SENIOR PROJECTS AND STUDENT RESEARCH
Below are just a few examples of recent senior projects and student research in MBC’s Biology department. To learn more about undergraduate research at Mary Baldwin College, visit www.mbc.edu/research.
Caitlin Combs ’11
The Effect of Docetaxel and Rapamycin on LNCaP and Neuroendocrine Differentiated LNCaP Cells
Prostate cancer is the most common cancer in men and the second leading cause of cancer death in American men (American Cancer Society, 2011). In many of these cases, the cancer may progress to a more invasive and aggressive form that does not respond to hormone therapy. During this time, some cells may undergo neuroendocrine differentiation and facilitate tumor progression. These neuroendocrine (NE) cells support the growth and survival of the surrounding cancer cells. Thus, developing treatments that target NE cells may aid in cancer therapy. In this study, we investigated whether docetaxel and rapamycin cause apoptosis in cancer cells and differentiated cancer cells. Docetaxel is a well-known and effective chemotherapeutic that is widely used in prostate cancer therapy. Rapamycin inhibits cell signaling pathways and reduces cell proliferation in other cancer types (Amato et.al, 2008). LNCaP cells were treated with Forskolin and IBMX to stimulate NE differentiation. MTT and Caspase 3 assays were used to determine if treatment arrested growth and caused apoptosis, respectively. The results of this study show that there is a significant decrease in cell number following all treatments except rapamycin (p = 0.000, d.f =7, F= 15.912). The results of this study indicate that NE cells are not more susceptible to treatment with docetaxel and rapamycin together, compared to undifferentiated LNCaP cells. In addition, the effects on Caspase 3 activity were not significant. One reason for this could be that the cells are not utilizing a Caspase 3 pathway while undergoing apoptosis. The results of the MTT assays may indicate that NE cells are susceptible to rapamycin but less vulnerable to chemotherapeutics overall.
April Lao ’11
Effect of CpG Oligonucleotide and LL-37 on Prostate Cancer Growth and Invasion
CpG oligonucleotides, short pieces of DNA with characteristics of bacterial DNA, have recently been considered as an alternative to chemotherapy. Some studies have shown CpGs to stimulate anti-tumor immune responses with none of the side effects associated with traditional chemotherapy. However, CpG’s effects are weak, and results are contradictory, with antitumor effects seen in ovarian cancer in mice but increased invasion and decreased growth in the PC-3, LNCaP, and DU-145 prostate cancer cell lines. LL-37 is an antimicrobial DNAbinding peptide with DNA-binding properties that allow it to increase the body’s immune response to CpG. LL-37 is found throughout the body and in higher amounts in breast, lung, and prostate cancer tumors. The combination of CpG and LL-37 has recently been shown to enhance the anti-tumor effects seen with CpG in ovarian cancer in mice. In this project, I investigated the effect of CpG in combination with LL-37 on prostate cancer cell line growth and invasion. I hypothesized that the addition of LL-37 would enhance the effects seen with CpG (i.e. decreased growth and increased invasion). The two cell lines studied were PC-3s, derived from an androgen-independent prostate cancer bone metastasis, and LNCaPs, derived from an androgen-responsive prostate cancer lymph node metastasis. Results indicate CpG+LL-37 increases growth in PC-3 cells but has no effect on LNCaP cell growth or invasion. These results indicate that, contrary to initial beliefs, CpG oligonucleotides in combination with LL-37 should not be used as a therapy.
Johanna A. Gleason ’10
The Effects of Different Latitudinal Characteristics on the Intensity of Avian Malaria in Red-eyed Vireos
Avian malaria is a parasitic disease caused by two blood parasites from the genera Haemoproteus and Plasmodium. The parasites enter the bird’s blood stream by insect vectors such as mosquitoes. These insect vectors tend to thrive better in warmer climates with high humidity. The warmer climate allows for a longer growing season for these insect vectors, which in turn, gives them a longer time to infect the birds. Climate conditions usually vary depending on latitude. The climate tends to be warmer in lower latitudes and cooler in higher latitudes. The purpose of this study was to determine if these different latitudinal characteristics affect the intensity of avian malaria in Red-eyed Vireos. Preliminary findings suggest that there is no difference in parasite load between lower and higher latitudes.
Garnett A. Mingledorff ’10
Neuroendocrine Differentiation Induced by Epidermal Growth Factor: Effects on and Implications for Chemoresistance in Androgen-Independent Prostate Cancer Cells
Neuroendocrine (NE) cells have been implicated in the progression of prostate cancer into a more metastatic and hormone- independent stage. NE cells are present in the normal prostate and help regulate cell growth and differentiation; however, there are known changes in the number, histology, and function of NE cells in association with prostate cancer progression. It is thought that NE cells in progressed prostate cancer express antiapoptotic proteins and induce neighboring cells to express similar factors, thus preventing cell death. Epidermal growth factor (EGF) has been shown in recent studies to induce NE differentiation in androgen-independent prostate cancer cells. To determine if EGF plays a role in our model of prostate cancer, androgen-independent PC3 cells were cultured and treated with varying of levels of EGF for three days and then treated with varying concentrations of the chemotherapeutic drugs Cisplatin or Docetaxel for two additional days. A cell proliferation assay was performed after treatment to gauge cell survival. Preliminary results indicate that NE differentiation is induced by EGF and may possibly protect these cells from Docetaxel and Cisplatin-induced cell death. By understanding the underlying mechanisms in prostate cancer progression and chemoresistance, we can develop better treatments to improve patient survival.
Samantha Lee Skiba ’10
Comparative Study of Avian Malaria Parasites Plasmodium and Haemoproteus in Relation to Foraging Height in Red-Eyed Vireos and Ovenbirds
Avian malaria is a disease caused by protozoans, Plasmodium and Haemoproteus, that parasitize the red blood cells of their hosts. The red-eyed vireo is a common songbird in North American forests, foraging high in the canopy, whereas ovenbirds forage on the forest floor. These different foraging heights allow the two species to be used to study whether a host-specific interaction exists between foraging height and parasite infection. Blood samples from red-eyed vireos and ovenbirds were collected from Augusta County, Virginia. Parasite infections were detected through polymerase chain reaction of parasite DNA extracted from bird blood samples. A restriction enzyme specific to Haemoproteus was used to distinguish between the infections. Preliminary results show that ovenbirds are infected with Plasmodium and red-eyed vireos are infected by both parasites. Research is in progress to determine whether a correlation exists with foraging height. Results of this research will help understand the infection dynamics of avian malaria.
Margaret Bivans ’10
Effects of the CB8 and 5-HT Complex on PC3 Cell Proliferation
Prostate cancer is one of the leading causes of death for men in the western world. With the increase in androgen-independent prostate cancer, treatment options are becoming more limited and less effective. A common characteristic in androgenindependent tumors is the presence of neuroendocrine-like cells that secrete growth factors, such as serotonin, that stimulate the proliferation of other cancer cells. Cucurbituril, a member of a recently discovered family of macrocyclic molecules, is capable of binding serotonin. We hypothesized that this binding will make serotonin inaccessible to cell surface receptors in prostate cancer cells and thus block their proliferation. Data show that addition of cucurbituril and serotonin to PC3 cell cultures decreased cell proliferation when compared with serotonin alone. This finding suggests a mechanism by which inhibiting binding of growth factors to prostate cancer cells may have therapeutic potential.
Elizabeth Gifford ’09
Stabilization of Lipase in Chitosan
Lipase, an enzyme that breaks down fats in the body, is heat-sensitive and loses activity over sixty-five degrees Celsius. This project explores the possibility of stabilizing a lipase in the polymer chitosan, which is derived from the shells of crustaceans. The success of this project holds implications for industry, where many enzymes are beneficial to processes that must be performed in high-heat environments.