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Profiling the cancer proteome

Waldemarson, Sofia LU (2007)
Abstract (Swedish)
Popular Abstract in Swedish

Cancer är en komplex och heterogen sjukdom där celler har börjat växa okontrollerat och denna sjukdom är idag ett stort hälsoproblem. På grund av diffusa symptom upptäcks cancern ofta i ett sent stadium. Otillräcklig kunskap om olika fenotyper hindrar utvecklingen av riktad behandling och patienter svarar därför väldigt olika på en given behandling.



Denna avhandling är baserad på fyra manuskript där masspetrometri-baserad proteomik har använts för att studera tre olika cancrar; bröst-, ovarial- och prostatacancer. 2D-gel elektrofores och LC-MS/MS-baserad analys har använts.



Ovarialcancer har ofta dålig prognos eftersom den ofta hittas i ett sent skede. Det... (More)
Popular Abstract in Swedish

Cancer är en komplex och heterogen sjukdom där celler har börjat växa okontrollerat och denna sjukdom är idag ett stort hälsoproblem. På grund av diffusa symptom upptäcks cancern ofta i ett sent stadium. Otillräcklig kunskap om olika fenotyper hindrar utvecklingen av riktad behandling och patienter svarar därför väldigt olika på en given behandling.



Denna avhandling är baserad på fyra manuskript där masspetrometri-baserad proteomik har använts för att studera tre olika cancrar; bröst-, ovarial- och prostatacancer. 2D-gel elektrofores och LC-MS/MS-baserad analys har använts.



Ovarialcancer har ofta dålig prognos eftersom den ofta hittas i ett sent skede. Det finns därför ett stort behov av diagnostiska markörer för tidig detektion av sjukdomen. I två studier i denna avhandling har ovarialcancertumörer analyserats för att detektera sådana markörer. Proteinexpressionsprofiler från 2D-DIGE-analys kunde separera subgrupper av tumörer och proteiner som skiljer sig i uttryck med ökande malign grad identifierades. En mer djupgående karaktärisering av benigna och maligna tumörer gjordes med LC-MS/MS där iTRAQ användes för kvantifiering.



Bröstcancer består av många patologiska subtyper med olika klinisk presentation och utgång. Med 2D-DIGE konstruerades proteinexpressionsprofiler för tumörer som tidigare analyserats för genexpression för att dela upp dessa tumörer i olika grupper. Subgrupperna som hittades överensstämmer väldigt väl med grupper som hittats på gennivå och dessa korrelerar väl med klinisk information. Proteiner som är karaktäristiska för dessa subgrupper skulle kunna vara användbara som prognostiska markörer.



Somatostatin kan potenitellt inhibera tumörväxt i avancerad hormonresistent prostatacancer. Ett derivat av somatostatin som ökar dess halveringstid i kroppen är intressant som potentiell behandling för denna cancer. Somatostatin och dess derivats effekter studerades i en prostatacancer cellinje med 2D-geler. Somatostatin och derivatet visade sig har liknande effekt på cellinjen och detta pekar på derivatet som potentiellt som behandling. (Less)
Abstract
Cancer is a complex and heterogeneous disease where cells have started to grow uncontrolled and this disease remains a major health problem. Because of diffuse symptoms it often presents at a late stage. Insufficient understanding of the different phenotypes hinders the development of targeted therapeutics and consequently patients show a diverse range of responses to a given treatment.



This thesis is based on four original papers where mass spectrometry based proteomics has been used to study three different cancers; breast, ovarian and prostate cancer. Two-dimensional gel electrophoresis and shotgun proteomics LC-MS/MS based analysis has been applied.



Ovarian cancers often have a bad prognosis... (More)
Cancer is a complex and heterogeneous disease where cells have started to grow uncontrolled and this disease remains a major health problem. Because of diffuse symptoms it often presents at a late stage. Insufficient understanding of the different phenotypes hinders the development of targeted therapeutics and consequently patients show a diverse range of responses to a given treatment.



This thesis is based on four original papers where mass spectrometry based proteomics has been used to study three different cancers; breast, ovarian and prostate cancer. Two-dimensional gel electrophoresis and shotgun proteomics LC-MS/MS based analysis has been applied.



Ovarian cancers often have a bad prognosis because of late presentation. Diagnostic markers for early detection are urgently needed. Two studies in this thesis analysed ovarian cancer tumours for this purpose. Protein expression profiles from 2D-DIGE could separate the tumour subgroups and proteins differentially expressed with increased malignancy were identified. A more in-depth characterisation of benign and malignant samples was done using a shotgun proteomics approach and iTRAQ for quantitation.



Breast cancer consists of several pathological subtypes with different clinical presentations and outcomes. Using 2D-DIGE protein expression profiles were constructed for tumours previously analysed for gene expression to stratify these tumours. The subgroups found agree very well with groups found on transcriptional level and these correlate well with clinical information. Proteins characterising these subgroups could be useful as prognostic markers in the clinic.



Somatostatin can potentially inhibit tumour growth in advance stage hormone refractory prostate cancer. A derivative of somatostatin that increases its half-life is interesting as a potential treatment. The effect of somatostatin and its derivative was studied in a prostate cancer cell line using 2DE. Differentially expressed proteins were identified. Somatostatin and its derivative were shown to exert the same effect on the cell line pointing at the derivate as a potential treatment. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Dunn, Michael, University College Dublin, Irland
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Cytologi, onkologi, cancer, Biotechnology, Bioteknik, cancerology, oncology, Cytology, iTRAQ, biomarkers, DIGE, two-dimensional gel electrophoresis, Proteomics
pages
116 pages
publisher
Department of Immunotechnology, Lund University
defense location
Segerfalksalen, BMC, Sölvegatan 17, Lund
defense date
2007-10-19 10:15
ISBN
ISBN 978-91-628-7282-3
language
English
LU publication?
yes
id
9ba4b158-52c8-49b6-bce8-620830059083 (old id 598989)
date added to LUP
2007-11-13 09:14:13
date last changed
2016-09-19 08:45:08
@misc{9ba4b158-52c8-49b6-bce8-620830059083,
  abstract     = {Cancer is a complex and heterogeneous disease where cells have started to grow uncontrolled and this disease remains a major health problem. Because of diffuse symptoms it often presents at a late stage. Insufficient understanding of the different phenotypes hinders the development of targeted therapeutics and consequently patients show a diverse range of responses to a given treatment.<br/><br>
<br/><br>
This thesis is based on four original papers where mass spectrometry based proteomics has been used to study three different cancers; breast, ovarian and prostate cancer. Two-dimensional gel electrophoresis and shotgun proteomics LC-MS/MS based analysis has been applied.<br/><br>
<br/><br>
Ovarian cancers often have a bad prognosis because of late presentation. Diagnostic markers for early detection are urgently needed. Two studies in this thesis analysed ovarian cancer tumours for this purpose. Protein expression profiles from 2D-DIGE could separate the tumour subgroups and proteins differentially expressed with increased malignancy were identified. A more in-depth characterisation of benign and malignant samples was done using a shotgun proteomics approach and iTRAQ for quantitation.<br/><br>
<br/><br>
Breast cancer consists of several pathological subtypes with different clinical presentations and outcomes. Using 2D-DIGE protein expression profiles were constructed for tumours previously analysed for gene expression to stratify these tumours. The subgroups found agree very well with groups found on transcriptional level and these correlate well with clinical information. Proteins characterising these subgroups could be useful as prognostic markers in the clinic.<br/><br>
<br/><br>
Somatostatin can potentially inhibit tumour growth in advance stage hormone refractory prostate cancer. A derivative of somatostatin that increases its half-life is interesting as a potential treatment. The effect of somatostatin and its derivative was studied in a prostate cancer cell line using 2DE. Differentially expressed proteins were identified. Somatostatin and its derivative were shown to exert the same effect on the cell line pointing at the derivate as a potential treatment.},
  author       = {Waldemarson, Sofia},
  isbn         = {ISBN 978-91-628-7282-3},
  keyword      = {Cytologi,onkologi,cancer,Biotechnology,Bioteknik,cancerology,oncology,Cytology,iTRAQ,biomarkers,DIGE,two-dimensional gel electrophoresis,Proteomics},
  language     = {eng},
  pages        = {116},
  publisher    = {ARRAY(0x873ea48)},
  title        = {Profiling the cancer proteome},
  year         = {2007},
}