Preface - Ous-research.no

Experimental microsurgery and Transplantation
Research topics
Genome-wide transcription profiles of endothelial cells
during cardiac allograft rejection
In this project, we have performed studies of the interaction
between the graft endothelial cells and the recipients immune
cells by characterization of the gene activation profile
in the vascular endothelium of allografts in acute rejection,
with the specific aim to investigate wether there are genetic
transcript profiles that can be linked to allograft rejection.
Heart transplantation have been performed in Lewis rats
with DA animals as donors., and Lewis isotransplants as
controls. In the allo-tx model, acute rejection develops in
the course of 4-6 days postoperatively. Grafts have been
harvested at day 0,2,3,4,5 and 6.
Transcriptome analyses of organ transplants have until
now usually focused on whole tissue samples containing
activation profiles from different cell populations. Here, we
enriched endothelial cells from rat cardiac allografts and
isografts, establishing their activation profile at baseline
and on days 2, 3 and 4 after transplantation. Modulated
transcripts were assigned to three categories based on their
regulation profile in allografts and isografts. Categories A
and B contained the majority of transcripts and showed
similar regulation in both graft types, appearing to represent
responses to surgical trauma. By contrast, category
C contained transcripts that were partly allograft-specific
and to a large extent associated with interferon-gammaresponsiveness.
Several transcripts were verified by immunohistochemical
analysis of graft lesions, among them the
matricellular protein periostin, which was one of the most
highly upregulated transcripts but has not been associated
with transplantation previously. In conclusion, the majority
of the differentially expressed genes in graft endothelial
cells are affected by the transplantation procedure whereas
relatively few are associated with allograft rejection.
Growth of hepatocellular carcinoma in the regenerating
liver
Hepatocellular carcinoma (HCC) ranks fifth in frequency
worldwide among all malignancies and is the third most
common cause of cancer mortality, with about 600000
cancer related deaths annually [1]. Liver resection or transplantation
represents the only potential curative treatment
modalities for most HCC patients. Despite successful
surgery achieving R0 resection, tumour recurrence is a
major problem and might be as high as 75 % at five years of
observation.
Recurrence after resection is presumably caused by undetected,
disseminated micrometastasis or de novo cancer
in the liver remnant. The cellular and molecular changes
Figure 4. Major growth factor receptor signallling pathways in
HCC:
resulting from hepatectomy, and the subsequent liver
regeneration process may influence the kinetics of tumor
growth and contribute to recurrence. Accumulating clinical
and experimental evidence suggests that factors involved in
liver regeneration may also stimulate the growth of occult
tumours and the reactivation of dormant micrometastasis.
Some of the most prominent growth factors are oulined in
Figure 1 (adapted from Höpfner M et al. World J Gastroenterol
2008 January 7; 14(1): 1-14)
The aim of this project was to test the hypothesis that a microscopic
HCC tumor in the setting of partial hepatectomy
will show enhanced growth and signs of increased invasiveness
corresponding to the size of the liver resection.
Varying grades of hepatectomy were performed in groups
of Buffalo rats with concomitant implantation of a fixed
number of hepatoma cells in the remnant liver. The following
groups were compared:
••
Group T0: Sham operated animals (n=6), laparotomy and
no hepatectomy with 1.0 ×106 tumor cells injec-tion.
••
Group T30: 30% hepatectomy group (n=6), resection of left
lateral lobe with 1.0 ×106 tumor cells injection;
••
Group C70: 70% hepatectomy without hepatoma group
(n=6), resection of left lateral and median lobes with no
hepatoma cell injection;
••
Group T70: 70% hepatectomy group (n=6), resection of
left lateral and median lobes with 1.0 ×106 tumor cells
injection;
40