Exam BIMM21, June 3rd 2016 1. Tumors of epithelial origin are the most common form of cancer in humans. Which of the following is classified as a tumor of epithelial origin: a) b) c) d) 2. c-myc overexpression is sufficient to induce lymphoma c-myc overexpression is likely not sufficient to induce lymphoma c-myc was expressed in few B cells, resulting in monoclonal growth c-myc is not a very potent oncogene Slow transforming retroviruses can be useful for studying: a) b) c) d) 5. hyperplasia; metaplasia; dysplasia dysplasia; metaplasia; hyperplasia hyperplasia; dysplasia; metaplasia metaplasia; dysplasia; hyperplasia In a transgenic mouse model of Burkitts lymphoma, the c-myc gene is placed under the control of IgH enhancer. At first, there is no sign of tumor but after some time the mice develop monoclonal B cell lymphomas. This suggests that: a) b) c) d) 4. melanoma glioma osteosarcoma adenocarcinoma In some cancers, a progressive development from normal to highly malignant cell types can be seen. The proposed order in which the different gradients of abnormality appear, starting from normal tissue and ending with malignant tissue, is: a) b) c) d) 3. Name: insertional mutagenesis oncogenes picked up by retroviruses loss of heterozygosity identification of tumor suppressor genes Cancer cells have a different metabolism as compared to normal cells. What is the main explanation as to why cancer cells use the type of metabolism often referred to as “the Warburg effect”? a) Many cancer cells have inadequate supply of oxygen and rely on anaerobic glycolysis for energy production b) Highly proliferative cells like cancer cells need high amounts of ATP c) Cancer cells are metabolically reprogrammed to use aerobic glycolysis d) Metabolic intermediates from the TCA cycle can then be used for other biosynthetic reactions 6. The myc oncogene can be activated by: a) b) c) d) 7. Which mechanism can lead to oncogene activation: a) b) c) d) 8. gene amplification chromosomal translocation proviral integration all of the above chromosomal translocation genetic mutation truncation all of the above The human papilloma virus is an oncogenic DNA virus that cause cervical cancer by: a) inhibiting p53 b) inhibiting pRb c) inhibiting both p53 and pRb d) inhibiting p53 and cyclin-dependent kinase inhibitor p16INK4A 9. Control of the pRb function is disturbed in principally all human tumors. Which type of deregulation would promote advancement through the cell cycle restriction point? a) b) c) d) promoter methylation of CDK4 amplification of p27Kip1 p27Kip1 degradation loss of cyclin D1 expression 10. Which of the following statements regarding NK cells is true? a) b) c) d) belong to the adaptive immune response require activation by T cells for killing tumor cells recognize tumor cells expressing MHCI-antigen complexes kill cells by releasing toxic compounds 11. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes methyl groups from DNA (most often on O6 guanine). In many glioma patients, the MGMT gene is affected by promoter methylation. These patients are therefore particularly sensitive to: a) b) c) d) temozolomide, an alkylating agent cisplatin, a DNA cross linker doxorubicin, a topoisomerase inhibitor 5-fluorouracil, a pyrimidine analogue 12. Trastuzumab (Herceptin) is a monoclonal antibody and used as a targeted treatment in a certain type of breast cancer. What does Herceptin target? a) b) c) d) a tyrosin kinase receptor an intracellular kinase a G-protein-coupled receptor extracellular VEGF 13. In hypoxic cells, the mechanism that leads to stabilization of the hypoxia inducible factor α subunit (HIF-α) involves: a) b) c) d) degradation of prolyl-4-hydroxylases (PHDs) loss of VHL function loss of HIF-α hydroxylation binding to the HIF-β subunit 14. The seed-and-soil hypothesis suggested by Paget in 1889 suggests that: a) b) c) d) circulating tumor cells are shielded from NK-cells by platelets tumor microenvironment is important for metastatic growth site-specific metastasis depends on anatomical location of the tumor factors are secreted by primary tumor cells that prepares distant sites for metastatic growth 15. Gleevec is a targeted therapy that is used for treatment of chronic myeloid leukemia. Its main mechanism of action is: a) b) c) d) induced differentiation of leukemic cells inhibition of a tyrosin kinase receptor inhibition of an intracellular tyrosin kinase inhibition of the proteasome 16. To become activated a T cell requires 3 signals. Which of the following is hampered by CTLA-4? a) b) c) d) antigen presentation signal co-stimulatory signal cytokine stimulated signal all of the above 17. Targeted therapeutics, in particular tyrosine kinase inhibitors, have revolutionized cancer treatment in recent years. Such drugs are particulary successful when: a) b) c) d) There is large intratumoral heterogeneity with regards to genetic aberrations Single specific mutations act as drivers of tumor growth Tumors have upregulated expression of drug efflux pumps There is a potent immune response towards the tumor 18. Clear cell renal cell carcinomas are unusually vascular tumors. What’s the primary reason? a) The normal kidney is an unusually vascular tissue b) Clear cell renal cell carcinomas have a pseudo-hypoxic phenotype resulting in excessive angiogenesis c) Renal cancer cells require more oxygen than other tumor cells d) VHL loss in clear cell renal cell carcinomas results in decreased degradation of VEGF, leading to increased angiogenesis 19. Tumor cells generally consume more glucose than normal cells. This fact can be exploited in the clinic. How? a) Glucose consumption by tumor cells allow for PET-CT-based imaging of 18F-FDG in tumor detection b) Glucose consumption by tumor cells allow for CT-MRI-based imaging of 18F-FDG in tumor detection c) Glucose consumption by tumor cells allow for bioluminescence-based imaging of 18F-FDG in tumor detection d) Glucose consumption by tumor cells allow for ultrasound-based imaging of 18F-FDG in tumor detection 20. Epithelial-to-mesenchymal transition is thought to promote: a) b) c) d) Tumor cell differentiation Tumor cell migration Tumor cell proliferation Tumor cell death 21. Tumors can acquire resistance to targeted therapeutics by a) b) c) d) Acquiring novel mutations Selection of pre-existing drug resistant clones Reversibly altering tumor cell phenotype All of the above 22. The cancer stem cell model is based primarily on the finding that: a) The most aggressive tumors have a stem cell-like phenotype, whereas differentiated tumors are less aggressive b) Only a minority of cells present in a tumor can propagate tumor growth when transplanted in mice c) Stem- and progenitor cells are easier to transform in mouse models than differentiated cells d) Cells undergoing EMT acquire a stem cell-like phenotype 23. Tumor blood vessels exhibit a) b) c) d) Non-hierarchical organization Leakiness Variable diameter All of the above 24. Cancer cells frequently use glycolysis rather than oxidative phosphorylation. This might seem surprising, as a) Glycolysis generates only 2 ATP/glucose, whereas oxidative phosphorylation generates 36 ATP/glucose b) Oxidative phosphorylation is faster than aerobic glycolysis c) Tumors are generally more hypoxic than normal tissues d) All of the above 25. Glycolytic cancer cells release lactate into the microenvironment. What is a consequence of this? a) Lactate will lower the pH in the microenvironment, leading to extracellular matrix remodeling b) Lactate will increase the pH in the microenvironment, leading to extracellular matrix remodeling c) Lactate activates the immune system to promote tumor growth d) Lactate activates the immune system to promote an anti-tumor immune response 26. Which of the following can be a late side-effect of radiation therapy? a) b) c) d) Carcinogenesis Infertility Fibrosis All of the above 27. Bevacizumab (Avastin) is a monoclonal antibody against VEGF. Which cell type is primarily targeted by anti-VEGF treatment? a) b) c) d) tumor cells pericytes cancer-associated fibroblasts endothelial cells 28. Cancer-associated fibroblasts (CAFs) contribute to many steps during tumorigenesis. Which of the following is true for CAFs? a) b) c) d) CAFs secrete molecules that increase extracellular matrix stiffness CAFs secrete factors that promote tumor cell proliferation CAFs have increased glycolysis All of the above 29. Panitumumab is a monoclonal antibody targeting the EGFR that is commonly used in the treatment of colon cancer. Many tumors develop resistance to panitumumab. Which is the most likely resistance mechanism? a) b) c) d) Upregulation of EGF ligand Downregulation of EGF ligand Downregulation of EGFR Acquired activating mutation in KRAS 30. Epithelial-to-mesenchymal transition (EMT) has been shown to induce stem cell characteristics of breast cancer cells. What’s the conclusion from these experiments? a) b) c) d) The cancer stem cell phenotype is plastic and reversible Cancer stem cells are derived from normal breast tissue stem cells EMT is required for tumor-initiation and metastatic spread EMT is required for therapeutic resistance
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