In conclusion, H-Ras and K-Ras
 had differential functions in proliferation and survival of primary
 hepatocytes. H-Ras was the major mediator of ERK-induced proliferation
 and survival, whereas H-Ras and K-Ras both mediated PI3K-induced survival.

Distinct functions of H-Ras and K-Ras in proliferation and survival of
 primary hepatocytes due to selective activation of ERK and PI3K.
Rosseland CM, Wierød L, Flinder LI, Oksvold MP, Skarpen E, Huitfeldt HS.
Laboratory for Toxicopathology, Institute of Pathology,
 Rikshospitalet-Radiumhospitalet Medical Centre,
University of Oslo, Norway. carola.rosseland@labmed.uio.no
Published in J Cell Physiol. 2008 Jun;215(3):818-26. Link 

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 In both models we observed a significant reduction of
 EGFR expression at the protein but not mRNA level.
CONCLUSION: Our results suggest that PKA may represent a target
 that when manipulated can maintain EGFR protein levels at the
single cell level as well as in intact animals.

Published in BMC Cell Biol. 2008 Apr 1;9:16.  Link

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This review by Grandal MV and  Madshus IH focuses on mechanisms involved in ligand-induced EGFR  activation and endocytic down-regulation. A better understanding of EGFR biology should allow development of more tumor-selective
therapeutic approaches targeting EGFR-induced signalling.

Published in J Cell Mol Med. 2008 Mar 4. [Epub ahead of print] Link

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Ben Davidson´s group publish a Methods for simultaneous measurement of apoptosis and cell surface phenotype of epithelial cells in effusions by flow cytometry in

Nat Protoc. 2008;3(6):955-64.

Dong HP, Kleinberg L, Davidson B, Risberg B.

Division of Pathology, Norwegian Radium Hospital, Rikshospitalet Medical Center, Ullernchaussen 70, Montebello, N-0310 Oslo, Norway.

We describe here a protocol for the detection of epithelial cells in effusions combined with quantification of apoptosis by flow cytometry (FCM). The procedure described consists of the following stages: culturing and induction of apoptosis by staurosporine in control ovarian carcinoma cell lines (SKOV-3 and OVCAR-8); preparation of effusion specimens and cell lines for staining; staining of cancer cells in effusions and cell lines for cell surface markers (Ber-EP4, EpCAM and CD45) and intracellular/nuclear markers of apoptosis (cleaved caspase-3 and caspase-8, and incorporated deoxyuridine triphosphates); and FCM analysis of stained cell lines and effusions. This protocol identifies a specific cell population in cytologically heterogeneous clinical specimens and applies two methods to measure different aspects of apoptosis in the cell population of interest. The cleaved caspase and deoxyuridine triphosphate incorporation FCM assays are run in parallel and require (including sample preparation, staining, instrument adjustment and data acquisition) 8 h. The culturing of cell lines requires 2-3 days and induction of apoptosis requires 16 h.

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Heier I, Hofgaard PO,
Brandtaeg P, Jahnsen FL, Karlsson M.
. Links
Depletion of CD4+ CD25+ regulatory T cells inhibits local tumour
growth in a mouse model of B cell lymphoma.
Clin Exp Immunol. 2008 May;152(2):381-7. Epub 2008 Mar

Regulatory T cells (T(regs)) may inhibit immunity against cancer.
 Induction and expansion of T(regs) in the immunosuppressive
microenvironment created by a growing tumour appear to be one
 of the mechanisms by which it can evade host defence. We studied
the impact of CD25+ T(regs) in a B cell lymphoma model in which
Rag2-/- mice received adoptive transfer of wild-type spleen cells
with or without CD25+ cells, and concurrently subcutaneous
inoculation of the B cell lymphoma cell line A20. We also examined
the effect of engaging the glucocorticoid-induced tumour necrosis
 factor receptor (GITR) - an approach reported previously to abrogate
 the suppressive effects of T(regs). Mice that received spleen cells
 depleted of CD25+ T(regs) showed significantly slower tumour growth
 and increased survival compared with mice that received unsorted
spleen cells. The T(reg)-depleted group also had significantly more
 CD8+ T cells infiltrating the tumours and higher levels of serum
immunoglobulin G subclasses. The anti-GITR treatment had no significant
 effect on tumour growth, survival or immunoglobulin production. In
the CD25-depleted group four of 10 mice developed clinical signs of
autoimmunity, in contrast to none in the non-depleted group. Forkhead
 box P3+ T cells were found in tumour-draining lymph nodes in mice
in the CD25-depleted group, suggesting an in vivo induction or
expansion of rare transferred donor T(regs). Thus, our study showed
 that removal of CD25+ T(regs) enhanced anti-tumour immunity against
local growth of a B cell lymphoma and that induction or expansion of
 T(regs) could be one mechanism by which the growing tumour evades
immune surveillance.

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Holt PG, Strickland DH, Wikström ME, Jahnsen FL.
Regulation of immunological homeostasis in the respiratory tract.
Nat Rev Immunol. 2008 Feb;8(2):142-52. Links
Telethon Institute for Child Health Research, Centre for Child Health
 Research, The University of Western Australia, Perth 6009, Western
Australia. patrick@ichr.uwa.edu.au

The respiratory tract has an approximate surface area of 70 m2 in
adult humans, which is in virtually direct contact with the outside
 environment. It contains a uniquely rich vascular bed containing
a large pool of marginated T cells, and harbours a layer of
single-cell-thick epithelial tissue through which re-oxygenation
of blood must occur uninterrupted for survival. It is therefore
not surprising that the respiratory tract is never more than a short
 step away from disaster. We have only a partial understanding of
 how immunological homeostasis is maintained in these tissues, but
it is becoming clear that the immune system has evolved a range of
specific mechanisms to deal with the unique problems encountered
 in this specialized microenvironment.

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Heier I, Malmström K, Pelkonen AS,
Malmberg SP, Kajosaari M, Turpeinen M, Lindahl H, Brandtzaeg P, Jahnsen FL,
Mäkelä MJ.
Bronchial response pattern of antigen presenting cells and regulatory
T cells in children below two years of age.
Thorax. 2008 Feb 4. [Epub ahead of print]

A well-developed HLA-DR+ network of antigen presenting cells
 was present in all samples, approximately 50% of the cells being
CD68+ macrophages and the remainder various subsets of dendritic cells.
 The density of HLA-DR+ cells increased significantly with age but was
 not related to atopy, clinical symptoms or lung function. Comparing
 the density of antigen-presenting cell subsets and clinical parameters,
 only the number of intraepithelial CD1a+ dendritic cells was
significantly increased in infants who had recently suffered a
respiratory infection. BALT structures were identified in 22 children,
 with no relation to lung function, atopic status or human rhinovirus
 positivity. Plasmacytoid dendritic cells and Foxp3+ Tregs were
 located primarily within these isolated lymphoid follicles.
CONCLUSION: A bronchial network of dendritic cells and macrophages
develops quite rapidly after birth, apparently independent of
clinical symptoms or atopy. The high frequency of BALT structures
containing putative tolerogenic dendritic cells and Tregs suggests
 that these lymphoid follicles play an important role in bronchial
immune homeostasis during infancy.

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Kleinberg L, Holth A, Trope CG, Reich R, Davidson B.
Claudin upregulation in ovarian carcinoma effusions is associated
with poor survival.
Hum Pathol. 2008 May;39(5):747-57.

Davidson B,  Wang TL, Shih IeM, Berner A
Expression of the chromatin remodeling factor Rsf-1 is down-regulated in breast carcinoma effusions.
 Hum Pathol. 2008 Apr;39(4):616-22. Epub 2008 Mar 4

 Davidson B, Hadar R, Schlossberg A, Sternlicht T,
 Slipicevic A, Skrede M, Risberg B, Flørenes VA, Kopolovic J, Reich R.
Expression and clinical role of DJ-1, a negative regulator of PTEN,
in ovarian carcinoma.
Hum Pathol. 2008 Jan;39(1):87-95. Epub 2007 Oct 18. Links

Dong HP, Kleinberg L, Silins I, Flørenes VA, Tropé CG, Risberg B,
Nesland JM, Davidson B.Davidson B
 Death receptor expression is associated with poor response to
 chemotherapy and shorter survival in metastatic ovarian carcinoma.
Cancer. 2008 Jan 1;112(1):84-93.

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Breland UM, Halvorsen B, Hol J, Oie E, Paulsson-Berne G, Yndestad A, Smith C, Otterdal K, Hedin U, Waehre T, SandbergWJ, Froland SS, Haraldsen G, Gullestad L, Damas JK, Hansson GK, Aukrust P. A Potential Role of the CXC Chemokine GROα in Atherosclerosis and Plaque Destabilization. Downregulatory Effects of Statins. Arterioscler Thromb Vasc Biol. 2008 Feb 14 [Epub ahead of print].

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Skarpen E, Flinder LI, Rosseland CM, Orstavik S, Wierød L, Oksvold MP, Skålhegg BS, Huitfeldt
HS.MEK1 and MEK2 regulate distinct functions by sorting ERK2 to different intracellular
compartments.FASEB J. 2008 Feb;22(2):466-76. Epub 2007 Oct 10.

Huitfeldts group propose that the requirement of adhesion for cells to proliferate in response to growth
factors, in part, may be explained by the MEK1 S298/T292 control of ERK2 nuclear translocation.
In addition, we suggest that ERK2 intracellular localization determines whether growth factors
mediate proliferation or survival and that the sorting occurs in an adhesion-dependent manner.

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