Treatment Modalities LC Flashcards

Question

sulforaphane modulating several signaling pathways involved in tumor growth and progression

Answer 1

Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Pathway: activate the Nrf2 pathway, regulates the expression of antioxidant and detoxification enzymes. Activation of Nrf2 leads to increased expression of glutathione S-transferases (GSTs) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Glutathione helps neutralize reactive oxygen species (ROS) and free radicals, which can damage DNA and promote cancer development. Anti-Inflammatory Pathways: inhibiting the production of pro-inflammatory cytokines and enzymes, such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). reducing chronic inflammation, suppress tumor-promoting processes and inhibit tumor growth Apoptosis (Programmed Cell Death) Pathway: upregulate pro-apoptotic proteins Bax and Bak while downregulating anti-apoptotic proteins Bcl-2. activate caspases, modulate cell cycle progression by arresting cancer cells at different checkpoints, such as the G1/S and G2/M transitions. Epigenetic Regulation: inhibit DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), leading to changes in gene expression patterns that may favor tumor suppression. Angiogenesis Inhibition: downregulate angiogenic factors like vascular endothelial growth factor (VEGF)

Answer 2

Clinical Trials: Study 1: A clinical trial investigated the effects of sulforaphane-rich broccoli sprout extract (BSE) in dogs with lymphoma. - no clinical response and no adverse events - affected proteome -14 proteins were significantly downregulated, and 10 proteins were significantly upregulated. Proteins and gene sets impacted by SFN were commonly involved in immunity, response to oxidative stress, gene transcription, apoptosis, protein transport, maturation and ubiquitination. In Vitro Studies: Study 1: effects of sulforaphane on canine osteosarcoma cells. SFN could not induce cell death at potentially physiological concentrations (<50 μM), but significantly diminished cell invasion and downregulation of focal adhesion kinase (FAK) signaling. Modest cell cycle changes were observed in each cell line

Answer 3

Epidemiologic evidence suggests that diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk In vitro studies have shown inhibition of bladder cancer cell lines, cell cycle arrest, and induction of apoptosis research shows dogs can absorb sulforaphane and it has activity

Answer 4

Dogs treated with PSP alone, female dogs, decreased HCT at diagnosis, and stage III disease associated with poor outcome Addition of PSP to dox post splenectomy did not improve survival This study shows the PSP alone does not improve survival compared to splenectomy alone

Answer 5

double-blind randomized multidose pilot study, high-dose PSP significantly delayed the progression of metastases and afforded the longest survival times reported in canine hemangiosarcoma 2012 - before the paper showing it had no effect Median time to development or progression of abdominal metastases was significantly delayed in dogs receiving 100 mg/kg/d I’m-Yunity (112 days ) compared with dogs receiving 25 mg/kg/d (30 days), but was not significantly different than in dogs receiving 50 mg/kg/d

Answer 6

extract was well-tolerated and induced no negative effects, no decrease greater than 50% (objective response) in lymph node size occurred in 13 of 15 dogs

Answer 7

More dogs receiving CCNU alone had an increase in ALT compared with dogs receiving CCNU with Denamarin (84% vs 68%)

Answer 8

genistein and GCP led to cell death via apoptosis, and the treated cells exhibited increased Bax:Bcl-2 ratios. GCP was also found to inhibit cell proliferation, increase apoptosis, and induce G2/M arrest in 3 human and 4 canine lymphoid cell lines. in vivo, dose-escalating pharmacokinetic study determined that therapeutic serum levels of genistein were not reached with oral dosing of GCP in normal dogs

Answer 9

nuclear condensation and fragmentation, typical of apoptosis Other reported antitumor effects are in human breast and prostate cancer and leukemia

Answer 10

Calcitriol induces G1/G0 cell-cycle arrest and apoptosis, while down-regulating Bcl-2, decreasing epidermal growth factor, and inhibiting tumor invasion through decreased metalloproteinase (MMP)-2 and metalloproteinase-9 activity. Calcitriol was synergistic with cisplatin using in vitro canine tumor cells and a phase I clinical study synergistic, antiproliferative in vitro activity when used with other chemotherapeutics, including CCNU, vinblastine, imatininib, or toceranib Calcitriol inhibited canine transitional cell carcinoma cells via G0/G1 cell-cycle arrest

Answer 11

A 42%-58% response rate (33% CR) to isotretinoin treatment has been seen in dogs with cutaneous lymphoma, and positive results have been seen with in vitro canine mast cells and osteosarcoma cell lines 25% of dogs experiencing adverse effects that resolve quickly or do not affect quality of life.

Answer 12

anticarcinogenic effect by reducing the naturally occurring genotoxic stress within the aging prostate. In a translational RCCT using 49 intact male elderly beagles, the extent of DNA damage in prostate cells and in peripheral blood lymphocytes was lower among the selenium-supplemented dogs. recommended to be discontinued during RT since rt works by oxidation

Answer 13

dogs fed menhaden oil had significantly higher plasma concentrations of DHA (increased by 500%) and EPA (200%), lower tissue inflammatory eicosanoids, and decreased resting energy expenditure (by 20%) compared with controls. Increased plasma DHA was significantly associated (P<.05) with decreased plasma lactic acid and MMPs. This study suggests EPA and DHA may reduce some detrimental inflammatory eicosanoids and metabolic consequences of RT

Answer 14

likely occur due to altered expression of the functional CYP450 isoenzymes that metabolize chemotherapeutic drugs Hypericum perforatum, more commonly known as St. John’s Wort (SJW), which interferes with both CYP450 isoenzymes and P-gp - vincristine, vinblastine, and EGFR-TK inhibitors

Answer 15

herbal supplement did cause dose and time dependent hemangiosarcoma cell death through initiation of caspase-mediated apoptosis

Answer 16

no induction of hypercoagulability.

Answer 17

no side effects attributed to the use of Yunnan Baiyao. The study did not show a significant improvement in survival time from the study dogs compared to the control dogs.

Answer 18

– recurrence < 34%, tx with metronomic chemotherapy, hypofract RT

Answer 19

therapeutic target : slowly proliferating tumor endothelium mechanisms - inhibition of tumor angiogenesis: possibly though thrombosponin-1 inhibiting vegf and blocking circulating endothelial cells - activation of anti-tumor immunity: decreases in the number and function of Treg (inhibiting their blocking of NK cell and inhibiting secretion of TGFb/IL10) , dendritic cell activation, and stimulation of tumor-specific cytotoxic T cells - induction of tumor dormancy AND inhibition of cancer stem cells; may be able to target CSCs and dormant tumor cells because of the tendency of both cell populations to reside in close proximity to tumor vasculature | function in acidic and hypoxic environments

Answer 20

decrease in Treg number and function without interfering with tumor-specific cytotoxic T cell function

Answer 21

COX inhibitors, tetracyclines, and thalidomide or those with more direct effects such as bevacizumab

Answer 22

pilot study of MC and celecoxib therapy in 15 dogs with various cancers found low baseline plasma VEGF was predictive of response

Answer 23

hypertension, edema, hemorrhage, thromboembolism, proteinuria, intestinal perfo- ration, and impaired wound healing

Answer 24

hypertension, protein- uria, dose-dependent gastrointestinal upset, bleeding, myelosup- pression, azotemia, anemia, lethargy, lameness, or disruption of the hypothalamic–pituitary–thyroid axis

Answer 25

true incidence of SHC may be more frequent in metronomic protocols. Recent reports document that cystitis may occur in up to 34% of cases, and SHC risk increases with longer treatment duration myelopthesis

Answer 26

MTD DOX with concurrent metronomic CYC 15 mg/m2 was found to be well tolerated in a recent phase I study - DOX was associated with nonselective depletion of circulating lymphocytes such that any potential benefits of Treg depletion by low- dose CYC would have been lost pRT plus daily oral piroxicam and thalidomide plus every other day oral CYC significantly longer OST compared with dogs treated with pRT alone (757 vs 286 days, respectively) RT has been combined with metronomic dosing of lomustine in the treatment of dogs with OSA - no diff in ost

Answer 27

- alternating cytox and etoposide daily with piroxicam let to similar efficacy to dox - cytox alone vs dox also similar but both were better than splenectomy alone- doxo 4.5 mths, mc ctx 2 mths, splenectomy 1.5 mths. doxo group had higher toxicity. - splenectomy and six doses of DOX, daily or every other day CYC plus an NSAID had no effect on PFS or OST

Answer 28

high incidence of adverse events occurred and led to the discontinuation of the therapy in nearly 30% ## Footnote 13 dogs with gastrointestinal toxicosis, 4 dogs with thrombocytopenia, 3 dogs with increased alanine transaminase, 1 dog with neutropenia, and 1 dog with progressive azotemia

Answer 29

renal tubular damage - azotemia hypocalcemia osteonecrosis of the jaw 1 report of allergic rxn

Answer 30

Palliative for pain 28% responded >4months, RT+dox+pam-bloodwork better but owner did not notice; Another RT+chemo+pam-the RT+pam group did the worst 69days

Answer 31

R1 (R2 determines amino-BP (ex. ZOL) vs. nonamino-BP (ex. clodronate))

Answer 32

binds to HAP via R1. uptake into the osteoclast Synthetic analogs of inorganic pyrophosphate **inhibits farnesyl pyrophosphate synthaze** preventing conversion of geranyl pp to farnesyl pp 1. Induction of osteoclast apoptosis net attenuation of pathologic bone resorption 2. Interfere with post translational prenylation of small GTP-binding proteins including Ras, Rho and Rac Inhibit bone resorption without inhibiting bone mineralization

Answer 33

reduced CXCR4 expression by 40% within primary tumor. ## Footnote cxcr4 is a transmembrane g protein coupled chemokine receptor involved in metastasis and growth

Answer 34

worked reports prev. Unreported allergic reaction in one dog. Otherwise well tolerated.

Answer 35

Chelation of iron-free radicals, resulting in reduced oxidative damage also poss dec in ROS

Answer 36

peak drug level ( within first 30- min) and total cumulative dose dosing 20 - 30 mg/m2 decreases cardiotox 96 hour infusion is less cardiotox

Answer 37

one study showed protective against Chemotherapy-induced neuropathy - may work against taxane or vinca neuro toxicity B6 intake from food is also associated with reduced risk of death from stroke, heart disease, and heart failure. B6 may reduce high blood pressure in animals Pyridoxal phosphate (PLP) is the major coenzyme form, the most abundant in animal tissue, and the cofactor for over 100 enzymes used in amino acid metabolism, including aminotransferases, decarboxylases, racemases, and dehydrases excess-pyridoxine diet actively influenced cell-mediated immunity via enhanced IFN-γ production and Th1-polarizatio

Answer 38

potentiates intracellular effects intracellularly in vitro

Answer 39

MESNA conjugates with acrolein in the urinary tract **in the bladder** to render it inactive. - cant work for cisplatin bc it only activates in bladder Mesna dimerizes to an inactive metabolite in blood so it does not affect the cytotoxicity of cyclophosphamide or ifosfamide

Answer 40

gemcitabine causes decreased NER DNA repair in s phase by inhiting dna polymerase - which is how carboplatin adducts are repaired (induces cell cycle arrest and apoptosis)

Answer 41

Methotrexate (can also “rescue” from methotrexate toxicity) o L-asparaginase depletes the asparagine reserve, and Elspar blocks conversion of MTX to polyglutamates as well as progression into S phase by depletion of asparagine so inhibits MTX action; upreg of MDR

Answer 42

Autooxidation → reduction (by GSHR) → conjugation with acrolein and other urotoxic metabolites in bladder

Answer 43

dec liver enzyme elevation 84% va 68%

Answer 44

is a water‐soluble disulfide form of mesna converted to mesna in the kidneys, which then locally inactivates the toxic platinum species - use as protectant form cisplatin Tavocept decreased the required diuresis time with cisplatin from > 6 hours to 90 minutes, while also decreasing occurrence of azotemia but may have reduced efficacy of platinum- dogs had worse rr than historic controls

Answer 45

used to protect kidneys from cisplatin sulfur compound that has the potential to limit severe mucositis caused by RT reduces neutropenia from cytox amifostine is not commonly used clinically for a variety of reasons. Clinically, it is difficult to administer, with hypotension being a major side effect.

Answer 46

dose dependent neutropenia reduce vinc dose myelosuppressive effects can be additive,

Answer 47

combination has shown synergistic effects, leading to enhanced tumor cell kill, particularly in lymphomas and sarcomas.

Answer 48

combining them can increase the risk of cardiotoxicity, as both drugs have cardiotoxic effects RARE

Answer 49

When used together, L-asparaginase and CCNU have shown synergistic effects against lymphoma cells, leading to enhanced tumor cell kill and improved treatment outcomes. ## Footnote inc rr fro ~50% ccnu alone to 77-87%

Answer 50

chronic low levels of cytotoxic chemotherapy exposure actually may have increased risk, because cytotoxic effects are less likely to occur with similar mutagenic effects

Answer 51

could harm a fetus, inc risk for other cancers Human healthcare workers (eg, pharmacy employees, nurses) handling chemotherapeutics have been found to have variably increased chromosomal aberrations compared to the general population, as well as urinary excretion of these drugs or their metabolites, which could lead to similar reproductive complications found in cancer patients treated with cytotoxic drugs incremental increased risk of infertility and early pregnancy loss with occupational exposure to chemotherapeutics increased risk was found for the development of multiple myeloma (6 cases out of 12 000), and a decreased risk for lung cancer

Answer 52

closed-system transfer devices (CSTD) biologic safety cabinets (BSCs) personal protective equipment (PPE) markedly decreases,but does not always eliminate, evidence of drug contamination

Answer 53

Chemotherapy-rated (ASTM International [American SocietyTesting Materials]) double-gloving Long-sleeved coated impermeable gown with back closure Shoe coverings Shoe & hair coverings to maintain sterility (if needed) Eye shield/Face shield if potential for splashing/aerosolization Respirator (fitted)

Answer 54

during compounding and administration and methods of preventing aerosol formation and spread of contamination mechanically prevents the escape of a drug or vapor out of the system into the environment. decrease the risk of needle accidents during administration adaptor for the drug vial, a piece that attaches to a luerlock syringe (needleless system), and adaptors to allow connection of the needleless syringe to the fluid lines FDA approved systems: Chemoclave/Chemolock Equashield Onguard PhaSeal

Answer 55

negative-pressure room preferred compounding aseptic containment isolator - vertical laminar flow, which carries contaminated air away from the operator (horizontal flow only protects the drug and not the worker); - High-efficiency particulate arrestance filter; 100% ventilation to the outside; and, a continuouslyrunning fan

Answer 56

during transfer of the drug from the vial to syringe and from the syringe into a fluid line

Answer 57

Orders and prescriptions should be independently calculated and verified by at least 2 separate individuals, but ideally including the prescribing clinician, a second person trained in handling Full PPE should be worn during preparation. A plastic-backed absorbent pad should be placed under the preparation site, and should be replaced at least once daily, or anytime a spill occurs or the pad is contaminated operations should be done at least 3 inches above the work surface. Fluid bags should be spiked and tubing should be primed with a compatible fluid before adding chemo. Outer gloves should be removed before final preparation andsurface decontamination. The outside of the container should be wiped with gauze moistened with a deactivating substance before removal work surface area in the BSC should be decontami-nated and disinfected. A fresh pair of outer gloves should be donned before removing the product inal product shouldbe clearly labeled as cytotoxic and sealed in a plastic bag that allowsvisualization of the product, then placed into the transport bag orplastic box

Answer 58

detergent and hypochlorite solution use of alcohol for primary disinfection will not deactivate chemo and may result in spread of contamination dont spray chemo directly disposed of in chemotherapy waste containers

Answer 59

found in urine, feces, saliva, vomitus, and sebum found in the urine for days to weeks after administration, although concentrations are markedly decreased within 3 days oral drug excretion for 5–7 days post-administration in the feces handle excreta from patients that have received injectable chemotherapy as contaminated for a minimum of 48–72 hours post-administration, and as long as 7 days after PO chemotherapy patient should be allowed to urinate and defecate outside in a separate, designated, sunny low-traffic area - ultraviolet light is believed to inactivate many drugs

Answer 60

If inadvertent direct contact with chemo or contaminated urine or feces of a patient occurs, the skin should be rinsed with water and washed using dishwashing detergent for a minimum of 5 minutes

Answer 61

Chemotherapy-rated gloves should be dispensed with any HD for use by the client when giving medications, and hands should be washed after each administration pet’s medications should not be stored with medications for humans, near food, or where accessible by children Animals receiving chemotherapy should remain in a controlledenvironment and not be allowed to urinate or defecate in communityareas, areas where children may be exposed, or areas that cannot beeasily cleaned for at least 48 hours after drug administration. Ideally alow-traffic, sunlit area would be preferred for elimination. If excreta arefound in the house, the area should be cleaned, and hands should bewashed afterwards Cat litter boxes should be cleaned daily and litter should be double-bagged and discarded with household trash. Any soft items (eg, bedding, towels, toys) should be washed twice, separately from other laundry, after exposure, and ideally bleached

Answer 62

Associated cardiac troponin with extracellular vesicle associated microRNAs Downregulation of miR-502 was detected before significant changes in cTnI concentrations or echocardiographic parameters

Answer 63

Vegf present in 77.8% of neoplastic samples Vegf present in 92% of inflammatory samples Only in 20% of normal samples

Answer 64

Somatic variants might initiate or perpetuate myelofibrosis in dogs. findings suggest the occurrence of clonal hematopoiesis in dogs, with increasing incidence with age, as observed in humans In humans, most primary myelofibrosis cases develop secondary to driver mutations in JAK2, CALR, or MPL.

Answer 65

CDC6 extracellular vesicle may be a non invasive biomarker to diagnose canine tumors in serum Various tumor types included (epithelial, neuroendocrine, round cell, melanoma, sarcoma)

Answer 66

There was a significant positive correlation between the neoplastic index, which was developed using ECPKA-Ab and CRP levels, and the presence of cancer in dogs ECPKA-Ab is a potential serum biomarker for a broad spectrum of cancers. Combined measurement of CRP and ECPKA-Ab levels in serum improves the sensitivity and accuracy of a diagnosis of cancer in dogs

Answer 67

54 SCC: 34 white coat/skin 3 groups sx with wide excision alone, marginal sx + ECT, and ECT alone Sig. correlation between fur coat color and skin tumors in sun exposure Animals with sun exposure had longer OST Sx + ECT resulted in 32% higher survival rate than Sx alone ECT with or without SX objective response rate 90.9% 35% of cats overall developed mets

Answer 68

surgical margins - 2-3 cm wide and 1 fascial plane deep Narrowest histologic margin <1 mm in 40 % mct and 37% of sts 4% low grade mct had local recurrence and 6% developed visceral mets One dog with high grade mct had local recurrence Not mets or local recurrence in sts these were mostly low grade tumors** cant make recs for high grade

Answer 69

residual tumor classification (“R”) scheme R1“tumor on ink” - incomplete R0 all other margin lengths - complete The R scheme resulted in higher retrospective percentage agreement in histological reporting than defining incomplete histological margin as tumor cells within ≤1 mm of the margin (83% vs 68% agreement) 26% MCT planned narrow excisions and 42% of STS PNEs resulted in R1 margins. R1 margins were more likely when performing PNE with 0-5 mm LMSM (55%) vs 6-10 mm lateral measured surgical margins (LMSMs) for MCTs (7%), but not STS Tumors recurred in 3/18 (17%) STSs and 2/18 (11%) MCTs ## Footnote in conclusion marginal excision of at least 1 cm = better

Answer 70

Definitions and criteria used to classify and report soft tissue and oncologic surgical complications are often absent, incomplete, or contradictory among studies. only 7.3% defined the term complication. Most (58%) reported complications could have been graded with a published veterinary adverse event classification scheme, although common intraoperative complications were notable exceptions.

Answer 71

mandibulectomy, matxillectomy, chest wall retention, liver lobectomy pre op autologous blood donation was well tolerated and led to uneventful autologous transfusion in 10/12 dogs

Answer 72

GI LSA and hepatocellular adenoma most common neoplastic cause No difference in survival compared to non neoplastic causes having cancer did not increase the risk of complications nor decrease the chance of survival ** CANCER is not a reason to not pursue treatment for septic peritonitis**

Answer 73

Histology provides more benefit as 5 cats had mets that were not identified on cyto There were 15 cats with neoplastic disease; LN biopsies confirmed metastatic disease in 10 and ruled out nodal involvement in five.

Answer 74

All dogs survived to hospital discharge. Follow-up ranged from 60 to 730 days (median, 264 days)

Answer 75

most common intraoperative complication was excessive surgical bleeding 53% - 43 had blood transfusions. significantly associated with tumor size and location, maxillectomy type, and surgical approach Dogs treated with a dorsolateral combined intraoral surgical approach were more likely to have excessive surgical bleeding [83%] and had a longer mean duration of surgery (106 minutes) than those treated with an intraoral approach [54%] and 77 minutes post op complications: epistaxis 51%, facial swelling 37%, facial pawing 37%, wound dehiscence 11%, infection 8% Complications associated with maxillectomy in dogs were generally minor. Aggressive surgical planning, preparedness for hemorrhage and transfusion, careful tissue dissection, and comprehensive pain control are recommended, particularly for dogs with large, caudally located oral tumors requiring extensive excision.

Answer 76

Overall complication rate of 37.3%, 62.1% minor Complication & complication rate similar between procedures. Transfusion is more often needed for maxillectomy. 11.6% fatality with maxillectomy, 4.4% with mandibulectomy. Increased surgical time associate with increased risk of complication 36% increase/hour Preoperative RT or chemo associated with increased odds of dehiscence or oral nasal fistula maxillectomy associated with increased risk for dehiscence or oral nasal fistula

Answer 77

16.7% intraoperative complication rate, 56.7% post op (hyporexia 20% for avg 7 days, dehiscence 20%) Local recurrence 18.3% metastatic rate 4.9% (benign tumors included) 1 & 2 year survival really high 94% fibrosarc, 83% SCC, 80% OSA poor prognostic factors - MI, adjuvant chemo, and local recurrence affected survival Maxillectomy is a viable treatment

Answer 78

IN order of tissue depth from greatest to least light penetration was adipose, skeletal muscle, fascia and sarcoma tissue. Neovascularization was observed in 53.2% sarcoma, and lines of fascia surrounding muscle bundles was present in 93.5% of skeletal muscle images OCT-guided pathology sections were able to detect incompletely excised MCT near the surgical margin with a sensitivity of 90% and specificity of 56.2% OCT was able to identify the presence of AGASACA at or within 1 mm of the surgical margin in all areas of interest OCT of FISS had overall sensitivity and specificity for classification of OCT images by evaluators were 78.9% and 77.6%, OCT of canine mammary tumors: The sensitivity and specificity for ex vivo images were 83.3% and 82.0% (observer 1) and 70.0% and 67.9% (observer 2). The sensitivity and specificity for in vivo images were 70.0% and 89.3% (observer 1) and 76.7% and 67.9% (observer 2) for canine sts OCT developed algorithm - accuracy of 97.1% with an excellent sensitivity of 94.3% on the validation set. model showed high sensitivity (0.98) for detecting cancerous tissues and a specificity of 0.97, which means that the misdiagnosis rate of the model for normal tissues was extremely low

Answer 79

Various dermal and/or SQ tumor types treated with short course RT then resected Acute RT SE in 40%; G1 50%, G2 43%, G3 7% Surgery complications in 17% mostly infection; 2 required medical intervention, 2 surgical and 1 died Tumors located on the extremity positive prognostic indicator overall well tolerated need study about outcome next

Answer 80

evaluate treatment effectiveness of ECT in as first line treatment objective response rate was stage I -100%, stage 2 - 89.5%, stage 3 - 57.7%, and stage 4 - 36.4%, Only patients in stage I, II and III with partial or complete response improved their quality of life Bette response if no boney involvement stage I - PFI 11 mths OST 16,5 mth stage II- PFI 7 mths OST 9 mths vs stage 3/4 - PFI 4 months ST 4.5-7.5 mths

Answer 81

intravenous 20 mg/m2 bleomycin, and the tumor bed and margins were infiltrated with cisplatin at the dose of 0.5 mg/cm2 5 min after the injection of the chemotherapy agents, sequences of eight biphasic pulses lasting 50 + 50 μsec each, were delivered in bursts of 1,300 V/cm using caliper electrodes second session was performed 2 wk later treatment was well tolerated and side effects were minimal. Twenty-six dogs had no evidence of recurrence at the time of manuscript writing; four had recurrence and one of the four recurring dogs died of lung metastases. Median estimated disease free was 857 d perivascular wall tumors were not diff in response compared to sts

Answer 82

compare the two IL-12 GET - peritumor vs intra tumoral local tumor control was significantly better in the ECT + GET i.t. group than in the ECT + GET peri.t. or ECT groups disease-free interval (DFI) and progression-free survival (PFS) were significantly longer in the ECT + GET i.t. group than in the other two groups did not observe any unwanted severe or long-lasting side effects rec response eval 2 months after treatment

Answer 83

investigate whether dynamic contrast-enhanced ultrasound (DCE-US) results of subcutaneous tumors differ between tumors with complete response (CR) and tumors without complete response (non-CR) in dogs treated with ECT and GET pIL-12 perfusion and perfusion heterogeneity were lower in CR tumors than in non-CR tumors

Answer 84

commercial gel having a conductivity of 0.2 S/m when used in combination with effective treatment planning may improve the outcome of electrochemotherapy procedures

Answer 85

ECT was not able to increase the overall survival of the patients evaluated and should be indicated carefully sig se - uroabdomen, hematuria one p had CR but developed tumor emboli and died of renal failure q]

Answer 86

All dogs developed transitory ulceration and swelling one-week after procedure that completely healed within 30 days post-ECT. Complete remission was achieved in all cases and lasted for 515 (oral case), 695 (one digit), 90 (another digit case) and 240 (lip) days.

Answer 87

electrical pulses lead to Increased membrane permeability allows drug to access cytosol → cell death and activation of APCs

Answer 88

primarily for the treatment of incompletely excised cutaneous and subcutaneous tumors, but also for the sole treatment of small primary tumors some efficacy in the treatment of canine mast cell tumors (MCTs), canine perianal adenomas and adenocarcinomas, canine nasal tumors, canine and feline localized lymphoma, and canine and feline spontaneous soft tissue sarcomas.

Answer 89

mct - 16% - 18% 53-1200 d 64-93% response rate

Answer 90

Dogs treated with ECT had significantly better 12- and 32-month survival rates (60% and 30%, respectively) than dogs treated with surgery and chemotherapy (10% and 0%, respectively).

Answer 91

incontinence (26%–37%), reobstruction (16%), and stent migration (11%), stranguria poststent placement is also a common finding Stent length diameter and location were NOT associated with incidence of incontinence

Answer 92

stent placement was found to be rapid, safe, and effective at restoring luminal patency 97 % rr

Answer 93

Temporary stents with red rubber Placed successfully in all 17 dogs - 9 had cancer 94% caused urinary incontinence - long stent removing all sphincter ability 3/17 dogs had migration

Answer 94

percutaneously gain access into the renal pelvis and place a guide wire across the obstruc- tion in an antegrade fashion. Dilation of a tract through the tumor then occurs from retrograde placement of a sheath and dilator. The ureteral stent is also passed retrograde through the stent and positioned with its pigtails in the renal pelvis and bladder.

Answer 95

In dogs with azotemia before stent place- ment, improvements in blood urea nitrogen (BUN) and serum creatinine concentrations were noted in all dogs improved hydronephrosis and hydroureter

Answer 96

all clinical improvement for a short time

Answer 97

dogs demonstrated resolution of clini- cal sings and extended survival times ranging from 7 to 20 months

Answer 98

greater target organ concentrations of drugs compared with intravenous requires anesthesia and sx procedure Side effects and toxicity were minimal - anemia, lethargy, and anorexia were sig- nificantly less likely in the group receiving IA chemotherapy com- pared with that receiving IV chemotherapy when IA cisplatin is administered with moderate doses of radiation, a high percent tumor necrosis was achieved in osa in bladder tumors the IA chemotherapy group had a significantly greater decrease in tumor length, length percentage, width percentage, longest unidimen- sional measurement, and longest unidimensional measurement percentage after treatment compared with the IV chemotherapy group

Answer 99

permanent vs temporary permanent used in cancer: particles (e.g., polyvinyl alcohol beads) and liquid agents (e.g., cyanoacrylate, alcohol, and ethylene vinyl alcohol copolymer)

Answer 100

directly targeting the specific blood supply of the tumor with the purpose of slowing or eliminating blood flow to that tumor results in ischemic tumor cell death

Answer 101

(1) treating a tumor primarily by diminishing the blood supply so that tumor death occurs, (2) preoperatively treating a tumor to decrease blood loss during a major surgical resection main reason for embolization currently in companion animals is as a primary treatment in cases that are deemed to be nonresectable or patients considered to be poor surgical candidates ie liver

Answer 102

chemotherapy is simultaneously delivered to a tumor at the time of embolization. This provides the theoretical advantages of IA chemotherapy After embolization, hypoxia within tumor cells increases vessel permeability, and these factors alter cell membrane function and cause chemotherapy to be sequestered in higher concentrations within tumor cells reduction of systemic drug exposure and a reported decrease in side effects and toxicity

Answer 103

slurry containing a contrast medium, embolic agent, and a chemotherapy agent - doxo, epi, cis, mitomycin c decribed in humans - also drug eluting beads

Answer 104

iodinated poppy seed lipid– based medium that has several proposed benefits: (1) it is radi- opaque and can be used in the slurry to replace contrast medium, (2) it acts as an embolic agent on its own, and (3) it preferentially concentrates in tumor tissue longer than in nontumor tissue

Answer 105

Clinical improvement was noted in the dog treated with bland embolization, but the dog died at home approximately 4 months post treatment. Doxorubicin was administered with polyvinyl alcohol particles and lipiodol in the dog treated with chemo- embolization; however, the dog died approximately 3 weeks after treatment as a consequence of an unrelated traumatic event both dogs demonstrated stable disease at 1 month, but progressive disease at 3 months after treatment went fine in normal does with temporary embolism

Answer 106

CT revealed a decrease in tumor size at 71 days posttreatment. Surgical resection was pursued 231 days after embolization and no recurrence was noted at 481 days after tumor removal

Answer 107

Experimentally, dogs have undergone PAE in a model of BPH. In this study, four of seven dogs with induced BPH had reduction of prostate size after embolization Ten dogs with confirmed prostatic carcinoma underwent PAE via a vascular approach in the left carotid artery. Tumor size was evaluated preembolization and approximately 1 month postembolization. In all dogs, prostatic tumor size decreased after embolization, and an improvement in clinical signs was noted based on an owner questionnaire

Answer 108

most common chemical ablation inject directly into lesion SE = inflammation of the tissue not talked about in Withrow

Answer 109

HCC, parathyroid tumors, Percutaneous ultrasound-guided ethanol ablation of parathyroid nodules achieves successful resolution of hypercalcemia in 95% of dogs with primary hyperparathyroidism Percutaneous ethanol ablation of hepatic and renal cysts has been performed without incident in dogs and cats

Answer 110

not a viable treatment for feline lingual/sublingual SCC; tumour volume was effectively reduced in some cats, but the simultaneous loss of lingual function was poorly tolerated

Answer 111

(1) Minimally Invasive: MWA requires only a small incision through which a probe is inserted into the tumor. This minimizes trauma to surrounding tissues compared to open surgery. (2) Precision: MWA precisely targets the tumor, delivering microwave energy to destroy cancerous cells while preserving healthy tissue. (3) Reduced Recovery Time: Because MWA is minimally invasive, it often leads to shorter hospital stays and quicker recovery times for animals. (4) Outpatient Procedure: In some cases, MWA can be performed on an outpatient basis, reducing stress for the animal and owner. (5) Effective for Inoperable Tumors: MWA can be used for tumors that are difficult to access surgically or for animals that are not good candidates for open surgery due to health issues. (6) does not require grounding pads (7) Higher intratumoral temperatures and faster ablations with less char and less pain are often achievable with MWA compared with RFA

Answer 112

1. Damage to Surrounding Tissues: While MWA is precise, there is still a risk of damaging nearby tissues, particularly if the tumor is located close to vital structures. 2. Incomplete Ablation: In some cases, MWA may not completely destroy the tumor, leading to potential regrowth. 3. Post-procedure Pain: Animals may experience some discomfort or pain after the procedure, though this is typically less severe than with traditional surgery. 4. Skin Burns: Skin burns can occur at the site of the probe insertion if not carefully managed.

Answer 113

Improved Visualization: VAS provides better visualization of the surgical site through a camera system, allowing for more precise surgical maneuvers. Reduced Trauma: VAS typically involves smaller incisions compared to open surgery, resulting in reduced trauma to the patient. Quicker Recovery: Animals undergoing VAS often experience faster recovery times and reduced post-operative pain compared to traditional open surgery. Less Blood Loss: Because VAS is minimally invasive, there is generally less blood loss during the procedure. Less Risk of Infection: Smaller incisions mean a decreased risk of post-operative infections.

Answer 114

1. Equipment Costs: VAS requires specialized equipment and training, which can increase the cost of the procedure. 2. Learning Curve: Veterinarians need to undergo specific training to perform VAS effectively, and there is a learning curve associated with mastering the technique. 3. Limited Accessibility: VAS may not be suitable for all types of tumors or in all locations within the body. 4. Risk of Complications: While rare, complications such as organ injury or bleeding can occur during VAS.

Answer 115

MWA uses electromagnetic energy to cause friction and heat, resulting in coagulative necrosis liver neoplasia in five dogs, a metastatic pulmonary lesion in one dog, and renal carcinoma in one dog No procedural complications were encountered

Answer 116

MWA is a feasible and potentially effective palliative treatment modality to stop bleeding from disintegrated mammary tumours in dogs under local anaesthesia

Answer 117

first PD-1/PDl1 inhbitor conditionally approved for melanoma and mct ## Footnote specifically PD 1 on t cells

Answer 118

classified as - interphase or proliferative or mitotic death *interphase death:* LYMPHS death via apoptosis. DSB leading to apoptosis. High levels of ROS cause oxidative stress, leading to mitochondrial dysfunction, DNA damage, and activation of apoptotic pathways. Radiation can activate p53, which in turn initiates the expression of pro-apoptotic genes. inhibit Bcl. activate death receptor Factors such as disruption of membrane structure and disorder of cell energy metabolism after irradiation are also important contributors to interphase death *proliferative or mitotic death* : all other cells - mitotic catastrophe caused by accumulation of chromosomal aberrations and erroneous repair after radiation induces a DNA double-strand breaks. After one or several division cycles, cells lose their ability to proliferate and begin to die

Answer 119

radiation-induced apoptosis closely correlates with radiosensitivity. A high apoptotic rate is strongly associated with good prognosis in cancer patients treated with radiation therapy most cell undergo proliferative or mitotic deathafter radiation

Answer 120

common technique used for detecting DNA fragmentation associated with apoptosis

Answer 121

Gr 1 - mild signs ie pain, erythema, cs associated with the organ (gi/urinary etc) Gr 2 - moderate signs ie intermittent pain, focal/patchy edema or desquamation affecting <50% of the area, moderate signs ass with organ ( cough, regurgitation diarrhea, neuro sx seizures mentally dull etc) Gr 3 - significant signs requiring intervention ie persistent pain, changes in behavior due to cs, edema or desquamation affecting >50% of the area, obtunded, blepharospasm, hearing loss, exercise intolerance, pericardial effusion, anorexia, 15-20% wt loss Gr 4 - Severe signs requiring hospitalization, ulceration, necrosis, perforation, O2 req, syncope, obstruction of urinary tract d/t hematuria with clots, wt los >20% Gr 5 - death

Answer 122

Gr-1 mild cs not changing daily life, pigment changes, subclinical neuro/musc deficits, eye changes, intermittent cough, subclinical ECG, subclinical fibrosis Gr-2 - moderate cs, fibrosis without impact on function, mental dullness, weakness, intermittent otitis, laryngeal dysfunction, ecg abnormalities requiring medication, intermittent v or diarrhea, chronic pollakiuria, or stranguria; dec tears tx with lubricant Gr 3 - significant cs that alter day to day life - fibrosis impacting function, ataxia, paresis, ulceration of th eye without depth, incomplete cataract, glaucoma req med, , blepharospasm, tear meds more than lube, hearing loss, coughing interfering with life, bark change, exercise intolerance, ulceration without bone exposure, persistent anorexia/v/d/r, subclinical ulceration or fistula, hydronephrosis Gr 4 - severe signs requiring hospitalization, necrosis and deep ulceration (skin, airway, brain, gi, bone) fracture, severe kcs, deep corneal ulcer desmetocele, complete cataract, glaucoma causing vision loss, complete stenosis, fistula formation , perforation, CHF, syncope, obstruction Gr - 5 death

Answer 123

1 joule of radiation energy per kg of matter. Unit of absorbed dose that measures the energy produced by ionizing radiation in a unit of mass of matter that is being irradiated

Answer 124

One monitor unit = 1 cGy of absorbed dose in water under specific calibration conditions for the linac. “Beam on” Charge passing through ionization center Used to standardize treatment machine within a single radiotherapy center and account for surface distance, scatter, field size

Answer 125

gross tumor volume

Answer 126

clinical target volume

Answer 127

planning target volume - bigger than CTV and accounts for movement, variation in positioning

Answer 128

Hypoxic cells are 2-3 x more resistant to radiation than oxic cells (*fractionated RT)

Answer 129

lymphocytes haematological cells, epithelial stem cells, hair follicles, gametes.

Answer 130

s- phase - synthesis phase Duplicated DNA provide a template for repair also G0

Answer 131

cells in the G2/M-phase are most sensitive to ionizing radiation law of Bergonie - tumors composed of rapidly multiplying cells, especially those of embryonal type and particularly those of the lymphoid group, are highly susceptible to radiation

Answer 132

Reoxygenation DNA repair radiosensitivity redistribution in the cell cycle repopulation

Answer 133

within 2-4 weeks following completion of a fractionated RT protocol

Answer 134

areas of rapidly dividing cells, fractionated protocols - low chronic dosing location - oral cavity, colon, eye typically heal eventually

Answer 135

high dose per treatment large field chemotherapy - doxo tissues with high rates of cellular turnover (e.g., mucosa, bone marrow) are more susceptible to late effects. Organs with limited regenerative capacity, such as the brain, eye, spinal cord and salivary glands, are particularly vulnerable to late toxicity. delays in radiation treatment - prolonged exposure never heal IMRT/SRT limit late tox by being precise

Answer 136

pain releif 2-4 months survival 4-10 mths

Answer 137

B. Adenocarcinoma ## Footnote chondrosarc - 1-2 years adeno - 14 mths scc- 6 mths

Answer 138

most common SE is mucositis but 10% develop oronasal and cutaneonasal fistulas

Answer 139

high a/b ration (7-20 Gy) fraction size and overall time both determine the radiation induce effect acute toxicity increases with higher doses per fraction skin mucosa

Answer 140

low a/b ration (0.5-6Gy) less sensitive to changes in dose per fraction and respond more to higher total dose. time does not effect radiation effect to this tissue late toxicity increases with higher total doses, lung, spinal cord, and connective tissues.

Answer 141

used to describe the sensitivity of tissues to changes in radiation dose per fraction. It represents the ratio of the linear (steepness of survival curve) (α) and quadratic (β) components of the linear-quadratic (LQ) model, which is commonly used to estimate the biological effect of radiation.

Answer 142

Fractionation schedules are designed to allow for repair of normal tissues while minimizing tumor repopulation. HRR and NHEJ of DSbreaks

Answer 143

increase in cell division of normal and cancer cells after radiation in response to a decreasing number of cells Accelerated fractionation or hypofractionation schedules may be employed to shorten treatment duration and reduce the opportunity for tumor repopulation accelerated repopulation phenomenon where, after 4-5 weeks, the growth fraction and doubling time are significantly increased. at each radiotherapy treatment, there are less clonogenic tumour cells (cells that can repopulate). The surviving clonogenic tumour cells increase their rate of proliferation and decrease cell loss, which reduces the radiotherapy treatment effectiveness and introduces resistance.

Answer 144

Intermittent hypoxia in tumors can reduce radiation effectiveness, so treatment schedules are designed to take advantage of reoxygenation. Fractionation allows for tumor reoxygenation between treatments, making tumors more sensitive to radiation - center of the tumor is hypo so kill form the outside in

Answer 145

Treatment plans are tailored based on the relative radiosensitivity of tumor and surrounding normal tissues. Advanced imaging techniques help delineate tumor volumes and critical structures, enabling precise targeting while sparing healthy tissue radio resistant tissue: myocytes, neurons, connective tissues, conjunctiva. Tumour cells such as melanoma, renal/pancreatic tumours.

Answer 146

moving from radioresistant s phase to radiosensitive g2/m Fractionation schedules are designed to exploit redistribution, ensuring that a higher proportion of tumor cells are in the radiosensitive phases during radiation delivery. give with vincas or taxanes to stop cells int he mitosis phase which keeps them in G2

Answer 147

Sublethal damage is repaired so survival curves have shallow shoulder and more reassortment, and repopulation then seen with single high fx

Answer 148

PD-1, CTLA-4, TIM-3, VISTA, BTLA, B7-H3, B7-H4, and LAG3 down regulate t cells impt to know PD1 is receptor on T cell and pdl1 is the ligand on tumor cells or other cells

Answer 149

CD28, OX40, GITR, ICOS, CD137, CD27, CD40L, and CD122 upregulat T cell

Answer 150

PD-1 and CTLA-4 are expressed primarily on T cells and NK cells, whereas PD-L1 is expressed by myeloid cells (monocytes, macrophages, and dendritic cells) and by certain tumor cells by inhibiting this axis you block the normal inhibition by PDL1 of T cells

Answer 151

gilvetmab Yervoy (Ipilimumab) targeting CTLA-4 and Keytruda (pembrolizumab) and Opdivo (nivolumab) targeting PD-1, for treatment of four different cancers (melanoma, head and neck cancer, bladder cancer, and Hodgkin lymphoma)

Answer 152

immune suppressive molecule that catalyzes the breakdown of AMP to adenosine in the TME tumors make a lot of adenosine to be immunosuppressive

Answer 153

granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3) IL 8? lead to mdsc release from bone marrow

Answer 154

immune suppression block NK cells via TGFb and down regulation of IL 12 increase Tregs via TGFb and IL10 - block T cells block T cells directly via arginine, iNOS, ROS, and cysteine deprivation inc TAM via IL10 - which then dec NK cells via decreasing IL12 and stimulate tumor angiogenesis and promote metastasis Block dendritic cells via IDO differentiate into macrophages or neutrophils and actively suppress the local antitumor immune responses and promote tumor invasion and metastasis via the production of matrix metalloproteinases (MMPs)

Answer 155

CCL1binds to CCR8 - CCL1 released by TAMS, CAFs, CSC (helps with treg activation recruitment, angiogenesis, proliferation) CCL5 binds to ccr 5- released by tams and CAFs to activate tregs and promote growth/proliferation of tumor

Answer 156

o released by T cells after activations and Activates naïve T cells via JAK/STAT, activates Macs, DC, and b cells, and NK cells o Promotes growth, survival, and differentiation of T-cells o Increases Bcl-2 and stimulates degradation of p27 o Increased production w IFNy and IL-4 from T-cells lots of toxicity as therapy in humans - mild gi tox in dogs with lsa but may not be efficacious made pulmonary mets go away in two dogs. also used in feline fibrosarc and canine melanoma and was safe and effective

Answer 157

o Secreted by DCs and macrophages and B cells, produced in response to TLRs o Promotes Th1 and NK cells o Stimulates activation and IFNy secretion down regulated by MDSC evade immune system therapeutic use cause sig tox in humans reduced tumor volume of 9 out of 11 dogs with mast cell tumors and increases in intratumoral IFN-γ and antiangiogenic effects in nine dogs with various cancers, and in six dogs treated with concurrent metronomic chemotherapy- no significant clinical responses were observed in these studies

Answer 158

o Inhibitory/anti-inflammatory/ pro cancer cytokine, secreted by T-regs and MDSC o IL-10 -> JAK1 and TYK2 to activate STAT3 o Inhibits macs and DCs o Inhibits IL-12 production o Inhibits co-stimulators

Answer 159

o IFN alpha, beta, gamma – pro-inflammatory, anti-angiogenic o IFN gamma- secreted by Ts and NKs – activation of macrophages o IFN alpha – direct anti-tumor effects - anti-angiogenic, induces TSGs, downregulates oncogenes, inhibits proliferation of tumor cells

Answer 160

Specialized DCs will ingest cells that are infected w virus and present the viral protein to a CD8 T cell

Answer 161

o CD40L on T cells recognizes CD40 on DCs and Macs -> B cell vaccine in dogs- CD40 o IFNy from T cells – activates macs o Chemokine receptor CCR7 on DCs

Answer 162

CD3+/-, CD5, CD4, and CD8+ in dogs, also NKp46 Innate cytotoxic cells – kill by perforin and granzymes and ADCC Secrete IFNy - activates macrophages Recognize cells that don’t express MHC I

Answer 163

costim mol on T cells binds to CD40 on apcs to enhance IL12 secretion and enhance B7 CD40 is expressed on B cells and interacts with CD40L on T cells to stimulate NFkB and AP1 and B cell proliferation target of b cell vaccine rituximab is cd20

Answer 164

o KIRs o C-type lectins o CD16 - binds Ag-Ag complexes for Antibody-dependent cellular cytotoxicity

Answer 165

B7-1 (CD80) and B7-2 (CD86) – expressed on activated APCs, are co-stimulatory bind to ctla4 CD28 – TCR CD40L on T cells binds to CD40 on APCs for activation CD4 and CD8 – bind MHC and interact w TCR ITAMS that are linked to CD3 delta chains – involved w activation T cells activated by IL-2 IL-12 – promotes T cell differentiation

Answer 166

Ig Receptor + CD40 costimulator molecule CD21 – recognizes Ab and activates Heavy chain – switches isotype V region – variable – antigen binding C region – constant region – what switches isotype, effector CD22 – inhibitor molecule

Answer 167

o C region of the heavy chain ## Footnote The domains include an antigen-binding fragment (Fab) domain that binds to antigens and a crystallizable fragment (Fc) domain that binds to host sensors that deploy effector functions

Answer 168

On T-cells – checkpoint inhibitor that will allow for immune recognition of tumor cells – binds B7 to inhibit T cell activation More important for CD4+ inhibition

Answer 169

On T-cells – inhibits activation of effector T cells when binds to PD-L1 on APCs or tumors More important for CD8+ inhibition

Answer 170

Membrane – CD4, CD25 Intracellular – FoxP3

Answer 171

Common myeloid progenitor cell > monocytes > CD1 (Langerhans, Follicular, Myeloid DC) > present to Th1 and Th17 Common myeloid progenitor cell > DC2 (plasmacytoid DC) > present to Th2 Histiocytoma - E-cadherin+ Histiocytic sarcoma (interstitial DCs) - CD1, CD11c, MHCII+ Reactive histiocytosis (activated interstitial DCs) - CD4, Thy1 + Hemophagocytic HS - CD11d +

Answer 172

live attenuated strain of mycobacterium Bovis infused into bladder to prevent relapse of tcc recruitment of neutrophils and their ability to promote urothelial cell turnover

Answer 173

inject into tumors and eat the necrotic and hypoxic cells and induced inflammation Phase I clinical trial, VNP20009 was administered to dogs with a variety of malignant tumors. In this study, 41 dogs received intravenous infusions of VNP20009 either weekly or biweekly at escalating doses. Fever and vomiting were reported as dose-limiting toxicities. Bacterial colonization was seen in approximately 40% of dogs and significant clinical responses observed in 15% of patients, with an over- all rate of 37% of dogs experiencing either a transient response or stable disease.

Answer 174

NOD2 receptor agonist, that when encapsulated in a liposome (L-MTP-PE) can efficiently activate monocytes and macrophages to produce proinflammatory cytokines, such as IL-1α and -β, IL-6, IL-7, IL-8, IL-12 and TNF-α used in human osa dogs receiving L-MTP-PE after limb amputation had a median survival time (MST) of 222 days whereas dogs that received placebo had a MST of 77 days. L-MTP-PE after treatment with cisplatin had a MST of 14.4 months ver- sus 9.8 months in dogs that received cisplatin only. Interestingly, only 73% of dogs receiving L-MTP-PE developed metastatic dis- ease compared with 93% in the cisplatin-only group. However, in a second trial, these investigators saw no significant survival advantage in dogs with OSA that received L-MTP-PE concurrently with cisplatin. cisplatin may have attenuated immune effects Dogs that received L-MTP- PE with chemotherapy after splenectomy had a MST of 9 months versus 5.7 months seen with dogs receiving chemotherapy alone. In another study only dogs with stage I oral melanoma that received L-MTP-PE had an increased survival over placebo- treated dogs

Answer 175

CpG oligonucleotides bind to TLR 9 stimulate the immune system largely through induction of NK cell activity and release of IFN-γ especially when complexed with cationic liposomes - cationic lipid–DNA complexes (CLDCs) may work as a standalone immune therapy dogs with osa inc ST compared to historic control RR in sts 15%

Answer 176

viruses capable of replicating in and lysing tumor cells Adenoviruses that have undergone genetic modification of their early genes, 1A (E1A) and 1B (E1B), preferentially target rapidly dividing tumor cells and have been used to target canine OSA cells also looked at pox virus, canine distemper virus, Newcastle disease virus, vesicular stomatitis virus (VSV), that expresses IFN-β and the sodium iodide symporter (NIS)

Answer 177

imiquimod - topical therapy meningioma with vaccine cats with scc

Answer 178

- stim Nk cells and promoted T cell proliferation - in vitro, recombinant IL-15 could expand canine NK cells and could cause expansion of lymphocytes in peripheral blood when administered to dogs intravenously. better bc: (1) it does not cause activation-induced cell death of CD4+ T cells after prolonged periods of exposure, but sustains T-cell proliferation (2) it plays a critical role in CD8+ T cell memory forma- tion and maintenance (3) unlike IL-2, it does not appear to play a role in the development of Tregs

Answer 179

proteins are other molecules that are either unique to cancer cells or significantly more abundant in cancer cells compared with normal cells - oncogenes, oncofetal proteins, and cancer testes antigens

Answer 180

- made from cell lines with similar tumor types - made directly from the patients tumor -made from other species - melanoma vax = huTyr

Answer 181

made by lethally irradiating tumor cells and/or tissues vs mechanically disrupting the tumor cells and/or tissues studies have added hGMCSF as adjuvant to help stem immune system

Answer 182

advantages 1. Off-the-shelf availability 2. Potential for broader immune response 3. Cost-effective Disadvantages: 1. Risk of rejection: Allogeneic vaccines carry a risk of inducing immune responses against the donor's tissue, leading to rejection. 2. Limited personalization 3. Efficacy can vary depending on the individual's immune response and tumor characteristics Allergic reactions: Management with antihistamines or corticosteroids. Autoimmune reactions: Treatment with immunosuppressive drugs, such as corticosteroids or TNF-alpha inhibitors.

Answer 183

Advantages: 1. Personalized therapy 2. Low risk of rejection 3. Potentially higher efficacy Disadvantages: 1. Time-consuming 2. Costly 3. Limited availability 4. tumor may change so the target may not be functional in the cancer AEs: 1. Injection site reactions: Typically managed with local measures like ice packs and analgesics. 2. Flu-like symptoms: Managed with supportive care, such as rest, fluids, and over-the-counter pain relievers. 3. Autoimmune reactions: Treated with immunosuppressive agents like corticosteroids or TNF-alpha inhibitors.

Answer 184

Advantages: 1. Wide array of antigens 2. Possibility of overcoming immune tolerance: Since xenogeneic antigens are foreign, they may overcome immune tolerance mechanisms. 3. Availability Disadvantages: 1. Immunogenicity concerns: Xenogeneic vaccines may induce strong immune responses, potentially leading to adverse reactions. 2. Safety concerns: There's a risk of cross-species transmission of pathogens or zoonoses. Adverse Events: 1. Immune-related adverse events (irAEs) 2. Allergic reactions: Treated with antihistamines or corticosteroids. 3. Pathogen transmission: Requires monitoring and appropriate treatment if cross-species transmission of pathogens occurs.

Answer 185

advantages: 1. Targeted delivery: Bispecific antibodies conjugated with bacteria can deliver therapeutic agents specifically to tumor cells, minimizing off-target effects. 2. Enhanced tumor penetration: Bacteria can penetrate deep into tumor tissues - into the necrotic hypoxic parts 3. Immune stimulation Disadvantages: 1. Risk of infection 2. Limited tumor selectivity: While efforts are made to target tumor cells specifically, there's a risk of non-specific binding to healthy tissues. 3. Immunogenicity: The use of bacteria can induce immune responses, leading to neutralization of the therapeutic effect or adverse reactions. Indications: 1. Solid tumors: including colorectal, pancreatic, and lung cancers. Refractory tumors Adverse Events: Infections Allergic reactions

Answer 186

Advantages: 1. Targeted chemotherapy delivery: Bispecific antibodies conjugated with chemotherapy drugs deliver cytotoxic agents directly to tumor cells, sparing healthy tissues. 2. Reduced systemic toxicity 3. Enhanced potency: Conjugation of chemotherapy drugs with bispecific antibodies can enhance their potency against tumor cells. Disadvantages: 1. Immunogenicity:increase the immunogenicity of chemotherapy drugs. 2. Limited tumor selectivity: There's a risk of non-specific binding to healthy tissues, leading to off-target effects. 3. Resistance development: Tumors may develop resistance to the chemotherapy drugs used in the conjugates. Indications: Solid tumors: including breast, ovarian, and lung cancers. Refractory tumors: AEs Hematologic toxicity: Gastrointestinal toxicity: Immunogenic reactions:

Answer 187

advantages: 1. Immune stimulation: Cytokine-conjugated bispecific antibodies can stimulate immune responses against tumor cells. 2. Targeted delivery of cytokines: Direct delivery of cytokines to specific tumor sites minimizes systemic toxicity. 3. Enhanced anti-tumor activity Disadvantages: 1. Cytokine toxicity: Cytokine release syndrome (CRS) and other cytokine-related toxicities can occur. 2. Limited tumor selectivity: There's a risk of non-specific binding to healthy tissues, leading to off-target effects. 3. Immunogenicity: Conjugation with bispecific antibodies may increase the immunogenicity of cytokines. Indications: Solid tumors and hematologic malignancies: including melanoma, renal cell carcinoma, and leukemia. Immunotherapy-resistant tumors Adverse Events: 1. Cytokine release syndrome (CRS): Managed with tocilizumab (IL-6 inhibitor) or corticosteroids. 2. Immune-related adverse events (irAEs): NHS-IL12- targets necrotic areas of the tumor and is linked to IL-12. increased infil- tration of CD8+ T cells

Answer 188

Using humanized antibodies improves antibody-dependent cell-mediated cytotoxicity (ADCC), improves antibody stability, and decreases immunogenicity of the antibody itself -omab are murine based, -ximab and -zumab are chimeric, and -umab are humanized versions of the antibodies canonized antibody that targets canine IL-31, which is involved in allergic skin disease and pruritus in dogs - cytopoint

Answer 189

cells are collected from a cancer patient, expanded, and activated in culture and then transferred back into the patient enhancement of tumor-specific T cells, it is labor intensive, expensive, and time-consuming; thus its use is limited in both human and veterinary patients lymphodepletion before ACT may overcome immunosuppression or isolating CD4 only CD4+ T cells are capable of activating both innate immune cells and CD8+ T cells

Answer 190

CAR-T cells are generated via transfection of antibody genes specific for a tumor target into a T cell engineered T cells specifically to the tumor tissue. Success with this technol- ogy has been seen in humans with chronic lymphocytic leuke- mia where the T cells target the CD19+ B cells some new research

Answer 191

culturing PBMCs in high concentrations of IL-2, thus selecting for a population of cells with potent tumor cell lysis ability limited to studies of cats with FeLV or FIV not successful in humans

Answer 192

tumor-infiltrating lymphocytes (TILs), when expanded using IL-2, exhibit potent cytolytic activity that is many folds higher than LAK cells against tumors in both a specific and nonspecific way considered the best source of T cells for ACT use in human medicine is limited bc time of isolation, the tumor they were isolated from, and the functional state of the cells when isolated not used in vet med

Treatment Modalities LC Flashcards

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