Thesis (M. Med. Sc.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 47-50).

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

published_or_final_version / Surgery / Master / Master of Medical Sciences

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

No description available.

Lee Kin-wah. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 187-203). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABBREVIATIONS --- p.ii / ABSTRACT --- p.vi / CHINESE ABSTRACT --- p.ix / TABLE OF CONTENTS --- p.xii / Chapter CHAPTER 1: --- GENERAL INTRODUCTION --- p.1 / Chapter 1.1 --- Neuroblastoma-An Overview --- p.1 / Chapter 1.1.1 --- Epidemiology of Neuroblastoma --- p.1 / Chapter 1.1.2 --- Clinical Presentations of Neuroblastoma --- p.2 / Chapter 1.1.3 --- Diagnosis of Neuroblastoma --- p.3 / Chapter 1.1.4 --- Staging of Neuroblastoma --- p.5 / Chapter 1.1.5 --- Prognostic Considerations of Neuroblastoma --- p.6 / Chapter 1.1.5.1 --- Age --- p.6 / Chapter 1.1.5.2 --- Primary Tumor Site --- p.6 / Chapter 1.1.5.3 --- Tumor Histopathology --- p.7 / Chapter 1.1.5.4 --- Serum Markers --- p.9 / Chapter 1.1.5.5 --- Genetic Markers --- p.9 / Chapter 1.1.6 --- Standard Treatment Modalities for Neuroblastoma --- p.11 / Chapter 1.1.6.1 --- Surgery --- p.11 / Chapter 1.1.6.2 --- Chemotherapy --- p.12 / Chapter 1.1.6.3 --- Radiotherapy --- p.13 / Chapter 1.1.7 --- Differentiation of Neuroblastoma In Vivo and In Vitro --- p.14 / Chapter 1.1.8 --- Differentiation Therapy of Neuroblastoma --- p.16 / Chapter 1.2 --- Glycyrrhizin ´ؤ the Major Active Component of Licorice --- p.17 / Chapter 1.2.1 --- Chemistry of Licorice --- p.17 / Chapter 1.2.2 --- Metabolism of Glycyrrhizin --- p.21 / Chapter 1.2.3 --- Pharmacological Effects of Glycyrrhizin and 18β-Glycyrrhetinic Acid --- p.22 / Chapter 1.2.3.1 --- Anti-inflammatory Effect --- p.22 / Chapter 1.2.3.2 --- Hepatoprotective Effect --- p.23 / Chapter 1.2.3.3 --- Anti-carcinogenic and Anti-tumor Effects --- p.25 / Chapter 1.2.3.4 --- Anti-viral Effect --- p.27 / Chapter 1.2.3.5 --- Immunomodulatory Effect --- p.29 / Chapter 1.2.3.6 --- Mineralocorticoid Effect --- p.30 / Chapter 1.2.4 --- Pharmacokinetics of Glycyrrhizin and Glycyrrhetinic Acid --- p.32 / Chapter 1.2.5 --- Health Hazards of Glycyrrhizin and Glycyrrhetinic Acid --- p.33 / Chapter 1.3 --- Aims and Scopes of This Study --- p.36 / Chapter CHAPTER 2: --- MATERIALS AND METHODS --- p.39 / Chapter 2.1 --- Materials --- p.39 / Chapter 2.1.1 --- Cell Lines --- p.39 / Chapter 2.1.2 --- "Cell Culture Media, Buffers and Other Reagents" --- p.39 / Chapter 2.1.3 --- Drugs and Chemicals --- p.43 / Chapter 2.1.4 --- Reagents for 3H-Thymidine Incorporation Assay --- p.44 / Chapter 2.1.5 --- Reagents for Neutral Red Assay --- p.45 / Chapter 2.1.6 --- Reagents for Clonogenic Assay --- p.45 / Chapter 2.1.7 --- Reagents and Buffers for Immunocytochemistry --- p.46 / Chapter 2.1.8 --- Reagents for DNA Extraction --- p.48 / Chapter 2.1.9 --- Reagent for DNA Staining --- p.49 / Chapter 2.1.10 --- Reagents and Buffers for Flow Cytometry --- p.49 / Chapter 2.1.11 --- Reagents for Total RNA Isolation --- p.50 / Chapter 2.1.12 --- Reagents and Buffers for RT-PCR --- p.50 / Chapter 2.1.13 --- Reagents and Buffers for Gel Electrophoresis --- p.55 / Chapter 2.1.14 --- Reagents and Buffers for Western Blot Analysis --- p.56 / Chapter 2.2 --- Methods --- p.62 / Chapter 2.2.1 --- Cell Culture Methodology --- p.62 / Chapter 2.2.2 --- Determination of Cell Proliferation --- p.62 / Chapter 2.2.3 --- Determination of Cell Viability by Trypan Blue Exclusion Test --- p.64 / Chapter 2.2.4 --- Limiting Dilution Assay --- p.65 / Chapter 2.2.5 --- Clonogenic Assay --- p.65 / Chapter 2.2.6 --- Measurement of Apoptosis by DNA Fragmentation Analysis --- p.66 / Chapter 2.2.7 --- Assessment of Apoptosis by Hoechst 33342 Staining --- p.67 / Chapter 2.2.8 --- Cell Morphological Study --- p.67 / Chapter 2.2.9 --- Immunocytochemistry --- p.68 / Chapter 2.2.10 --- Flow Cytometric Analysis of Cell Cycle Profile --- p.69 / Chapter 2.2.11 --- Gene Expression Study --- p.70 / Chapter 2.2.12 --- Protein Expression Study --- p.73 / Chapter 2.2.13 --- Statistical Analysis --- p.76 / Chapter CHAPTER 3: --- ANTI-PROLIFERATIVE EFFECTS OF GLYCYRRHIZIN AND 18β-GLYCYRRHETINIC ACID ON NEUROBLASTOMA CELLS --- p.77 / Chapter 3.1 --- Introduction --- p.77 / Chapter 3.2 --- Results --- p.79 / Chapter 3.2.1 --- Differential Anti-proliferative Effect of Glycyrrhizin and 18β- Glycyrrhetinic Acid on Various Neuroblastoma Cell Lines In Vitro --- p.79 / Chapter 3.2.2 --- Effect of 18P-Glycyrrhetinic Acid on the Clonogenicity of the Murine Neuroblastoma BU-1 Cells In Vitro --- p.91 / Chapter 3.2.3 --- Kinetic and Reversibility Studies of the Anti-proliferative Effect of Glycyrrhizin and 18β-Glycyrrhetinic Acid on the Neuroblastoma BU-1 Cells --- p.93 / Chapter 3.2.4 --- Cytotoxic Effect of Glycyrrhizin and 18β-Glycyrrhetinic Acid on the Neuroblastoma BU-1 Cells In Vitro --- p.100 / Chapter 3.2.5 --- Inability of Glycyrrhizin and 18β-Glycyrrhetinic Acid to Induce DNA Fragmentation in the Neuroblastoma BU-1 Cells --- p.102 / Chapter 3.3 --- Discussion --- p.107 / Chapter CHAPTER 4: --- DIFFERENTIATION-INDUCING EFFECTS OF GLYCYRRHIZIN AND 18β-GLYCYRRHETINIC ACID ON NEUROBLASTOMA CELLS --- p.112 / Chapter 4.1 --- Introduction --- p.112 / Chapter 4.2 --- Results --- p.114 / Chapter 4.2.1 --- Morphological Changes in Glycyrrhizin and 18β-Glycyrrhetinic Acid-treated Neuroblastoma BU-1 Cells --- p.114 / Chapter 4.2.2 --- Immunocytochemistry of Glycyrrhizin and 18β-Glycyrrhetinic Acid-treated Neuroblastoma BU-1 Cells --- p.118 / Chapter 4.2.3 --- Effect of 18β-Glycyrrhetinic Acid on the Expression of Proto-oncogenes in Neuroblastoma BU-1 Cells --- p.124 / Chapter 4.2.4 --- Effect of 18β-Glycyrrhetinic Acid on the Expression of Differentiation-Related Genes in Neuroblastoma BU-1 Cells --- p.127 / Chapter 4.3 --- Discussion --- p.130 / Chapter CHAPTER 5: --- MECHANISTIC STUDIES ON THE ANTI-PROLIFERATIVE AND DIFFERENTIATION-INDUCING EFFECTS OF GLYCYRRHIZIN AND 18β-GLYCYRRHETINIC ACID --- p.136 / Chapter 5.1 --- Introduction --- p.136 / Chapter 5.2 --- Results --- p.139 / Chapter 5.2.1 --- Effects of Glycyrrhizin and 18β-Glycyrrhetinic Acid on the Cell Cycle Kinetics of Neuroblastoma BU-1 Cells In Vitro --- p.139 / Chapter 5.2.2 --- Modulatory Effects of 18β-Glycyrrhetinic Acid on the Expression of Cell Cycle Regulatory Genes and Proteins --- p.145 / Chapter 5.2.3 --- "Combined Effects of Glycyrrhizin, 18β-Glycyrrhetinic Acid and All-Trans Retinoic Acid on the Proliferation of Neuroblastoma BU-1 Cells In Vitro" --- p.149 / Chapter 5.2.4 --- "Combined Effects of Glycyrrhizin, 18β-Glycyrrhetinic Acid and All-Trans Retinoic Acid on the Differentiation of Neuroblastoma BU-1 Cells In Vitro" --- p.153 / Chapter 5.2.5 --- Modulatory Effect of 18β-Glycyrrhetinic Acid on the Expression of PKC Isoforms in Neuroblastoma BU-1 Cells --- p.156 / Chapter 5.2.6 --- The Possible Involvement of Protein Kinase C in the Anti-proliferative and Differentiation-Inducing Effects of 18β-Glycyrrhetinic Acid on the Neuroblastoma BU-1 Cells --- p.158 / Chapter 5.2.7 --- The Possible Involvement of Protein Kinase A in the Anti-proliferative and Differentiation-Inducing Effects of 18β-Glycyrrhetinic Acid on the Neuroblastoma BU-1 Cells --- p.165 / Chapter 5.3 --- Discussion --- p.173 / Chapter CHAPTER 6: --- CONCLUSIONS AND FUTURE PERSPECTIVES --- p.182 / REFERENCES --- p.187

Introdução: Os neuroblastomas apresentam grande diversidade de comportamento clínico, evoluindo desde remissão espontânea à rápida progressão e morte. Heterogeneidade clínica e biológica tem implicado em grande variedade de respostas terapêuticas, inclusive em crianças maiores de 1 ano e em estádios avançados. Objetivo: estudar quadro clínico, aspectos epidemiológicos, características laboratoriais, genéticas e histológicas em crianças maiores de 1 ano portadoras de neuroblastoma disseminado, correlacionando-os com a evolução clínica e tentando definir fatores de risco que possam influir na sobrevida e na possibilidade da indicação do transplante de medula óssea (TMO). Casuística e Métodos: as informações foram obtidas de 53 pacientes admitidos na Unidade de Oncologia (ITACI) do Instituto da Criança do HC-FMUSP no período de 1997 a 2007. Os pacientes foram estudados quanto aos seguintes fatores: sexo, idade, raça, estado nutricional, DHL, Hb, ferritina, VMA, características tumorais (tamanho, localização, metástases, histologia, MYCN), terapêutica utilizada e evolução clínica. Estudamos separadamente também os fatores preditivos para TMO. Resultados: devem ser destacados: 1) crianças submetidas à cirurgia retardada completa apresentam 5 vezes menor chance de óbito do que as demais; 2) pacientes submetidos a TMO apresentam maior sobrevida total e livre de eventos em relação ao grupo não submetido a essa modalidade terapêutica 3) a utilização de retinóides gera 14 vezes menor chance de óbito em relação ao grupo que não os utiliza. 4) surpreendentemente, pacientes com ferritina abaixo de 334 n/ug/l apresentam 8 vezes maior chance de óbito. Conclusões: Não identificamos parâmetros clínicos e laboratoriais, práticos e facilmente disponíveis, de prognóstico para subpopulações de neuroblastomas de prognóstico avançado, sendo o estudo de fatores de ordem molecular e biológicos essenciais, apesar das dificuldades em realizá-lo / Introduction: Neuroblastomas (NB) have widely diverse clinical behavior, moving from spontaneous remission to progression and death. Clinical and biological heterogeneity factors determine different survival, even with children older than 1 year in advanced stages. Objective: to study the clinical presentation, epidemiology, laboratory findings, genetics and histopathologic characteristics in children older than 1 year with advanced neuroblastoma and their correlation with the survival. Also defining prognostic variables for bone marrow transplantation (BMT) indication. Casuistic and Methods: 53 selected medical records from patients older than 1 year with advanced NB admitted to the Instituto da Criança do HC-FMUSP from 1997 to 2007 were reviewed. The following risk factors were analyzed: age, sex, race, nutritional status, LDH, hemoglobin level, ferritin level, urinary VMA, tumor characteristics such as: site, histology, size, metastases, MYCN, treatment and clinical course. Results: it should be mentioned that: 1) possibility of death in children who underwent complete second look is 5 times lower than remaining ones; 2) patients who underwent BMT have better overall survival and event-free survival in comparison to the group not receiving this treatment modality. 3) the use of retinoids generates 14 times less chance of death in comparison to the group not receiving them. 4) patients whose ferritin level was below 334 n/ug/l had surprisingly 8 times more chances to die from diseases Conclusions: no simple and easily obtainable prognostic variables in a subpopulation of patients with advanced stage neuroblastoma, suitable to be widely employed in a country as ours, were identified. The study of molecular and biologics factors remains essential for precise characterization of these patients

Introdução: Os neuroblastomas apresentam grande diversidade de comportamento clínico, evoluindo desde remissão espontânea à rápida progressão e morte. Heterogeneidade clínica e biológica tem implicado em grande variedade de respostas terapêuticas, inclusive em crianças maiores de 1 ano e em estádios avançados. Objetivo: estudar quadro clínico, aspectos epidemiológicos, características laboratoriais, genéticas e histológicas em crianças maiores de 1 ano portadoras de neuroblastoma disseminado, correlacionando-os com a evolução clínica e tentando definir fatores de risco que possam influir na sobrevida e na possibilidade da indicação do transplante de medula óssea (TMO). Casuística e Métodos: as informações foram obtidas de 53 pacientes admitidos na Unidade de Oncologia (ITACI) do Instituto da Criança do HC-FMUSP no período de 1997 a 2007. Os pacientes foram estudados quanto aos seguintes fatores: sexo, idade, raça, estado nutricional, DHL, Hb, ferritina, VMA, características tumorais (tamanho, localização, metástases, histologia, MYCN), terapêutica utilizada e evolução clínica. Estudamos separadamente também os fatores preditivos para TMO. Resultados: devem ser destacados: 1) crianças submetidas à cirurgia retardada completa apresentam 5 vezes menor chance de óbito do que as demais; 2) pacientes submetidos a TMO apresentam maior sobrevida total e livre de eventos em relação ao grupo não submetido a essa modalidade terapêutica 3) a utilização de retinóides gera 14 vezes menor chance de óbito em relação ao grupo que não os utiliza. 4) surpreendentemente, pacientes com ferritina abaixo de 334 n/ug/l apresentam 8 vezes maior chance de óbito. Conclusões: Não identificamos parâmetros clínicos e laboratoriais, práticos e facilmente disponíveis, de prognóstico para subpopulações de neuroblastomas de prognóstico avançado, sendo o estudo de fatores de ordem molecular e biológicos essenciais, apesar das dificuldades em realizá-lo / Introduction: Neuroblastomas (NB) have widely diverse clinical behavior, moving from spontaneous remission to progression and death. Clinical and biological heterogeneity factors determine different survival, even with children older than 1 year in advanced stages. Objective: to study the clinical presentation, epidemiology, laboratory findings, genetics and histopathologic characteristics in children older than 1 year with advanced neuroblastoma and their correlation with the survival. Also defining prognostic variables for bone marrow transplantation (BMT) indication. Casuistic and Methods: 53 selected medical records from patients older than 1 year with advanced NB admitted to the Instituto da Criança do HC-FMUSP from 1997 to 2007 were reviewed. The following risk factors were analyzed: age, sex, race, nutritional status, LDH, hemoglobin level, ferritin level, urinary VMA, tumor characteristics such as: site, histology, size, metastases, MYCN, treatment and clinical course. Results: it should be mentioned that: 1) possibility of death in children who underwent complete second look is 5 times lower than remaining ones; 2) patients who underwent BMT have better overall survival and event-free survival in comparison to the group not receiving this treatment modality. 3) the use of retinoids generates 14 times less chance of death in comparison to the group not receiving them. 4) patients whose ferritin level was below 334 n/ug/l had surprisingly 8 times more chances to die from diseases Conclusions: no simple and easily obtainable prognostic variables in a subpopulation of patients with advanced stage neuroblastoma, suitable to be widely employed in a country as ours, were identified. The study of molecular and biologics factors remains essential for precise characterization of these patients

Neuroblastoma is considered a pediatric malignancy as over 95% of cases are diagnosed in patients less than or equal to 10years old. This cancer is extremely rare in elderly patients. We conducted a Surveillance, Epidemiology, and End Results (SEER) database analysis in the USA between 1973-2007 that revealed only 35 elderly patients (>60years of age) with neuroblastoma of whom only 2 patients had primary mediastinal neuroblastoma. There is a paucity of treatment and survival outcomes data for the elderly owing to the rarity of neuroblastoma in this population. Currently there are no standard guidelines or protocols for treatment of adult neuroblastoma. We report a rare and challenging case of an 86-year old patient presenting with mediastinal neuroblastoma and syndrome of inappropriate antidiuretic hormone secretion (SIADH) successfully treated with resection. Herein, we also provide a review of the literature and updated survival data on neuroblastoma based on results of our SEER database review.

published_or_final_version / abstract / Anatomy / Master / Master of Philosophy