Title:

Molecular factors modulating expression of MET rhabdomyosarcoma

Author:

Dulęba, Marcin

Subject:

MET ; HGF ; RMS ; methylation ; rhabdomyosarcoma

Abstract:

Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas diagnosed in children. It represents approximately 5% of all malignant tumors occurring in children and adolescents. Basing on clinical features and molecular biology, three subtypes of RMS can be identified: embryonal, alveolar and pleomorphic. Treatment of RMS includes surgery, chemo- and radiotherapy. The probability of successful therapy in early detected cases, patients with ERMS with no metastatic tumors detected, is estimated to be approximately 60%. This percentage dramatically decreases in case of relapse, which occurs mostly in 3 years from diagnosis. In patients with recurrent disease, only 20% are likely to overcome disease, in others the prognosis is very unfavorable with survival up to five years.The aim of this study was to investigate the MET promoter sequence, epigenetic profile and the impact of external molecular factors on expression of this receptor in RMS cells. Also the effect of stress and cellular differentiation on the transcription, surface expression level and gene promoter methylation profile of MET was investigated. Results revealed the presence of polymorphisms in the studied cells that may be associated with impaired differentiation of these lines. Epigenetic profile of MET promoter demonstrated vulnerability to influence of external factors, especially radiation and hypoxia. O ; btained results appear to be interesting from the clinical point of view. Improving the effectiveness of current therapies as well as the perspective of developing new therapies and diagnostic methods, with use of gained experience seem to be possible.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

onkologia

Degree grantor:

Wydział Lekarski

Promoter:

Majka, Marcin

Date:

2012

Date issued:

2012

Type:

Praca doktorska

Call number:

ZB-117823

Language:

pol

Access rights:

nieograniczony

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