Ch 25 Onocology Flashcards
Generally speaking, what alterations results in the formation of cancer?
Activation of tumour-promoting factors via oncogenes
or
Loss of innate tumour inhibitory effects via tumour suppressor genes (e.g. p53 “guardian of the genome”)
What are the phenotypic characterisitics of cancer cells?(6)
Self-sufficiency in growth signals
Insensitivity to anti-growth signals
Tissue invasion and metastasis
Limitless replicative potential > Both human and canine neoplastic tissues have been shown to exhibit high levels of telomerase activity
Sustained angiogenesis
Evasion of apoptosis > Lack of apoptosis is considered a hallmark of carcinogenesis and a key characteristic of cancer cells
tumor suppressor gene p53
Oncogenes can be activated by
chromosomal translocation
gene amplification
point mutations
viral insertions
Point mutations can be induced by ionizing radiation and chemical carcinogens or may involve mutations in proto-oncogenes such as K-ras, the epidermal growth factor receptor, and the c-kit growth factor receptor
cell division - what the main phases and checkpoints?
interphase
- starts with doubling of genetic material
- GI, G2, and S phases.
- GI and G2 serve as checkpoints that ensure normal DNA synthesis and cell division
- restriction point = critical checkpoint for continued progression of the cell cycle
- S phase = synthesis/doubling of new DNA
mitosis (M)
- division of the doubled genetic material into two daughter cells
- Regulation via proteins called cyclin-dependent kinases
Initiation, promotion, and progression of a cell toward a malignant phenotype
applied to genetic factors leading to cancer formation, as well as to chemical carcinogenesis.
Which forms of neoplasia have confirmed, true genetic heritability in animals?
Osteosarcoma of Scottish Deerhounds
Renal cystadenocarcinoma in GSD
Nodular dermatofibrosis in GSD
List some biologic carcinogens in animals
FeLV and lymphoproliferative diseases
Feline sarcoma virus and FSA (must also be infected with FeLV)
Papillomavirus in puppies. Papilloma can klead to formation of SCC in rare cases
Spircocerca lupi and viral oesophageal sarcomas in dogs
Transmissible venereal tumour by direct cellular transmission
List some physical carcinogens (5)
Asbestos and mesothelioma in humans
Injection-site sarcoma in cats
Post-trauma ocular sarcomas
Microchip-associated FSA
TPLO metallurgy and canine OSA
List the four possible mechanisms which can transform genes into oncogenes
Oncogenes are mutated versions of normal genes that drive the formation of cancer. The normal counterparts of these genes, called protooncogenes, become transformed by
- Retrovirus-mediated transduction
- Translocation mutation
- Amplification
- Proviral insertion
In neoplasia, such as canine mast cell tumor, internal tandem duplication mutations lead to a constitutively active c-kit receptor tyrosine kinase receptor (i.e., ligand binding by stem cell factor is no longer needed for proliferative activity). The c-kit receptor falls under a group of growth factor receptors called platelet-derived growth factor receptors (PDGFRs).
Translation of oncogenes leads to transcription of key proteins such as….
Growth factors
Growth factor receptors
Cytoplasmic kinases/Ras
Transcription factors
Antiapoptotic proteins
What are Ras oncogenes
Lead to production of membrane-associated proteins that have a key role in cell signalling leading to activation of various cell-proliferative pathways
What are the two forms of tumour suppressor genes
Gate keepers - Inhibit growth while promoting cell death (eg. p53)
Care takers - Ensure DNA repair while maintaining genomic stability
p53 is one of the most common mutations. It is crucial for normal cell cycle and serves as a checkpoint for entry into apoptosis
Three major routes of metastasis are
(1) hematogenous,
(2) lymphatic, and
(3) direct seeding.
In general, how do carcinomas, round cell tumoura and sarcomas metastasise?
Carcinomas and round cell tumours via lymphatics
Sarcomas via haematogenous routes
How do metastatic cells survive in their new environment?
Progressive hypoxia due to proliferation (need to be 100-200mcm from capillary bed for continued growth)
Hypoxia activates hypoxia-induced factor (HIF1alpha), an oxygen-dependant transcription factor
HIF-1a induced transcription of tumour-derived growth factos such as VEGF
Growth factors lead to endothelial recruitment and eventual organisation in capillaries
Tumor staging is a diagnostic process in which the extent of disease progression from the primary site is determined. The diagnostic tests indicated are dictated by tumor type, so staging is often performed after the tumor type has been determined.
What factors need to be considered when choosing a biopsy?
Invasiveness of procedure
Potential for haemorrhage
Seeding of tumour cells
Will it change the treatment plan
incisional biopsy
perform if knowing the specific behavior of a tumor may affect sx treatment or when knowing the identity of the tumor would alter the treatment plan.
excisional biopsy
The main advantage > biopsy and gross tumor removal are performed in a single procedure. disadvantage> if the tumor is highly invasive
frozen histologic sections can be performed quickly on samples obtained at the time of surgery, and this information can be used when making intraoperative decisions; however, frozen sections can be prone to sampling error and tissue artifacts.
imaging
radiography
three-view (ventrodorsal, left lateral, and right lateral projections) thoracic radiographs to evaluate for pulmonary metastatic
Ultrasonography
evaluation of intra-abdominal neoplasia, particularly hepatic, adrenal, and urogenital tumors, and sublumbar node metastasis.
Guide needles and needle-core biopsy for tissue sampling
CT
evaluation of primary tumors of the axial skeleton, particularly skull, vertebral, and pelvic tumors, and for evaluation of primary and metastatic intrathoracic tumors
3D reconstructions can be manipulated at a computer workstation to help the surgeon
CT-guided biopsy
MRI
preferred for tumors of the central and peripheral nervous system and perhaps intra-abdominal organs.
determining the proximity of tumors to important neurovascular structures ((STIR) MRI)
How can nuclear scintigraphy be applied to dogs with OSA? What substance is used for this?
Technetium-99m hydromethylene diphosphate used for a whole body scan to detect aymphtomatic synchronous or asymptomatic lesions
In one study, 7.8% of 399 dogs with appendicular OSA were diagnosed with a second asymptomatic lesion. Not good candidates for amputation
List some uses of nuclear scintigraphy
Technetium-99m hydromethyl diphosphate for OSA to detect multiple lesions or to define margins for limb-sparing
Technetium-99m diethylenetriaminepentaacetic acid for GFR prior to nephrectomy
Technetium-99m for thyroid tumours to identify metastatic or ectopic disease
Indium-111 pentetreotide (somatostatin receptor scan) to identify primary and metastatic lesions in dogs with functional insulinomas
What is a PET-CT?
What are its limitations?
A radiopharmaceutical (F-fluorodeoxyglucose FDG) is used with is transported into and trapped inside tumour cells because it is not utlised in the glycolic pathway. Signal is higher in tumour cells as they have a higher uptake of glucose
Limitations
- Not all tumours will have increased uptake
- Non-specific (inflammation reacts similarly)
- Not readily available
What size metastatic lesions can be seen on thoracic radiographs and CT?
6mm on radiographs
1mm on CT
What are the major potential side effects of doxorubicine and cisplatin?
Doxorubicine can cause cardiotoxicity
Cisplatin can cause nephrotoxicity
What are the 4 categories of tumour excision?
surgical dose
Debulking
Marginal
Wide
Radical
Perioperative Management
Comorbid Conditions
Chemotherapy, radiation therapy, and/or surgery can be altered, incorporated, or eliminated on the basis of comorbid conditions
Pain and Analgesia
Tumor-associated pain
Wide and Radical Resections
provides the best chance for cure
considered curative-intent surgeries because the intention is to resect both macroscopic and microscopic disease, including biopsy tracts, and thus prevent local tumor recurrence and improve overall survival times
evidence suggests that tumor size also influences the extent of microscopic tumor extension, with larger tumors of the same histologic type having greater microscopic extension and hence requiring larger margins than smaller tumors. 28 Margins are three-dimensional; hence, lateral and deep margins must be considered when planning surgical resections of tumors
Deep margins are determined by natural tissue barriers because deep margins (1 to 3 cm) may not be possible
> muscle fascia
> cartilage
> bone
are resistant to neoplastic invasion and provide a good natural tissue barrier
Radical resection, which is defined as the removal of an entire tissue compartment
The deep margin is the most common site of failure.