New Molecular Approaches to Glioblastoma Therapy

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Sökning: WFRF:(Baskaran Sathishkumar) > New Molecular Appro...

Baskaran, Sathishkumar,1988-Uppsala universitet,Neuroonkologi,Department of IGP, Uppsala University,Dr.Sven Nelander (författare)

New Molecular Approaches to Glioblastoma Therapy

BokEngelska2017

Förlag, utgivningsår, omfång ...

Uppsala :Acta Universitatis Upsaliensis,2017
48 s.
electronicrdacarrier

Nummerbeteckningar

LIBRIS-ID:oai:DiVA.org:uu-329745
ISBN:9789151301266
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-329745URI

Kompletterande språkuppgifter

Språk:engelska
Sammanfattning på:engelska

Ingår i deldatabas

SwePubSwePub

Klassifikation

Ämneskategori:vet swepub-contenttype
Ämneskategori:dok swepub-publicationtype

Serie

Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,1651-6206 ;1389

Anmärkningar

Glioblastoma (GBM) is the most common high-grade brain tumor diagnosed in patients who are more than 50 years of age. The standard of care treatment is surgery, followed by radiotherapy and chemotherapy. The median life expectancy of patients is only between 12 to 15 months after receiving current treatment regimes. Hence, identification of new therapeutic compounds and gene targets are highly warranted. This thesis describes four interlinked studies to attain this goal. In study 1, we explored drug combination effects in a material of 41 patient-derived GBM cell (GC) cultures. Synergies between three compounds, pterostilbene, gefitinib, and sertraline, resulted in effective killing of GC and can be predicted by biomarkers. In study 2, we performed a large-scale screening of FDA approved compounds (n=1544) in a larger panel of GCs (n=106). By combining the large-scale drug response data with GCs genomics data, we built a novel computational model to predict the sensitivity of each compound for a given GC. A notable finding was that GCs respond very differently to proteasome inhibitors in both in-vitro and in-vivo. In study 3, we explored new gene targets by RNAi (n=1112) in a panel of GC cells. We found that loss of transcription factor ZBTB16/PLZF inhibits GC cell viability, proliferation, migration, and invasion. These effects were due to downregulation of c-MYC and Cyclin B1 after the treatment. In study 4, we tested the genomic stability of three GCs upon multiple passaging. Using molecular and mathematical analyses, we showed that the GCs undergo both systematic adaptations and sequential clonal takeovers. Such changes tend to affect a broad spectrum of pathways. Therefore, a systematic analysis of cell culture stability will be essential to make use of primary cells for translational oncology.Taken together, these studies deepen our knowledge of the weak points of GBM and provide several targets and biomarkers for further investigation. The work in this thesis can potentially facilitate the development of targeted therapies and result in more accurate tools for patient diagnostics and stratification.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi Medicinsk bioteknologi hsv//swe
MEDICAL AND HEALTH SCIENCES Medical Biotechnology Medical Biotechnology hsv//eng
Glioblastoma
GBM
ZBTB16
PLZF
Heterogeneity
Proteasome inhibitors
Bortezomib
Pterostilbene
drug combinations
Oncology
Onkologi
Biological Research on Drug Dependence
Biologisk beroendeforskning
Biology with specialization in Molecular Biology
Biologi med inriktning mot molekylärbiologi
Biomedical Laboratory Science
Biomedicinsk laboratorievetenskap
Medicinsk vetenskap
Medical Science
Molekylär medicin
Molecular Medicine

Biuppslag (personer, institutioner, konferenser, titlar ...)

Nelander, Sven,Associate ProfessorUppsala universitet,Neuroonkologi (preses)
Forsberg Nilsson, Karin,ProfessorUppsala universitet,Neuroonkologi (preses)
Marino, Silvia,ProfessorQueen Mary University of London, UK (opponent)
Uppsala universitetNeuroonkologi (creator_code:org_t)

Internetlänk

Hitta via bibliotek

New Molecular Approaches to Glioblastoma Therapy (Sök publikationen i LIBRIS)

Till lärosätets databas

Hitta mer i SwePub

Av författaren/redakt...: Baskaran, Sathis ...; Nelander, Sven, ...; Forsberg Nilsson ...; Marino, Silvia, ...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Cell och molekyl ...

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinsk biotek ...; och Medicinsk biotek ...

Delar i serien: Digital Comprehe ...

Av lärosätet: Uppsala universitet

Sök utanför SwePub

Sök vidare i:: Google; Google Book Search; Google Scholar

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.

LIBRIS.kb.se