ASF - Neoplasia (Lewin) Flashcards
What is a promotor and how can it lead to carcinogenesis?
Promotor - region of DNA that is involved in cell proliferation
Chemical carcinogens can cause mutations of promotor regions of DNA to induce unregulated cell proliferation, which leads to neoplasia
Which toxin is associated with urothelial carcinoma of the bladder?
Naphthylamine (form cigarette smoke)
What is p53 and what happens when it is deleted?
p53 is a DNA stabilization protein that binds to damaged DNA. It stops the cell cycle, regulates apoptosis, and induces production of p21 (involved in DNA repair) and allows DNA repair before cell cycle continues
Deletion of p53 leads to uninhibited cell proliferation and propagation of mutated DNA
Differentiate between the inherited and sporadic forms of retinoblastoma.
- Inherited form
- One germ-line mutation passed from parent (present in all cells)
- Second hit - spontaneous somatic cell mutation in retinal cell
- Sporadic form
- Two normal alleles become mutated after birth in somatic cells of the eye
Which cancers are associated with asbestos?
Lung cancer and mesothelioma
UV radiation is responsible for the induction of what types of cancers?
Melanoma, squamous cell carcinoma, and basal cell carcinoma
Overproduction of KiT is associated with which cancer?
Gastrointestinal stromal tumor
What antigen is overexpressed in some breast and ovary cancers?
Her2/neu
Underglycosylation of a cell membrane can express some foreign epitopes. Give an example, and with what cancers is it assoicated?
MUC-1
MUC-1 is normally hidden under mucins, and is protected from immune reactions. Lack of mucus decreases this protection and unmasks MUC-1, causing an immune response
Associated with: pancreas, ovary, and breast cancer
Alkylating agents are associated with which types of cancers?
Lymphomas and leukemias
These cancers arise secondary of alkylating drugs used as chemo for a primary cancer treatment.
Overexpression of ____ is associated with MEN2A, MEN2B, and medullary carcinoma of the thyroid.
RET gene
What toxin is associated with angiosarcoma of the liver?
Vinyl chloride
What is the pathogenesis of follicular cell lymphoma?
Follicular cell lymphoma is caused by a t(14:18), which increases levels of Bcl-2. Bcl-2 is an anti-apoptotic factor that inactivates caspases, which decreases apoptosis and leads to hyperproliferation of cells.
Arsenic is associated with which cancers?
Squamous cell carcinoma of skin, lung cancer, and angiosarcoma of liver
Overexpression of n-myc is associated with what type of tumor?
Neuroblastoma
Alcohol is associated with which types of cancers?
Oropharyngeal, upper esophageal, hepatocellular carcinoma and pancreatic carcinoma
Overexpression of what GF receptor leads to the formation of breast cancer?
Her2/neu
Burkitt Lymphoma is associated with which translocation?
t(8:14)
Translocation of c-myc (from chromosome 8) to Ig heavy chain gene (on chromosome 14)
What are the two components of Knudson’s two-hit hypothesis
- First hit - inherited germline mutation from parent –> mutation present in all cells
- Second hit - spontaneous mutation of second allele –> disease phenotype
Typically involved in tumor suppressor gene mutations, which require both alleles to be mutated to cause cancer (ex: retinoblastoma)
What is the concept of multistep carcinogenisis?
The notion that carcinogenesis takes multiple steps before it becomes a malignant threat
What are examples of direct-acting alkylating agents? What are they typically used for?
Cyclophosphamide, chlorambucil, nitrosureas
Used as chemotherapeutic agents
Helicobacter pylori is most commonly associated with what type of cancer?
MALT lymphoma and gastric lymphoma
Breast cancer associated with an over-expression of Her2/neu is treated by?
Trastuzumab
How do indirect chemical agents work as carcinogens?
Indirect carcinogens must be converted into an active carcinogen by phase I liver enzymes before it can cause mutations
Overexpression of cyclin D1 is associated with what type of cancer?
t(11:14)
Cyclin D gene translocated to Ig heavy chain gene –> upregulation of cyclin D
High levels of cyclin D promotes G1 to S phase in cell cycle
True or False: Curing a patient of Helicobacter pylori will eliminate their induced MALT-lymphoma.
True
