Download Biology 207 Research Paper and Presentation on Cancer

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

RNA-Seq wikipedia , lookup

Gene therapy of the human retina wikipedia , lookup

Genome (book) wikipedia , lookup

Vectors in gene therapy wikipedia , lookup

Mir-92 microRNA precursor family wikipedia , lookup

Polycomb Group Proteins and Cancer wikipedia , lookup

Oncogenomics wikipedia , lookup

NEDD9 wikipedia , lookup

Transcript
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