Thesis (Ph.D.)--Indiana University, 2008. / Title from screen (viewed on August 27, 2009). School of Nursing, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Joan Haase, Janet Carpenter, Patricia Ebright, Rangaraj Ramanujam. Includes vita. Includes bibliographical references (leaves 303-316).

Thesis (M.S.W.)--Smith College School for Social Work, Northampton, Mass., 2009. / Includes bibliographical references (p. 50-51).

Thesis (M.S.)--University of Michigan, 1990.

Bakgrund: Varje år drabbas 55 000 personer i Sverige av cancer och behandlas oftast med kombinerade behandlingar. Den vanligaste biverkningen och det mest påfrestande symtomet vid cancer är fatigue. Fatigue betyder extrem trötthet/utmattninig och är en subjektiv upplevelse. Fatigue är inte en trötthet som går över efter sömn och vila. Syfte: Syftet med denna litteraturstudie är att beskriva hur det är att leva med fatigue vid cancer och cancerbehandling. Metod: En systematisk litteraturstudie som bygger på 15 vetenskapliga artiklar. Artiklarna är både kvalitativa och kvantitativa och har kvalitetsgranskats utifrån Fribergs kriterier för analys av vetenskapliga studier. Litteraturstudien utgår från det teoretiska begreppet livskvalitet. Resultat: Resultatet utmynnade i tre teman; Aspekter som påverkar graden av fatigue, Fatigues negativa påverkan på livskvalitet samt Sätt att hantera fatigue. I det första temat framkom det att fatigue är föränderligt beroende på vilken cancerdiagnos samt cancerbehandling personer genomgår. Det framkom hur fatigue är ett multidimensionellt begrepp där flera andra symtom är relaterade till fatigue. Andra temat innefattar hur avsaknad av energi och social isolation påverkar personers livskvalitet negativt. Det tredje temat innefattar hur personer hittar individuella strategier för att hantera sin fatigue och att fysisk aktivitet är den strategi som visats sig ha mest positiv inverkan på att minska graden av fatigue. Diskussion: I resultatdiskussionen diskuteras begreppet livskvalitet som är den teoretiska utgångspunkten i examensarbetet. Livskvalitet berör både sjukdomsspecifika aspekter samt biverkningar av behandlingen som bidrar till ohälsa. Detta är tillämpbart eftersom fatigue upplevs som psykiskt, fysisk och socialt påfrestande. Livskvalitet är något föränderligt och förändras då personer får en svår sjukdomsdiagnos. Även sjuksköterskans arbete är viktigt i mötet med personer med fatigue då sjuksköterkan kan komma med förslag på strategier som kan göra fatigue mindre påfrestande. / Background: Each year, 55 000people in Sweden affected by cancer and is usually treated with combined treatments. The most common side effect and the most distressing symptom of cancer is fatigue. Fatigue means extreme tiredness/exhaustion and it’s a subjective experience. Fatigue is not tiredness that goes over after sleep or rest. Aim: The aim of this study is to describe what it's like to live with fatigue in cancer and cancer treatment. Methods: A systematic literature review based on 15 scientific articles. The articles are both qualitative and quantitative and quality reviewed for Friberg's criteria for analyzing scientific studies. The literature review is based on the theoretical concept of quality of life. Results: The analysis resulted in three themes: Aspects that affect the level of fatigue, Fatigues negative impact on quality of life and method for managing fatigue. In the first place it was found that fatigue is constantly changing depending on the diagnosis of cancer and cancer treatment that people receiving. It also reached the conclusion how fatigue is a multidimensional concept where several other symptoms are related to fatigue. The Second theme includes the lack of energy and social isolation affects people's quality of life negatively. The third theme involves how people find individual strategies to deal with their fatigue and physical activity is the strategy that proved to have the most positive impact on reducing the severity of fatigue. Discussions: The results discussed the concept of quality of life, the theoretical concept in the literature review. Quality of life concerns both disease-specific aspects and treatment side effects that contribute to ill health. This is applicable because fatigue is experienced as mental, physical and social discomfort. Quality of life is something changing and change as people get a severe disease diagnosis. Even the nurse's work is important when meeting people with fatigue when nurses can make suggestions on strategies that can make fatigue less strenuous.

Thesis (MTech (Radiography))--Cape Peninsula University of Technology, 2012 / Introduction: Brachytherapy plays an essential role in the management of patients with cervical cancer. The high cervical cancer burden in Africa presents challenges with regard to provision and sustainability of these services. This study analysed treatment outcomes of two brachytherapy modalities, high dose rate (HDR) and low dose rate (LDR) intracavitary treatment for patients with cervical cancer, and evaluated the problems and challenges of the provision of these services within the African context. Methodology: The study was conducted using a case study approach with mixed methods at two sites in Africa, one in South Africa (Centre I) and the other in Kenya (Centre II). The study explored factors and issues affecting definitive radiotherapy of the patient with cervical cancer at the two sites with a focus on the brachytherapy treatment. The case study provided an opportunity to collect in-depth data consisting of quantitative and qualitative components that generated numeric and textual data. Treatment outcomes of one site treating with HDR and the other LDR intracavitary brachytherapy were retrospectively analysed for a maximum sample size of 193 (91%) patients in the HDR group and 49 (100%) patients in the LDR group. All patients were treated with external beam radiation therapy (EBRT) using parallel opposed beams (POP) for the patients that received LDR brachytherapy, and four field box technique or POP for those that received HDR brachytherapy. The linear quadratic formula was used to calculate the equivalent dose in 2 Gy fractions (EQD2) between the two groups.

Orientador: Debora Aparecida Pires de Campos Zuccari / Banca: Ana Elizabete Silva / Banca: Lílian Castiglioni / Banca: Ana Carolina Prado Ribeiro / Banca: Dorotéia Rossi Silva Souza / Resumo: O câncer oral é o tipo mais comum de câncer de cabeça e pescoço e o seu alto índice de mortalidade e morbidade está intimamente relacionado com os processos de angiogênese e metástase. A superexpressão do fator induzível por hipóxia - HIF1- -, do fator de crescimento endotelial vascular - VEGF - e da quinase associada à proteína Rho - ROCK1 - estão relacionados com prognóstico desfavorável em carcinoma oral. A melatonina apresenta propriedades oncostáticas, antiangiogênicas e antimetastáticas em vários tipos de neoplasias, no entanto, a sua ação no câncer oral é pouco explorada. O presente trabalho teve por objetivo analisara expressão dos genes nos processos de angiogênese e metástase em linhagens de carcinoma epidermóide de língua, após tratamento com melatonina. As linhagens SCC4, SCC9, SCC15 e SCC25 foram testadas, e as linhagens SCC9 e SCC25 foram selecionadas para este trabalho. A ação da melatonina foi verificada em condições de normóxia e hipóxia por qRT-PCR quantitativa e por imunocitoquímica, na expressão gênica e proteica de HIF1- , VEGF e ROCK1. Os resultados demonstraram que houve diminuição da viabilidade celular em ambas as linhagens após o tratamento com melatonina. A análise gênica mostrou a inibição da expressão dos genes proangiogênicos HIF1- (P < 0,001) e VEGF (P < 0,001) em condições de hipóxia, e do gene prometastático ROCK1 (P < 0,0001) na linhagem SCC9, após tratamento com 1 mM de melatonina. A análise imunocitoquímica confirmou os dados de expressão gênica, validando os resultados de qRT-PCR quantitativa da linhagem SCC9. O tratamento com melatonina não demonstrou inibição da expressão dos genes HIF-1 , VEGF e ROCK1 na linhagem SCC25, a qual apresenta características moleculares diferenciadas e um grau de malignidade maior quando comparada à linhagem SCC9. Em conclusão a melatonina reduziu a viabilidade celular na linhagem SCC25 e inibe a expressão dos ... / Abstract: Oral cancer is the most common type of cancer of the head and neck and its high mortality and morbidity is closely related to the processes of angiogenesis and metastasis. Overexpression of Hypoxia-inducible factor 1-alpha - HIF1 - -, Vascular Endothelial Growth Factor - VEGF - and Rho-associated serine-threonine protein kinase - ROCK1 - are related to poor prognosis in oral carcinoma. Melatonin has oncostatics, antiangiogenic and antimetastatics properties in several types of cancer, however, its action in oral cancer is underexplored This study aimed to analyze the expression of genes in the process of angiogenesis and metastasis in squamous cell carcinoma cell lines of tongue after treatment with melatonin. The lines SCC4, SCC9, SCC15 and SCC25 were tested, and the lines SCC9 and SCC25 were selected for this study. The action of melatonin was observed under conditions of normoxia and hypoxia by quantitative qRT-PCR and immunocytochemistry in gene and protein expression of HIF1 - , VEGF and ROCK1. The results showed that there was a decrease in cell viability in SCC25 strains after the treatment with melatonin. The analysis showed the inhibition of gene expression of proangiogenics genes HIF1 - (P < 0.001) and VEGF (p <0.001) under hypoxic conditions and prometastatic gene ROCK1 (P < 0.0001) in the line SCC9 , after treatment with 1 mM melatonin. The immunocytochemistry analysis confirmed the gene expression data, validating the results of quantitative qRTPCR of lineage SCC9. Treatment with melatonin did not show inhibition of the expression of HIF- 1 , VEGF and ROCK1 in the line SCC25, which has different molecular characteristics and degree of malignancy greater when compared to the line SCC9. In conclusion melatonin affects cell viability in the strains SCC9 and SCC25 and inhibits gene expression of HIF1 - , VEGF and ROCK1 in the line SCC9. The potential therapeutic effect of melatonin in these subtypes of oral cancer can be ... / Doutor

Orientador: Gilberto Uemura / Coorientador: Maria Cristina Ferreira Sena / Banca: Eduardo Carvalho Pessoa / Banca: Adriano Bueno Tavares / Resumo: A super-expressão do HER-2 tem sido associada a maior agressividade biológica do tumor e a resistência a alguns tipos de tratamento. O objetivo deste trabalho é avaliar o valor prognóstico da super-expressão do HER-2, nas pacientes portadoras de câncer de mama. Estudo coorte que analisou 90 pacientes com diagnóstico de carcinoma ductal infi ltrante de mama atendidas no Hospital Regional de Sobradinho no período de 1 de Janeiro de 2005 até o 31 de dezembro de 2010. A investigação da super-expressão do HER-2 foi realizada por técnica de Imunohistoquimica. As pacientes foram divididas em dois grupos: Grupo A presença de super-expressão do HER-2 (HER-2 positivo) e grupo B ausência de super-expressão (HER-2 negativo). Ambos os grupos foram comparados às características clinicas, patológicas, eventos adversos, sobrevida global e sobrevida livre de doença. A prevalência da presença do HER-2 na amostra foi de 15,55%. A meia de idade no momento do diagnóstico, o tamanho do tumor, o estado menstrual, o estádio clinico e estado linfonodal não foram fatores signifi cativos de prevalência para a presença do HER-2 positivo. O receptor de estrogênio (p=0,0356), receptor de progesterona (p=0,0059) e mostraram associação signifi cativa com o HER-2. A análise multivariada mostrou que a prevalência do HER-2, em pacientes com câncer é 2,92 vezes maior naqueles com receptor de estrogênio negativo (p= 0,0007) e 8,84 vezes maior naqueles com receptor de progesterona positivo (p< 0,0001). A sobrevida livre de doença e sobrevida global é igual em pacientes com HER-2 positivo. A sobrevida livre de doença para pacientes com axila com mais de 4 linfonodos comprometidos é menor (p=0,0009) assim como a sobrevida global (p<0,0001). O tamanho tumoral também é fator adverso mostrando que tumores maiores de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The overexpression of HER-2 has been associated with increased aggressiveness of the tumor and resistance to some types of treatment. The objective of this study is to evaluate the prognostic value of overexpression of HER-2 in patients with breast cancer. A cohort study that analyzed 90 patients diagnosed with infi ltrating ductal carcinoma breast treated at the Regional Hospital Sobradinho the period 1 January 2005 until December 31, 2010. The investigation of the presence of overexpression of HER-2 was performed by immunohistochemical techniques. The patients were divided into two groups: Group A who had the overexpression of HER-2 and the B group who had no overexpression and compared the clinical, pathological, adverse events, overall survival and disease-free survival. The prevalence of the presence of HER-2 in the sample was 15.55%. The age at diagnosis, tumor size, menopausal status, clinical stage and lymph node status were not signifi cant factors prevalence for the presence of HER-2. The estrogen receptor (p = 0.0356), progesterone receptor (p = 0.0059) and showed signifi cant association with HER-2. Multivariate analysis showed that the prevalence of HER-2 in cancer patients is 2.92 times higher in those with estrogen receptor negative (p = 0.0007) and 8.84 times higher in those with progesterone receptor positive (p < 0.0001). The disease-free survival and overall survival is equal in patients with HER-2 positive. The disease-free survival for patients with more than 4 axillary lymph nodes is lower (p = 0.0009) and overall survival (p <0.0001). The tumor size is also an adverse factor showing that tumors larger than 2 cm have a lower disease-free survival (p = 0.0103) and shorter overall survival (p = 0.0103). The presence of over-expression of... (Complete abstract click electronic access below) / Mestre

Class of 2017 Abstract / Objectives: The specific aims of this project were to evaluate the incidence of carboplatin HSR in patients with the BRCA1 or BRCA2 mutations compared to those without these mutations. Secondary objectives were to identify carboplatin cycles where reactions occurred, grade of reaction, and treatment outcomes. Methods: This retrospective chart review included 167 ovarian, fallopian tube, and primary peritoneal cancer patients at the University of Arizona Cancer Center who underwent a regimen with carboplatin from 2013-2015. Results: 126 out of 167 patients were analyzed. HSR occurred in 4 patients with BRCA mutations, and in 9 patients without mutations, though incidence was not significant with respect to the groups (3.1% versus 17.4%, P=0.5291). Overall, there were 11 grade 1 reactions, 14 grade 2 reactions, and 16 grade 3 reactions to carboplatin. Conclusions: Presence of a BRCA1/2 mutation was not associated with a higher incidence of HSR in carboplatin. More studies are needed to clarify the impact of BRCA mutations on developing carboplatin HSR.

Hop (the Hsp90/Hsp70 organising protein) is a co-chaperone that acts as an adapter between the major molecular chaperones Hsp90 and Hsp70 during the cellular assembly of the Hsp90 complex. The Hsp90 complex regulates the stability and conformational maturation of a range of important cellular proteins, many of which are deregulated in cancer. In this study, we hypothesised that Hop knockdown inhibits proliferation and migration of cancer cells. We characterised the expression of Hop in cell models of different cancerous status, and provided evidence that Hop was upregulated in tumour cells compared to normal cell counterparts. Using an RNA interference approach, a 60-90% knockdown of Hop was achieved for up to 144 hours in the MDA-MB-231 and Hs578T breast cancer cell lines. Hop knockdown resulted in downregulation of the Hsp90 client proteins, Akt and Stat3, as well as a change in the expression of other Hsp90 co-chaperones, p23, Cdc37 and Aha1, while no change in the levels of Hsp90 or Hsp70 was observed. Silencing of Hop impaired cell proliferation in Hs578T cells but an increase in proliferation in MDA-MB-231, suggesting that the role of Hop in cancer cell proliferation was dependent on type of cancer cell. Hop knockdown in Hs578T and MDA-MB- 231 cells did not lead to any significant changes in the half maximal inhibitory concentrations (IC50) of selected small molecule inhibitors (paclitaxel, geldanamycin and novobiocin) in these cell lines after 72 hours. Hop knockdown cells were however, more sensitive than control cells to the Hsp90 inhibitors geldanamycin and novobiocin at earlier time points and in the presence of the drug transporter inhibitor, verapamil. Hop knockdown caused a decrease in cell migration as measured by the wound healing assay in both Hs578T and MDA-MB-231 cells. Hop was present in purified pseudopodia fractions of migrating cells, and immunofluorescence analysis showed that Hop colocalised with actin at the leading edges of pseudopodia, points of adhesion and at intercellular junctions of cells that have been stimulated to migrate with the chemokine stromal derived factor-1. Hop was able to bind to actin in vitro using actin cosedimentation assays, and silencing of Hop dramatically reduced the capacity of Hs578T cells to form pseudopodia. These results establish a correlation between Hop and actin dynamics, pseudopodia formation and migration in the context of Hop silencing, and collectively suggest that Hop plays a role in cancer cell migration. This study presents experimental evidence for a promising alternative to targeting Hsp90 and Hsp70 chaperones, a novel drug target in cancer therapy.

Thesis (M. Sc. (Biochemistry)) -- University of Limpopo, 2019 / Cervical cancer is the fourth most common cancer in females, and the seventh of all cancer types in both genders, with an estimated 500,000 new cases each year. As with liver cancer, a large majority (around 85%) of the global burden occurs in the less developed regions, where it accounts for almost 12% of all female cancers. About 90% of cervical cases are associated with human papillomavirus (HPV) as a causative agent and this virus is frequently transmitted through sexual contact involving exchange of fluids (Walboomers et al., 1997). Due to the ineffectiveness, undesirable side effects and costly treatment for the disease the current study was aimed at determining the anti-proliferative effects of extracts of selected medicinal plants for their anticancer activity on HeLa cell line invitro. In order to accomplish the outcome of this research study, medicinal plants (Toona cilliata, Seriphium plumosum and Schkuhria pinnata) from Limpopo Province (South Africa) with history of traditional use on cervical cancer-associated patients were selected. The Toona cilliata plant leaves were collected from Tzaneen, area while Seriphium plumosum and Schkuhria pinnata leaves were collected from Mankweng area. The dried leaves were grounded into powder and extracted using acetone. Thereafter, extracted leaf materials of selected plants were subjected to fingerprint profiling using TLC silicon coated plates immersed in tanks with different mobile phases (TEA, CEF and EMW) of various increasing polarities since. The plates were sprayed with vanillin/H2SO4, dried and visualised under UV light. Scavenging ability of the plant extracts was determined through investigating the presence of antioxidant activities using 0.2% of the 2,2- diphenyl-1- picrylhydrazyl (DPPH) indicator. The quantitative presence of total phenolic and flavonoids contents was also determined using garlic and quercetin as standards, respectively. Quantitative antioxidant scavenging activities were also determined and ascorbic acid was used as a positive control. This was followed by quantitative determination of ferric reducing power and thereafter the EC50 values of the extracts were determined by linear regression. Cell proliferation or viability was determined using the 3[4, 5 dimethylthiazol-2-yl]-2-5 diphenyltetrazolium (MTT) assay with actinomycin as a xv positive control and untreated cells as the negative control. Apoptotic effects of the extracts were determined using the Annexin V Fluos staining kit. This was followed by determining whether apoptosis was calcium dependent or independent using a calorimetric assay. In comparing the acetone extract yield per 10 g leaves of plants, Toona cilliata leaves exhibited the highest yield followed by Seriphium plumosum and with the least yield from Schkuhria pinnata. The finger print profile showed the prominent separation and was achieved from all the plants when using the non-polar TEA solvent. All plants were shown to contain extracts with varying levels of antioxidant activity especially when using CEF and EMW mobile phases. When evaluating the total phenolic and flavonoids contents all plant extracts exhibited presence of phenolic compounds with high presence observed in Seriphium plumosum and Toona cilliata. Extracts from Seriphium plumosum and Toona cilliata showed to have higher concentrations of phytochemicals that may be of a benefit in antioxidant activities as compared to Schkuhria pinnata in relation to the positive control and a similar trend were observed in the ferric reducing power assay. Extracts from Seriphium plumosum were shown to have the best IC50 scavenging values followed by Toona cilliata and Schkuhria pinnata respectively. All the plants exhibited free radical scavenging abilities with Seriphium plumosum shown to possess higher activities in comparison with the positive control. All the plants exhibited a dose-dependent cytotoxicity activity against the HeLa cervical cell line. Evidence of induced apoptotic activity was observed in HeLa cells when using extracts from Seriphium plumosum and Toona cilliata. Induction of apoptosis by plant extracts was shown to be calcium dependent as there was a decrease in calcium concentration with a decrease in the number of viable cells. In conclusion, the leaf extracts from Toona cilliata, Seriphium plumosum and Schkuhria pinnata contain compounds of various polarities with freeradical, antioxidant and anti-cancerous activities that may be beneficial if further studies are conducted to identify chemical compounds that may inhibit anticervical cancer activities.