Oncology Flashcards

Question

What are tumour supressor genes?

Answer 1

Antigrowth genes -> keep cells in a senecent state Loss/inactivation of TSGs can result in cellular transformation and give rise to cancer

Answer 2

Retinoblastoma susceptibility (RB1), p53 (TP53) and PTEN genes Mutations are dominant recessive

Answer 3

– Genetic mechanisms * Loss of heterozygosity * Deletion * Point mutations – Epigenetic mechanisms (Gene silencing) * Promoter methylation

Answer 4

PI3K/AKT pathway activation due to PTEN deletion; - In dogs, this occurs through HOMOZYGOUS DELETION (both copies of the PTEN gene) about 30-40% of the time - In humans, this occurs through METHYLATION of a CpG island required for the induction of PTEN more than 80% of the time

Answer 5

Loss of TSGs seems to occur more frequently than activation of proto-oncogenes

Answer 6

Normal - clear division of arterioles -> capilallaries -> venuoles - Regular shapes - organised Abnormal * Tortuous * Irregularly shaped * Unstable and leaky * Disorganized

Answer 7

*Inhibition of angiogenesis alone does not have a substantive impact to prevent, delay, or reverse tumor progression * Inhibition of angiogenesis can result in blood vessel normalization, or restoration of the normal phenotype of blood vessel cells and patterns of circulation

Answer 8

* Maintain a suitable oxygen environment and provide access to nutrients * Evade apoptosis, necrosis, necroptosis, ferroptosis, and autophagy * Microvessel density often shows a positive correlation with biological behavior

Answer 9

Blood vessel normalization can improve systemic drug delivery * The only drug approved for companion animals that has a potential (small) antiangiogenic effect is toceranib

Answer 10

Not a direct extension of the primary tumor (distinct from invasion)

Answer 11

* Detach from primary mass (motility) * Invade basement membrane (MMPs) * Intravasation * Survive in circulation (avoid anoikis, evade immune surveillance, resist physical stress) * Arrest in circulation (marginate and adhere to vessel or lodge in capillary bed) * Extravasation * Invade basement membrane (MMPs) * Create new tumor mass (survive, proliferate, grow, promote angiogenesis) * Repeat (metastasis form metastasis)

Answer 12

*Direct seeding of body cavities and surfaces * Lymphatic spread * Hematogenous spread * bronchogenic

Answer 13

* Occurs whenever malignant neoplasm penetrates into the body cavity * Peritoneal cavity is most commonly involved * Other cavities: – Pleural, pericardial – Subarachnoid, joint spaces * It is a characteristic of carcinomas resulting in a condition called “carcinomatosis” – Pancreatic exocrine adenocarcinoma – Ovarian carcinoma

Answer 14

Seeding of carcinomas into a body cavity or surface – Pancreatic exocrine adenocarcinoma – Ovarian carcinoma

Answer 15

lymphatics

Answer 16

* Direct blood vessel invasion * Indirect route via lymphatic system * Carcinomas and sarcomas * Lung – 1st capillary bed after vena cava * Liver – 1st capillary bed after portal vein * Arterial metastasis occurs less frequently in the liver because of their thick muscular walls * Bone metastases

Answer 17

It is the reliance of cancer cells on aerobic glycolysis. Normal cells rely on mitochondrial oxidative phosphorylation to generate energy (ATP) - it is unclear why cancer uses this ineficient aerobic gycolisis pathway

Answer 18

Response to therapy is predicted by the ability to disrupt glucose metabolism as measured by FDG-PET -> ie Anticancer therapies decrease the glucose metabolism by tumours

Answer 19

* Tumors disable DNA replication and mitosis checkpoints * Rapid cell division prevents efficient and appropriate repair of DNA damage or replication-induced mutations * DNA damage repair machinery is in hyperdrive, creating poorly repaired and chaotic genomes * Instability begets instability

Answer 20

No, multiple are needed

Answer 21

* Initial spectrum of mutations determines biological behavior * Later mutations do not provide an advantage to gain a foothold in the presence of a highly heterogeneous cell population

Answer 22

in vitro suggests 2. Usually, 5-10 are needed to estimate cancer traits

Answer 23

Dogs spayed before their first estrous cycle have a greatly reduced risk of developing breast cancer, with the risk rising to 26% for dogs that are spayed after their second estrus

Answer 24

Mammary tumors pri- marily affect late middle-aged (9 to 11 years) female intact dogs, with an increased incidence beginning at approximately 6 years of age.6

Answer 25

Sexual steroid hormones likely have their primary effect on target cells during the very early stages of mammary carcinogenesis in dogs; thus, the protective effect of spaying is lost with time. In addition to the influence of ovarian hormones on breast cancer development, the use of medroxyprogesterone acetate (progestin and estrogen combination) products to prevent estrus or to treat pseudopregnancy has been linked to an increased incidence of mammary tumor development in dogs

Answer 26

No, prostatic hyperplasia is, and in man prostatic neoplasia is. To the contrary, neutered dogs have been shown to be at increased risk. Castration is likely not an initiating event, but is thought to favor tumor progression.

Answer 27

Squamous; grade 1->3. features of improtance are Overall differentiation, mitotic index, nuclear pleomorphism, invasion, stromal reaction Hemangiosarcoma; grade 1->3. Overall differentiation, nuclear pleomorphism, mitotic index, necrosis Soft tissue sarcoma (dog); grade 1, 2, 3 or mitotic index >9,* mitotic index <9*. Overall differentiation, mitotic index, necrosis

Answer 28

Obesity, high dietary fat intake, late age at spay, and some breeds (e.g., English Springer spaniel, Pointer, Poodle, Boston terrier, Dachshund, German shepherd, Chihuahua)

Answer 29

High weight, high height, early castration/spay, some breeds (e.g., Irish wolfhound, Saint Bernard, Great Dane, Rottweiler, Irish setter, Doberman Pinscher, golden retriever, Labrador retriever, Leonberger)

Answer 30

Being neutered, exposure to phenoxy-acid containing herbicides, frequent flea dipping, some breeds (e.g., Scottish terrier, Beagle, Shetland sheepdog, Wirehaired fox terrier, West Highland white terrier)

Answer 31

Some breeds (e.g., Boxer, Rhodesian ridgeback, Vizsla, Boston terrier, Weimaraner, Chinese Shar-Pei, Bullmastiff, Dutch pug, Labrador retriever, American Staffordshire terrier, golden retriever, English setter, English pointer)

Answer 32

ETS, exposure to chemicals containing 2,4-dichlorophenoxyacetic acid, some breeds (e.g., Bullmastiff, Boxer, Scottish terrier, Gordon setter, Irish wolfhound, Basset hound, golden retriever)

Answer 33

FeLV, FIV, environmental tobacco smoke

Answer 34

Vaccine injection

Answer 35

Solar irradiation

Answer 36

Paraneoplastic syndromes (PNSs) are neoplasm-associated alter- ations in bodily structure and/or function that occur distant to the tumor.

Answer 37

The weight loss and metabolic alterations observed in cancer patients despite adequate nutritional intake are termed cancer cachexia, whereas alterations observed as the result of poor nutritional intake are termed cancer anorexia.

Answer 38

approximately 20% of cancer deaths patients with cancer cachexia can have significantly reduced survival times, and many patients are unable to undergo appropriate therapy because of their poor clinical status.

Answer 39

A plasmid-DNA–mediated approach utilizing growth hormone–releasing hormone (GHRH) in dogs appears to increase insulin-like growth factor-1 (IGF-1) levels (a measure of GHRH activity) and may represent a mecha- nism for attenuating cancer cachexia

Answer 40

impaired synthesis and/or increased loss into the GI tract or urine - PLE is thought to result from an increase in mucosal serum protein per- meability because of mucosal erosion, ulceration, or lymphatic obstruction.

Answer 41

The treatment for PLE consists of treating the primary malignancy; however, those patients with a lymphangiectasia-related PLE may also be treated with medium-chain triglycerides that do not undergo trans- port by intestinal lymphatics. 83

Answer 42

gastroduodenal ulceration is mast cell tumor (MCT). excess histamine seen in MCTs stimulates gastric H2 receptors, leading to increased gastric acid secretion. Clinical manifestations of mucosal damage and/or ulceration with gastric vessel thrombosis occur in association with gastric hyperacidity. Plasma histamine concentrations are elevated in approximately 75% of dogs with macroscopic MCT, although only 30% have GI signs

Answer 43

Gastroduodenal ulceration in mast cell tuomorst due to histamine stimulating H2 cells to produce acid. Symptomatic therapies such as proton- pump inhibitors, H2 blockers, misoprostol, sucralfate, and rehydra- tion may be helpful in combating PNS-associated gastroduodenal ulceration.

Answer 44

gastrinoma (gastrin-secreting non–islet cell pancreatic tumor).

Answer 45

Most common are; Lymphoma (10-35%) Anal sac apocrine gland adenocarcinoma (25%) Multiple myeloma (20% Parathyroid tumors Renal angiomyxoma Mammary tumors Thymoma

Answer 46

two-thirds of dogs and one-third of cats with hypercalcemia.

Answer 47

Lymphoma is the most common cause of HM (10% to 35% occurrence)

Answer 48

The causes of HM are varied and include; - ectopic production of parathormone (PTH) - PTH-related peptide (PTH-rp) by the tumor - extensive and usually multifocal lyticbone metastases, - primary hyperparathyroidism, - tumor-associated prostaglandins (PGE1/2), - interleukin-1-β (IL-1β, previously known as osteoclast-activating factor [OAF]), - transforming growth factor-β (TGF-β), and receptor activator of nuclear factor kappa-B ligand (RANKL).

Answer 49

TGF-β1 regulates the mRNA stability of PTH-rp. HM seen in lymphoma and anal sac apocrine gland adenocarcinoma is commonly caused by tumor- associated PTH-rp.

Answer 50

16-kDa protein with significant sequence identity to PTH, suggesting it may act and function like PTH. This is upregulated by TGF-ß1 which is commonly secreted in lymphoma and AGASACA

Answer 51

hypercalcemia differential diagno- ses include “lab error” (lipemia and hemolysis), acute renal failure, hypervitaminosis D, hypoadrenocorticism, and granulomatous disease.

Answer 52

Ionized calcium. Otherwise interpret the calcium value in relation to the level of serum albumin if ionized calcium determination is not available. Adjustedcalcium(mg/dL)= [Calcium (mg / dL) − albumin (g / dL)] + 3.5

Answer 53

Acidotic HM patients may have an increase in clinical signs of hypercalcemia when compared to nonacidotic HM patients.

Answer 54

calcium > 18 mg/dL

Answer 55

primary clinical manifestations of HM are due to renal function impairment. An inability to concentrate urine is the initial manifestation of hypercalcemia and is due to decreased responsiveness to antidiuretic hormone (ADH) at the distal tubule; the calcium then decreases renal blood flow and glomerular filtra- tion rate (GFR) as the result of severe vasoconstriction. Calcium salt deposition in the renal parenchyma may also contribute to renal azotemia, although this is uncommon. The urinary epithe- lium may then undergo degeneration, and in severe cases, necrosis results in exposure of the basement membrane of the renal tubule. The situation worsens as the patient becomes polyuric and polydip- sic, resulting in progressive dehydration. I

Answer 56

Renal function impairment constipation, hypertension, twitching, weakness, shaking, depression, vomiting, bradycardia, stupor, and possibly coma and/or death.

Answer 57

Find the cause (stage for lymphoma, rectal for agasaca ) and see table

Answer 58

Typically have low PTH and high PTH-rp concentrations; however, the cause of the HM can usually be delineated with appropriate diagnostics before the return of PTH/PTH-rp assay results, and such tests may not be routinely needed.

Answer 59

The premature administration of symptomatic therapy that includes the use of corticosteroids can mask the neoplasia. f lymphoma is the under- lying cause of the HM, the use of corticosteroids may interfere with the ability to confirm a diagnosis, necessitating either additional diagnostics and/or waiting to determine if the lymphoma reappears after glucocorticoid withdrawal. In addition, glucocorticoids may induce resistance to other chemotherapy agents with a decrease in the ability to induce a complete remission, as well as a decrease in the length of survival.

Answer 60

management of existing dehydration and to expand the extracellular fluid volume, increase GFR, increase calciuresis and natriure- sis, and decrease calcium reabsorption by the kidneys. Once rehydrated, the loop diuretic furosemide with continued normosa- line diuresis can be utilized to potently inhibit calcium reabsorption in the ascending loop of Henle

Answer 61

they inhibit PGE, OAF (IL-1β), vitamin D, and intestinal calcium absorption. We should try and reach a diagnosis first, as they can mask lymphoma and provide chemotherapy resistance

Answer 62

insulinoma Nonislet cell tumors can also serve as sources of ectopic hormone production with resultant hypoglycemia in dogs and humans. Nonislet cell tumors with PNS hypoglycemia have been most commonly associated with hepatocellular carcinomas; however, lymphoma, hemangiosarcoma, oral melanoma, hepatoma, plasma cell tumor, multiple myeloma, smooth muscle tumors (leio- myoma and leiomyosarcoma), mammary tumors, renal tumors, and salivary gland tumors have also been reported.

Answer 63

The hypoglyce- mia of extrapancreatic tumors has interestingly been associated with low insulin levels, whereas pancreatic beta-islet cell tumors . Nonislet cell tumors may induce hypoglycemia by increased tumor utilization of glucose, decreased hepatic glycogenolysis or gluconeo- genesis, or the secretion of insulin or IGF-1 and IGF-2. Additional mechanisms include upregulation of insulin receptors, increased insulin binding by M proteins in myeloma, and increased produc- tion of somatomedins.

Answer 64

insulinoma, nonislet cell tumor hyperinsulinism, nonislet cell tumor, hypoadrenocorticism, starvation, sepsis, liver dysfunction, toxin, and laboratory error (lack of timely serum separation).

Answer 65

Tumors associated with extrapancreatic hypoglycemia are often extremely large, and therefore, radiographs/ultrasound of the abdomen and/or thorax may be helpful. Provocative testing via glucagon or glucose tolerance testing may be useful in cases when the diagnosis is uncertain.

Answer 66

reported to occur in primary lung tumors and a single case of an abdominal neuroendocrine tumor.

Answer 67

CTH, ACTH pre- cursors, endorphins, enkephalins, and melanocyte-stimulating hormone (MSH). All result in excessive production of steroids from the adrenal glands resulting in clinical signs similar to those seen in hyperadrenocorticism (Cushing’s disease).

Answer 68

The predominant active molecules in this PNS are ACTH, while Invariably, these tumors are dexamethasone insuppressible. The diagnosis of this PNS is made by the concomitant presentation of Cushing’s-like signs with an abnormal dexamethasone suppression test and a localizable tumor.

Answer 69

treatment of choice is removal of the underlying cause by surgical extirpation of the tumor. When necessary, the medical therapy for this PNS centers on inhibiting cortisol production by mitotane or ketoconazole.

Answer 70

Monoclonal gammopathies - same thing

Answer 71

excessive production of proteins from a monoclonal line of immunoglobulin (Ig)-producing plasma cells or lymphocytes. When production of these Igs, partial Igs, heavy chains, and/or light chains becomes extreme, clinical signs of hyperviscosity (ataxia, depression, demen- tia, cardiac disease and/or failure, seizures, and coma), tissue hypoxia, bleeding (poor platelet aggregation, platelet coating with Igs, and release of platelet factor III), and/or ocular disorders (e.g., papilledema, retinal hemorrhage, detachment) may occur.

Answer 72

These proteins may be identified by performing a protein electrophoresis on the serum and/or urine ( light chain production may be detected in the urine as Bence-Jones proteins)

Answer 73

Plasma cell tumours - e.g. multiple myeloma

Answer 74

plasma cell tumours (number 1) , lymphomas, lymphocytic leukemias, and primary macroglobulinemia can also cause this PNS.

Answer 75

vast majority are due to either anemia of chronic disease (ACD), immune-mediated hemolytic anemia (IMHA), blood loss anemia, or microangiopathic hemolytic anemia (MAHA).

Answer 76

This anemia is due to disordered iron storage and metabolism, shortened red blood cell (RBC) lifespan, and occasionally decreased bone marrow response.

Answer 77

ACD is normocytic/normochromic, and evaluation of the bone marrow does not suggest significant problems with cellularity.

Answer 78

The diagnosis of PNS IMHA is typically established by a Coombs’ slide agglutination test, and many patients will have con- current spherocytosis and a regenerative anemia.

Answer 79

The treatment of choice is removal of the tumor; however, if this is not immediately possible, the use of immunosuppressive dosages of prednisone (1 to 2 mg/kg daily to two times a day by mouth [BID PO]) may be indicated if a diagnosis has been established. Similar to non-PNS IMHA, the use of additional agents such as azathioprine (1 to 2 mg/ kg daily for 4 to 7 days, then 0.5 to 1 mg/kg every 48 hrs PO), cyclosporine, cyclophosphamide, and others may be necessary for complicated IMHA cases

Answer 80

decreased hemoglobin content, the RBCs in blood loss anemia are microcytic/hypochromic. In addition, decreased serum iron, increased total iron-binding capacity, and poikilocytosis may also be noted.

Answer 81

The treatment of choice is removal of the tumor, although severe anemia may necessitate blood transfusions. The use of oral and/or injectable iron may be a useful adjunct therapy.

Answer 82

Microangiopathic Hemolytic Anemia (MAHA) is a secondary phenomenon to hemolysis and is typically due to fibrin deposition and/or endothelial damage. The most common causes of MAHA are PNS disseminated intravascular coagulation (DIC) and RBC shearing as the result of hemangiosarcoma

Answer 83

Schistocytosis and hemolysis are common indicators of ongoing MAHA.

Answer 84

While any tumor can cause DIC and subsequent MAHA, hemangiosarcoma is the most common.

Answer 85

It is common in humans, but not in veterinary medicine. The degree of anemia seen in veterinary cancer patients undergoing chemotherapy is generally mild, with typical packed cell volumes hovering in the 28% to 32% range for dogs and 24% to 28% range for cats.

Answer 86

Erythrocytosis (polycythemia) is a relatively uncommon PNS. Tumors that have been associated with PNS erythrocytosis include renal tumors (primary and secondary), lymphoma (including renal origin), lung or liver tumors, cecal leiomyosarcoma, nasal fibrosarcoma, and transmissible venereal tumor (TVT)

Answer 87

Taxanes and Vincas

Answer 88

Antimetabolites

Answer 89

S stage and G0

Answer 90

platinum analogues, alkalating agents

Answer 91

use of chemo to increase sensitivity of a cell to radiation

Answer 92

Consolidation therapy -> re-intensification of therapy after remission is attained to further reduce the likelihood of relapse -> Used most commonly with hematopoietic cancers Maintenance therapy -> also used after remission is attained but involves low-intensity therapy given over a protracted period of time

Answer 93

decrease in tumour volume >50% or tumour diameter by >30%

Answer 94

No change in size - e.g. <30% volume reduction or <20% increase in tumour diameter

Answer 95

increase in tumour volume >25% or increase in tumour maximum diameter >25%

Answer 96

the median value for a group of individuals treated with a given therapy in terms of the length of time they achieve a completer or partial remission (MRD) or length of survival after implementation of therapy (MST)

Answer 97

PFI; the amount of time elapsed without evidence of progressive tumour growth PFS; survival without progressive growth of the tumour from treatment start

Answer 98

DFI; the amount of time elapsed without disease recurrence DFS; the amount of time or survival of the patient after therapy

Answer 99

no - early on tumours grow exponentially (this is the most effective time to give chemo as they are rapidly dividing)

Answer 100

-> Large growth fraction early = more sensitive to chemotherapy -> Once tumor is detectable = fewer cells dividing

Answer 101

Large tumor = high interstitial pressure & less chemotherapy penetration

Answer 102

Tumors are clinically detectable after 30 doublings -> 1 billion (1 x 10 9) tumor cells -> 1 gram / 1 cm3 Once the tumor has reached 1 million cells, it is likely that chemotherapy resistant cells have developed due to mutations Therefore single agent chemotherapy is rarely curative

Answer 103

Maximum Tolerated Dose Optimized tumor cell kill which requires a break period to allow recovery of normal cell populations

Answer 104

ASAP - if surgery performed at 10-14 days (suture removal)

Answer 105

10-14 days. Chemo is often cytotoxic to rapidly dividing cells. If given while the incision is healing this will inadvertently kill the cells trying to close the wound

Answer 106

because there are often mutations confering resistance to one agent. Drugs with different mechanisms of action -> avoids cross resistance Non-overlapping toxicities Differing cell cycle specificities Have to use drugs that would be effective as single agents though

Answer 107

can only act on cells in specific phase of cell cycle - Antimetabolites (hydroxyurea) - Antimicrotubule agents (vinca alkaloids & taxanes)

Answer 108

active throughout all phases - Alkylating agents (cyclophosphamide) - Antitumor antibiotics (doxorubicin) - Platinum agents (carboplatin)

Answer 109

Vincristine-> inhibition of microtuble agregation of alpha and beta tubulin -> cell cycle arrest as chromosomes cannot separate paclitaxel-> inhibition of microtubule disaggregation -> orevent breakdown of tubules post chromosomal division ->cell cycle arrest and apoptosis

Answer 110

Oxaliplatin, cisplatin, vincristine and paclitaxel -> alter the function of the ETC increasing ROS and resulting in cell death Oxaciplatin and cisplation; inhibit mDNA replication and transcription All of these alter mitochondrial function and lead to apoptosis

Answer 111

L-asparaginase

Answer 112

it is not, it is resistant

Answer 113

-Increased drug efflux (increased MDR expression, P-glycoprotein pump) - Reduced uptake (drugs that require active transport) - Decreased activation of drug - Increased drug catabolism - Increased de-activation (e.g. glutathione binding) - Increased or decreased target expression - Increased DNA repair - Evasion of apoptosis

Answer 114

altered topoisomerase II structure

Answer 115

decreased expression of folate transporter prevents drug uptake, or amplified DHFR or TS, or decreased folypolyglutamul synthase

Answer 116

p53 mutations, bcl2 activation or oversupression

Answer 117

Increased MDR expression by MDR gene amplification. Affects doxorubicin, etoposide, vinca alkaloids, pacitaxel, topotecan

Answer 118

decrease dose in proportion to the reduction in creatinine clearance below 60 mL/min Affects renally excreted drugs; - bleomycin, - carbo and cisplatin - etoposide - fludarabine - hydroxyurea - methotrexate - pentostatin - topotecan

Answer 119

Dose reduction of anticancer drugs that require hepatic metabolism cyp450. This is mased on; 1.5-3.0 mg/100 mL -> 50% dose reduction >3.0 - > 75% dose reduction - Bunsulfan - cyclophosphamide - ifosfamide - imatinib - paclitaxel - thiotepa - vinca alkaloids

Answer 120

doxorubicin ifinotecan vinca alkaloids

Answer 121

- bleomycin, - carbo and cisplatin - etoposide - fludarabine - hydroxyurea - methotrexate - pentostatin - topotecan

Answer 122

Overall ~20-30% of canine / feline patients experience some toxicity -> most are mild, self-limiting, or non-clinical ≤ 5% are severe, often needing hospitalization -> reduce dose, eliminate drug, stop chemo ≤ 1% are life-threatening

Answer 123

Toxicity is patient, drug, and dose dependent

Answer 124

All rapidly dividing cells - Tumor cells - Bone marrow stems cells - GI crypt stem cells - Growing hair follicle cells

Answer 125

Bone marrow toxicity Alopetia Gastrointestinal toxicity

Answer 126

Breeds with continually growing hair coats -> Poodles, Schnauzers, Bichons, Afghans, Old English Sheepdogs

Answer 127

Chemo affects dividing cells = immature or early precursor cells.

Answer 128

Becomes evident in peripheral blood depending on lifespan of cell -> earliest affected are those being replaced first WBC t1⁄2 = hours (12-24 hrs) Platelet t1⁄2 = days (3-4 days) RBC t1⁄2 = months Lymphocyte t1⁄2 = years Some variability in sensitivity to specific drugs Nadir = low point Neutrophil nadir = 7-10 days Platelet = 3-4 weeks RBC = long survival (mild, low grade)

Answer 129

Nadir = low point Neutrophil nadir = 7-10 days Platelet = 3-4 weeks RBC = long survival (mild, low grade)

Answer 130

Acute - Uncommon - Direct stimulation of chemoreceptor trigger zone - vomiting - Ex: cisplatin, streptozotocin, dacarbazine - Tx = IVFs, prophylactic anti-emetics (i.e. maropitant, ondansetron) Delayed (2-5 days) - Common - Nausea, hypo/anorexia, vomiting, soft stools, diarrhea - Effect of chemo on GI crypt cells - Mucositis common in people – basal cells

Answer 131

- Caused by damage to intestinal epithelium - Small bowel - Colitis (doxorubicin) - Manageable with diet alterations, probiotics +/- metronidazole or tylosin

Answer 132

Direct stimulation of chemoreceptor trigger zone - vomiting - Ex: cisplatin, streptozotocin, dacarbazine Or Local irritation of GI tract days after chemo Manageable with prophilactic anti-emetics

Answer 133

veterinary cooperative oncology group -common terminology criteria for adverse events

Answer 134

Encodes the P-glycoprotein drug transport pump - Limits drug absorption & distribution, esp. to brain - Enhances excretion of drugs MDR1 mutant patients have defective pumps & are more susceptible to side effects Found in; collies, long haired whippet, australian shepherds (normal and mini) High risk drugs - Vinca alkaloids, paclitaxel & doxorubicin -> documented to cause problems - Etoposide, mitoxantrone -> p-glycoprotein substrates in humans, unknown in dogs

Answer 135

Loperamide (Imodium®), Ivermectin

Answer 136

MDR1 (ABCB1) allele mutation test available at washinton state university

Answer 137

homoxygotes yes but dose adjustment is recommended. Unkown the risk for heterozygotes if a full dose is given

Answer 138

MDR1 mutation carriers Encodes the P-glycoprotein drug transport pump - Limits drug absorption & distribution, esp. to brain - Enhances excretion of drug Can substitute p-glycoprotein drugs with alkalating agents

Answer 139

Nitrogen mustards = mechlorethamine, melphalan, cyclophosphamide, ifosfamide, chlorambucil Nitrosureas = lomustine, BCNU, streptozotocin Non classical alkylating agents (known as methylating agent) = Procarbazine, dacarbazine, temozolomide

Answer 140

Biologic activity results from polyfunctional alkylation of DNA alkylation of DNA bases through formation of reactive intermediates that attack neutrophilic sites - Cause inter- and intrastrand cross-links - Induce apoptosis

Answer 141

urine & feces

Answer 142

Increased capacity to repair alkylated lesions - Increased guanine O6-alkyl transferase in nitrosureas & methylating agents - Increased expression of glutathione-associated enzymes (the glutamyls) - Increased ALDH = aldehyde dehydrogenase (cyclophosphamide) - Decreased expression or mutation of p53 - Enhanced DNA damage repair (increased nucleotide excision repair) - decrease drug uptake (altered leucine pumps)

Answer 143

They are alkylating agents; Cyclophosphamide & ifosfamide - Metabolism = hydrolysis to phosphoramide mustard (active) & acrolein metabolites - Sterile hemorrhagic cystitis (5%) - Due to excretion of the metabolite acrolein which directly irritates bladder mucosa - MESNA (2-MErcaptoethane SulfoNAte) used to prevent SHC – hydrolyzes in urine to yield active parent that conjugates with alkylating species to prevent cystitis - Prevention: Give Cytoxan in morning, fresh water, prednisone / furosemide - Dx & Tx: Culture to rule out UTI, never give drug again! anti-inflammatories, pain control, anti-spasmodics, time

Answer 144

IT is an alkylating agent Enters cells via passive diffusion Side effects - BAG - Myelosuppression common & often severe - 2/3 dogs develop -Hepatotoxic - ≤ 70-80% of dogs develop increases in ALT with repeated doses - Monitor liver enzymes -> delay/discontinue/dose reduce

Answer 145

Alkalating agent used to treat pancreatic beta cell tumours Side effects include pancreatitis and renal toxicity. Administer IV with diuresis to avoid nephrotoxicity

Answer 146

enters the cell by passive diffusion. Irreversible thrombocytopenia with chronic tx-> ~40% of dogs on tx > 1 year Cannot be treated unless a bone marrow transplant is performed.

Answer 147

CCNU Oral capsule

Answer 148

cyclophosphamide

Answer 149

anti-angiogenic cell cycle non specific Directly binds to blood vessels inhibiting. Suppression of T regulatory lymphocytes leading to blood vessel inhibition

Answer 150

Cyclophosphamide  Ifosfamide Dacarbazine Procarbazine

Answer 151

Cisplatin, carboplatin, oxaliplatin

Answer 152

MOA = Actively transported into and out of the cell. Bind to DNA & form inter- and intra-strand crosslinks MORs that result in increased tolerance to DNA damage: - Alterations in transmembrane cellular accumulation of drug - Cytosolic inactivation of drug - DNA damage repair (increased nucleotide excision repair) - Resistance to apoptosis - Cisplatin MOR = defective recognition of DNA adducts (missmatch repair defect)

Answer 153

cis analog = clinically active trans analog = not active

Answer 154

BAG Stimulation of CRTZ -> vomiting, use prophylactic anti-emetics Nephrotoxicity -> diuresis minimizes the risk Cisplatin toxicity in cats = Fatal idiosyncratic pulmonary edema (“cisplatin makes cats go splat”)

Answer 155

unique delayed or double nadir -> 10-14 days, 21 days (up to 28+ days in cats)

Answer 156

carboplatin 0-14 days, 21 days (up to 28+ days in cats)

Answer 157

Derived from yeast and affect Cell cycle activity in all areas of cell cycle Doxorubicin, mitoxantrone, epirubicin

Answer 158

Antitumor antibiotics / Anthracenediones

Answer 159

adriamycin

Answer 160

- Intercalation into DNA - Inhibition of topoisomerase II & DNA/RNA polymerases - Alkylation of DNA - Production of free radicals (except mitoxantrone) - Cell membrane damage via changes in intercellular calcium homeostasis

Answer 161

Glutathione/GSH inactivation, increased drug efflux (increased MDR expression or MDR gene amplification), absent or mutated drug target

Answer 162

Cardiotoxicity in dogs (irreversible) - Typically if cumulative dose >180 mg/m2 (>6 doses) - Appears clinically similar to CHF & tx is similar BAG in dog and cat Nephrotoxicity in cats Histamine release - anaphylaxis possible (rate of infusion matters) Severe vesicant if extravasated - COLD COMPRESS

Answer 163

5-fluorouracil, cytarabine, gemcitabine, methotrexate, hydroxyurea, Tanovea®

Answer 164

Cell cycle phase specific (S phase) MOA = Nucleotide analogs that resemble DNA metabolites-> Incorporate into replicating DNA strand to disrupt DNA synthesis MOR = decreased drug activation, increased drug target Toxicities; - BAG in dogs - Longer infusion = more myelosuppression - Do NOT use 5-FU in cats  neurotoxicity

Answer 165

It is an antimetabolite (2,2-difluorodeoxy-cytidine (dFdC) analog) MOA = incorporation into DNA terminates chain elongation, inhibits ribonucleotide reductase, depletes physiological deoxynucleotides MOR = Inhibition of nucleoside transporter systems, deficiency of activating enzyme (deoxycytidine kinase)

Answer 166

Gemcitabine most potent before RT, due to ribonucleotide reductase inhibition

Answer 167

Antimetabolite Other name; cytosine arabinoside it is an arabinose nucleoside analogue. MOA = competitively inhibits DNA polymerase alpha, incorporated into DNA, terminates DNA chain elongation MOR = decreased drug activation (decreased deoxycytidine kinase)

Answer 168

Antimetaboline - purine analogue Enters cells by passive diffusion - MOA = Inhibits ribonucleotide reductase - MOR = Increased synthesis of cellular ribonucleotide reductase

Answer 169

5-Fluorouracil, it is an antimetabolite chemotherapy Halogenated analog of uracil MOA = Incorporation of 5-FdUMP into RNA interferes with RNA processing & function; 5-FdUMP inhibits thymidylate synthetase MOR = Increased drug target (amplified TS) Do NOT use 5-FU in cats  neurotoxicity

Answer 170

Lomustine (CCNU) Cytarabine Hydroxyurea Lipophilic & penetrate the CNS -> Procarbazine, temozolomide, dacarbazine

Answer 171

antimetabolite Folate analog - MOA = Inhibits dihydrofolate reductase -> prevents formation of reduced folates required for DNA synthesis - MOR = Decreased drug uptake (decreased expression of the folate transporter), decreased drug activation (decreased folylpolyglutamyl synthetase), increased drug target (amplified DHFR)

Answer 172

rabacfosadine for injection it is an antimetabolite Double prodrug of the guanine nucleotide analog PMEG which is approved for treatment of canine LSA MOA= inhibits DNA synthesis by inhibiting DNA polymerases leading to S phase arrest & apoptosis Toxicity; - BAG - ~25% of dogs develop cumulative dermatologic adverse effects - <5% develop pulmonary fibrosis (not recomended for westies)

Answer 173

Westies. less than 5% of patients on tanovea will develop pulmonary fibrosis, but it should not be used in an at high risk group

Answer 174

- Tanovea - Bleomycin (cumulative) - CCNU (one cat) - BCNU - Hydroxyurea - Mitomycin C

Answer 175

Vinca alkaloids-> Vincristine, vinBLASTine, vinorelbine

Answer 176

MOA = Bind to tubulin -> inhibit microtubule assembly -> prevent mitotic spindle formation -> metaphase arrest -> apoptosis

Answer 177

M-phase (hence they target spindles)

Answer 178

Increased drug efflux (increased MDR expression or MDR gene amplification), altered drug target (i.e. microtubules)

Answer 179

- BAG - Minimally myelosuppressive - Ileus - Peripheral neuropathy (rare in pets) - Tissue irritation if extravasated (vesicant) -> HOT COMPRESS

Answer 180

Doxo -> COLD compress Vinca -> HOT compress

Answer 181

spindle toxins e.g. Paclitaxel and docetaxel

Answer 182

Vinca alakaloids ->Vincristine, vinBLASTine, vinorelbine Taxanes -> Paclitaxel and docetaxel

Answer 183

Paclitaxel and docetaxel

Answer 184

Stabilise microtubules->prevent dissassembly of mitotic spindle

Answer 185

Increased drug efflux (increased MDR expression or MDR gene amplification), altered drug target (i.e. microtubules)

Answer 186

- BAG - Original formulation of paclitaxel causes hypersensitivity due to Cremaphor (whater insolluble adjuvant)

Answer 187

Cremaphor, which was a water insoluble adjuvant which can cause hypersensitivity can be prevented with Paccal Vet-CA1 which is has a water sulluble formulaiton

Answer 188

brand name of paclitaxel

Answer 189

Camptothecin TOP1 inhibitors - Topotecan - Irinotecan Intercalating and nonintercalating TOP2 inhibitors - Intercalators = doxorubicin, daunorubicin, mitoxantrone - Nonintercalating epipodophyllotoxins = etoposide, teniposide

Answer 190

nonintercalating TOP2 inhibitors - Intercalators = doxorubicin, daunorubicin, mitoxantrone - Nonintercalating epipodophyllotoxins = etoposide, teniposide

Answer 191

MOA= degrade topoisomerase that. TOP1 makes single stranded cuts in DNA, allowing double helix to rotate TOP2 makes double stranded DNA cuts allowing knots and tangles to be undone. MOR = Increased drug efflux (increased MDR expression or MDR gene amplification)

Answer 192

myelosuppression, GI, elevated liver function tests

Answer 193

L-asparaginase

Answer 194

MOA = depletion of the amino acid asparaginase leads to inhibition of protein synthesis MOR (resistance emerges rapidly when used as a single agent) -> Upregulation of L-asparagine synthetase - Increased uptake/retention of L-glutamine and L-asparagine by tumor cells

Answer 195

lymphoma and othe hematopoietic tumours

Answer 196

L-asparagine synthetase is present in normal cells, but not in lymphocytes, hence they are relient on external sources

Answer 197

Methotrexate

Answer 198

L-asparaginase as this blocks MTX action

Answer 199

Minimal toxicity - hypersenisitivity ->premed with diphenhydramine - decreased protein synthesis (albumin, insulin, clotting factors, ATIII) - Pancreatitis - Nausea, vomiting, fever, chills

Answer 200

L-asparagine cannot enter all the cell. In the blood, L-asparagine is converted into L-aspartic acid by L-asparaginase. L-aspartic acid can then be uptaken by the cell and then bound to L-glutamine, which is converted to L-asparagine + L-glutamine again by L-asparagine synthase

Answer 201

Doxo Dactininomicin MTX Danorubicin Idarubicin Actinomicin-D Epirubicin (all the anthracyclins)

Answer 202

COLD compress for 20min TID for 1-2 days and neutralise with Dexrazoxane

Answer 203

Vincristine, vinblastine, Vinorelebine (all the vins - aka vinca alakaloids) and taxanes

Answer 204

HOT compress area for 20min TID for 1-2 days

Answer 205

HOT compress area for 20min TID for 1-2 days

Answer 206

1) veterinary staff 2) patient 3) owner

Answer 207

- all staff needs to be trained - familiarise yourself with the drugs - drugs must be stored in a secure place and clearly labeled - special waste containes - no drink/food in chemo area - wash hands before and after - draw up and under a hood - use luer lck fittings or ideal PhaSeal or Equashiedl closed systems - PPE - Chemo spill kit

Answer 208

- make aware of excretion path - never crush/cut pulls - no liquid formulations - latex gloves to clean urine/faeces/vomit most drugs pose minimal risk after 72h

Answer 209

it is a tyrosine kinase inhibitor (TKI). KIT is involved in cell grrowth and survival. Also involved in the spread of mast cell tumours .

Answer 210

toceranib phosphate

Answer 211

Diarrhea Vomiting Loss of appetite Weight loss Skin changes Bone marrow suppression

Answer 212

Palladia is approved for the treatment of grade II or III cutaneous mast cell tumors in dogs, with or without lymph node involvement. It may also be used off-label for other types of cancer in dogs and cats

Answer 213

approved for the treatment of grade two or three cutaneous mast cell tumors with or without lymph node involvement in dogs

Answer 214

- Palladia works by inhibiting receptor tyrosine kinases (RTKs), which are proteins that play a role in cell growth and division. - t also has anti-angiogenic properties, meaning it can help starve tumors by blocking the formation of new blood vessels that supply them with nutrients and oxygen

Answer 215

no technically it is an anti-cancer drug as it prevents the formation of new blood vessels which reduces nutrient delivery to the tumour.

Answer 216

Because drugs are calculated on body surface area which is thought to be a better representation of metabolic rate, however, smaller animals have a larger body surface area. Melphalan overcomes this by being in mg/Kg. The others have a seperate, lower dose per M2 for dugs <10-15kg

Answer 217

This is the MDR1 gene mutation, also known as P glycoprotein mutation seen in Collies, australian shephers and long haired whippets. Vincristine - increase neutrpenia an thrombocytopaenia DOXO extreme GI tox Also potentiates Vinblastine, vinorelebine, mitoxantron, dactinomcin, docetaxel, paclitaxel and etoposide Alkylating agents, antimetabolites, and platinum chemotherapy drugs are not impacted by ABCB1.

Answer 218

Alkylating agents, antimetabolites, and platinum chemotherapy drugs are not impacted by ABCB1.

Answer 219

becuase of the half life of cells. RBC half life is a few weeks and thus persist longer in the blood stream compared to neutrophils which have a half life of a few days

Answer 220

Bone marrow apsirates - especially if cytopaenic. You may need to administer chemo when they are cytopaenic, but it is ideal to start with less mylotoxic drugs such as L-asparaginase

Answer 221

NEU 500 to 2500/μl and platelet counts should be 50,000 to 100,000/μl or more on the day of treatment.

Answer 222

- Day of chemo - if cytopaenic re-test 3-7 days later - recheck at nadir for the drug

Answer 223

- Antibioitics (high dose NOT reomended) -> amoxyclav/enro/TMS common choises - Reduce dose of chemo by 10-25% in subsequent treatments (regardless of whether an infection is developed or not)

Answer 224

Bacterial translocation from gut (sometimes skin) which is usually increased due to damage to the GIT epithelium and coupled with the fact that most chemos are myelosupressive

Answer 225

becuase the WBC are responsible for fever development and these have been supressed

Answer 226

chest and abdominal imaging to look for a nidus of infection. Blood cultures are not routine

Answer 227

Carboplatin, lomustine, dacarbazine, melphalan, and occasionally DOX These drugs should be discontinued in patients with persistent platelet counts below 75,000 to 100,000/μl.

Answer 228

These affect the CTZ Drugs that can cause acute vomiting include cisplatin, dacarbazine, streptozocin, and occasionally mustargen and DOX

Answer 229

Often non clinical and you see systolic duysfunction on echo. Can manifest as arrhtyhmias alone or in combo with signs of DCM

Answer 230

It is cumulative -> manifests as a decrease in myocardial contractility with or without secondary arrhythmias

Answer 231

primarily by oxidative injury to the sarcoplasmic reticulum. The heart is particularly susceptible to oxidative injury because cardiac myocytes are rich in ironcontaining proteins (such as myoglobin) that can donate their metal to catalyze strong oxidant formation. Additionally, cardiac tissue has limited ability to scavenge these free radicals: it has very low levels of catalase, and DOX causes a transient drop in the level of glutathione peroxidase.

Answer 232

cumulative doses above 180 to 240 mg/m2 Dexrazoxane (Zinecard; 10 mg/1 mg of DOX IV) can be administered immediately before DOX to reduce its cardiotoxic effects substantially. In people, there is debate as to whether dexrazoxane can reduce the antitumor efficacy of DOX;

Answer 233

Cisplatin, ifosfamide, and streptozocin all are nephro- toxic and require intensive saline diuresis during admin- istration. Serum creatinine concentration should be measured before each treat- ment, and these drugs should be discontinued if creatinine concentration becomes elevated.

Answer 234

Cisplatin, ifosfamide, and streptozocin all are nephrotoxic

Answer 235

In cats specifically, DOX treatment is associated with cumulative nephrotoxicity. However, the renal toxicity is neither as consistent nor as rapidly progressive. It can be used cautiously in cats with underlying renal disease as long as renal parameters are monitored closely

Answer 236

Cisplatin IS, Carboplatin is NOT

Answer 237

cyclophosphamide or ifosfamide -> Acrolein, an inactive metabolite, can cause direct contact irritation of the bladder mucoss K9 receiving standard dose shold be given furosemide (2 mg/kg IV or SC) dilute the acrolein and encourage urination. For dogs receiving oral cyclophosphamide at home, owners should give the medication when they are able to take the dog outside regularly. Mesna (sodium 2-mercaptoethane sulfonate) binds to acrolein within the urinary bladder to help prevent irritation

Answer 238

This is Mesna. It binds acroelin metabolite from cyclophospamide treatment. Not needed (usually) at normal doses, but maybe used when high doses are given (e.g. high dose pre whole body radiation for lymphoma) Ifosfamide generates more acroelin than cyclophosphamide so this is more routinely given with this drug

Answer 239

lower in cats than in dogs, likely due to differences in their urination behavior

Answer 240

Mesna to bind acroelin Nonsteroidal antiinflammatory drugs are recommended to reduce inflammation and pain. Phenoxybenzamine (dogs: 0.25 mg/kg q8-12h PO) or oxybutynin (dogs: 0.2 to 0.3 mg/kg q8-12h PO) also can help alleviate muscle spasms.

Answer 241

lomustine - usually cumulative tox, although acute hepatic failiure can occur after one treatment

Answer 242

ALT Can be hepatotoxic. Not every dog with an elevated ALT concentration develops clinical hepatic failure. However, if ALT level is four or more times the upper limit of the normal reference range, further treatment with lomustine should be discontinued

Answer 243

Lomustine is hepatotoxic. Denamarin, a nutraceutical containing S-adenosylmethionine and silybin, decreases the risk that ALT will become elevated and reduces the magnitude of any elevations in ALT, AMT, BIL, ALP

Answer 244

Type I) Immediate hypersensitivity -> IgE. hay fever, anaphylaxis, hives Type II) Cytotoxic hypersensitivity -> IgG or IgM; blood transfusion reaction, autoimmune disease (myasthenia), chemo Type III) Immune complex hypersensitivity -> mediated by immun complexes (antibody-antigen complex) Type IV) Delayed T-type hypersensitivity -> T-cells; contact dermatitis, tuberculosis

Answer 245

- L-asparafinase is the main - Type I hypersensitivity caused by IgE - Give diphenhydramine as a pre-treatment (15-30min pre) Dox,Docetaxel, paclitaxel, and etoposide can cause anaphilactoid hypersensitivitiues manifested by head shaking, flushing, pruritus, or urticaria

Answer 246

Reactions against polysorbate 80 (carrier molecule) for docetaxel and etopiside . Chemophor EL carrier is behind paclitaxel

Answer 247

Rapid administration can cause non–immunoglobulin E–mediated mast cell degranulation. Pretreatment with diphenhydramine typically is not needed as long as the drug is administered over at least 20 to 30 minutes,

Answer 248

cyclosporine Increases incidence of GIT side effects

Answer 249

Vincristine, vinblastine, vinorelbine, DOX, epirubicin, dactinomycin, and mustargen are vesicants. Think alkylating agents and vincas

Answer 250

Mitoxantrone, cisplatin, dacarbazine, docetaxel, paclitaxel, and streptozocin

Answer 251

- clean stick - vein must not have been used in previous 24h - patentcy assessed by drawing back never flushing If extravasion occurs - draw back as much chemo as possible - aspirate while catheter is slowly removed - f a subcutaneous blister persists, additional aspirations can be performed using a new needle and syringe each time. What should not be done - flush forwards to confirm patency - Moist compresses and occlusive ban- dages should not be used because they can further spread the extravasated drug and worsen tissue damage.

Answer 252

1-2 weeks A tissue slough should be treated like any other open wound with débriding as needed, pain medications, and antibiotic therapy. In severe cases, amputation might be required.

Answer 253

-Aspirate as much chemo through catherer as possible - chemo maybe aspirated by seperate needle aspiration if a bleb is present - Immediately after extravasation 6 ml of saline can be infused around the affected area, divided into four to six small injections and using a new needle for each one - sodium hyaluronidase (150 U/1 ml of extravasated drug) to the saline has been reported, but it is not widely available. - Warm compresses should be applied to the affected site four times a day, 1 hour initially and then 20 minutes all subsequent times, for 3 to 5 days. - Dimethyl sulfoxide (DMSO) and fluocinolone ace- tonide (Synotic) mixed with 10 mg flunixin meglumine (Banamine) should be applied topically after each heat application

Answer 254

-Aspirate as much chemo through catherer as possible - COLD compress for 1h intially, then 20min 4x per day for 3-5 days - DMSO of questionable benefit - Dexrazoxane 10mg/1mg DOX, should be given at time of extravasion IV, and then repeated at 24h and 48h

Answer 255

sodium thiosulfate (0.17 mol/l, or 2.5%) should be administered through the catheter before it is removed, or it can be injected directly into the affected site after the catheter is removed

Answer 256

Cisplatin should not be given intravenously to cats because of the potential for fatal pulmonary edema Cysplatin makes Cats go splat 5-fluorouracil is contra- indicated because of the high incidence of fatal neurotox- icity with systemic or topical use

Answer 257

first canine anti cancer vaccine which targets MELANOMA antigen (tyrosinase) for immune recognition by T-cells. Form of immunotherapy

Answer 258

Natural killer cells, macrophages, and dendritic cells are the primary effector cells responsible for generating antitumor activity following the administration of nonspecific immune activators. Release of innate immune cytokines, especially interferon-α (IFN-α) and IFN-γ, also contributes significantly to antitumor activity by suppressing tumor cell growth and by inhibiting tumor angiogenesis.

Answer 259

Toll like receptors (TLR) and Nucleotide-binding oligomerazation domain-like receptors (NLRs) - TLR 3; activated by double-stranded RNA from viruses - TLR4; activated by lipopolysaccharide - TLR 7 and 8; activated by viral nucleic acids and synthetic molecules such as imiquimod - TLR 9; activated by bacterial DNA while NLRs - expressed in the cytoplasm of immune and non immune cells recognize bacterial wall peptides Nod1 and Nod2, as well as viral nucleic acids (retinoic acid- inducible gene RIG1)

Answer 260

they are protein rich exudates they are a negative prognostic indicator

Answer 261

similar for both - lymphoma most common - Carcinoma associated (carcinomatosis) second, mostly from metastasis of mammary, ovarian, pulmonary, urothelial, hepatic, or gastrointestinal carcinomas - Sarcoma associated are rare but maybe seen with metastatic lesions

Answer 262

Carcinoma is cancer that starts in the epithelial cells (lining of organs and skin), sarcoma is cancer that starts in connective tissues (bone, muscle, fat), and an adenoma is a benign (non-cancerous) tumor that develops from glandular tissue

Answer 263

Most common cause - Lymphatic infiltration and obstruction in addition to increases lymphatic and vascular permeability - metastasis to lymph nodes causing obstruciton - in addition to decreased lymphatic drainage increased angiogenesis results in more fluid production Other less common - implantation of tumour cells onto surfaces causing inflammation ( e.g. mesothelioma) - obstruction of venous drainage -> oedema

Answer 264

vascular endothelial growth factor [VEGF]) is produced by tumor cells, mesothelial cells, macrophages, monocytes, and tumor-infiltrating T lymphocytes. VEGF induce the proliferation of new vasculature, which is more permeable than normal vessels and it also increases the permeability of existing vasculature.

Answer 265

Vascular endothelial growth factor -> commonly secreted by tumours to promote angiogenesis. Additionally, the new angiogenic vessels are leaky, and VEGF increases leakiness of pre-existing vessels which leads to malignant effusions .

Answer 266

If there is diffuse involvement with implanted cancer cells on the parietal and visceral surfaces. Therefore cancer cells are more likely to be found in ascitic or pleural fluid of patients with carcinomatosis (97%) than in the fluid of patients with lymphoma and those with deep visceral (e.g., pulmonary or liver) metastases.

Answer 267

Lymphoma. If no cells seen on cyto; immunohisto can be performed using CD3 and CD79a (or other Blymphocyte markers) as well as stains for intermediate filaments (e.g., cytokeratins, which are markers for epithelium-derived cells). May help differentiate between carcinoma and lymphoma. Other tests include PCR (testing for antigen receptor rearrangements ) and flow cytometry

Answer 268

Both thoracic and abdo surfaces have mesothelial cells. These become reactive in effusions and are hard to differentiate betwen just being reactive and neoplastic

Answer 269

treatment for re-occuring thoracic effusions. introduction of sclerosing agents may create attachment of the visceral and parietal pleural surfaces, which prevents fluid accumulation Bleomycin and tetracycines have been used (70% success). Humans use absbestos-free sterilized Talc which has an 80-100% success rate. Not thought to be as successfull on dogs (used to treat chylous effusuon though)

Answer 270

No, they have a 23% risk of major comlications. Some studies show complications as high as 73%

Answer 271

- pleurodesis - intra cavitary chemotherapy (Cisplatin [not in cats], bleomycin, 5-fluorouracil, thiotepa, and doxorubicin

Answer 272

Dog; Cisplatin, bleomycin, 5-fluorouracil, thiotepa, and doxorubicin Cat; same, but you cannot give cisplatin (fatal pulmonary oedema develops). Doxo can be used, but in general it is not recomended due to the risk of tissue necrosis

Answer 273

The superficial cells causing effusions are likely less perfused and giving intracavitary drugs will expose them to a significantly higher concentration of drug which is not going systemically

Answer 274

Priming the line with saline reduces the risk of chemo exposure when it is placed in the patient and we are checking that there is approrpriate fluid flow. 250ml/2 for thorax, 1000ml/2 for abdomen - these volumes allow distribution of the drug without clinical signs of effusions to develope

Answer 275

75-85% of the liver blood supply comes from the portal system, while 85-100% of the neoplasms comes from the hepatic artery. This allows the blood supply to a hepatic tumor can be interrupted and the normal liver can remain virtually unaffected

Answer 276

Intraarterial delivery of a radiosensitizing chemo- therapeutic agent such as cisplatin directly to a tumor that is being irradiated may improve the efficacy of RT. A combination of intraarterial chemotherapy and RT has been described in several clinical reports

Answer 277

Cisplatin can induce cell cycle arrest, specifically at the G1-S phase, a time when cells are more sensitive to radiation Hypoxia: Cisplatin can increase the sensitivity of hypoxic tissues to radiation by generating reactive oxygen species (ROS) (radiation generally does not work as well in tissues that are O2 poor) Cisplatin lesions can inhibit the DNA-PKcs kinase, a key enzyme involved in NHEJ, a major DNA repair pathway

Answer 278

Palladia; rally bioavailable small-molecule inhibitor that blocks a variety of receptor tyrosine kinases (RTKs) expressed on the cell surface by acting as a reversible competitive inhibitor of ATP, thus preventing downstream signaling. Toceranib mainly inhibits; - RTKs -VEGF-R2 - PDGFRβ (platelet derived growth factor receptor ß) - KIT - JAK

Answer 279

start at 3.5mk/kg q48 and then reduce based on clinical adverse effects (most drugs you start low, work up).

Answer 280

D+, anorexia, lameness, weight loss, and hematochezia

Answer 281

Carb -> urine, faeces, sebum, cerumen -> 21 days Cyclo -> urne ->1-4days Doxo-> urine -> 21 Vinbl-> urine -> 7 Vinc -> urine -> 3

Answer 282

Monoclonal antibodies -> eg RituxiMAB Small molecular inhibitors -> eg ToceraNIB These are drugs that target cancer-specific proteins, cancer-upregulated pathways, or cancer-signaling pathways, so the drugs are very specific and should target just neoplastic cells. This should reduce side effects (some of these pathways are found in normal cells though).

Answer 283

They phosphorylate tyrosine molecules and are expressed on the cell surface, cytoplasm or nucleus. Those on the surface are receptor tyrosine kinases (RTK) and bind growth hormones. These are very important receptors for cancer growth/upregulation and angiogenesis

Answer 284

c-kit -> gastrointestinal stromal tumour, mast cell neoplasia BCR-ABL -> chronic myeloid leukemia (dogs) EGFR (epidermal growth factor) -> carcinomas like breast cancer, lung cancer, head and neck but also some sarcomas like haemangio B-raf -> melanoma (humans Met -> osteosarcoma (dog)

Answer 285

Glivac (imatinib) - targeted ATP pocket of ABL, preventing phosphorylation of the signal. This can also target ckit

Answer 286

Translocation of BCR-ABL between chromosome 9 and 26

Answer 287

Targets c-Kit ( on target ) RTK which is essential for mast cell tumour survival. 30% of dogs will have mutations of c-kit which makes the tumours more aggressive but also good targets for small molecular inhibitors. Off target effects include PDGFR, FLK-1 and VEGFR2 (last is antiangiogenic)

Answer 288

AGASACA, Thyroid Carcinoma, head/neck carcinoma, nasal carcinoma

Answer 289

50% D+ 40% anorexia 5-30% vomiting 46% neutropenia at maximum tolerated but we use lower ->still monitor CBC 15% hindlimb weakness, pain and tremors Proteinuria, pancreatitis, GI perf also reported (biochem done to monitor and some will give famotadine or omeprazole off the bat)

Answer 290

CBC , body weight @ 2 weeks then every 4 weeks for 3 months, then 8-12 weeks (PE, CBC/chem+UA) D+ can still happen in ~50% of cases, while anorexia 40% and vomiting 5-30%. Neutropenia at high doses is also seen in 46% of cases. 50% will need a dose reduction or a drug holiday during treatment

Answer 291

depends on tumour type and condition of the dog/cat. Avg is every 3 months at UMN

Answer 292

Laverdia - it is small molecular inhibitor of the nuclear export protein XPO-1. This XPO-1 is responsible for transporting tumour suppressor proteins out of the nucleus (p53, p21, RB, FOXO). By inhibiting XPO-1 we are trying to keep these proteins inside the nucleus.

Answer 293

Verdinexor can cause hyporexia at high doses

Answer 294

treatment of lymphoma in addition to multimodal chemo or if they did not want to do chemo

Answer 295

1) non specific; increased immune system activation -> increases risk for autoimmunity. Not target enough for onco therapy 2) monoclonal antibodies 3) active immunotherapy; using cancer vaccines (using whole tumour cells or tumour cell lysates to make an autologous vaccine / allogenic [different patients tumour] vaccine) -> Onsept is one of these

Answer 296

Blontress (Aratana) -> chimeric AB against CD20 for canine B cell lymphoma. Does not have reproducible efficacy over 7 IV injections. it is safe Tactress-> chimeric AB against CD52 for canine T cell lymphoma. Efficacy also not reproducible

Answer 297

These are the immunological breaks that downregulate the immune system. Tumour cells often upregulate these and therefore the remove the breaks, or in some cases upregulate them so that things like lymphocytes struggle to get activated - CTLA-4 (cytotoxic T-lymphocyte associated protein 4 - PD1 (programmed cell death) - PD-L1 (ligang for PD1, found in canine melanoma, MCT and renal carcinoma)

Answer 298

MEasuring the mass size and seeing for shrinkage. This is a problem for monoclonal antibodies as these can recruit immune cells to the tumour causing it to grow. There are no current guidelines for immunotherapy

Answer 299

- whole cell ro tumour lysate - peptide antiges - plasmid DNA - Immune cells activated against a turmour

Answer 300

Tyrosinase is involved in the production of melanin and is therefore specifically expressed on melanocytes (normal and cancerous) -> melanoma, especially pigments, have overactivation of this. However, it contains human tyrosinase which cross reacts so the dog should build an immune reaction against it. Used in stage II or III melanoma in conjunction with local control

Answer 301

Controversial, some studies find benefit, others not. MST 475 days

Answer 302

establishes that chemo kills a constant fraction of the tumour cells, rather than a constant total number of tumour cells. Thus the kill number is proportional to the number of cells present and changes in proportion to tumour growth. In the case of leukemias, where the cell growth is exponential, the kill number for a given dose of chemo is logarhythmic. This is not the same for all solid tumours

Answer 303

Cisplatin, oxaliplatin, carboplatin, chlorambucil, cyclophosphamide, mechlorethamine, and melphalan

Answer 304

doxorubicin, epirubicin and idarubicin

Answer 305

inhibit DNA transcription into RNA, preventing protein synthesis and the production of new cells Cyclophosphamide Ifosfamide Mechlorethamine Chlorambucil Melphalan

Answer 306

disrupt cancer cell DNA by poisoning topoisomerase, an enzyme that unwinds DNA for replication.

Answer 307

Inactivation of p53 and PTEN inactivation are associated with malignant transformation in vascular endothelial cells Over expression of VEGF (vascular endothelial growth factor) and VEGF1R (vegf receptor 1) which increases vascular proliferation Basic fibroelastic growth factor which also has angiogenic properties Matrix metalloproteinases have been shown to increase and have a role extracellular matrix protein breakdown