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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Design and cancer-targeting potential of antibody-based molecules directed against carcinoembryonic antigen

Huhalov, Alexandra January 2004 (has links)
This thesis examines the use of protein engineering to create antibody-based molecules for cancer treatment. The targeting unit used for these molecules was the single chain Fv antibody fragment MFE-23, which is directed against the tumour-associated marker carcinoembryonic antigen (CEA). It was hypothesised that implementation of molecular design features such as humanisation, high affinity, multivalency and mannose glycosylation to accelerate systemic clearance would result in the favourable in vivo performance of the molecules. Bioinformatic and recombinant approaches were applied to test this hypothesis. First the molecular interaction between the MFE-23 and its cognate antigen, CEA, was investigated. A recombinant form of the N-terminal N-A1 domain pair of CEA was expressed in bacteria and its specific interaction with MFE-23 was confirmed. Mass spectrometry in combination with proteolysis of the MFE-23/ CEA (N-Al) complex was used to obtain detailed sequence information on the putative region where MFE-23 binds to CEA, supporting structural predictions and the future design of MFE-23-based molecules. A series of divalent MFE-based molecules were then created. These were genetically linked by polypeptide chains or human serum albumin (HSA). A humanised, high affinity version of MFE-23 (M10b) was also investigated as part of the molecular design. In vivo studies demonstrated that the M10b-HSA assemblies, termed HSAbodies, specifically localised to tumour cells whilst clearing rapidly from normal tissues, resulting in improved tumour: tissue ratios compared to an anti-CEA IgG and higher overall uptake in tumour compared to monovalent MFE-23. Glycosylation sites were engineered into the HSA linker, which resulted in accelerated systemic clearance, further improving tumour: tissue ratios. The combination of functional affinity and controllable clearance resulted in a superior CEA-targeting molecule. These results support the proposed hypothesis and suggest a clear therapeutic and diagnostic potential for HSAbodies in both native and glycosylated form.
2

Competing risks methodology applied to the analysis of cancer therapy outcome

Ataman, Ozlem January 2003 (has links)
No description available.
3

Non-pharmacological interventions in the management of chronic pain associated with breast cancer treatment

Robb, Karen Anne January 2003 (has links)
No description available.
4

The uptake of post-surgical treatment in cancer patients

Simmons, Kingsley Lorraine January 2005 (has links)
No description available.
5

A randomised controlled trial to evaluate the effectiveness of a brief psychoeducational intervention in reducing the level of, and distress associated with, cancer-related fatigue

Armes, Patricia Joanne January 2005 (has links)
No description available.
6

The biological and cytotoxic effects of a genetically modified herpes simplex virus 1 and its potential application in clinical oncology

Hu, Jennifer Cho Chun January 2006 (has links)
No description available.
7

Production and study of polysialylated antibodies for improved cancer therapy

Constantinou, Antony January 2006 (has links)
No description available.
8

Magnetic resonance guided tumour ablation

Dick, Elizabeth Ann January 2003 (has links)
No description available.
9

Tumour-selective depletion of thymidine and activity of raltitrexed

Graham, Claire L. January 2004 (has links)
No description available.
10

Naturally occurring attentional strategies in the self-management of cancer pain

Buck, Rhiannon January 2004 (has links)
No description available.

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