Introdução: Náuseas e vômitos pós-operatórios são queixas importantes no período pós-operatório e seu controle adequado em pacientes oncológicos ainda é um desafio. Na avaliação de fatores de risco relacionados à NVPO é importante melhorar a estratificação dos pacientes a serem submetidos à anestesia e cirurgia, de maneira a propor intervenções que diminuam a NVPO. Neste estudo avaliou-se as variáveis náuseas e vômitos induzidos por quimioterapia (NVIQ), o uso crônico de opioides prévio à cirurgia, a história detalhada de tabagismo e o processo de cessação do tabagismo no período anterior à cirurgia em pacientes oncológicos. Métodos: Foi realizado um estudo observacional, prospectivo de 1829 pacientes oncológicos submetidos à cirurgia oncológicas de médio e grande porte entre maio de 2014 e novembro de 2015 no Instituto do Câncer do Estado de São Paulo (ICESP), Brasil. NVPO foram avaliados nas primeiras 24 horas de pós-operatório. Os dados foram obtidos por meio de entrevistas e de consulta aos prontuários. Foi realizada análise bivariada para estudar os potenciais fatores associados à NVPO. A análise de regressão logística múltipla identificou um novo modelo para previsão de NVPO através do estado de tabagismo detalhado. Resultados: A incidência global de NVPO foi de 30,8%. Houve correlação entre NVPO e as variáveis sexo feminino, idade, não tabagismo, NVIQ e história de cinetose. O risco de NVPO em fumantes foi de 14,1%, de 18,1% naqueles que pararam de fumar até um mês, 24,7% naqueles que pararam de fumar entre um mês e seis meses, 29,4% naqueles que pararam de fumar há mais de seis meses e 33,9% naqueles que nunca fumaram. Esta correlação gerou um novo modelo preditor para previsão de NVPO incluindo o histórico de tabagismo detalhado ao invés da variável dicotômica usada pelo modelo de Apfel, curva ROC com modelo de Apfel - AUC: 63,7% e novo modelo: 67,9%. Não foi encontrada relação entre o tipo de cirurgia e uso opioide crônico com NVPO. Conclusão: As variáveis sexo feminino, idade, não tabagismo, NVIQ, história prévia de cinetose foram confirmadas como fatores de risco para NVPO e um novo modelo preditor foi identificado pela associação entre NVPO e a história tabágica na população oncológica / Introduction: Nausea and vomiting are the main sources of discomfort in the postoperative period and their adequate control in oncological patients is still defiant. During the evaluation of PONV risk factor it is important to better stratify the patients to be submitted to anesthesia and surgery, in order to propose interventions that lead to the decrease in PONV. In this study, we evaluated chemotherapy induced nausea and vomiting (CINV), chronic use of opioid prior to surgery and the detailed history of smoking and of smoking quitting in oncological patients. Methods: This was an observational prospective study of 1829 oncological patients submitted to surgery from May 2014 and November 2015 in the Institute of Cancer of the State of São Paulo (ICESP), Brazil. PONV was evaluated in the first 24 hours after surgery. The data was obtained by interviews and medical records consultation. Bivariate analysis was performed to study potential factors associated to PONV. Multiple logistics analysis identified a new prediction model to PONV adding detailed smoking status. Results: Incidence of PONV was of 30.8%. There was correlation among PONV and female sex, age, non-smoking, CINV and previous motion sickness. Risk of PONV was of 14.1% in smokers, 18.1% in individuals that quit smoking in less than a month, 24.7% in individuals that quit smoking between one and six months, 29.4% in those who quit smoking more than six months and 33.9% in individuals that never smoked. This correlation generated a new PONV prediction model, including detailed smoking status rather than the Apfel dichotomous variable of smoking (yes/no), ROC curve using Apfel´s model - AUC - 63.7% and new model - 67.9%. There was no correlation between type of surgery, chronic opioid use and PONV. Conclusion: Female sex, age, non-smoking, CINV, previous motion sickness was confirmed as risk factors for PONV and a new PONV prediction model was identified through the association between PONV and the detailed history of smoking and smoking quitting in the oncological population

Nas últimas décadas, o câncer tornou-se um problema de saúde pública mundial; seu diagnóstico e tratamento causam significantes morbidades físicas e psicológicas, comprometendo a Qualidade de Vida Relacionada à Saúde (QVRS) dos sobreviventes. Terapias Complementares e Alternativas, como as terapias mente-corpo, tem sido usadas por pacientes com câncer para reduzir sintomas e outros efeitos colaterais do tratamento. Objetivo: avaliar o efeito da intervenção de Enfermagem: Relaxamento com Imagem Guiada (visualização) sobre a QVRS e sobre a depressão de pacientes adultos com câncer durante o tratamento quimioterápico. Metodologia: estudo quantitativo, quase-experimental, longitudinal e prospectivo, realizado no Centro Especializado de Oncologia e na Central de Quimioterapia do Hospital das Clínicas, Ribeirão Preto-SP, Brasil. Os pacientes foram divididos em dois Grupos: Controle e Intervenção (GC e GI) e o GI foi submetido às sessões de relaxamento com imagem guiada durante o tratamento quimioterápico; ambos os grupos responderam aos questionários de QVRS (EORTC QLQ-C30) e de depressão (Inventário de Depressão de Beck) no início, meio e final do tratamento. Resultados: a amostra total e por grupo (baseline) foi composta na maioria por mulheres, entre 40 e 59 anos, casadas, aposentadas ou donas de casa, católicas, residentes em Ribeirão Preto, com baixo nível de escolaridade (ensino fundamental). Os cânceres mais frequentes foram: mama, intestinal e gástrico. No tempo 1, ambos os grupos apresentaram como sintomas mais frequentes: dor, fadiga, insônia e perda de apetite e estavam \'sem depressão\'. No decorrer do estudo, na comparação entre grupos, diferenças estatisticamente significantes foram encontradas, em T1 com o GC apresentando melhores escores para EGS/ QV geral, função social e náuseas e vômitos. Em T2, as diferenças foram significantes para função física e em T3 para as funções física, emocional, desempenho de papel, fadiga e náuseas e vômitos, com melhores escores para o GI. Na comparação entre os tempos, o GC teve prejuízo nas funções física, emocional e social, náuseas e vômitos e constipação, enquanto que o GI apresentou melhora da função emocional. De acordo com o IDB, as diferenças foram estatisticamente significantes entre os grupos e entre os tempos, com o GI apresentando mais pacientes \'sem depressão\' do que o GC. Conclusão: Os resultados evidenciaram que a intervenção de relaxamento com imagem guiada foi eficaz para melhorar a QVRS em várias funções (física, emocional, desempenho de papel), sintomas (náuseas e vômitos, dor, insônia, perda de apetite) e depressão. Esta técnica simples, de baixo-custo, segura e benéfica levou a um relaxamento físico e mental do paciente, observado através dos parâmetros fisiológicos e instrumentos de QVRS e depressão utilizados, confirmando a hipótese de que o Relaxamento com Imagem Guiada proporciona melhora na QVRS e na depressão de pacientes adultos com câncer em tratamento quimioterápico. Espera-se que a prática da intervenção Relaxamento com Imagem Guiada seja divulgada e difundida no trabalho do dia-a-dia do enfermeiro, para que em um futuro próximo, possa beneficiar os pacientes oncológicos com estas terapias. / In recent decades, cancer has become a public health problem worldwide; the diagnosis and its treatment cause significant physical and psychological morbidity, compromising Health- Related Quality of Life (HRQoL) of survivors. Complementary and Alternative Therapies, such as mind-body therapies, has been used by cancer patients to reduce symptoms and other side effects of treatment. Objective: To evaluate the effects of nursing interventions: Relaxation with Guided Imagery (visualization) on HRQoL and on depression in adult patients with cancer during chemotherapy. Methodology: quantitative, quasi-experimental, longitudinal and prospective study conducted in the Specialized Oncology Center and in the Chemotherapy Center of Clinical Hospital, Ribeirão Preto-SP, Brazil. The patients were divided into two groups: Control and Intervention (CG and IG) and IG received relaxation sessions with guided imagery during chemotherapy, both groups responded to questionnaires about HRQoL (EORTC QLQ-C30) and depression (Beck Depression Inventory) at the beginning, middle and end of treatment. Results: The total sample and by group (baseline) was composed mostly of women, between 40 and 59 years old, married, retired or housewives, Catholic, living in Ribeirão Preto, with a low educational level (elementary school). The most common cancers were breast, bowel and gastric. At one time, both groups showed most common symptoms: pain, fatigue, insomnia and loss of appetite and were \'not depressed\'. During the study, the comparison between groups, statistically significant differences were found in T1 with CG showing better scores for global QoL, social functioning, and nausea and vomiting. In T2, the differences were significant for physical functioning and T3 to physical functioning, emotional functioning, role functioning, fatigue, and nausea and vomiting, with better scores for IG. Comparing the times, the CG had impairment in physical, emotional and social functioning, nausea and vomiting, and constipation, while the IG showed improvement in emotional functioning. According to the BDI, the differences were statistically significant between groups and between times, with most patients of IG presenting \'no depression\' than the CG. Conclusion: The results showed that the intervention of relaxation with guided imagery was effective for improving HRQoL in various functions (physical, emotional and role functioning), symptoms (nausea and vomiting, pain, insomnia, loss of appetite) and depression. This technique is simple, low-cost, safe and beneficial and this intervention led to a physical and mental relaxation of the patient, observed through the physiological parameters and HRQoL and depression instruments used, confirming the hypothesis that Relaxation with Guided Imagery provides improvement in HRQoL and depression in adult cancer patients undergoing chemotherapy. It is hoped that the practice of intervention of Relaxation with Guided Imagery is disclosed and disseminated in the day-to-day nursing, so that in the near future, patients with cancer can benefit from these therapies

INTRODUÇÃO: A síndrome coronariana aguda (SCA) é uma das manifestações clínicas da doença arterial coronariana. A Estratégia de Registro em Insuficiência Coronariana (ERICO) é uma coorte de indivíduos atendidos no Hospital Universitário da Universidade de São Paulo por SCA. O presente trabalho teve por objetivo descrever a frequência de uso o tempo para administração dos medicamentos habitualmente usados no tratamento das SCA nos participantes do estudo ERICO. MÉTODOS: Foram incluídos 746 participantes ERICO, entre fevereiro de 2009 e dezembro de 2012 que procuraram diretamente o hospital (N=656) ou que se dirigiram inicialmente a unidades de atenção primária à saúde (APS; N=90). Avaliamos o tempo do contato médico ao tratamento com aspirina, clopidogrel, heparina e trombolíticos, de acordo com a unidade de primeiro contato, utilizando modelos de regressão logística. Posteriormente, foram revisados os prontuários de 563 (85,8%) participantes que vieram diretamente ao hospital, e descritas as frequências de administração de aspirina, clopidogrel, heparinas, betabloqueadores, inibidores da enzima conversora de angiotensina (IECA) / bloqueadores dos receptores da angiotensina II (BRA), estatinas, nitratos e morfina. Os motivos de não-administração ou suspensão da aspirina, clopidogrel, heparinas, betabloqueadores e IECA/BRA foram obtidos dos registros em prontuário. RESULTADOS: Observamos que 93,6%, 86,1% e 86,5% dos participantes do estudo receberam aspirina, clopidogrel e heparina, respectivamente, durante as primeiras 24 horas de internação. Em modelos ajustados, indivíduos encaminhados de unidades de APS tinham mais chance de receber aspirina nas primeiras 3 horas (Razão de chances [RC]: 3,65; intervalo de confiança de 95% [IC95%]: 2,04-6,52), mas menor chance de receber heparina (RC: 0,32; IC95%: 0,16-0,62) ou clopidogrel (RC: 0,49; IC95%: 0,29-0,83) no mesmo intervalo de tempo. Entretanto, 24,4% dos participantes encaminhados das unidades de APS não receberam aspirina antes da transferência ao hospital. A não administração de aspirina, clopidogrel e heparina ao longo da internação foi um evento raro, e geralmente ligada a um maior risco de sangramento. Os betabloqueadores não foram prescritos para 15,8% dos participantes, e a principal causa encontrada foi a insuficiência cardíaca descompensada. IECA/BRA não foram prescritos para 16,7%, e a principal causa foi choque ou hipotensão. Entretanto, as causas de não-administração (64,0%) e de suspensão (26,4%) frequentemente não estavam descritas. CONCLUSÕES: Em nosso estudo, participantes que primeiramente foram a unidades de atenção primária tiveram uma maior probabilidade de receber tratamento precoce com aspirina, em comparação aos participantes que foram diretamente ao hospital. Entretanto, proporção significativa não recebeu o medicamento antes da transferência, apontando espaço para potenciais melhorias no atendimento. A frequência do uso de medicamentos no estudo ERICO foi, em geral, igual ou superior à maior parte dos estudos encontrados. A falha de registro adequado dos motivos de não-administração e suspensão em prontuário foi um achado frequente, e que também aponta para oportunidade de aperfeiçoamento da assistência / BACKGROUND: Acute coronary syndrome (ACS) is one of the clinical manifestations of coronary artery disease. The Strategy of Registry of Acute Coronary Syndrome (ERICO) is a cohort of individuals treated at the Hospital Universitário da Universidade de São Paulo due to an ACS event. The aim of this study was to describe the frequency of use and time-to-treatment for drugs commonly used in ACS treatment, in the ERICO study. METHODS: We included 746 ERICO participants enrolled from February 2009 to December 2012 who either sought the hospital directly (N = 656) or were initially referred to primary care units (N = 90). We evaluated the time-to-treatment with aspirin, clopidogrel, heparins and thrombolytics, according to the unit of first contact, using logistic regression models. Subsequently, the medical records of 563 (85.8%) participants who came directly to the hospital were reviewed and the frequency of aspirin, clopidogrel, heparins, beta-blockers, angiotensin-converting enzyme inhibitors (ACEI) / angiotensin II receptor blockers (ARB), statins, nitrates and morphine use. The reasons for non-administration and/or withdrawal of aspirin, clopidogrel, heparins, beta-blockers and ACEI / BRA were obtained from medical records. RESULTS: We observed that 93.6%, 86.1% and 86.5% of study participants received aspirin, clopidogrel and heparin, respectively, during the first 24 hours of hospitalization. In adjusted models, individuals referred from primary care units were more likely to receive aspirin within the first 3 hours (odds ratio [OR]: 3.65, 95% confidence interval [95%CI]: 2.04-6.52), But less likely to receive heparin (OR: 0.32; 95%CI: 0.16-0.62) or clopidogrel (OR: 0.49; 95%CI: 0.29-0.83) in the same time interval. However, 24.4% of the participants referred from primary care units did not receive aspirin before transfer to hospital. Non-administration of aspirin, clopidogrel, and heparin during hospitalization was a rare event, and generally linked to an increased risk of bleeding. Beta-blockers were not prescribed for 15.8% of the participants, and the main cause was decompensated heart failure. ACEI / ARB were not prescribed for 16.7%, and the main cause was shock or hypotension. However, the causes of non-administration (64.0%) and withdrawal (26.4%) were often not described. CONCLUSIONS: In our study, participants who first went to primary care units were more likely to receive early treatment with aspirin compared to those who went directly to the hospital. However, a significant proportion did not receive the drug prior to the transfer, indicating room for potential improvements in care. The frequency of medication use in the ERICO study was generally equal to or greater than those described in other studies. Failure to properly register the reasons for drug non-administration and treatment withdrawal was a frequent finding, pointing to an opportunity for improved care

A farmacoterapia complexa com múltiplos medicamentos aumenta a probabilidade de interações medicamentosas (IM) e eventos adversos a medicamentos(EAM) em pacientes de unidade de terapia intensiva (UTI). Este estudo teve como objetivos: analisar e classificar as IM potenciais dos tipos fármaco-fármaco e fármaco-nutrição enteral e os EAM detectados, durante a internação de pacientes, na UTI de um hospital de ensino, identificar os EAM relacionados a IM e investigar os fatores associados com IM e EAM. O estudo transversal, correlacional, retrospectivo investigou 299 prontuários de pacientes internados por cinco ou mais dias na UTI. As IM potenciais foram identificadas e classificadas empregando o software Drug Reax. Investigou-se IM em prescrições de três momentos: 24 horas de internação, mediana da internação e alta. Os EAM foram identificados empregando o método de monitorização intensiva e também critérios de rastreabilidade de EAM. Os EAM foram classificados em relação à causalidade e à gravidade Os dados foram analisados empregando análise descritiva, univariada e regressão logística múltipla. A maioria da casuística era do sexo feminino (50,5%) e com mediana de idade de 57 anos. Em 24 horas a prevalência de pacientes com IM potenciais foi 68,6%. A maior frequência de pacientes com IM potenciais foi 73,9% na mediana da internação. Na alta detectou-se que 69,6% dos pacientes apresentaram IM potenciais. Cerca de 99% das interações era do tipo fármaco-fármaco. As interações fármaco-nutrição enteral foram mais frequentes em prescrições de pacientes em alta. Em relação a gravidade a maioria das IM eram graves e moderadas. O número de medicamentos administrados e o uso de medicamentos do sistema cardiovascular foram os fatores associados com a ocorrência de IM, de forma independente, nos três momentos da internação. Detectou-se que 34,1% dos pacientes apresentaram EAM. Os EAM mais frequentes foram reações adversas a medicamentos (RAM) do Tipo A, de causalidade possível e gravidade moderada. Os pacientes com EAM relacionados a IM corresponderam a 7% da casuística. O tempo de internação e a administração de medicamentos cardiovasculares apresentaram associação com a ocorrência de EAM na regressão logística . Os resultados desta investigação mostraram que apesar da frequência elevada de IM potenciais, o número de EAM relacionados a IM foi reduzido, entretanto envolveu RAM de significância clínica como nefrotoxicidade e sedação excessiva que podem comprometer a segurança do paciente. / Complex pharmacotherapy with multiple medications increases the chances of drug interactions (DI) and adverse drug events (ADE) in patients at intensive care units (ICU). This study aimed to analyze and classify potential drug interactions of the following types: drug-drug and drug-enteral nutrition and also ADE detected during patients\' hospitalization in the ICU of a teaching hospital; to identify drug adverse events related to DI; and investigate factors associated with DI and ADE. This crosssectional, correlational and retrospective study investigated 299 medical records of patients hospitalized for five or more days in the ICU. Potential DI were identified and classified through the software Drug-Reax. Interactions in prescriptions were identified in three occasions: at 24 hours of hospitalization, at median of stay and at discharge of ICU stay . ADE were identified through the method of intensive monitoring and also adverse drug event trigger. ADE were classified regarding causality and severity.Data were analyzed through descriptive analysis, univariate and multiple logistic regression. The majority was female (50.5%) and median age was 57 years. The prevalence of patients with potential DI at 24h was 68.6%. The highest frequency of patients with potential DI was 73.9% in the median of hospitalization. We found that 69.6% of patients presented potential DI at discharge. About 99% were drug-drug interactions. The drug-enteral nutrition interactions were more frequent in patients\' prescriptions at discharge. Most IM were severe or moderate.The number of administered medication and the use of medication for the cardiovascular system were the factors independently associated with the occurrence of DI in the three occasions of hospitalization. The study also detected that 34.1% of patients presented ADE The most frequent ADE were adverse drug reactions (ADR) type A, of possible causality and moderate severity. Patients with ADE related to DI corresponded to 7% of the sample. The multiple logistic regression revealed that time of hospitalization and administration of cardiovascular medication were associated with the occurrence of ADE. This study\'s results revealed that despite the high frequency of potential DI, the number of ADE related to DI was small, however, these involved ADR of clinical significance such as nephrotoxicity and oversedation, which might compromise patient safety.

Wang Deqing. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 236-277). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Despite numerous studies have demonstrated an association of type 2 diabetes mellitus (T2DM) and osteoporosis, the underlying mechanism connecting these two conditions remains elusive. Clinically, combined calcium and vitamin D supplement is the commonest osteoporosis therapy; however, recent studies have suggested an increase in cardiovascular risks associated with calcium plus vitamin D supplementation. Therefore, an alternative strategy in treating osteoporosis patients with T2DM is urgently needed. In this study, we hypothesized that combined administration of menaquinone-4 (vitamin K₂, biologically active form of vitamin K) and 1α,25-dihydroxyvitamin D₃ (vitamin D₃, biologically active form of vitamin D) as a novel therapy in treating osteoporosis of T2DM patients. Anabolic effect of vitamin K₂ and vitamin D₃, alone or in combination, was assessed on primary osteoblasts harvested from the iliac crests of C57BL/KsJ lean (db⁺/m⁺) and obese/diabetic (db⁺/db⁺, leptin receptor-deficient) mice. Furthermore, the underlying cellular mechanism was also investigated. Serum undercarboxylated osteocalcin (an indication of vitamin K₂ level) level was higher whereas vitamin D₃ level was lower in db⁺/db⁺ mice, and sections of the iliac crests of db⁺/db⁺ mice illustrated extensive porous structures filled with enlarged adipocytes compared with db⁺/m⁺ mice. Lower levels of bone anabolic markers and bone formation transcription factors (osteocalcin, Runx2, Dlx5, ATF4, type I collagen, OSX, alkaline phosphatase (ALP) activity, p-Smad1/5/8 and p-ERK1/2) were observed in the osteoblasts of db⁺/db⁺ mice. Acute vitamin D₃ (10 nM) application elicited a more sustained and greater magnitude of increase of [Ca²⁺]ᵢ in osteoblasts of db⁺/m⁺ mice when compared with db⁺/db⁺ mice. A significantly higher level of calcium deposits in osteoblasts was observed in db⁺/m⁺ mice when compared to db⁺/db⁺ mice. Co-administration of vitamin K₂ (10 nM) and vitamin D₃ (10 nM) caused an enhancement of calcium deposits in osteoblasts in both strains of mice. Vitamins K₂ and D₃ co-administration time-dependently (7, 14 and 21 days) increased the levels of bone anabolic markers and transcription factors for bone formation, with a greater magnitude of increase observed in osteoblasts of db⁺/db⁺ mice. Suppressed expression of calcium-sensing receptor (CaSR), F-actin, V-ATPase, vitamin D receptor (VDR) and pregnane X receptor (PXR) observed in osteoblasts of db⁺/db⁺ mice were partially reversed by combined vitamins treatment. Moreover, combined vitamins K₂ plus D₃ treatment significantly enhanced migration and the appearance of surface microvilli and ruffles of osteoblasts of db⁺/db⁺ mice. Effects of combined vitamins K₂ plus D₃ treatment observed in osteoblasts of db⁺/db⁺ and db⁺/m⁺ mice were eradicated by warfarin (20 µM, a vitamin K epoxide reductase inhibitor). Thus, our results illustrate that vitamins K₂ plus D₃ supplementation is a novel therapeutic strategy in treating osteoporosis of T2DM patients. / 儘管大量研究已證明第二類型糖尿病和骨質疏鬆症的關聯，連接這兩個病症的基本機制仍然是難以捉摸的。在臨床上，鈣和維生素D的綜合補充劑是最常見的骨質疏鬆症治療，然而最近的研究卻表明服用鈣和維生素D的綜合補充劑會增加患者的心血管風險，因此急切需要尋找可以給予同時患有骨質疏鬆症和第二類型糖尿病患者的替代治療。在本研究中，我們假設甲萘醌-4（維生素K₂，維生素K生物活性形式）和1α，25 - 二羥基維生素D₃（維生素D₃，維生素D的生物活性形式）可以嘗試在同時患有骨質疏鬆症和第二類型糖尿病患者身上作為一種革新的療法。本研究從C57BL/KsJ瘦削/非糖尿病 (db⁺/m⁺) 的小鼠和肥胖/帶有第二類型糖尿病基因 (db⁺/db⁺) 兼有瘦素受體缺陷的小鼠的髂嵴原始成骨細胞上對維生素K₂和維生素D₃單獨或組合使用的合成代謝作用進行了評估。此外，我們也對該成骨細胞的底層機制進行了一系列的研究。 / 在肥胖/帶有第二類型糖尿病基因的小鼠血清內低羧骨鈣素水平（維生素K₂水平的指標）較高而維生素D水平較低，另外，它們的髂嵴的部分與瘦削/非糖尿病的小鼠相比，呈現出比較廣泛的多孔結構並填滿了擴大的脂肪細胞。從肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞中，可以觀察到它們的骨合成代謝的標誌物和骨骼形成的轉錄因子 (骨鈣蛋白，Runx2，Dlx5，ATF4，第一類型骨膠原，OSX，鹼性磷酸酶 (ALP) 活性，p-Smad1/5/8和p-ERK1/2) 的水平比較低。急性維生素D₃ (10 nM) 的應用在瘦削/非糖尿病小鼠的成骨細胞比起在肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞引起更持續和更大幅度的細胞內鈣變化增加。在瘦削/非糖尿病小鼠的成骨細胞中比起在肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞有顯著較高的鈣沉積形成。維生素K₂ (10 nM) 和維生素D₃ (10 nM) 的綜合藥在兩種小鼠的成骨細胞中可以有效地增強鈣沉積的形成。維生素K₂和維生素D₃的綜合藥對增加骨合成代謝的標誌物和骨形成轉錄因子的水平有時間依賴性 (7，14和21日)，療程越長至21日，在肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞中有更大的幅度的增加。合併維生素治療能部分有效地逆轉在肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞中被抑制表達的鈣敏感受體 (CASR)，F-肌動蛋白，V-ATP酶，維生素D受體 (VDR) 和孕烷X受體 (PXR)。此外，結合維生素K₂加維生素D₃治療顯著增強了肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞的細胞遷移和增加了成骨細胞表面外觀的微絨毛和褶皺。在瘦削/非糖尿病小鼠的成骨細胞及肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞上結合維生素K₂加維生素D₃的治療效果被華法林 (20 μM，維生素K環氧化物還原酶抑製劑) 根除。因此，我們的結果証明了維生素K₂加維生素D₃補充劑的結合使用可有效地作為治療第二類型糖尿病患者並患有骨質疏鬆症的一種新的治療策略。 / Poon, Chui Wa Christina. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014.n5203 / Includes bibliographical references (leaves 135-151). / Abstracts also in Chinese. / Title from PDF title page (viewed on 26, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Fan, Rongrong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 130-150). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

TCP-1是一种新型的定向于肿瘤血管的多肽，通过小鼠体内的噬菌体展示技术筛选得到。在之前的研究中，我们已证明TCP-1具有定向于肿瘤血管并有效靶向运输抗肿瘤药物和显像剂的特性。本研究的目的是进一步研究在原位结肠癌模型中定向运输抗肿瘤药物肿瘤坏死因子(TNFα)，以及在结肠癌临床样本中运输显像剂异硫氰酸荧光素(FITC)的能力。并对TCP-1与肿瘤坏死因子的融合蛋白TCP-1/TNFα的抗肿瘤机制进行阐述。 / 本研究中，我们首先尝试用TCP-1作为载体，将增强绿色荧光蛋白靶向运输至肿瘤血管。结果证明TCP-1可以成功将蛋白运输到在肿瘤血管而非其它正常的组织器官上。TCP-1还可以靶向运输肿瘤坏死因子并增强其抗肿瘤作用。和肿瘤坏死因子比较，融合蛋白TCP-1/TNFα处理组的凋亡细胞数量增多，肿瘤微血管数目减少，并且无明显毒副作用。与结肠癌的一线化疗药物5-氟尿嘧啶(5-FU)联合给药后，与TNFα与5-FU联合给药相比较，融合蛋白TCP-1/TNFα联合5-FU在以下方面具有更明显的作用：抑制肿瘤生长，增加肿瘤细胞凋亡和抑制肿瘤细胞增殖，促进肿瘤血管正常化，升高瘤内免疫细胞以及减轻骨髓和脾内的免疫抑制反应。经检测TCP-1的靶向运输增加了瘤内的TNFα以及5-FU的浓度。这些都表明TCP-1不但可以靶向运输TCP-1/TNFα至肿瘤血管，还可以增加CD8+细胞的浸润增加瘤内免疫反应以及增加血管对抗肿瘤药物的通透性。以上都对抗肿瘤起到重要作用。 / 在临床的结肠癌样本中，TCP-1对肿瘤血管的结合能力也得到了证实。48.98%的结肠癌样本对TCP-1的结合为阳性。统计学分析显示TCP-1的结合与结肠癌的分期和肿瘤位置有关，对于N2期，位于乙状结肠的肿瘤的结合尤为明显。本研究的主要目的是将分离鉴定出的TCP-1发展成为结肠癌的生物标记，并且作为运输抗肿瘤药物和显像剂的载体应用于结肠癌的诊断和治疗中。鉴于TCP-1的靶向运输特点，将会有机会研发更多的抗肿瘤药物，同时增强传统化疗药的抗肿瘤作用。这些都可以优化肿瘤治疗的方案。综上所述，TCP-1是一种在结肠癌治疗诊断中具有广阔前景的多肽。 / TCP-1 is a novel vasculature-targeting peptide. It was discovered through the in vivo phage library selection in mice. It was demonstrated that TCP-1 peptide exhibited a homing ability to the neovasculature of colon tumors and was capable of efficiently delivering imaging agents and chemotherapeutic drugs to this target site. The current study is to further investigate the targeting ability of TCP-1 to deliver a known immunomodulator, tumor necrosis factor α (TNFα) as an example of anti-cancer drug in an orthotopic colorectal cancer (CRC) model and fluorescein isothiocyanate (FITC) as imaging agent for testing the binding capacity for tumors in colorectal cancer patients. The mechanisms for the action of this novel biologic TCP-1/TNFα in the treatment of colon cancer in mice were also defined. / In this study, we observed that TCP-1 peptide delivered enhanced green fluorescent protein (EGFP) only to tumor blood vessel other than normal organs after TCP- 1/EGFP injection. This was not observed after EGFP injection. This finding showed that TCP-1 can deliver biologic protein to the tumor blood vessels. Furthermore, results from TNFα or TCP-1/TNFα targeted delivery experiments showed that TCP- 1/TNFα displayed stronger anti-cancer effects than TNFα alone on the induction of apoptosis and reduction in number of microvessels in the tumors, without significant effect in systemic toxicity. In the combined therapy with 5-fluorouracil (5-FU), a standard drug for colon cancer treatment, pretreatment with low dose (1 ng TNFα /mouse) of TNFα or TCP-1/TNFα potentiated the anti-cancer action of 5-FU. In this regard, TCP-1/TNFα could significantly reduce tumor size and weight, increase number of apoptotic cells, inhibit tumor cell proliferation, normalize tumor blood vessels, facilitate infiltration of immune cells to tumor mass and attenuate immunosuppression in bone marrow and spleen. Moreover, TCP-1 could significantly increase intratumoral levels of TNFα and 5-FU. It was also suggested that TCP-1 could selectively deliver TNFα to the tumor blood vessels and modulate the immune response by increasing CD8+ cells infiltration to tumors and increase vascular permeability to 5-FU. These observations may be the key actions to reduce tumor growth. / The binding ability of TCP-1 was also detected in clinical samples from colorectal cancer patients in which 24/49 (48.98%) tumor tissues were positive with TCP-1 binding signal. Statistical analysis showed that TCP-1 had a strong and significant binding with colorectal cancer at the N2 stage among the different colorectal cancer stages (P=0.028) and location in the colon at the sigmoid (P<0.001). / Our study also focused on the isolation and identification of the binding molecule of TCP-1 in order to develop it into a biomarker for CRC and using TCP-1 as a carrier in delivering anti-cancer drugs and imaging agents to colon tumors for cancer therapy and diagnosis. With the homing property of TCP-1 on colon tumor blood vessels, new types of anti-cancer drugs will be developed and their combinations with conventional chemotherapy drugs will optimize the therapeutic outcome and improve regimen of treatment for CRC. Taken together, TCP-1 peptide appears to be a promising agent in molecular imaging and drug delivery for CRC diagnosis and therapy. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Lu, Lan. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 157-177). / Abstracts also in Chinese. / Lu, Lan.

Lim Sze Nee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 165-176). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract (Chinese Version) --- p.iii / Acknowledgements --- p.v / Table of Contents --- p.vi / List of Tables --- p.xi / List of Figures --- p.xiii / List of Abbreviation --- p.xvii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1. --- General Introduction --- p.1 / Chapter 1.1 --- Classification of algae --- p.2 / Chapter 1.2 --- Chemical and mineral composition of marine macroalgae --- p.4 / Chapter 1.3 --- Uses of marine macroalgae --- p.7 / Chapter 1.3.1 --- Food --- p.7 / Chapter 1.3.2 --- Industrial uses --- p.8 / Chapter 1.3.3 --- Agricultural uses --- p.9 / Chapter 1.3.3.1 --- Fertilizer --- p.9 / Chapter 1.3.3.2 --- Fodder --- p.9 / Chapter 1.3.4 --- Medicinal properties --- p.10 / Chapter 1.4 --- Pharmacological effects of marine macroalgae --- p.11 / Chapter 1.4.1 --- Antioxidant activity --- p.11 / Chapter 1.4.2 --- Hypotensive activity --- p.11 / Chapter 1.4.3 --- Antiviral activity --- p.12 / Chapter 1.4.4 --- Antimicrobial activity --- p.12 / Chapter 1.4.5 --- Antitumor activity --- p.13 / Chapter 1.4.6 --- Hypocholesterolemic activity --- p.14 / Chapter 1.5 --- Objectives --- p.14 / Chapter CHAPTER 2 --- Free Radical Scavenging and Antioxidative Activities of Marine Macroalgae --- p.16 / Chapter 2.1 --- Introduction --- p.16 / Chapter 2.1.1 --- Free radicals: definition and sources --- p.16 / Chapter 2.1.2 --- Free radical-induced damage --- p.16 / Chapter 2.1.2.1 --- Biological lipid peroxidation --- p.16 / Chapter 2.1.2.2 --- Lipid oxidation of foods --- p.18 / Chapter 2.1.3 --- Antioxidants --- p.19 / Chapter 2.1.3.1 --- Antioxidants --- p.19 / Chapter 2.1.3.2 --- Antioxidant mechanisms --- p.20 / Chapter 2.1.4 --- Synthetic antioxidants --- p.21 / Chapter 2.1.5 --- Natural antioxidants --- p.24 / Chapter 2.1.6 --- Objectives --- p.27 / Chapter 2.2 --- Methods and Materials --- p.28 / Chapter 2.2.1 --- Preparation of algae extracts --- p.28 / Chapter 2.2.2 --- Determination of free radical scavenging activities --- p.32 / Chapter 2.2.2.1 --- Superoxide anions scavenging activity --- p.32 / Chapter 2.2.3 --- Antioxidative activity using hemolysis assay --- p.33 / Chapter 2.2.3.1 --- Preparation of red blood cell (RBC) --- p.33 / Chapter 2.2.3.2 --- Hemolysis assay --- p.33 / Chapter 2.2.4 --- Lipid peroxidation assay --- p.34 / Chapter 2.2.4.1 --- Preparation of rat brain homogenates --- p.34 / Chapter 2.2.4.2 --- Measurement of lipid peroxidation --- p.34 / Chapter 2.2.5 --- Statistics --- p.35 / Chapter 2.3 --- Results --- p.36 / Chapter 2.3.1 --- Superoxide radical scavenging activity of algal extracts --- p.36 / Chapter 2.3.2 --- Effects of algae extracts on hemolysis assay --- p.41 / Chapter 2.3.3 --- Effects of algae extracts on lipid peroxidation --- p.44 / Chapter 2.4 --- Discussion --- p.50 / Chapter CHAPTER 3 --- Isolation of Antioxidative Phenolic Compounds from Sargassum siliquastrum --- p.60 / Chapter 3.1 --- Introduction --- p.60 / Chapter 3.1.1 --- Phenolic compounds --- p.60 / Chapter 3.1.2 --- Major classes of phenolic compounds --- p.60 / Chapter 3.1.3 --- Functional aspects of phenolic compounds --- p.61 / Chapter 3.1.3.1 --- Functions of phenolic compounds in plants --- p.61 / Chapter 3.1.3.2 --- Biological and pharmacological activities --- p.64 / Chapter 3.1.3.3 --- Food industry --- p.65 / Chapter 3.1.4 --- Polyphenolic compounds in brown algae --- p.66 / Chapter 3.1.5 --- Objectives --- p.68 / Chapter 3.2 --- Methods and Materials --- p.69 / Chapter 3.2.1 --- Extraction and isolation of antioxidant components from S siliquastrum --- p.69 / Chapter 3.2.2 --- Thin-Layer chromatography --- p.70 / Chapter 3.2.3 --- Antioxidant activity --- p.71 / Chapter 3.2.4 --- Determination of total phenolics --- p.71 / Chapter 3.2.5 --- Infrared spectra --- p.72 / Chapter 3.2.6 --- Ultra-violet and visible (UV-vis) spectrophotometry --- p.72 / Chapter 3.2.7 --- Statistics --- p.73 / Chapter 3.3 --- Results --- p.73 / Chapter 3.3.1 --- Identification of phenolic compounds from various solvent extracts of S. siliquastrum --- p.73 / Chapter 3.3.2 --- Isolation of dichloromethane fraction by liquid chromatography --- p.81 / Chapter 3.3.3 --- Phenolic content of isolated compounds --- p.86 / Chapter 3.3.4 --- IR and UV-vis spectra --- p.86 / Chapter 3.4 --- Discussion --- p.92 / Chapter 3.4.1 --- Antioxidative activities --- p.92 / Chapter 3.4.2 --- Relationship between phenolic contents and antioxidant activity --- p.95 / Chapter 3.4.3 --- Identification of antioxidant compounds --- p.97 / Chapter CHAPTER 4 --- Hypotensive Activities of Marine Algae in the Rat --- p.102 / Chapter 4.1 --- Introduction --- p.102 / Chapter 4.1.1 --- Basic principles of cardiovascular system --- p.102 / Chapter 4.1.2 --- Regulation of arterial pressure --- p.105 / Chapter 4.1.2.1 --- Short-term regulation of arterial pressure --- p.105 / Chapter 4.1.2.2 --- Long-term regulation of arterial pressure --- p.107 / Chapter 4.1.3 --- Hypertension --- p.108 / Chapter 4.1.3.1 --- Causes of hypertension --- p.109 / Chapter 4.1.3.2 --- Where do antihypertensive or hypotensive agents act? --- p.114 / Chapter 4.1.3.2.1 --- Sympathetic nervous system inhibitors --- p.115 / Chapter 4.1.3.2.2 --- Diuretics --- p.120 / Chapter 4.1.3.2.3 --- Vasodilators --- p.121 / Chapter 4.1.3.2.4 --- Calcium antagonist (Calcium channel blockers) --- p.121 / Chapter 4.1.3.2.5 --- Angiotensin-converting enzyme (ACE) inhibitors --- p.122 / Chapter 4.1.3.2.6 --- Antihypertensive drug combination --- p.122 / Chapter 4.1.4 --- The relationship between hypertension and free radicals --- p.123 / Chapter 4.1.5 --- Development of new antihypertensive agenrs --- p.124 / Chapter 4.2 --- Materials and methods --- p.125 / Chapter 4.2.1 --- Animal care --- p.125 / Chapter 4.2.2 --- Preparation of the blood pressure measurement in rats --- p.125 / Chapter 4.2.2.1 --- Effects of seaweed extracts on arterial blood pressure of rat --- p.126 / Chapter 4.2.2.1.1 --- Single-dose response curve --- p.126 / Chapter 4.2.2.1.2 --- Cumulative-dose response curve --- p.126 / Chapter 4.2.2.2 --- Pharmacological blocker studies --- p.128 / Chapter 4.2.3 --- Statistics --- p.131 / Chapter 4.3 --- Results --- p.131 / Chapter 4.3.1 --- Hypotensive effects of marine algal extracts --- p.131 / Chapter 4.3.2 --- Effects of pharmacological blockers on MAP --- p.135 / Chapter 4.4 --- Discussion --- p.150 / Chapter 4.4.1 --- Hypotensive effects of the marine algal extracts --- p.150 / Chapter 4.4.2 --- Pharmacological action of marine algal extracts --- p.152 / Chapter CHAPTER 5 --- Conclusion --- p.160 / REFERENCES --- p.165 / RELATED PUBLICATIONS --- p.177

Tsang Yuen-Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 200-218). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABBREVIATIONS --- p.iii / ABSTRACT --- p.vii / CHINESE ABSTRACT --- p.xi / TABLE OF CONTENTS --- p.xiii / Chapter CHAPTER 1: --- GENERAL INTRODUCTION / Chapter 1.1 --- Hematopoiesis --- p.1 / Chapter 1.1.1 --- An Overview on Hematopoiesis --- p.1 / Chapter 1.1.2 --- Role of Cytokines in the Control of Hematopoiesis --- p.4 / Chapter 1.2 --- Leukemia --- p.5 / Chapter 1.2.1 --- Abnormalities in Hematopoietic Cell Development --- p.5 / Chapter 1.2.2 --- Classification of Leukemia --- p.7 / Chapter 1.2.3 --- Etiology and Symptoms of Leukemia --- p.9 / Chapter 1.2.4 --- Therapeutic Strategies for Leukemia --- p.10 / Chapter 1.2.4.1 --- Conventional Therapies --- p.10 / Chapter 1.2.4.2 --- Differentiation Therapy and Induction of Apoptosis in Leukemia --- p.11 / Chapter 1.2.5 --- Regulation of Apoptosis and Cell Cycle Progression --- p.12 / Chapter 1.2.5.1 --- Apoptosis --- p.12 / Chapter 1.2.5.2 --- Cell Cycle --- p.13 / Chapter 1.2.5.3 --- Disregulation of Apoptosis and Cell Cycle Contribute to the Development of Leukemia --- p.14 / Chapter 1.3 --- Licorice --- p.16 / Chapter 1.3.1 --- Chemistry of Licorice --- p.16 / Chapter 1.3.2 --- Pharmacological Activities of Glycyrrhizin and 18-β Glycyrrhetinic Acid --- p.22 / Chapter 1.3.2.1 --- Mineralocorticoid Activity --- p.22 / Chapter 1.3.2.2 --- Anti-inflammatory Effect --- p.23 / Chapter 1.3.2.3 --- Anti-allergic Effect --- p.24 / Chapter 1.3.2.4 --- Enhancement of Immune Response --- p.24 / Chapter 1.3.2.5 --- Anti-hepatotoxic Effects --- p.26 / Chapter 1.3.2.6 --- Anti-viral Activity --- p.27 / Chapter 1.3.2.7 --- Anti-carcinogenic and Anti-tumor Effects --- p.28 / Chapter 1.3.3 --- Other Biological Activities of Licorice --- p.30 / Chapter 1.3.4 --- A 96-kDa Glycyrrhizin-Binding Protein (gb96) --- p.31 / Chapter 1.3.5 --- Evaluation of Health Hazard --- p.32 / Chapter 1.4 --- Aims and Scopes of This Research --- p.34 / Chapter CHAPTER 2: --- MATERIALS AND METHODS / Chapter 2.1 --- Materials --- p.37 / Chapter 2.1.1 --- Animals --- p.37 / Chapter 2.1.2 --- Cell Lines --- p.37 / Chapter 2.1.3 --- "Cell Culture Medium, Buffers and Reagents" --- p.39 / Chapter 2.1.4 --- Recombinant Cytokines --- p.42 / Chapter 2.1.5 --- [methyl-3H] Thymidine (3H-TdR) --- p.43 / Chapter 2.1.6 --- Liquid Scintillation Cocktail --- p.44 / Chapter 2.1.7 --- Reagents and Buffers for Flow Cytometry --- p.44 / Chapter 2.1.8 --- Monoclonal Antibodies --- p.45 / Chapter 2.1.9 --- Reagents for DNA Extraction --- p.47 / Chapter 2.1.10 --- Reagents for Total RNA Isolation --- p.48 / Chapter 2.1.11 --- Reagents and Buffers for RT-PCR Study --- p.49 / Chapter 2.1.12 --- Reagents and Buffers for Gel Electrophoresis --- p.55 / Chapter 2.1.13 --- Reagents and Buffers for Western Blot Analysis --- p.56 / Chapter 2.2 --- Methods --- p.63 / Chapter 2.2.1 --- Culture of the Tumor Cell Lines --- p.63 / Chapter 2.2.2 --- "Isolation, Preparation and Culture of Primary Mouse Cells" --- p.63 / Chapter 2.2.3 --- Determination of Cell Proliferation by [3H]-TdR Incorporation Assay --- p.64 / Chapter 2.2.4 --- Determination of Cell Viability --- p.65 / Chapter 2.2.5 --- Cell Morphology Study --- p.66 / Chapter 2.2.6 --- Apoptosis Study by DNA Fragmentation --- p.66 / Chapter 2.2.7 --- Flow Cytometric Analysis --- p.67 / Chapter 2.2.8 --- Cell Cycle/DNA Content Evaluation --- p.68 / Chapter 2.2.9 --- Gene Expression Study --- p.69 / Chapter 2.2.10 --- Protein Expression Study --- p.72 / Chapter 2.2.11 --- Statistical Analysis --- p.75 / Chapter CHAPTER 3: --- THE ANTI-TUMOR EFFECTS OF GLYCYRRHIZIN AND 18-β GLYCYRRHETINIC ACID ON VARIOUS LEUKEMIC CELL LINES / Chapter 3.1 --- Introduction --- p.76 / Chapter 3.2 --- Results --- p.78 / Chapter 3.2.1 --- The Growth Inhibitory Effects of Glycyrrhizin on Various Leukemic Cell Lines --- p.78 / Chapter 3.2.1.1 --- Differential Anti-proliferative Effects of Glycyrrhizin on Various Leukemic Cell Lines In Vitro --- p.78 / Chapter 3.2.1.2 --- Effects of Glycyrrhizin on the Viability of Various Leukemic Cell Lines and Normal Hematopoietic Cells In Vitro --- p.89 / Chapter 3.2.1.3 --- Induction of DNA Fragmentation in Leukemia Cells by Glycyrrhizin --- p.94 / Chapter 3.2.1.4 --- Effect of Glycyrrhizin on the Cell Cycle Kinetics of HL-60 Cells In Vitro --- p.97 / Chapter 3.2.1.5 --- Effect of Glycyrrhizin on the Cell Cycle Kinetics of JCS Cells In Vitro --- p.100 / Chapter 3.2.1.6 --- Effect of Glycyrrhizin on the In Vivo Tumorigenicity of the Murine Myeloid Leukemia JCS Cells --- p.103 / Chapter 3.2.2 --- The Growth Inhibitory Effects of 18-β Glycyrrhetinic Acid on Various Leukemic Cells Lines --- p.105 / Chapter 3.2.2.1 --- Differential Anti-proliferative Effect of 18-β Glycyrrhetinic Acid on Various Leukemic Cell Lines In Vitro --- p.105 / Chapter 3.2.2.2 --- Effects of 18-β Glycyrrhetinic Acid on the Viability of Various Leukemic Cell Lines and Normal Hematopoietic Cells In Vitro --- p.115 / Chapter 3.2.2.3 --- Induction of DNA Fragmentation in Leukemia Cells by 18-β Glycyrrhetinic Acid --- p.120 / Chapter 3.2.2.4 --- Effect of 18-β Glycyrrhetinic Acid on the Cell Cycle Kinetics of HL-60 Cells In Vitro --- p.123 / Chapter 3.2.2.5 --- Effect of 18-β Glycyrrhetinic Acid on the Cell Cycle Kinetics of JCS Cells In Vitro --- p.126 / Chapter 3.2.2.6 --- Effect of 18-β Glycyrrhetinic acid on the In Vivo Tumorigenicity of the Murine Myeloid Leukemia JCS Cells --- p.129 / Chapter 3.3 --- Discussion --- p.131 / Chapter CHAPTER 4: --- THE DIFFERENTIATION-INDUCING EFFECTS OF GLYCYRRHIZIN AND 18-β GLYCYRRHETINIC ACID ON MURINE MYELOID LEUKEMIA CELLS / Chapter 4.1 --- Introduction --- p.135 / Chapter 4.2 --- Results --- p.138 / Chapter 4.2.1 --- Morphological Changes in Glycyrrhizin or 18-β Glycyrrhetinic Acid-treated JCS Cells --- p.138 / Chapter 4.2.2 --- Surface Antigen Immunophenotyping of Glycyrrhizin or 18-β Glycyrrhetinic Acid-treated JCS Cells --- p.141 / Chapter 4.2.3 --- Endocytic Activity of Glycyrrhizin or 18-β Glycyrrhetinic Acid-treated JCS Cells --- p.155 / Chapter 4.3 --- Discussion --- p.158 / Chapter CHAPTER 5: --- MECHANISTIC STUDIES ON THE ANTI LEUKEMIC ACTIVITIES OF GLYCYRRHIZIN AND 18-P GLYCYRRHETINIC ACID / Chapter 5.1 --- Introduction --- p.161 / Chapter 5.2 --- Results --- p.164 / Chapter 5.2.1 --- Combining Effect of Glycyrrhizin or 18-β Glycyrrhetinic Acid with Hematopoietic Cytokines in Modulating the Proliferation of the Murine Myeloid Leukemia JCS Cells --- p.164 / Chapter 5.2.1.1 --- Combining Effect of Glycyrrhizin and IL-lα on the Proliferation of JCS Cells --- p.164 / Chapter 5.2.1.2 --- Combining Effects of Glycyrrhizin with IFN-γ or TNF-α on the Proliferation of JCS Cells --- p.166 / Chapter 5.2.1.3 --- Combining Effect of 18-β Glycyrrhetinic Acid and IL-lα on the Proliferation of JCS Cells --- p.169 / Chapter 5.2.1.4 --- Combining Effects of 18-β Glycyrrhetinic Acid with IFN-γ or TNF-α on the Proliferation of JCS Cells --- p.169 / Chapter 5.2.2 --- Elucidation of the Molecular Mechanisms of Glycyrrhizin or 18-β Glycyrrhetinic Acid on Leukemic Cell Differentiation and Growth Arrest --- p.173 / Chapter 5.2.2.1 --- Modulatory Effects of Glycyrrhizin and 18-β Glycyrrhetinic Acid on the Expression of Cytokine Genes in the Leukemia JCS Cells --- p.173 / Chapter 5.2.2.2 --- Modulatory Effects of Glycyrrhizin and 18-β Glycyrrhetinic Acid on the Expression of PKC Isoforms in the Leukemia JCS Cells --- p.176 / Chapter 5.2.2.3 --- Modulatory Effects of Glycyrrhizin and 18-β Glycyrrhetinic Acid on the Expression of Growth- regulatory Genes in the Leukemia JCS Cells --- p.180 / Chapter 5.2.2.4 --- Modulatory Effects of 18-β Glycyrrhetinic Acid on the Expression of Apoptosis-related Genes in the Leukemia JCS Cells --- p.183 / Chapter 5.2.2.5 --- Modulatory Effects of 18-β Glycyrrhetinic Acid on the Expression of Growth-regulatory and Apoptosis-related Proteins in JCS Cells --- p.185 / Chapter 5.3 --- Discussion --- p.187 / Chapter CHAPTER 6: --- CONCLUSIONS AND FUTURE PERSPECTIVES --- p.194 / REFERENCES --- p.200