Cancer

Cytogenetics is a study on the genetic considerations associated with structural and functional aspects of the cells with reference to chromosomal inclusions. Chromosomes are structures within the cells containing body's information in the form of strings of DNA. When atypical version or structural abnormality in one or more chromosomes prevails, it is defined as chromosomal aberrations (CA) depicting certain genetic pathogeny (known as genetic disorders). The present study assumes the presence of normal and abnormal chromosomal sets in varying proportions in the cytogenetic complex ; and, stochastical mixture theory is invoked to ascertain the information redundancy as a function of fractional abnormal chromosome population. This bioinformatic measure of redundancy is indicated as a track-parameter towards the progression of genetic disorder, for example, the growth of cancer. Lastly, using the results obtained, conclusions are enumerated, inferences are outlined and directions for future studies are considered.

The function and role of PAK6, serine/threonone kinase, in cancer progressionhas not yet been clearly identified. Several studies reveal that PAK6 may participate in key changes contributing to cancer progression such as cell survival, cell motility, and invasiveness. Basedon the membrane localization of PAK6 in prostate and breast cancer cells,we speculated that PAK6 plays a rolein cancer progression cells by localizing on the membrane and modifying proteins linked to motility and proliferation. We isolated the raft domain of breast cancer cells expressing either wild type (WT), constitutively active (SN), or kinase dead PAK6 (KM) and found that PAK6 is a membrane associated kinase which translocates from the plasma membrane to the cytosol when activated. The downstream effects of PAK6 are unknown ; however, results from cell proliferation assays suggest a growth regulatory mechanism.

MicroRNAs (miRNAs) may serve as diagnostic and predictive biomarkers for cancer. The aim of this study was to identify novel cancer biomarkers from miRNA datasets, in addition to those already known. Three published miRNA cancer datasets (liver, breast, and brain) were evaluated, and the performance of the entire feature set was compared to the performance of individual feature filters, an ensemble of those filters, and a support vector machine (SVM) wrapper. In addition to confirming many known biomarkers, the main contribution of this study is that seven miRNAs have been newly identified by our ensemble methodology as possible important biomarkers for hepatocellular carcinoma or breast cancer, pending wet lab confirmation. These biomarkers were identified from miRNA expression datasets by combining multiple feature selection techniques (i.e., creating an ensemble) or by the SVM-wrapper, and then classified by different learners. Generally speaking, creating a subset of features by selecting only the highest ranking features (miRNAs) improved upon results generated when using all the miRNAs, and the ensemble and SVM-wrapper approaches outperformed individual feature selection methods. Finally, an algorithm to determine the number of top-ranked features to include in the creation of feature subsets was developed. This algorithm takes into account the performance improvement gained by adding additional features compared to the cost of adding those features.

A simple method to verify the total treatment time generated by the treatment planning system (TPS) when the CONTURA MLB or the SAVI applicator are used for APBI treatments has been developed. The method compares the time generated by the TPS to a predicted time, calculated by inserting parameters obtained from the TPS in equations generated in this Thesis. The equations were generated by linearly fitting data from clinical cases that had been treated using the Contura MLB or the SAVI applicator at the Lynn Cancer Institute of the Boca Raton Regional Hospital. The parameters used were the PTV coverage, Air Kerma Strength, Balloon Volume (Contura data fit) and Evaluation PTV (SAVI data fit). As an outcome of this research, it is recommended that the plan should be reevaluated when the percent difference between the generated and the predicted times exceeds 5% for the Contura MLB, or 10% for the SAVI.

This study investigated potential apoptotic and anti-proliferative effects of the phytochemicals, genistein and anthocyanin extract, as single and combined treatments in MCF-7 human breast cancer cells. Cells were exposed to single and combined treatments with the phytochemiclas for 48 and 72 hours. Cell viability was assessed using the MTT bioassay. Apoptosis induction was assessed using acridine orange ethidium bromide and rhodamine 123 ethidium bromide fluorescence assays. Both singe and combination treatments induced dose- and time-dependent apoptotic cell death in MCF-7 cells. The percentage of apoptosis was higher in combination treatments than single treatments with either phytochemical, although the difference was not statistically significant. The combination of genistein and anthocyanin extract peaked in efficacy at 48 hours of treatment, to exhibit significantly greater (P<. O5) dose- and time-dependent cell cytotoxicity than single treatments. This study reveals potential chemopreventive implications for the complementary effects of genistein and anthocyanin extract.

In sea turtles, the study of the etiology and development of fibropapillomatosis is not fully understood. Sea turtle fibropapillomatosis is a disease characterized by the proliferation of skin fibropapillomas and occasional internal fibromas. In this study, sea turtle fibropapilloma tumor and healthy tissue samples were used to look at VEGF, BCL-2 and Bax expression. Cancer tumors have a well established pattern of protein expression that involves overexpression of vascular endothelial growth factor (VEGF), responsible for the growth of new blood vessels, and a high BCL-2 to Bax ratio that leads to uncontrolled cell proliferation. Real time PCR was used to analyze VEGF expression, and Western blot techniques were used to measure BCL-2 and Bax expression. The results indicated that expression of VEGF was not significantly higher in tumor vs. skin tissue. For the differential expression of BCL-2 and Bax, the results were not in agreement with the established levels found in cancer studies, showing no significant change in BCL-2 expression and significantly higher levels of Bax in tumor vs. healthy tissue.

Prostate cancer is the most common form of non-skin cancer and the second leading cause of cancer deaths within the United States. The five year survival rate has increased from 69% to 99% over the last 25 years for the local and regional disease, but has remained fairly low (approximately 34%) for the advanced disease. Therefore, current research is aimed at finding complementary or alternative treatments that will specifically target components of the signal transduction, cell-cycle and apoptosis pathways to induce cell death, with little or no toxic side effects to the patient. In this study we investigated the effect of genistein on expression levels of genes involved in these pathways. Genistein is a (4 , 5 , 7-trihydroxyisoflavone) is a major isoflavone constituent of soy that has been shown to inhibit growth proliferation and induce apoptosis in cancer cells. The mechanism of genistein-induced cell death and potential molecular targets for genistein in LNCaP prostate cancer c ells was investigated using several techniques. The chemosensitivity of genistein towards the prostate cancer cells was investigated using the ATP and MTS assays and apoptosis induction was determined using apoptosis and caspase assays. Several molecular targets were also identified using cDNA microarray and RT-PCR analysis. Our results revealed that genistein induces cell death in a time and dose-dependent manner and regulates expression levels of several genes involved in carcinogenesis and immunogenicity. Several cell cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin dependent kinases, indicating that genistein is able to halt cell cycle progression through the regulation of genes involved in this process.

Breast and prostate cancers are the most commonly diagnosed forms of cancer in women and men in the United States. The federal government has played an active role in dedicating resources toward breast and prostate cancers since the early 1990s, when policy actors successfully lobbied Congress to adopt policies that increased awareness and spending. Using theories of social construction, I argue that the key to their success was the ability of these policy actors to socially construct the illnesses of breast and prostate cancers into politically attractive public issues that appealed to federal policymakers. Through the use of embedded collective case study and content analysis of newspaper coverage and congressional data, this dissertation demonstrates how the social constructions of these illnesses impacted the way that breast and prostate cancers were treated as they moved through the policy process. The way in which social construction influenced the types of policies that were adopted to deal with these illnesses is also examined. Because social construction is a multidimensional and dynamic process, several different elements of this process were examined in this dissertation: the ways that policy actors attracted attention to these illnesses, how gender influenced advocacy efforts, the symbolic aspects of these illnesses, and the way the illnesses were defined on systemic and institutional agendas. Since this dissertation examines two different policy issues, the similarities and differences in breast and prostate cancer policymaking were analyzed. I found that discussing breast and prostate cancers in relation to their social constructions provides support for the importance of symbolism and non-rational policy-making processes.

This mixed methods sequential research study was performed to explore the role of identity in posttraumatic growth and psychological adjustment for adults with cancer. One hundred nineteen individuals participated in an online survey which included items from Brief COPE, Mini-Mental Adjustment to Cancer (Mini-MAC), Brief Illness Perception Questionnaire (BIPQ), Sense of Coherence Scale - 3 items (SOC-3), Posttraumatic Growth Inventory (PTGI), Illness Intrusiveness Ratings Scale (IIRS), and Centrality of Event Scale (CES). A two-step cluster analysis divided the sample into two clusters based on the integration of cancer into identity: High Cancer Identity Cluster (cancer identity scores above M) with strong cancer identity and Low Cancer Identity Cluster (scores below the M) with a weak or absent cancer identity. HCIC yielded positive and negative subgroups. A discriminant analysis revealed which variables are significant predictors of group membership: PTG factor New Possibilities (Wilks'l = .781, F (1, 119) = 32.834, p = .000), Psychological Adjustment factor Anxious Preoccupation (Wilks' l= .863, F (1, 119) = 18.612, p = .000), Illness Intrusiveness factor Intimate Relationships (Wilks' l= .794, F (1, 119) = 30.348, p = .000), and Illness Perception factor Perceived Life Impact of Cancer (Wilks' l= .783, F (1, 119) = 32.412, p = .000). From the sample, 17 individuals and spouses/partners were interviewed to obtain a deeper understanding of the lived experience of cancer. Qualitative themes of suffering, woundedness, and uncertainty were found. Narrative data corroborated the quantitative data and contributed depth to the analysis. A new Cancer Identity Process Model was offered in which assimilative and accommodative efforts are informed by identity structures.

Cancer is the second leading cause of death in the western world. In order to treat various types of cancer, platinum-based drugs are most widely employed as metal-containing chemotherapeutic agents. However, their clinical usage is hindered by toxic side effects, and by the emergence of drug resistance. Our focus was to replace platinum with less toxic metal like tin which can give better alternatives for cancer treatment. The major aim of our study was to synthesize novel organotin polyethers (Sn-O) which can be used to combat cancer. Preliminary results from our laboratory using organotin polyethers, that were synthesized by varying the structure of diols showed growth inhibition in Balb-3T3 cells. This study directly led us to hypothesize the two structural windows, first by changing the distance between diol and second, by presence of unsaturation in diols, the biological activity of organotin polyethers (Sn-O) can be enhanced significantly. Different series of polymeric compounds were synthesized based upon these two structural windows and the formation of products was validated using standard techniques like infrared spectroscopy (IR), light scattering photometer, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and nuclear magnetic resonance (NMR). The synthesized polymers arrested the growth of cancer cell lines including bone, prostate, colon, breast, pancreas and lung cancer derived cell lines in vitro. In number of instances where chemotherapeutic index values of two and greater were found that these polymers are significantly more active against cancer cells than non-cancerous cells in culture.