Thesis (Ph. D.) -- University of Texas Southwestern Medical Center at Dallas, 2005. / Vita. Bibliography: 49-53.

No description available.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2007. / Härtill 5 uppsatser.

Malignant brain tumors, known as H3K27-altered diffuse midline glioma (DMG) and H3G34-mutant diffuse hemispheric glioma (DHG), can affect individuals of all ages and are classified as CNS WHO grade 4. We comprehensively characterized 390 H3F3A-mutant diffuse gliomas (201 females, 189 males) arising in pediatric patients (under 20 years old) and adults (20 years and older) evaluated by the CGP program at Foundation Medicine between 2013 and 2020. We assessed information from pathology reports, histopathology review, and clinical data. The cohort included 304 H3K27M-mutant DMG (156 females, 148 males) and 86 H3G34-mutant DHG (45 females, 41 males). Median patient age was 20 years (1–74 years). The frequency of H3K27M-mutant DMG was similar in both pediatric and adult patients in our cohort—48.6% of the patients were over 20 years old, 31.5% over 30, and 18% over 40 at initial diagnosis. FGFR1 hotspot point mutations (N546K and K656E) were exclusively identified in H3K27M-mutant DMG tumors (64/304, 21%; p = 0.0001); these tend to occur in older patients (median age: 32.5 years) and mainly arose in the diencephalon. H3K27M-mutant DMG had higher rates of mutations in NF1 (31.0 vs 8.1%; p = 0.0001) and PIK3CA/PIK3R1 (27.9% vs 15.1%; p = 0.016) compared to H3G34-mutant DHG. However, H3G34-mutant DHG had higher rates of targetable alterations in cell-cycle pathway genes (CDK4 and CDK6 amplification; CDKN2A/B deletion) (27.0 vs 9.0%). Potentially targetable PDGFRA alterations were identified in ~ 20% of both H3G34-mutant DHG and H3K27M-mutant DMG. Overall, in the present study H3K27M-mutant DMG occurred at similar rates in both adult and patient patients. Through our analysis, we were able to identify molecular features characteristic of DMG and DHG. By identifying the recurrent co-mutations including actionable FGFR1 point mutations found in nearly one-third of H3K27M-mutant DMG in young adults, our findings can inform clinical translational studies, patient diagnosis, and clinical trial design.

by Chan Ka Kui. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 104-113). / Abstracts in English and Chinese. / ABSTRACT --- p.1 / Chapter 1 --- INTRODUCTION --- p.5 / Chapter 1.1 --- Incidence rate of breast cancer in Hong Kong --- p.5 / Chapter 1.2 --- Estrogen and breast cancer --- p.6 / Chapter 1.3 --- The relation between glucose transporters and breast cancer --- p.7 / Chapter 1.4 --- Antisense oligonucleotide --- p.10 / Chapter 1.5 --- Action mechanisms of antisense oligonucleotide --- p.11 / Chapter 1.6 --- Modification of the oligonucleotide --- p.13 / Chapter 1.7 --- Length --- p.16 / Chapter 1.8 --- Sequence selection of the antisense oligonucleotide --- p.16 / Chapter 1.9 --- Delivery means in antisense oligonucleotide --- p.18 / Chapter 1.10 --- The therapeutic role of antisense oligonucleotide --- p.19 / Chapter 1.11 --- Objective of the project --- p.21 / Chapter 2 --- MATERIAL AND METHODS --- p.23 / Chapter 2.1 --- Materials --- p.23 / Chapter 2.2 --- Methods --- p.26 / Chapter 3 --- RESULTS --- p.37 / Chapter 3.1 --- The characteristics of MCF-7 and MDA-MB-231 cells --- p.37 / Chapter 3.2 --- Trend of uptake of antisense oligonucleotides in MCF-7 and MDA- MB-231 cells --- p.41 / Chapter 3.3 --- The integrity of the oligonucleotide in serum-free medium during transfection --- p.48 / Chapter 3.4 --- Detection of effects of Glut5 antisense oligonucleotides of breast tumor cells-MTT assay --- p.50 / Chapter 3.5 --- Detection of the antiproliferative effect by trypan blue exclusion assay and thymidine incorporation --- p.56 / Chapter 3.6 --- Cell cycle analysis and DNA extraction --- p.61 / Chapter 3.7 --- Suppression of Glut5 mRNA detected by RT-PCR --- p.66 / Chapter 3.8 --- Suppression of translation of Glut5 proteins as indicated by Western blotting --- p.73 / Chapter 3.9 --- Measurement of the fructose and glucose uptake in MCF-7 and MDA -MB-231 cells after antisense treatment --- p.76 / Chapter 3.10 --- Change of the phosphofructokinase-1 (PFK-1) activities in MDA- MB-231 cells --- p.82 / Chapter 3.11 --- Measurement of the change in the intracellular pH of the breast tumor cells --- p.84 / Chapter 4 --- DISCUSSION --- p.89 / Chapter 4.1 --- The insights of Glut5 antisense oligonucleotide into cancer therapy --- p.89 / Chapter 4.2 --- The uptake pattern of Glut5 antisense oligonucleotides in breast tumor cells --- p.90 / Chapter 4.3 --- Stability of antisense oligonucleotide during transfection --- p.92 / Chapter 4.4 --- Effects of Glut5 antisense oligonucleotide on MCF-7 and MDA-MB- 231cells --- p.93 / Chapter 4.5 --- Proofs of undergoing antisense action mechanism --- p.95 / Chapter 4.6 --- Physiological changes in breast tumor cells after antisense treatment --- p.97 / Chapter 5 --- CONCLUSION --- p.103 / Chapter 6 --- References --- p.104

Jia, Lin. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 124-146). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Yeung Sze-wan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references. / Abstracts in English and Chinese. / ACKNOWLEDGEMENT --- p.i / ABSTRACT --- p.ii / ABBREVIATIONS --- p.vii / TABLE OF CONTENTS --- p.ix / Chapter CHAPTER 1 --- INTRODUCTION --- p.1-1 / Chapter 1.1 --- Anatomy of the Cervix --- p.1-1 / Chapter 1.2 --- Histology --- p.1-1 / Chapter 1.2.1 --- Squamous Epithelium --- p.1-1 / Chapter 1.2.2 --- The Endocervical Epithelium --- p.1-3 / Chapter 1.2.3 --- The Squamo-columnar Junction --- p.1-4 / Chapter 1.2.3.1 --- The Embryology --- p.1-4 / Chapter 1.2.3.2 --- Definition --- p.1-4 / Chapter 1.3 --- Human Papillomaviruses (HPVs) --- p.1-6 / Chapter 1.3.1 --- Structure of the Viruses --- p.1-6 / Chapter 1.3.2 --- The Nomenclature --- p.1-7 / Chapter 1.3.3 --- HPVs Genomic Structure and Properties of Gene Products --- p.1-7 / Chapter 1.3.4 --- Target Tissues --- p.1-8 / Chapter 1.3.5 --- Role of HPVs in the Carcinogenesis of Lesions --- p.1-9 / Chapter 1.3.6 --- Risk Groups of HPVs --- p.1-10 / Chapter 1.4 --- Pathology --- p.1-11 / Chapter 1.4.1 --- Macroscopic Features --- p.1-11 / Chapter 1.4.2 --- Symptoms and Diagnosis --- p.1-12 / Chapter 1.4.3 --- Histopathology --- p.1-13 / Chapter 1.4.3.1 --- Histopathological Grading of Cervical Intraepithelial Neoplasia --- p.1-19 / Chapter 1.4.3.2 --- Staging of Cervical Cancer --- p.1-24 / Chapter 1.5 --- Epidemiology of Cervical Intraepithelial Neoplasia and Cervical Cancer --- p.1-27 / Chapter 1.5.1 --- Descriptive Epidemiology --- p.1-28 / Chapter 1.5.2 --- Risk Factors --- p.1-30 / Chapter 1.6 --- Human Papillomavirus Type 16 --- p.1-42 / Chapter 1.6.1 --- Role of HPV16 in CIN and Cervical Carcinoma --- p.1-42 / Chapter 1.6.2 --- Viral Load of HPV 16 in CIN --- p.1-43 / Chapter 1.6.3 --- HPV 16 Viral Load as a Screening Tool --- p.1-46 / Chapter 1.7 --- Quantitation of HPV 16 --- p.1-48 / Chapter 1.7.1 --- Methods in Viral Quantification --- p.1-48 / Chapter 1.7.2 --- Selection of Methodology --- p.1-51 / Chapter 1.7.3 --- Correlation of HPV 16 Viral Loading with Severity of Cervical Lesions --- p.1-54 / Chapter CHAPTER 2 --- AIMS OF STUDY --- p.2-1 / Chapter CHAPTER 3 --- MATERIALS AND METHODS --- p.3-1 / Chapter 3.1 --- Materials --- p.3-1 / Chapter 3.1.1 --- Patients and Specimens --- p.3-1 / Chapter 3.2 --- Methods --- p.3-3 / Chapter 3.2.1 --- DNA Extraction --- p.3-3 / Chapter 3.2.2 --- Polymerase Chain Reaction --- p.3-7 / Chapter 3.2.3 --- Gel Electrophoresis --- p.3-8 / Chapter 3.2.4 --- Real-time Quantitation Polymerase Chain Reaction --- p.3-11 / Chapter 3.2.5 --- Statistical Analysis --- p.3-15 / Chapter CHAPTER 4 --- RESULTS --- p.4-1 / Chapter 4.1 --- Grading of Cervical Smears --- p.4-1 / Chapter 4.2 --- Incidence of HPV 16 Detected in Cervical Smears --- p.4-2 / Chapter 4.2.1 --- Detection of HPV 16 in Women for Routine Pap Smear --- p.4-2 / Chapter 4.2.2 --- Detection of HPV 16 in Women for Colposcopic Examination --- p.4-5 / Chapter 4.3 --- Quantification of HPV 16 by Real-time PCR --- p.4-5 / Chapter 4.3.1 --- Range of Detection --- p.4-10 / Chapter 4.3.2 --- Standard Curve --- p.4-12 / Chapter 4.3.3 --- Reproducibility of Quantitative Real-time PCR --- p.4-17 / Chapter 4.3.4 --- Sensitivity of Quantitative Real-time PCR --- p.4-17 / Chapter 4.3.5 --- Detection and Quantification of HPV 16 E6/7 Genes in HPV16 Positive Cervical Scrapes --- p.4-21 / Chapter 4.4 --- Comparison of HPV 16 Copy Number Detected among Three Lesion Groups --- p.4-22 / Chapter 4.5 --- Clinical Analysis --- p.4-27 / Chapter 4.6 --- HPV 16 DNA Copy Number in Lesion Groups --- p.4-28 / Chapter CHAPTER 5 --- DISCUSSION --- p.5-1 / Chapter 5.1 --- Selection of Material (Scrapes) --- p.5-1 / Chapter 5.2 --- Detection of HPV 16 in Cervical Scrapes --- p.5-3 / Chapter 5.2.1 --- Selection of HPV Type --- p.5-3 / Chapter 5.2.2 --- Techniques in Detecting HPV Viral Load --- p.5-3 / Chapter 5.2.2.1 --- Advantages of Quantitative Real-time PCR --- p.5-6 / Chapter 5.2.2.2 --- Parameters Affecting the Performance of Real-time PCR --- p.5-8 / Chapter 5.2.3 --- Selection of Detection Sites --- p.5-9 / Chapter 5.2.4 --- Standard Curve Establishment --- p.5-10 / Chapter 5.3 --- Comparison between Real-time PCR and Traditional PCR --- p.5-12 / Chapter 5.4 --- Role of HPV Viral Load in Cervical Neoplasm --- p.5-13 / Chapter 5.5 --- HPV Infection in Hong Kong Chinese Women --- p.5-17 / Chapter 5.6 --- Clinical Significance of HPV 16 Viral Load Detected in Cervical Neoplasm --- p.5-18 / Chapter 5.7 --- Future Prospect --- p.5-20 / Chapter CHAPTER 6 --- CONCLUSION --- p.6-1 / REFERENCES --- p.R-I

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009.

Background: Although rare relative to adult cancers, cancer is still the leading cause of disease-related death in children in developed countries, including Canada. Few studies have specifically examined the epidemiology and public health significance of diagnosis and treatment delays in childhood cancer. This study aimed to investigate the nature of delays in care for children and adolescents with cancer in Canada and to assess the potential impact of such delays on clinical outcomes. / Study Design: I conducted a prospective cohort study to investigate the delays of cancer symptoms reporting, diagnosis, and treatment in children between 0-19 years of age in Canada. This study used a database from Health Canada's Treatment and Outcomes component of the Canadian Childhood Cancer Surveillance and Control Program. / Methodology: Patients were identified from 17 paediatric cancer centres across Canada. Subjects included in this study were residents of Canada, aged less than 20 years, diagnosed with a malignant tumour and had information on date of first symptoms, diagnosis, treatment and outcome available. Descriptive statistics and regression techniques (linear, logistic and Cox regression) were used as appropriate. I measured the individual impact of patient and provider delays on disease severity and prognosis by using judicious control for potential confounding mechanisms and mediating factors. / Study Findings and Significance: By measuring various types of delays in Canada, I found that varying lengths of patient and referral delay, across age groups, types of cancers, and Canadian settings, are the main contributors to diagnosis, HCS and overall delay. Factors relating to the patients, the parents, healthcare and the cancer may all exert different influences on different segments of cancer care. I also found a negative association between diagnosis delay and disease severity for lymphoma and CNS tumour patients. Furthermore, I found that diagnosis and physician delay had a negative effect, while patient delay had a positive effect, on survival for patients diagnosed with CNS tumours. The information provided from this study may form the basis for new effective policies aimed at eliminating obstacles in cancer the diagnostic and care trajectories for Canadian children with cancer and for improving their prognosis.