Thesis (M.S.)--University of Wisconsin--Madison, 1982. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 83-86).

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 41-49).

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2009. / Härtill 4 uppsatser.

Ovarian carcinoma is considered to be the most deadly of the gynaecological malignancies which in its earliest stages is usually asymptomatic. The unsatisfactory survival rates of patients on conventional chemotherapy regimens, necessitates vehicles capable of carrying cytotoxic agents directly to the malignant cells. This mode of targeted delivery allows for efficient tumour cell kill whilst sparing surrounding normal tissue and substantially reducing side-effects. This project examined the possible therapeutic role of a targetable sustained drug delivery system, albumin immunomicrospheres containing the chemotherapeutic agents, cisplatin and 5-fluorouracil, for the treatment of ovarian adenocarcinoma. A rodent cell line, as a model, has proved to be similar to its human counterpart and also has shown to be transplantable from one animal to another. Such a model could therefore be useful for performing experiments relating to drug delivery targetability and therapeutic trials, as well as survival studies, in cases of ovarian adenocarcinoma. In particular, this project examines the efficacy of the immunospecific microspheres containing the drugs in a highly concentrated form, administered intraperitoneally and targeted to an ovarian adenocarcinoma, in an attempt to enhance tumour cell kill whilst largely sparing surrounding normal tissue. It is widely recognized that the effectiveness of most chemotherapeutic drugs would be enhanced if they were to act selectively where they are needed. In order to achieve a therapeutically relevant dose in tumour cells, the amount of drug required usually proves also to be highly toxic to normal tissues. It was postulated that, to overcome the above, it may be feasible to develop a sustained immunospecific drug delivery system to optimize the action of cisplatin and 5-fluorouracil at the target site. With the attainment of the above, it was further postulated that higher doses of drugs could be delivered to the target area effecting higher tumour cell kill, that less normal tissue damage should occur and that toxic side effects of the drugs should be reduced. The rationale for selecting combination therapy of cisplatin and 5-fluorouracil is that, although it has been inferred that DNA intrastrand and interstrand cross-links produced by the cisplatin often repair, this repair can be blocked by 5-fluorouracil by inhibition of thymidylate synthetase, thus preventing DNA strand repair. Albumin immunomicrospheres are relatively innocuous in terms of toxicity, non-antigenic and are capable of accommodating chemotherapeutic agents in a non-specific fashion. We showed that they were capable of a 0. 94% entrapment of 5-fluorouracil and 1.23% cisplatin. Delivery of these drugs at a target site, and at these concentrations, should effect extensive cell kill. As the microspheres are chemically stable and can be manipulated to offload the entrapped drugs satisfactorily, in vitro drug release profiles were performed employing immunospecific microspheres directed towards its target cells. Slow degradation of the drug- containing albumin immunomicrospheres showed that 0.283 μg cisplatin/ml plasma and 0. 799 μg 5-fluorouracil/ml plasma could be made available at the target site over a 14-day period. These concentrations could be maintained over at least another 14 days and effect tumour cell kill satisfactorily. In order to assess the tumour cell kill, we performed clonogenic assays, cell survival growth curves, MTT cytotoxicity assays and assessed the induction of micronuclei in the tumour cells. The synergism between 5-fluorouracil and cisplatin showed a modulation of cisplatin cytotoxicity and total tumour cell kill was achieved at concentrations of 0.5 μg/ml 5-fluorouracil and 0.1 μg/ml cisplat in at the target site. The above-mentioned evidence of effective targeting of the drugs was then investigated in female Wistar rats with ovarian adenocarcinoma to assess comparative survival times when treated with free drugs or immunospecific albumin microspheres containing the drugs. Animals given a free drug dose of 5 mg/kg cisplatin and 20mg/kg 5-fluorouracil, followed by a repeat dose at the same concentrations 7 days later showed that only 14% of the animals survived a 90-day trial period. Animals given an intraperitoneal bolus dose of immunomicrospheres at a dose of 1 O mg/kg cisplatin and 40 mg/kg 5-fluorouracil showed that 60% of the animals survived the 90-day trial period. This data indicated to us that the survival probability of animals treated with drug-containing immunomicrospheres was substantially superior to other protocols employed in this study.

No description available.

Thesis (Ph. D.)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Biochemistry. Bibliography: leaves 149-174. Also available online via the Internet.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Choi, Pui Wah. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 202-232). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

Wong Wai Yin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references. / Abstracts in English and Chinese. / Acknowledgement --- p.i / Abstract --- p.iii / Abbreviation --- p.vii / Chapter CHAPTER 1 --- INTRODUCTION --- p.1-1 / Chapter 1.1 --- Classification of common epithelial ovarian tumors --- p.1-2 / Chapter 1.1.1 --- Serous tumors --- p.1-4 / Chapter 1.1.2 --- Mucinous tumors --- p.1-5 / Chapter 1.1.3 --- Endometrioid tumors --- p.1-6 / Chapter 1.1.4 --- Clear cell tumors --- p.1-6 / Chapter 1.1.5 --- Cancer staging --- p.1-7 / Chapter 1.1.6 --- Tumor grading --- p.1-8 / Chapter 1.2 --- Etiology --- p.1-10 / Chapter 1.2.1 --- Factors associated with increased risks --- p.1-10 / Chapter 1.2.2 --- Factors associated with decreased risks --- p.1-12 / Chapter 1.2.3 --- Other factors --- p.1-13 / Chapter 1.3 --- Understanding of progression of ovarian carcinoma --- p.1-13 / Chapter 1.4 --- Current screening test for ovarian cancer --- p.1-15 / Chapter 1.4.1 --- Transvaginal utrasound --- p.1-15 / Chapter 1.4.2 --- Serum tumor markers --- p.1-16 / Chapter 1.5 --- Molecular basis of ovarian cancer --- p.1-18 / Chapter 1.5.1 --- Loss of heterozygosity --- p.1-18 / Chapter 1.5.2 --- Microsatellite instability --- p.1-19 / Chapter 1.5.3 --- Oncogenes --- p.1-19 / Chapter 1.5.4 --- Tumor suppressor genes --- p.1-21 / Chapter 1.6 --- Microarray gene expression profiling analysis --- p.1-25 / Chapter 1.6.1 --- Princeple of DNA micorarray --- p.1-26 / Chapter 1.6.2 --- Types of microarray --- p.1-29 / Chapter 1.7 --- Gene expression profiling of ovarian cancer --- p.1-29 / Chapter 1.7.1 --- Up-regulated genes in ovarian cancer --- p.1-30 / Chapter 1.7.2 --- Down-regulated genes in ovarian cancer --- p.1-32 / Chapter 1.8 --- Project aims --- p.1-35 / Chapter CHPATER 2 --- MATERIALS AND METHODS --- p.2-1 / Chapter 2.1 --- Materials --- p.2-1 / Chapter 2.1.1 --- Patients --- p.2-1 / Chapter 2.1.2 --- Ovarian tissue specimen --- p.2-1 / Chapter 2.2 --- Methods --- p.2-2 / Chapter 2.2.1 --- Preparation of OCT-embedded Specimen Sections --- p.2-2 / Chapter 2.2.2 --- Microdissection of Tumor Cells from Specimen Sections --- p.2-3 / Chapter 2.2.3 --- Disruption of normal ovarian frozen tissue --- p.2-3 / Chapter 2.2.4 --- Total RNA Extraction --- p.2-3 / Chapter 2.2.4.1 --- RNA Isolation --- p.2-4 / Chapter 2.2.4.2 --- DNase I Digestion --- p.2-4 / Chapter 2.2.4.3 --- RNA Cleanup and Elution --- p.2-5 / Chapter 2.2.5 --- Oligonucleotide Microarray --- p.2-6 / Chapter 2.2.5.1 --- Two-Cycle cDNA Synthesis --- p.2-6 / Chapter 2.2.5.2 --- Synthesis of Biotin-Labeled cRNA --- p.2-9 / Chapter 2.2.5.3 --- Fragmenting the cRNA for Target Preparation --- p.2-9 / Chapter 2.2.5.4 --- Target Hybridization --- p.2-10 / Chapter 2.2.5.5 --- "Array Washing, Staining, and Scanning" --- p.2-11 / Chapter 2.2.5.6 --- Statistical Analysis of Microarray Data --- p.2-11 / Chapter 2.2.6 --- Quantitative Real-time Polymerase Chain Reaction --- p.2-13 / Chapter 2.2.6.1 --- Primer and Probe --- p.2-13 / Chapter 2.2.6.2 --- Reverse-transcription --- p.2-13 / Chapter 2.2.6.3 --- Plate Setup --- p.2-14 / Chapter 2.2.6.4 --- Fluocogenic PCR --- p.2-14 / Chapter 2.2.6.5 --- Statistical Analysis of Quantitative Real-time PCR Data --- p.2-15 / Chapter CHAPTER 3 --- RESULTS --- p.3-1 / Chapter 3.1 --- Microarray gene expression data analysis --- p.3-1 / Chapter 3.1.1 --- Unsupervised Gene Selection --- p.3-1 / Chapter 3.1.2 --- Supervised Gene Selection --- p.3-3 / Chapter 3.1.2.1 --- Gene expression profiles distinguish Serous Epithelial Ovarian Tumor from Normal Ovary and identifydifferentially expressed genes --- p.3-3 / Chapter 3.1.2.2 --- Gene expression profiles distinguish Advanced Stage Serous Epithelial Ovarian Tumor from Early Stage Serous Epithelial Ovarian Tumor and identify differentially expressed genes --- p.3-22 / Chapter 3.1.2.3 --- Gene expression profiles distinguish Metastatic Serous Epithelial Ovarian Tumor from Primary Serous Epithelial Ovarian Tumor and identify differentially expressed genes --- p.3-24 / Chapter 3.2 --- Validation of microarray data by quantitative Real-time PCR --- p.3-27 / Chapter 3.2.1 --- Fold change of candidate genes --- p.3-27 / Chapter 3.2.2 --- Correlation between microarray and quantitative real-time PCR results --- p.3-29 / Chapter 3.2.3 --- Comparison of the expression of candidates genes among the different histological types of epithelial ovarian tumors --- p.3-32 / Chapter CHAPTER 4 --- DISCUSSION --- p.4-1 / Chapter 4.1 --- Global gene expression profiling using oligonucleotide microarray --- p.4-1 / Chapter 4.1.1 --- "Sensitivity, specificity and reproducibility of the Affymetrix GeneChip® microarray" --- p.4-1 / Chapter 4.1.2 --- Microarray analysis software --- p.4-3 / Chapter 4.1.2.1 --- DNA-Chip Analyzer software --- p.4-3 / Chapter 4.1.2.2 --- Comparison of statistical methods for analysis of Affymetrix GeneChip® microarray data --- p.4-5 / Chapter 4.2 --- Validation of microarray data --- p.4-7 / Chapter 4.2.1 --- Advantages of using real-time PCR for mRNA quantification --- p.4-8 / Chapter 4.2.2 --- Comparison of mRNA gene expression by RT-PCR and DNA microarray --- p.4-9 / Chapter 4.3 --- Gene expression profiling in serous ovarian cancer compared with normal ovarian epithelium --- p.4-10 / Chapter 4.3.1 --- Potential biomarkers or therapeutic targets in ovarian cancer --- p.4-12 / Chapter 4.4 --- Gene expression profiling in advanced serous ovarian cancer compared with early ovarian cancer --- p.4-16 / Chapter 4.4.1 --- Potential prognostic markers or therapeutic targets in advanced ovarian cancer --- p.4-17 / Chapter 4.5 --- Gene expression profiling in metastatic cancer compared with primary ovarian cancer --- p.4-22 / Chapter 4.5.1 --- Potential predictive markers or therapeutic targets in metastatic cancer of ovary origin --- p.4-23 / Chapter CHAPTER 5 --- CONCLUSIONS --- p.5-1 / Chapter CHAPTER 6 --- FUTURE PROSPECT --- p.6-1 / REFERENCES --- p.R-1