Term
| What percentage of all dogs die of cancer? What percentage of those aged >10 years? |
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Definition
| 23% of all dogs; 45% of those aged >10 |
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Term
| What is paraneoplastic syndrome? Example(s)? |
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Definition
| A collection of signs/symptoms that often present with cancer. Certain types of cancer have characteristic concurrent signs, which may include endocrine, hematologic, or dermatologic abnormalities. E.g. lymphoma and anal sac adenocarcinoma often present with hypercalcemia due to PTHrp released from tumor cells, which results in Ca++ release from bone. |
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Term
| What is one way to characterize/categorize neoplasia based on standard histologic examination (i.e. H&E stain)? |
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Definition
Tumor cell morphology:
1) Mesenchymal (spindle cell or round cell)
2) Epithelial or glandular (based on how cells cluster - into acini or tubules) |
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Term
| What is a way to characterize neoplasia based on immunohistochemistry? |
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Definition
| Stain for specific tumor cell markers such as lymphoid cell markers, cytokeratin, vimentin |
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Term
| What are the 7 histologic criteria differentiating benign from malignant neoplasia? |
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Definition
1) Demarcation from surrounding tissue (clear borders?)
2) Differentiation (are the cells organized into recognizable structures such as acini, cords, etc., or don't they resemble normal tissue at all?)
3) Pleomorphism (do the cells all look the same, or are there various types - indicating mutation?)
4) Mitotic rate + other indicators of growth
5) Necrosis
6) Inflammation
7) Molecular diagnostics (aberrant proteins, mutations - seen with special stains?) |
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Term
| Describe a typical benign tumor. |
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Definition
| Well-demarcated, well-differentiated, with little pleomorphism, mitotic figures, necrosis. |
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Term
| What are the principal targets of genetic damage in neoplastic cells? |
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Definition
| Regulatory genes (such as p53, etc.) |
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Term
| What are the 2 basic sources of genetic damage to cells? |
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Definition
1) acquired (e.g. UV, chemical, endogenous agents such as reactive oxygen species)
2) inherited (mutations in germ line) |
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Term
| Can tumors be described as a clonal population? |
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Definition
| Maybe...all tumor cells are thought to originate from a single precursor cell, and yet mutations may continue to occur so that not all progeny are identical. In certain tumors (such as devil facial tumor), all cells in all tumors are identical (same karyotype) - thought to result from allograft of one original tumor. |
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Term
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Definition
| Fibrous response to a tumor: surrounds tumor. |
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Term
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Definition
| Spread of carcinoma in body cavity: appears as nodules on serosa. |
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Term
| General gene types/gene products involved in oncogenesis: |
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Definition
1) Proto-oncogenes (mutation = GAIN of function)
2) Tumor regulator genes (mutation = LOSS of function for this and all below)
3) Genes involved in apoptosis
4) Genes involved in DNA repair
5) miRNA (via their role in post-transcriptional gene silencing, esp. of genes involved in cell growth/proliferation) |
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Term
| Steps in normal cell proliferation: |
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Definition
1) Binding of growth factor
2) activation (limited) of GF receptor
3) Signal transduction
4) Nuclear signals inducing DNA transcription
5) Entry into cell cycle |
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Term
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Definition
Gene that promotes AUTONOMOUS cell growth (via oncoproteins). Mutation in oncogene results in GAIN of function.
2 classes:
1) Growth factors
2) Protein kinases |
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Term
| What is a proto-oncogene? |
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Definition
| Normal cell cycle components (eg. GF genes, GF receptor genes) which can become oncogenic when mutated. |
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Term
| What effect does mutant Ras have? |
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Definition
| Active Ras (which promotes gene transcription through MAP kinase pathway) is normally dephosphorylated to become deactivated. The dephosphorylation is blocked by mutant Ras so it is always "on." |
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Term
What are all the following:
1) TGF-B receptor
2) NF-1
3) PTEN
4) SMAD2 and 4 |
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Definition
Non-nuclear factors in growth inhibition.
1) TGF-B receptor (growth inhibitor)
2) NF-1 (cytoskeletal stability)
3) PTEN (signal transduction)
4) SMAD2 and 4 (signal transduction) |
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Term
What are the following:
1) RB1
2) p53
3) WT1
4) BRCA1 and 2 |
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Definition
Nuclear factors involved in growth inhibition
1) RB1 (cell cycle: prevents entry to S phase)
2) p53 (cell cycle: prevents entry to S phase; also involved in apoptosis)
3) WT1 (transcription)
4) BRCA1 and 2 (DNA repair) |
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Term
| Do you need 2 copies of an oncogene in order to get cancer phenotype, or just 1? |
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Definition
| Just 1 (oncogenic allele is dominant because uninhibited growth can occur despite presence of one normal allele). |
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Term
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Definition
| Chemical substance promoting cell division. |
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Term
| Do you need 2 mutated copies of a tumor suppressor gene in order to get cancer phenotype, or just 1? |
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Definition
| 2, since if there is one normal copy, tumor suppression will happen normally and inhibit cancerous growth. |
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Term
| What is neoplastic progression? |
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Definition
| Neoplastic progression results in tumor cell heterogeneity via the evolution and spread of subpopulations of cells that arise as the tumor grows, a process founded on inherent tumor genetic instability. |
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Term
| When speaking of a tumor, what is the growth fraction? |
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Definition
| Proportion of tumor cells that are in the cell cycle and actively dividing. |
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Term
| What is the largest a tumor can grow in the absence of angiogenesis? |
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Definition
| 1-2 mm only! Beyond that, tumors need a blood supply. |
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Term
| What are 2 ways a tumor can stimulate angiogenesis? |
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Definition
1) Act directly on endothelial cells.
2) Stimulate inflammatory cells to promote capillary formation. |
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Term
| What are the steps in a tumor invasion of adjacent tissue? |
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Definition
1) Expression of adhesion molecules (ICAM-1, VCAM-1, MUC18, cadherins, etc.)
2) Expression of proteolytic enzymes
3) Degradation of ECM |
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Term
| What are 4 basic ways tumors can spread, and which tumors characteristically use these methods? |
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Definition
1) Local direct invasion (not metastasis, but characteristic of many malignancies)
2) Lymphatic spread (characteristic of carcinomas)
3) Hematogenous spread (characteristic of sarcomas)
4) Seeding of body cavities (ovarian, colon, melanoma) |
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Term
| What are general characteristics of common sites of metastasis? |
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Definition
1) Lots of blood flow
2) Low pressure blood flow |
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Term
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Definition
| Reversible substitution of one type of fully differentiated cell for another type. It is an adaptation to abnormal environmental changes or new functional demands. |
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Term
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Definition
| Disordered growth or development. May be reversible. |
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Term
| In what general tissue type is cancer most likely? |
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Definition
| Proliferative tissues that normally undergo cell division at a fairly high rate. |
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Term
| Examples of communicable tumors? |
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Definition
| Devil facial tumor (neurectodermal derivative - rarely resolves). Transmissible Venereal Tumor in dog (histiocytic origin - can resolve). |
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Term
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Definition
| Lack of differentiated features. More anaplastic = more aggressive. |
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Term
| What is the TNM staging system? |
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Definition
Defines stage of cancer.
T = size of original tumor
N = number/distribution of regional lymph node metastases
M = number/distribution of distant metastases |
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Term
| What are tumor-associated fetal antigens? |
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Definition
| Class of constituents that are normally present during fetal development, absent or not detectable in mature individuals, but present in tumors. |
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Term
| What are some ways cancer cells can evade an immune response? |
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Definition
1) Antigen negative variants
2) Loss or reduction of MHC molecules in order to escape detection by CTLs
3) Lack of co-stimulation prevents sensitization of T cells (may result in T cell anergy or apoptosis)
4) Antigen masking (antigens may be hidden by polysaccharide molecules) |
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