Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 90-109).

<p>Targeted radionuclide therapy (TRT) holds great promise for the treatment of cancer. In TRT, radioactive nuclides are delivered specifically to tumours by molecules that recognise and bind to structures overexpressed by, or specific to, cancer cells. Human epidermal growth factor receptor like protein 2 (HER-2) is an oncogene product overexpressed in e.g. urological, breast, or ovarian cancers that have been correlated to poor prognosis and resistance to hormonal therapy. There is also evidence that tumour cells retain their HER-2 overexpression in metastases.</p><p>Trastuzumab and pertuzumab are two humanised monoclonal antibodies targeting different parts of HER-2. This thesis describes the radiolabelling of these antibodies for use in TRT and diagnostics. The thesis also investigates possible methods for modifying uptake and retention of radioactivity delivered with antibodies binding to HER-2. Modification of the cellular retention of ¹²⁵I by using polyhedral boron anion based linker molecules (DABI and NBI) is investigated, and it is shown that linking ¹²⁵I to trastuzumab using DABI increases cellular accumulation of radioactivity by 33%. It is also shown that trastuzumab can be efficiently coupled to the positron emitter ⁷⁶Br by using NBI. Furthermore, it is shown that cellular uptake of ¹²⁵I can be modified by stimulating EGFR (HER-1) with EGF.</p><p>When labelled with the alpha emitter ²¹¹At, trastuzumab could specifically kill cells in vitro. This cell killing effect could be prevented by saturating the receptors of the target cells with non-radiolabelled trastuzumab.</p><p>Pertuzumab was radiolabelled with the low energy beta emitter ¹⁷⁷Lu without losing affinity or immunocompetence. [¹⁷⁷Lu]pertuzumab was specific to HER-2 in vitro and in vivo. This targeting conjugate was shown to increase median time to tumour progression in mice bearing xenografts of the radioresistant SKOV-3 cell line. </p><p>In conclusion, antibodies against HER-2, especially pertuzumab radiolabelled with ¹⁷⁷Lu, show promise as TRT agents.</p>

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 89-103).

BACKGROUND: Organ transplantation is one of the best modalities for treating fatal organ failure. Despite the success of this procedure, an increasing incidence of cancer in this population has drawn the attention of public health officials in recent years. OBJECTIVES: The overall objective of this study is to conduct a detailed examination of adverse health outcomes among Canadian organ transplant recipients, with an emphasis on cancer incidence and mortality. METHODS: This project employed a retrospective cohort follow-up study design, whereby Canadian Organ Replacement Registry records were linked to the Canadian Mortality Database and the Canadian Cancer Registry Database. The study population consisted of more than 16,000 solid organ transplant recipients registered between January 1, 1981 and December 31, 1998. This study was designed to assess the risks of developing cancer, overall and site-specific, in transplant recipients in comparison to the general Canadian population using Standardized Incidence Ratios (SIR), Standardized Mortality Ratios (SMR), and Proportionate Mortality Ratios (PMR). In addition, Cox and logistic models were used to assess the effects of various risk factors on cancer incidence and mortality in transplant sub-populations, while cumulative incidence was used to study the patient survival pattern. Lastly, Population Attributable Risk (PAR) was used to quantify the impact of organ transplantation on cancer incidence and mortality. RESULTS: Among major causes of death, the highest PMRs are due to genitourinary diseases, followed by endocrine, nutritional and metabolic diseases, and infectious diseases. SIRs indicate that cancer incidence and mortality were relatively lower than that observed for other major causes of death, and slightly higher than that observed in the general Canadian population. Lastly, logistic regression results indicate that age, year of surgery, and smoking status were significant risk factors in mortality due to all causes, while the Cox regression model shows that age, sex and year of surgery were significant risk factors for cancer incidence. Overall, the PAR in this cohort was very minimal, indicating that the risk in mortality and cancer incidence due to organ transplantation is negligible. CONCLUSION: Life threatening diseases such as those of the genitourinary system, as well as endocrine, nutritional and metabolic diseases and infectious diseases are leading causes of death. Future research should be directed at ways of reducing incidence and subsequent mortality due to these causes.

Syfte: Syftet med litteraturstudien var att beskriva allmänsjuksköterskans palliativa omvårdnadsarbete med cancersjuka patienter. Metod: Deskriptiv litteraturstudie baserad på 15 artiklar som sökts i databaserna PubMed och Cinahl. Analysen identifierade fyra huvudkategorier som ligger till grund för resultatet. Huvudresultat: Att arbeta med palliativ vård är ett arbete som sjuksköterskor anser påverkar patienter inom flera olika aspekter, både fysiskt, psykiskt, socialt och andligt. Ett sätt som sjuksköterskan kan hjälpa patienten är att informera och utbilda patienter vilket har visat ge en viss lindring hos patientens symtom. Sjuksköterskan har även en viktig roll i att koordinera omvårdnadsarbetet och framförallt se till att patienten har det så bra som omständigheterna tillåter. Stöd av erfarna kollegor ansågs vara ett bra hjälpmedel och sambandet mellan erfarenhet och trygghet i yrkesrollen bidrog till en trygghet som förs vidare till patienten. Slutsats: De viktigaste perspektiven som framkom inom palliativ vård var fysiskt, psykiskt och socialt. Det andliga perspektivet skiljer sig dock från olika kulturer och behöver studeras mer i Sverige för att kunna tillämpa riktlinjer och arbetssätt. Det framkom även att utbildning behövs för att känna sig trygg i sin arbetsroll när sjuksköterskor arbetar med döende människor som vårdas palliativt. / Aim: The aim of this study was describe nurses’ palliative care with patients who suffer from cancer. Method: Descriptive study based on 15 articles sought in the databases PubMed and Cinahl. The analysis identified four main categories underpinning for the results. Main result: Working with palliative care is a task that nurses believe affects patients in various aspects, physically, mentally, socially and spiritually. One way that the nurse can help the patients is to inform and educate them, which has been shown to give some relief of the patient's symptoms. The nurse also has an important role in coordinating nursing care and, above all, to ensure that the patient is as comfortable as circumstances permit. The support of experienced colleagues was considered a great tool and the relationship between experience and confidence in the professional role led to a security that is passed on to the patient. Conclusion: Within palliative care it is revealed that the strongest perspectives were physically, mentally and socially. The spiritual perspective differs from different cultures and needs to be studied more in Sweden to be able to apply guidelines and procedures. It also emerged that education is needed to feel secure in the role as a nurse when working with dying people who are cared for palliative

BACKGROUND: Organ transplantation is one of the best modalities for treating fatal organ failure. Despite the success of this procedure, an increasing incidence of cancer in this population has drawn the attention of public health officials in recent years. OBJECTIVES: The overall objective of this study is to conduct a detailed examination of adverse health outcomes among Canadian organ transplant recipients, with an emphasis on cancer incidence and mortality. METHODS: This project employed a retrospective cohort follow-up study design, whereby Canadian Organ Replacement Registry records were linked to the Canadian Mortality Database and the Canadian Cancer Registry Database. The study population consisted of more than 16,000 solid organ transplant recipients registered between January 1, 1981 and December 31, 1998. This study was designed to assess the risks of developing cancer, overall and site-specific, in transplant recipients in comparison to the general Canadian population using Standardized Incidence Ratios (SIR), Standardized Mortality Ratios (SMR), and Proportionate Mortality Ratios (PMR). In addition, Cox and logistic models were used to assess the effects of various risk factors on cancer incidence and mortality in transplant sub-populations, while cumulative incidence was used to study the patient survival pattern. Lastly, Population Attributable Risk (PAR) was used to quantify the impact of organ transplantation on cancer incidence and mortality. RESULTS: Among major causes of death, the highest PMRs are due to genitourinary diseases, followed by endocrine, nutritional and metabolic diseases, and infectious diseases. SIRs indicate that cancer incidence and mortality were relatively lower than that observed for other major causes of death, and slightly higher than that observed in the general Canadian population. Lastly, logistic regression results indicate that age, year of surgery, and smoking status were significant risk factors in mortality due to all causes, while the Cox regression model shows that age, sex and year of surgery were significant risk factors for cancer incidence. Overall, the PAR in this cohort was very minimal, indicating that the risk in mortality and cancer incidence due to organ transplantation is negligible. CONCLUSION: Life threatening diseases such as those of the genitourinary system, as well as endocrine, nutritional and metabolic diseases and infectious diseases are leading causes of death. Future research should be directed at ways of reducing incidence and subsequent mortality due to these causes.

As pediatric brain tumor survival rates increase, research has begun to further explore the influence of brain tumors and their treatment on functioning. The current study explored the ability of attention, learning, and memory abilities as measured by the Rey Auditory Verbal Learning Test and receptive language abilities as measured by the Peabody Picture Vocabulary Test to predict adaptive functioning on the Vineland Adaptive Behavior Scales. Children with tumors of the cerebellar region were hypothesized to display relative impairments in attention, whereas children with tumors of the third ventricle region were hypothesized to display relative impairments in learning and memory. The cognitive measures also were hypothesized to be differentially predictive of adaptive functioning performance. No significant differences were found between the groups on cognitive performance, but attention was the best predictor of adaptive functioning in the cerebellar group, whereas receptive verbal knowledge was the best predictor for the third ventricle group.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 97-114).

Thesis (Ph.D.)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Pharmaceutics. Title from title-page of electronic thesis. Bibliography: leaves 289-311.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 80-96).