Miscellaneous Flashcards
Name the 6 hallmarks of cancer
Self sufficiency in growth signals Insensitivity to inhibitory signals Evasion of apoptosis Limitless replicative potential Sustained angiogenesis Potential for metastasis/invasion
Name two BONUS hallmarks of cancer
Modified energy metabolism
Immune escape
What phase of cell signal is most critical for development of neoplastic phenotype?
G0-G1 transition (aka R point, restriction point)
Define anoikis
Cell suicide occurring when cell loses integrin-mediated attachment to ECM.
Describe the forces that shift the oxygen hemoglobin dissociation curve
Temperature
PCO2
H+
2,3DPG
Increases shift right, decreases shift left
Ki67
- putative function?
- clinical utility
- change throughout cell cycle
Function unknown: ribosomal RNA synth?
Only expressed in proliferating cells
Located in nucleolus during interphase, moves to perichromosomal location during mitosis.
AgNOR
- stands for?
- what are the two main proteins?
Argyrophilic staining of Nucleolar Organizing Regions
Nucleolin and nucleophosmin
What is the Philadelphia chromosome?
- disease its associated with
- rearrangement
- drug target
CML
9 and 22 translocation
Gleevec
Identify the most correct statement in regards to the cancer stem cell hypothesis.
a. All cancer cells have the potential to self-renew, proliferate indefinitely and differentiate to give rise to more differentiated tumor cells
b. Only a minority of cancer cells has the potential to self-renew, proliferate indefinitely and differentiate to give rise to more differentiated tumor cells
c. Every cancer stem cell is fated to form new metastasis
d. Terminally differentiated cells are the only cells of origin in most cancers
Answer: b
Explanation:
a. This is incorrect because not all cancer cells have the potential to self-renew, proliferate, or differentiate
c. Not every CSC is fated to form a new metastasis (p. 299)
d. Somatic stem and progenitor cells are likely to be the cell or origin in some (perhaps most) cancers, but some terminally differentiated cells, which can be much longer-lived than previously assumed, may have sufficient time to acquire oncogenic mutations in a stepwise fashion, allowing them to evade apoptosis and senescence, proliferate independently of microenvironmental signals, and reactivate their self-renewal potential.
In regards to targeting cancer stem cells, identify the most correct answer in regards to the type of cancer, the targets, and the interventions used for treatment.
a. Breast carcinoma: VEGF, Hedgehog, BMPR2: Perifosine, Cyclopamine, Gemcitabine
b. Melanoma: AKT, NOTCH, IL-4: Rapamycin, Gamma-secretase inhibitor
c. Pancreatic carcinoma: BMPR2, NF-κβ, MHC and NK ligands: Parthenolide, Bevacizumab
d. Acute myeloid leukemia: mTOR, CD44, CD47: Rapamycin, Anti-CD44 antibody, Anti-CD-47 antibody
Answer: d
You have isolated some cells that you believe are cancer stem cells (CSCs) from a human breast cancer sample. When injected into an immunocompromised mouse, a tumor is formed. According to the CSC hypothesis, what additional piece of information is necessary to prove these are CSCs?
a. Identify the new tumor’s metastatic potential
b. Confirm genotype and phenotype heterogeneity is identical to the original tumor
c. Remove cells from the xenograft and successfully implant into a different host
d. Determine that the tumor is resistant to all cytotoxic chemotherapy
e. Successfully regrow the tumor in a growth factor-deficient media
Answer: b
CSCs are characterized by their ability to generate tumors upon serial transplantation in immune deficient animals AND their ability to recapitulate the genetic and phenotypic heterogeneity of the original tumor.
Which of the following types of mice would be most successful for xenotransplantation (e.g., least likely to reject the xenograft)?
a. Irradiated mice
b. Athymic nude mice
c. SCID mice
d. NOD/SCID mice
e. NSG mice
Answer: e
These are listed from earliest to most recent, with NSG mice being the newest and preferred option. NSG mice (aka NOD/SCID/IL2Yγ-/- mice) lack NK-cell activity as well as B- and T-cell activity.
Identify a type of cancer in which most of the malignant cells are tumor-initiating cells (TICs).
a. Acute myeloid leukemia
b. Colorectal carcinoma
c. Malignant melanoma
d. Glioblastoma
e. Mammary carcinoma
Answer: c
Explanation: T&H, page 307-8. The cancer stem cell hypothesis was criticized when TICs were commonly identified in melanomas. About 1 in 4 unselected melanoma cells could form a xenograft. Alternatively, TICs are rare in epithelial cancers and leukemia.
Which of the following immunophenotype would be expected for a suspected cancer stem cell?
a. CD44-/CD24+/CD3-/CD31-
b. CD44+/CD24-/CD3-/CD31-
c. CD133-/CD24+/CD3+/CD31-
d. CD133-/CD24-/CD3-/CD31+
Answer: b
Which of the following is the correct definition of totipotent?
a. Ability of stem cells to differentiate into any cell
b. Ability of a cell to differentiate into several different types of cells
c. Ability of a cell to differentiate into one other type of cell
d. Ability of a differentiated epithelial cell to transform to have a mesenchymal phenotype
Answer: a
Which of the following most accurately describes Paget’s “seed and soil” theory?
a. It is the concept behind a technique, SS Technique, used to identify cancer stem cells.
b. A normal cell within its respective organ is the seed and the surrounding stroma represents that “soil”. Under the right stromal environment the cell may transform into a malignant cell and form a tumor.
c. The stromal cells within an organ represent the “seeds” and the organ represents the “soil”
d. Cancer cells represent the “seeds” and the organs represent the potential “soil” for seeds to implant and develop into a tumor
Answer: d
- Which of the following is/are upregulated during epithelial to mesenchymal transition?
i. desmin
ii. metalloproteinases
iii. vimentin
iv. E-cadherin
a. i, iv
b. ii, iii, iv
c. iii, iv
d. i, ii, iii
Answer: d.
Explanation: desmin is associated with reorganization of the cytoskeleton. MMPs are associated with degradation of the surrounding ECM. Vimentin is associated with migration through the local environment.
Which of the following cell surface marker phenotypes would help identify the cell expressing it as a cancer stem cell?
i. CD34++/CD38-
ii. CD34+/CD38+
iii. CD133+
iv. CD45+
a. i, iii, iv
b. i, iii
c. ii, iii, iv
d. iii, iv
Answer: b.
Which of the following are characteristic of normal and cancer stem cells?
i. Ability to efflux water soluble flurorescent dyes such as Hoechst 33342
ii. Retention of lipophilic fluorescent dyes such as PKH26 even after several passages in culture
iii. Fluorescing in the presence of propidium iodide
iv. Fluorescing in presence of a dye that requires liberation by aldehyde dehydrogenase
a. i, iii
b. i, iii, iv
c. i, ii, iv
d. ii, iii
Answer: c.
(i) (ii) and (iv) are expected of normal and cancer stem cells. PI is membrane impermeable and should only be taken up by leaky (ie dead) cells. See p. 302
The mechanism of action of cyclopamine is:
a. Inhibition of mTOR pathway b. Inhibition of the NOTCH pathway c. Inhibition of the Hedgehog pathway d. Inhibition of the AKT pathway e. CD44 antibody
Answer: C
Which of the following have been associated with epithelial-to-mesenchymal transition?
i. TGF-β ii. Fas iii. Wnt iv. PDGF v. caspase 8
a. I, ii, iii
b. I, iii, iv
c. ii, iii, iv
d. iii, iv, v
e. ii, iv, v
Answer: b.
Which of the following is TRUE regarding cell proliferation in tumors?
a. The rate of cell proliferation in tumors is typically greater than that in rapidly proliferating normal tissues (bone marrow, intestine).
b. The low growth fraction of tumors is the key contributor to chemotherapy resistance.
c. The unlimited population of stem cells within a tumor contributes to its ability regenerate after cytotoxic treatment.
d. The rate of cell proliferation is exponentially higher than the rate of cell death.
e. Tumor cells further from blood vessels have a higher rate of proliferation to meet their nutrient requirements.
Answer: b
a) Tumor cell proliferation is generally less than cells of normal renewing tissues. c) Tumor cells likely have a limited amount of stem cells for regeneration. d) The rate of cell production is only marginally higher than the rate of cell death (the rate of cell death is 75-90% of the rate of production). e) Tumor cells further from blood vessels have a lower rate of proliferation, which further contributes to their chemotherapy resistance.
Which of the following characteristics is likely predictive of a poor outcome in cancer patients?
a. Acidic intracellular pH
b. Elevated interstitial fluid pressure
c. Downregulation in PERK and IRE-1 signaling
d. Upregulation of VHL protein
e. Low levels of CA9 and GLUT-1
Answer: b
. a) Although extracellular pH is often acidic (and correlated with a poor outcome), intracellular pH is typically normal or basic. b) Elevated IFP is caused from a build-up of fluid in the extracellular space due to a lack of functional lymphatics and abnormal/leaky blood vessels. This predicts a poor outcome for some solid tumors in humans. c) PERK and IRE-1 signaling mediate the unfolded protein response, which promotes adaptation to hypoxic stress. Therefore, defects in UPR would result in intolerability to hypoxia. d) VHL is responsible for ubiquitination of HIF-1α and HIF-2α, leading to their degradation. e) CA9 and GLUT-1 are target genes of HIF and should be increased in hypoxic tumors.
Match the tumor suppressor gene with its correct downstream target.
a. Tuberous sclerosis 1 (TSC) : upregulation of mTOR
b. PTEN : inhibition of AKT1
c. Rb : increased activity of p21
d. p53 : downregulation of NRF2
e. p53 : decreased glutathione production
Answer: b
Loss of tumor suppressor genes increases oxidative stress. Their usual mechanisms include the following: a) TSC inhibits mTOR; b) PTEN inhibits AKT1 and subsequently the FOXO transcription factor; c) Rb apparently does a bunch of things that was not worth mentioning in the chart; d&e) p53 increases NFR2 (via p21) and stimulates glutathione production (via GLS2).
