The purpose of the study was to describe the personal experience of individuals undergoing cancer treatment in an outpatient clinic by examining their perceived supportive care needs. The theoretical basis of the study lies in Alfred Adler's holistic view of human beings as unique and indivisible (1927/1954). Six individuals recently diagnosed with cancer were recruited from the same regional outpatient cancer clinic located at a major university medical center. A semi-structured interview process with open-ended questions was utilized to understand how people individually and collectively experience cancer and cancer treatment. The 17 factors of the wellness model (Witmer, Sweeney, & Myers, 1998) were used to assess the perceived supportive care needs of the study's participants. Data were analyzed using Interpretative Phenomenological Analysis (Smith, 1998) to ascertain emergent themes and interpret the meanings of the perceptions patients have of their cancer experience. The data resulted in eight major themes being present including facing mortality; uncertainty about the future; understanding cancer diagnosis and treatment; reliance on faith; maintaining control; love and support from family; physical impact of cancer; and importance of self-care. These themes provide insight into the perceived supportive care needs that patients experience during cancer treatment. With the exception of cultural and gender domains, the holistic assessment process identified patients' needs. The factors of wellness appear to capture the experience of individuals during cancer treatment. As an approach to assessing the coping skills of cancer patients, the wellness model seems appropriate for use by clinical mental health counselors. Implications for counselor theory, training, and practice with this unique client population are discussed.

RNA-Sequencing (RNA-Seq) has become one of the most widely used techniques to interrogate the transcriptome of an organism since the advent of next generation sequencing technologies [1]. A plethora of tools have been developed to analyze and visualize the transcriptome data from RNA-Seq experiments, solving the problem of mapping reads back to the host organism's genome [2] [3]. This allows for analysis of most reads produced by the experiments, but these tools typically discard reads that do not match well with the reference genome. This additional information could reveal important insight into the experiment and possible contributing factors to the condition under consideration. We introduce PARSES, a pipeline constructed from existing sequence analysis tools, which allows the user to interrogate RNA-Sequencing experiments for possible biological contamination or the presence of exogenous sequences that may shed light on other factors influencing an organism's condition.

M.Sc. / Heat shock (HS) proteins and HS transcription factors (HSFs) have been coined as the ‘Achilles Heel’ for cancer therapy, since they have been found to be overexpressed in cancer cells and are required for cell survival during tumour progression and metastasis. Hsp70 and other members of the Hsp family have been shown to inhibit apoptosis at several different stages, contributing to resistance to chemotherapy. NSAIDs, like salicylates and aspirin, are used for the treatment and prevention of cancers such as breast cancer. SA has been shown to enhance HSF-DNA binding and results in the increased expression of heat-induced Hsp70 which is antiapoptotic. We hypothesise that SA treatment can result in the potentiation of Hsp70 in MCF-7 cells further increasing their resistance to apoptosis and thus the aim of this study was to investigate the dose-responsive effects of salicylic acid (SA) in the presence and absence of heat shock on components of the pro and antiapoptotic components of the apoptotic pathway. MCF-7 cells, which naturally overexpress Hsp70, were treated with several doses of SA in the presence and absence of a mild heat shock, followed by analysis of Hsp70 and several pro and antiapoptotic members of intrinsic and extrinsic apoptotic pathways, including Bcl-2, Bax, caspase 6 and 8, JNK, AIF and APAF-1. Induced Hsp70 accumulation by the SA treatments in the presence and absence of heat shock enhanced apoptosis in cells exposed to SA whereas higher concentrations of SA combination with heat shock induced necrosis and a decrease in Hsp70 accumulation in MCF-7 cells. Identification of the effects which specific concentrations of SA in the presence and absence of heat shock had on the apoptotic pathway constituents helped highlight potential pathways by which cell death could occur in MCF-7 cells through the downregulation of Hsp70. It is most likely that MCF-7 cell death is occurring due to the release of reactive oxygen species (ROS) which in turn lead to necrosis or death may be achieved via a cathepsin-B-mediated cell death pathway where both of these possibilities need to be further investigated.

This dissertation presents an ethnographic account of a socially diverse, public breast cancer clinic in Johannesburg. The findings of this qualitative research radically challenge the unproblematised and overdetermined use of the categories of race and gender in existing literature concerning this disease. The growing breast cancer epidemic in South Africa affects all demographic categories of women including young women. Yet, previous research frames this as a racialised and gendered crisis. Black women have been depicted as ignorant “problem patients” who resist biomedical treatment, and all women are described as having a particular relationship to their breasted bodies and a deep fear of mastectomy. Departing from these stereotypes, this ethnography reveals unanticipated data showing, firstly, that race, class, age and level of education did not determine women’s relationship to breast cancer and biomedicine. Secondly, socially diverse women commonly experienced breast cancer as a life-threatening disease that evoked confrontation with existential concerns regarding suffering, death, family, and faith. Due to these commonalities, an intimate and powerful sociality existed amongst women at this clinic. Thirdly, within this sociality, women accepted mastectomy as a necessity in creating a healthy body. Breastlessness was normalised and women generally were reluctant of breast reconstruction, thus destabilising the conceptual relationship between breasts and gender. This dissertation’s deconstruction of the use of hegemonic social categories is a significant intervention in a context where these categories are often viewed as absolute determinants of social and health phenomena, and therefore prompts more nuanced approaches to understanding experiences of illness in post-apartheid South Africa.

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of requirements for the degree of Master of Science. Johannesburg 2015. / Ovarian cancer is the most lethal gynaecological cancer. About 90% of ovarian cancers are epithelial (ovarian carcinomas), thought to arise from the ovarian surface epithelium. Diagnosed usually at clinically advanced stages, many patients show poor response to chemotherapy, with resistance and recurrent disease being prevalent. siRNA technology is currently being explored in clinical trials as a form of targeted therapeutic strategy in the disease. RBBP6 is a 250kD protein that enhances MDM2-mediated ubiquitination of p53 and also plays a role in cell cycle regulation and cell differentiation. It is upregulated in numerous cancers such as lung, oesophageal, colorectal and cervical cancer. RBBP6 suppresses p53 binding to DNA thereby inhibiting p53-dependent gene transcription. RBBP6 was knocked down using 30 nM siRNA in RMG-1 cells for 48 hours, after which the cells were treated with 50 nM paclitaxel and 0.5μM camptothecin for 24 hours. xCELLigence real time cell analysis was used to evaluate cell proliferation. qPCR and western blot were used to evaluate both gene expression and protein expressions respectively, of Bax, Bcl-2, MDM2, p53 and p21. Flow cytometry was used to determine the mode of cell death elicited apoptosis and also analyse changes in cell cycle progression. qPCR and Western blot analyses showed that RBBP6 expression reduced by approximately 57%. There was a significant upregulation of p53 and a significant downregulation of Bcl-2 in siRBBP6 transfected cells (p<0.05). Knockdown of RBBP6 resulted in a 37±5.8% cell death. There was a significant increase in cell death in paclitaxel and siRBBP6 co-treated cells (81.6±0.79%) as compared to cells treated with paclitaxel only (76.±1.14%). siRNA-mediated knock down of RBBP6 induces cell death in RMG-1 ovarian carcinoma cells. In addition, paclitaxel-induced cell death in RMG-1 cells is potentiated by RBBP6 siRNA transfection. A combination of chemotherapy with paclitaxel or camptothecin and RBBP6 siRNA could be a possible therapeutic strategy in combatting ovarian carcinomas.

Studies have shown that tumor cells are susceptible to pharmacological targeting of their altered glycolytic metabolism with a variety of compounds that result in apoptosis. One such compound, 3-bromopyruvate (3-BP), has been shown to eradicate cancer in an animal model. However, no studies have shown whether the apoptotic fragments resulting from 3-BP treatment have the capacity to elicit an immunogenic cell death that activates dendritic cells, the primary antigen presenting cell in the immune system. Immunogenic cell death is critical to eliciting an effective adaptive immune response that selectively kills additional target cells and generates immunological memory. We demonstrated that 3-bromopyruvate induced apoptosis in a number of different murine breast cancer cell lines, including the highly metastatic 4T1 line. The dying tumor cells stimulated immature dendritic cells (DCs) of the immortal JAWS II cell line to produce high levels of the pro-inflammatory cytokine IL-12, and increased their expression of key co-stimulatory molecules CD80 and CD86. The activated dendritic cells showed increased uptake of fragments from dying tumor cells that correlated with the increased levels of calreticulin on the surface and release of high group motility box 1 (HMGB1) of the latter following 3-BP treatment. Additionally, the anti-phagocytic signal CD47 present on breast cancer cells was reduced by treatment with 3-bromopyruvate when compared to the levels on untreated 4T1 cells. 3-BP treated breast cancer cells were able to activate dendritic cells through TLR4 signaling. Signaling was dependent on both the expression of surface calreticulin and on the extracellular release of high mobility group box 1 protein (HMGB1) during the process of immunogenic cell death. Killing by 3-BP was compared to mitoxantrone and doxorubicin, among the few chemotherapeutics that induce immunogenic cell death. 3-BP killing was likewise compared to camptothecin, a compound that fails to induce immunogenic cell death. Importantly, 3-BP did not markedly decrease the levels of the key peptide presenting molecule MHC I on DCs that were co-cultivated with dying tumor cells. Treatment of the highly aggressive triple negative BT-20 human breast cancer cell line with 3-BP also induced an immunogenic cell death, activating human dendritic cells in vitro. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection

Extracellular stimuli may influence the M1/M2 phenotypic polarization of macrophages. We examined M1/M2 biomarkers, phagocytic activity, and tumoricidal activity in RAW 264.7 mouse macrophages. Macrophages were treated with conditioned media (CM) from 4T1 breast cancer cells, curcumin, 22-oxacalcitriol, LPS, or a combination of the previously listed. Arginase activity, a M2 phenotypic biomarker, was upregulated by the treatment of macrophages with conditioned media. Curcumin, 22- oxacalcitriol, and LPS partially inhibited RAW 264.7 arginase activity in the presence of 4T1 breast cancer media. 22-oxacalcitriol increased the phagocytic ability of RAW 264.7 macrophages in the presence of M2 polarizing substances produced by the 4T1 breast cancer cells. Also, LPS increased RAW 264.7 phagocytic ability in the presence of 4T1 breast cancer CM. This study looked at the potential substances that would possibly reverse the M2 tumor promoting macrophage phenotype seen in the breast cancer tumor environment. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection

In recent years more and more researchers have begun to use data mining and machine learning tools to analyze gene microarray data. In this thesis we have collected a selection of datasets revolving around prediction of patient response in the specific area of breast cancer treatment. The datasets collected in this paper are all obtained from gene chips, which have become the industry standard in measurement of gene expression. In this thesis we will discuss the methods and procedures used in the studies to analyze the datasets and their effects on treatment prediction with a particular interest in the selection of genes for predicting patient response. We will also analyze the datasets on our own in a uniform manner to determine the validity of these datasets in terms of learning potential and provide strategies for future work which explore how to best identify gene signatures. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

Uma nova alternativa para o tratamento do câncer foi proposta em estudos anteriores, consistindo no uso de uma nanoemulsão lipídica como transportadora de agentes quimioterápicos às células neoplásicas. A redução da toxicidade da quimioterapia promovida pelo direcionamento específico de quimioterápicos às células tumorais nos levou a testar o potencial de aplicação do sistema de nanopartículas lipídicas na terapêutica combinada do paclitaxel com a sinvastatina, um agente hipolipemiante que pode ser empregado como coadjuvante no tratamento do câncer. Nos dias 11, 14 e 19 após a inoculação de células de melanoma B16F10, camundongos C57BL/6J receberam pela via intraperitoneal soluções de oleato de paclitaxel associado à nanoemulsão lipídica 17,5&#181;mol/kg (Nano-paclitaxel), formulação comercial do paclitaxel 17,5&#181;mol/kg, nanoemulsão lipídica (Nanoemulsão) e solução salina (Controle). A sinvastatina 50mg/kg/dia foi administrada por gavagem do 11° ao 19° dia após a inoculação do tumor em um dos grupos de animais tratados com o Nano-paclitaxel (Nano-paclitaxel + Sinva), no grupo tratado com a formulação comercial do paclitaxel (Paclitaxel + Sinva) e como monoterapia (Sinva). Camundongos Balb-c saudáveis receberam os mesmos tratamentos para avaliação dos possíveis efeitos tóxicos dos diferentes tratamentos. A terapia combinada Nano-paclitaxel + Sinva apresentou toxicidade negligível em comparação com a terapia combinada Paclitaxel + Sinva que provocou perda de peso e mielossupressão nos animais. Nos animais portadores de tumor, o tratamento Nano-paclitaxel + Sinva inibiu 95% do crescimento tumoral, comparado à inibição de 44% promovida pelo tratamento Paclitaxel + Sinva. Além disso, apenas 37% dos animais portadores de melanoma submetidos ao tratamento com Nano-paclitaxel + Sinva apresentaram metástases, em contraste com 90% dos tratados com Paclitaxel + Sinva. A probabilidade de sobrevida também foi maior nos camundongos tratados com o Nano-paclitaxel + Sinva em comparação aos tratados com Paclitaxel + Sinva. A análise de amostras de tumores por citometria de fluxo mostrou que somente nos grupos de animais tratados com Sinva, Nano-paclitaxel ou com a combinação Nano-paclitaxel + Sinva houve aumento na expressão de p21 em comparação ao grupo Controle. Da mesma forma, apenas nos grupos Sinva e Nano-paclitaxel + Sinva houve redução na expressão de ciclina D1 em comparação ao grupo Controle. O teste de viabilidade celular com rodamina 123 mostrou despolarização da membrana mitocondrial com redução no número de células tumorais viáveis em todos os grupos de tratamentos em comparação aos grupos Nanoemulsão e Controle. A avaliação histológica dos tumores demonstrou que os grupos Nanoemulsão e Controle apresentaram alta densidade de células tumorais, diferentemente dos demais grupos de tratamento e que apenas os tumores do grupo Nano-paclitaxel + Sinva apresentaram aumento na presença de fibras de colágeno tipo I e III. Em comparação ao grupo Controle, os tumores dos grupos Sinva, Paclitaxel + Sinva, Nano-paclitaxel e Nano-paclitaxel + Sinva apresentaram redução na expressão imunohistoquímica de ICAM, MCP-1 e MMP-9 sendo que o grupo Nano-paclitaxel + Sinva apresentou a menor porcentagem de área marcada positivamente para a MMP-9. A terapia combinada com Nano-paclitaxel + Sinva é menos tóxica e mais efetiva na inibição do crescimento tumoral do que a mesma terapia com a formulação comercial do paclitaxel. / In previous studies we have proposed a novel approach for cancer treatment consisting of the use of a lipid nanoemulsion as a vehicle to direct chemotherapeutic agents to neoplastic cells. Reduction of chemotherapy toxicity promoted by specific targeting of antineoplastic agents to tumor cells led us to test the application of the lipidic nanoparticle system in combined treatment with paclitaxel and simvastatin, a cholesterol-lowering drug that can be used as coadjuvant in cancer treatment. On days 11, 14 and 19 after B16F10 melanoma cells inoculation, C57BL/6J mice were intraperitoneally injected with paclitaxel oleate associated to the lipidic nanoemulsion 17.5 &#181;mol/kg (Nano-paclitaxel), commercial formulation of paclitaxel 17.5 &#181;mol/kg, lipidic nanoemulsion (Nanoemulsion) or saline solution (Control). Simvastatin 50 mg/kg/day was administered by gavage from days 11 to 19 after tumor inoculation in one group of animals treated with Nano-paclitaxel (Nano-paclitaxel + Simva), in the group treated with commercial formulation of paclitaxel (Paclitaxel + Simva) and as monotherapy (Simva). Evaluation of possible toxic effects of the treatments was accessed in healthy Balb-c mice. Combined therapy with Nano-paclitaxel + Simva showed negligible toxicity as compared with the combination of Paclitaxel + Simva which resulted in animal weight loss and myelosuppression. In tumor-bearing animals, treatment with Nano-paclitaxel + Simva resulted in a remarkable tumor growth inhibition rate of 95%, compared to a 44% inhibition rate promoted by treatment with Paclitaxel + Simva. Moreover, only 37% of melanoma bearing animals treated with Nano-paclitaxel + Simva developed metastasis, in contrast to 90% of those treated with Paclitaxel + Simva. Survival rates were also higher in mice treated with Nano-paclitaxel + Simva in comparison to Paclitaxel + Simva treated animals. Analysis of tumor samples by flow cytometry showed that only animals treated with Simva, Nano-paclitaxel or Nano-paclitaxel + Simva increased the expression of p21 in comparison to Control group. Also, tumors from animals treated with Simva or Nano-paclitaxel + Simva presented a decrease in the expression of cyclin D1 in comparison to Control group. Cell viability test with rhodamine 123 showed mitochondrial membrane depolarization with reduction of tumor viable cells in all treatment groups in comparison to Nanoemulsion and Control groups. The histological study revealed that in contrast to drugs treated groups, tumors from Nanoemulsion and Control groups presented high tumor cell density and only Nano-paclitaxel + Simva treated animals presented tumors with increased presence of collagen fibers I and III. In comparison to Control group, tumors from groups Simva, Paclitaxel + Simva, Nano-paclitaxel and Nano-paclitaxel + Simva showed a reduction in immunohistochemical expression of ICAM, MCP-1 and MMP-9 and the group Nano-paclitaxel + Simva presented the lowest percentage of area positively stained for MMP-9. Combined therapy with Nano-paclitaxel + Simva was less toxic and more effective in promoting tumor growth inhibiton than the same combined therapy with the commercial formulation of paclitaxel.

An improved method is introduced for prediction of local tumor control following lung stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) patients using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). A normalized background-corrected tumor maximum Standard Uptake Value (SUVcmax) is introduced using the mean uptake of adjacent aorta (SUVref), instead of the maximum uptake of lung tumor (SUVmax). This method minimizes the variations associated with SUVmax and objectively demonstrates a strong correlation between the low SUVcmax (< 2.5-3.0) and local control of post lung SBRT. The false positive rates of both SUVmax and SUVcmax increase with inclusion of early (<6 months) PET scans, therefore such inclusion is not recommended for assessing local tumor control of post lung SBRT. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2013.