Adolescence is the period of physical and emotional development from childhood to adulthood. As an adolescent develops they struggle with many issues including developing independence from their parents, embracing peer culture, an increase in the importance of body image and the development of sexual, vocational, and moral identity. The diagnosis and treatment for cancer can interfere with the adolescent meeting these goals, and subsequently cause the experience of adolescence to be more difficult. The aim of this study was to identify how adolescents with cancer cope with their situation. The objectives were to determine the resources adolescents utilise to cope with their experience, and the coping strategies adolescents use to cope with their experience. A thorough literature review identified that there had previously been only limited research with adolescents with cancer. In particular there had been very few qualitative studies investigating the specific coping strategies used by adolescents with cancer, with no such research being undertaken in Queensland. This study was conducted under the epistemological stance of constructionism. Meaning was constructed for this study of adolescents with cancer through the use of grounded theory methods, and secondary analysis of data. Interviews were collected by the researcher for a project at the Royal Children’s Hospital. Using grounded theory methods, seven of the interviews were analysed. In the process of developing a central category, Schatzman's Dimensional Matrix was used to assign codes into context, processes, consequences, and conditions, under the central category of “conquering the cancer experience”. The experience of diagnosis and treatment for cancer was difficult for these adolescents, however they ultimately coped and became stronger as a result of their experience. The key findings of this study identified that adolescents were able to cope with their experience. These finding were discussed in relation to factors which enhanced their coping, factors which influenced their ability to cope and how the experience changed the adolescent. Recommendations were also made with the aim of improving the experience of adolescents undergoing treatment for cancer in Queensland. Through the implementation of the recommendations of this study, hopefully the journey of adolescents with cancer can be made easier.

Older people represent an increasing proportion of new cancer diagnoses yet little is known about their experiences with cancer or their knowledge about risk factors, benefits of lifestyle modification to decrease risk or participation in early detection programs. Two studies were conducted, the first to document a lived experience with a new cancer diagnosis and the second to test for relationships between knowledge and attitude to cancer and self-reported participation in screening for breast, prostate and colorectal cancers. / http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1297244 / Thesis (D.Nurs.) -- School of Population Health and Clinical Practice, 2007

University of Macau / Institute of Chinese Medical Sciences

Lateral diffusion of membrane components (lipids and proteins) is an important membrane property to measure since the essential process of absorption of anti-cancer and other drugs -some of which are not soluble in lipids and therefore would not be able to penetrate the cell membrane through passive diffusion- lies on it. In particular, the procedure of diffusion into the cell cytoplasm is reliant on free volumes in the membrane (passive diffusion) as well as carrier proteins (facilitated diffusion). By enhancing the mobility of lipids and/or proteins, the possibility of the carrier protein to "encapsulate" pharmacological components maxim- izes, as a "scanning" of the proteins gets performed due to the fluid phase of a biological membrane. At the same time, the increased mobility of the lipids facilitates the passage of lipid-soluble molecules into the cell. Thus, given that the success of anticancer treatments heavily depends on their absorption by the cell, a significant enhancement of the cell mem- brane permeability (permeabilisation) is rendered vital to the applicability of the technique. For this reason, there is augmented interest in combined methods such as Nanotechnology based drug delivery that is focused on the development of optimally designed therapeutic agents along with the application of shock waves to enhance the membrane permeability to the agents. This study examines the impact of shock waves on a numerical model of a biological membrane. Cont/d.

No description available.

Gold nanoparticles strongly absorb and scatter visible and near infrared light because of the strongly enhanced electric fields at the surface. This provides the potential of designing novel optically active reagents for simultaneous molecular imaging and photothermal cancer therapy. In this thesis, gold nanospheres and nanorods conjugated with anti-epidermal growth factor receptor (anti-EGFR) antibodies that specifically target EGFR on the cell surface are shown to be used for dual diagnostics and therapy. Using micro-absorption spectroscopy and light scattering imaging, cancerous (HOC 313 and HSC 3) and noncancerous cells (HaCat) can be differentiated due to the overexpression of EGFR on the surface of cancer cells. By irradiating the cells with a CW laser, selective photothermal cancer therapy is realized in visible region by using gold nanospheres and in near infrared region by using gold nanorods. The use of nanorods allow for in vivo therapy due to the fact that their absorption is in the near infrared region at which the laser light meets less interference from the tissue absorption. In addition, the catalytic effect of gold nanoparticles on the oxidization of NADH to NAD+ is investigated. The addition of gold nanoparticles is found to quench the NADH fluorescence intensities but has no effect on the fluorescence lifetime. This suggests that the fluorescence quenching is not due to coupling with the excited state, but due to changing the ground state of NADH. The intensity of the 340 nm absorption band of NADH is found to decrease while that of the 260 nm band of NAD+ is found to increase as the concentration of gold nanoparticles increase. This conversion reaction is further supported by nuclear magnetic resonance and mass spectroscopy. The linear relationship between the initial reaction rate of NADH and the concentration of gold nanoparticles strongly supports that NADH is surface catalyzed by the gold nanoparticles. The catalytic property of this important reaction might have important future applications in biological and medical fields.

Thesis (M. Pharm. (Pharmacy Practice)--North-West University, Potchefstroom Campus, 2009.

Insensitivity to chemotherapy is an ongoing issue in cancer treatment, one that appears to be highly dependent on patient-specific variations. It has been shown clinically that while a subset of patients will successfully respond to a particular chemotherapeutic regimen, there exists another subset of patients who when exposed to the same course of therapy will remain resistant to treatment or exhibit signs of relapse after treatment has been administered. This discrepancy raises interesting questions regarding the role that patient-specific variations play in controlling the efficacy of chemotherapy treatment regimens. Doxorubicin (Dox) is a common chemotherapeutic agent used in the treatment of a variety of solid tumors and leukemias and resistance to Dox treatment is a major issue in cancer chemotherapy, oftentimes leading to patient relapse. To gain a deeper understanding of the processes that influence Dox resistance, we must first understand the mechanisms that underlie and contribute to Dox's toxicity. To this end, the metabolic reactions that activate Dox have been implicated as major determinants of Dox cytoxicity and as possible factors that control Dox resistance in cancer cells. There are several lines of evidence that redox-dependent metabolism plays a large role in Dox toxicity. The Dox bioactivation network is comprised of a system of reduction/oxidation (redox) reactions that lead to the formation of toxic Dox metabolites and reactive oxygen species (ROS). Moreover, multi-drug resistant acute lymphoblastic leukemia cells derived from relapsed patients have elevated levels of the antioxidant glutathione and show insensitivity to Dox treatment. The redox dependence of Dox bioactivation, the understanding that Dox treatment generates ROS, and the evidence that Dox resistant cells exhibit increased antioxidant capacity, suggest the possibility that redox pathways modulate the efficacy of Dox treatment in cancer cells. The overall objectives of the proposed dissertation, therefore, were to investigate how the redox properties of the Dox bioactivation network influence Dox toxicity in acute lymphoblastic leukemia cells, and to provide evidence that cell-specific variations in the intracellular levels of these redox components influences the degree to which Dox treatment will induce cancer cell death. The significant findings of this study are that the redox reactions involved in Dox metabolism are dual-natured, containing a toxicity-generating module characterized by nicotinamide adenine dinucleotide phosphate (NADPH)-dependent Dox reductive conversion, as well as an ROS signal-generating module characterized by NADPH- and oxygen-dependent Dox redox cycling. The balance between the coupled redox reactions that comprise the toxicity- and ROS signal-generating modules of Dox bioactivation determines the sensitivity-phenotype of leukemia cells and phenotypic changes in the Dox-sensitivity of leukemia cells can be induced by the successful modulation of the Dox bioactivation network through the pharmacological inhibition of NADPH in a concentration- and cell type-dependent manner. This study highlights the importance of the intracellular redox network in controlling chemotherapy-induced ROS. The unequal distribution in antioxidant burden across the various intracellular antioxidant enzymes suggests a significant role for NADPH supply, as controlled by the enzyme glucose-6-phosphate dehydrogenase (G6PD), to the intracellular ROS buffering capacity of cells during instances of oxidative stress. Changes in G6PD activity were shown to promote protein-S-glutathionylation during oxidative stress conditions, thereby implicating G6PD in the modulation of redox-sensitive signal transduction pathways. The intracellular glutathione redox balance, a measure of the intracellular redox environment, can effectively regulate Dox-induced NF-κB signal transduction in leukemia cells. The systematic modulation of intracellular glutathione redox balance in leukemia cells by N-acetylcysteine (NAC) revealed an important role for protein S-glutathionylation mechanisms in the control of NF-κB signal transduction induced by Dox treatment. These findings identify the glutathione redox network as a potential therapeutic target for the systematic modulation of Dox sensitivity in cancer cells and elucidate the complex role that antioxidants such as NAC can play in modulating the effectiveness of Dox chemotherapy treatment regimens. Lastly, this study highlights the need for and the capacity of computational models to accurately describe the complex redox-reactions that contribute to Dox metabolism in leukemia cells. This study is groundbreaking in its use of computational modeling to analyze reversible electron transfer events between proteins using mass-action kinetics. The models developed in this study can accurately explain cytosolic doxorubicin bioactivation, intracellular hydrogen peroxide clearance, and kinase-specific S-glutathionylation, thereby showing that the use of comprehensive and/or relatively simple computational models can provide semi-quantitative predictions about the behavior of redox systems in mammalian cells as they relate to Dox-induced toxicity and Dox-induced cell signaling.

The overproduction of reactive oxygen species (ROS) have been linked to diseases and other pathologies. As therapeutic agents, antioxidants have been tested and some shown to attenuate these diseases by relieving oxidative stress. The May laboratory has previously developed a family of phenylaminoalkyl selenides and has demonstrated the antihypertensive and antioxidant properties of these compounds. To further understand the antioxidant property of these selenide compounds, the two step mechanism of the reaction between the selenoxide form and glutathione was investigated by stopped-flow and mass spectrometry, leading to the detection and characterization of a novel thioselenurane intermediate. Mass spectrometry studies supported the redox cycle of the selenide compounds as a straightforward cycle with no byproducts or side reactions and was the first evidence reported of a thioselenurane intermediate present in a reduction reaction of a selenoxide. The therapeutic potential of these compounds was further supported by cell and histological studies demonstrating their ability to alleviate the cardiotoxic effect of anthracyclines without affecting the anti-cancer property of the drugs. Codosage of a phenylaminoethyl selenide with Doxorubicin decreased the infiltration of inflammation cells in the myocardium of mice. Phenylaminoethyl selenides were also able to maintain the body weight of mice treated with Doxorubicin, compared to mice treated with Doxorubicin alone. In order to make the possibility of using Phenylaminoalkyl selenides as therapeutic agents or supplements with other agents, delivery of the compounds was investigated. N acetyl phenylaminoethyl selenides were successfully encapsulated into poly(lactic-co-glycolic) (PLGA) nanoparticles using the nanoprecipitation technique. An attempt was made to demonstrate the ability of these selenide- nanoparticles to reduce cellular oxidative stress caused by incubation with LPS. Future studies are needed to optimize the loading of the selenide compounds into nanocarriers and to demonstrate the ability of the encapsulated drug to work as the free drug. The long term goal of this research is to fully understand the potential of phenylaminoalkyl selenides as an efficient therapeutic agent for ailments derived from increased levels of ROS and a state of oxidative stress. As a supplemental project funded by the National Science Foundation, the Center for Innovative Biomaterial Education and Research (CIBER) was created. Enzymatically catalyzed reaction and polymerizations were investigated using Candida antarctica Lipase B (CALB). Several CALB catalyzed Michael addition reactions were successful and yielded compounds that could be used as future reactants and monomers. As an education requirement of the project a website was created in order to educate the public of the importance, sources and uses of biomaterials. The website provides information for all levels of students and educators. This center has allowed The Georgia Institute of Technology to form relationships and exchange programs with leading universities around the world allowing the exchange of knowledge and research in biomaterials.

Photothermal cancer therapy is a potential alternative to surgery and involves selective tissue destruction using thermal energy. Targeted photoabsorbers, used in conjunction with matching a continuous wave laser, make photothermal therapy both noninvasive and tumor-specific. However, to become clinically relevant, there is a need to develop an imaging technique to identify tissue composition and to detect the presence of photoabsorbers in the tumor volume before therapy; to monitor the temperature rise during therapy; and to assess the tumor damage after therapy. In this study, a combined ultrasound and photoacoustic imaging system was designed to assist photothermal therapy. The imaging system was tested on tissue mimicking phantoms, ex-vivo porcine tissue samples, ex-vivo mice and in-vivo mice. First, ultrasound imaging was utilized to differentiate between water-based and lipidbearing tissue. A combined ultrasound and photoacoustic imaging system was then assembled to identify the presence and spatial location of gold nanoparticles. Multiwavelength photoacoustic imaging was used to further confirm the presence of nanoparticles. Temperature monitoring algorithms, using both temperature-dependent time shifts in ultrasound signals and amplitude changes in photoacoustic signals, were developed. Finally, photothermal therapy was carried out on tumor-bearing nude mice using in-vivo ultrasound and photoacoustic imaging to identify the tumor boundary, detect the nanoparticles and monitor the temperature elevation. The results of the studies show that ultrasound and photoacoustic imaging provide complementary and clinically relevant information. Overall, there is potential of using the ultrasound and photoacoustic imaging system to plan, guide and monitor photothermal therapy. / text