Ochratoxin A (OTA), a nephrotoxic mycotoxin, is a contaminant of several agricultural food products consumed by animals and humans. Apart from renal toxicity, in particular renal tumours, OTA may also result in teratogenicity, neurotoxicity and immunotoxicity. Sutherlandia frutescens, an indigenous medicinal plant, has shown significant potential in strengthening the immune system and in cancer treatment, with minimal side effects. The objective of this study was to determine the effects of OTA in male Wistar rats and ascertain if these effects may be reduced by S. frutescens. Rats were treated by intraperitoneal injection (i.p) with either a control (EtOH:dH20;30:70), S. frutescens (1.0mg/kg body weight), OTA (0.5mg/kg body weight) or a combination of OTA and S. frutescens for a period of 1 or 7 days (n=4). Genotoxicity and metabolic activity in peripheral blood mononuclear cells (PBMCs) were quantified using single cell gel electrophoresis (SCGE) and the methylthiazol tetrazolium (MTT) assay, respectively. Lymphocyte apoptosis and mitochondrial depolarisation were measured by flow cytometry. Fluorescence microscopy was utilised to determine renal tissue apoptosis (Hoechst staining) and OTA localisation using immunohistochemistry (IRC). SDS-PAGE and Western blot were utilised to determine protein expression in kidney tissue and serum. Ochratoxin A significantly reduced PBMC viability (14%) after 7 days, compared with Day 1 (p<0.001). Lymphocyte mitochondrial depolarisation was 56.5% and 66.2% in the OTA-only and combination groups, respectively after 7 days (p<0.001). Ochratoxin A produced an increase in DNA damage compared to the control (p<0.01). The renal tissue displayed typical signs of apoptosis such as chromatin condensation. Ochratoxin A was immunolocalised within the glomerulus. The protein analysis showed a decreased expression in the kidney mitochondrial protein fraction. Ochratoxin A preferentially bound to serum albumin and a 120kDa protein in the OTA-only and co-treatment groups after the 1-and 7-day regimes. Protein band intensities significantly decreased after the 7-day co-treatment (p<0.01). The data highlights that OTA toxicity is mediated by mitochondrial dysfunction. Furthermore, OTA disruptions in immune function may play a role in renal damage. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Westville, 2009.

No description available.

Doctor of Health Science / It is well documented that for prostate cancer patients undergoing radiation therapy there is a correlation between target volume displacement and changes in bladder and rectal volumes. However, these studies have used a methodology that has captured only a subset of all treatment positions. This research used daily Computer Tomography (CT) imaging to comprehensively assess organ volumes, organ motion and their effect on dose, something that has never been performed previously, thus adding considerably to the understanding of the topic. Daily CT images were obtained using a Siemens Primus Linear Accelerator equipped with an in-room Somatom CT unit in the accelerator suite, marketed as ‘Primatom’, to accurately position the patient prior to treatment delivery. The internal structures of interest were contoured on the planning workstation by the investigator. The daily volume and location of the organs were derived from the computer to assess and analyse internal organ motion. The planned dose distribution was then imported onto the treatment CT datasets and used to compare the planned dose to i) the actual isocentre, where the isocentre was actually placed for that fraction, ii) the uncorrected isocentre, by un-doing any on-line corrections performed by the treatment staff prior to treatment delivery, and iii) the future isocentre, by placing the isocentre relative to internal organ motion on a daily basis. The results of this study did not confirm a statistically significant decrease in rectum volumes over time (hypothesis 1), however large fluctuations in bladder volume were confirmed (hypothesis 2). Internal organ motion for the rectum and bladder was demonstrated to be related to organ filling. Ideal planning volumes for these organs have been reported to minimise systematic and random uncertainty in the treatment volumes. An observed decrease in prostate volume over time, a systematic uncertainty in the location of the prostate at the time of the planning CT scan and a significant relationship between prostate centre of volume and rectum and bladder volumes has resulted in a recommendation that patients should be re-scanned during treatment to ensure appropriate clinical target volume coverage. A significant relationship between rectal and bladder volumes and the dose delivered to these organs was found (hypothesis 3). The dose delivered to the planning target volume was not related to the rectal or bladder volumes, although it was related to the motion of these organs. Despite these results only minimal effects on the dose delivered to any of the three isocentres occurred, indicating that the planned dose was accurately delivered using the methodology presented here (hypothesis 4). However the results do indicate that the patient preparation instructions need to be improved if margins are to be reduced in the future. It is unrealistic to assume that Image Guided Radiation Therapy will ever become routine practice due to infrastructure costs and time limitations. This research will inform radiation therapy centres of the variables associated with prostate cancer treatment on a daily basis, something that has never before been realistically achievable. As a result centres will be able to devise protocols to improve treatment outcomes.

Bakgrund: Varje år drabbas 55 000 personer i Sverige av cancer och behandlas oftast med kombinerade behandlingar. Den vanligaste biverkningen och det mest påfrestande symtomet vid cancer är fatigue. Fatigue betyder extrem trötthet/utmattninig och är en subjektiv upplevelse. Fatigue är inte en trötthet som går över efter sömn och vila. Syfte: Syftet med denna litteraturstudie är att beskriva hur det är att leva med fatigue vid cancer och cancerbehandling. Metod: En systematisk litteraturstudie som bygger på 15 vetenskapliga artiklar. Artiklarna är både kvalitativa och kvantitativa och har kvalitetsgranskats utifrån Fribergs kriterier för analys av vetenskapliga studier. Litteraturstudien utgår från det teoretiska begreppet livskvalitet. Resultat: Resultatet utmynnade i tre teman; Aspekter som påverkar graden av fatigue, Fatigues negativa påverkan på livskvalitet samt Sätt att hantera fatigue. I det första temat framkom det att fatigue är föränderligt beroende på vilken cancerdiagnos samt cancerbehandling personer genomgår. Det framkom hur fatigue är ett multidimensionellt begrepp där flera andra symtom är relaterade till fatigue. Andra temat innefattar hur avsaknad av energi och social isolation påverkar personers livskvalitet negativt. Det tredje temat innefattar hur personer hittar individuella strategier för att hantera sin fatigue och att fysisk aktivitet är den strategi som visats sig ha mest positiv inverkan på att minska graden av fatigue. Diskussion: I resultatdiskussionen diskuteras begreppet livskvalitet som är den teoretiska utgångspunkten i examensarbetet. Livskvalitet berör både sjukdomsspecifika aspekter samt biverkningar av behandlingen som bidrar till ohälsa. Detta är tillämpbart eftersom fatigue upplevs som psykiskt, fysisk och socialt påfrestande. Livskvalitet är något föränderligt och förändras då personer får en svår sjukdomsdiagnos. Även sjuksköterskans arbete är viktigt i mötet med personer med fatigue då sjuksköterkan kan komma med förslag på strategier som kan göra fatigue mindre påfrestande. / Background: Each year, 55 000people in Sweden affected by cancer and is usually treated with combined treatments. The most common side effect and the most distressing symptom of cancer is fatigue. Fatigue means extreme tiredness/exhaustion and it’s a subjective experience. Fatigue is not tiredness that goes over after sleep or rest. Aim: The aim of this study is to describe what it's like to live with fatigue in cancer and cancer treatment. Methods: A systematic literature review based on 15 scientific articles. The articles are both qualitative and quantitative and quality reviewed for Friberg's criteria for analyzing scientific studies. The literature review is based on the theoretical concept of quality of life. Results: The analysis resulted in three themes: Aspects that affect the level of fatigue, Fatigues negative impact on quality of life and method for managing fatigue. In the first place it was found that fatigue is constantly changing depending on the diagnosis of cancer and cancer treatment that people receiving. It also reached the conclusion how fatigue is a multidimensional concept where several other symptoms are related to fatigue. The Second theme includes the lack of energy and social isolation affects people's quality of life negatively. The third theme involves how people find individual strategies to deal with their fatigue and physical activity is the strategy that proved to have the most positive impact on reducing the severity of fatigue. Discussions: The results discussed the concept of quality of life, the theoretical concept in the literature review. Quality of life concerns both disease-specific aspects and treatment side effects that contribute to ill health. This is applicable because fatigue is experienced as mental, physical and social discomfort. Quality of life is something changing and change as people get a severe disease diagnosis. Even the nurse's work is important when meeting people with fatigue when nurses can make suggestions on strategies that can make fatigue less strenuous.

Thesis (M.Sc.Eng.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Nanoparticle-based drug delivery has been explored to circumvent the often-toxic chemotherapy treatments used today by providing a more efficient and specific delivery to diseased tissues. Recently we have developed polymeric pH-responsive expansile nanoparticles (eNPs) for intracellular delivery of paclitaxel (Pax) as an improvement upon the traditional methods of delivery of Pax with using Cremophor/ethanol. As eNPs are internalized by the cell, the hydrophobic protecting groups found on side chains along the polymer backbone are hydrolyzed, leaving behind hydrophilic moieties that cause the eNPs to slowly swell with water. In this manner, the encapsulation and controlled release of a hydrophobic drug can be achieved. By altering the surface characteristics of the eNPs, one can change the behavior of the delivery vehicle as well as the biological response. To explore this approach, two surfactant strategies were employed. Specifically, the original sodium dodecyl sulfate (SDS) surfactant has been substituted with PEGylated surfactants (either lipids or poloxamer) to improve circulation and in vivo stability. In addition, these surfactants were functionalized to target the folate receptor (FR), which is overexpressed in several cancers, in order to increase cancer cell-specific localization and uptake. The resulting eNPs retained their swelling characteristics while demonstrating improved cellular uptake in folate receptor-expressing KB and MDA-MB-231 carcinoma cells with no change in uptake in A549 cells, which do not express the folate receptor. / 2031-01-01

University of Macau / Institute of Chinese Medical Sciences

A series of structurally related BODIPY dyes were synthesised and characterised. Their photophysical properties were studied in order to determine whether they would be suitable candidates for use as photosensitisers in the photodynamic therapy (PDT) treatment of cancer. The synthesis of two highly fluorescent BODIPY cores was achieved via the acid-catalysed condensation of a pyrrole and a functionalised aldehyde. In order to promote intersystem crossing, and hence improve the singlet oxygen generation of these dyes, bromine atoms were added at the 2,6-positions of the BODIPY core. These dibrominated analogues showed good singlet oxygen quantum yields, and excellent photostability in ethanol. In order to red-shift the main spectral bands of the BODIPY dyes towards the therapeutic window, vinyl/ styryl groups were introduced at the 3-, 5-, and 7-positions via a modified Knoevengal condensation reaction. The addition of vinyl/ styryl groups to the BODIPY core caused an increase in fluorescence quantum yield as well as a decrease in singlet oxygen quantum yield with respect to the dibrominated analogues. However, two of the red-shifted BODIPY dyes still showed moderate singlet oxygen quantum yields. The use of BODIPY dyes in nonlinear optics (NLO) was explored. The nonlinear optical characterisations and optical limiting properties of a series of 3,5-dithienylenevinylene BODIPY dyes were studied, both in dimethylformamide (DMF) solution and when embedded in poly(bisphenol A carbonate) (PBC) as thin films. The 3,5-dithienylenevinylene BODIPY dyes showed typical nonlinear absorption behaviour, with reverse saturable absorption (RSA) profiles, indicating that they have potential as optical limiters. The second-order hyperpolarizability (Y), and third-order nonlinear susceptibility (/m[/(3)]) values are also reported for these dyes. The optical limiting values of one of the BODIPY dyes in solution, and two of the BODIPY-embedded PBC films, were below the maximum threshold of 0.95 J-cm-2. The effect of addition of substituents on the electronic structure of the BODIPY dyes was investigated using TD-DFT calculations. The calculated trends closely followed those determined experimentally.

M.Sc. / The ideal cancer treatment modality should not only cause tumour regression and eradication but also induce a systemic antitumour response, which is essential for the control of metastatic tumours and long-term tumour resistance. Photodynamic Therapy (PDT) is a current approach in the treatment of various cancers. It involves the administration of a tumour-localizing photoreactive compound, which is activated at a specific wavelength of light. This therapy results in a sequence of photochemical and photobiological processes that cause irreversible photodamage to tumour tissues. Eradication is achieved by anti-tumour effects induced in the parenchyma and tumour vascular network. PDT can lead to a rapid cell death response in malignant cells, which has provided insight into the mechanisms behind photokilling. Oesophageal cancer is the seventh leading cause of cancer death worldwide, and in South Africa remains a problem of epidemic proportions affecting predominantly black males. The appearance of a number of new photosensitizers being developed will not only extend the number of choices for treating specific cancers, but also aid in the effective destruction of various tumour tissues. PDT has been an experimental clinical modality for the past two xii decades and has been shown to be successful for the treatment of advanced oesophageal cancer where other options have failed. The full potential of PDT as a treatment modality has not been clearly evaluated, which is one of the objectives of this study. Overall, PDT has the potential of being a promising therapeutic option in the effective treatment of oesophageal cancer, and through this study and the elucidation of the mechanisms of PDT action, it will provide a better future for those suffering from oesophageal cancer. A new photosensitizer known as Zinc Sulphophthalo-cyanine (ZnPcSmix) was studied on an oesophageal SNO cancer cell line in order to determine treatment-induced cell viability, cytotoxicity and the pathway followed to cell death. The major observations of this study revealed that PDT using ZnPcSmix resulted in a decrease in cell viability and proliferation, resulting in a cytotoxic response experienced by the cell. The outcome of this study revealed that the SNO cells experience a necrotic mode of cell death after using ZnPcSmix to induce photodamage. This was examined by light microscopy and confirmed by the lack of DNA fragmentation and decreased caspase-3 and caspase-7 expression levels. Hsp70 levels decreased resulting in lowered cytokine TNF-α release from necrotic cells. Hoechst nuclear staining revealed a disorganized nuclear pattern characteristic of necrotic release of cellular contents. The major findings of this study revealed the efficacy of ZnPcSmix as a new photosensitizing drug used during PDT to treat oesophageal cancer resulting in a decrease in cell viability and proliferation. Necrosis was the primary mechanism by which cells pursued death, which was dependent on the photosensitizer dose, cell type and irradiation fluence. ZnPcSmix–induced photodamage seen during PDT offers a new treatment option for patients suffering from oesophageal cancer and shows great promise in effectively treating early-stage oesophageal cancer.

No description available.

Magister Artium - MA / Breast cancer is a common cause of death among women worldwide. It has long been recognized as a major public health burden in high-income countries, however, the majority of cases are said to occur in low and middle-income countries, such as in South Africa. A breast cancer diagnosis and treatment heralds a series of frightening events and can be a traumatic experience. The manner in which women perceive and cope with their illness is predictive of emotional and physical health outcomes. It is thus imperative to explore the experiences of South African women, whose voices may have been silenced in the past. The purpose of my study was to explore the subjective lived experiences of women with early stage breast cancer undergoing treatment. The objectives of the study were to; explore the emotional experiences of women with early stage breast cancer undergoing treatment and secondly to explore how women perceive their bodies through their experience of early stage breast cancer while undergoing treatment. Phenomenology was used as the theoretical position conceptualising the study as well as the research design. This research study adopted a qualitative approach utilising in-depth face to face semi-structures interviews for collecting data. The participants were selected through purposive sampling and comprised six women aged between 30 and 40 who are undergoing treatment for early stage breast cancer. The data was analysed using interpretative phenomenological analysis. Emotions experienced were characterised by the shock of the diagnosis due to factors such as lack of family history and age. Participants reported positive changes and viewpoints which they gained through their breast cancer journey. Emotions were heightened during treatment due to the physical change experienced and the effects this had on family members and the general public. Furthermore, results indicated that participants, even though they discovered a new found love for life and for their wellbeing, neglected their emotional needs in order to protect family members. An additional reason for this neglect centered on the lack of understanding other individuals may have regarding the experiences of participants. Recommendations involves the encouragement of accessing counselling services and that interventions tailored to the needs of each patient especially according to age. All ethical considerations as stipulated by the University of the Western Cape were adhered to.