Pancreatic cancer kills over 1700 people each year in Australia. In 2000, there were 1908 new cases diagnosed and it remains one of the least treatable malignancies. In the USA, it was the fourth leading cause of cancer death in 2004, with 31,860 new cases and 31,270 recorded deaths. Photodynamic therapy (PDT) is a novel, potentially useful treatment for locally advanced pancreatic cancer with only limited research and clinical work addressing this until now. PDT induces non-thermal, cytotoxic and ischaemic injury to a targeted volume of tissue. During PDT, a photosensitizer is activated by non-thermal light in the presence of oxygen, generating cytotoxic oxygen species and inducing cellular injury and microvascular occlusion. The aim of this thesis was to conduct an animal safety study using two second generation photosensitizers, talaporfin sodium and verteporfin, to assess the risks of pancreatic PDT by looking at injury to organs adjacent to the pancreas and assessing recovery from PDT treatment of the pancreas. The Syrian Golden hamster animal model was used to compare the results of this research to previous work by other authors. The study design incorporated a number of additional experiments, including quantitative tissue fluorescence techniques, plasma level analysis and histopathology techniques. The methods for the animal safety study were similar to the approach used in the clinical setting and provided vital data on the likely risks and side effects of phototherapy in humans. The first study, looking at talaporfin sodium, found likely risks of duodenal injury, gastric injury and death with a limited effect on normal pancreas at photosensitizer doses likely to be employed for pancreatic cancer PDT. The second study, using verteporfin, found similar results with a more potent effect on the normal pancreas at studied drug doses. Both agents had short drug-light intervals, ranging from 15 minutes to 2 hours, reducing the need for pre-treatment hospitalization and short photosensitivity periods of about one to two weeks. Some animals suffered minor cutaneous photosensitivity injuries. A human pancreatic cancer PDT pilot study is feasible and the risks and complications should be acceptable.

Paper V reprinted with kind permission of Elsevier, sciencedirect.com.

Paper V reprinted with kind permission of Elsevier, sciencedirect.com.

Background: The p63 gene is a member of the p53 transcription factor family and can produce six different proteins using two promoters and differential splicing. Expression of p63 is required for proper formation of epithelial tissues. Studies on the transcriptional control of specific genes involved in cell survival, proliferation, differentiation and adhesion have revealed the contributions of p63 to the continuously renewing stratified epithelium. In this thesis, the aim was to improve our understanding of the roles of p63 in epithelial homeostasis by investigating expression of p63 in normal and benign hyper-proliferative epithelia and exploring the influence of p63 deregulation on cancer progression. Materials and methods: Using quantitative real time RT-PCR and immunohistochemistry, we first examined the expression of different p63 isoforms in patients diagnosed with psoriasis - a benign hyper-proliferative and inflammatory skin disease. Afterwards, we investigated responses of p63 in psoriatic epidermis upon Narrowband-UVB (NB-UVB) phototherapy. At the same time, we studied the potential impact of p63 in carcinogenesis by searching for p63 transcriptional targets in a cell line derived from squamous cell carcinoma of the head and neck (SCCHN) - the sixth most common cancer worldwide with over-expression of the ∆Np63α protein as a common feature. p63 gene silencing and microarray were used to identify p63 regulated genes. Real time RT-PCR, western blot, immunohistochemistry, chromatin immunoprecipitation, transient transfection and reporter assays were performed to confirm specific genes as direct p63 targets. Results: Significant down-regulation of p63 mRNA levels was found in psoriatic lesions compared to patients’ own clinically normal skin. Moreover, a trend of decreased TAp63 mRNA levels was seen in patients’ normal skin compared to age- and sex-matched healthy controls. Following NB-UVB phototherapy, an effective first line therapy for psoriasis, expression of p63 was not significantly affected. However, significant changes in p53, FABP5, miR-21 and miR-125b were found. Surprisingly, location and expression levels of p63 proteins detected by immunohistochemistry were similar under all skin conditions. A direct transcriptional regulation of TRAF4 by p63 was seen in the SCCHN cell line and we further found that the localization of the TRAF4 protein was associated with histological differentiation of SCCHN cells. However, unlike its over-expression in SCCHN, similar TRAF4 mRNA expression levels were seen in psoriatic lesions as compared to healthy controls. Besides TRAF4, a total of 127 genes were identified as potentially p63 regulated in the SCCHN cell line and strikingly, about 20% of these genes are involved in cell adhesion or migration. Conclusions: Dysregulation of p63 isoforms in psoriatic epidermis, especially decreased TAp63 expression, and their resistance to NB-UVB phototherapy implicated a contribution of p63 to the psoriasis phenotype. Transcriptional regulation of genes involved in multiple biological pathways indicated that over-expression of p63 in SCCHN might account for altered cell differentiation, adhesion and migration, thus contributing to SCCHN. In conclusion, our studies have found additional mechanisms through which p63 guarded homeostasis of the established epithelium. Deregulation of p63 might play a role in distinct pathological conditions by participating in diverse cellular pathways under different microenvironments.

The rising desire for individualized medical physics models has sparked a transition from the use of tangible phantoms toward the employment of computational software for medical physics applications. One such computational software for radiation transport modeling is the Monte Carlo N-Particle (MCNP) radiation transport code. However, no comprehensive document has been written to introduce the use of the MCNP code for simulating medical physics applications. This document, a primer, addresses this need by leading the medical physics user through the basic use of MCNP and its particular application to the medical physics field. This primer is designed to teach by example, with the aim that each example will illustrate a practical use of particular features in MCNP that are useful in medical physics applications. These examples along with the instructions for reproducing them are the results of this thesis research. These results include simulations of: dose from Tc-99m diagnostic therapy, calculation of Medical Internal Radiation Dose (MIRD) specific absorbed fraction (SAF) values using the ORNL MIRD phantom, x-ray phototherapy effectiveness, prostate brachytherapy lifetime dose calculations, and a radiograph of the head using the Zubal head phantom. Also included are a set of appendices that include useful reference data, code syntax, and a database of input decks including the examples in the primer. The sections in conjunction with the appendices should provide a foundation of knowledge regarding the MCNP commands and their uses as well as enable users to utilize the MCNP manual effectively for situations not specifically addressed by the primer.

碩士 / 國立臺灣大學 / 預防醫學研究所 / 92 / Background: Early prediction of hyperbilirubinemia has regained attention in recent years partly because kernicterus and minor neurological abnormalities has occasionally been reported, and partly because of early discharge due to the change of managed care policy. Objectives: The aims of this thesis were (1) to build up the nomogram of Taiwanese infants, (2) to predict neonatal hyperbilirubinemia by conventional models and a five-state transition model, and (3) to analyze their related risk factors. Materials and Methods: A hospital-based prospective cohort study consisted of 531 infants were term or near-term infants eligible for caring at the well-baby nursery. All infants’ transcutaneous bilirubin (TcB) were recorded regularly at least every 8 hours. Birth weights, maternal age, sex, presence of ABO incompatibility, feeding method, type of delivery, gestational history, and body weight change were recorded. All babies were invited to come back to follow-up clinic after discharge. Nomogram was plotted according to percentile data at a four-hour interval. Sensitivity, specificity, and receiver operator characteristic (ROC) curve were analyzed at age of 24 and 48 hours old. A five-state transition model was built to predict the progression or regression of bilirubin level. Risk factors were analyzed by both linear mixed model , generalized linear mixed model, proportional hazards transitional model. Later-onset neonatal hyperbilirubinemia was analyzed by logistic regression model. Results: According to hour-specific nomogram, infants reached their peak bilirubin level at mean and median age of 79.5 and 76 hours old. Both mean and median peak bilirubin level were about 13.7 mg/dL. Infants received phototherapy at a mean and median age of 80 and 76-hour-old. The areas under ROC cure were 0.873 for predicting need for phototherapy and 0.844 for clinically significant jaundice at age of 48-hour-old. The areas under ROC cure were both 0.773 at 24-hour-old. Non-homogenous process by the division of 48 hours may be a critical point for differentiating transition rate in the transition model. First pregnancy and ABO incompatibility were two risk factors attributed to biological reasons. Conclusion: The present study used a series of TcB measurement to predict hyperbilirubinemia or the need for phototherapy using conventional method or a novel five-state transition model. The results found 48-hour-old TcB level may be a good predictor. Primiparity, incompatibility of ABO blood type, and G6PD deficiency were significant risk factors. Other established significant factors were largely influenced by the neonatal care policy of national health insurance. All infants should receive non-invasive bilirubin measurement before discharge. High risk infants should be followed up within several days after discharge.

碩士 / 高雄師範大學 / 美術學系 / 97 / This study offers a critical interpretation of the family album, phototherapy and projects on women’s health produced by the English postmodern feminist and photographic artist, Jo Spence, during the period from 1979 to 1992. Based on the autobiography of Spence, critical visual methodologies, as well as the perspective of feminist theories and history of feminist practices, the author proposed that the images of the female body in the photographic works of Spence constitute a symbolic presentation of feminism photographic art and social practices. This study discusses the distinctive characteristics of Spence’s works according to the historical perspectives of photographic art, and explores the values and contributions of her works. The greatest finding of this study was that the phototherapy invented by Spence reflected a skill that matched photography with the field of gestalt therapy; the naming and contents of her photographic works mostly conformed to the practical skills of gestalt therapy. This reversed the perspectives of some of the critics who positioned her works as “iconoclasme” or “playing a female role under stereotype”. This study also deconstructs the statements of these critics by probing into the therapeutic field, and opens up another way to interpret the construction of Spence’s works.

碩士 / 國立暨南國際大學 / 生物醫學科技研究所 / 96 / This thesis presents a multi-function driving circuit design with feedback control for phototherapy and electrical stimulation system. It is an all-in-one therapeutic instrument. It includes LCD component, switch circuit and constant current driving circuit. It has been designed by PIC to make up a multi-functional therapy system with light and electrical stimulation for medical application. This text will recommend the treatment of the light and electrical stimulation( micro current electrical stimulation ) to develop at first and overall system structure and theory secondly. Then, we have explained the sub circuit in the system structure, for instance: the driving circuit design and how to reject the offset voltage of op Amp. The phototherapy which is red, blue and green light has different power (under the frequency= 100Hz, duty cycle= 6% and current= 100mA) 12.34mW/cm2, 11.92 mW/cm2, 7 mW/cm2. separately. In this condition(frequency= 100Hz, duty cycle= 6% and current= 100mA ), we can find the better efficiency. After calculation, it can reach the record in the other paper. Micro-current electrical stimulation works at different constant current under frequency= 100Hz and we can find the better linearity at various loading resistance.

碩士 / 國立暨南國際大學 / 生物醫學科技研究所 / 94 / As the brightness be elevated and blue light invented, the LEDs are becoming more and more applications. This thesis applies Nichia corporation full color LEDs to accomplish phototherapy system. The type of full color LED integrates with red, green and blue color LEDs. Color mixture can mix white color and modulate other spectrums. Three PMW circuits achieve optical power and spectrum modulation. The temperature of environment increases, the forward voltage of the LED is decreasing. The LED can be acted temperature detection and instead of temperature sensor with the semiconductor characteristics. In this thesis, we have designed an adjustable optical power and spectrum for 90 LEDs Array. Temperature detection and temperature control PWM sensor used the same LEDs. The wavelengths cover 460 to 636nm. The maximum optical power of single LED is 38mW/cm2 for red, 20mW/cm2 for green and 34mW/cm2 for blue respectively. The range of temperature detection is 10 to 70℃. When temperature is stable, the accuracy error can reduce to within ±1℃.

The persistence of high global mortality rates directly attributable to cardiovascular disease drives ongoing research into novel approaches for improved diagnosis and treatment of its primary underlying cause, atherosclerosis. Combined intravascular ultrasound and photoacoustic (IVUS/IVPA) imaging is one such modality, actively being developed as a tool for improved characterization of high-risk atherosclerotic plaques. The pathophysiology associated with progression and destabilization of atherosclerotic plaques leads to characteristic changes in arterial morphology and composition. IVUS/IVPA imaging seeks to expand upon the ability of clinically utilized intravascular ultrasound (IVUS) imaging to assess vessel anatomy by adding improved sensitivity to image the underlying cellular and molecular composition through intravascular photoacoustic (IVPA) imaging of either endogenous chromophores (e.g. lipid) or exogenously delivered contrast agents. This dissertation focuses on the expansion of IVUS/IVPA imaging using exogenous contrast agents to enable the detection and subsequent optically-triggered therapy of atherosclerotic plaques. The passive extravasation and aggregation of systemically injected plasmonic gold nanorods absorbing within the near infrared tissue optical window within plaques of atherosclerotic rabbit models is first demonstrated, along with the ability to localize the contrast agents using ex vivo IVUS/IVPA imaging. The motivation for nanoparticle labeling of atherosclerosis is then expanded from that of purely image contrast agents to vehicles for image-guided, dual-modality phototherapy. The integrated IVUS/IVPA imaging catheter is utilized for photothermal delivery with simultaneous IVPA temperature monitoring using the high optical absorption of gold nanorod contrast agents to enable localized heating. Subsequently, the potential role for IVUS/IVPA-guided phototherapy is further expanded through the characterization and in vitro assessment of novel multifunctional theranostic nanoparticles comprised of a gold nanorod core with a degradable, photosensitizer-doped silica shell. Together, the results presented within this dissertation provide a framework for ongoing research into the expansion of IVUS/IVPA imaging as a platform for complimentary diagnosis and local treatment of atherosclerotic plaques using multifunctional theranostic nanoparticle contrast agents. / text