Exam 4: Neoplasia 2 Flashcards
What are the direct effects of neoplasia?
Replace normal tissues Compression of neighbor tissue Obstruction or rupture Disrupt anatomical relationships Vascular compression/infiltration- infarction --> necrosis Erosion of vessels- rupture, hemorrhage
What are the paraneoplastic effects of neoplasia in the systemic system?
Anorexia/cachexia, fever
What are the paraneoplastic effects of neoplasia in the endocrine system?
Hypercalcemia
Hypoglycemia
Hyperestrogenism
Thyrotoxicosis
What are the paraneoplastic effects of neoplasia in the skeletal system?
Myelofibrosis
Hypertrophic osteopathy
What are the paraneoplastic effects of neoplasia in the vascular/hematopoietic system?
Leukocytosis
Leukopenia
Anemia
DIC
What are the paraneoplastic effects of neoplasia in the neruologic system?
Myasthenia gravis
Peripherial neuropathy
What are the paraneoplastic effects of neoplasia in the cutaneous system?
Alopecia
Nodular dematofibrosis
What can paraneoplastic effects facilitate?
Early tumor detection
What is cachexia?
Weigh loss and debility associated with cancer
Muscle and fat are lost
No compensatory decrease in basal metabolism
Added caloric intake does bot alleviate
TNF-α, IL-1, IL-6
What do thyroid carcinomas cause?
Hyperthyroidism
What do pancreas islet cell carcinomas (insulinomas) of β cells cause?
Hyperinsuilinemia/hypoglycemia
What is ectopic hormone production?
Production of hormone not normally found in tissue of origin
This is a paraneoplastic effect
What causes hypercalcemia?
Parathyroid hormone-related peptide: humoral hypercalcemia of malignancy
Adenocarcinoma of the apocrine glands of the anal sac
Lymphoma
Multiple myeloma
How does Parathyroid hormone-related peptide cause hypercalcemia?
It mimics the function of PTH, inducing calcium release from bone, reabsorption from kidneys, and absorption from intestine
What are the hematopoietic/vascular paraneoplastic effects?
Eosinophilia, neutrophilia, basophilia, mast cells- cytokines
Anemia- chronic disease, blood loss, bone marrow invasion, hemolysis
Thrombocytopenia- immune mediated, hemangiosarcoma
Gastric mast cell tumors- histamine release, ulcerations
What are the hallmarks of cancer?
Avoiding immune destruction Evading growth suppressors Enabling replicative immortality Tumor-promoting inflammation Activating invasion and metastasis Genomic instability Inducing angiogenesis Resisting cell death Deregulating cellular energetics Sustaining proliferative signaling
What are heritable alterations to neoplasia?
A progressive accumulation of genetic and epigenetic abnormalities
What do heritable alterations lead to?
Cell growth, death, differentiation, DNA repair
What are cancer phenotypes due to?
DNA mutations
Epigenetic changes
Chromosomal alterations
What is karyotype?
Number and arrangement of chromosomes
What are telomeres?
Terminal DNA sequences that protect cells from DNA damage
What are molecular determinants of neoplasia?
Driver mutations (oncogenes, tumor suppressor genes)
Multiple changes needed for neoplasia to occur
Proto-oncogenes
Mutation leads to overexpression (oncogene) and cells become less responsive to inhibitory signals
What are proto-oncogenes?
Normal genes that regulate growth
What is a tumor suppressor gene?
Genes that control cell cycle, apoptosis, DNA repair
What is p53?
A tumor suppressor gene that is commonly mutated in cancer
What happens to a cell with a normal p53?
DNA damage increases p53 levels
Transcription dependent and independent p53 effects on targets
p21 is upregulated causing G1 to arrest, GADD 45 directs DNA repair or causes apoptosis with no DNA repair, and BAX upregulation causes apoptosis
What happens to a cell with p53 mutation or loss?
DNA damage
No p53 activation
No cell cycle arrest, DNA repair, sensescence, or apoptosis
Mutant cells are produced
Expansion and additional mutations leading to a malignant tumor
What causes carcinogenesis?
Chemicals
What is direct carcinogenesis?
Effective in causing damage in the form encountered
What is indirect carcinogenesis?
Require metabolic activation in the body
What is radiation?
A complete carcinogen (can initiate and promote)
What are examples of oncogenic viruses?
Feline leukemia virus (leukemia/lymphoma)
Bovine leukemia virus (leukemia/lymphoma)
Feline immunodeficiency virus (lymphoma)
Poxviruses
What are round cell tumors?
Histiocytoma Cutaneous lymphoma Plasmacytoma Mast cell tumors Transmissible venereal tumors
What are histiocytomas?
Only in dogs (most common skin tumor) Young Rapid growth, button-like Skin around head most common Spontaneous regression Round to oval cells Oval nuclei, fine chromatin Abundant pale blue cytoplasm, few vacuoles Ulcerated/alopecici Junctional activity/epitheliotropism
Describe cutaneous lymphoma
Can be epitheliotropic (mycosis fungoides) or nonepitheliptrophic
B and T cells
Large cells, abundant cytoplasm, nucleoli
Describe plasmacytoma
Benign, older dogs, head feet
Rarely functional
Round cells, dense, chromatin, 1-3 nuclei
Abundant blue cytoplasm, prominent Golgi zone
Describe mast cell tumors
Nodules, well circumscribed or poorly defined/edematous Solitary or multiple Older dogs All are potentially malignant Dermal (graded) Subcutaneous Eosinophils Abundant metachromatic cytoplasmic granules
What is an example of transmissible tumors?
Transmissible venereal tumor of dogs
Describe transmissible venereal tumor of dogs
Direct physical spread/contact
Cells in all tumors have similar genetic and cytologic character that differ from the host (dog)
A single tumor that disseminated to multiple hosts
Which cells produce tumors?
Undifferentiated stem cells
How many cells does it take to produce a tumor?
1
What are the angiogenesis factors?
Vascular endothelial growth factor
TGF-β
Angiogenin
How do RNA viruses make tumors?
RNA viruses transcribe RNA backwards into DNA using reverse transcriptase. They insert that DNA copy of the viral genome in the host DNA - a provirus. They steal the genes from the cell and turn them into oncogenes or tumor genes
How do DNA viruses make tumors?
No stolen oncogenes are associated with DNA viruses, but they may carry genes that code for transforming genes
What is carcinomatosis?
The diffuse seeding or spread via lymphatics of carcinomas on serosal surfaces
