Cancer Research Highlights at LBNL

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 This section deals with current cancer research being conducted at Lawrence Berkeley National Laboratory. It is based on actual interviews with LBNL scientists, and it is somewhat more technical that the rest of the presentation.


M.H. BARCELLOS-HOFF

Dr. Mary Helen Barcellos-Hoff is a biologist in LBNL's Life Sciences Division. Her research primarily involves studying the effects of ionized radiation (the type used during cancer treatment) on tissues of the body, in particular, epithelial tissue. (Epithelial cells form tissues that line the gut and make up the external surface of the skin.) Her group's main areas of interest are:
1) The effects of radiation that cause cancer
2) The use of radiation to treat cancer

Dr. Barcellos-Hoff's research involves examining the way radiation changes the environment in which the cells live. The epithelial cells that she is examining are the ones associated with the mammary glands (breasts). She is examining how healthy tissue cells respond to radiation, and what triggers the repair of these cells when damaged. By studying how the cells respond, she hopes to develop a strategy that might reduce some of the negative side effects that occur during radiation therapy for cancer.

Whenever the body is exposed to ionized radiation, it stimulates a change in the cell's gene expression - that is, what proteins the cell makes. One of the negative results of this change is the development of radiogenic fibrosis , a hardening of the affected tissue that is common following radiation therapy.

The ultimate goal of the research is to identify the events that lead to fibrosis and hopefully block these events. One of the events that has been identified is that ionizing radiation activates an over-production of transforming growth factor-beta (TGFb), a molecule known for its role in producing scar tissue. One aspect of the research involves testing whether TGFb blockers would block fibrosis and therefore reduce the negative side effects of radiation therapy.


PAUL YASWEN

Dr. Paul Yaswen is a biologist working in the Life Science Division. His research also primarily involves examining the epithelial cells that are found in the mammary glands. The vast majority of tumors in humans are developed from the epithelial cells. Therefore, Dr. Yaswen is hoping that by examining the role of epithelial cells, we will get a better understanding of how cancer develops in the breasts and skin. One of the lab's objectives is to examine what makes epithelial cells grow (or stop growing) and what makes them organize in the tissues.

One area of Dr. Yaswen's research involves examining the cellular model of an epithelial cell in order to look for substances that are present in normal epithelial cells, but are not present in tumor cells. For example, the lab has isolated a calcium-binding protein which is present only in normal tissue. Dr. Yaswen is trying to find out what are some of the proteins normally found in epithelial cells and whether these proteins sometimes block or interfere with the development of a tumor.

The more opportunities cells have to divide, the greater the probability that some type of cell alteration or DNA damage will induce the onset of cancer. When cells are multiplying rapidly in your body, the natural repair system does not always have a chance to work properly. Dr. Yaswen is trying to find a way to repair the cancer cells' ability to control their own cell division.

Dr. Yaswen's work also could possibly lead to the discovery of genetic markers that may serve to warn of the early onset of cancer.


JUDY CAMPISI

Dr. Judy Campisi, another scientist in the Life Sciences Division, is investigating the life cycle of cells in the human body, in particular the cells of the breast. By attaining a better understanding of the developmental biology of the breast, Dr. Campisi hopes to determine where the common forms of breast cancer arise. Another aspect of Dr. Campisi's work involves examining the fibroblasts (cells that help to form structure on which many organs sit) which are found in most organs of the body. Fibroblasts make up part of an organ's basement membrane.

All cells in the body undergo a process called senescence, which is the natural process of aging and then dying off. There is now increasing evidence that senescent cells accumulate during aging, where they may contribute to the dysfunction of some tissues. In addition, cells can acquire mutations that allow them to "break away" from the control mechanisms of senescence. Such cells are said to be "immortal". This breaking away phenomenon is very common in cancer cells, and immortal cells can lead to metastasis, which is the spreading of the cancer to other parts of the body. By taking a closer look at the senescence of a normal cell, Dr. Campisi hopes to gain a better understanding about the relationship between aging and cancer.

Dr. Campisi's lab also is working closely with Dr. Mina Bissell's lab. They are examining the epithelial cells found in the breast. Through this collaboration, both scientists are hoping to gain a better understanding of how growth and differentiation are regulated in the epithelial cells. There is some evidence suggesting that genes similar to those that control muscle differentiation also may regulate mammary epithelial cells. Since muscle cells undergo a form of differentiation that prevents them from becoming cancer cells, Bissell and Campisi and their colleagues hope to uncover ways to control the growth of breast cancer cells.


COLIN COLLINS

Dr. Colin Collins is a researcher at LBNL who is working in conjunction with the University of California, San Francisco at the Resource for Molecular Cytogentics. Dr. Collins' lab is working in collaboration with Joe Gray, Dan Pinkel and other researchers at UCSF. The goal of their research is to develop probes for analyzing genes in malignant tumor cells. Using a special technique called Comparative Genomic Hybridization (CGH), Dr. Collins and other scientists at the lab have been able to determine the physical location on a chromosome at which a person has lost one copy of a gene. These areas on the chromosome are where oncogenes (cancer-causing genes) or tumor suppressor genes likely will appear.

By examining over one hundred tumors that are at a similar developmental stage and performing CGH on these tumors, scientists at the lab are trying to find the common region on a chromosome where oncogenes or tumor suppressor genes are most likely to be gained or lost. The portion of the genome that the lab currently is examining lies on Chromosome 20. Metastasis (spreading of the cancer to other parts of the body) is often a fatal occurrence during cancer treatment. By examining other tumors that have metastasized and then completing another CGH, scientists are able to see new regions in the genome where oncogenes or tumor suppressor genes have appeared. By gaining a better understanding of how cancerous genes spread genetically, scientists are hoping to determine the factors that promote the growth and progression of a cancerous cell.

Another tool that is an integral part of Dr. Collins research is fluorescence in situ hybridization (FISH). Using this probe, scientists are able to further isolate the cancer-inducing region of the chromosome. The fluorescent signals that are emitted help to precisely map the possible oncogenes. Eventually, one can determine the exact locations of the oncogenes on the chromosomes. By localizing these genes, scientists are hoping to further the development of molecular therapies. The utilization of these probes may prove to very important for the future treatment of cancer.

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