Diss. (sammanfattning) Linköping : Univ., 2001. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

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

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 5 uppsatser.

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg, February 2015 / Androgen Insensitivity Syndrome (AIS) is an X-linked disorder caused by mutations in the androgen receptor (AR) gene. The phenotype is variable and ranges from a complete feminine syndrome to simple gynecomastia. The phenotypes are described in terms of complete, partial and mild forms (CAIS, PAIS and MAIS). We describe novel and previously reported (recurrent) mutations in the AR gene for a family in which segregation of breast cancer (BC) and gynecomastia/MAIS is present. Methods: We studied a family of 16 members spanning four generations. Based on the presentation of symptoms, the family was divided into affected, unaffected, and control groups. Seven patients (six males diagnosed with MAIS and one female diagnosed with BC) formed the affected group, four genetically related individuals (two males and two females) formed the unaffected group and five genetically unrelated family members (one male and four females) served as controls. In each of these individuals, PCR amplification, cloning and the sequencing of exon 1 were carried out. Exons 2-8 were sequenced directly after PCR amplification. Exon 1 (CAG)n and (GGN)n repeats were classified according to their length: short (S) (n<23), long (L) (n>23) and wild type (WT) (n=23). Results: Part 1-The (CAG)n repeats varied among individuals and generations. In the 2nd generation, the unaffected male was S and the control female was WT. In the 3rd generation, three affected males were S, 2 of the controls were WT, one control was L and the other S. In the 4th generation, the 4 affected individuals were L, 1 of the unaffected was WT and the other 2 unaffected were L. Part 2- The (GGN)n variations also differed among individuals and generations. In the 2nd generation, the unaffected male and the control were S. In the 3rd generation, all three affected family members were S and among the controls, 1 was WT, 1 was L and 2 were S. In the 4th generation, 3 of the affected were S and one was WT and among the 3 unaffected, 2 were S and one was WT. Part 3- 30 unreported (novel) mutations as well as 13 recurrent (previously reported) mutations in exon 1 of the AR gene were identified. 17 novel and 5 reported mutations were identified in the affected group, 8 novel and 5 reported mutations, including one premature stop codon mutation, were identified in the related unaffected group and 7 novel and 4 reported mutations were found in the controls. Of the above-mentioned mutations, four mutations were identified in the activation function-1 (AF-1) domain of exon 1 in 4 members (3 affected: M-2, F-1 and 1 unaffected: F-1) of the family. All the point mutations identified were somatic in nature and were present in heterogeneous form i.e wild and mutant (mixture) as determined by cloning. The analysis of exons 2 through 8 revealed completely WT sequences. Conclusions: The (CAG)n and (GGN)n repeat analysis showed an indeterminate association with MAIS and BC in the family. Generation specific patterns of (CAG)n were detected and suggest generation specific modulation of the AR. Novel mutations including AF-1 region mutations were identified in exon 1. The disruption of the AF-1 domain may affect the transactivation activity of the AR.

by Choy Kwong Wai. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 120-138). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Mak, Ko Fung. / Thesis submitted in: July 2003. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 113-138). / Abstracts in English and Chinese. / Chapter CHAPTER I: --- INTRODUCTION --- p.1 / Chapter I. --- AIM OF STUDY --- p.1 / Chapter II. --- LITERATURE REVIEW --- p.2 / Chapter 1. --- Epidemiology --- p.2 / Chapter 2. --- Etiology --- p.4 / Chapter A. --- Heredity --- p.4 / Chapter i. --- Family History --- p.4 / Chapter ii. --- Inherited Predisposition --- p.4 / Chapter B. --- Hormonal --- p.7 / Chapter C. --- Environmental --- p.9 / Chapter i. --- Diet --- p.9 / Chapter ii. --- Radiation --- p.10 / Chapter iii. --- Physical Activity --- p.11 / Chapter 3. --- Histopathology --- p.12 / Chapter 4. --- Clonality Nature of Cancer --- p.13 / Chapter 5. --- "Knudson ""two-hit"" Hypothesis on Cancer Development" --- p.14 / Chapter 6. --- Molecular Genetic Studies of Breast Cancer --- p.15 / Chapter A. --- Loss of Heterozygosity --- p.16 / Chapter B. --- Comparative Genomic Hybridization --- p.19 / Chapter C. --- Epigenetic Changes --- p.20 / Chapter 7. --- Genetic Changes in Breast Cancer --- p.21 / Chapter A. --- Chromosome 1 --- p.21 / 14-3-3σ Gene --- p.21 / Chapter B. --- Chromosome 3 --- p.22 / Chapter i. --- Retionoic Acid Receptor p2 Gene --- p.22 / Chapter ii. --- Fragile Histidine Traid Gene --- p.24 / Chapter iii. --- Ras Associated Domain Family 1A Gene --- p.25 / Chapter iv. --- Thyroid Hormone Receptor β1 Gene --- p.26 / Chapter C. --- Chromosome 5 --- p.27 / Adenomatous Polyposis Coli Gene --- p.27 / Chapter D. --- Chromosome 6 --- p.28 / Estrogen Receptor Gene --- p.28 / Chapter E. --- Chromosome 9 --- p.29 / p16 Gene --- p.29 / Chapter F. --- Chromosome 13 --- p.30 / Chapter i. --- BRCA2 Gene --- p.31 / Chapter ii. --- Retinoblastoma Gene --- p.32 / Chapter G. --- Chromosome 16 --- p.33 / E-cadherin Gene --- p.33 / Chapter H. --- Chromosome 17 --- p.34 / Chapter i. --- TP53 Gene --- p.34 / Chapter ii. --- BRCA1 Gene --- p.36 / Chapter CHAPTER II: --- MATERIALS AND METHODS --- p.38 / Chapter I. --- PATIENTS AND SPECIMENS --- p.38 / Chapter II. --- FROZEN SECTIONS AND MICRODISSECTION --- p.41 / Chapter III. --- DNA EXTRACTION --- p.43 / Chapter IV. --- ALLELOTYPING --- p.44 / Chapter 1. --- Polymerase Chain Reaction --- p.44 / Chapter 2. --- Electrophoresis --- p.45 / Chapter 3. --- Data Analysis --- p.46 / Chapter CHAPTER III: --- RESULTS --- p.49 / Chapter I. --- ALLELOTYPING ANALYSIS --- p.49 / Chapter II. --- FREQUENCY OF LOH --- p.68 / Chapter III. --- FRACTIONAL ALLELIC LOSS --- p.70 / Chapter IV. --- MINIMAL DELETION REGIONS --- p.72 / Chapter 1. --- Chromosome 6q --- p.83 / Chapter 2. --- Chromosome 8p --- p.83 / Chapter 3. --- Chromosome 8q --- p.84 / Chapter 4. --- Chromosome 10q --- p.84 / Chapter 5. --- Chromosome 13q --- p.85 / Chapter 6. --- Chromosome 14q --- p.85 / Chapter 7. --- Chromosome 16q --- p.86 / Chapter V. --- MICROSATELLITE INSTABILITY --- p.86 / Chapter CHATPER IV: --- DISCUSSION --- p.88 / Chapter I. --- COMPARISONS OF CHROMOSOMAL ALTERATIONS --- p.88 / Chapter II. --- MICROSATELLITE INSTABILITY --- p.92 / Chapter III. --- CHROMOSOMAL GAINS AND LOSSES --- p.93 / Chapter IV. --- CHROMOSOME 17 --- p.95 / Chapter V. --- MINIMAL DELETION REGIONS --- p.96 / Chapter 1. --- Chromosome 6q --- p.97 / Chapter 2. --- Chromosome 8p --- p.99 / Chapter A. --- 8p23.3.-22 --- p.99 / Chapter B. --- 8p21.3-12 --- p.101 / Chapter C. --- 8p22-21 --- p.103 / Chapter 3. --- Chromosome 8q --- p.104 / Chapter 4. --- Chromosome 10q --- p.106 / Haploinsufficiency and PTEN --- p.107 / Chapter 5. --- Chromosome 13q --- p.108 / Chapter 6. --- Chromosome 14q --- p.109 / Chapter 7. --- Chromosome 16q --- p.110 / Chapter CHAPTER V: --- CONCLUSION --- p.112 / REFERENCES --- p.113

Wang Ya-Ping. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 152-161). / 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.

Background. B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various cancer such as non-small cell lung cancer, colon cancer, gastric cancer, bladder cancer and nasopharyngeal cancer (NPC). / Methods. Immunohistochemistry was performed to evaluate Bmi-1 expression in 252 breast cancer samples. The correlations were analyzed between Bmi-1 expression and clinicopathologic parameters, including age, tumor size, lymph nodal involvement, distant metastasis, clinical stages, hormone receptor (ER, PR) and Human Epidermal Growth Factor Receptor 2 (HER-2). The overall survivals were compared by Kaplan-Meier analysis based on Bmi-1 expression. / Results. Bmi-1 expression was significantly increased in primary cancer tissues than in matched adjacent non-cancerous tissues ( P&lt;0.001). Only 35.9% (14 of 39) of adjacent non-cancerous tissues displayed high expression compared with 72.2% (182 of 252) in primary cancer tissues. Among adjacent non-cancerous tissues, no Bmi-1 staining signal was detected in 30.8% (12 in 39) samples. Only 28.2% (11 in 39) samples showed nucleus staining and the remaining 41.0% (16 in 39) samples exhibited cytoplasm staining. Of those cancer tissues, however, 75.4% (190 in 252) was stained in the nucleus and 24.6% (62 in 252) located in the cytoplasm. The elevated Bmi-1 expression was correlated with advanced clinicopathologic classifications (T, N, M) and clinical stages (P&lt;0.001, respectively). A high level of Bmi-1 expression displayed unfavorable overall survival ( P&lt;0.001). The overall survival rate, assessed by the Kaplan-Meier method, was 85.1% (57 in 67) in low Bmi-1 expression group, whereas it was only 59.9% (103 in 172) in high Bmi-1 expression group. In addition, Bmi-1 serves as a high risk for breast cancer and the relative risk increased almost four fold in patients with high Bmi-1 expression compared with that with low Bmi-1 expression by univariate Cox regression analyses. After the adjustment of the confounding factors, Bmi-1 was still found to predict the poor survival (P=0.042), which indicated Bmi-1 was an independent prognostic factor. The overexpression of Bmi-1 increased the mobility and invasiveness in 76N-TERT and MCF-10A, concurrent EMT-like molecular changes, the stabilization of Snail protein and the activation of Akt/GSK3beta pathway. Consistent with these observations, the repression of Bmi-1 in MDA-MB-435S remarkably attenuated the cellular mobility, invasiveness and transformation, as well as tumorigenesis and spontaneous lung metastases in nude mice. In addition, the repression of Bmi-1 reversed the EMT markers and inhibited the Akt/GSK3beta/Snail pathway. However, ectopic Bmi-1 alone was not able to lead to the phenotype of HMECs. Additionally, discordant mRNA expression levels of Bmi-1 and E-cadherin were detected between primary cancer tissues and matched adjacent non-cancerous tissues. The mRNA level of Bmi-1 was strongly up-regulated in breast cancer tissues compared with paired non-cancerous tissues ( P=0.001), whereas the mRNA level of E-cadherin was markedly down-regulated (P=0.042). Furthermore, there was a converse correlation between Bmi-1 and E-cadherin expression at the transcriptional level ( P=0.041). (Abstract shortened by UMI.) / Guo, Baohong. / Adviser: Kung, Hsiang Fu. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 161-183). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.