Browsing by Subject "Breast Cancer"
Now showing 1 - 7 of 7
- Results Per Page
- Sort Options
Item A Comparative Breast Cancer Study: Stage & Mortality in El Paso County's non-Hispanic white and Hispanic population(2003-05-01) Aravind, Raven; Russel HovermanAravind, Raven, A Comparative Breast Cancer Study: Stage & Mortality in El PasoCounty's non-Hispanic white and Hispanic population, 1990-2000. Master of Public Health (Epidemiology), May 2003, 17pp., 1 table, 3 figures, bibliography, 43 titles. This retrospective breast cancer study compares the stage of breast cancer diagnosis and mortality between Hispanic (HS) and non-Hispanic white women (NHW). The study includes 874 Hispanic women and 802 non-Hispanic white women diagnosed with breast cancer between January 1990 and December 2000 at the El Paso Cancer Treatment Center, El Paso Texas. The objectives of the study were: 1) to determine if this population of Hispanic women is being diagnosed at a later stage of breast cancer 2) to ascertain the relative survival of non-Hispanic white and Hispanic women 3) to verify if Hispanic women were being diagnosed at a younger age; and 4) to examine tumor size at diagnosis to determine if there is a need for more assertive screening measures in this population of women.Item ANTI-TUMOR IMMUNE RESPONSES AGAINST MTLn3 MAMMARY ADENOCARCINOMA(2014-03) Carter, KiahRae J.; Orlowski, Ashley; Hodge, LisaBreast cancer is the leading cause of cancer-related deaths. More research needs to be done to examine the role of the lymphatic system during metastasis and therapies directed at the lymphatic system. Our rat model was used because it closely mimics human breast cancer. These results will allow for the future studies of therapies targeting the lymphatic system and if they will prevent metastasis. Purpose (a): Breast cancer is the leading cause of cancer-related morbidity and mortality. New research suggests the lymphatic vessels play a key role during the metastasis of breast cancer and therapies directed at the lymph system may aid in the treatment of breast cancer. MTLn3 is a mammary adenocarcinoma that is commonly used to study the effects of tumor metastasis in Fischer 344 rats. MTLn3 closely mimics human breast cancer pathogenesis, making it ideal for the study of breast cancer disease; however, little is known about the role of the lymphatic and immune systems in this disease model. The purpose of this study was to identify the type of immune response generated during MTLn3 disease. Specifically, we proposed that natural killer cells (NK), T cells, B cells and macrophages (MO) would increase in response to disease. Methods (b): To test our hypothesis, rats were randomized into control group or were sub-cutaneously injected in the right mammary fat pad with 1x106 MTLn3 tumor cells/mL on day 0. At days 0, 7, 14, 21 and 25 post-injection, lungs, tumor-adjacent lymph nodes (ALN), tumor–opposite lymph nodes (OLN) and spleens were removed and the concentration of leukocytes was determined. Primary tumors were excised and measured to calculate tumor volume. Blood was analyzed for the complete blood count and serum was measured for cancer-specific biomarkers. Results (c): All animals gained weight until day 14 post-injection. However, rats injected with MTLn3 suffered weight loss between days 14-25 post-injection. Furthermore, primary tumor size significantly (p < 0.05) increased during this time, suggesting weight loss may be related to disease. CD4+ T cells, B cells and MO in the spleen at day 21 decreased by day 25. Tumor adjacent lymph nodes experienced an increase in all cell populations, T cells, B Cells, MO, dendritic cells and NK. There were no differences in cell populations between ALN and OLN, except MO were significantly (p < 0.05) increased in ALN at Day 25. There was no change in pulmonary leukocytes by day 25. Neutrophils, monocytes and lymphocytes in the blood were significantly (p < 0.05) increased between control and 25 days post-injection rats, suggesting there is an immune response against MTLn3 tumor cells. Conclusions (d): Collectively, our results suggest MTLn3 initiates an immune response mediated by T cells, B cells, macrophages and NK cells between days 14-25 of disease. Of interest, these cells increase in the ALN at day 25 post-injection, suggesting they migrate into the lymph nodes in response to disease. In future studies, we will determine if MTLn3 metastasizes to the sentinel lymph nodes and the lung and determine if therapies targeting the lymphatic system inhibit this process.Item Anti-Tumor Immune Responses Against MTLn3 Mammary Adenocarcinoma(2014-05-01) Carter, KiahRae J.; Hodge, Lisa M.Lymphatic pump treatment (LPT) is used as a lymph enhancing therapy to treat edema. In animals, LPT enhanced lymphatic flow, released leukocytes and inflammatory mediators into lymph, and inhibited pulmonary tumor formation. Therefore, we hypothesized the administration of LPT would enhance immunity and inhibit primary breast tumor growth. Rats were subcutaneously injected with MTLn3 and divided into MTLn3, MTLn3+Sham-LPT and MTLn3+LTP group. Sham group received light touch under anesthesia and LPT group received treatment under anesthesia. There were no changes in tumor growth between groups. Administration of Sham-LPT resulted in an increase in tumor-adjacent lymph node weight. Collectively, our data suggests LPT did not enhance primary tumor growth and may also protect against the pathogenesis exhibited by sham-LPT.Item Dissecting the Role of Protein Kinase C-Epsilon in Breast Cancer(2013-12-01) Jain, Kirti; Basu, AlakanandaProtein kinase C-epsilon (PKCε) has pro-tumor functions in many cancers including breast cancer. The purpose of this dissertation is to understand the role of PKCε in fundamental processes that are associated with breast cancer development and progression. PKCε is known to promote the survival of breast cancer cells. Autophagy is a process of cellular self-digestion that can mediate cell survival during stress. We have found that PKCε overexpression increases the basal autophagy in breast cancer cells while its depletion reduces it. Moreover, the effect of PKCε on autophagy is isozyme specific. Regulation by PKCε is not limited to basal autophagy as it also mediated starvation-induced autophagy. Looking for the possible mechanisms, we found that PKCε negatively regulates mammalian target of rapamycin (mTOR), which is the master regulator of autophagy. These results show that PKCε positively regulates autophagy, likely, via inhibition of mTOR. PKCε overexpression in mammary epithelial cells led to morphological changes indicating its role in regulation of cell plasticity. Further analysis revealed that PKCε promotes epithelial to mesenchymal transition (EMT), which is an early step in cancer metastasis. In addition, PKCε mediated transforming growth factor-beta (TGFβ)-induced EMT partially via Snail, which is a crucial EMT effector. Moreover, PKCε promoted cell migration and anoikis Ii resistance which are hallmarks of EMT. To examine the phenotypic effect of PKCε manipulation in a physiologically relevant context, we employed three dimensional (3D) cell culture model. We found that PKCε overexpression led to disruption of acinar morphogenesis in 3D culture. These results indicate a causal role for PKCε in breast tumor development and progressionItem FACTORS ASSOCIATED WITH MAMMOGRAPHY UTILIZATION IN UNDERSERVED WOMEN IN SOUTH DALLAS, TX(2013-04-12) Chen, JingPurpose: To explore the association between self-reported mammography history, demographic characteristics, and medical care services. Methods: 430 women, aged 40 years and older, recruited between 2010 and 2012 for a breast cancer prevention program, were surveyed at baseline. Surveys were paper questionnaires administered with help from lay health educators. We tested the association between previous mammogram history of the participants and demographic characteristics, as well as medical care characteristics using chi-square tests and a multivariable logistic regression. Variable selection into the model was performed with a stepwise method. Results: In the univariate analysis, results from the chi-square test indicated that four demographic variables were significantly associated (P < 0.05) with having ever received a mammogram: age, race, family income, and marital status. Seven medical care variables were significantly associated with having ever received a mammogram: (1) health insurance, (2) ever performed a breast self-examination in the last month, (3) ever had a clinical breast examination in the previous year, (4) having a personal doctor, (5) regular check-ups, (6) ever talked to a doctor about breast cancer, and (7) talking to a doctor about receiving a mammogram. In the multivariable logistic analysis, age, marital status, insurance, and talking to doctor on mammogram remained significant: 65-74 years old vs. 40-49 years old (OR = 10.9, 95% CI: 1.4-85.0), 50-64 years old vs. 40-49 years old (OR=1.8, 95%C: 1.1-2.9), ever married vs. never married (OR = 1.8, 95% CI: 1.1-3.1), having health insurance vs. not (OR = 1.8, 95% CI: 1.1-3.0), and having ever talked to a doctor about receiving a mammogram vs. not (OR = 3.2, 95% CI: 1.9-5.2). Conclusions: Being older, married, having health insurance, and ever talked to a doctor about receiving a mammogram were positively associated with past mammography. On the other hand, there is a need to develop specific strategies for promoting mammography among younger, unmarried, or underinsured women. Further study needs to be conducted in a more racially-diverse population to support these findings.Item MIMICKING INFECTION FOR IMMUNOTHERAPY AGAINST BREAST CANCER-FOOLING THE IMMUNE SYSTEM(2014-03) Kokate, Rutika; Thamake, Sanjay; Chaudhary, Pankaj; Mott, Brittney; Vishwanatha, Jamboor K.; Jones, Harlan P.Immunotherapy represents a potential and innovative means to combat cancer. It essentially harnesses the body’s immune system to fight against cancer. Previous literature suggests that cancer vaccines designed against a specific tumor antigen have been efficiently utilized to trigger immune responses against tumor cells. Despite the preliminary evidence in animal models, low immunogenicity is one of the major hurdles in the development of vaccines in humans. In order to surmount this obstacle, several approaches including the use of an “ideal” tumor antigen, appropriate delivery techniques, immune boosting strategies with co-stimulatory molecules are being explored. Purpose (a): The purpose of this study was to develop “bacteriomimetic nanoparticles” to enhance adaptive cell-mediated immune responses (CD4+ and CD8+ T cell responses) against tumor antigen as a therapeutic option for cancer treatment. Methods (b): NPs were prepared by modified solid/oil/water solvent evaporation method using an ultrasonic processor UP200H system (Hielscher Ultrasonics GmbH, Germany). We used membrane preparations of the 4T1 mouse mammary cancer cell line as a tumor antigen and CpG ODN’s as a “bacteriomimetic” stimulant. Fourteen days before tumor challenge BALB/c female mice (6-8 weeks) were pre-immunized with CpG followed by secondary immunization using respective NPs encapsulated with the membrane antigen preparation. Subsequently, mice (n=4) were challenged with 105 tumor cells intravenously (IV). Mice were sacrificed and tumors were harvested at days 3, 7 and 14 respectively. CD4+ and CD8+ T cell responses were measured in lower respiratory node and spleen using flow cytometry. In another experimental set, following the same immunization schedule as mentioned above, mice (n=5) were challenged subcutaneously (SC) with 105 tumor cells. Primary tumor size was monitored using vernier caliper and bioluminiscence imaging (Caliper Life Sciences Inc., MA, USA). Mice were sacrificed on day fourteen after tumor challenge; spleen cells were used for flow cytometric analysis and primary tumor tissue was used to evaluate CD4+ and CD8+ T cell via immunohistochemistry. Results (c): We found significant reduction in progression of tumor growth in mice immunized with CpG coated NPs containing tumor antigen (CpG-NP-Tag). Histological analysis confirmed that tumors in CpG-NP-Tag mice were relatively well differentiated and of lower grade in contrast to CpG-Blank tumors. Immunofluorescence (IF) data further revealed that CpG-NP-Tag tumors had lesser proliferation and higher apoptotic activity. Tumor CD4+ T cell infiltration as well as T cell response in spleen was found be higher in CpG-NP-Tag NP immunized mice as compared to the controls. Conclusions (d): Primary tumor size, IHC, IF and flow cytometry analysis indicate that CpG-NP-Tag NPs were successfully employed to boost the immune response against tumor cells.Item PREPARATION AND CHARACTERIZATION OF NOVEL MULTIFUNCTIONAL LIPOPOLYMERIC HYBRID NANOSYSTEMS FOR IMAGING AND THERAPY OF HIGHLY METASTATIC BREAST CANCER(2013-04-12) Mukerjee, AninditaPurpose: The technology based design of nanosystems has become more complex over the years since it now combines multiple functionalities within nanoparticles as a single delivery system. One such design involves combining the advantages of biodegradable polymeric nanoparticles with the biomimetic properties of liposomes. In this study, we have successfully engineered a multifunctional lipopolymeric hybrid nanosystem encapsulating an anticancer agent, curcumin, with a fluorescently labeled dye for imaging and therapy of breast cancer. Methods: Functionalized curcumin loaded hybrid nanoparticles for was prepared by nanoprecipitation method. The hybrid nanoparticles thus formulated were then characterized for drug loading, particle size, zeta potential and surface morphology. To evaluate our nanosystems, intracellular uptake of these drug loaded nanosystems along with its effect on cellular migration in non-malignant (MCF10A) and highly malignant metastatic breast cancer cell lines (MCF10CA1a) was determined. Further, functional assays like cell viability assay were carried out to determine the functional integrity of the encapsulated drug. Long-term stability analysis of the hybrid nanoparticles were carried out for 6 days at room temperature. Results: The formulation of the lipopolymeric hybrid nanosystem by nanoprecipitation was found to be successful with a drug loading of 12.4 ± 0.8 µg/mg of nanoparticles for curcumin. The particle size distribution was narrow with the mean particle size being 116.8 ±10 nm. The zeta potential of these hybrid nanoparticles was determined to be -31.66mV.The surface morphology of the hybrid nanoparticles was determined by Transmission Electron Microscopy. Results revealed smooth and spherical nanoparticles. Intracellular uptake studies were carried out in highly malignant breast cancer cell line, MCF10CA1a. Confocal Microscopy scans show robust cellular uptake of the fluorescently labeled hybrid nanosystems. Long-term stability analysis results reveal that these hybrid nanoparticles are stable in PBS for as long as 6 days with only ±5 nm change observed in mean particle size. Conclusions: We successfully formulated the lipopolymeric hybrid nanosystem with a fluorescently labeled dye and an anticancer agent. This type of a combinatorial theranostic system platform would allow for imaging and therapy with much less side effects than the traditional treatments because it will use anticancer agents at lower doses than used in current chemotherapies.