nÃo hà / A elaboraÃÃo de materiais educativos de orientaÃÃo a pacientes em tratamento quimioterÃpico visa melhorar a qualidade da assistÃncia prestada pois entende-se que quando bem orientados sobre como lidar com a terapÃutica a que sÃo submetidos aumenta-se a adesÃo; as informaÃÃes os tornam mais seguros e colabora-se para o sucesso do tratamento O objetivo do estudo foi construir e validar uma cartilha de orientaÃÃo sobre o tratamento quimioterÃpico Trata-se de uma pesquisa metodolÃgica que seguiu as seguintes etapas para construÃÃo e validaÃÃo de manuais para a educaÃÃo em saÃde: submissÃo do projeto ao comità de Ãtica levantamento bibliogrÃfico construÃÃo do manual educativo e validaÃÃo do material construÃdo Para a construÃÃo da cartilha realizou-se um levantamento bibliogrÃfico nas seguintes bases de dados: Scielo Lilacs Cochrane e Pubmed utilizando os descritores: âcÃncerâ âquimioterapiaâ âantineoplÃsicosâ âtoxicidade de drogasâ e âcuidados de enfermagemâ contemplando o perÃodo de 2003 a 2013 A sÃntese de 19 artigos selecionados norteou orientaÃÃes sobre os principais efeitos colaterais da quimioterapia (enjoos vÃmitos diarreia ferimentos na boca queda do cabelo baixa imunidade reaÃÃes cutÃneas e outros) e cuidados de enfermagem para estes pacientes ApÃs a escolha do conteÃdo procurou-se produzir um material educativo rico em cores a fim de descontrair e incentivar a leitura as imagens foram cuidadosamente selecionadas com a ajuda de um profissional de designer grÃfico buscando-se em todos os momentos adequar Ãs orientaÃÃes da literatura as caracterÃsticas do instrumento idealizado A construÃÃo da cartilha ocorreu no perÃodo de novembro de 2013 a janeiro de 2014 Em seguida a cartilha foi validada por nove juÃzes quanto aos aspectos tÃcnicos todos com vasta experiÃncia na Ãrea do cÃncer e quimioterapia A anÃlise dos dados foi realizada de forma descritiva A valoraÃÃo atribuÃda pelos juÃzes aos itens foi em sua grande maioria Totalmente adequado e Adequado As maiores consideraÃÃes feitas pelos juÃzes foram sobre substituiÃÃo de termos tÃcnicos por expressÃes que possam ser compreendidas pelo pÃblico alvo e correÃÃo de orientaÃÃes confusas As alteraÃÃes feitas tiveram o objetivo de evitar complexidade no conteÃdo da cartilha Acredita-se que a cartilha pode contribuir na melhoria das informaÃÃes a essa clientela amenizando os efeitos do desconhecimento da doenÃa e seu tratamento fomentando o diÃlogo o esclarecimento de dÃvidas e facilitando a prÃtica educativa do enfermeiro / The development of educational guidance materials to patients undergoing chemotherapy aims to improve the quality of care since it is understood that when properly instructed on how to deal with the treatment they undergo increases the adhesion the information make the safer and contributes to the success of the treatment The aim of the study was to construct and validate a primer guidance on chemotherapy This is a methodological research which followed the following steps to develop and validate manuals for health education: project submission to the ethics committee bibliographic and production of an educational manual validation of material built For the construction of the booklet we performed a bibliographic survey of the following databases: SciELO LILACS Cochrane and PubMed using the keywords " cancer " " chemotherapy " " antineoplastic " " drug toxicity " and " care nursing " covering the period 2003-2013 synthesis of 19 articles selected guided guidance on the main side effects of chemotherapy ( nausea vomiting diarrhea mouth ulcers hair loss low immunity skin reactions and other ) and nursing care for these patients After choosing the content we sought to produce a rich educational material color to unwind and encourage reading the images have been carefully selected with the help of a professional graphic designer seeking at all times conform to the guidelines literature idealized characteristics of the instrument The construction of the booklet occurred from November 2013 to January 2014 Then the primer was validated by nine justices on the technical aspects all with extensive experience in the area of cancer and chemotherapy Data analysis was performed descriptively The rating assigned by judges to the items was mostly Totally appropriate and suitable The major considerations were made by the judges on Replacement technical expressions by terms that can be understood by the target audience and correction confusing guidelines The changes were intended to avoid complexity in the content of the booklet It is believed that the primer can contribute to the improvement of information to this population mitigating the effects of ignorance of the disease and its treatment fostering dialogue answering questions and facilitating educational practice nurses

Made available in DSpace on 2015-04-22T22:14:14Z (GMT). No. of bitstreams: 1 Marina Valente Maia.pdf: 5078341 bytes, checksum: 01644b70bc08b473565219d3cfbca193 (MD5) Previous issue date: 2012-04-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / After introduction of multi-drug therapy (MDT/OMS) there were decline in prevalence coefficients and new cases detections, however, the records of drug resistance and relapse cases are threatening factors against lepra control, therefore, the importance of new alternative schemes and monitoring adverse effects, avoiding abandonment or irregularity to treatment. Objectives: Describe side-effects of multi-drug regimen containing minocycline, ofloxacin and clofazimine in multibacillary (MB) leprosy patients and analyse the clinicalbacteriologic indices. Materials and Methods: A prospective, descriptive and observational study, in multibacillary patients, including intolerance cases of standard MDT and relapse cases, carried out in Alfredo da Matta Foundation, Manaus, Amazonas, Brazil, during april 2010 and january 2012. The side-effects were recorded of every individual patient, filled during the course of alternative treatment. The patients received alternative therapy with daily self-administered doses of 100mg of minocycline, 400 mg of ofloxacin and 50mg of clofazimine and a month supervised dose of 300mg of clofazimine for 06 months, thereafter 18 months of daily self-administered doses of ofloxacin 400mg, clofazimine 50mg and month supervised dose of clofazimine 300mg. Results and Discussions: During research 26 patients were treated, however, of these, only 21 cases were included in this study. The mild and not persistent side-effects occurred in 33,3% of patients. From the 37 side-effects, 45,9% episodes was attributed to ofloxacin, such as abdominal pain, nausea, vomiting, headache and insomnia; 21,6% due to clofazimine, 100% of patients with skin pigmentation; however, no side-effets due to minocycline. Mean duration for the development of adverse effects from the start of therapy was 15,2 days. The media interval of follow-up was 13,7 months and 23,8% of patients completed the 24 months trerapy. All the patients tolerated the drugs well and the adhesion was satisfactory, among 15 patients that completed the first treatment year, 14 took 12 doses at 12 months from alternative regimen. Conclusion: The alternative therapy had a similar feasibility and operational mode from MB/MDT, with safe, well tolerated and good adhesion with no serious events. The side-effects attributed to alternative regimen were comparable to previous studies, however this new three drugs combination indicates the importance of these research results. No drug was stopped unlike others standard MDT studies which had treatment interruption by side-effects. There was significant correlation (p<0,001) between clinical classification and histopatologic diagnosis. At the end of first year, there was clinical improvement and bacteriologic index reduction. Nevertheless, it s necessary a follow-up and new inclusions to guarantee the efficacy and safe for the alternative regimen. / Após introdução do esquema poliquimioterápico padrão (PQT/OMS), houve declínio nos coeficientes de prevalência e detecção de casos novos, entretanto, os registros de resistência medicamentosa e casos de recidiva representam ameaça para o controle da hanseníase, por isso a importância da proposição de novos esquemas alternativos e a necessidade de monitorar seus efeitos adversos, evitando-se casos de abandono ou irregularidade ao tratamento. Objetivos: Descrever os efeitos adversos do esquema terapêutico alternativo, contendo a associação clofazimina, ofloxacina e minociclina, em pacientes com hanseníase multibacilar e análise da evolução clínico-baciloscópica dos pacientes. Materiais e Métodos: Estudo prospectivo, descritivo e observacional, de casos multibacilares, incluindo casos de recidiva da doença ou intolerância à poliquimioterapia padrão, realizado na Fundação Alfredo da Matta, Manaus, Amazonas, Brasil, no período de abril de 2010 e janeiro de 2012. Os efeitos adversos foram registrados em formulários individuais para cada paciente, preenchidos ao longo do tratamento. Os indivíduos receberam o esquema alternativo, composto de doses diárias auto-administradas de 100mg de minociclina, 400mg de ofloxacina e 50mg de clofazimina e dose mensal supervisionada de 300mg de clofazimina por seis meses, seguida de 18 meses de doses diárias autoadministradas de ofloxacina 400mg, clofazimina 50 mg e dose supervisionada mensal de clofazimina 300mg. Resultados: Durante o período foram selecionados 26 pacientes, dos quais 21 foram incluídos no estudo. Efeitos adversos leves e transitórios foram observados em 33,3% dos pacientes. Do total de 37 efeitos secundários, 45,9% foram atribuídos à ofloxacina, como dor abdominal, náuseas, vômitos, cefaléia e insônia; 21,6% associados à clofazimina, com relatos e observação em 100% dos pacientes de hiperpigmentação cutânea; entretanto, nenhum efeito foi relacionado à minociclina, especificamente. O tempo médio de desenvolvimento das reações adversas a partir do início do esquema foi de 15,2 dias. A duração média do acompanhamento dos pacientes foi de 13,7 meses, sendo que 23,8% dos pacientes já concluíram o tratamento em 24 meses. A adesão e regularidade ao esquema foram satisfatórias, dos 15 pacientes que já completaram o primeiro ano de tratamento, 14 indivíduos realizaram 12 doses do esquema proposto em 12 meses. Discussão/Conclusão: O esquema alternativo demonstrou viabilidade e operacionalização semelhantes ao esquema PQT/MB, com segurança, boa tolerabilidade e adesão dos pacientes. A porcentagem de efeitos adversos às drogas foi compatível a de outros trabalhos, contudo, a inovação na combinação das três drogas acima, demonstra a importância dos resultados desta pesquisa. Não houve registros de casos graves que indicassem à suspensão ou interrupção do tratamento. Houve correlação significativa (p<0,001) entre a classificação clínica e o diagnóstico histopatológico. Ao fim do primeiro ano do esquema alternativo, os pacientes apresentaram melhora clínica e redução do índice baciloscópico médio. Todavia, há necessidade de acompanhamento dos indivíduos e aumento do número amostral para garantir a eficácia e segurança ao tratamento em longo prazo.

Objetivos: O objetivo deste estudo foi o de identificar compostos seletivamente tóxicos ao carcinoma espinocelular de boca in vitro por meio do reposicionamento de fármacos. Material e Métodos: Por meio de um escaneamento baseado na viabilidade celular de 1.280 fármacos, nós selecionamos três princípios ativos (luteolin, metixene hydrochloride e nitazoxanide) letais às células de câncer de boca SCC-25 e pouco tóxicos às células de queratinócitos cutâneos imortalizados HaCaT. Os fármacos candidatos foram investigados quanto à sua dose- e tempo-resposta bem como comparados e combinados à agentes quimioterápicos padrão por meio do ensaio por colorimetria com brometo de tiazolil azul de tetrazolio (MTT). O impacto dos fármacos na motilidade do SCC-25 e do HaCaT foi verificado pelo ensaio de migração celular e seus mecanismos de ação também foram explorados por meio da verificação dos níveis das proteínas fosforiladas pelo western blotting. Todos os experimentos foram realizados em triplicata e, pelo menos, três vezes independentes. O teste t de student foi utilizado para confrontar as variáveis e nível de significância de 5% foi estabelecido para todos os testes. Resultados: O flavonoide natural luteolin exerceu citotoxicidade potente contra as células de câncer de boca in vitro, apresentando baixa toxicidade ao HaCaT e alta eficiência quando comparado a quimioterápicos como a cisplatina e o AG1478. Do ponto de vista molecular, a luteolin ativou a via de sinalização do dano do DNA e, combinada com um inibidor do Chk, apresentou efeitos potencializados. Além disso, nós demonstramos que a nitazoxanide e o metixene hydrochloride são capazes de destruir células SCC-25 porém não as HaCaT de maneira proporcional à dose e ao tempo de tratamento. As combinações entre os três fármacos hit e com a cisplatina ou o AG1478 potencializaram seus efeitos contra as células malignas. Conclusões: O presente estudo traz a luteolin, o metixene hydrochloride e a nitazoxanide como fortes candidatos a agentes terapêuticos contra o câncer de boca uma vez que estes compostos apresentam maior eficácia contra células de câncer de boca e menor toxicidade contra células não tumorais in vitro do que agentes quimioterápicos convencionais. / Objectives: Here we aimed at identifying and reposition approved drugs that could be selectively toxic towards oral squamous cell carcinoma cells. Materials and Methods: Through a cell-based drug screening of 1,280 chemical molecules, we selected 3 compounds (luteolin, metixene hydrochloride, and nitazoxanide) lethal to oral cancer SCC-25 cells, while sparing immortalized keratinocyte HaCaT cells. The drugs were then further challenged for their time- and dose-responses, as well as their comparison and combination to standard chemotherapeutic agents by colorimetric assay 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan, Thiazolyl blue formazan (MTT). The impact on SCC-25 and HaCaT motility as well as the mode of action of the drugs was then further explored by scratching assay and western blotting, respectively. All the experiments were performed in triplicated and, at least, three independent times. Students t test was performed to verify the differences among the variables and the level of significance was set at 5%. Results: The natural flavonoid luteolin was a potent cytotoxic agent against oral cancer cells in vitro, presenting low toxicity against HaCaT cells and high efficiency as compared to standard-of-care, such as cisplatin and AG1478. From a molecular standpoint, luteolin coopted the DNA-damage pathway and could be efficiently combined with Chk pharmacological inhibitor. Moreover, we demonstrated that nitazoxanide and metixene hydrochloride kill the SCC-25 but not the HaCaT cells in a dose- and time-dependent. The combinations among the three drugs hit and with cisplatin and AG1478 improved their effect against the malignant cells. Conclusions: Luteolin, metixene hydrochloride, and nitazoxanide emerge as strong cytotoxic and/or adjuvant therapy in oral cancer, as these compounds present higher efficiency and lower toxicity against oral cancer cells in vitro than conventional chemotherapeutic agents.

INTRODUÇÃO: As neoplasias do sistema nervoso central são frequentes nafaixa etária pediátrica e o tratamento antineoplásico pode resultar em efeitos adversos agudos ou tardios na cavidade oral. As anormalidades dentárias de forma, tamanho e número de dentes podem ocorrer se o tratamento por radioterapia de crânio e coluna, quimioterapia ou ambas forem coincidentes com a época de formação dentária em pacientes pediátricos. A gravidade das alterações depende do tipo de tratamento e da idade do paciente ao diagnóstico. OBJETIVOS: Avaliar a frequência de anormalidades dentárias em pacientes tratados para neoplasias do sistema nervoso central. MÉTODOS: Neste estudo transversal foram avaliados 31 pacientes com diagnóstico de neoplasia do sistema nervoso central que estavam fora de terapia há pelo menos um ano, comparativamente com um grupo controle composto por 31 pacientes saudáveis, pareados por idade com o grupo de estudo. As anormalidades dentárias foram avaliadas por meio de radiografias panorâmicas. RESULTADOS: A idade média ao diagnóstico dos pacientes do grupo de estudo foi de 7,3 ± 3,9 anos e as neoplasias mais frequentemente observadas foram meduloblastoma (58,1%), astrocitoma (25,8%) e ependimoma (3,2%). Não se observou diferença na frequência de anormalidades dentárias entre os grupos. As anormalidades mais frequentemente observadas nos pacientes do grupo de estudo foram microdontia (9,7%) e encurtamento radicular grau III (16,1%). Microdontia foi mais frequente em crianças que tiveram o diagnóstico antes dos 5 anos de idade, com diferença significante. Encurtamento radicular grau III foi observado em pacientes com mais de 10 anos de idade no momento do exame radiográfico, também com diferença significante. Pacientes tratados por radioterapia associada à quimioterapia apresentaram maior frequência de anormalidades dentárias, comparativamente com pacientes tratados somente por radioterapia ou quimioterapia isoladamente. Microdontia apresentou alta correlação com os dentes segundos premolares e segundos molares em pacientes tratados para neoplasias do sistema nervoso central. CONCLUSÕES: Pacientes tratados para neoplasias do sistema nervoso central apresentam alta frequência de anormalidades dentárias, porém neste estudo não houve diferença entre os grupos de estudo e controle. Microdontia foi a anormalidade dentária mais frequente em pacientes submetidos ao tratamento antineoplásico antes dos 5 anos de idade, com significância estatística. Encurtamento radicular grau III foi observado nos pacientes com mais de 10 anos de idade no momento do exame radiográfico, com diferença estatisticamente significante. Pacientes submetidos à radioterapia associada à quimioterapia apresentaram maior frequência de anormalidades dentárias / INTRODUCTION: Central nervous system neoplasms are frequent in pediatric patients and antineoplastic treatment may result in acute or late adverse effects in the oral cavity. Tooth abnormalities of shape, size and number of teeth can occur if craniospinal irradiation, drug therapy or both are coincident with the time of tooth development. Severity of these alterations depends on the type of treatment and the patient´s age at diagnosis. OBJECTIVES: To evaluate the frequency of tooth abnormalities in pediatric patients treated for central nervous system neoplasms. METHODS: This cross-sectional study assessed 31 patients with central nervous system neoplasms, who were off therapy for at least one year, comparatively with a control group of 31 healthy patients matched for age with the study group. Tooth abnormalities were evaluated by panoramic radiographs. RESULTS: Study group´s mean age at diagnosis was 7.3 ± 3.9 years and the most frequent neoplasms were medulloblastoma (58.1%), astrocytoma (25.8%) and ependyoma (3.2%). There was no difference in the frequency of tooth abnormalities between groups. The most frequently tooth abnormalities observed in the study group were microdontia (9.7%) and root shortening grade III (16.1%). Microdontia was the most common abnormality in children who were diagnosed before 5 years of age, with a significant difference. Root shortening grade III was observed in patients over 10 years of age at the time of radiographic examination, also with a significant difference. Patients treated with craniospinal irradiation combined with drug therapy presented more frequency of tooth abnormalities compared with patients treated only by craniospinal irradiation or drug therapy alone. Microdontia was highly correlated with the teeth second premolars and second molars. CONCLUSIONS: Patients treated for central nervous system neoplasms present high frequency of tooth abnormalities; however in this study there was no difference between study and control groups. Microdontia was the most frequent tooth abnormality in patients submitted to antineoplastic treatment before 5 years of age, with statistical significance. Root shortening grade III was observed in patients over 10 years of age at the time of radiographic examination, with statistically significant difference. Patients undergoing craniospinal irradiation combined with drug therapy showed high frequency of tooth abnormalities

Cheung, Ka Yan. / "Aug 2010." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 157-167). / Abstracts in English and Chinese. / Abstract --- p.i / 摘要 --- p.iii / Acknowledgments --- p.v / Table of Contents --- p.vi / List of Figures --- p.x / List of Tables --- p.xi / Abbreviations --- p.xii / Chapter Chapter1 --- General Introduction --- p.1 / Chapter 1.1 --- Cancer epidemiology and managements --- p.2 / Chapter 1.2 --- Photodynamic therapy (PDT) as cancer treatment --- p.7 / Chapter 1.3 --- Pheophorbide a (Pa) as a photosensitizer for PDT --- p.13 / Chapter 1.4 --- Aim of study --- p.15 / Chapter Chapter2 --- The anti-proliferative effect of pheophorbide a- mediated photodynamic therapy on human breast adenocarcinoma cell line MCF-7 --- p.17 / Chapter 2.1 --- Introduction / Chapter 2.1.1 --- Cell cycle regulation --- p.18 / Chapter 2.1.2 --- Growth arrest and DNA damage inducible (GADD) genes as cell cycle regulators --- p.22 / Chapter 2.2 --- Materials and Methods / Chapter 2.2.1 --- Materials / Chapter 2.2.1.1 --- Cell line --- p.29 / Chapter 2.2.1.2 --- "Cell culture medium, supplements and other reagents" --- p.29 / Chapter 2.2.1.3 --- Gene expression assay reagents --- p.30 / Chapter 2.2.1.4 --- Reagents and buffers for Western blotting --- p.32 / Chapter 2.2.1.5 --- Cell cycle analysis reagents --- p.35 / Chapter 2.2.2 --- Methods / Chapter 2.2.2.1 --- Cell line propagation and subculture --- p.36 / Chapter 2.2.2.2 --- Whole-transcript expression micro array analysis --- p.37 / Chapter 2.2.2.3 --- GADD genes expression assay- RT-PCR --- p.37 / Chapter 2.2.2.4 --- Cell cycle analysis --- p.40 / Chapter 2.2.2.5 --- Western Blotting --- p.41 / Chapter 2.2.2.6 --- Statistical analysis --- p.43 / Chapter 2.3 --- Results / Chapter 2.3.1 --- Effect of Pa-PDT on GADD genes expression by whole-transcript expression microarray analysis --- p.44 / Chapter 2.3.2 --- Effect of Pa-PDT on GADD genes expression by RT-PCR --- p.46 / Chapter 2.3.3 --- Temporal change in the cell cycle profile after Pa-PDT --- p.48 / Chapter 2.3.4 --- Effect of Pa-PDT on cell cycle associated proteins --- p.65 / Chapter 2.4 --- Discussion --- p.67 / Chapter Chapter3 --- Development of drug resistance in human breast adenocarcinoma cell line MDA and the circumvention by pheophorbide a-mediated photodynamic therapy --- p.77 / Chapter 3.1 --- Introduction / Chapter 3.1.1 --- Clinical Importance of multidrug resistance (MDR) --- p.78 / Chapter 3.1.2 --- Mechanisms of MDR --- p.78 / Chapter 3.1.3 --- Development of MDR cell lines --- p.82 / Chapter 3.1.4 --- Reversal of MDR by P-glycoprotein modulators --- p.83 / Chapter 3.1.5 --- Therapeutic potential of Pa-PDT in treating MDR cancers --- p.83 / Chapter 3.2 --- Materials and Methods / Chapter 3.2.1 --- Materials / Chapter 3.2.1.1 --- Cell line --- p.85 / Chapter 3.2.1.2 --- "Cell culture medium, supplements and other reagents" --- p.85 / Chapter 3.2.1.3 --- Cell viability assay reagents --- p.85 / Chapter 3.2.1.4 --- Gene expression assay reagents --- p.86 / Chapter 3.2.2 --- Methods / Chapter 3.2.2.1 --- Cell line propagation and subculture --- p.87 / Chapter 3.2.2.2 --- Drug-resistance development --- p.88 / Chapter 3.2.2.3 --- Measurement of cell viability - MTT reduction assay --- p.88 / Chapter 3.2.2.4 --- ABCB1 expression assay- RT-PCR --- p.89 / Chapter 3.2.2.5 --- Doxorubicin uptake assay --- p.91 / Chapter 3.2.2.6 --- Pheophorbide a uptake assay --- p.91 / Chapter 3.2.2.7 --- Statistical analysis --- p.92 / Chapter 3.3 --- Results / Chapter 3.3.1 --- Cytotoxicity of doxorubicin on MDA and MDA-R cells --- p.93 / Chapter 3.3.2 --- mRNA expression of ABCB1 (P-glycoprotein) in MDA and MDA-R cells --- p.96 / Chapter 3.3.3 --- Doxorubicin uptake by MDA and MDA-R cells --- p.98 / Chapter 3.3.4 --- Circumvention of drug resistance in MDA-R cells by Pa-PDT --- p.102 / Chapter 3.3.5 --- Pheophorbide a uptake by MDA and MDA-R cells --- p.104 / Chapter 3.4 --- Discussion --- p.106 / Chapter Chapter4 --- Synergistic anti-proliferation of pheophorbide a-mediated photodynamic therapy and doxorubicin on multidrug resistant uterine sarcoma cell line Dx5 --- p.113 / Chapter 4.1 --- Introduction / Chapter 4.1.1 --- Clinical limitations of doxorubicin as chemotherapeutic drug --- p.114 / Chapter 4.1.2 --- Clinical limitations of photodynamic therapy --- p.115 / Chapter 4.1.3 --- Combination therapy with Dox and Pa-PDT --- p.117 / Chapter 4.1.4 --- Uterine sarcoma cell line Dx5 as in vitro model for combination therapy --- p.118 / Chapter 4.2 --- Materials and Methods / Chapter 4.2.1 --- Materials / Chapter 4.2.1.1 --- Cell line --- p.120 / Chapter 4.2.1.2 --- "Cell culture medium, supplements and other reagents" --- p.120 / Chapter 4.2.1.3 --- Anti-cancer drugs --- p.121 / Chapter 4.2.1.4 --- "ROS inhibitor, α-tocopherol" --- p.121 / Chapter 4.2.1.5 --- Cell viability assay reagents --- p.122 / Chapter 4.2.1.6 --- P-glycoprotein activity assay reagents --- p.122 / Chapter 4.2.2 --- Methods - / Chapter 4.2.2.1 --- Cell line propagation and subculture --- p.123 / Chapter 4.2.2.2 --- Cell viability assay --- p.123 / Chapter 4.2.2.3 --- P-glycoprotein activity assay --- p.124 / Chapter 4.2.2.4 --- Statistical analysis --- p.125 / Chapter 4.3 --- Results / Chapter 4.3.1 --- Combination therapy of Pa-PDT and doxorubicin in Dx5 cells --- p.126 / Chapter 4.3.2 --- Effect of α-tocopherol on the synergism between Pa-PDT and doxorubicin in Dx5 cells --- p.129 / Chapter 4.3.3 --- Effect of Pa-PDT on P-glycoprotein activity in Dx5 cells --- p.132 / Chapter 4.3.4 --- Combination therapy of Pa-PDT and doxorubicin in SA cells --- p.138 / Chapter 4.4 --- Discussion --- p.141 / Chapter Chapter5 --- General Discussion --- p.148 / Chapter 5.1 --- Pa-PDT induced growth arrest and DNA fragmentation in breast cancer MCF-7 cells --- p.149 / Chapter 5.2 --- Circumvention of doxorubicin resistance by Pa-PDT in breast cancer MDA cells --- p.151 / Chapter 5.3 --- Synergistic anti-proliferation of Pa-PDT and doxorubicin on uterine sarcoma cell line Dx5 --- p.151 / Chapter 5.4 --- Clinical implication --- p.153 / Chapter 5.5 --- Conclusions and future perspectives --- p.153 / References --- p.157

Yuen, Ka Leung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 95-104). / Abstracts in English and Chinese. / Chapter 1 --- Introduction / Chapter 1.1 --- CANCER / Chapter 1.1.1 --- OVERVIEW OF CANCER --- p.1 / Chapter 1.1.2 --- DEVELOPMENT OF CANCER --- p.1 / Chapter 1.1.3 --- CHARACTERISTICS OF CANCER CELLS --- p.3 / Chapter 1.1.4 --- CATEGORIZATION OF CANCER --- p.6 / Chapter 1.1.5 --- RISK FACTORS IN CANCER DEVELOPMENT --- p.7 / Chapter 1.1.6 --- EPIDEMIOLOGY OF CANCER --- p.11 / Chapter 1.1.7 --- CANCER THERAPIES --- p.13 / Chapter 1.2 --- SOYBEANS AND ISOFLAVONES / Chapter 1.2.1 --- GENERAL INTRODUCTION OF ISOFLAVONES --- p.18 / Chapter 1.2.2 --- NATURAL FUNCTIONS OF ISOFLAVONES --- p.19 / Chapter 1.2.3 --- STRUCTURES OF ISOFLAVONES --- p.19 / Chapter 1.2.4 --- BIOACTIVITIES OF SOY ISOFLAVONES --- p.20 / Chapter 1.2.5 --- PRODUCTION OF SOY ISOFLAVONES CAN BE AFFECTED BY MANY FACTORS --- p.21 / Chapter 1.3 --- THE AIM AND OBJECTIVES OF THE PROJECT / Chapter 1.3.1 --- AIM OF THE PROJECT --- p.22 / Chapter 1.3.2 --- OBJECTIVES OF THE PROJECT --- p.23 / Chapter 2 --- Materials / Chapter 2.1 --- 19 DROUGHT TOLERANT SOYBEAN LINES --- p.24 / Chapter 2.2 --- 5 HUMAN CANCER CELL LINES --- p.25 / Chapter 2.3 --- CHEMICALS --- p.25 / Chapter 2.4 --- REAGENTS --- p.26 / Chapter 2.5 --- SOLUTIONS --- p.26 / Chapter 2.6 --- MAJOR EQUIPMENTS AND MATERIALS --- p.28 / Chapter 3 --- Methodology / Chapter 3.1 --- PREPARATION OF SOYBEAN EXTRACTS --- p.29 / Chapter 3.2 --- HIGH PERFORMANCE LIQUID CHROMATOGRAPHY(HPLC) ANALYSIS OF SOYBEAN EXTRACTS / Chapter 3.2.1 --- PREPARATION OF SOYBEAN EXTRACTS FOR HPLC ANALYS --- p.30 / Chapter 3.2.2 --- HPLC ANALYSIS --- p.30 / Chapter 3.3 --- PREPARATION OF 5 HUMAN CANCER CELL LINES FOR ANTI-PROLIFERATION ASSAY / Chapter 3.3.1 --- THAWING OF THE C Y R O P R E S E R V E D CELL LINES --- p.31 / Chapter 3.3.2 --- MAINTAINING OF CELL LINES --- p.32 / Chapter 3.3.3 --- ANTI-PROLIFERATION TEST WITH MTT ASSAY --- p.33 / Chapter 3.4 --- STATISTICS --- p.35 / Chapter 4 --- Results / Chapter 4.1 --- PREPARARTION OF SOYBEAN EXTRACTS --- p.36 / Chapter 4.2 --- HPLC ANALYSIS OF 5 SELECTED ISOFLAVONES IN 19 SOYBEAN SAMPLES --- p.36 / Chapter 4.3 --- COMPARISON OF SUM OF 5 SELECTED ISOFLAVONES FROM THE PARENT SOYBEAN AND VARIETIES HARVESTED FROM IRRIGATED LAND --- p.43 / Chapter 4.4 --- COMPARISON OF SUM OF 5 SELECTED ISOFLAVONES FROM THE SOYBEAN VARIETIES HARVESTED FROM DROUGHT LAND --- p.45 / Chapter 4.5 --- COMPARISON OF SELECTED ISOFLAVONES FROM THE PARENT SOYBEAN AND VARIETIES HARVESTED FROM IRRIGATED LAND --- p.47 / Chapter 4.6 --- COMPARISON OF SELECTED ISOFLAVONES FROM THE PARENT SOYBEAN AND VARIETIES HARVESTED FROM DAROUGHT LAND --- p.54 / Chapter 4.7 --- COMPARISON OF SUM OF SELECTED ISOFLAVONES AMONG THE SOYBEANS HARVESTED FROM IRRIGATED LAND AND DROUGHT LAND --- p.59 / Chapter 4.8 --- DETERMINATION OF ANTI-PROLIFERATION ABILITIES OF SOYBEAN SAMPLES --- p.19 / Chapter 4.8.1 --- ANTI-PROLIFERATION TEST OF ETHANOL AND 2-PHEN YLCHROMONE --- p.61 / Chapter 4.8.2 --- ANTI-PROLIFERATION ACTIVITIES OF 19 SOYBEAN SAMPLES ON 5 HUMAN CANCER CELL LINES --- p.61 / Chapter 4.9 --- COMPARISON OF ANTI-PROLIFERATION POTENCIES OF19 SOYBEAN SAMPLES WITH SUM OF SELECTED ISOFLAVONES --- p.70 / Chapter 4.10 --- COMPARISON OF ANTI-PROLIFERATION POTENCIES OF19 SOYBEAN SAMPLES --- p.72 / Chapter 4.11 --- ANTI-PROLIFERATION EFFECT OF INDIVIDUAL ISOFLAVONES ON FIVE CANCER CELL LINES --- p.74 / Chapter 5 --- Discussion / Chapter 5.1 --- EXTRACTION OF 19 SOYBEAN LINES --- p.77 / Chapter 5.2 --- DETERMINATION OF QUANTITIES OF SELECTED ISOFLAVONES IN 19 SOYBEAN SAMPLES BY HPLC ANALYSIS --- p.77 / Chapter 5.3 --- COMPARISON OF SELECTED ISOFLAVONES AMONG 19 SOYBEAN SAMPLES / Chapter 5.3.1 --- COMPARISON OF SUM OF SELECTED ISOFLAVONES BETWEEN PARENT AND SOYBEANS HARVESTED FROM IRRIGATED LAND --- p.80 / Chapter 5.3.2 --- COMPARISON OF SUM OF SELECTED ISOFLAVONES BETWEEN SOYBEANS HARVESTED FROM DROUGHT LAND --- p.81 / Chapter 5.3.3 --- COMPARISON OF SELECTED ISOFLAVONES BETWEEN SOYBEANS HARVESTED FROM IRRIGATED LAND --- p.81 / Chapter 5.3.4 --- COMPARISON OF SELECTED ISOFLAVONES BETWEEN SOYBEANS HARVESTED FROM DROUGHT LAND --- p.82 / Chapter 5.3.5 --- COMPARISON OF SUM OF SELECTED ISOFLAVONES BETWEEN SOYBEANS HARVESTED FROM IRRIGATED LAND AND DROUGHT LAND --- p.83 / Chapter 5.4 --- COMPARISON OF ANTI-PROLIFERATION ACTIVITIES OF 19 SOYBEAN SAMPLES / Chapter 5.4.1 --- COMPARISON OF ANTI-PROLIFERATION ACTIVITIES OF19 SOYBEAN SAMPLES AMONG 5 CANCER CELL LINES --- p.84 / Chapter 5.4.2 --- COMPARISON OF ANTI-PROLIFERATION POTENCIES OF19 SOYBEAN SAMPLES --- p.85 / Chapter 5.4.3 --- COMPARISON OF ANTI-PROLIFERATION ACTIVITIES OF19 SOYBEAN SAMPLES AND CORRESPONDING SUM OF SELECTED ISOFLAVONES --- p.86 / Chapter 5.4.4 --- COMPARISON OF IC50S FROM SOYBEANS HARVESTED FROM IRRIGATED LAND AND DROUGHT LAND --- p.87 / Chapter 5.4.5 --- CORRELATION OF ISOFLAVONES AND ANTI-PROLIFERATION POTENCIES --- p.88 / Chapter 6 --- Conclusion --- p.90 / Chapter 7 --- References --- p.91 / Chapter 8 --- Appendix --- p.S1

Ho, Lai Ying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 213-238). / Abstract also in Chinese. / Abstract --- p.i / Abstract in Chinese (摘要） --- p.iv / Acknowledgements --- p.vii / List of abbreviations --- p.ix / Table of contents --- p.xiv / Chapter Chapter One: --- General Introduction_ --- p.1 / Chapter 1.1 --- Neuroblastoma --- p.2 / Chapter 1.1.1 --- An overview on neuroblastoma --- p.2 / Chapter 1.1.2 --- Classification of neuroblastoma --- p.4 / Chapter 1.1.3 --- Epidemiology of neuroblastoma --- p.7 / Chapter 1.1.4 --- Clinical manifestation of neuroblastoma --- p.10 / Chapter 1.1.5 --- Diagnosis of neuroblastoma --- p.10 / Chapter 1.1.6 --- Conventional therapy of neuroblastoma --- p.12 / Chapter 1.1.7 --- Novel treatments of neuroblastoma --- p.14 / Chapter 1.2 --- Conjugated linolenic acid (CLN) --- p.16 / Chapter 1.2.1 --- An overview of polyunsaturated fatty acids and conjugated fatty acids --- p.16 / Chapter 1.2.2 --- Chemical structure and physical properties of CLNs --- p.18 / Chapter 1.2.3 --- Natural occurrence of CLNs --- p.21 / Chapter 1.2.4 --- Synthesis of CLNs --- p.22 / Chapter 1.2.5 --- Metabolism and pharmacokinetics of CLNs --- p.24 / Chapter 1.2.6 --- Major biological and pharmacological activities of CLNs --- p.25 / Chapter 1.2.6.1 --- Hypolipidemic and anti-obese effects --- p.25 / Chapter 1.2.6.2 --- Anti-cancer effects --- p.27 / Chapter 1.2.6.2.1 --- Anti-proliferation --- p.27 / Chapter 1.2.6.2.2 --- Chemoprevention --- p.28 / Chapter 1.2.6.2.3 --- Apoptosis-inducing --- p.28 / Chapter 1.3 --- Aims and scope of the study --- p.31 / Chapter Chapter Two: --- Materials and Methods_ --- p.34 / Chapter 2.1 --- Materials --- p.35 / Chapter 2.1.1 --- Animals --- p.35 / Chapter 2.1.2 --- Cell lines --- p.35 / Chapter 2.1.3 --- "Cell culture medium, buffers and other reagents" --- p.37 / Chapter 2.1.4 --- Reagents for DNA extraction --- p.46 / Chapter 2.1.5 --- Reagents for gel electrophoresis of nucleic acids --- p.47 / Chapter 2.1.6 --- Reagents and buffers for flow cytometry --- p.49 / Chapter 2.1.7 --- Reagents and buffers for measuring caspase activity --- p.50 / Chapter 2.1.8 --- Reagents for Hoechst staining --- p.53 / Chapter 2.1.9 --- Reagents and buffers for RNA extraction --- p.53 / Chapter 2.1.10 --- Reagents and buffers for DNA digestion --- p.54 / Chapter 2.1.11 --- Reagents and buffers for reverse transcription --- p.55 / Chapter 2.1.12 --- Reagents for real-time polymerase chain reaction --- p.57 / Chapter 2.1.13 --- Reagents and buffers for Western blotting --- p.59 / Chapter 2.2 --- Methods --- p.64 / Chapter 2.2.1 --- Culture of cell lines --- p.64 / Chapter 2.2.2 --- Preparation of NIH-3T3 conditioned medium --- p.65 / Chapter 2.2.3 --- Determination of cell viability --- p.65 / Chapter 2.2.4 --- Determination of cell proliferation by tritiated thymidine incorporation assay --- p.66 / Chapter 2.2.5 --- Cytotoxicity test of CLNs on murine peritoneal macrophages --- p.67 / Chapter 2.2.6 --- Cytotoxicity test of CLNs on murine bone marrow cells --- p.68 / Chapter 2.2.7 --- Cytotoxicity test of CLNs on murine splenocytes --- p.68 / Chapter 2.2.8 --- Cytotoxicity tests of CLNs on human peripheral blood mononuclear cells --- p.69 / Chapter 2.2.9 --- Carboxyfluorescein diacetate succinimidyl ester (CFSE) staining analyzed by flow cytometry --- p.69 / Chapter 2.2.10 --- Determination of colony forming ability --- p.70 / Chapter 2.2.11 --- Determination of cell invasiveness --- p.70 / Chapter 2.2.12 --- In vivo tumorigenicity assay --- p.71 / Chapter 2.2.13 --- Analysis of cell cycle profile/ DNA content by flow cytometry --- p.72 / Chapter 2.1.14 --- Measurements of apoptosis --- p.72 / Chapter 2.1.15 --- Measurements of differentiation --- p.77 / Chapter 2.1.16 --- Gene expression study --- p.78 / Chapter 2.2.17 --- Protein expression study --- p.81 / Chapter 2.2.18 --- Statistical Analysis --- p.84 / Chapter Chapter Three: --- Anti-proliferative Effect of CLN Isomers on Human Neuroblastoma cells --- p.86 / Chapter 3.1 --- Introduction --- p.87 / Chapter 3.2 --- Results --- p.89 / Chapter 3.2.1 --- Anti-proliferative effect of CLN isomers on various human neuroblastoma cell lines in vitro --- p.89 / Chapter 3.2.2 --- Direct cytotoxic effect of jacaric acid on neuroblastoma LA-N-1 cells in vitro --- p.100 / Chapter 3.2.3 --- Cytotoxicity of jacaric acid on primary murine cells and human normal cell lines --- p.103 / Chapter 3.2.4 --- Kinetic and reversibility studies of the anti-proliferative effect of jacaric acid on LA-N-1 cells --- p.106 / Chapter 3.2.5 --- Synergistic anti-proliferative effect of jacaric acid with daidzein and retinoic acid on LA-N-1 cells in vitro --- p.110 / Chapter 3.2.6 --- Modulatory effect of jacaric acid on the number of cell division in LA-N-1 cells --- p.113 / Chapter 3.2.7 --- Effect of jacaric acid on the cell cycle profile of LA-N-1 cells --- p.115 / Chapter 3.2.8 --- Effect of jacaric acid on the invasiveness of LA-N-1 cells --- p.118 / Chapter 3.2.9 --- Effect of jacaric acid on the colony forming ability of LA-N-1 cells in soft agar --- p.120 / Chapter 3.2.10 --- Effect of jacaric acid on the in vivo tumorigenicity of the LA-N-1 cells --- p.122 / Chapter 3.3 --- Discussion --- p.124 / Chapter Chapter Four: --- Apoptosis- and Differentiation-inducing Effects of Jacaric Acid on Human Neuroblastoma Cells --- p.133 / Chapter 4.1 --- Introduction --- p.134 / Chapter 4.2 --- Results --- p.138 / Chapter 4.2.1 --- Induction of DNA fragmentation and apoptotic ultrastructural changes in LA-N-1 cells by jacaric acid --- p.138 / Chapter 4.2.2 --- Induction of phosphatidylserine externalization by jacaric acid in human neuroblastoma cells as detected by Annexin V-GFP/ PI dual staining --- p.142 / Chapter 4.2.3 --- Effect of jacaric acid on the mitochondrial membrane potential in human neuroblastoma cells --- p.146 / Chapter 4.2.4 --- Effect of jacaric acid on the caspase-3 activity in LA-N-1 cells --- p.150 / Chapter 4.2.5 --- Effect of jacaric acid on the reactive oxygen species (ROS) generation in human neuroblastoma cells --- p.153 / Chapter 4.2.6 --- Morphological changes induced by jacaric acid in SH-SY5Y cells --- p.158 / Chapter 4.3 --- Discussion --- p.162 / Chapter Chapter Five: --- Mechanistic Studies of Anti-proliferative Effect of Jacaric Acid on Human Neuroblastoma Cells --- p.171 / Chapter 5.1 --- Introduction --- p.172 / Chapter 5.2 --- Results --- p.178 / Chapter 5.2.1 --- Effect of antioxidant a-tocopherol on the anti-proliferative effect of jacaric acid on LA-N-1 cells --- p.178 / Chapter 5.2.2 --- Effect of caspase inhibitors on the anti-proliferative effect of jacaric acid on LA-N-1 cells --- p.180 / Chapter 5.2.3 --- Jacaric acid modulated the mRNA expression of N-myc and other related transcription factors in LA-N-1 cells --- p.182 / Chapter 5.2.4 --- Jacaric acid modulated the protein expression of N-myc --- p.186 / Chapter 5.2.5 --- Jacaric acid modulated the mRNA expression of apoptosis-associated genes --- p.188 / Chapter 5.3 --- Discussion --- p.191 / Chapter Chapter Six: --- Conclusions and Future Perspectives --- p.202 / References --- p.212

Choi, Mei Yuk. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 79-89). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.iii / Abstract (Chinese) --- p.v / List of Abbreviations --- p.vii / List of Figures --- p.viii / Chapter Chapter 1 --- Introduction / Chapter 1.1. --- General introduction of cancer --- p.1 / Chapter 1.2. --- Overview of apoptosis --- p.2 / Chapter 1.2.1. --- The extrinsic death receptor pathway --- p.4 / Chapter 1.2.2. --- The intrinsic mitochondrial pathway --- p.4 / Chapter 1.2.3. --- Cross-talk between the intrinsic and extrinsic pathways --- p.5 / Chapter 1.3. --- Overview of selenium --- p.6 / Chapter 1.3.1. --- Selenium and prostate cancer --- p.7 / Chapter i. --- Epidemiological studies --- p.7 / Chapter ii. --- Clinical trials --- p.8 / Chapter iii. --- Preclinical investigations --- p.10 / Chapter a. --- in vivo studies --- p.11 / Chapter b. --- in vitro studies --- p.12 / Chapter c. --- selenocystine and prostate cancer --- p.13 / Chapter 1.4. --- Objective --- p.15 / Chapter Chapter 2 --- Materials and methods / Chapter 2.1. --- Materials --- p.18 / Chapter 2.2. --- Methods --- p.19 / Chapter 2.2.1. --- Cell culture --- p.19 / Chapter 2.2.2. --- MTT assay --- p.19 / Chapter 2.2.3. --- Cell cycle distribution analysis --- p.20 / Chapter 2.2.4. --- TUNEL assay and DAPI staining --- p.20 / Chapter 2.2.5. --- Evaluation of mitochondrial membrane potential (ΔΨm) --- p.21 / Chapter 2.2.6. --- Measurement of superoxide generation (DHE assay) --- p.22 / Chapter 2.2.7. --- Inhibition of superoxide generation --- p.22 / Chapter 2.2.8. --- Western blot analysis --- p.23 / Chapter 2.2.9. --- Statistical analysis --- p.24 / Chapter Chapter 3 --- Results / Chapter 3.1. --- The antiproliferatvie effect of SeC on LNCaP and PC-3 cells --- p.25 / Chapter 3.2. --- The role of caspases in SeC-induced apoptosis --- p.34 / Chapter 3.3. --- The effect of SeC on the mitochondrial membrane potential --- p.39 / Chapter 3.4. --- The involvement of p53 in SeC-treated LNCaP cells --- p.44 / Chapter 3.5. --- MAPK and PI3K/Akt signaling pathways --- p.47 / Chapter 3.6. --- The role of superoxide in SeC-induced apoptosis --- p.52 / Chapter Chapter 4 --- Discussion --- p.62 / Chapter Chapter 5 --- Conclusion --- p.74 / References --- p.79

Chin, Chi Hou. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves [165]-178). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract in Chinese (摘要） --- p.iv / Acknowledgements --- p.vi / Abbreviations --- p.vii / List of Figures and Tables --- p.xi / Publications --- p.xv / Chapter Chapter 1 --- General Introduction / Chapter 1.1. --- Hematopoiesis and Leukemia --- p.2 / Chapter 1.1.1. --- Hematopoiesis --- p.2 / Chapter 1.1.2. --- Leukemia --- p.8 / Chapter 1.1.2.1. --- Overview of leukemia --- p.8 / Chapter 1.1.2.2. --- Symptoms and diagnosis of leukemia --- p.9 / Chapter 1.1.2.3. --- Classification of leukemia --- p.9 / Chapter 1.1.2.4. --- Epidemiology of leukemia --- p.13 / Chapter 1.1.2.5. --- Conventional treatments for leukemia --- p.15 / Chapter 1.1.2.6. --- Novel approaches to leukemia treatment --- p.18 / Chapter 1.2. --- Statins --- p.22 / Chapter 1.2.1. --- Overview of statins --- p.22 / Chapter 1.2.2. --- Chemical structures of statins --- p.24 / Chapter 1.2.3. --- Pharmacokinetics of statins --- p.26 / Chapter 1.2.4. --- Pleiotropic effects of statins --- p.29 / Chapter 1.2.4.1. --- Anti-inflammatory and immunomodulatory effects of statins --- p.29 / Chapter 1.2.4.2. --- Anti-angiogenic effects of statins --- p.30 / Chapter 1.2.4.3. --- Anti-tumor effects of statins --- p.31 / Chapter 1.3. --- Objectives and scope of the present study --- p.33 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1. --- Materials --- p.36 / Chapter 2.1.1. --- Animals --- p.36 / Chapter 2.1.2. --- Cell lines --- p.36 / Chapter 2.1.3. --- "Cell culture media, buffers and other reagents" --- p.37 / Chapter 2.1.3.1. --- Cell culture media and reagents --- p.37 / Chapter 2.1.3.2. --- Drugs and chemicals --- p.40 / Chapter 2.1.3.3. --- Reagents and buffers for primary culture --- p.42 / Chapter 2.1.3.4. --- Dye solutions --- p.43 / Chapter 2.1.3.5. --- Reagents for cell proliferation assays --- p.44 / Chapter 2.1.3.6. --- Reagents and buffers for flow cytometry --- p.44 / Chapter 2.1.3.7. --- Reagents for Hoechst staining --- p.45 / Chapter 2.1.3.8. --- Reagents and buffers for DNA isolation --- p.46 / Chapter 2.1.3.9. --- Reagents and buffers for DNA agarose gel electrophoresis --- p.48 / Chapter 2.1.3.10. --- Reagents and buffers for Cell Death ELISA --- p.50 / Chapter 2.1.3.11. --- Reagents and buffers for measuring caspase activity --- p.51 / Chapter 2.1.3.12. --- Reagents and buffers for Western blotting --- p.55 / Chapter 2.1.3.13. --- Reagents for determining nitric oxide production --- p.63 / Chapter 2.2. --- Methods --- p.64 / Chapter 2.2.1. --- Culture of tumor cell lines --- p.64 / Chapter 2.2.2. --- "Isolation, preparation and culture of murine peritoneal macrophages" --- p.64 / Chapter 2.2.3. --- Cell proliferation and cytotoxicity studies --- p.66 / Chapter 2.2.4. --- In vivo tumorigenicity study --- p.68 / Chapter 2.2.5. --- Cell cycle profile and flow cytometric analysis --- p.69 / Chapter 2.2.6. --- Hoechst staining --- p.69 / Chapter 2.2.7. --- DNA fragmentation analysis --- p.70 / Chapter 2.2.8. --- Cell Death ELISA --- p.71 / Chapter 2.2.9. --- Mitochondrial membrane potential analysis --- p.73 / Chapter 2.2.10. --- Measurement of caspase activity --- p.73 / Chapter 2.2.11. --- Protein expression study --- p.75 / Chapter 2.2.12. --- Cell morphological staining --- p.80 / Chapter 2.2.13. --- Cell size and granularity analysis by flow cytometry --- p.81 / Chapter 2.2.14. --- Determination of nitric oxide production by macrophages --- p.81 / Chapter 2.2.15. --- Statistical analysis --- p.82 / Chapter Chapter 3 --- Anti-Proliferative Effect of Statins on Myeloid Leukemia Cells / Chapter 3.1. --- Introduction --- p.84 / Chapter 3.2. --- Results --- p.86 / Chapter 3.2.1. --- Anti-proliferative effect of statins on various murine and human myeloid leukemia cells --- p.86 / Chapter 3.2.2. --- Cytotoxicity of fluvastatin on murine myelomonocytic leukemia WEHI-3B JCS cells --- p.93 / Chapter 3.2.3. --- Cytotoxicity of fluvastatin on primary murine myeloid cells --- p.96 / Chapter 3.2.4. --- Kinetic and reversibility studies on the anti-proliferative effect of fluvastatin on WEHI-3B JCS cells --- p.98 / Chapter 3.2.5. --- Relationship between the anti-proliferative effect of fluvastatin and the cholesterol biosynthesis pathway in WEHI-3B JCS cells --- p.102 / Chapter 3.2.6. --- Effect of fluvastatin on the in vivo tumorigenicity of WEHI-3B JCS cells --- p.106 / Chapter 3.2.7. --- Effect of fluvastatin on the cell cycle profile of WEHI-3B JCS cells --- p.108 / Chapter 3.2.8. --- Effect of fluvastatin on the expression of cell cycle regulatory proteins inWEHI-3B JCS cells --- p.113 / Chapter 3.3. --- Discussion --- p.116 / Chapter Chapter 4 --- Apoptosis- and Differentiation-inducing Effects of Fluvastatin on Murine Myelomonocytic Leukemia WEHI-3B JCS Cells / Chapter 4.1. --- Introduction --- p.124 / Chapter 4.2. --- Results --- p.128 / Chapter 4.2.1. --- Induction of chromatin condensation in WEHI-3B JCS cells by fluvastatin --- p.128 / Chapter 4.2.2. --- Induction of DNA fragmentation in WEHI-3B JCS cells by fluvastatin --- p.130 / Chapter 4.2.3. --- Effect of fluvastatin on the mitochondrial membrane potential in WEHI-3B JCS cells --- p.134 / Chapter 4.2.4. --- Effect of fluvastatin on the caspase activities in WEHI-3B JCS cells --- p.138 / Chapter 4.2.5. --- Effect of fluvastatin on the expression of pro-apoptotic protein AIF in WEHI-3B JCS cells --- p.144 / Chapter 4.2.6. --- Effect of fluvastatin on the morphology of WEHI-3B JCS cells --- p.147 / Chapter 4.2.7. --- Effect of fluvastatin on the cell size and granularity of WEHI-3B JCS cells --- p.149 / Chapter 4.2.8. --- Immunomodulation of murine peritoneal macrophages by fluvastatin --- p.151 / Chapter 4.3. --- Discussion --- p.153 / Chapter Chapter 5 --- Conclusions and Future Perspectives --- p.160 / References --- p.165

Tong, Kit Fong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 91-104). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.vi / Table of Contents --- p.vii / List of Figures --- p.x / List of Tables --- p.xii / List of Abbreviations --- p.xiii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Cancer --- p.2 / Chapter 1.1.1 --- Tumor development --- p.2 / Chapter 1.1.2 --- Cell cycle --- p.4 / Chapter 1.1.3 --- Apoptosis --- p.9 / Chapter 1.1.3.1 --- The extrinsic pathway --- p.14 / Chapter 1.1.3.2 --- The intrinsic pathway --- p.16 / Chapter 1.1.3.3 --- The Bcl-2 family proteins --- p.17 / Chapter 1.1.3.4 --- Execution of apoptosis --- p.20 / Chapter 1.1.4 --- Melanoma --- p.22 / Chapter 1.2 --- Polyunsaturated fatty acids (PUFAs) --- p.24 / Chapter 1.2.1 --- "Chemistry, classification, metabolic conversion and sources …" --- p.24 / Chapter 1.2.2 --- Epidemiology studies --- p.27 / Chapter 1.2.3 --- Docosahexaenoic acid (DHA) --- p.28 / Chapter 1.2.3.1 --- Sources --- p.28 / Chapter 1.2.3.2 --- DHA and cancer --- p.29 / Chapter 1.3 --- Objectives --- p.33 / Chapter Chapter 2 --- Materials and Methods --- p.34 / Chapter 2.1 --- In vitro studies of DHA on growth and survival of human cancer cells --- p.34 / Chapter 2.1.1 --- Cell cultures --- p.34 / Chapter 2.1.2 --- Studies of growth inhibition of DHA on human cancer cells --- p.35 / Chapter 2.1.2.1 --- MTT assay --- p.35 / Chapter 2.1.2.2 --- Chemiluminescent-bromodeoxyuridine (Chemi-BrdU) immunoassay --- p.36 / Chapter 2.1.3 --- Studies of growth inhibitory mechanism of DHA on A375 cells. --- p.38 / Chapter 2.1.3.1 --- DNA -flow cytometry analysis --- p.38 / Chapter 2.1.3.2 --- Western blot analysis --- p.39 / Chapter 2.1.3.3 --- Caspase inhibitor studies --- p.42 / Chapter 2.1.3.4 --- Mitochondrial membrane potential analysis --- p.42 / Chapter 2.2 --- In vivo study of the anticancer effect of DHA on A375 cells --- p.44 / Chapter 2.2.1 --- Animals --- p.44 / Chapter 2.2.2 --- Cell inoculation and treatments --- p.44 / Chapter 2.2.3 --- Western blot analysis --- p.45 / Chapter 2.3 --- Statistical analysis --- p.46 / Chapter Chapter 3 --- Results --- p.47 / Chapter 3.1 --- In vitro studies of DHA on growth and survival of human canccr cells --- p.47 / Chapter 3.1.1 --- DHA reduced proliferation and survival of human cancer cells --- p.47 / Chapter 3.1.2 --- DHA modulated cell cycle of A375 cells --- p.52 / Chapter 3.1.3 --- DHA induced apoptosis in A375 cells --- p.55 / Chapter 3.1.4 --- Caspase activations were involved in the DHA-induced apoptosis in A375 cells --- p.59 / Chapter 3.1.5 --- "Caspase 3´ة 6, 8 and 9 were activated in DHA-induced apoptosis of A375 cells" --- p.62 / Chapter 3.1.6 --- DHA dissipated mitochondrial membrane potential in A375 cells --- p.66 / Chapter 3.1.7 --- DHA triggered the mitochondrial pathway of apoptosis --- p.68 / Chapter 3.1.8 --- DHA triggered the death receptor pathway of apoptosis --- p.71 / Chapter 3.2 --- In vivo study of the anticancer effect of DHA on A375 cells --- p.74 / Chapter 3.2.1 --- Effect of DHA on the growth ofA375 xenograft in athymic Bαlb/c mice --- p.74 / Chapter 3.2.2 --- DR4 and TRAIL were upregulated by DHA treatment in A375 solid tumor --- p.77 / Chapter Chapter 4 --- Discussion --- p.79 / References --- p.91