Photodynamic therapy (PDT) is a cancer treatment method in which a photosensitizer, light of a particular wavelength, and also oxygen are used to destroy cancerous cells. Cancer cells absorb the photosensitizing agent which is injected into the body, and it is triggered to cause cell destruction upon absorption of light. This occurs because of the excitation of the photosensitizer produces reactive oxygen species that induce a cascade of cellular and molecular events in the body. Photosensitizing agents that can photo-cleave DNA at long wavelengths are highly demanded in PDT, because the long wavelengths of light can penetrate through tissue deeply compared to visible light. While most of the photosensitizers are activated at wavelengths less than 690 nm, penetration of light continues to increase at increasing wavelengths. In this thesis, photosensitizers that can be activated to oxidize DNA with long wavelengths of light will be discussed. Using quinoline cyanine dyes, here we report the first example of DNA photocleavage at a wavelength of light above 800 nm.

M.A. / The aim of this study was to ascertain the coping methods of women in long term follow-up of breast cancer treatment. Furthermore, personality traits that deal with the spectrum of positive affectivity were introduced to determine whether these impact on women's appraisal of their situation and their subsequent choice of coping mechanism. Thus, a process approach to exploring coping strategies and a goal-attainment conceptualization of hope were used to determine whether hope is associated with coping appraisal in the long term follow-up of breast cancer treatment. Furthermore, high hope women were expected to use more problem focused coping methods and low hope women were expected to use more emotion focused coping skills. Women in cancer remission who attend yearly or six-monthly check-ups at the Johannesburg hospital were approached to complete the questionnaire and brief interview. Although the study did not confirm that low hope and high hope women use different kinds of coping strategies, the predicted relationship between hope and challenge appraisals was supported by significant correlations. However, it was found that hope may be analogous to positive affect, thus indicating the need for further validation of the Hope Scale. Finally, it was concluded that breast cancer need not be seen as a devitalising disease and that there are a variety of coping strategies which can be utilized to enhance patient's positive emotional state. The women in this study use the emotion focused coping skill of positive reappraisal which concentrates on the possibilities for mastery and growth that inhere in their long term follow-up treatment. Moreover, women are extremely positive and hopeful in their daily outlook and while this personality trait seems to suggest that denial is at play, it is more likely that women in long term remission have a strong belief in their own personal qualities and future. Women in this study choose to distance themselves from the implicit trauma of the threat of recurrence in favour of an active belief in their personal resilience to overcome any stressful event or outcome.

Medication adherence in individuals taking multiple medications has received little research attention, despite its importance in clinical treatment and its relevance to achieving optimal health outcomes. With the growth of the aging population and prevalence of chronic diseases, adherence to multiple medication regimens has become a critical issue. This project, consisting of three related studies, investigated medication adherence of cancer patients who received an allogeneic hematopoietic cell transplant (alloHCT) and whose conditions require adherence to complex, multiple medication regimens for prolonged periods of time. The Information-Motivation-Behavioral Skills (IMB) model was the theoretical framework for the study. This model posits that well-informed, highly motivated individuals have better adherence behaviors. In addition to having optimal information and motivation, patients also need to develop the appropriate behavioral skills to maximize the value of information, motivation and aid adherence. Thus, within this framework, the link between information, motivation, and adherence is mediated by behavioral skills. Using the IMB model, the aim of this project was to examine different approaches to facilitating medication adherence after transplant. The first study used a mixed-methods approach to examine the feasibility of using an electronic pillbox for assessing adherence to multiple medications. The second study utilized patient interview data to assess the link between social support and adherence to multiple medications. The third study also used patient interview data to identify adherence determinants and strategies that patients used after transplant. The results of the first study show that even though some features of the electronic pillbox need to be modified, it is feasible to use it to facilitate medication adherence for patients after transplant. The second study demonstrated the importance of social support from lay caregivers, such as spouse and family members, as well as healthcare providers, for adherence tasks after transplant. Lay caregivers provided emotional and practical support, whereas healthcare providers were the main source of informational and medical support. The third study identified various determinants that facilitated and hindered medication adherence. The study also suggests practical lessons for adherence to multiple medications. Collectively, the findings provide a foundation for developing intervention approaches for this particular patient population.

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the Master of Science degree. 2 November 2017. / Screening methodologies have identified specific targets that could serve as potential therapeutic markers in cancer drug design, and the Retinoblastoma binding protein 6 (RBBP6) which is predominately expressed in lung and breast cancers is one critical protein identified. This study seeks to understand the 3D structure of RBBP6 domains, with emphasis on cancer. Three of these domains have been studied in this project, i.e. the Domain With No Name (DWNN), RING Finger, and the p53-binding domain. The ubiquitin-like structure of the DWNN has implicated this domain as a ubiquitin-like modifier of other proteins such as p53, whilst the RING Finger domain has intrinsic E3 Ligase activity like MDM2 the prototypical negative regulator of p53. The DWNN and RING Finger domains have resolved solution NMR structures, whilst the p53-binding domain has none. Thus, the first initiative undertaken was to model the RBBP6 p53-binding domain using I-TASSER and eThread-Modeller web-severs. Our results demonstrated that this domain mainly constitutes of alpha-helices and loop structures. Structural quality validations of both I-TASSER and eThread-Modeller models were further assessed using Swiss-Model and ProSA (Protein structure analysis) web-servers. Analyses were focussed on specific statistical parameters (Anolea, DFire, QMEAN, ProCheck and the ProSA Z-score). Results from these analyses show that the first I-TASSER model is the best possible representation of the RBBP6 p53-binding domain depicting minimal deviation from native state. Furthermore, screening and docking studies were performed using Schrödinger-Maestro v10.7: Glide SP and drug-like molecules that would potentially serve as agonist or antagonist of RBBP6 were identified. / MT 2018

A simple method to verify the total treatment time generated by the treatment planning system (TPS) when the CONTURA MLB or the SAVI applicator are used for APBI treatments has been developed. The method compares the time generated by the TPS to a predicted time, calculated by inserting parameters obtained from the TPS in equations generated in this Thesis. The equations were generated by linearly fitting data from clinical cases that had been treated using the Contura MLB or the SAVI applicator at the Lynn Cancer Institute of the Boca Raton Regional Hospital. The parameters used were the PTV coverage, Air Kerma Strength, Balloon Volume (Contura data fit) and Evaluation PTV (SAVI data fit). As an outcome of this research, it is recommended that the plan should be reevaluated when the percent difference between the generated and the predicted times exceeds 5% for the Contura MLB, or 10% for the SAVI. / by Andreas Kyriacou. / Thesis (M.S.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

Ma, Buig Yue Brigette. / Thesis M.D. Chinese University of Hong Kong 2014. / Includes bibliographical references (leaves 232-270). / Title from PDF title page (viewed on 18, November, 2016).

Liu, Yanan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 87-98). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

Cancer is currently the second most common cause of death in the U.S. with over 600,000 people expected to die from cancer this year alone. The diagnosis of cancer steadily increased through most of the 20th century due to a rise in tobacco usage, causing a relatively recent growth in cancer research. In the past several decades, treatments for cancer have been rapidly changing and advancing, and it is vital to understand how these medications affect the human skeleton. Presently, little research has been conducted on how medications alter the human skeleton and impact the biological profile. One of the primary side effects of drug and radiation-based treatments for a neoplasm is cancer treatment-induced bone loss (CTIBL), which may impact the expression of sexual dimorphism in morphological traits. It is hypothesized that CTIBL would decrease the robusticity of sexually dimorphic nonmetric traits and skew the ordinal scores towards gracile. A total of 178 individuals with documented cancer and/or treatment and 178 individuals without documented cancer from the William M. Bass Donated Skeletal Collection at the University of Tennessee, Knoxville, were assessed following conventional sex assessment standards for the skull and os coxa. These methods presented by Buikstra and Ubelaker (1994), Klales et al. (2012), and Walker (2005) were applied to the os coxa and Walker’s (2008) method for the skull. The individuals ranged in age from 26 to 97 years and included 350 European Americans, two African Americans, one Asian/Polynesian, and three Native Americans. The control group was designed to parallel the experimental group by demographic information including sex, ancestry, and age-at-death. The experimental group was also subdivided into two groups that included individuals that underwent chemotherapy and/or radiation (drug subgroup) and individuals who only underwent surgery as a form of treatment (surgery subgroup). Thirty-six randomly selected individuals were also rescored to test for intraobserver agreement. IBM’s Statistical Package for Social Sciences (SPSS) was used to calculate Chi-Square, ANOVA, ANCOVA, and Cohen’s Kappa analyses. The Chi-Square and ANOVA analyses were used to determine if there was any statistically significant relationship between cancer treatment status and the scores of the morphological traits. The results indicated no significant relationship between cancer treatment status and the trait scores (p > 0.05) for all analyses except for the Chi-square analysis of the glabella for females in the pooled sample (p=0.047) and the ANOVA analysis of the ventral arc in the surgery group when sex was not considered (p=0.010). It is possible that these traits are affected by cancer treatment status. However, it is more likely that these results were due to natural variation between the control and experimental groups. Intraobserver agreement was calculated using Cohen’s Kappa analysis. Intraobserver agreement ranged from fair to substantial with most traits indicating moderate intraobserver agreement. Some possible confounders of the study include the unknown duration of cancer treatments, the use of a history of cancer as a proxy for cancer treatment, not knowing when the individual underwent cancer treatment before death, and the assumption that the individuals included in the sample were accurately documented. Cancer Treatment-Induced Bone Loss may only affect bone mineral density as opposed to the expression of sexually dimorphic traits as many of these visually assessed traits are sites of muscle attachments. Though CTIBL does not appear to affect morphological sex assessment, further research should be conducted on the possible effects of CTIBL for other components of the biological profile.

This dissertation presents novel sequential dose-finding designs that adjust for inter-individual pharmacokinetic variability in phase I cancer clinical trials. Unlike most traditional dose-finding designs whose primary goals are the determination of a maximum safe dose, the goal of our proposed designs is to estimate a patient-specific dosing function such that the responses of patients can achieve a target safety level. Extending from a single compartment model in the pharmacokinetic theory, we first postulate a linear model to describe the relationship between the area under concentration-time curve, dose and predicted clearance. We propose a repeated least squares procedure that aims to sequentially determine dose according to individual ability of metabolizing the drug. To guarantee consistent estimation of the individualized dosing function at the end of a trial, we apply repeated least squares subject to a consistency constraint based on an eigenvalue theory for stochastic linear regression. We empirically determine the convergence rate of the eigenvalue constraint using a real data set from an irinotecan study in colorectal carcinoma patients, and calibrate the procedure to minimize a loss function that accounts for the dosing costs of study subjects and future patients. When compared to the traditional body surface area and an equation based dosing methods, the simulation results demonstrate that the repeated least squares procedure control the dosing cost and allow for precise estimation of the dosing function. Furthermore, in order to enhance the generality and robustness of the dose-finding designs, we generalize the linear association to a nonlinear relationship between the response and a linear combination of dose and predicted clearance. We propose a two-stage sequential design, the semiparametric link-adapted recursion, which targets at individualizing dose assignments meanwhile adapting for an unknown nonlinear link function connecting the response and dose along with predicted clearance. The repeat least squares with eigenvalue constraint design is utilized as the first stage, and the second stage recursively applies an iterative semiparametric least squares approach to estimate the dosing function and determine dosage for next patient. The simulation results demonstrate that: at first, the performance of repeated least squares with eigenvalue constraint design is acceptably robust to model misspecifications; at second, as its performance is close to that of repeated least squares procedure under parametric models, the semiparametric link-adapted recursion does not sacrifice much estimation accuracy to gain robustness against model misspecifications; at last, compared to the repeated least squares procedure, the semiparametric link-adapted recursion can significantly improve the dosing costs and estimation precision under the semiparametric models.

肺癌是導致男性死亡的最常見原因以及是排在乳腺癌和結腸癌之後的導致女性死亡的第三大原因。雖然肺癌如此嚴重，但是如今治疗肺癌仍然是一个挑战。現今對肺癌的治療主要集中在化學治療和靶點藥物治療，但是由於這些治療有著很大的副作用和低治愈率，尋找其他的醫學替代方法十分迫切。甘草是其中最常用的中藥，它常常用作食品工業中的甜味劑。以往的研究表明，甘草具有多種的生物活性。但是甘草提取物對於肺癌的治療卻是十分匱乏的。 / 本論文主要目的是評價甘草提取物以及其中的有效成份對非小型肺癌細胞株A549 的影響，以及其作用的機理。我們的數據表明，甘草的乙酸乙酯（EAL）成份比甘草的乙醇提取物有著比較強的抑制癌細胞的作用。另外，對甘草的五個單體進行的測試中發現lico-3 是最具有抑制肺癌作用的。利用高效液相色譜法對甘草活性成份分析表明，lico-3 是EAL中的其中一個單體。 / 乳酸脫氫酶滲漏（LDH）的檢測結果以及异硫氰酸荧光素-碘化丙啶（FITC-PI）雙染的結果表明，EAL 能夠引起肺癌細胞的凋亡現象而非壞死現象。實驗結果表明由EAL引起的A549細胞凋亡是跟Bcl-2家族及Caspase家族有關係，同時EAL還能夠抑制Akt途徑從而導致細胞的死亡。 / 致肺癌細胞死亡的原因進行進一步研究表明，EAL還能夠引起抑制細胞週期的運作，停留在G2/M 時期。這可能是由於EAL引發了p53與p21的上調作用從而抑制了細胞的生長與增殖。 / 實驗結果說明了EAL引起的肺癌細胞株A549的凋亡作用是跟多重細胞通路有關， 同時表明了EAL是具有抗擊肺癌作用的潛能，能夠作為治療肺癌的藥物。 / Lung cancer is the most common cause of cancer death in men and third in women followed by breast cancer and colon cancer, yet treatment of lung cancer remains a challenge. Current treatments including chemotherapy and targeted drug treatment come with side-effects and low successful rate. Alternative medicine for treatment of lung cancer is warranted. Glycyrrhiza uralensis (Gan-Cao), commonly called “licorice, is one of the most commonly used herbs in traditional Chinese medicine (TCM). It is also used as flavoring and sweetening agents in many of food products. Previous studies have indicated that licorice exhibits a variety of biological activities. However, anticancer effects of licorice extract on lung cancer remain unclear. / In this study, we evaluated effects of licorice extract and its chemical components on human lung cancer cell line A549, and studied its mode of action. Our results showed the ethyl acetate fraction of licorice (EAL) was more effective in inhibition of A549 cell growth followed by ETL (IC₅₀: 50μg/mL). Moreover, among the five compounds tested, lico-3 was more potent compound. The HPLC analysis of the active fraction indicated that lico-3 was one of the compounds distributed in the EA fraction. / The results of LDH assay and FITC-PI co-staining method suggested low concentration of EAL can trigger apoptosis but not necrosis. The experimental findings show that EAL induce apoptosis in A549 cell lines involved in Bcl-2 family and caspase cascade. Also, EAL can arrest the Akt survival pathway in A549. Furthermore, the results indicate that EAL triggered G2/M phase arrest. The studies suggest EAL can up-regulate p53 and p21 to promote cell cycle arrest resulting in inhibition of proliferation. / Experimental results indicate that EAL is involved in multiple signal pathways to induce lung cancer cell death. The result suggests EAL is a potential candidate for lung cancer therapy. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Zhou, Yanling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 99-110). / Abstracts in Chinese. / Abstract --- p.III / 論文摘要 --- p.V / Acknowledgement --- p.VII / List of Contents --- p.VIII / List of Figures --- p.X / List of Tables --- p.XI / List of Abbreviations --- p.XII / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Lung cancer --- p.1 / Chapter 1.1.1 --- Overview --- p.1 / Chapter 1.1.2 --- Risk factors --- p.2 / Chapter 1.1.3 --- Types of lung cancer --- p.4 / Chapter 1.1.4 --- Stages and treatment of lung cancer --- p.5 / Chapter 1.1.5 --- Chemotherapy for lung cancer treatment --- p.8 / Chapter 1.2 --- Traditional Chinese Medicines --- p.11 / Chapter 1.2.1 --- Overview --- p.11 / Chapter 1.2.2 --- Licorice --- p.14 / Chapter 1.2.3 --- Chemical study of licorice --- p.16 / Chapter 1.2.4 --- Pharmacological activities of licorice --- p.16 / Chapter 1.3 --- Molecular mechanism of apoptosis --- p.21 / Chapter 1.3.1 --- Overview --- p.21 / Chapter 1.3.2 --- Bcl2 family --- p.21 / Chapter 1.3.3 --- Caspase pathway --- p.23 / Chapter 1.3.4 --- Akt pathway --- p.24 / Chapter 1.3.5 --- p53 protein --- p.26 / Chapter 1.3.6 --- Apoptosis and cancer --- p.27 / Chapter 1.4 --- Cell cycle --- p.29 / Chapter 1.4.1 --- Overview --- p.29 / Chapter 1.4.2 --- Cell cycle and p53 --- p.29 / Chapter 1.4.3 --- Cell cycle and cancer --- p.30 / Chapter 1.5 --- Aims of study --- p.32 / Chapter Chapter 2 --- Materials and Methods --- p.33 / Chapter 2.1 --- Cell culture and treatment --- p.33 / Chapter 2.1.1 --- Cell line --- p.33 / Chapter 2.1.2 --- Chemicals and reagents --- p.34 / Chapter 2.1.3 --- Preparation of solutions --- p.34 / Chapter 2.2 --- Preparation of Licorice sample --- p.35 / Chapter 2.3 --- HPLC analysis --- p.35 / Chapter 2.3.1 --- Chemical and materials --- p.35 / Chapter 2.3.2 --- Instrumentation --- p.36 / Chapter 2.3.3 --- Preparation of Standard solutions --- p.36 / Chapter 2.3.4 --- Preparation of samples --- p.37 / Chapter 2.3.5 --- HPLC conditions --- p.37 / Chapter 2.3.6 --- Method validation --- p.37 / Chapter 2.4 --- Cell viable assay --- p.38 / Chapter 2.4.1 --- Samples preparation --- p.39 / Chapter 2.4.2 --- Procedure --- p.39 / Chapter 2.5 --- LDH assay --- p.40 / Chapter 2.5.1 --- Reagent preparation --- p.40 / Chapter 2.5.2 --- Procedure --- p.41 / Chapter 2.6 --- Annexin V assay --- p.41 / Chapter 2.6.1 --- Reagent --- p.42 / Chapter 2.6.2 --- Procedure --- p.42 / Chapter 2.7 --- Cell cycle study --- p.43 / Chapter 2.7.1 --- Chemicals and reagent --- p.43 / Chapter 2.7.2 --- Procedure --- p.44 / Chapter 2.8 --- Caspase3/7 Assay --- p.44 / Chapter 2.8.1 --- Reagent preparation --- p.45 / Chapter 2.8.2 --- Procedure --- p.46 / Chapter 2.9 --- Western blotting --- p.46 / Chapter 2.9.1 --- Reagent and antibodies --- p.46 / Chapter 2.9.2 --- Procedure --- p.50 / Chapter 2.9.3 --- Determination of protein concentration --- p.51 / Chapter 2.10 --- Data analysis --- p.51 / Chapter Chapter 3 --- Results --- p.52 / Chapter 3.1 --- Chromatographic conditions and HPLC identity conformation --- p.52 / Chapter 3.1.1 --- Linearity, limits of detection and quantification --- p.56 / Chapter 3.1.2 --- Reproducibility --- p.56 / Chapter 3.1.3 --- Analysis of ethyl acetate of licorice (EAL) using the validated method --- p.56 / Chapter 3.2 --- Licorice induces apoptosis in nonsmall cell lung carcinoma --- p.61 / Chapter 3.2.1 --- Cell viability assay --- p.61 / Chapter 3.2.2 --- LDH leakage assay --- p.71 / Chapter 3.2.3 --- Annexin V and PI staining --- p.73 / Chapter 3.3 --- Protein expression in EALinduced apoptotic cells --- p.75 / Chapter 3.3.1 --- Bcl2 family --- p.75 / Chapter 3.3.2 --- Activation of caspases by EAL treatment --- p.77 / Chapter 3.4 --- EAL could block Akt survival pathway --- p.79 / Chapter 3.5 --- EAL induces cell cycle arrest in nonsmall cell lung carcinoma --- p.83 / Chapter Chapter 4 --- Discussion --- p.85 / Chapter 4.1 --- Chemical analysis of licorice --- p.85 / Chapter 4.2 --- Licorice induced apoptosis but not necrosis on lung cancer cell A549 --- p.86 / Chapter 4.2.1 --- Licorice exhibits specific cytotoxicity to different cancer cells in vitro --- p.86 / Chapter 4.2.2 --- EAL induces cell death via apoptosis but not necrosis --- p.87 / Chapter 4.3 --- Growth inhibition by EAL inducing apoptosis --- p.89 / Chapter 4.3.1 --- EAL induces apoptotic cell death through modification of Bcl2 family --- p.89 / Chapter 4.3.2 --- EAL activate the caspase proteins --- p.90 / Chapter 4.4 --- Growth inhibition by EAL inducing survival pathway arrest --- p.92 / Chapter 4.5 --- Growth inhibition by EAL inducing cellcycle arrest --- p.94 / Chapter 4.6 --- General discussion --- p.96 / Reference --- p.99