eRapport

Kjernefasilitet for væskestrømscytometri og celle-sortering

Prosjekt
Prosjektnummer
911505
Ansvarlig person
Bjørn Tore Gjertsen
Institusjon
Helse Bergen HF
Prosjektkategori
Forskningsprosjekt
Helsekategori
Blood, Cancer, Infection, Inflammatory and Immune System, Generic Health Relevance
Forskningsaktivitet
1. Underpinning, 4. Detection and Diagnosis
Rapporter
2014 - sluttrapport
Kjernefasiliteten for flowcytometri har pr 31.12.2014 tre fullt operative maskiner for analyse og sortering i tillegg til en celleteller. Alle instrumentene har vært i full drift hele året. En laser måtte byttes ut på instrumentet for sortering; BD FACS Aria IIu (innkjøpt i 2006). Utgiftene dekkes over driftsbudsjettet. Totalt 38 grupper fra UiB, HUS og eksterne brukere har benyttet seg av kjernefasiliteten i 2014. Instrumentene på enheten er i bruk 2564 timer i 2014 mot ca 3000 i 2013. Dette er en nedgang som skyldes en forskningsgruppe som har fullført sitt cellesorteringsporsjekt, og illustrerer hvordan produksjonen kan variere fra år til år. For den avanserte analysemaskinen BD Fortessa er det en svak økning på antall timer fra 1140 i 2013 til 1229 i 2014. Driftsutgifter totalt i 2014: 477 238 (Budsjetterte driftsutgifter: 465 000) Balanse: 45 069 Akkumulert overskudd i tillegg til bevilgning fra K2 instituttet er planlagt benyttet i 2015 til innkjøp av sorterer nr 2 i kjernefasiliteten noe som vil styrke stabilitet og kapasitet. AKTIVITETER I 2014: Halvdags seminar arrangert av AH diagnostics om FlowRNA, cytokinerog multicolor flow cytometry. Foredrag arrangert av BD(Becton, Dickinson and Company) med presentasjon av nye produkter og hvordan implementere disse i panelbygging under planlegging av eksperimenter. Seminar med presentasjon av Fluidigm sitt instrument CyTOF og foredrag av Jorrit Enserink, UiO. Presentasjon av kjernefasiliteten under IBM sitt teknikerforum. Presentasjon av kjernefasiliteten under K2 sitt teknikerforum. Arrangert en ukes kurs HUIMM307 basic course in flow cytometry. Undervisning ved BMED380 om flowcytometri. Innlegg ved MEDMET1 kurset om kjernefasiliteten. VIDERE PLANER I 2014 ble to Strategiske statsninger innvilget ved Helse Vest, hvor beggge vil produsere data ved hjelp av kjernefasiliteten. Stamcelle-konsortiet vil være avhenging av avansert cellsortering og analyse ved Kjernefasiliteten. Persontilpassa kreftbehandling vil bruke kjernefasiliteten til å analysere sirkulerende kreftceller og sirkulerende tumor-assosierte progenitor enotelceller. Kjernefasiliteten var sentral i søknad om tungt vitenskapelig utstyr til Norges forskningsråd. Søkanden CELLMASS innsendt oktober 2014 omhandler massespektrometrisk analyse av enkeltceller og etablering av metoden i Norge. Midlene er overført til 2015 for å sluttføre metodeetablering av massecytometri og innkjøp av ny cellesorterer, en anskaffelse hvor ca NOK 400 000 av totalsum 1000 000 vil bli brukt. Bevilgning fra Klinisk insitutt 2 er innvilget. Sorterer nr 2 vil styrke stabilitet og kapasitet. Maskinen kjøpes inn via UiB Innkjløpsavdelingen og driftes videre av UiB Klinisk insitutt 2. Kjernefasiliteten er ikke selvfinansierende når avskrivning og planlagte nyanskaffelser, og Helse Vest-støtte har vært helt sentral for å etablere enheten. Kjernefasiliteten er nødvednig for å utvikle nye metoder til helseundersøkelser og klinisk utprøving. Eksempelvis er forsknigsposten sentral for å kunne være med å prøve ut nye medisiner. Forskningsposten for voksne, Helse Bergen, gennomfører nå en fase I utprøving av en ny medisin mot kreft, BGB324. Flowcytomteri er en sentral metode for å bestemme hvilke pasienter som skal kunne rekrutteres til utprøvingen.
2013 - sluttrapport
Kjernefasilitet for flowcytometri UiB/HUS The flow cytometry core facility has now been organized as a formal technology platform at the Faculty of medicine and dentistry, University of Bergen, for two years. An advisory board with members from Helse Bergen and the university is formed, and this board had two meetings in 2013. In general the interest for flow cytometry, use of instruments and activity are still increasing. Scientific supervisor is Bjørn Tore Gjertsen with co-supervisor Einar Kristoffersen. In 2013 the core facility had 1116 hours of cell sorting (1086 in 2012). Model: BD FACS Aria, acquired 2007, upgrade 2011) including training of new users and maintenance. The advanced analyser had 1140 hours (1152 in 2012) of use including training of new users and maintenance. Model: BD Fortessa, acquired 2011, upgrade 2012 with one lasers and detectors. The entrance level/beginner analyser had 748 hours (668 hours in 2012) including training of new users and maintenance. Model: Accuri C6 acquired 2009. All instruments have a full service contract. A new cel counter instrument for sample pre-preparation was purchased in 2013, Merck Millipore Muse. This is a kit based cell counter with the ability to analyse cell cycle and apoptosis in different stages. Different groups at the Dept. of Clinical Science and Dept. of Biomedicine have tested different kits and are very satisfied. The instrument is routinely used as a cell counter. Three new licenses of the analysis software FlowJo are acquired in 2013 due to great interest among the users of the platform. The core facility is involved in teaching introduction to flow cytometry at BMED320 and MEDMET 1 and is involved in organizing two new flow cytometry hands-on courses for masterstudents at the University of Bergen (HUIMM307/HUIMM308). The daily manager was involved as a chair for the flowcytometry meeting organized by BBB Junior Scientist Mini-Symposium and she is also doing a master degree project and will finish 1st March 2014. Budget 2013: Rental proceeds kr. 600.000,- Expences inclung service contracts instruments kr. 400.000,- Balance end 2013: kr. 200.000,- Kjernefasiliteten har vært med å trekke til seg kliniske studier ved Helse Bergen. Pasienter har fått mulighet til å delta i klinisk utprøving som man ellers ikke ville få mulighet til. I fremtiden vil kjernefasiliteten være med på å overføre teknologi for diagnostikk for autoimmune sykdommer, infeksjoner og blodkreft med nye og mer følsomme målemetoder.
2012
The flow cytometry core facility has been organized as a formal technology platform at the Faculty of medicine and dentistry, University of Bergen, for a year and the interest for flow cytometry, use of instruments and activity is increasing. This project has made it possible to establish a high quality service for Helse Bergen and UoB users.The flow cytometry core facility has been organized as a formal technology platform at the Faculty of medicine and dentistry for a year now and the interest for flow cytometry, use of instruments and activity are increasing. In 2012 the core facility had 1086 hours of cell sorting (BD FACS Aria, acquired 2007) including training of new users and maintenance. A laser not covered by the service contract has been replaced. The advanced analyser (BD Fortessa, acquired 2011) had 1152 hours of use including training of new users and maintenance. Fortessa is also upgraded with a new laser and five more detectors, in total 4 lasers and 17 colors designed in collaboration with Associate Professor Yenan Bryceson, Karolinska Inst. Sweden. The beginner instrument Accuri C6 had 668 hours including training of new users and maintenance. The old instrument FACS Calibur was not in registered use in 2011 and the lasers are almost dead, it will be closed down in cooperation with “Medisinsk Teknisk avdeling”. There is the same distribution of users on the instruments as in 2011. A new instrument ordered in 2012, a kit based cell counter with the ability to analyse cell cycle and apoptosis in different stages, Merck Millipore Muse. The instrument is expected in the end of January 2013. Three new licenses of the analysis software FlowJo and one licence of a statistical advanced software are acquired during 2012. Meeting/seminar activity: • A full day seminar 15 March with both international and local lecturers to celebrate the official opening of the Flow Cytometry Core Facility. • Multi Color flow cytometry half day seminar sponsored by BD. • Software half day seminar sponsored by FlowJo analysis software. • A lecture about new methods/technology recently available in Europe, Mass Cytometry and software handling large datasets presented by Bernd Bodenmiller, a group leader from the University of Zurich, Switzerland. • A one-day introduction course in Multivariat Data analysis(MVA) with the software the Unscrambler. The core facility is involved in teaching introduction to flow cytometry at BMED320 and MEDMET 1 and are involved in the planning of a new flow cytometry hands-on course for master- and PhD students at the University of Bergen. The daily manager Marianne Enger is doing a master degree project 2012/13. Scientific supervisor is Bjørn Tore Gjertsen with co-supervisor Einar Kristoffersen. The advisory board have had two meetings in 2012. The board was established in 2012 and The Gade institute, Inst. of Medicine, Inst. of Biomedicine and Haukeland University hospital are represented.
2011
The Unit is now organized as a formal technology platform at the University of Bergen, and the formal opening will be March , 2012, Gades institute. This is an historical interesting event, reintroducing this vital technology as a core unit in the department that introduced the technology in the 1970 led by Professor OD Lærum.An advisory board of active flow cytometry researchers from various departments and research fields including the hosiptal will secure its development. The Gade Institute has invested personel, founds and time to secure its operations, and has seamless arranged access to the unit for all users. The unit has contributed to several high impact publications (e.g. McCormack et al. Leukemia 2011), and several manuscripts are prepared for 2012 with potential for high impact publication. The core facility has secured collaborative pharmacodynamics project in international clinical trials. This illustrate a potential for closer collaboration between researchers performing various clinical trials and support from a technology platform. In 2011 the flow core unit had 876 hours of cell sorting (Aria, acquired jan 2007, upgrade 2011 700 kNOK by University of Bergen) and 774 hours on the analyzer instrument Accuri C6 (acquired oct 2009), 71 hours on the 14 years old analyzer instrument Calibur and 436 hours on the new analyzer instrument Fortessa (acquired in April 2011) financed by University of Bergen, Gades Institute. Time allocation based on users and maintenance: Dept. of Biomed: 44%, Inst. of Med: 22%, Gades Inst.: 11%, HUS: 3% Commercial users: 8% Other users: 6%, Maintenance: 5%. General activity A 3-day international EU COST financed Phosphoflow workshop was arranged in September by the facility with invited lecturers from Stanford Univ., California, Oslo and Bergen. The unit manager Marianne Enger has been teaching Medical Biology masterstudents Introduction to flowcytometry (BMED320) and has presented the facility at Gades institute, Inst. of Medicine and to the PhD students. She gave a talk at a seminar organized by Gades in November and also at a meeting organized by the Norwegian Society for Immunology, Bergen branch. The manager has attended to a 2-day course on Data Analysis for Flow Cytometry and one international congress about Cytometry. She is the chairman of the Norwegian Society for Flow Cytometry and was responsible for the Norwegian contribution to the Scandinavian Flow Cytometry meeting in Sweden in April 2011. Prospects for 2012 We will work to establish an enhanced service in magnetic sorting (AutoMACS) in a semi-sterile environment. Application for a new NRC AVIT is prepared, including state of the art A high-end flow cytometer coupled to mass spectrometry determination. The previous application Autumn 2010 was scored 6 of 7, and a national network was requested. Furthermore, a medium range analyzer is planned, and on a 3-5 horizon a new high end cell sorter will be needed. Extra- and intra-mural applications will be prepared for this equipment. The Helse Vest founds will be used to compentece build up and advanced training, supplement personel, cell counter and possible an additional laser. More colours/channels is feasible on the advanced analyzer. The effort in in vivo imaging will be strongly supported by the possibility for cell sorting based on near-infrared dyes, and the possibility for a near-infrared laser under consideration. There is tentatively planned one advanced user course in September and during a short introduction course. We apply for transfer of founds NOK 220 000,- from 2011 to 2012 for upgrading or cell counter.
2010
The Flow Cytometry Core Unit has provided cell sorting and analysis service to several high impact projects (Gjerdrum et al. PNAS 2010, Vuoriluoto K et al. Oncogene 2010, Semaeva E et al. J Immunology 2010, Prestegarden L et al. Cancer Res 2010, Torsvik A et al. Cancer Res 2010).In 2010 the flow core unit had 1088 hours of cell sorting (Aria) and 666 hours of analysis. 77 hours where spent on maintenance and quality control on the instruments. The low threshold analyzer Accuri C6 with autosampler for analysis of 96/48 well plates has been used for 515 hours. The 13 year old BD Calibur has been used for 151 hours, mainly for completing ongoing projects. The users are distributed as follows: Inst of Biomed. 64%, Inst of Med. 13%, Gades inst. 8%, HUS 2 %, Other/commercial users 13%. Financial overview 2010 • 900k from Helse Vest pr year covered – One senior engineer (488k) – Running Costs & Upgrades 234k – Travels (39k) – Accumulation for upgrades in 2011 (135k) • User fees (381k in 2010) covered: – All running costs (95k in 2010) – Remaining deficit from transfer from UniResearch (129k Aria sorter) – Acccumulation of 60% funds for needed 2011 maintenance/upgrades (157k) PROSPECTS FOR 2011 The working group of the flow core has in October 2010 submitted an infrastructure application to UiB/Norwegian Research Council “A National Technology Platform for Advanced Flow Cytometry and High Throughput Single Cell Analysis – NORFLOW”. NORFLOW outline a five year plan in instrumentation upgrade and replacements based on high-end research projects in new national research programmes including NANOMAT and BIOPROSP. We will work to establish a enhanced service in magnetic sorting (AutoMACS) and flow particle multiplex analysis (Luminex). There is planned one advanced user course in September financed by EU COST. We are currently planning a short introduction course. An upgrade the sorter FACS Aria to FACS Aria III is planned for 2011, financed by user fees and grant from Helse Bergen. In 2011, University of Bergen Gades Insititute, will be responsible for this platform on a permanent basis, and locate the unit in hospital Laboratory Building 5th floor, in immediate closeness to Department of Biomedicine. To support the user basis and to develop the service for hospital and university scientists, we will apply Helse Vest for two additional years of support. We will work for organization that fulfill the requirement of University of Bergen and Helse Bergen for a core facility. A high-end flow cytometer for analysis of multiparameter samples (UV, near-IR, automated sample loading/robotics) has been proposed and applied for through AVIT and in intramural calls. This work will continue, since the demand for such an instrument is increasing. We think our core unit has a competitive edge in customer support and user training through its enthusiastic manager Marianne Enger, and strengthening of the unit’s personnel is prioritized for the next years. GENRAL ACTIVITY 2010 Operation of BD FACS Aria cell sorter has been without break downs. BD Norway has performed two services. The service contract is continued in 2011 in collaboration with Helse Bergen (routine instruments at Haukeland University Hospital). The activity has increased with 222 hours since 2009. Training of new users on the new Accuri C6 machine is half of time needed on conventional machines (BD Calibur). The manager Marianne Enger has been teaching master students in Medical Biology Introduction to flow cytometry (BMED320) and has presented the core facility for users at the Neurology dept. at HUS. Enger is the chairman of the Norwegian Society for Flow cytometry.
2009
The Flow Cytometry Core Unit is proud to present an outstanding list of publications for 2009. Of special interest it two publications in Blood, one in Cancer Research and one in PNAS (Gjerdrum et al. was online Dec 30, 2009). The unit’s cell sorter has been pivotal for these publications.University of Bergen and Helse Vest has over several years invested in a core facility for flow cytometry. The technical development in this area is advancing with a high pace with need for regular replacement, and the high-end instruments are so costly that small research groups or single researchers have limited ability to purchase for own use. Furthermore, the advanced machines provide highly competent technicians. Together, organization of flow cytometry as a core unit seems the only possible solution for our region. In comparison, the Oslo-region has three similar core facilities, located at Ullevål, Rikshospitalet and Ullevål, respectively. These are well operated, and secure the Oslo-region a competitive edge in stem cell research and regenerative medicine, in addition to the conventional use in the fields of immunology, cell and molecular biology. We will suggest that University of Bergen and Helse Vest secure a flow cytometry core unit on a permanent basis, with mechanisms of management that secure continuing development and innovation. The management of the Flow Cytometry Core Unit has taken initiative towards Institute of Medicine, Department of Biomedicine (70% of user time vs 24% use by Hospital/IFI/Gades) and Gades Institute for formalization of the platform, and useer meetings and a tentative advisory board will be initiated in 2010, proposed by Institute of Medicine and Gades Institute. The tentative advisory board will invite representatives from all user-groups and institutes, and discuss the physical location. The final organization of the flow core unit need to be formalized by the Faculty and Departments. A high-end flow cytometer for analysis of multiparameter samples has been proposed and applied for through AVIT and in intramural calls. This work will continue, since the demand for such an instrument is increasing. We think our core unit has a competitive edge in customer support and user training through its enthusiastic manager Marianne Enger, and strengthening of the unit’s personnel is prioritized for the next years. The flow cytometri core unit is a major success as a core facility, the instrumentation being used a total of more than 1200 effective hours. Service is provided at equal terms for all university sector users in Norway. This is in order to facilitate as much research as possible with the available instrumentation and skilled staff. Financial overview • 900k from Helse Vest pr year – One senior engineer – 300k in upgrades/new instrumentation • User fees (380k in 2009) are budgeted to cover: – All running costs (160k in 2009) – Maintenance/upgrades of equipment • Contributions/Funds applied for/granted covers: – New instruments/major upgrades (750k in 2009) General activity A new low entrace machine (2 lasers, four colors) financed by University of Bergen Translational Medicine Program was purchased in October 2009, Accuri C6. This machine will replace the aging Calibur. Eight persons are trained in advanced cell sorting (Inst for Biomed., Gades inst., Nevrologisk avd HUS, BergenBio AS). A new PC/work station is purchased with software for analysis. The unit has participated in training course in Advanced phosphprotein flow cytometry, and the manager Marianne Enger has arranged the national meeting in Flow Cytometry at Solstrand, Bergen.
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McCormack Emmet, Silden Elisabeth, West Richard M, Pavlin Tina, Micklem David R, Lorens James B, Haug Bengt Erik, Cooper Michael E, Gjertsen Bjørn Tore

Nitroreductase, a near-infrared reporter platform for in vivo time-domain optical imaging of metastatic cancer.

Cancer Res 2013 Feb 15;73(4):1276-86. Epub 2012 des 10

PMID: 23233739

McCormack Emmet, Mujic Maja, Osdal Tereza, Bruserud Øystein, Gjertsen Bjørn Tore

Multiplexed mAbs: a new strategy in preclinical time-domain imaging of acute myeloid leukemia.

Blood 2013 Feb 14;121(7):e34-42. Epub 2012 des 12

PMID: 23243270

McCormack Emmet, Adams Katherine J, Hassan Namir J, Kotian Akhil, Lissin Nikolai M, Sami Malkit, Mujic Maja, Osdal Tereza, Gjertsen Bjørn Tore, Baker Deborah, Powlesland Alex S, Aleksic Milos, Vuidepot Annelise, Morteau Olivier, Sutton Deborah H, June Carl H, Kalos Michael, Ashfield Rebecca, Jakobsen Bent K

Bi-specific TCR-anti CD3 redirected T-cell targeting of NY-ESO-1- and LAGE-1-positive tumors.

Cancer Immunol Immunother 2013 Apr;62(4):773-85. Epub 2012 des 22

PMID: 23263452

Mustjoki S, Richter J, Barbany G, Ehrencrona H, Fioretos T, Gedde-Dahl T, Gjertsen B T, Hovland R, Hernesniemi S, Josefsen D, Koskenvesa P, Dybedal I, Markevärn B, Olofsson T, Olsson-Strömberg U, Rapakko K, Thunberg S, Stenke L, Simonsson B, Porkka K, Hjorth-Hansen H, Nordic CML Study Group (NCMLSG)

Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients.

Leukemia 2013 Jul;27(7):1520-6. Epub 2013 jan 18

PMID: 23328954

Silden Elisabeth, Hjelle Sigrun M, Wergeland Line, Sulen André, Andresen Vibeke, Bourdon Jean-Christophe, Micklem David R, McCormack Emmet, Gjertsen Bjørn Tore

Expression of TP53 isoforms p53ß or p53? enhances chemosensitivity in TP53(null) cell lines.

PLoS One 2013;8(2):e56276. Epub 2013 feb 11

PMID: 23409163

Gausdal G, Wergeland A, Skavland J, Nguyen E, Pendino F, Rouhee N, McCormack E, Herfindal L, Kleppe R, Havemann U, Schwede F, Bruserud O, Gjertsen B T, Lanotte M, Ségal-Bendirdjian E, Døskeland S O

Cyclic AMP can promote APL progression and protect myeloid leukemia cells against anthracycline-induced apoptosis.

Cell Death Dis 2013;4():e516. Epub 2013 feb 28

PMID: 23449452

Kloster Martine Müller, Naderi Elin Hallan, Haaland Ingvild, Gjertsen Bjørn Tore, Blomhoff Heidi Kiil, Naderi Soheil

cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases.

Int J Oncol 2013 May;42(5):1815-21. Epub 2013 mar 8

PMID: 23483263

Reikvam Håkon, Nepstad Ina, Sulen André, Gjertsen Bjørn Tore, Hatfield Kimberley Joanne, Bruserud Øystein

Increased antileukemic effects in human acute myeloid leukemia by combining HSP70 and HSP90 inhibitors.

Expert Opin Investig Drugs 2013 May;22(5):551-63.

PMID: 23586877

Andresen V, Wang X, Ghimire S, Omsland M, Gjertsen B T, Gerdes H H

Tunneling nanotube (TNT) formation is independent of p53 expression.

Cell Death Differ 2013 Aug;20(8):1124. Epub 2013 jun 14

PMID: 23764777

Øye Ola Kristoffer, Jørgensen Katarina M, Hjelle Sigrun M, Sulen André, Ulvang Dag Magne, Gjertsen Bjørn Tore

Gel2DE - a software tool for correlation analysis of 2D gel electrophoresis data.

BMC Bioinformatics 2013;14():215. Epub 2013 jul 6

PMID: 23829206

Herfindal Lars, Myhren Lene, Gjertsen Bjørn Tore, Døskeland Stein Ove, Gausdal Gro

Functional p53 is required for rapid restoration of daunorubicin-induced lesions of the spleen.

BMC Cancer 2013;13():341. Epub 2013 jul 11

PMID: 23841896

Bredholt Therese, Ersvær Elisabeth, Erikstein Bjarte Skoe, Sulen André, Reikvam Håkon, Aarstad Hans Jørgen, Johannessen Anne Christine, Vintermyr Olav Karsten, Bruserud Øystein, Gjertsen Bjørn Tore

Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine-like cathinone, cathine or norephedrine.

BMC Pharmacol Toxicol 2013;14():35. Epub 2013 jul 11

PMID: 23845085

Fredly Hanne, Gjertsen Bjørn Tore, Bruserud Oystein

Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents.

Clin Epigenetics 2013;5(1):12. Epub 2013 jul 30

PMID: 23898968

Fredly Hanne, Ersvær Elisabeth, Kittang Astrid Olsnes, Tsykunova Galina, Gjertsen Bjørn Tore, Bruserud Oystein

The combination of valproic acid, all-trans retinoic acid and low-dose cytarabine as disease-stabilizing treatment in acute myeloid leukemia.

Clin Epigenetics 2013;5(1):13. Epub 2013 aug 1

PMID: 23915396

Pemovska Tea, Kontro Mika, Yadav Bhagwan, Edgren Henrik, Eldfors Samuli, Szwajda Agnieszka, Almusa Henrikki, Bespalov Maxim M, Ellonen Pekka, Elonen Erkki, Gjertsen Bjørn T, Karjalainen Riikka, Kulesskiy Evgeny, Lagström Sonja, Lehto Anna, Lepistö Maija, Lundán Tuija, Majumder Muntasir Mamun, Marti Jesus M Lopez, Mattila Pirkko, Murumägi Astrid, Mustjoki Satu, Palva Aino, Parsons Alun, Pirttinen Tero, Rämet Maria E, Suvela Minna, Turunen Laura, Västrik Imre, Wolf Maija, Knowles Jonathan, Aittokallio Tero, Heckman Caroline A, Porkka Kimmo, Kallioniemi Olli, Wennerberg Krister

Individualized systems medicine strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia.

Cancer Discov 2013 Dec;3(12):1416-29. Epub 2013 sep 20

PMID: 24056683

Ben-Batalla Isabel, Schultze Alexander, Wroblewski Mark, Erdmann Robert, Heuser Michael, Waizenegger Jonas S, Riecken Kristoffer, Binder Mascha, Schewe Denis, Sawall Stefanie, Witzke Victoria, Cubas-Cordova Miguel, Janning Melanie, Wellbrock Jasmin, Fehse Boris, Hagel Christian, Krauter Jürgen, Ganser Arnold, Lorens James B, Fiedler Walter, Carmeliet Peter, Pantel Klaus, Bokemeyer Carsten, Loges Sonja

Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma.

Blood 2013 Oct 3;122(14):2443-52. Epub 2013 aug 27

PMID: 23982172

Olsen Jan Roger, Oyan Anne Margrete, Rostad Kari, Hellem Margrete R, Liu Jie, Li Lisha, Micklem David R, Haugen Hallvard, Lorens James B, Rotter Varda, Ke Xi-Song, Lin Biaoyang, Kalland Karl-Henning

p63 attenuates epithelial to mesenchymal potential in an experimental prostate cell model.

PLoS One 2013;8(5):e62547. Epub 2013 mai 1

PMID: 23658742

Abrahamsen Iren, Lorens James B

Evaluating extracellular matrix influence on adherent cell signaling by cold trypsin phosphorylation-specific flow cytometry.

BMC Cell Biol 2013;14():36. Epub 2013 aug 19

PMID: 23957395

Volchenkov R, Karlsen M, Jonsson R, Appel S

Type 1 regulatory T cells and regulatory B cells induced by tolerogenic dendritic cells.

Scand J Immunol 2013 Apr;77(4):246-54.

PMID: 23442246

Haldorsen K, Appel S, Le Hellard S, Bruland O, Brun J G, Omdal R, Kristjansdottir G, Theander E, Fernandes C P D, Kvarnström M, Eriksson P, Rönnblom L, Herlenius M W, Nordmark G, Jonsson R, Bolstad A I

No association of primary Sjögren's syndrome with Fc? receptor gene variants.

Genes Immun 2013 Jun;14(4):234-7. Epub 2013 apr 4

PMID: 23552400

Sandvik L F, Volchenkov R, Jonsson R, Appel S

Characterization of monocyte-derived dendritic cells from immunosuppressed renal transplant recipients with and without squamous cell carcinomas.

Scand J Immunol 2013 Sep;78(3):291-7.

PMID: 23790073

Volchenkov Roman, Brun Johan G, Jonsson Roland, Appel Silke

In vitro suppression of immune responses using monocyte-derived tolerogenic dendritic cells from patients with primary Sjögren's syndrome.

Arthritis Res Ther 2013;15(5):R114.

PMID: 24025795

Hagland Hanne R, Nilsson Linn I H, Burri Lena, Nikolaisen Julie, Berge Rolf K, Tronstad Karl J

Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA).

Biochem Biophys Res Commun 2013 Jan 11;430(2):573-8. Epub 2012 des 7

PMID: 23228666

Poli Aurélie, Wang Jian, Domingues Olivia, Planagumà Jesús, Yan Tao, Rygh Cecilie Brekke, Skaftnesmo Kai Ove, Thorsen Frits, McCormack Emmet, Hentges François, Pedersen Paal Henning, Zimmer Jacques, Enger Per Øyvind, Chekenya Martha

Targeting glioblastoma with NK cells and mAb against NG2/CSPG4 prolongs animal survival.

Oncotarget 2013 Sep;4(9):1527-46.

PMID: 24127551

Kmiecik Justyna, Poli Aurélie, Brons Nicolaas H C, Waha Andreas, Eide Geir Egil, Enger Per Øyvind, Zimmer Jacques, Chekenya Martha

Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level.

J Neuroimmunol 2013 Nov 15;264(1-2):71-83. Epub 2013 aug 31

PMID: 24045166

Jacobsen Hege Karine, Sleire Linda, Wang Jian, Netland Inger Anne, Mutlu Ercan, Førde Hilde, Pedersen Paal-Henning, Gullberg Donald, Enger Per Øyvind

Establishment of a novel dsRed NOD/Scid mouse strain to investigate the host and tumor cell compartments.

Cancer Invest 2013 May;31(4):221-30. Epub 2013 mar 22

PMID: 23521006

Talasila Krishna M, Soentgerath Anke, Euskirchen Philipp, Rosland Gro V, Wang Jian, Huszthy Peter C, Prestegarden Lars, Skaftnesmo Kai Ove, Sakariassen Per Øystein, Eskilsson Eskil, Stieber Daniel, Keunen Olivier, Brekka Narve, Moen Ingrid, Nigro Janice M, Vintermyr Olav K, Lund-Johansen Morten, Niclou Simone, Mørk Sverre J, Enger Per Oyvind, Bjerkvig Rolf, Miletic Hrvoje

EGFR wild-type amplification and activation promote invasion and development of glioblastoma independent of angiogenesis.

Acta Neuropathol 2013 May;125(5):683-98. Epub 2013 feb 22

PMID: 23429996

Mørch Kristine, Hanevik Kurt, Rivenes Ann C, Bødtker Jørn E, Næss Halvor, Stubhaug Bjarte, Wensaas Knut-Arne, Rortveit Guri, Eide Geir E, Hausken Trygve, Langeland Nina

Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural course.

BMC Gastroenterol 2013;13():28. Epub 2013 feb 12

PMID: 23399438

McCormack E, Haaland I, Venås G, Forthun R B, Huseby S, Gausdal G, Knappskog S, Micklem D R, Lorens J B, Bruserud O, Gjertsen B T

Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia.

Leukemia 2012 May;26(5):910-7. Epub 2011 nov 8

PMID: 22064349

Christodoulou Michael S, Zunino Franco, Zuco Valentina, Borrelli Stella, Comi Daniela, Fontana Gabriele, Martinelli Marisa, Lorens James B, Evensen Lasse, Sironi Maurizio, Pieraccini Stefano, Dalla Via Lisa, Gia Ornella Maria, Passarella Daniele

Camptothecin-7-yl-methanthiole: semisynthesis and biological evaluation.

ChemMedChem 2012 Dec;7(12):2134-43. Epub 2012 okt 19

PMID: 23086693

Hatfield Kimberley J, Evensen Lasse, Reikvam Håkon, Lorens James B, Bruserud Øystein

Soluble mediators released by acute myeloid leukemia cells increase capillary-like networks.

Eur J Haematol 2012 Dec;89(6):478-90. Epub 2012 okt 26

PMID: 23046151

Oveland Eystein, Wergeland Line, Hovland Randi, Lorens James B, Gjertsen Bjørn Tore, Fladmark Kari E

Ectopic expression of Flt3 kinase inhibits proliferation and promotes cell death in different human cancer cell lines.

Cell Biol Toxicol 2012 Aug;28(4):201-12. Epub 2012 mar 16

PMID: 22422053

Gavasso S, Gjertsen BT, Anderssen E, Myhr KM, Vedeler C

Immunogenic effects of recombinant interferon-beta therapy disrupt the JAK/STAT pathway in primary immune cells from patients with multiple sclerosis.

Mult Scler 2012 Aug;18(8):1116-24. Epub 2012 jan 27

PMID: 22287540

Hovden Arnt-Ove, Karlsen Marie, Jonsson Roland, Appel Silke

The bacterial preparation OK432 induces IL-12p70 secretion in human dendritic cells in a TLR3 dependent manner.

PLoS One 2012;7(2):e31217. Epub 2012 feb 21

PMID: 22363584

Willingham Stephen B, Volkmer Jens-Peter, Gentles Andrew J, Sahoo Debashis, Dalerba Piero, Mitra Siddhartha S, Wang Jian, Contreras-Trujillo Humberto, Martin Robin, Cohen Justin D, Lovelace Patricia, Scheeren Ferenc A, Chao Mark P, Weiskopf Kipp, Tang Chad, Volkmer Anne Kathrin, Naik Tejaswitha J, Storm Theresa A, Mosley Adriane R, Edris Badreddin, Schmid Seraina M, Sun Chris K, Chua Mei-Sze, Murillo Oihana, Rajendran Pradeep, Cha Adriel C, Chin Robert K, Kim Dongkyoon, Adorno Maddalena, Raveh Tal, Tseng Diane, Jaiswal Siddhartha, Enger Per Øyvind, Steinberg Gary K, Li Gordon, So Samuel K, Majeti Ravindra, Harsh Griffith R, van de Rijn Matt, Teng Nelson N H, Sunwoo John B, Alizadeh Ash A, Clarke Michael F, Weissman Irving L

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors.

Proc Natl Acad Sci U S A 2012 Apr;109(17):6662-7. Epub 2012 mar 26

PMID: 22451913

Moen Ingrid, Jevne Charlotte, Wang Jian, Kalland Karl-Henning, Chekenya Martha, Akslen Lars A, Sleire Linda, Enger Per Ø, Reed Rolf K, Øyan Anne M, Stuhr Linda E B

Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation.

BMC Cancer 2012;12():21. Epub 2012 jan 17

PMID: 22251838

Lee Jungwoo, Li Matthew, Milwid Jack, Dunham Joshua, Vinegoni Claudio, Gorbatov Rostic, Iwamoto Yoshiko, Wang Fangjing, Shen Keyue, Hatfield Kimberley, Enger Marianne, Shafiee Sahba, McCormack Emmet, Ebert Benjamin L, Weissleder Ralph, Yarmush Martin L, Parekkadan Biju

Implantable microenvironments to attract hematopoietic stem/cancer cells.

Proc Natl Acad Sci U S A 2012 Nov;109(48):19638-43. Epub 2012 nov 12

PMID: 23150542

Sapkota Dipak, Costea Daniela Elena, Blø Magnus, Bruland Ove, Lorens James B, Vasstrand Endre N, Ibrahim Salah O

S100A14 inhibits proliferation of oral carcinoma derived cells through G1-arrest.

Oral Oncol 2012 Mar;48(3):219-25. Epub 2011 okt 26

PMID: 22032898

Wang J, Daphu I, Pedersen P-H, Miletic H, Hovland R, Mørk S, Bjerkvig R, Tiron C, McCormack E, Micklem D, Lorens J B, Immervoll H, Thorsen F

A novel brain metastases model developed in immunodeficient rats closely mimics the growth of metastatic brain tumours in patients.

Neuropathol Appl Neurobiol 2011 Feb;37(2):189-205.

PMID: 20819169

Wang Jian, Svendsen Agnete, Kmiecik Justyna, Immervoll Heike, Skaftnesmo Kai Ove, Planagumà Jesús, Reed Rolf Kåre, Bjerkvig Rolf, Miletic Hrvoje, Enger Per Øyvind, Rygh Cecilie Brekke, Chekenya Martha

Targeting the NG2/CSPG4 proteoglycan retards tumour growth and angiogenesis in preclinical models of GBM and melanoma.

PLoS One 2011;6(7):e23062. Epub 2011 jul 29

PMID: 21829586

Golebiewska Anna, Brons Nicolaas H C, Bjerkvig Rolf, Niclou Simone P

Critical appraisal of the side population assay in stem cell and cancer stem cell research.

Cell Stem Cell 2011 Feb;8(2):136-47.

PMID: 21295271

Szyszko Ewa A, Skarstein Kathrine, Jonsson Roland, Brokstad Karl A

Distinct phenotypes of plasma cells in spleen and bone marrow of autoimmune NOD.B10.H2b mice.

Autoimmunity 2011 Aug;44(5):415-26. Epub 2011 feb 21

PMID: 21332424

Hovden Arnt-Ove, Karlsen Marie, Jonsson Roland, Aarstad Hans Jørgen, Appel Silke

Maturation of monocyte derived dendritic cells with OK432 boosts IL-12p70 secretion and conveys strong T-cell responses.

BMC Immunol 2011;12():2. Epub 2011 jan 5

PMID: 21208424

Szyszko E A, Brun J G, Skarstein K, Peck A B, Jonsson R, Brokstad K A

Phenotypic diversity of peripheral blood plasma cells in primary Sjögren's syndrome.

Scand J Immunol 2011 Jan;73(1):18-28.

PMID: 21128999

Lied Gülen A, Vogelsang Petra, Berstad Arnold, Appel Silke

Dendritic cell populations in patients with self-reported food hypersensitivity.

Int J Gen Med 2011;4():389-96. Epub 2011 mai 15

PMID: 21625415

Karlsen M, Hovden A-O, Vogelsang P, Tysnes B B, Appel S

Bromelain treatment leads to maturation of monocyte-derived dendritic cells but cannot replace PGE2 in a cocktail of IL-1ß, IL-6, TNF-a and PGE2.

Scand J Immunol 2011 Aug;74(2):135-43.

PMID: 21449940

Hegen Anja, Blois Anna, Tiron Crina E, Hellesøy Monica, Micklem David R, Nör Jacques E, Akslen Lars A, Lorens James B

Efficient in vivo vascularization of tissue-engineering scaffolds.

J Tissue Eng Regen Med 2011 Apr;5(4):e52-62. Epub 2010 sep 23

PMID: 20865694

Svendsen Agnete, Verhoeff Joost J C, Immervoll Heike, Brøgger Jan C, Kmiecik Justyna, Poli Aurelie, Netland Inger A, Prestegarden Lars, Planagumà Jesús, Torsvik Anja, Kjersem Anneli Bohne, Sakariassen Per Ø, Heggdal Jan I, Van Furth Wouter R, Bjerkvig Rolf, Lund-Johansen Morten, Enger Per Ø, Felsberg Joerg, Brons Nicolaas H C, Tronstad Karl J, Waha Andreas, Chekenya Martha

Expression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastoma.

Acta Neuropathol 2011 Oct;122(4):495-510. Epub 2011 aug 24

PMID: 21863242

Olsnes C, Olofsson J, Aarstad H J

MAPKs ERK and p38, but not JNK phosphorylation, modulate IL-6 and TNF-a secretion following OK-432 in vitro stimulation of purified human monocytes.

Scand J Immunol 2011 Aug;74(2):114-25.

PMID: 21388428

Reikvam Håkon, Hatfield Kimberley J, Ersvaer Elisabeth, Hovland Randi, Skavland Jørn, Gjertsen Bjørn T, Petersen Kjell, Bruserud Oystein

Expression profile of heat shock proteins in acute myeloid leukaemia patients reveals a distinct signature strongly associated with FLT3 mutation status--consequences and potentials for pharmacological intervention.

Br J Haematol 2012 Feb;156(4):468-80. Epub 2011 des 13

PMID: 22150087

Gjerdrum Christine, Tiron Crina, Høiby Torill, Stefansson Ingunn, Haugen Hallvard, Sandal Tone, Collett Karin, Li Shan, McCormack Emmet, Gjertsen Bjørn Tore, Micklem David R, Akslen Lars A, Glackin Carlotta, Lorens James B

Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival.

Proc Natl Acad Sci U S A 2010 Jan;107(3):1124-9. Epub 2009 des 28

PMID: 20080645

Semaeva Elvira, Tenstad Olav, Skavland Jørn, Enger Marianne, Iversen Per Ole, Gjertsen Bjørn Tore, Wiig Helge

Access to the spleen microenvironment through lymph shows local cytokine production, increased cell flux, and altered signaling of immune cells during lipopolysaccharide-induced acute inflammation.

J Immunol 2010 Apr;184(8):4547-56. Epub 2010 mar 17

PMID: 20237290

Vuoriluoto K, Haugen H, Kiviluoto S, Mpindi J-P, Nevo J, Gjerdrum C, Tiron C, Lorens J B, Ivaska J

Vimentin regulates EMT induction by Slug and oncogenic H-Ras and migration by governing Axl expression in breast cancer.

Oncogene 2011 Mar;30(12):1436-48. Epub 2010 nov 8

PMID: 21057535

Zanella Fabian, Lorens James B, Link Wolfgang

High content screening: seeing is believing.

Trends Biotechnol 2010 May;28(5):237-45. Epub 2010 mar 24

PMID: 20346526

Torsvik Anja, Røsland Gro V, Svendsen Agnete, Molven Anders, Immervoll Heike, McCormack Emmet, Lønning Per Eystein, Primon Monika, Sobala Ewa, Tonn Joerg-Christian, Goldbrunner Roland, Schichor Christian, Mysliwietz Josef, Lah Tamara T, Motaln Helena, Knappskog Stian, Bjerkvig Rolf

Spontaneous malignant transformation of human mesenchymal stem cells reflects cross-contamination: putting the research field on track - letter.

Cancer Res 2010 Aug;70(15):6393-6. Epub 2010 jul 14

PMID: 20631079

Prestegarden Lars, Svendsen Agnete, Wang Jian, Sleire Linda, Skaftnesmo Kai Ove, Bjerkvig Rolf, Yan Tao, Askland Lasse, Persson Andreas, Sakariassen Per Øystein, Enger Per Øyvind

Glioma cell populations grouped by different cell type markers drive brain tumor growth.

Cancer Res 2010 Jun;70(11):4274-9. Epub 2010 mai 11

PMID: 20460538

Kögel Tanja, Rudolf Rüdiger, Hodneland Erlend, Hellwig Andrea, Kuznetsov Sergei A, Seiler Florian, Söllner Thomas H, Barroso João, Gerdes Hans-Hermann

Distinct roles of myosin Va in membrane remodeling and exocytosis of secretory granules.

Traffic 2010 May;11(5):637-50.

PMID: 20149155

Evensen Lasse, Micklem David R, Link Wolfgang, Lorens James B

A novel imaging-based high-throughput screening approach to anti-angiogenic drug discovery.

Cytometry A 2010 Jan;77(1):41-51.

PMID: 19834964

Goplen Dorota, Bougnaud Sébastien, Rajcevic Uros, Bøe Stig O, Skaftnesmo Kai O, Voges Juergen, Enger Per Ø, Wang Jian, Tysnes Berit B, Laerum Ole D, Niclou Simone, Bjerkvig Rolf

aB-crystallin is elevated in highly infiltrative apoptosis-resistant glioblastoma cells.

Am J Pathol 2010 Oct;177(4):1618-28. Epub 2010 sep 2

PMID: 20813964

Røsland Gro Vatne, Svendsen Agnete, Torsvik Anja, Sobala Ewa, McCormack Emmet, Immervoll Heike, Mysliwietz Josef, Tonn Joerg-Christian, Goldbrunner Roland, Lønning Per Eystein, Bjerkvig Rolf, Schichor Christian

Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation.

Cancer Res 2009 Jul;69(13):5331-9. Epub 2009 jun 9

PMID: 19509230

Parlati Francesco, Lee Susan J, Aujay Monette, Suzuki Erika, Levitsky Konstantin, Lorens James B, Micklem David R, Ruurs Paulina, Sylvain Catherine, Lu Yan, Shenk Kevin D, Bennett Mark K

Carfilzomib can induce tumor cell death through selective inhibition of the chymotrypsin-like activity of the proteasome.

Blood 2009 Oct;114(16):3439-47. Epub 2009 aug 11

PMID: 19671918

Huszthy Peter C, Giroglou Tsanan, Tsinkalovsky Oleg, Euskirchen Philipp, Skaftnesmo Kai Ove, Bjerkvig Rolf, von Laer Dorothee, Miletic Hrvoje

Remission of invasive, cancer stem-like glioblastoma xenografts using lentiviral vector-mediated suicide gene therapy.

PLoS One 2009;4(7):e6314. Epub 2009 jul 20

PMID: 19617915

Bredholt Therese, Dimba Elizabeth Ao, Hagland Hanne R, Wergeland Line, Skavland Jørn, Fossan Kjell O, Tronstad Karl J, Johannessen Anne C, Vintermyr Olav K, Gjertsen Bjørn T

Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines.

Mol Cancer 2009;8():101. Epub 2009 nov 13

PMID: 19912650

Erikstein Bjarte Skoe, McCormack Emmet, Tronstad Karl Johan, Schwede Frank, Berge Rolf, Gjertsen Bjørn Tore

Protein kinase A activators and the pan-PPAR agonist tetradecylthioacetic acid elicit synergistic anti-leukaemic effects in AML through CREB.

Leuk Res 2010 Jan;34(1):77-84. Epub 2009 sep 27

PMID: 19786302

Oveland Eystein, Gjertsen Bjørn Tore, Wergeland Line, Selheim Frode, Fladmark Kari E, Hovland Randi

Ligand-induced Flt3-downregulation modulates cell death associated proteins and enhances chemosensitivity to idarubicin in THP-1 acute myeloid leukemia cells.

Leuk Res 2009 Feb;33(2):276-87. Epub 2008 aug 8

PMID: 18691757

Pendino Frédéric, Nguyen Eric, Jonassen Inge, Dysvik Bjarte, Azouz Abdulkader, Lanotte Michel, Ségal-Bendirdjian Evelyne, Lillehaug Johan R

Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis.

Blood 2009 Apr;113(14):3172-81. Epub 2009 jan 30

PMID: 19182210

Skavland J, Jørgensen KM, Hadziavdic K, Hovland R, Jonassen I, Bruserud Ø, Gjertsen BT.

Specific cellular signal-transduction responses to in vivo combination therapy with ATRA, valproic acid and theophylline in acut

Blood Cancer J. 2011: 1, e4 (doi:10.1038/bcj.2011.2)

Doktorgrader
Jørn Skavland

Risk stratification and therapy response monitoring by phosphoprotein profiles in acute myeloid leukaemia

Disputert:
august 2013
Hovedveileder:
Bjørn Tore Gjertsen
Deltagere
  • Rebecca Jane Cox Brokstad Prosjektdeltaker
  • Kurt Hanevik Prosjektdeltaker
  • Sonia Gavasso Prosjektdeltaker
  • Martha Chekenya Enger Prosjektdeltaker
  • Silke Appel Prosjektdeltaker
  • Bjørn Tore Gjertsen Prosjektdeltaker
  • James Lorens Prosjektdeltaker
  • Per Øyvind Enger Prosjektdeltaker
  • Andre Sulen Ph.d.-kandidat
  • Jørn Skavland Postdoktor
  • Yenan Bryceson Prosjektdeltaker
  • Sten Ture Roland Jonsson Prosjektdeltaker
  • Einar Klæboe Kristoffersen Prosjektdeltaker
  • Marianne Enger Prosjektdeltaker

eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT

Alle henvendelser rettes til Faglig rapportering, Helse Vest

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