عنوان

Pharmacological evaluation of the inhibition of polysialyltransferases as a therapeutic strategy in cancer :

شماره

TLets577878

عنوان اصلي

Pharmacological evaluation of the inhibition of polysialyltransferases as a therapeutic strategy in cancer :

نام عام مواد

[Thesis]

نام نخستين پديدآور

Al-Saraireh, Y. M. J.

عنوان اصلي به قلم نويسنده ديگر

characterisation of models for evaluating polysialic acid as a potential therapeutic target and pharmacological assessment of novel polysialyltransferase inhibitors

نام ساير پديدآوران

Shnyder, Steven D.; Falconer, Robert A.

نام ناشر، پخش کننده و غيره

University of Bradford

تاریخ نشرو بخش و غیره

2012

جزئيات پايان نامه و نوع درجه آن

Thesis (Ph.D.)

امتياز متن

2012

متن يادداشت

Neuroblastoma is a highly metastatic and invasive tumour with poor prognosis. Despite recent advances in the treatment of neuroblastoma, mortality is still high due to uncontrolled metastatic disease, and novel therapeutic approaches for the treatment of neuroblastoma are therefore desperately needed. A potential novel approach for therapy of neuroblastoma relates to the polysialic acid decoration of the neural cell adhesion molecule (PSANCAM). PSA-NCAM is selectively re-expressed in a number of tumours including neuroblastoma, where it is thought to modulate tumour dissemination. Expression is strongly associated with poor clinical prognosis and an aggressive tumour phenotype. Inhibition of the enzymes responsible for synthesis of PSA, the polysialyltransferases (polySTs) presents a novel and selective therapeutic opportunity. The aims of the studies described in this thesis are to evaluate PSANCAM expression and function in neuroblastoma, and to develop and utilise cell-based models to pharmacologically investigate novel polyST inhibitors. PSA-NCAM was seen to be highly expressed in neuroblastoma clinical specimens and associated with phenotypes of tumour aggressiveness. A screening panel consisting of cell lines with a range of PSA-NCAM expression types was established and utilised to develop assays for pharmacologically assessing novel polyST inhibitors. Using cytidine monophosphate (CMP), a naturally-occurring inhibitor of polySTs, the robustness of the assays was confirmed before progression to evaluate novel molecules. From 16 compounds identified in an in vitro screen of polyST inhibition, three promising polyST inhibitors were identified. These promising polyST inhibitors modulated PSA-NCAM expression on the tumour cell surface and led to a significant reduction in cell migration. Therefore the work presented in this thesis suggests that targeting polySTs is a promising novel therapeutic strategy for neuroblastoma and further research in this area is warranted.

موضوع مستند نشده

Pharmacological models ; Chemotherapy ; Neuroblastoma ; Cancer ; Polysialyltransferases ; ; Neural cell adhesion molecule ; Polysialic acid ; Therapeutic strategy

مستند نام اشخاص تاييد نشده

Al-Saraireh, Y. M. J.

مستند نام اشخاص تاييد نشده

Shnyder, Steven D.; Falconer, Robert A.

مستند نام تنالگان تاييد نشده

University of Bradford

نام الکترونيکي

فرمت انتشار

p

نوع ماده

[Thesis]

کد کاربرگه

276903

سطح دسترسي

a

تكميل شده

Y