A thesis submitted to the Faculty of Science under the school of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Doctor of Philosophy. Gauteng, Johannesburg, 2016. / Overexpression of RBBP6 in cancers of the colon, lung and oesophagus makes it a potential target in anticancer therapy. This is especially important because it associates with the tumour suppressor gene p53, inactivation of which has been linked to over 50% of all cancer types. Cancer is an enormous burden of a disease globally. Today, more people die from cancer than HIV/AIDS, tuberculosis and malaria combined. And in females, breast and cervical malignancies remain the most common types. Currently, cervical cancer is the most diagnosed gynaecological cancer type, whose mortality rate is the highest in developing countries due to the asymptomatic nature of the disease coupled with inadequate cancer control tools and facilities. Breast cancer incidence rate has increased beyond that of lung cancer, making it the most common malignancy among women. / GR2016

MSc., Faculty of Science, University of the Witwatersrand, 2011 / Aim: This study aimed at evaluating the accuracy of the treatment setup margin in external beam radiotherapy in cervical cancer patients treated supine with or without the CIVCO “kneefix and feetfix”TM immobilizing devices. Methods and materials: 2 groups of 30 cervical cancer patients each, who were treated supine with two parallel opposed fields or a four-field “box” technique were selected randomly. The treatment fields were planned with a 2 cm setup margin defined radiographically. The first group was treated without any immobilization and the second group was treated with the “kneefix and feetfix”TM immobilization device. Both groups of patients were selected from the patients treated on one of two linear accelerators (linac), which had weekly mechanical quality control (QC). All patients had pre-treatment verifications on the treatment machine in which a megavoltage Xray film was taken to compare with the planning simulation film. Both films were approved by the radiation oncologist managing the patient. In this study the position of the treatment couch as at the approved machine film was taken as the intended or planned position for the immobilized patients. The digital readouts of the daily treatment position of the couch were recorded for each patient as the absolute X (lateral), Y (longitudinal), and Z (vertical) position of the couch from the record and verify system interfaced to the treatment machine. A total of 1241 (582 for the immobilized and 659 for the non-immobilized patient group) daily treatment setup positions were recorded in terms of the X, Y and Z coordinates of the couch corresponding to the Medio-lateral (ML), Supero-inferior (SI) and Antero-posterior (AP) directions of the patient, respectively. The daily translational setup deviation of the patient was calculated by taking the difference between the planned (approved) and daily treatment setup positions in each direction. Each patient’s systematic setup error (mi) and the population mean setup deviation (M), was calculated. Random ( ) and systematic ( ) setup errors were then calculated for each group in each direction. The translational setup variations found in the AP, iii ML, SI directions were compared with the 2 cm x 2 cm x 2 cm Planning Target Volume (PTV). Couch tolerance limits with the immobilization device were suggested based on the ± 2SD (standard deviation) obtained for each translational movement of the treatment couch. Result: The random and systematic errors for the immobilized patient group were less than those for the non-immobilized patient group. For the immobilized patient group, the systematic setup error was greater than the random error in the ML and SI direction as shown in Table I. Table I: The random and systematic errors in the setup in the Antero-posterior (AP), Medio-lateral (ML) and Supero-inferior (SI) directions and the suggested couch tolerance limits for both patient groups. Almost all treatment setup positions had less than 2 cm variation in the AP setup for both patient groups however; one third of the immobilized positions had more than 2 cm variation in the setup in the ML and SI directions. Conclusion: The “kneefix and feetfix”TM immobilizing device resulted in a minor improvement in both the random and systematic setup errors. The systematic setup errors need to be investigated further. There are measurable patient rotations of more than 2 cm in the setup margin with the immobilizing device and this should be confirmed with an imaging study. The 2 cm margin in the ML and SI directions Immobilized patient group Non-immobilized patient group AP (cm) ML (cm) SI (cm) AP (cm) ML (cm) SI (cm) Random error (!) 0.30 1.35 1.26 0.37 2.74 7.83 Systematic error (") 0.19 1.55 1.64 0.33 1.70 8.11 Suggested couch tolerance limits (±2SD) 0.70 4.04 4.08 0.88 4.76 N/A iv established at simulation should not be changed for these patients. A 1 cm tolerance in the AP setup margin could be introduced at this institution.

Eva Tsui Yuen. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 124-140). / SUMMARY / ACKNOWLEDGEMENT / Chapter CHAPTER I --- INTRODUCTION --- p.1 / Chapter CHAPTER II --- LITERATURE REVIEWS --- p.5 / Chapter 2.1 --- Anatomy and Histology of Uterine Cervix --- p.6 / Chapter 2.2 --- Premalignant and Malignant Lesions of Uterine Cervix --- p.9 / Chapter 2.2.1 --- Incidence --- p.9 / Chapter 2.2.2 --- Etiological Factors --- p.10 / Chapter 2.2.3 --- Classification and Histopathology --- p.13 / Chapter A. --- Condyloma --- p.13 / Chapter B. --- Cervical Intraepithelial Neoplasia (CIN) --- p.16 / Chapter C. --- Microinvasive Squamous Cell Carcinoma --- p.19 / Chapter D. --- Invasive Squamous Cell Carcinoma --- p.22 / Chapter E. --- Adenosquamous Carcinoma --- p.25 / Chapter F. --- Adenocarcinoma --- p.26 / Chapter 2.3 --- Human Papillomavirus (HPV) --- p.28 / Chapter 2.3.1 --- Organization of the Viral Genome --- p.28 / Chapter 2.3.2 --- Classification --- p.35 / Chapter 2.4 --- The Impact of Human Papillomavirus (HPV)in Premalignant and Malignant Lesions of Uterine Cervix --- p.35 / Chapter 2.5 --- Cervical Screening --- p.40 / Chapter 2.5.1 --- Cervical Smear --- p.40 / Chapter 2.5.2 --- Cervicography --- p.41 / Chapter 2.5.3 --- HPV Detection --- p.43 / Chapter CHAPTER III --- MATERIALS AND METHODS --- p.54 / Chapter 3.1 --- Study Population --- p.55 / Chapter 3.2 --- Specimen Collection --- p.56 / Chapter 3.3 --- Extraction of Genomic DNA --- p.56 / Chapter 3.4 --- Polymerase Chain Reaction (PCR) --- p.60 / Chapter 3.4.1 --- Oligonucleotide Primers and Positive Controls --- p.60 / Chapter 3.4.2 --- Polymerase Chain Reaction Procedure --- p.62 / Chapter A. --- PCR Optimization --- p.62 / Chapter B. --- Multiplex PCR --- p.63 / Chapter C. --- Single Primer PCR --- p.64 / Chapter 3.4.3 --- Gel Electrophoresis --- p.65 / Chapter 3.5 --- Southern-blot and Hybridization --- p.69 / Chapter 3.5.1 --- Southern-blot --- p.69 / Chapter 3.5.2 --- Nucleic Acid Hybridization --- p.71 / Chapter A. --- Oligonucleotide Probes --- p.71 / Chapter B. --- Radioactive Labelling of Probes --- p.73 / Chapter C. --- Hybridization --- p.74 / Chapter D. --- Removal of Labelled Probes --- p.77 / Chapter CHAPTER IV --- RESULTS --- p.78 / Chapter 4.1 --- Cytological Findings of Cervical Scrapes --- p.79 / Chapter 4.1.1 --- Colposcopy Group --- p.79 / Chapter 4.1.2 --- General Gynaecology Group --- p.81 / Chapter 4.1.3 --- Antenatal Group --- p.81 / Chapter 4.2 --- PCR Optimization --- p.84 / Chapter 4.3 --- Detection of HPV DNA by Multiplex PCR --- p.86 / Chapter 4.3.1 --- Colposcopy Group --- p.86 / Chapter 4.3.2 --- General Gynaecology Group --- p.89 / Chapter 4.3.3 --- Antenatal Group --- p.91 / Chapter 4.4 --- Detection of HPV DNA by Southern-blot Hybridization --- p.91 / Chapter 4.5 --- Detection of HPV DNA by Single Primer PCR --- p.104 / Chapter CHAPTER V --- DISCUSSION --- p.110 / Chapter CHAPTER VI --- CONCLUSION --- p.121 / REFERENCES --- p.124

The cervix serves as the passage for the fetus during birth. The mechanical function of the cervix is crucial for a healthy term pregnancy: 1) prior to term it must remain closed and resist the increasing mechanical load from the growing pregnancy and 2) at time of parturition it must soften, deform and dilate to allow for delivery of the fetus. After delivery, the cervix must repair and close. The timing and characteristics of this remodeling behavior is currently an active research focus because it is hypothesized that premature remodeling in pregnancy can lead to preterm birth, a leading cause of neonatal death or significant neonatal morbidity. The research goal was to measure and characterize anisotropic material properties because they contribute to keeping cervix shut. In this thesis, the collagen fiber network orientation and dispersion of non-pregnant and pregnant human cervical tissue samples were analyzed using optical coherence tomography, and the samples were tested using mechanical indentation and digital image correlation techniques. Human cervices were acquired from non-pregnant and pregnant consented patients that went through hysterectomy. Axial cervical slices were imaged using optical coherence tomography and fiber orientation and dispersion data was analyzed using a new pixel-wise fiber orientation algorithm and was compared among four anatomical quadrants and among patients with different obstetric backgrounds. Two radial zones with different fiber orientations were found. The posterior and anterior quadrants of the outer zone were found to have distinct fiber dispersion features and their fiber dispersion shifted most dramatically from non-pregnant to pregnant. In an effort to characterize the compressive mechanical behavior of human cervical tissue, we present a novel indentation test with digital correlation imaging to visualize the real-time deformation of cervical slice during indentation and measure the compressive mechanical properties through coupled finite element analysis with collagen fiber orientation and dispersion information informed by OCT of non-pregnant and term pregnant cervical tissue. Heterogeneity within the same cervix and difference between non-pregnant and pregnant cervices were found. The upper cervix was found to have a stronger ground substance. The anterior and posterior quadrants were less compressible than the left and right quadrants for non-pregnant specimens. The upper cervix of non-pregnant patients had a stronger ground substance than that of pregnant patients. A workflow of optical, mechanical, and chemical experiments on the same piece of specimen with most fibers intact was also proposed in this thesis and these experiments would validate and inform each other.

Thesis (M.Sc. (Medical Laboratory Sciences)) -- University of the North, 1986 / Refer to the document

This thesis is concerned with cervical cancer amongst New Zealand women, particularly Maori women. Maori women have an alarmingly high incidence of cervical cancer, approximately three times higher than non-Maori women. Maori women experience one of the highest rates of cervical cancer in the world. Chapter one, two and three form the introductory section of the thesis, Section A. Chapter one provides an overview of cervical cancer incidence in the world, followed by a more detailed analysis of the occurrence of cervical cancer in New Zealand and a discussion of the aetiological factors of cervical cancer. Cervical screening is discussed in Chapter two. The ethnic differences in incidence and mortality of cervical cancer between Maori and non-Maori and possible reasons for these differences are studied in Chapter three. Section B consists of the original work undertaken. A pilot study (Chapter four) was conducted to trial the methods for the national study (Chapter five). The national study was a retrospective review of the cervical smear histories of Maori women first diagnosed with invasive cervical cancer over a recent two year period in order to investigate why Maori women have not had their disease detected by screening and treated at the intraepithelial stage. Maori women�s knowledge of and attitudes towards cervical screening were obtained in a survey in Ruatoria (Chapter six). Section C concludes with a chapter (Chapter seven) on the conclusions and recommendations based on the material reviewed and the work undertaken.

Thesis (M. Phil.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references. Available also from UMI/Dissertation Abstracts International.

Thesis (M. Med. Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 48-53).

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences