SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Baker J)
 

Sökning: WFRF:(Baker J) > Doktorsavhandling > From Genes to Thera...

From Genes to Therapy : Modeling and Novel Therapeutic Strategies for Brain Tumors

Čančer, Matko, 1989- (författare)
Uppsala universitet,Neuroonkologi,Fredrik Swartling
Swartling, Fredrik, Associate professor (preses)
Uppsala universitet,Institutionen för immunologi, genetik och patologi
Uhrbom, Lene, Associate professor (preses)
Uppsala universitet,Institutionen för immunologi, genetik och patologi
visa fler...
Baker, Suzanne J., Professor (opponent)
St. Jude Children’s Research Hospital, Memphis, TN, USA
visa färre...
 (creator_code:org_t)
ISBN 9789151301839
Uppsala : Acta Universitatis Upsaliensis, 2018
Engelska 62 s.
Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 1409
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
Stäng  
  • Medulloblastoma is the most common malignant pediatric brain tumor and is molecularly divided into four subgroups – WNT, SHH, Group 3 and Group 4. Two thirds of medulloblastoma patients survive, but survivors often suffer from severe, lifelong side-effects. The MYCN oncogene is deregulated in many medulloblastoma patients. Glioblastoma is the most common malignant brain tumor in adults, with a median survival of about one year. Glioblastoma is a highly heterogeneous tumor where targeted therapy has, so far, not been successful and most glioblastoma patients unfortunately die.In our first study we developed three novel humanized models of MYCN-driven SHH medulloblastoma. Histologically and molecularly these models closely resembled the infant class of SHH tumors. Further, we identified a set of clinically relevant genes that had prognostic significance among patients. mTOR signaling pathway was identified as a major contributor to invasion and dissemination, and we showed that mTOR specific inhibition suppressed migration and viability in vitro.In the second study we performed a forward genetic screen of retrovirally-induced murine PDGFB-driven gliomas and identified more than fifty candidate cancer-causing genes, of which many were mutated or deregulated in glioblastoma. One of the genes identified in this screen was PPFIBP1, found to be differentially expressed from obstructive retroviral integrations in PDGFB-driven glioma clones. Lower PPFIBP1 expression significantly decreased survival of mice and was found to be suppressed in glioblastoma patients. We propose PPFIBP1 to be a novel tumor suppressor gene that contributes to glioblastoma development.In the last study we used a panel of 19 patient-derived glioblastoma cell lines and identified a characteristic expression signature that predicts sensitivity to BET inhibition. BET inhibition resulted in apoptosis and senescence, cell cycle arrest and modulation of DNA damage response. The inhibitory effects of BET inhibition were further enhanced in combination with temozolomide, suggesting a promising future therapy for distinct subgroups of glioblastoma patients.This thesis addresses novel molecular findings in medulloblastoma and glioblastoma development, presents clinically relevant brain tumor models, and promising therapeutic approaches that can be used in future clinical trials in malignant pediatric and adult brain tumors.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Nyckelord

Medulloblastoma
Glioblastoma
MYCN
PDGF
Cancer Therapy
BET bromodomains
Temozolomide
Medicinsk vetenskap
Medical Science
Oncology
Onkologi

Publikations- och innehållstyp

vet (ämneskategori)
dok (ämneskategori)

Hitta via bibliotek

Till lärosätets databas

Sök utanför SwePub

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy