Cancer Bio Final Exam (NEW)

MHC I and II

-Present antigen fragments to T cells and bind T-cell receptors (TCRs).

How does cancer avoid the immune system?

1. Avoid Apoptosis 2. Down regulation of MHC expression 3. Express immunosuppressive proteins 4. Recruit immune suppressive cells

Name four parts of normal epithelial tissue

1. Epithelium 2. Lumen 3. Basement Membrane 4. Stroma

Name the types of point mutations

1. Missense 2. Nonsense 3. Frameshift (Indels)

Double stranded DNA breaks Repair Mechanisms (2)

1. Non-Homologous End Joining 2. Homologous Recombination

How do oncogenes go from good to bad?

1. Point Mutations 2. Gene amplification 3. Chromosomal Translocations

What are the six stages of metastasis?

1. Primary Tumor Formation 2. Local Invasion 3. Intravasation 4. Circulating Tumor Cells 5. Extravasion 6. Colonization

Name 3 tumor promoters

1. Toxic Compounds 2. Mitogens 3. Chronic Inflammation

Name 3 immunotherapy approaches

1. Tumor-specific antibodies 2. Checkpoint Inhibitors 3. CAR-T cells

What are the characteristics of transformed cells?

1. growth factor -independence 2. anchorage-independence (resists anoikis) 3. tumorigenesis (ability to form tumors) 4. ability to proliferate indefinitely (immortal) 5. loss of contact inhibition 6. oncogene tolerance

Cytotoxic T cells

A type of lymphocyte that kills infected body cells and cancer cells, very potent and specific killers. Anything binding MHC and foreign antigen.

A high proportion of these TIL's portends a poor prognosis

CD25+ regulatory T cells

A defect in which of the following repair pathways would NOT be expected to cause a missense mutation in the TP53 gene encoding the p53 protein?

Homologous Recombination

Which of the following would likely result from TGF-β pathway activation in NORMAL cells?

Increased p15INK4B CDK inhibitor

A defect in which of the following repair pathways WOULD be expected to cause a missense mutation in the TP53 gene encoding the p53 protein?

Mismatch Repair, Base Excision Repair, Nucleotide Excision Repair

Gamma-secretase inhibitors are the front line drug targeting cancers with constitutive activation of this pathway-

Notch

PIP3 (phosphatidy-inositol (3,4,5) -triphosphate) is a _____ domain

PH

Antibodies

Protein that is produced by lymphocytes (B cells) and that attaches to a specific antigen.

EGFR and PDGFR are both membrane-bound, ligand activated RTK's that can activate-

Src, PI3K, AKT, Ras, MAPK

B- (Beta) catenin is an important oncogene signaling downstream of the Akt and Wnt/Frizzled growth factor signaling pathways. What is the function of B-Catenin?

Transcription Factor

Field cancerization is a phenomenon where two or more tumors arise in a single organ... note that just one tumor is a highly unlikely event- let alone two or more. Which of the following best describes why field cancerization occurs?

a single cell accumulates multiple growth-promoting mutations and goes on to populate the organ before becoming malignant

T helper cells

activate B cells and cytotoxic T cells

The E2F family of proteins-

bind the DNA promoters of genes expressed in S phase

Which of the following would NOT qualify as a heterotypic signaling relationship within a tumor-

carcinoma cells expressing the EMT transcription factor Slug to encourage other neighboring carcinoma cells to also undergo an EMT

Tumors of epithelial origin are collectively classified as ______________, while all tumors originating in the blood system are _________________ cancers.

carcinomas / hematological

Hydrostatic shear forces, tumor cell rigidity, tumor cell size and blood vessel diameter are key factors determining tumor cell fate during this stage of metastasis-

circulating tumor cells

Data from X-inactivation experiments in females demonstrate that the genetically damaged tumor cells-

clonally derived from a single parental or progenitor cell

chromosomal instability

deletions, insertions, translocations

Which of the following is FALSE regarding the normal tissue vasculature (blood and associated vessels)?

epithelial cells create cell to cell adherens junctions with endothelial cells lining capillary beds

Which of the following does NOT correctly associate the category of DNA damage with the specific cause-

exogenous / base deamination

The APC tumor suppressor protein is commonly mutated in colorectal cancers. APC would be categorized as a _____________ type of tumor suppressor because of its inhibitor actions on ______________.

gatekeeper / beta-catenin

Tumor formation bears many similarities to the 'wound healing' mechanism... this is generally believed to occur because:

genetically mutated neoplastic cells come in direct contact with genetically normal stromal cells

Which is TRUE of the BRCA1 gene found in our human genome?

its product normally functions in double-stranded break repair, germline mutations in this gene are associated with an increased risk for breast and ovarian cancers, tumors with mutated BRCA1 typically show a high prevalence of indels (insertions-deletions) due to NHEJ activity.

Which cells are a part of the 'intravasation triad':

macrophages, genetically-damaged tumor cell, endothelial cells

The least common type of single base mutation expected to afflict the reading frame of a tumor suppressor protein:

missense

The ____________ cells are part of the innate immune system and are responsible for interrogating the presentation of cellular proteins (peptides) on MHC I complexes on normal and tumor cells; whereas __________ cells react to TH stimulation by secreting antigen specific antibodies.

natural killer / B cells

natural killer cells

non-specific killer cells

Two main categories of genes dictate the behavior of transformed cancer cells- the ______________ which stimulate proliferation and survival, and ________________ which inhibit proliferation and promote apoptosis.

oncogenes/tumor suppressor genes

Which tumor suppressor gene is the most commonly mutated across all cancer types?

p53

Normal heterotypic interactions between epithelial and stromal cells involve ___________ signaling mechanisms by exchange of growth factors through the _____________.

paracrine / basement membrane

As an initial 'hit' to a cell's genome, a tumor suppressor gene like p16 can be 'mutated' and rendered non-functional by:

promoter hypermethylation

Women and men carrying mutations in BRCA1 (or BRCA2) have an increased lifetime cancer risk because of-

reduced efficiency of homologous recombination, an inability to repair double-stranded breaks in DNA, the failure to repair mutations resulting from stalled replication forks

The ___________ is an enzyme responsible for translating mRNAs into proteins and is constructed from ___________ and ____________ molecules.

ribosome / protein & RNA

Microsatellite instability

single base, point mutations

Regulatory T Cells (Tregs)

tell cytotoxic T cells to cool down

The term phenotype means the 'look and behavior' of something, in this case a cell. In cancer, the term 'tumor heterogeneity' implies that-

the 'rules' of cellular differentiation within a normal tissue still preside in the malignant tumor and this underlies phenotypic differences amongst the tumor cells

Malignant carcinoma cells often 'remember their roots' and typically exhibit characteristics consistent with their epithelial cell origin. How do these 'epithelial-like' tumor cells become metastatic?

the cells become more motile and invasive via an epithelial mesenchymal transition EMT

A distinct advantage of angiogenesis targeted therapies is that-

the target cell population is genetically normal and is unlikely to evolve resistance to the drug

The cancer stem cell (CSC) hypothesis suggests that a rare population of 'tumor initiating, stem-like cells' are responsible for the initiation, maintenance of growth and cellular heterogeneity within a malignant tumor. If this hypothesis proves to be true, which of the following does NOT correctly describe its implications for cancer treatment?

therapies must consider treating the majority of cells in the tumor because they can all metastasize and form tumors

XP individuals develop skin cancer with a high frequency because-

they cannot repair thymine dimers in their DNA following exposure to UVB light, their nucleotide excision repair pathway is lacking the fundamental enzymes necessary to function in DNA repair, they experience many single base pair mutations in their skin cell genomes leading to MIN.

From the tumor cell's perspective, colonization is the most difficult stage of the metastatic process. Which best describes the behavior of cells that deposit in the remote tissue before they truly 'colonize'?

they do not proliferate and they do not die, they persist at the remote site- at times for decades

Mitogens such as the sex steroids estrogen and testosterone, chronic inflammatory conditions such as hepatitis infection, and some toxic compounds such as those found in cigarette smoke can behave as:

tumor promoters that stimulate cell overgrowth

Src is the original member of this class of kinases and all subsequent Src homologues share a common ______ domain.

tyrosine (Y) / SH1