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Biology 207 Research Paper and Presentation on Cancer Assignment: To locate several articles and references relevant to a cancer topic, write a brief research paper (6-10 pages double-spaced) and present some aspect of your research to the class either as an oral report or as part of one of the poster sessions on April 29 or May 1, 2002. The paper will be due in class on May 6, 2002. Time Table: (1) Research your topic and decide on one or two articles to focus on. Obtain additional references that help you understand or explain the article. Be sure to plan ahead so you have plenty of time to obtain materials by interlibrary loan. (2) Briefly meet with instructor regarding your paper topic and/or paper outline before Mar. 18, 2002. (3) Begin writing your paper. Submit drafts to the instructor, the writing center or to classmates for feedback. (4) Think about how you can present some aspect of the paper to the class. I will assume you are presenting a poster unless you contact me to schedule an oral presentation. Prepare diagrams, photographs, illustrations and text to make your topic understandable. I will provide poster board which you can pick up a week or two before the poster session. (5) The poster sessions are on Mon. Apr. 29 and Wed. May 1, 2002 during class. Students with last names beginning with A-H will present on Monday; those with last names J-W will present on Wednesday. (6) The final version of the paper is due in class on May 6, 2002. Suggested format and sample paper For many papers the following sample draft can serve as a model. For clarity, I’ve left in the major subheadings I used to write the paper. Note that this example is shorter than what is requested in the assignment. Title: Cancer and Cell Death: The Role of Bcl-2 Author: Nancy Bachman Course: Biology 207 Outline: 1. Introduction to cancer genes Cancer is a disease of cells. A single cell moves down the path toward cancer as the result of a series of environmentally induced changes to critical genes. The genes affected in cancer may fall into any of three classes (Craig, 1995). One class comprises the so-called “oncogenes”, the genes that code for proteins that promote cell proliferation. 1 Another class called tumor suppressors encode proteins that provide a protective role in the body. A third class is represented by the gene Bcl-2 and consists of genes that influence cell viability or cell death. The significance of the third class is that it suggests that cancer can result not only from the overgrowth of cells, but also from a lack of cell death. 2. Lymphomas Lymphomas are cancers that develop from lymphocytes or macrophages (Cooper, 1992). Lymphocytes are produced in the bone marrow (B-cells) or thymus gland (Tcells) as the result of division of a “stem cell” that has the potential to give rise to a variety of cell types (Alberts et al., 1994), including cells that can differentiate to form lymphocytes. Lymphocytes normally function in immunity. B-cells function in the production of circulating antibodies and T-cells in determining cell mediated immunity and tissue compatability. Lymphomas result when there is a hyperproliferation of a lymphocyte precursor. Different types of lymphomas result when the cancer affects different cells or through different modes of cancer progression. The most frequent type of lymphoma is Hodgkin’s disease which affects the lymph nodes and is identified by a particular cell type, the Reed-Sternberg cell (Cooper, 1992). 3. Isolation of the Bcl-2 gene Gross changes in the appearance or arrangement of chromosomes has been observed in several types of cancers. In a B-cell lymphoma, a rearrangement was found in tumor cells involving the translocation (transfer) of a portion of the long arm of chromosome 18 to the long arm of chromosome 14 (Craig, 1995). This causes a gene to be moved from its normal location into the locus for a gene encoding an antibody. Analysis of the gene involved lead to the identification of Bcl-2, which has turned out to 2 represent a new family of genes involved in cancer. The Bcl-2 gene encodes a mitochondrial protein that ordinarily prevents cells from undergoing premature cell death (Craig, 1995; Adams and Cory, 1998). When this gene is altered by mutation or by genetic rearrangement, cells that would ordinarily undergo a process called apoptosis or programmed cell death continue to thrive. Proliferation of cells that ordinarily die leads to cancer. 4. Role of Bcl-2 in cancer Bcl-2 is one of a family of proteins implicated in cancer and cell death pathways. The translocation of Bcl-2 has been associated with several types of lymphomas including 85% of follicular lymphomas (Sheer, 1997) and some cases of diffuse large cell lymphoma and chronic lymphocytic leukemia (Adams and Cory, 1998). Studies in transgenic mice (in which the gene for Bcl-2 is overexpressed by genetic engineering) showed that synthesis of Bcl-2 results in accumulation of excess mature B lymphocytes and additional genetic changes (especially in the oncogene myc) associated with lymphomas (reviewed in Adams and Cory, 1998). The “Bcl-2 family” of proteins are a group of proteins related to each other based on their amino acid sequences. Some of the other members, including Bcl-xL, promote cell survival, and may also be oncogenes. Other family members, such as Bax, may act as tumor suppressors. Bax is mutated in human gastrointestinal cancer and in some leukemias (reviewed in Adams and Cory, 1998). Prediction of the effects of these family members in promoting or preventing cancers is further complicated by the ability of the different types to interact with each other to form heterodimers (proteins of two subunits, one of each type). 3 5. New therapies based on cell death Understanding the mechanism that Bcl-2 and its family members use to promote either survival or cell death may help suggest new types of therapies for cancer. Traditional therapies for lymphomas have mostly utilized radiation and chemotherapy (Cooper, 1992). These traditional treatments are quite cytotoxic and can have extreme side effects; Bcl-2 may be able to reduce the cytotoxic effects of anti-cancer agents by inhibiting cell death pathways. Combination chemotherapy (utilizing several drugs in combination) and radiation have greatly improved cure rates for the disease, yet both have the drawback of potentially inducing additional cancers at some time in the future. This drawback is severe in that lymphomas often strike children and teens who may win their initial battles only to succumb to cancer later in life. In the future, Bcl-2 and its family members might serve as potential targets for new rational therapies for cancer. Bcl-2 plays a key role in what appears to be a complex pathway controlling cell death and survival. Understanding the basic biology of these processes may suggest new ways in which cancer might be controlled. Some of these new treatments may prove to be both effective in fighting cancer and less toxic to cells, as was proven to be the case for the recently developed Her-2 antibody used in treating certain patients with receptor-positive breast cancer. References: 1. Adams, J. M. and Cory, S. 1998. The Bcl-2 protein family: Arbiters of cell survival. Science 281: 1322-1326. 2. Alberts, B., Bray, D., Lewis, J., Raff, M., Roberts, K. and Watson, J. D. 1994. Differentiated cells and the maintenance of tissues. In Molecular Biology of the Cell, third edition. Garland, New York, NY pp. 1161-1175. 3. Craig, R. W. 1995. The Bcl-2 gene family. Seminars in Cancer Biology 6: 35-43. 4. Cooper, G. 1992. Leukemias and lymphomas. In Elements of Human Cancer. Jones and Bartlett, Sudbury, MA pp. 267-281. 4 5. Sheer, D. 1997. Chromosomes and cancer. In Introduction to the Cellular and Molecular Biology of Cancer (Franks, L. M. and Teich, N. M., eds.). Oxford University Press, Oxford, UK. pp. 213-217. Key features to include in your paper: 1. Brief descriptive title. If it is especially catchy, you may want to use the same title for your paper and your poster. 2. Start with an introduction and end with a summary or a concluding section that emphasizes the significance of the topic. 3. Organize the topics in your paper with an outline. Add to your outline any additional biology topics relevant to your paper that might not be familiar to a general audience. 4. Consult and cite at least four sources of information (at least 3 sources other than the Cooper textbook). At least one source should be an article (either a review article or research article from a scientific or medical journal). Textbooks are very useful sources for the basic biology; you may want to consult texts in genetics, cell biology, immunology or pathology. Limit yourself to one source from the internet and give the URL address in the citation. 5. Be consistent in citing references. I like to cite the sources as I go along (by author, year) then give the full reference in a section at the end labeled “references” or “literature cited”. I would prefer if you would not use internal numbered footnotes as they allow for less flexibility in writing and revising drafts. Use the same format for your citations as given in my example (refs. 1 and 3 are articles, refs. 2, 4, and 5 are book chapters). Things to keep in mind: 1. Focus your paper. Stick with what is most interesting and forms the most cohesive unit of information. 2. Consider your paper as a “work in progress”. There are always things you can do to improve your paper. Be sure to check spelling, grammar and format. Also allow some time to have a friend or roommate check it for “readability”--are there major concepts that still need to be explained to understand the rest of the paper? For example, my sample paper would be more readable if I explained terms like follicular lymphoma and if I distinguished among the different kinds of cancers caused by Bcl-2. 3. You may include one or two illustrations in your paper if their inclusion helps to clarify what you’ve written. 5 Sample Poster Title: Cancer and Cell Death: The Role of Bcl-2 Author: Nancy Bachman ABSTRACT: Three classes of genes contribute to cancer, those that promote cell growth, tumor suppressor genes and a third class that influence cell death. Bcl-2 is an oncogene first identified in a B-cell lymphoma containing a chromosomal translocation. Translocation of Bcl-2 has been associated with several types of lymphomas, including follicular lymphomas, diffuse large cell lymphoma and chronic lymphocytic leukemia. Bcl-2 and several related proteins are crucial for determining whether cells live or die. Future treatments for lymphomas and other cancers may use knowledge of Bcl-2 and pathways of cell death in the design of effective and non-toxic drugs. Fig. 1 Genes in cancer Fig. 2 Origin of blood cell types ROLE OF BCL-2 IN CANCER: Many cancer cells have altered chromosomes. The translocation (chromosome rearrangement) involving the oncogene Bcl-2 has been associated with several types of lymphomas and leukemias, including 85% of follicular lymphomas (Sheer, 1997) and some cases of diffuse large cell lymphoma and chronic lymphocytic leukemia (Adams and Cory, 1998). Lymphomas and leukemias are cancers that arise from the stem cells in the bone marrow (Fig. 2). Lymphomas are usually solid tumors, while leukemias affect circulating blood cells. The “Bcl-2 family” of proteins are a group of related proteins encoded by several different genes (Fig. 3). Bcl-2 and some of the other members, including Bcl-xL, promote cell survival, and may also be oncogenes. Other family members, such as Bax, may act as tumor suppressors. 6 Fig. 3 The Bcl-2 protein family Fig. 4 Pathways of cell death NEW CANCER THERAPIES BASED ON CELL DEATH: Traditional therapies for lymphomas have mostly utilized radiation and chemotherapy (Cooper, 1992). These treatments are quite toxic to normal cells and can have extreme side effects. Bcl-2 may be able to reduce the cytotoxic effects of anti-cancer drugs by inhibiting cell death pathways. Bcl-2 plays a key role in a complex process controlling cell death and survival (Fig. 4). The pathways of cell death may suggest new ways in which cancer might be controlled. Some of these new treatments may prove to be both effective in fighting cancer and less toxic to cells. References: 1. Adams, J. M. and Cory, S. 1998. The Bcl-2 protein family: Arbiters of cell survival. Science 281: 1322-1326. 2. Alberts, B., Bray, D., Lewis, J., Raff, M., Roberts, K. and Watson, J. D. 1994. Differentiated cells and the maintenance of tissues. In Molecular Biology of the Cell, third edition. Garland, New York, NY pp. 1161-1175. 3. Craig, R. W. 1995. The Bcl-2 gene family. Seminars in Cancer Biology 6: 35-43. 4. Cooper, G. 1992. Leukemias and lymphomas. In Elements of Human Cancer. Jones and Bartlett, Sudbury, MA pp. 267-281. 5. Sheer, D. 1997. Chromosomes and cancer. In Introduction to the Cellular and Molecular Biology of Cancer (Franks, L. M. and Teich, N. M., eds.). Oxford University Press, Oxford, UK. pp. 213217. Poster hints: 1. Keep it short. Select only the essential elements from your paper to use on your poster. Short paragraphs (like the abstract) or short itemized lists (like the section on the role of Bcl-2 in cancer) are easiest to read on a poster. Do not just enlarge the text from your paper to use as your poster. Do feel free to bring your full paper with you to refer to during the poster session, in case the details have slipped your mind. 2. A picture is worth a thousand words. Find diagrams, photographs, figures or tables to illustrate important points. Use color or contrast to make your message stand out. 3. Bigger is better. Use large fonts and enlarge illustrations so they can be seen from several feet away. 7 4. Reveal your sources. Although you should keep the text short, do include a list of references. 5. Hold it all together. Attach text and illustrations to poster board with glue, glue stick or spray adhesive. There will be some supplies for you to use for assembling posters the weeks prior to the poster session. Grading/Evaluation 1. 2. 3. 4. The overall assignment (paper and poster) is worth 75 points. Papers will be evaluated by the instructor. Posters will be reviewed by both student peers and the instructor. Your involvement as a peer reviewer is required as part of the poster grade. 8