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Tumor targeting with a ⁹⁹̳mTcMAG-3 labeled molecular engineSlauson, Marjorie E. 08 February 2006 (has links)
A unique tumor targeted method, which may be able to deliver a molecule to the
surface of a tumor cell using the pH gradient between hypoxic tumor cells and
normal tissue has recently been developed. Since solid tumors have been found to
have a lower extra cellular pH compared to normal tissue (6.5 to 6.9 for tumors
verses an average 7.4 for normal tissue), the pH gradient is used as a source of
power to activate a strategically designed "molecular engine" capable of delivering
a diagnostic or therapeutic agent to tumor cells. To test this hypothesis, a 22-
sequence amino acid, which reorganizes to alpha helical form at pH 6.9 causing
the molecule to become lipophilic and embed into the plasma membrane of nearby
cells was synthesized. The molecule was then attached to 99mTc via a MAG-3
chelating molecule. In-vivo nuclear imaging was performed and showed apparent
significant uptake in primary tumors as well as lung and liver in Lewis lung cell
model C57blk-J6 mice with confirmed primary tumors at the base of the tail or
lungs. This study shows significant promise for early diagnosis and treatment of
cancer on a molecular level. / Graduation date: 2006
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Gastric lymphoma of MALT type: the etiologic factors and the molecular basis of pathogenesis徐維勝, Xu, Wei-sheng. January 1998 (has links)
published_or_final_version / Pathology / Doctoral / Doctor of Philosophy
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Study of the role of DNA methylation and PIK3CA mutations in human breast cancerLi, Shao Ying January 2006 (has links)
[Truncated abstract] Introduction: Breast cancer is a heterogeneous disease, resulting in very different outcomes for women with apparently similar tumour characteristics. In order for patients to have optimal treatment, a better understanding of the molecular nature of their disease is required. Aims: The aims of this thesis were: 1) To determine whether methylation of RARβ2, ER, CDH1, BRCA1, CCND2, p16 and TWIST genes are associated with phenotypic features of breast cancer and the prognostic significance of methylation of these genes. 2) To investigate for possible associations between the frequency of methylation at RARβ2, CDH1, ER, BRCA1, CCND2, p16 and TWIST genes and the presence of germ-line variants in the TS, MTHFR, MS, CBS, MTHFD1 and DNMT3B genes, as well as for possible correlations between these polymorphisms and clincopathological features of breast cancer including patient outcome. 3) To determine whether PIK3CA mutations determined clinical phenotype and the prognostic significance of PIK3CA mutations in a large and well characterized cohort of breast cancer patients. Methods: A large and well characterized series of primary breast tumours were selected for methylation of RARβ2, ER, CDH1, BRCA1, CCND2, p16 and TWIST genes using MSP, and for polymorphisms in TS, MTHFR, MS, CBS, MTHFD1 and DNMT3B genes using PCR, PCR-RFLP and PCR-SSCP. Mutations to PIK3CA were detected using F-SSCP. Results and Conclusions: Methylation frequencies ranged from 11% for CCND2 to 84% for ER. More frequent hypermethylation was observed in tumours with poor histological differentiation compared to those with well/moderate differentiation, as well as trends for association with larger tumour size and mutant TP53. Tumours with ER and CDH1 methylation were associated with significantly lower hormone receptor levels, younger age at diagnosis and the presence of mutant p53. TWIST methylation is firstly reported to be associated with significantly older patient age at diagnosis and larger tumour size. Our data suggests that gene methylation may be linked to various pathological features of breast cancer. However, there appears to be little support for a distinctive CpG island methylator phenotype in breast cancer.
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