1. Which angiopoetin is associated with immature, angiogenic blood vessels characteristic of tumors?

Transcription

1 Hello, my name is: Radiation and Cancer Biology Lecture Series Fall Semester Quiz December 18-28, 2018 Please indicate the one best answer in the space provided. 1. Which angiopoetin is associated with immature, angiogenic blood vessels characteristic of tumors? A. Ang1 B. Ang2 C. VEGF Answer: D. Tie2 E. TIMP-1 2. A particular cell line is characterized by a radiation survival curve with a D 0 of 1.5 Gy and an n of 4.0. A mutated version of the same type of cell has a survival curve with a D 0 of 1.5 Gy, but an n of Which of the following statements best describes the relationship between the two cell survival curves? A. The mutated cell has a shallower final slope to its survival curve. B. The normal cell has a shallower final slope to its survival curve. C. The normal cell has a steeper shoulder to its survival curve. Answer: D. The mutated cell has a steeper shoulder to its survival curve. 3. Which statement concerning vasculogenesis is TRUE? Vasculogenesis: 4. mirnas: A. is only relevant during embryological development. B. involves the de novo creation of lymphatic vessels only. C. and angiogenesis are mutually exclusive processes. Answer: D. may be crucial for local tumor recurrence following radiotherapy. E. utilizes pre-existing blood vessels. A. bind to and inhibit the replication of target genes. B. stimulate ribosomal and transfer RNA synthesis. C. average 100 kb in size. Answer: D. enhance transcription factor binding to DNA. E. post-transcriptionally regulate gene expression. 1

2 5. Homologous recombination (HR) repair of DNA double strand breaks is most likely to occur: A. in G 0 phase. B. in late G 1 phase. C. in early S phase. Answer: D. in G 2 phase. E. in M phase. 6. Which is NOT a property of the epithelial to mesenchymal transition (EMT)? A. promotes cell detachment B. increases cell motility C. increases E-cadherin Answer: D. promotes extracellular matrix degradation E. increases vimentin 7. Which PET imaging agent can be used to detect hypoxic regions in human tumors? A. 18 F FHBG B. 18 F FDG C. 18 F FAZA Answer: D. 28 Mg ATSM 8. On average, the radiobiological hypoxic fraction in rodent tumors is: A. 0.15%. B. 1.5%. C. 15%. Answer: D. 45%. E. 60%. 9. HIF signaling metabolically reprograms cancer cells by: A. up-regulating glucose transporters. B. increasing oxidative phosphorylation. C. increasing conversion of pyruvate to acetyl-co A. Answer: D. decreasing glycolysis. 10. Which statement concerning radiation-induced apoptosis is FALSE? Apoptosis: A. plays a major role in the local control of most solid tumors. B. can occur after relatively low radiation doses. C. can begin within a few hours of irradiation. Answer: D. in thymocytes requires wild-type TP Ongoing clinical trials are testing mdm2 inhibitors, which may cause tumor regression by activating: A. ATM B. E2F C. myc Answer: D. p16 E. p53 2

3 12. Mammalian cells are most sensitive to ionizing radiation in the phase of the cell cycle. A. G 1 B. S C. G 2 Answer: D. M E. G If a cell line s D 0 is equal to its D 37, then n equals: A B C. 1.0 Answer: D The average annual dose equivalent to the US population from natural background radiation is approximately: A. 30 µsv B. 100 µsv C. 300 µsv Answer: D. 3 msv E. 10 msv 15. If 25 radiation workers were involved in a nuclear power plant accident that exposed them acutely to 1.0 Sv, about how many excess, fatal cancers would be expected to develop over the workers' lifetimes? A. none B. about 2 C. about 5 Answer: D. about 10 E. about Which second cancer is most likely to have been induced by prior radiation therapy? A. ovarian cancer 11 years after breast-conserving therapy B. angiosarcoma of the breast 12 years after breast-conserving therapy C. leukemia 2 years after chemoradiotherapy for lymphoma Answer: D. NSCLC in a smoker treated for SCLC 4 years earlier 17. From the perspective of a radiobiologist, "cell death" means: A. cessation of metabolic activity B. loss of membrane integrity C. loss of clonogenicity Answer: D. cessation of cell cycle transit 18. The b component of the linear-quadratic model: A. is a measure of irreparable DNA damage. B. approximates 1.0 for low LET radiation. C. correlates positively with the LET of the radiation. Answer: D. decreases with increasing fractionation/protraction. E. has units of Gy -1. 3

4 19. The regrowth delay assay is: A. a clonogenic assay for irradiated normal tissues. B. a clonogenic assay for irradiated tumors. C. a non-clonogenic assay for irradiated normal tissues. Answer: D. a non-clonogenic assay for irradiated tumors. 20. Which statement comparing carbon ion with proton beam radiotherapy is FALSE? A. Carbon ions are even better suited than protons for the type of precision radiotherapy needed to treat tumors located near critical structures. B. One advantage common to both carbon ion and proton radiotherapy is a reduced OER. C. Both beams exhibit a Bragg peak. Answer: D. The RBE for carbon ions is greater than for protons. 21. The term stochastic is used to describe an effect of radiation in which the: A. severity of the effect increases with increasing dose above a dose threshold. B. severity of the effect increases with increasing dose without a threshold. C. probability of the effect increases with increasing dose above a threshold. Answer: D. probability of the effect increases with increasing dose without a threshold. E. probability of the effect increases with increasing age at exposure. 22. Which radiation-induced effect in members of the general public exposed to fallout from the Chernobyl accident was significantly elevated? A. leukemia B. thyroid cancer C. non-specific life shortening Answer: D. congenital abnormalities (in offspring) E. cataracts 23. The main difference between effective dose and equivalent dose is: A. whether the radiation exposure was internal or external. B. the application of a radiation weighting factor. C. the application of a tissue weighting factor. Answer: D. that the former is measured in Sv and the latter in Gy. E. that the former is applied to populations and the latter to individuals. 24. Colorectal cancer cells that are hypermutated have defects in: A. mismatch repair. B. nucleotide excision repair. C. base excision repair. Answer: D. homologous recombination. E. non homologous end joining. 4

5 25. Once a pregnancy is declared, the maximum permissible dose to the fetus is: A msv per month B msv per month C. 0.5 msv per month Answer: D. 5 msv per month E. 50 msv per month 26. Less damage occurs per unit dose for x-irradiated DNA in a powdered state than in an aqueous solution because: A. dry DNA tends to become more hypoxic than DNA dissolved in solution. B. chromatin conformation is more open in a dry versus aqueous form, affecting the DNA's radiosensitivity. C. DNA repair half-times are much longer for DNA in an aqueous Answer: solution than in the dry form. D. free radicals liberated by the radiolysis of water account for most of the total radiation-induced DNA damage. 27. Which statement is TRUE concerning the roles Bcl-2 family member proteins play in the apoptosis process? A. Bax inhibits apoptosis while Bcl-2 promotes it. B. Bax promotes apoptosis while Bcl-2 inhibits it. C. Both the Bax and Bcl-2 proteins inhibit apoptosis. Answer: D. Both the Bax and Bcl-2 proteins promote apoptosis. 28. Which statement about the metastatic cascade is TRUE? A. There is no normal counterpart to the epithelial-mesenchymal transition process. B. E-cadherin and β-catenin are upregulated in metastatic cells. C. Host myeloid and stromal cells facilitate tumor invasion and metastasis. D. Tumor hypoxia and acidic conditions discourage metastasis. E. Inhibitors of matrix metalloproteinases increase metastatic potential. Answer: 29. At a partial pressure of O 2 of 25 mm Hg, the D 0 for a population of cells is 1.5 Gy. If the partial pressure of O 2 increased to 250 mm Hg, the new D 0 would be approximately: A. 0.5 Gy B Gy C. 1.5 Gy Answer: D. 3.0 Gy E. 4.5 Gy 30. Which statement concerning tumor hypoxia is FALSE? A. Hypoxia induces apoptosis in cells with wild-type TP53. B. Hypoxia markers can only detect hypoxic cells more than 200 µm from a blood vessel. C. Hypoxia selects for tumor cells bearing mutant p53. Answer: D. The OER for low LET radiation is greater than for high LET radiation. E. Tumors containing clonogenic hypoxic cells have biphasic, acute dose x-ray survival curves. 5

6 31. In respiring tissue, the maximum diffusion distance of oxygen from a capillary before hypoxia develops is approximately: A. 10 µm. B. 70 µm. C. 150 µm. Answer: D. 300 µm. E. 1.0 mm. 32. Which statement about epigenetics is FALSE? A. Epigenetic modification alters chromatin structure but does not alter DNA sequence. B. Epigenetic modification alters both chromatin structure and DNA sequence. C. Histone methylation is an example of epigenetic modification. D. Histone acetylation is an example of epigenetic modification. E. DNA methylation is an example of epigenetic modification. Answer: 33. The approximate dose range thought to double the spontaneous incidence of a germ line mutation in humans is: A msv B msv C msv Answer: D msv E. 1-2 Sv 34. Which radiation-induced malignancy has the shortest latency period? A. breast cancer B. leukemia C. lung cancer Answer: D. prostate cancer E. soft tissue sarcoma 35. Which type of radiation would produce a cell survival curve with the broadest shoulder? A. 250 kvp X-rays B. 5 MeV electrons C. 1 MeV neutrons Answer: D. 2 MeV a-particles E. 275 MeV/nucleon carbon ions 36. Which statement about cancer stem cells (CSCs) is FALSE? A. CSCs can both self-renew and give rise to progenitor cells. B. HIF-1 plays a role in maintaining the stemness of CSCs. C. CSCs may be responsible for therapeutic resistance. Answer: D. CSCs proliferate rapidly. E. CSCs reside in hypoxic niches. 6

7 37. Which cells are main contributors to neovascularization following definitive radiation therapy? A. Bone marrow-derived progenitor cells that are recruited to irradiated tumors B. Pericytes surrounding tumor vasculature that form new endothelial cells C. Tumor-associated fibroblasts that survive a course of radiotherapy Answer: D. Trans-differentiated cancer stem cells that form new endothelial cells 38. Which statement regarding radiation and tumor hypoxia is TRUE? A. Irradiation under hypoxic conditions yields more DNA strand breaks than under aerated conditions. B. At a partial pressure of O 2 of 100 mm Hg, a tumor would be considered clinically hypoxic. C. Oxygen need only be present during or within milliseconds following irradiation to act as a radiosensitizer. D. The OER for protons is higher than for X-rays. Answer: 39. The HIF-1 transcription factor is stabilized under hypoxic conditions because of: A. increased activity of VHL. B. increased transcription of HIF-1α. C. reduced stability of HIF-1β. Answer: D. reduced hydroxylation of HIF-1α. 40. All of the following processes are regulated by HIF-1, EXCEPT: A. angiogenesis. B. EPO production. C. glycolysis. Answer: D. p53 activation. E. ph regulation. 41. Which radiochemical processes best describes chemical restitution? (Assume that T represents some target molecule whose inactivation results in a biological effect.) A. TH ---> T + H B. TH + OH ---> T + H2O C. T + O2 ---> T-O-O Answer: D. T + HS-CH2-CH2-NH2 ---> TH + S-CH2-CH2-NH2 42. Which organ has the highest tissue weighting factor (W T)? A. breast B. bladder C. brain Answer: D. gonads E. kidney 7

8 43. Which statement about the vascular normalization phenomenon is FALSE? A. Treatment with bevacizumab can cause improved tumor oxygenation and response to radiation and chemotherapy. B. Vascular normalization occurs when the use of anti-angiogenic drugs rebalances the ratio of pro- to anti-angiogenesis signals in the tumor. C. Vascular normalization is universal and permanent after anti-angiogenic therapy. D. Some tyrosine kinase inhibitors cause vascular normalization by decreasing both VEGF and tumor vascularity in general. Answer: 44. Which statement about PARP1 and its inhibition is TRUE? PARP1: A. is a transcription factor. B. is an pro-apoptotic protein. C. is a protein kinase. Answer: D. inhibition can produce synthetic lethality. E. phosphorylates histone H2AX. 45. What is responsible for approximately two-thirds of driver mutations in human cancers? A. Heredity B. Replication errors C. Smoking Answer: d. Ionizing radiation 46. Mutant Ras is locked in a/an bound state. A. GDP B. GTP C. ADP Answer: D. ATP E. EGFR 47. Which statement about the DNA damage response is FALSE? A. DNA-PKcs, ATM and ATR are serine-threonine kinases. B. DNA-PKcs, ATM and ATR are tyrosine kinases. C. ATM phosphorylates Chk2 and p53. Answer: D. ATM phosphorylates substrates with the amino acid motif ps/t-q E. Histone H2AX is a substrate for ATM. 48. All of the following are possible mechanisms by which ionizing radiation initiates or promotes carcinogenesis, EXCEPT: A. contributing to genomic instability B. promoting cell death Answer: C. increasing inflammation D. generating reactive oxygen species 8

9 49. Increasing a tumor s vascular density will: A. increase perfusion due to greater blood volume within the tumor. B. decrease perfusion due to additional shunting of blood flow. C. increase drug and oxygen delivery, leading to radiosensitization. Answer: D. have complex, variable effects based on the vascular network s geometry. 50. As a radiation oncologist who employs radiation-generating equipment and radioactive sources occupationally, which two radiation safety enforcement agencies are you most answerable to? A. BEIR and NCRP B. DHS and OSHA C. DOE and EPA Answer: D. DOT and EPA E. FDA and NRC 51. According to the Life Span Study of Japanese a-bomb survivors, what best describes the dose response and time dependence for radiation-induced leukemia? A. Linear dose response, with excess risk increasing over time B. Linear dose response with excess risk decreasing over time C. Linear-quadratic dose response, with excess risk increasing over time Answer: D. Linear-quadratic dose response, with excess risk decreasing over time 52. What is the radiation weighting factor (W R) used to calculate equivalent dose of protons? A. 1 B. 2 C. 20 Answer: D Tumor cells develop multi-drug resistance to chemotherapeutics by: A. silencing genes associated with drug metabolism. B. upregulating genes that code for DNA repair proteins. C. overexpressing p-glycoprotein on their outer cell membranes. Answer: D. increasing hepatic detoxification and clearance of the chemotherapy drug(s). 54. Which is NOT a contributor to intermittent tumor hypoxia? A. high interstitial fluid pressure B. vascular stasis C. aberrant blood vessel geometry Answer: D. low oxygen consumption E. shunting of blood flow 55. If the surviving fraction after a single dose of 2.0 Gy is 0.52, what is the surviving fraction for a tumor receiving once daily 2.0 Gy fractions to a total dose of 66 Gy? A. 2.7 x 10-1 B. 5.2 x 10-6 C. 4.2 x Answer: D. 1.8 x

10 56. Which of the following is an exogenous marker of tumor hypoxia? A. carbonic acid anhydrase B. lysyl oxidase C. pimonidazole hydrochloride Answer: D. osteopontin E. hexokinase 57. Which of the following is NOT a characteristic of tumor cells that have become invasive? A. increased matrix metalloproteinase activity B. loss of mesenchymal phenotype C. enhanced motility Answer: D. loss of cell-cell adhesion E. reprograming of stromal cells in the tumor microenvironment 58. The APC protein, which is defective in familial adenomatous polyposis: A. binds to telomerase at the ends of chromosomes. B. binds to Rb to promote phosphorylation of CDKs. C. binds to p53 to promote ubiquitination of MDM2. Answer: D. binds to GSK-3b to promote phosphorylation of b-catenin. E. binds to Wnt to promote phosphorylation of Tcf/LEF. 59. If 1,000 cells are seeded into a petri dish, irradiated with 4 Gy, and 25 colonies form, what is the approximate percent survival assuming the cell line has a plating efficiency of 40%? A. 6% B. 16% C. 26% Answer: D. 36% E. 46% 60. The carbon ion RBE for hypoxic cells compared to aerated cells is: A. equal B. lower C. higher Answer: D. dependent on the endpoint Indicate true or false for each of the following statements. 61. Inactivation of telomerase causes cellular immortalization. 62. Radical scavenging agents such as glutathione can reduce radiationinduced DNA damage, and therefore, cell killing. 63. Oxygen participates in free radical reactions by contributing to the restitution process. 10

11 64. The efficiency of the metastatic cascade is approximately 1%. 65. Patients with tumors having low median values of po 2 show reduced 5 year survival following radiotherapy alone. 66. Patients with tumors having low median values of po 2 show reduced 5 year survival following surgery alone. 67. The OER increases with increasing LET of the type of radiation. 68. Multifraction survival curves have smaller D 0's than for their corresponding single dose survival curves. 69. One way tumor cells evade immune system detection is to express PD-L1 on their outer cell membranes. 70. Oncogene activation can promote tumor angiogenesis, even in the absence of hypoxia. 71. The types of chromosome aberrations most associated with radiation carcinogenesis are translocations and inversions. 72. Ionizing radiations of extremely high LET (e.g., 2,000 kev/µm) are less biologically efficient than moderately high LET radiations. 73. Hypoxia is a selective pressure for more aggressive tumor cell phenotypes. 74. For radiation protection purposes, the dose response curve for radiation-induced solid tumors in humans is assumed to be linear-quadratic. 75. The Cyclin E CDK2 complex helps regulate the G 1 cell cycle checkpoint. 76. One Gy of a-particles corresponds to an equivalent dose of 10 Sv. 77. The most significant source of natural background radiation exposure to the public is from cosmic rays. 78. The premetastatic niche is populated with exosomes, bone-marrow derived progenitor cells, and tumor-associated fibroblast and macrophages. 79. For radiation protection purposes, we assume that embryos and fetuses are about times more sensitive to radiation carcinogenesis than adults. 80. Basic fibroblast growth factor (bfgf) is a negative regulator of angiogenesis. 81. HIF-1α is constitutively active and bound to the promoters of hypoxiaresponsive genes. 82. Increased cancer mortality has been detected in Japanese a-bomb survivors who received doses comparable to those delivered by modern CT scanners. 83. The CDKN2A gene that codes for the p16 cell cycle-related protein is a transcriptional target of p Once established at a distant site, micrometastases can become dormant, and remain so for weeks, months or years. 11

12 85. Vascular remodeling occurs continuously over a tumor s lifetime. 86. Lysyl oxidase (LOX) is an endogenous hypoxia marker. 87. In many cases, drug resistant tumor cells pre-date exposure to the drug. 88. The annual radiation exposure limits set by the NCRP have not changed in over 30 years. 89. Thrombospondin-1 is a negative regulator of angiogenesis. 90. Cells that have undergone mitotic catastrophe often contain micronuclei. 91. The Cyclin D CDK4/6 complex is active during G 2 phase of the cell cycle. 92. Tumor cells that have lost RB activity become insensitive to growth suppression. 93. HIF-1 upregulation following irradiation helps protect tumor blood vessels, which facilitates further angiogenesis and tumor regrowth. 94. Patients with metastatic colon cancer with mutant KRAS expression do not benefit from the addition of cetuximab. 95. Resistance to the mutant BRAF-targeted agent vemurafenib develops because the drug is rapidly effluxed from tumor cells. 12