Embryology Biology 441 Spring 2010 Albert Harris
Last set of review questions for Embryology 2010
Does it make sense to use these methods to compare amounts of contact inhibition in cancerous cells as compared with normal, non-invasive cells? Explain the logic? *Are there any differentiated cell types (non-cancerous) cell types which you would expect to lack contact inhibition? Why? Would you expect that embryonic cells might start out being less sensitive to contact inhibition, but gradually become more contact inhibited, later in development? *Might it be possible to explain sorting out of dissociated cells, according to differentiated cell type, by differences in contact inhibition, instead of by differences in adhesiveness or differences in active contractility along boundaries between different kinds of cells? Abercrombie noticed that cells often retract away from one another when undergoing contact inhibition: What are at least two alternative explanations for this induction of retraction (in terms of adhesion or contractility), and by what experimental criteria could you reasonably hope to test which alternative is correct? What is (are) the difference(s) between carcinomas and sarcomas? What are similarities between leukemia and lymphoma? What are analogies between teratomas and neuroblastomas? Why are neuroblastomas the closest thing to nerve cell cancerts. What are adenomas? What is the process of metastasis? What is a metastasis (in the sense of an object)? In what different fluids can metastasis occur? How is the question of whether cancer can be cured by surgery related to whether metastasis has occurred? By what criteria of shape can malignant cancerous cells be distinguished from "benign" tumor cells, and from normal cells of a given differentiated cell type? If you had a microscope that could somehow "see" the strengths of contractility of different cells in the body (or in histological sections), then what differences might you expect to see? * How can weakened traction be related to increased invasiveness, and/or to reduced contact inhibition? In class, and on the web site videos and photographs, what differences did you see between malignant (cancerous) cells as compared with normal cells. What method was used to convert tissue culture cells temporarily to cancerous behavior? What two major changes were seen in the videos shown in class? Some scientists reported that treating certain cancerous cells with high concentrations of cyclic AMP would cause them to behave more like normal cells: propose some experiments to do using this method. Could you test the specificity of anti-cancer drugs using cyclicAMP treatment. Others reported that cancer cells have consistently reduced amounts of fibronectin (the protein that links cell surfaces to collagen), and can be converted back toward normal behavior by adding large concentrations of fibronectin to their medium: Please suggests what experiments you might do to test if fibronectin increases contact inhibition, or changes cell contractility or cell adhesiveness. Regarding "chemotaxis": Please describe at least two (very) different behaviors of cells to chemical concentration gradients that many scientists would consider to be chemotaxis. If you can quickly move the source from which the chemotactic attractant substance is diffusing, how would that help you to distinguish which different form of chemotaxis is occurring? *Are the different forms of ehemotaxis mutually exclusive, or could a combination of different mechanisms occur in the same cells at the same time? What are at least 4 specific examples in which one or another form of chemotaxis occurs? *Could cancer sometimes possibly be caused if cells had an inheritable mutation that caused them to become abnormally over-sensitive to some form of chemotaxis? * What about cancer being partly caused by a mutation that made cells less sensitive to chemotaxis than they normally are? Suppose you had a population that were sensitive to negative chemotaxis in response to some chemical that these cells themselves secreted, and you used AbercrombieÕs tests for contact inhibition: would any of the tests seem to be detecting contact inhibition, when the real cause was mutual negative chemotaxis? Please invent some additional experiments by which you could distinguish between contact inhibition and negative chemotaxis. [Hint: remember how Bonner proved to occurrence of positive chemotaxis.] What is the apical ectodermal ridge? Where does it occur? It is along the border between the ____ and the _____halves of developing vertebrate limb buds. It is oriented along the ____-____ axis of the body. What did John Saunders discover when he surgically removed the apical ectodermal ridge from developing chicken embryo wing and leg buds? It has been discovered that surgical implantation of a source of what protein can substitute for the apical ectodermal ridge? (i.e. if you remove the AER, but then implant a source of this protein, limb development is normal.) Which taxonomic order of vertebrates doesnÕt form an apical ectodermal ridge (besides snakes, of course). How are caspase enzymes related to programmed cell death? What does a cell look like when it undergoes programmed cell death? What is the effect of over-expression of the bcl-2 gene? How did bcl-2 get its name? Can cancer be caused by chromosome breaking and rejoining at the wrong location? (called "translocation") What are some specific examples in which cancers are caused in this way? What genes can cause cancer when over expressed? What are some examples of oncogenes? Can cancer also result from mutations that change the amino acid sequences of oncogenes. In most cases, is cancer caused by over-activity of an oncogene, or from under-activity of an oncogene? Does this depend on which oncogene we are considering. Please figure out why frame-shift mutagens are less carcinogenic than any other category of mutagens. [Hint, if a mutation adds or removes one base pair, then the reading frame will be shifted, and a wildly different amino acid sequence will be produced. And therefore...?] Why would it be useful to invent a chemical that 1) Could diffuse into cells 2) would have phosphates added to its chemical structure by over-active kinases and 3) would become poisonous when phosphorylated? What about a diffusible chemical that would activate caspase enzymes, but only under certain conditions, such as in the presense of much higher than normal concentrations of lactic acid? Or over-active kinases? Or underactive GTPases. Or less than normal concentrations of fibronectin? Conversely: what medical uses would there be for a diffusible chemical that would temporarily inhibit caspases? [Hint: heart attack, strokes] Please explain the possible usefulness of such a chemical. Please explain why you are surprised/not surprised by the effectiveness of the anti-cancer drug Gleevek, which selectively blocks an abnormal kinase (that attaches phosphates to -OH groups on proteins). What are "spindle poisons" and what is the logical motivation for using them as anti-cancer drugs? *Do you remember what Professor Barbara Danowski discovered about the effects of most spindle poisons on contractility and actin organization in tissue culture cells? *Suggest how this effect might be related to the anti-cancerous effects of spindle poisons? What is meant by "nitrogen mustard" anti-cancer drugs, like phosphamide? Do they have anything to do with mustard, of the kind you put on hot dogs? List 5 or 6 consistent abnormalities of cancer cells, as compared with normal cells. *For each of these abnormalities, invent one or more possible ways to kill just those cells that have that particular abnormality.
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