Faculty Questions Flashcards
Why is high dose cyclophosphamide used for bone marrow ablation/conditioning phase prior to autologous stem cell transplantation?
- Spares stem cells = not completely myeloablative
- Causes release of proteases and the cleavage of key adhesion molecules (e.g. VCAM-1 and CXCR4)–> release of hematopoietic stem cells into the periphery
- Spares platelets
- Highly immunosuppressive
- Little nonhematologic side effects compared to other chemos (e.g. not as GI toxic as other chemos)
What cell type are osteoclasts?
Macrophage lineage
Kiupel MCT grading criteria for high grade MCT
Any one of the following:
- ≥7 mitotic figures/10hpf (i.e. MI ≥ 7)
- ≥3 multinucleated (= ≥3 nuclei) cells/10hpf
- ≥3 bizarre nuclei/10hpf
- karyomegaly (at least 10% of cells vary by 2x)
What are the criteria of malignancy considered in Kiupel MCT grading scheme?
- mitotic index
- multinucleation
- bizarre nuclei
- karyomegaly
What parameters are considered in Patnaik grading scheme
- location
- cell morphology
- nuclear morphology
- architecture/cellularity
- mitotic figures
- edema and necrosis
Patnaik grade I MCT:
- location
- cell morphology
- nuclear morphology
- architecture/cellularity
- mitotic figures
- edema and necrosis
- location = dermis
- cell morphology = round
- nuclear morphology = round, condensed chromatin
- architecture/cellularity = rows/groups
- mitotic figures = none
- edema and necrosis = minimal
Patnaik grade II MCT:
- location
- cell morphology
- nuclear morphology
- architecture/cellularity
- mitotic figures
- edema and necrosis
- location = infiltrates the SQ +/- musculature
- cell morphology = round to ovoid; finer granules
- nuclear morphology = round to indented; some double nuclei
- architecture/cellularity = thin fibrovascular stroma
- mitotic figures = rare (0-2/hpf)
- edema and necrosis = areas of diffuse
Patnaik grade III MCT:
- location
- cell morphology
- nuclear morphology
- architecture/cellularity
- mitotic figures
- edema and necrosis
- location = replaces SQ and deep tissue
- cell morphology = pleomorphic; indistinct granules
- nuclear morphology = indented; common binucleation
- architecture/cellularity = packed sheets
- mitotic figures = common (≥3/hpf)
- edema and necrosis = common
What is the published total dose for feline nasal LSA?
> 32 Gray
Genes of four common DNA repair disorders due to genetic deficiencies that are associated with clinical radiation sensitivity
- ATM
- FA gene complex
- NBS1
- LIG4
% of silken windhounds with MDR mutation
30%
DNA repair disorder associated with ATM gene deficiency and associated deficiency
- disease = ataxia telangiectasia (A-T)
- deficiency = signal transduction
DNA repair disorder associated with FA gene complex deficiency and associated deficiency
- disease = Fanconi anemia (FA)
- deficiency = damage recognition and HR
DNA repair disorder associated with NBS1 gene deficiency and associated deficiency
- disease = Nijmegen breakage syndrome
- deficiency = damage recognition
DNA repair disorder associated with LIG4 gene deficiency and associated deficiency
- disease = DNA ligase IV deficiency
- deficiency = NHEJ
Hallmarks of cancer
SARCOMA GIME:
- S - self-sufficiency of growth signaling
- A - apoptosis evasion
- R - resistance to anti-growth factor signaling
- Co - continuous replication (immortality)
- M - metastasis
- A - angiogenesis
- G - genomic instability
- I - inflammation
- M - metabolic deregulation
- E - evasion of the immune system
Flow markers for thymomas
CD4+ CD8+
Flow markers for T cell lymphoma/leukemia
CD4+ CD5-
% of feline renal transplant cats that develop neoplasia
25% develop lymphoid neoplasia
*higher than what is seen in transplants with humans
Reason for increased risk of lymphoid neoplasia in renal transplant cats
Cyclosporine–>immunoediting
*NOTE: cyclosporine and transplants in humans and cats = risk factors for cancer
Which metastasizes to bone more frequently: prostatic carcinoma vs. UCC
Prostatic carcinoma
What is the size cutoff for canine adrenocortical that is indicative of malignancy?
> 2cm
Grading criteria for canine mammary tumors
- tubule formation
- nuclear pleomorphism
- mitoses/10hpf (MI)
% of incidentalomas seen with ultrasound? CT?
- ultrasound: 4%
- CT: 9.3%
Morphologic (histopath) criteria significantly associated with adrenocortical carcinomas
- > 2cm diameter
- peripheral fibrosis
- capsular invasion
- trabecular growth pattern
- hemorrhage
- necrosis
- single-cell necrosis
Morphologic (histopath) criteria significantly associated with adrenocortical adenomas
- hematopoiesis
- fibrin thrombi
- cytoplasmic vacuolation
Histologic grading system for canine mammary carcinoma
- tubule formation
1: >75%
2: 10-75%
3: <10% - nuclear pleomorphism
1: uniform/regular small nucleus, occasional nucleoli
2: moderate anisokaryosis, hyperchromatic nucleus, presence of nucleoli
3: marked anisokaryosis, often with ≥1 prominent nucleoli - MI
1: 0-9
2: 10-19
3: ≥20 - points
3-5: grade I/low grade
6-7: grade II/intermediate grade
8-9: grade III/high grade
Histologic grading system for canine mammary carcinoma
- tubule formation
1: >75%
2: 10-75%
3: <10% - nuclear pleomorphism
1: uniform/regular small nucleus, occasional nucleoli
2: moderate anisokaryosis, hyperchromatic nucleus, presence of nucleoli
3: marked anisokaryosis, often with ≥1 prominent nucleoli - MI
1: 0-9
2: 10-19
3: ≥20 - points
3-5: grade I/low grade
6-7: grade II/intermediate grade
8-9: grade III/high grade
% of dogs with MCTs with GI ulceration based on endoscopy
> 80%
**need to find paper
Hypocholesterolemia may be indicative of what neoplasm? What % of dogs with this neoplasm exhibit hypocholesterolemia?
- hemophagocytic histiocytic sarcoma
- 69%
Immunophenotypes of histiocytic proliferative diseases in dogs and cats
Withrow Table 34.4
Neoplasms associated with paraneoplastic eosinophilia? Mechanism?
- MCT
- T cell lymphoma
- others: dogs - oral fibrosarcoma, mammary carcinoma, leiomyosarcoma; cats - oral SCC, bladder TCC
- MOA: production of IL-5
Define overall response rate
CR + PR
Define clinical benefit
CR + PR + SD
Define progression free survival (PFS)
= date of randomization to date of first progressive disease
Define best overall response rate (BORR)
= the proportion of dogs with CR or PR at any time, based on target, nontarget, and new lesions in relation to total number of dogs; i.e. the best response recorded from the start of the treatment until disease progression/recurrence
Difference between ORR and BORR
BORR is overall course of the study?
***LOOK UP better explanation
Criteria needed for FDA approval of a drug
Prove that the drug is
- Safe
- Efficacious (superior efficacy compared to the standard of care)
Univariate prognostic indicator in a lot of Tanovea papers
Sex - females do significantly better
% of ALLs that are CD34+
37-76%
Negative prognostic factor
CD34
= surface antigen on hematopoietic PROGENITOR cells that is NOT normally on mature leukocytes
Chemotherapeutic in the same family/has the same mechanism as Tanovea that you can add to CHOP to improve LSA outcome
Cytosar (cytarabine)
MOA of rabacfosadine (Tanovea, VDC1101, GS-9219)
= double prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl) guanine (PMEG)
MOA = preferentially targets lymphoid cells and inhibits DNA polymerases–>inhibition of DNA synthesis (= S phase specific)
% of OSA patients that develop hypertrophic osteopathy (HO)
5-29%
% of dogs with thyroid neoplasia that are:
- euthyroid
- hypothyroid
- hyperthyroid
- euthyroid: 55-60%
- hypothyroid: 30%
- hyperthyroid: 10-15%
M1 macrophage phenotype
Antitumor
M2 macrophage phenotype
Protumor–>progression and tissue remodeling via Th2 secretion of IL-4 and IL-13
MOA of metronomic chemotherapy
- inhibit tumor angiogenesis
2. suppress Tregs
% of canine inflammatory mammary carcinomas with coagulopathies
21%
Timeframe of urethral stricture post-RT for UCC/TCC
3-6 months post-RT
