is detected in immunofluorescent assay tests (IFAs) and enzyme linked immuno sorbent assays (ELISAs)
P27
47
Cats infected with subgroups _ and _ of FeLV often develop thymic lymphoma
and myeloproliferative disease
A and B
48
Cats carrying FeLV-_ have developed severe erythroid hypoplasia and anemia and usually die within 1 to 2 months
C
49
What percentage of cats infected with FeLV develop lymphoid cancer
20%
50
__% of cats with nonlymphoid hematopoietic neoplasia (myeloproliferative disease) test positive for FeLV
70% to 90%
51
The relative risk of developing lymphoma is __ times higher in FeLV-positive cats
62
52
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.
TRUE
53
Most spontaneous lymphomas of cats that test positive for FeLV arise from __ cells, whereas FeLV-negative
lymphoma frequently is of alimentary or __-cell origin
T ; B
54
Cats that have felines sarcoma virus always test positive for what
FeLV
55
Sarcoma virus induced tumors are most frequently found in what age group
Young cats
56
Metastasis to the lungs or other organs occurs with approximately __% of virally induced fibrosarcomas in cats
30
57
How would you differentiate a feline virally induced fibrosarcoma from an injection sites sarcoma
Wally induced fibrosarcoma are always FeLV positive
58
Prognosis for cats with multicentric feline sarcoma virus induce tumors
Very poor
59
FIV is what kind of virus
enveloped, single-stranded RNA virus
Lentivirus
RNA is copied into the DNA in the infected host by RT in the virus
60
T/F: prevalence of neoplasms in FIV-positive cats ranges from 1% to 62%
TRUE
61
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
5.6
Cats with combined infections had a 77% greater likelihood of developing lymphoma or leukemia than noninfected cats
62
In contrast to FeLV-associated lymphomas, FIV-associated lymphomas most often develop in __ sites and occur in older cats (mean age, 8.7 years).
Extranodal
63
FIV-positive cats with lymphoma have extremely low CD_ lymphocyte counts
4
64
Progression through the cell cycle lasts approximately how many hours?
12-24
65
Phosphorylation of CDK/cyclin complexes at what residues suppresses their activity
Serine and threonine
66
CDK inhibitors can block G1/S progression by binding CDKs/cyclin complexes and can be classified into what two groups
INK4A family (p15INK4b, p16INK4a, p18INK4c, and p19INK4d)
CIP/KIP family (p21Cip1, p27Kip1, and p57Kip2)
67
INK4A CDKIs act primarily on what CDKs
CDK4 and CDK6 complexes and prevent the association with cyclin D
68
T/F: CIP/KIP family CDKIs are more specific than INK4As
FALSE - These are less specific and can inactivate various cyclin/CDK complexes
69
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.
Rb ; E2F
70
Cell cycle checkpoints occur in the G1 phase in response to
DNA damage
71
Cell cycle checkpoints occur in S phase to
monitor the quality of DNA replication and the occurrence of DNA damage
72
Cell cycle checkpoints occur during the G2/M phase to
examine the status of the spindle
73
What are the two sensor kinases
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.
74
The p53 response to stress is largely mediated through the__ kinase
ATM
75
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.
p21
76
Cellular levels of p53 protein are regulated by the product of what gene
mouse double minute 2 oncogene (MDM2)
77
How does MDM2 regulate p53 activity
1 - targets it for ubiquitylation leading to degradation
2 - suppresses p53 transcriptional activity
78
What are nutlins
cis-imidazoline analogs which inhibit the interaction between mdm2 and tumor suppressor p53
79
necrosis is characterized by __, apoptosis is marked by __
swelling of the cell and lysis
cellular and nuclear shrinkage followed by fragmentation and subsequent phagocytosis
80
Describe the difference between activation of a proton-oncogene versus a tumor suppressor gene
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.
81
the __ gene, which is frequently activated in feline T-cell lymphomas
myc
82
Inheritance of retinoblastoma is
Autosomal dominant with incomplete penetrance
83
Rb function can be
abrogated by point mutations, deletions, or complex formation with viral oncoproteins, such as
SV40 large T antigen and adenoviral E1a protein
84
What areare two prominent signaling molecules in the formation of blood vessels in tumors
VEGF and basic fibroblast growth factor
85
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.
Ezrin
Ezrin is a membrane-cytoskeleton linker protein that functionally and physically connects the actin cytoskeleton to the cell membrane.
86
Steps in metastatic cascade
Intravasation —> circulation and resistance of anoikis —> immune evasion —> arrest/localization —> adherence —> extravasation —> survival/proliferation/angiogenesis —> metastasis
87
specific mechanisms used by cancer cells
to invade and intravasate
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
88
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
Matrix metalloproteases
89
What transcription factors are important for EMT
twist, snail, slug
90
__ is a loss of differentiation or atypical differentiation and is a feature of many, but not all, malignancies.
Anaplasia
91
Benign tumors of both epithelial and mesenchymal origin typi-
cally are associated with the suffix
-oma
92
Malignant tumors of epithelial origin are typically
carcinoma
93
Malignant tumors of mesenchymal origin are
Sarcomas
94
Round cell tumors
MCT
Lymphoma
Histiocytic sarcoma
Melanoma
TVT
95
Important mediators of tumoral neoangiogenesis
VEGF
Thrombospondin-1
Hypoxia-inducible factor-1alpha (HIF-1alpha)
96
Internal tandem duplications in exon __ of the c-kit proto-oncogene have been linked to tumor grade, survival, and response of TKI therapy
11
97
Describe WHO TNM tumor grading system
T = tumor size and/or invasion
N = nodal involvement
M = metastasis
Varies for each tumor type
98
Masson trichrome stain recognizes
Collagen / fibrocytic tumors
99
Alcian blue stain recognizes
Proteoglycans / myxoma, myxosarcoma
100
Congo red recognizes
Amyloid / plasma cell tumors, amyloid producing odontogenic tumors
101
AgNOR staining has prognostic value in what canine tumor types
Lymphoma
MCTs
Mammary tumors
102
Process of IHC staining
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
103
Periodic acid-Schiff (PAS) stain is used for what tumor type
Granular cell tumors
104
Oil Red-O or Sudan stains are used for what tumors
Liposarcomas / lipid-rich neoplasms
105
Stains used for MCTs
Toluidine blue
Giemsa
PAS
106
Special stain used for melanoma
Fontana-Masson
107
Silver stains can be used for what tumors
Neuroendocrine tumors
108
Phosphotungstic acid-hematoxylin is used for what tumors
Rhabdomyosarcoma
109
Number of newly diagnosed cancer cases divided by total population at risk over a specified period of time
Incidence
110
Number of total cancer cases divided by the number of dogs in the population at risk at one point in time
Prevalence
111
Proportional morbidity ratio
(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)
112
Risk ratio formula
Incidence among exposed subjects / incidence among unexposed subjects
113
Odds ratio formula
(Number of exposed cases / number of unexposed cases) / (number of exposed controls / number of unexposed controls)
114
For risk ratio and odds ratio, a value greater than __ indicates the exposure is positively associated with disease (increases risk)
1.0
Value <1.0 indicates exposure is inversely associated with disease (decreases risk)
Value = 1.0 means no association between exposure and disease
115
If the 95% confidence interval includes 1.0, the RR or OR are considered __
Statistically nonsignificant
116
Environmental tobacco smoke exposure in dogs is linked to increased risk of what tumors
Lymphoma and sinonasal cancers
3.4-fold increased risk of
117
What cytokines interfere with normal balance of anorexigenic and orexigenic signals, thus contributing to cancer cachexia
IL-1
IL-6
TNF-alpha
118
Cytokines release in cancer cachexia results from
Activation of NF-kappaB signaling
119
TNF-alpha, via NF-kappaB signaling, upregulates the __ pathway as well as __, a member of the TGF-beta superfamily that negatively regulates muscle mass
Ubiquitin proteasome
Myostatin
120
Ways TNF-alpha contributes to cachexia
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
121
What percentage of weight loss in people is considered consistent with cancer cachexia
30-70%
122
In a study of cancer cachexia in cats, what factors were identified as negative prognostic indicators
Low body weight
Low BCS
123
__ are the most common cause of paraneoplastic GI ulceration
Mast cell tumors
124
What is the driver of MCT related GI ulceration
Hyperhistaminemia
125
What other tumor type is associated with paraneoplastic gastroduodenal ulceration
Gastrinoma
126
What percentage of dogs vs cats with hypercalcemia are diagnosed with cancer?
Dogs - 60%
Cats - 30%
127
What percentage of dogs with T cell lymphoma develop hypercalcemia of malignancy
35-55%
128
What percentage of dogs with AGASACA develop hypercalcemia of malignancy
25%
129
What tumor types in cats are most commonly associated with hypercalcemia of malignancy
Lymphoma, squamous cell carcinoma, multiple myeloma
130
Primary hyperparathyroidism is usually caused by what tumor types
Parathyroid adenoma or adenomatous hyperplasia
131
What are some mediators of hypercalcemia of malignancy
PTHrP - most common
IL-1
IL-6
TNF
Calcitriol
132
T/F: Hypercalcemia of malignancy can be caused by osteoblasts when tumors invade or metastasize to bone
True
133
Symptoms of hypercalcemia in dogs
Polyuria
Polydipsia
Anorexia
Vomiting
Muscle weakness or twitching
134
Signs of hypercalcemia in cats
Anorexia and vomiting most common
PU/PD is much less common
135
What is the mechanism of PU/PD from hypercalcemia
Impaired action of antidiuretic hormone (ADH) on tubular cells of the collecting duct
136
Serum phosphate should be __ in dogs and cats with hypercalcemia of malignancy that are euhydrated and not azotemic
low to low-normal
137
Serum PTH should be __ in hypercalcemia of malignancy, and serum PTHrP is usually __
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
When should supportive care for hypercalcemia be considered
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
What IV fluid is recommended for correcting dehydration in hypercalcemia of malignancy patients
0.9% NaCl
The high sodium content competes with calcium for renal tubular absorption which enhances calciuresis
140
What diuretic can be added to continued saline diuretics to further promote urinary calcium loss in hypercalcemia of malignancy
Furosemide
141
If IV diuresis is unsuccessful what other therapies can be used to treat hypercalcemia of malignancy
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
T/F: In humans, zoledronate is more effective at inducing normocalcemia and maintains normocalcemia for longer duration compared to pamidronate
True
143
The most common cause of paraneoplastic hypoglycemia in dogs is __
Insulinoma
144
What is the mechanism of hypoglycemia in dogs with insulinoma
Produce excessive amounts of insulin
Rarely can also release IGF-1 or IGF-2
145
What are the most common non-islet cell tumors associated with paraneoplastic hypoglycemia
Liver tumors (HCC and hepatocellular adenomas)
Smooth muscle tumors (leiomyosarcoma and leiomyoma, especially hepatic and GI ones)
146
What is the most common mechanism of paraneoplastic hypoglycemia in non-islet cell tumors
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
How are insulinomas usually diagnosed
Hypoglycemia with inappropriately elevated serum insulin
(Usually not visible on AUS)
148
What tumor is most commonly associated with hyperestrongenism
Sertoli cell tumors
149
What % of dogs with Sertoli cell tumors will display clinical signs of hyperestrogenism
25-50%
150
Dogs with Sertoli cell tumors have significantly higher plasma __ levels compared with healthy controls
Estradiol-17beta
151
Clinical signs of hyperestrogenism
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
Bone marrow toxicity with hyperestrogenism is characterized by
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
T/F: Clinical signs of hyperestrogenism do not resolve with surgical removal of the Sertoli cell tumor
False - they do, can take several months
Mortality rate for dogs with severe myelotoxicosis and pancytopenia is high
154
Feline acromegaly is caused by
Hypersomatropism - excessive growth hormone secretion by a functional pituitary adenoma rising from somatotroph cells
155
Canine acromegaly most commonly results from
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
Signs of acromegaly in cats
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
Measurement of __ in blood is the most practical way to confirm acromegaly
IGF-1
158
3-5% of people with small cell lung cancer develop
Hyperadrenocorticism
due to ectopic production of ACTH or ACTH-like substances
159
Expression of the __ gene, which contains ACTH, is responsible for hyperadrenocorticism in human small cell lung cancer
Proopiomelanocortin gene
Gene contains ACTH but also melanocyte-stimulating hormone, lipoprotein, endorphins, and enkephalins
160
Clinical signs of ectopic ACTH production
Cushing’s signs
Hyperpigmentation
161
How is ectopic ACTH diagnosed in people
Urine cortisol
Dex suppression test
Elevated plasma levels of ACTH or ACTH precursors
162
Myeloma related disorders tumor cells typically produce an overabundance of a single type or component of immunoglobulin, which is referred to as the __ component.
M
163
M components can interfere with coagulation primarily by
coating platelets
inhibiting platelet aggregation to damaged endothelial surfaces
release of platelet factor 3
164
Bence jones proteinuria results from
Excessive free light chain due to an imbalance of production of heavy and light chains by plasma cells
165
T/F: Bence Jones proteinuria can be detected on a urine dipstick
FALSE - need to do urine electrophoresis
166
Bence jones proteins can cause renal tubular casts, leading to
Interstitial nephritis and possibly renal failure
167
Hyperviscosity syndrome is associated with what conditions
Myeloma related disorders
Polycythemia Vera
Paraneoplastic erythrocytosis
168
In patients with myeloma related disorders, hyperviscosity syndrome occurs most frequently in patients with __ macroglobulinemia
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
What are some clinical signs of hyperviscosity syndrome
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
If hyperviscosity syndrome is caused by serum proteins, __ should be performed as emergency treatment if presentation is severe
Plasmapheresis
(If due to erythrocytosis, phlebotomy and IV fluids)
171
What percentage of dogs with lymphoma present with anemia
30-43%
172
What percentage of cats with lymphoma present with anemia
43-58%
173
T/F: Anemia at diagnosis is a negative prognostic factor for both dogs and cats with lymphoma
True
174
Anemia secondary to hemorrhage is NONREGENERATIVE/REGENERATIVE
Regenerative
175
How long after hemorrhage can it take for reticulocytosis to manifest
2-3 days
176
Iron deficiency anemia can develop with
GI ulceration (any chronic external hemorrhage)
177
CBC findings with iron deficiency anemia
Microcytosis
Hypochromasia
Anemia
also get low serum iron and low saturation of transferrin
178
CBC findings with immune mediated hemolytic anemia
Regenerative anemia (usually but not always)
Spherocytes
Autoagglutination
Hemoglobinemia and/or hyperbilirubinemia are also commonly seen
May have positive Coombs test
179
IMHA is most commonly __ in dogs and __ in cats
Idiopathic in dogs
Secondary to FeLV in cats
180
What cancers are most frequently associated with IMHA
Lymphomas and leukemias
181
Non-immune mediated hemolytic anemia can arise secondary to what
Microangiopathy
Tumor cell erythrophagocytosis
Oxidative damage to erythrocytes
182
Microangiopathic hemolytic anemia (MAHA) is caused by
Endothelial cell injury and fibrin deposition
Most commonly seen in patients with DIC, and by inherent abnormalities in tumor vasculature (think HSA)
183
Clinically significant tumor cell erythrophagocytosis is seen most commonly with
Histiocytic sarcoma especially the hemophagocytic variant
184
Clinicopathologic abnormalities of non-immune mediated hemolytic anemia
Markedly regenerative anemia
Negative direct agglutination test
Thrombocytopenia
Hypoalbuminemia
Hypocholesterolemia
185
CBC findings with anemia of inflammatory disease/anemia of chronic disease
Mild to moderate nonregenerative normocytic, normochromic anemia
186
What inflammatory cytokines reduce production of endogenous erythropoietin in the face of hypothermia and suppress the erythroid progenitor response to erythropoietin
TNF-alpha
IFN-gamma
IL-1
IL-6
IL-10
187
__ increases production of hepcidin by the liver
IL-6
End result is sequestration of iron resulting in hypoferremia and decreased availability of iron for erythropoiesis
188
__ is an acute phase protein that causes increased cellular internalization and degradation of ferroportin
Hepcidin
189
__ is a membrane bound protein that exports iron from macrophages, hepatocytes, and duodenal enterocytes into peripheral blood
Ferroportin
190
Paraneoplastic erythrocytosis has been reported in dogs with what tumor types
Various renal tumors
Nasal fibrosarcoma
Cecal leiomyosarcoma
Spinal cord schwannoma
191
Paraneoplastic erythrocytosis is associated with increased serum
EPO
192
What causes increased EPO in paraneoplastic erythrocytosis
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
Primary absolute erythrocytosis is
Polycythemia Vera
194
Causes of secondary absolute erythrocytosis
Chronic respiratory disease
Heart disease causing L to R shunting
Nonneoplastic renal disease
195
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
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
Eosinophilia is uncommon in dogs and cats but is seen most commonly with what tumor types
MCT
Lymphoma (especially T cell)
197
Mast cells produce what eosinophilic cytokine
IL-5
(Human T cell lymphomas have been documented to produce this too)
198
Cancer-associated immune mediated thrombocytopenia is most commonly associated with what tumor types
Lymphoma
Multiple myeloma
Histiocytic sarcoma
199
The most common clotting factor dysfunction seen in veterinary cancer patients results from the release of __ by MCT
Heparin
200
Heparin acts as a cofactor for what coagulation protein
Antithrombin III
Antithrombin III inactivates clotting factors XII, XI, X, IX
201
Hyper or hypocoagulability is more common in cancer patients
Hypercoagulability
202
In some studies, TEG documented hypercoagulability in __% of dogs with lymphoma and __% of dogs with various other cancers
56% of dogs with lymphoma
50% of dogs with various other cancers
203
What tumor types have the most common incidence of DIC
HSA
Mammary adenocarcinoma (especially inflammatory form)
Pulmonary adenocarcinoma
204
__, expressed on monocytes and endothelial cells dur-
ing inflammation and on some cancer cells, complexes with factor
VIIa to activate the extrinsic clotting cascade
Tissue factor
205
__ is a paraneoplastic syndrome characterized by multiple slowly growing cutaneous collagenous nodules in association with bilateral renal cystadenocarcinomas or cystadenomas
Nodular fibrosis
206
What breed of dog is most commonly (almost always) reported in cases of nodular dermatofibrosis
GSDs
Pedigree analysis strongly indicates autosomal dominant inheritance
207
The nodular dermatofibrosis-associated mutation was mapped to the __ gene on chromosome __ that encodes __
BHD gene on chromosome 5 that encodes folliculin
208
The BHD gene is the causative gene for what human renal cancer syndrome that is similar to renal cystadenocarcinoma/nodular dermatofibrosis in dogs
Birt-Hogg-Dube syndrome
209
Female dogs affected with nodular dermatofibrosis almost always have what concurrent tumor
Uterine leiomyomas
210
Superficial necrolytic dermatitis is seen most commonly in dogs with
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
Major dermatological findings of superficial necrolytic dermatitis
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
Feline paraneoplastic alopecia has been reported in cats with what tumor types
Pancreatic carcinoma
Biliary carcinoma
213
Paraneoplastic exfoliative dermatitis has been reported in cats with what tumor type
Thymomas
214
Paraneoplastic myasthenia gravis is reported most commonly in dogs and cats with what tumor type
Thymoma
215
T/F: in recent studies both myasthenia gravis and megaesophagus affected prognosis in dogs and cats with thymoma
FALSE: neither affected prognosis
216
What tumor types were associated with paraneoplastic neuropathies in one study
Bronchogenic carcinoma
Mammary adenocarcinoma
Melanoma
Insulinoma
Osteosarcoma
217
__ is a generalized osteoproductive disorder of periosteum that affects the long bones of the extremities, typically beginning on the digits and then progressing proximally
Hypertrophic osteopathy
218
Paraneoplastic hypertrophic osteopathy is most commonly associated with what tumor types
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
What nonneoplastic diseases have been associated with HO
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
Radiographic findings of HO
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
Fever is mediated primarily by what things
TNF-alpha
IL-1
IL-6
Hypothalamus
222
Cytokines that mediate fever (TNF-alpha, IL-1, IL-6) activate the __ cascade, producing __ which acts on the thermoregulatory center of the hypothalamus
Activate the arachidonic acid cascade producing prostaglandin E2
223
CT can detect pulmonary nodules as small as __mm in diameter whereas radiographs are limited to those at least __mm in diameter
CT: 1mm
X-ray: 7-9mm
224
Pure ground-glass lesions __mm have a high probability of malignancy, whereas those __ are considered benign
>8mm have high probability of malignancy
<4mm are considered benign
225
Fluid is brighter on what sequence MRI
T2
226
What hepatocyte specific MR contrast agent can potentially allow for differentiation between benign and malignant liver nodules
Gadoxetate disodium (Gd-EOB-DTPA)
227
T/F: Scintigraphy can detect between benign inflammatory lesions and malignant lesions
FALSE - lacks specificity, cannot do this
228
What compound is used in thyroid scintigraphy
99m-technetium pertechnetate (99mTcO4− There is a superscript negative sign beside the O and over the 4.)
229
What is the most commonly used radiopharmaceutical for PET imaging
2-deoxy-2-18F-fluorodeoxy-glucose (FDG) bound to the positron emitter fluorine-18 (F-18)
230
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
True
231
PET agents other than FDG and their mechanism
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
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.
>2.5
No specific cut-offs established in vet med
233
F-18 FDG was shown to correlate with grade of what tumor in a study of a small group of dogs
MCTs
234
Special cytochemical stains for cytoplasmic/nuclear structures
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
Immunocytochemical staining - Common antibodies used in veterinary oncology
CD3 (T cells)
CD79a and CD20 (B cells)
cytokeratin (epithelial cells)
vimentin (mesenchymal cells)
Melan A (melanocytes)
236
Cellular and cytoplasmic criteria of malignancy
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
Nuclear criteria of malignancy
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
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.
CCND1
239
Canine mast cell tumors typically have internal tandem duplications of what exons
8 and 11
240
What percentage of canine mass cell tumors have a duplication in either exon 8 or exon 11
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
What percentage of canine TCC have a single nucleotide change in the BRAF gene
80%
V595E mutation
This is the V600E mutation in people present in a variety of cancers, particularly melanoma
242
droplet digital PCR (ddPCR). ddPCR can detect the V595E mutation when it is present in
as little as __% of the DNA
.01%
243
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
42% (8 dogs)
244
In a recent study, indirect lymphography was successful at identifying the sentinel lymph node in __% of veterinary patients with solid tumors of various histologies.
96.6%
245
What chemo drugs are typically used in electrochemotherapy
Bleomycin
Cisplatin
246
ratio between the toxic dose and the therapeutic dose for that drug
Therapeutic index
247
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
Maximum tolerated dose
248
measured response at a putative target or surrogate that is related
to the mechanism of action of the agent
Biologically effective dose
249
measure of dose
per unit of time; allows comparisons between protracted
and compacted dosing schedules
Dose intensity
250
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
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
used most commonly with hematopoietic cancers
the reintensification of therapy after remission is
attained to further reduce the likelihood of relapse.
Consolidation therapy
252
also used after remission is attained but involves low-
intensity therapy given over a protracted period of time
Maintenance therapy
253
enhancement of cytotoxicity when irradiation and chemotherapeutic agents are combined such that a therapeutic gain
is obtained
Radiosensitization
254
basis for chemotherapeutic exposure leading to
enhanced radiosensitivity can be multifaceted and involve
(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
Chemosensitivity depends on a number of factors, including
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
__ 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
Melphalan
257
__ levels can play a role in the sen-
sitivity of tumor cells to doxorubicin (DOX)
topoisomerase IIα
258
increased levels of __ correlate with a decrease in sensitivity to 5-FU
thymidylate synthetase
259
Induction of __ has been shown to be a mechanism by which tumor
cells can acquire resistance to nitrogen mustards.
glutathione-S-transferases
260
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
dihydropyrimidine dehydrogenase
261
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 __
deoxycytidine kinase
262
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
FALSE: does NOT
263
T/F: Alcohol will deactivate chemotherapy drugs
FALSE - Alcohol will not deactivate chemotherapy drugs and can spread contamination.
264
BSA formula
m2 = [A x (weight in grams)^2/3] / 10,000
A for dogs = 10.1
A for cats = 10.0
265
What excipient (drug carrier) in earlier paclitaxel formulations was the cause of hypersensitivity reactions in dogs
Cremaphor-EL
Newer formulations use water-soluble micellar formulations of paclitaxel but are not yet commercially available
266
MOA of alylators
Covalent binding of alkyl groups to DNA to form monofunctional or bifunctional adducts that generate inter- or intrastrand cross-links
267
Classes of alylators
Nitrogen mustards (mustargen, melphalan, cyclophosphamide, ifosfamide, chlorambucil)
Nitrosureas (CCNU, streptozotocin)
Others - dacarbazine and procarbazine
268
MOA of antitumor antibiotics
Diverse - specific to each drug in the class
269
Drugs classified as antitumor antibiotics
Doxorubicin
Mitoxantrone
Actinomycin D (Dactinomycin)
270
MOA of antimetabolites
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
Drugs classified as antimetabolites
Cytosine arabinoside (cytarabine, Ara-C)
Methotrexate
Gemcitabine 5-FU
Rabacfosadine (Tanovea)
272
MOA of antimicrotubule agents
Interference with the polymerization or depolymerization of the microtubule
273
Classes of antimicrotubule agents
Taxanes - paclitaxel, docetaxel
Vinca alkaloids - vinblastine, vincristine, vindesine, vinorelbine
274
MOA of topoisomerase inhibitors
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
Classes of topoisomerase II inhibitors
Anthracyclines
Epipodophyllotoxins - etoposide, teniposide
276
Major class of topoisomerase I inhibitors
Camptothecins - little to no use in vet med, more common in people
277
MOA of platinum agents
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
Major intrastrand adducts of platinum agents
N7-d(GpG)
N7-d(ApG)
279
MOA of hydroxyurea
Inhibitor of ribonucleotide reductive —> results in depletion of deoxyribonucleotide pools
280
MOA of L-asparaginase
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
Mechlorethamine undergoes spontaneous hydrolysis to __ and __, yielding nucleophilic reactive centers capable of forming DNA cross-links
2-hydroxyethyl-2-chloroethylmethylamine and bis-2-hydroxyethylmethylamine
282
What are the dose limiting toxicities of mechlorethamine-containing protocols
GI toxicity
Bone marrow toxicity
283
Mechlorethamine is a strong vesicant - how should extravasation be treated?
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
Uptake of melphalan into tumor cells by anime acid transporters can be blocked by what amino acid
Leucine
285
T/F: Melphalan requires activation prior to exerting alkylating activity
FALSE - has direct alkylating activity, doesn’t require metabolic activation
286
What is the oral bioavailability of melphalan
30%
287
T/F: Cyclophosphamide and ifosfamide are prodrugs that require metabolic activation by
microsomal mixed function oxidases
TRUE
288
How is cyclophosphamide activated
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
Most active CP metabolite; it is capable of bifunctional alkylation and cross-linking
Phosphoramide mustard
290
DLT of cyclophosphamide
Neutropenia
291
T/F: incidence of sterile hemorrhagic cystitis is higher with chronic oral dosing, and a cumulative dose is a risk factor.
True
292
Substitute for patients that get sterile hemorrhagic cystitis
Chlorambucil
293
Treatment for sterile hemorrhagic cystitis
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
__ accounts for up to 25% of the metabolism of ifosfamide
dechloroethylation
295
neurotoxic metabolite that develops after ifosfamide dosing
chloracetaldehyde
296
DLT for ifosfamide
Dose related myelosuppression
nephrotoxicity and damage
to the bladder epithelium are not uncommon
297
__, a urinary
epithelial protectant, must be administered with ifosfamide to avoid severe cystitis
Also given in people who get high dose cytoxan
sodium 2-mercaptoethane sulfonate
Aka mesna
298
primary metabolite of chlorambucil that is presumably responsible for much of the clinical activity
phenylacetic acid
299
DLT of chlorambucil
Myelosuppression
300
CCNU can cross the blood brain barrier because it is highly
Lipophilic
301
Metabolism of CCNU
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
DLT for CCNU
myelosuppression with acute neutropenia followed by cumulative and potentially irreversible thrombocytopenia
303
For cats that receive CCNU, when does the neutrophil nadir occur
anywhere from 1 to 4 weeks post-
treatment
304
MOA of denamarin
Increases glutathione levels and acts as an antioxidant
305
What side effect of CCNU has been rarely reported in cats
Pulmonary fibrosis
306
Cat dose of CCNU
40-60mg/m2
Dogs 70-90mg/m2
307
Cellular uptake of streptozotocin is dependent on the __ transporter and
GLUT2
expression of this transporter determines sensitivity of both
insulinoma and pancreatic beta cells
308
T/F: Streptozotocin can induce diabetes in animals
True
309
Dacarbazine is a prodrug that requires metabolic activation by the ___ system
Hepatic cytochrome P450 system
310
Activation of dacarbazine results in what
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
Use of dacarbazine is not recommended in cats because
Lack of info regarding ability to convert it to the active form
312
DLT of dacarbazine
GI toxicity
Severe myelosuppression can be observed
313
T/F: Procarbazine is a prodrug
True - requires activation to active metabolites
314
Route of administration for procarbazine
Oral
IV has been tested in people but caused neurotoxicity
315
MOAs of doxorubicin
- 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
Elimination of doxorubicin occurs through
Renal and biliary elimination
Also is metabolized to doxorubicinol and the 7-hydroxy a glycine
317
Rapid administration of doxorubicin can cause
Anaphylactoid-like reactions
Administer over 15-30mins to avoid this
318
Doxorubicin is a VESICANT/IRRITANT; in the event of extravasation, __ should be applied
Vesicant
Cold compress
319
__ 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
Dexrazoxane (Zinecard)
10mg per 1mg of doxorubicin given
Given in different vein from site of extravasation
320
Acute DLTs with doxorubicin
Myelosuppression and GI toxicity
321
Acute cardiotoxicity from doxorubicin manifests as
Transient arrhythmias associated with transient increases in circulating histamine and catecholamines
ACUTE is usually of little clinical significance
322
Cytosine arabinoside is phosphorylated in cells to generate __ which acts as a competitive inhibitor of __
Arabinosylcytosine triphosphate (ara-CTP)
DNA polymerase alpha
323
MOA of cytarabine
Ara-CTP is incorporated into DNA and cannot be excised —> inhibitors both the function of the DNA template and subsequent synthesis
324
primary targets of toceranib
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)
