Nós avaliamos a utilidade de um painel de anticorpos constituído por CD5, CD10, CD23, CD43, bcl-2 e ciclina D1 na classificação de 134 linfomas de pequenas células B. O CD10, positivo nos linfomas foliculares, o CD23, positivo nos linfomas linfocíticos/LLC, e a ciclina D1, expressa nos linfoma do manto, foram os que mais contribuíram na diferenciação destes linfomas, firmando o diagnóstico em 88,1% dos casos. A ausência de aspecto nodular e de células dendríticas, e a presença de centros de proliferação diferencia o linfoma linfocítico/LLC dos outros tipos. A expressão de proteína p53 e de antígeno Ki-67 > 20% foi associada com tempo de sobrevida menor, principalmente no linfoma do manto / We evaluated the usefulness of a panel of antibodies comprising CD5, CD10, CD23, CD43, bcl-2 and cyclin D1 in the classification of 134 small B-cell lymphomas. CD10, positive in follicular lymphomas, CD23, positive in lymphocytic lymphoma/CLL and cyclin D1 expressed in mantle cell lymphoma were the ones that contributed the most in the differentiation of these lymphomas, confirming the diagnosis in 88.1% of the cases. The absence of nodular aspect and dendritic cells and the presence of proliferation centers differentiate the lymphocytic lymphoma/CLL from the other types. The expression of p53 protein and Ki-67 > 20% was associated to a shorter survival, especially in mantle cell lymphoma

Ping Zhang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 131-144). / 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.

Nós avaliamos a utilidade de um painel de anticorpos constituído por CD5, CD10, CD23, CD43, bcl-2 e ciclina D1 na classificação de 134 linfomas de pequenas células B. O CD10, positivo nos linfomas foliculares, o CD23, positivo nos linfomas linfocíticos/LLC, e a ciclina D1, expressa nos linfoma do manto, foram os que mais contribuíram na diferenciação destes linfomas, firmando o diagnóstico em 88,1% dos casos. A ausência de aspecto nodular e de células dendríticas, e a presença de centros de proliferação diferencia o linfoma linfocítico/LLC dos outros tipos. A expressão de proteína p53 e de antígeno Ki-67 > 20% foi associada com tempo de sobrevida menor, principalmente no linfoma do manto / We evaluated the usefulness of a panel of antibodies comprising CD5, CD10, CD23, CD43, bcl-2 and cyclin D1 in the classification of 134 small B-cell lymphomas. CD10, positive in follicular lymphomas, CD23, positive in lymphocytic lymphoma/CLL and cyclin D1 expressed in mantle cell lymphoma were the ones that contributed the most in the differentiation of these lymphomas, confirming the diagnosis in 88.1% of the cases. The absence of nodular aspect and dendritic cells and the presence of proliferation centers differentiate the lymphocytic lymphoma/CLL from the other types. The expression of p53 protein and Ki-67 > 20% was associated to a shorter survival, especially in mantle cell lymphoma

Yung, Kam Fai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 107-129). / Abstracts in English and Chinese. / ABSTRACT --- p.ii / 摘要 --- p.iv / ACKNOWLEDGEMENTS --- p.vi / TABLE OF CONTENTS --- p.vii / PUBLICATION --- p.ix / LIST OF TABLES --- p.x / LIST OF FIGURES --- p.xi / LIST OF ABBREVIATIONS --- p.xii / Chapter SECTION I: --- BACKGROUND --- p.1 / Chapter CHAPTER 1: --- "The biology, diagnostics and management of lung cancer" --- p.2 / Chapter 1.1 --- "Basic biology, classification and diagnostics" --- p.2 / Chapter 1.1.1 --- Epidemiology and etiology of lung cancer --- p.2 / Chapter 1.1.2 --- Clinical Presentation and Diagnostics of Lung Cancer --- p.3 / Chapter 1.2 --- Treatment of lung cancer --- p.9 / Chapter 1.2.2 --- Radiotherapy --- p.10 / Chapter 1.2.3 --- Chemotherapy --- p.11 / Chapter CHAPTER 2: --- Epidermal Growth Factor Receptor Mutations in Lung Cancer --- p.13 / Chapter 2.1 --- The Epidermal Growth Factor Receptor --- p.13 / Chapter 2.2 --- Overexpression of EGFR in NSCLC --- p.14 / Chapter 2.3 --- The development of EGFR inhibitors --- p.15 / Chapter 2.3.1 --- Monoclonal Antibodies --- p.16 / Chapter 2.3.2 --- Small-molecule inhibitors --- p.17 / Chapter 2.3.2.1 --- Gefitinib --- p.17 / Chapter 2.3.2.2 --- Erlotinib --- p.19 / Chapter 2.3.2.3 --- Other small-molecule inhibitors --- p.20 / Chapter 2.4 --- Mutations of EGFR in NSCLC --- p.21 / Chapter 2.4.1 --- Activating Mutations conferring sensitivity to tyrosine kinase inhibitors --- p.21 / Chapter 2.4.2 --- Secondary mutations associated with resistance to tyrosine kinase inhibitors --- p.23 / Chapter 2.5 --- EGFR gene amplification --- p.24 / Chapter 2.6 --- Detection of EGFR mutations --- p.25 / Chapter 2.7 --- Aim of the thesis --- p.31 / Chapter SECTION II: --- DETECTION OF EGFR MUTATIONS IN TUMOR AND PLASMA SAMPLES BY MASS SPECTROMETRY AND DIGITAL PCR --- p.33 / Chapter CHAPTER 3: --- Detection of EGFR mutations by mass spectrometric methods --- p.34 / Chapter 3.1 --- Introduction --- p.34 / Chapter 3.1.1 --- Principles of Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) --- p.34 / Chapter 3.1.2 --- The MassARRAY Homogenous MassEXTEND (hME) assay --- p.35 / Chapter 3.1.3 --- The Single-Allele Base Extension Reaction (SABER) and the Allele-Specific Base Extension Reaction (ASBER) --- p.36 / Chapter 3.2 --- Materials and Methods --- p.36 / Chapter 3.2.1 --- The protocol for the detection of EGFR exon 21 point mutation by Mass Spectrometric Methods --- p.37 / Chapter 3.3 --- Results --- p.42 / Chapter 3.4 --- Discussion --- p.49 / Chapter CHAPTER 4: --- Evaluation of the detection limit and sensitivity of the digital PCR assays --- p.51 / Chapter 4.1 --- Introduction --- p.51 / Chapter 4.1.1 --- The theoretical basis of digital PCR quantification and the relationship with the Poisson distribution --- p.51 / Chapter 4.1.2 --- Assessment of Assay Detection Limit --- p.54 / Chapter 4.1.3 --- Comparing Digital PCR with sequencing after conformation sensitive gel electrophoresis (CSGE) --- p.59 / Chapter 4.2 --- Materials and Methods --- p.59 / Chapter 4.2.1 --- Design of digital PCR assay for the detection of EGFR exon21 L858R point mutation --- p.59 / Chapter 4.2.2 --- Design of digital PCR assay for the detection of EGFR exon19 deletion --- p.60 / Chapter 4.2.3 --- The protocols of digital PCR assays for EGFR mutation detection --- p.64 / Chapter 4.2.4 --- Single molecule detection test --- p.65 / Chapter 4.2.5 --- Artificial mixtures of mutant and wild-type DNA --- p.66 / Chapter 4.2.6 --- Sequencing after CSGE --- p.66 / Chapter 4.3 --- Results --- p.67 / Chapter 4.3.1 --- Results of the single molecule detection test and artificial mixture analysis --- p.67 / Chapter 4.3.2 --- Results of CSGE and sequencing compared with digital PCR --- p.73 / Chapter 4.4 --- Discussion --- p.75 / Chapter CHAPTER 5: --- Detection of EGFR mutations in prospectively collected tumor samples of NSCLC patients --- p.77 / Chapter 5.1 --- Introduction --- p.77 / Chapter 5.2 --- Materials and Methods --- p.78 / Chapter 5.2.1 --- Sample preparation and DNA extraction of tumor tissues --- p.78 / Chapter 5.3 --- Results --- p.79 / Chapter 5.4 --- Discussion --- p.82 / Chapter CHAPTER 6: --- Detection of EGFR mutations in prospectively collected plasma samples of NSCLC patients --- p.85 / Chapter 6.1 --- Introduction --- p.85 / Chapter 6.2 --- Materials and Methods --- p.87 / Chapter 6.2.1 --- Sample preparation and DNA extraction of plasma samples --- p.87 / Chapter 6.3 --- Results --- p.88 / Chapter 6.3.1 --- Digital PCR analysis of EGFR mutations in plasma samples of NSCLC patient --- p.88 / Chapter 6.3.2 --- Variations in plasma EGFR mutation concentration after TKI treatment --- p.93 / Chapter 6.4 --- Discussion --- p.96 / Chapter SECTION III: --- CONCLUDING REMARKS --- p.100 / Chapter CHAPTER 7: --- Conclusion and future perspectives --- p.101 / Chapter 7.1 --- Mass spectrometric analysis --- p.101 / Chapter 7.2 --- Microfluidics Digital PCR --- p.102 / Chapter 7.3 --- Future perspectives --- p.105 / References --- p.107

No description available.

Non-Small-Cell-Lung Cancer (NSCLC) patients with mutations in EGFR have greater response rates and survival when treated with the tyrosine kinase inhibitor erlotinib. To elucidate how erlotinib inhibits EGFR, this study included: 1) inhibiting an EGFR mutant cell line to reveal EGFR regulated phosphotyrosine (pY) sites; 2) comparing erlotinib sensitive and insensitive cell lines to reveal functionally important pY sites; 3) revealing novel pY sites. Observations were collected using the LTQ-Orbitrap mass spectrometer. This study identified five new EGFR regulated pY sites and five pY sites that correlated with erlotinib sensitivity; the majority of them are related to cell-cell interactions. By comparing all observed pY sites to the Phosphosite and PhosphoELM database, our results included 67 unregistered sites. This study has identified novel biomarkers and potential therapeutic targets, many of which were associated with cell migration and adhesion function. Further functional validation is necessary.

Non-Small-Cell-Lung Cancer (NSCLC) patients with mutations in EGFR have greater response rates and survival when treated with the tyrosine kinase inhibitor erlotinib. To elucidate how erlotinib inhibits EGFR, this study included: 1) inhibiting an EGFR mutant cell line to reveal EGFR regulated phosphotyrosine (pY) sites; 2) comparing erlotinib sensitive and insensitive cell lines to reveal functionally important pY sites; 3) revealing novel pY sites. Observations were collected using the LTQ-Orbitrap mass spectrometer. This study identified five new EGFR regulated pY sites and five pY sites that correlated with erlotinib sensitivity; the majority of them are related to cell-cell interactions. By comparing all observed pY sites to the Phosphosite and PhosphoELM database, our results included 67 unregistered sites. This study has identified novel biomarkers and potential therapeutic targets, many of which were associated with cell migration and adhesion function. Further functional validation is necessary.

Thesis (Ph. D.)--University of Nevada, Reno, 1999. / Includes bibliographical references. Online version available on the World Wide Web.

Yearly, 22, 200 Canadians are diagnosed with lung cancer, with 80-85% of the cases being non-small cell lung cancer (NSCLC). With diagnoses being predominantly in the advanced stages, prognosis is poor and quality of life (QoL) becomes the focus of treatment. The main symptom cachexia, issues a loss of strength and impacts on an important aspect of QoL, physical function. Physical function is predominately assessed subjectively. Lately performance-based measures are gaining in popularity. One performance measure, the chair rise test, has not been validated in the NSCLC population and was the objective of this study. / Subjects completed the chair rise test, 6MWT, hand grip, and the SF-36 pre and post chemotherapy. Evidence for construct and discriminant validity but not predictive validity was provided for the chair rise test. The 60-second chair rise may be too strenuous for persons with severe disability but a standardized timed-based chair rise test is needed.

Background: Randomized controlled trials (RCTs) are the gold standard for assessing the efficacy of a medical treatment. However, the efficacy demonstrated by trials does not automatically translate into a comparable level of effectiveness in the real world. RCTs may vary from routine clinical practice in several ways; the patients themselves, the delivery of the treatment, and the collateral care provided during treatment. Phase IV studies that assess outcomes of a treatment in the real-world provide a mechanism for assessing treatment effectiveness. Objectives: The objectives of this study were to: describe the characteristics of patients receiving standard, first-line, palliative, platinum-doublet chemotherapy (PPDC) for non-small cell lung cancer (NSCLC) in routine care; describe the effectiveness of PPDC in terms of wellbeing and symptom control; identify patient characteristics associated with change in wellbeing with treatment; and compare reported treatment efficacy to the effectiveness observed in the current study. Methods: This study was a retrospective cohort study of patients treated at Ontario’s Regional Cancer Centres (RCCs). Patients’ Edmonton Symptom Assessment System (ESAS) scores were used to describe patients’ symptomatic status and wellbeing. The proportions of patients whose wellbeing improved, remained stable or deteriorated at two months were calculated. Using logistic regression, patient and disease characteristics were assessed for association with change in wellbeing at two months (dichotomized as improved/stable and deteriorated). In comparing trial results to this study, adjustments were made for differences in case mix. Results: Patients’ median age was 65, 55% were male and the majority had stage IV disease and adenocarcinoma histology. Patients’ baseline wellbeing and symptomatic status varied widely. 61.3% (95% CI: 55.8 – 66.6%) of patients had improved or stable wellbeing at two months. Histology and baseline wellbeing score were associated with change in wellbeing at two months. The case mix adjusted estimates of the proportion of improved/stable patients (60.0% (95% CI 54.5 – 65.3) and 60.5% (95% CI 54.9 – 65.6)) were consistent with the proportion of patients achieving general quality of life improvement or stabilization in RCTs (55% and 63%). Conclusion: The effectiveness of PPDC delivered in Ontario’s RCCs is consistent with that expected based on the results of RCTs. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2012-04-23 11:53:33.491