Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Spatial proteomic analysi… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Spatial proteomic analysis of GOT1 human small intestine neuroendocrine tumor in nude mice following 177Lu-octreotate therapy

Konferensbidrag (offentliggjort, men ej förlagsutgivet)
Författare Johan Spetz
Mikael Montelius
Maria Ljungberg
Khalil Helou
Eva Forssell-Aronsson
Publicerad i 62nd Annual International Meeting Radiation Research Society, Waikoloa, HI, USA, October 16-19, 2016
Publiceringsår 2016
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för radiofysik
Institutionen för kliniska vetenskaper, Avdelningen för onkologi
Sahlgrenska Cancer Center
Språk en
Ämneskategorier Bioinformatik och systembiologi, Cell- och molekylärbiologi, Medicinsk mikrobiologi, Cancer och onkologi, Radiofysik, Strålningsbiologi

Sammanfattning

Background: 177Lu-octreotate can be used for therapy of somatostatin receptor expressing neuroendocrine tumors (NET). 177Lu-octreotate therapy has achieved high cure rates in GOT1 (human small intestine NET) transplanted to nude mice. However, clinical studies result in moderate response, and complete tumor remission is rarely seen. Solid tumors often develop necrotic cores during growth due to e.g. insufficient vascularization, which may account for the different uptake kinetics and varying therapeutic success seen after 177Lu-octreotate treatment. It is therefore important to explore the cellular effects of 177Lu-octreotate to further optimize treatment parameters and identify biomarkers for treatment response assessment. Aim: To detect significant changes in protein profiles from peripheral and central samples of GOT1 tumor after 177Lu-octreotate therapy. Methods: GOT1 bearing BALB/c nude mice were i.v. injected with 15 MBq 177Lu-octreotate (corresponding to 4 Gy tumor absorbed dose) and killed after 13 days. Total cellular proteins were extracted from the peripheral and central parts of surgically excised tumor samples. Proteomic profiling was generated using liquid chromatography tandem-mass spectrometry (LC-MS/MS), followed by database-based protein identification and relative quantification. Functional annotation of proteins was performed using the DAVID bioinformatics resource tool. Results: The LC-MS/MS analysis identified 58 differentially expressed proteins (p<0.05, Fold Change>1.2) between the peripheral and central parts of tumor samples. Forty of these showed higher levels in the peripheral compared with the central samples, and among them were proteins associated with blood vessel/vasculature development (e.g. FAK1, H6ST1, LMA4, and SYWM), regulation of cell cycle and apoptosis (e.g. FAK1 and MK01), and cellular integrity (e.g. PDLI5, CALD1, FERM2, and NEB2). Conclusions: Taken together, these findings suggest spatial differences in tumor response to 177Lu-octreotate, mainly constituted by differences in vascularization and cellular integrity. These findings indicate potential venues for prognostic evaluation of NET therapy using 177Lu-octreotate. However, further studies are needed to determine whether these effects are time- and/or dose-dependent.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?