Flashcards in Exam 1: Cancer Deck (64):
Abnormal growth of tissue resulting from loss of response to growth control signals
Cancer of epithelial origin
Cancer of mesenchymal origin
Examples of carcinomas:
Examples of sarcomas:
Increased number of normal cells
Cellular and nuclear changes leading to loss of uniformity, abnormal organization
Undifferentiated atypical cells varying in size/shape, loss of organization
At what level of abnormal growth does disorganization begin?
What is the key characteristic of anaplasia?
Undifferentiation of cells
Characteristics of benign tumors:
Well differentiated cells with preserved functions
Demarcated, often encapsulated, no invasion
Characteristics of malignant tumors:
Anaplastic/lack of differentiation
Types of normal adult cells that proliferate:
Bone marrow myeloblasts
Normally cellular damage is controlled by:
Seven features of a cancer cell:
Insensitivity to growth inhibitory signals
Evasion of apoptosis
Limitless replicative potential
Ability to invade and metastasize
Evasion of host immune response
Genes that encode proteins that normally stimulate cell proliferation
Altered forms of proto-oncogenes
In cancer, they have alterations that sustain gain of function
Type of mutation that typically happens to proto-oncogenes:
Dominant mutations in somatic cells
Oncogenes' impact on growth factors:
Overexpression of autocrine (self-affecting) growth factors
Oncogenes' effect on growth factor receptors:
Upregulation in amount or activation
Growth factor receptor associated with breast ca:
Massive # of HER2 found in breast ca
Oncogenes' effect on signal transducing proteins:
Keeps them turned on (GTP remains unhydrolyzed and activated) so there is constant signal input from GF receptors
Chemical substance (usually protein) that encourages mitosis.
What is RAS?
Gene that encodes the p21 G protein
What does the p21 G protein do?
Promotes cell division/propagation
Transmits a mitogenic signal from activated growth factor receptors
What is notable about the RAS gene?
Most common gene abnormality in human cancers, especially colon and pancreatic
What is MYC? What are CDKs? How are they related?
MYC: Nuclear transcription factor that stimulates CDKs
CDKs: Cyclin-dependent kinases - growth related genes
How is MYC related to cancer?
Most common nuclear transcription factor involved in cancer; particularly breast, lung, and other ca's
What role do CDKs play in the cell cycle?
Check the DNA during each phase of the cell cycle, particularly between G1 and S
Why is the G1 to S cell cycle phase transition so important in cancer?
Most common disregulations affect proteins involved in G1-S transition
Role of tumor suppressor genes:
Inhibit proliferation and stimulate apoptosis when cell is damaged
How are proto-oncogenes and tumor suppressor genes related?
Normally are balanced in opposition
Most tumor suppressor genes are:
Most oncogene mutations are:
Hereditary cancers vs. sporadic malignancy:
Hereditary: earlier development, more locations
Sporadic: later in life, more likely isolated
What is p53? How does it act under normal circumstances?
Tumor suppressor gene/protein that is normally bound to MDM2, which inhibits/degrades it
How does p53 act under stress?
Releases from MDM2 and stimulates transcription of p21 (not the same p21 as RAS encodes for) which leads to G1 growth arrest and activates DNA repair systems
Relationship between p53 and cancer:
Loss of quality control; leads to accumulation/propagation of damaged/mutated cells
Structure of p53:
Three types of p53 mutations and their consequences:
Loss of function: not harmful alone, does not interfere with complex's function
Gain of function: changes transcription process; activates different genes; stops cell cycle arrest/apoptosis; can even stimulate proliferation
Dominant mutant allele: prevents complex from functioning altogether; cannot even bind to target gene promoters
Relationship between DNA repair genes and cancer:
Lack of DNA repair activity --> more mutations in oncogenes, tumor suppressor genes
DNA repair genes implicated in breast ca:
BRCA1 predisposes women to:
Breast and ovarian ca; mutation is almost entirely familial, not sporadic
BRCA2 predisposes women to:
How do cancer cells achieve limitless replicative potential?
Upregulation of telomerase
What four features of cancer cells are internal?
Self-sufficiency in growth hormones
Insensitivity to growth inhibition signals
Evasion of apoptosis
Limitless replicative potential
What three features of cancer cells involve their interaction with the environment?
Ability to invade/metastasize
Evasion of immune response
Which vessels typically carry metastatic cancer cells?
Veins (easier to degrade, get cells into)
What stimulates angiogenesis?
What organs typically host metastatic tumors?
Liver and lungs due to rich blood supply
What do we call the turning point between a tumor being aneovascular and the start of angiogenesis?
How do cells invade the extracellular matrix?
Alterations in cell-cell adhesion molecules
Changes in attachment to basement membrane
Increased activity of matrix degrading enzymes
Autocrine motility factors/chemoattractants
How do tumors evade the immune system?
No MHC-1 or costimulant; T and B cells ignore the cancer cells
Secretion of immunosuppressant (TGF-b)
Causes of cancer:
Chemicals (genotoxic and non-genotoxic)
How does HPV cause cancer?
Synthesizes proteins that inactivate human genes involved in the cell cycle control
How does HBV (hep B) cause cancer?
Expresses proteins that stimulate proliferation
Injures tissues leading to regenerative processes
Name the associated cancers:
Human T-cell lymphotrophic virus
Kaposi's sarcoma-associated herpes virus
Adult T-cell lymphoma
General tumor progression pathway:
Mutation inactivates suppressor gene (p53)
Mutations inactivate DNA repair genes (BRCA)
Proto-oncogenes mutate to oncogenes (MYC)
More mutations, more genetic instability, metastatic disease
What physiologic factors can keep tumors dormant for long periods of time?
Lack of sufficient genetic mutation
Lack of blood supply
Immune response of host
Nonspecific s/s of cancer:
Imaging dx of cancer:
X-ray, US, CT, PET, MRI, thermal imaging
CD99 is specific to: