Cutaneous Neoplasia and Paraneoplastic Syndromes Flashcards
What does interphase consist of?
G1: cell growth
S: DNA replication
G2: preparation for mitosis
What are the common places where the cell cycle becomes unregulated?
Loss of normal checkpoints
Overexpression of growth factors
Loss of signal to die
Loss of repair mechanisms in S phase
What are two major proteins that regulate the cell cycle?
cyclins
cyclin-dependent kinases (CDKs)
How can some cancers use telomerase?
Some cancer cells utilize telomerase to add telomeric sections to the ends of DNA during DNA replication, allowing these cancer cells to live and divide much longer than other somatic cells
What is p27?
a protein thought to maintain cells in G0 and which may be decreased in cancers like squamous cell carcinoma
What is the most common phase of the cell cycle for veterinary chemotherapeutic agents to work on?
S phase (DNA replication)
What stage of the cell cycle do antimetabolite chemotherapeutics work on?
S
What stage of the cell cycle do alkylating agent chemotherapeutics work on?
S
What stage of the cell cycle do cross-linking agent chemotherapeutics work on?
S
What stage of the cell cycle do topoisomerase inhibitor chemotherapeutics work on?
S
What stage of the cell cycle do antimicrotubule agent chemotherapeutics work on?
M
What stage of the cell cycle do signal transduction inhibitor chemotherapeutics work on?
the level of signal transduction that starts the cell cycle
When are cells most resistant to radiation therapy?
in S phase
In addition to making the tumor smaller, what can be a benefit of debulking surgery?
may stimulate cells to divide –>
may force them into a phase of the cell cycle more susceptible to other therapies.
What is a proto-oncogene?
are a group of normal genes in cells which can cause cells to become cancerous when the genes are mutated
- normally help cells grow and
divide or stay alive
Usually produce proteins that
- stimulate cell division
- inhibit cell differentiation
- halt cell death
What is an oncogene?
what a proto-oncogene is called once it has mutated
mutations are usually dominant and increase the level of activity
What is c-kit?
a proto-oncogene that encodes the receptor tyrosine kinase protein
- aka KIT, CD117, or mast/stem cell growth factor receptor (SCFR)
activating mutations lead to cancer
not restricted to mast cell tumors but is a prognostic indicator in them
What is the role of tyrosine kinase protein (KIT)?
a transmembrane cytokine receptor
on the surface of hematopoietic stem cells, interstitial cells, melanocytes, and mast cells
binds to stem cell factor (steel factor)
- forms a dimer
- activates its intrinsic activity
- leads to phosphorylation
- activation of signal cascades
promotes cell survival, proliferation, and differentiation
also involved in fibronectin adhesion, chemotaxis, and degranulation of mast cell tumors
What is c-myc?
a proto-oncogene
encodes a transcription factor that regulates the cell cycle
Aberrant expression c-myc is present in many feline and canine cutaneous tumors
What are tumor suppressor genes?
normal genes that slow down cell division or tell cells to die at the right time
- ex TP53 that encodes p53
- ex retinoblastoma protein
What is TP53?
a tumor suppressor gene
encodes for the p53 protein
- most frequently mutated
protein in all human cancers
regulates apoptosis in response to genotoxic or cellular stress
What is retinoblastoma protein (pRB)?
a tumor suppressor protein
- normally inhibits cell cycle progression until a cell is ready to divide
- papilloma E7 binds to and inhibits it
What are DNA repair genes?
normal genes that help fix mistakes made when the cell copies its DNA in cell division
If they can’t fix the cell, they trigger cell death
- ex BRCA in some breast cancers
What are 13 hallmarks of cancer?
(1) Genomic instability and mutation
(2) Replicative immortality
(3) Insensitivity to growth suppressive signals
(4) Ability to evade programmed cell death
(5) Reprogrammed energy metabolism
(6) Sustained angiogenesis
(7) Immune destruction evasion
(8) Tumor-promoting inflammation
(9) Self-sufficiency in growth signals/replicative immortality
(10) Tissue invasion and metastasis
(11) Phenotypic plasticity and disrupted differentiation
(12) Non-mutational epigenetic reprogramming
(13) The microbiome changes