Uppsala Centre of Excellence Neuroendocrine tumours

22/10/2017

On October 19th our study regarding prophylactic surgery for asymptomatic stage 4 SI-NETs was published in JAMA Oncology!

This cohort study assesses the association of locoregional surgery at diagnosis for small intestine neuroendocrine tumors with survival among Swedish patients.

03/12/2016

By using the nested case control study-technqiue we (John Eriksson et al) have now in Annals of Surgocal Oncology (https://www.ncbi.nlm.nih.gov/pubmed/27904972) published our first article in a series, studying a nationwide cohort of patients with small intestinal NETs. In 1150 patients we have studied risk factor for death, and in the present publication the patients with symptomatic disease had an increased risk of dying. The indication for primary surgery influenced survival, showing a more negative prognosis for elective surgery. The WHO stage influenced survival, and stage 4 patients had an almost threefold risk of dying compared with stages 1 to 3b patients. The strength with this publication is the method, the one being closest to a randomized study that is possible in a retrospective material.

Ann Surg Oncol. 2016 Nov 30. [Epub ahead of print]

28/11/2016

We continue to publish! Now online in BJS we have in the paper: "Clinical signs of fibrosis in small intestinal neuroendocrine tumours." by Daskalakis, Karakatsanis, Stålberg, Norlén, Hellman described how fibrosis can cause abdominal problems for patients with small intestinal NET. Compression of the superior mesenteric vein or the ureters may occur in a subset of patients.

31/10/2016

Neuroendocrinology has (Oct 2016) now accepted our manuscript "DcR3, TFF3 and Midkine are Novel Serum Biomarkers in Small Intestinal Neuroendocrine Tumors" by Katarina Edfeldt, Kosmas Daskalakis and others. In this paper we conclude that by using a proximity ligation assay or the refined method protein extension assay it is possible to detect minute concentrations of peptides in serum in patients with small intestinal NETs. In our assays covering 69+78 markers, we identified DcR3, TFF3 and Midkine as having higher levels as the control cohort. Moreover they were associated to poor survival, liver metastases (DcR3) and may be novel diagnostic markers for SI-NET (TFF3 and Midkine).

23/10/2016

Kan någon längta efter att få feber och ont i hela kroppen? Jan-Erik Jansson från Norrtälje gör det. Han är den första patienten i en världsunik prövning av ett virusbaserat cancerläkemedel.

08/05/2016

On Saturday May 7th, Tobias Åkerström defended his thesis "Genetic alterations ans Molecular Signatures in Aldosterone producing Adenomas". The thesis is based on three papers published in PlosOne, Endocrine Related Cancer and Scientific Reports and a fourth not yet published manuscript.

Primary Aldosteronism (PA) is caused by autonomous overproduction of aldosterone. Aldosterone is necessary for fluid and ion homeostasis. Aberrant overproduction leads to hypertension and cardiovascular damage. With a prevalence of over 5% in the worlds’ hypertensive community, and with over a billi...

02/05/2016

Edfeldt, Hellman, Westin & Stålberg have recently published in BMC Endocrine disorders. In this article we describe that ACTG2 (Actin gamma smooth muscle 2) may be important in SI-NETs. 24 SI-NETs and, as a control, enterochromaffine cells, were investigated. Eight primary tumors and two lymph node metastases displayed variable levels of positive staining of ACTG2, while 14 SI-NETs as well as normal enterochromaffin cells stained negatively. Growth of the SI-NET cell line CNDT2.5 was inhibited by overexpression of ACTG2. Treatment with DZNep or transfection with miR-145 induced ACTG2 expression (>10-fold). Thus, miR-145 may be a tumpr suppressor and identifying ways to induce its expression may be a therapeutical target.

http://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-016-0100-3

BMC Endocrine Disorders is an open access journal publishing original peer-reviewed research articles in all aspects of the prevention, diagnosis and management of endocrine disorders, as well as related molecular genetics, pathophysiology, and epidemiology.

29/01/2016

Now we have published in Scientific reports that 5.1% of the aldosterone-producing adenomas have a mutation in CTNNB1, mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D, causing stabilization of β-catenin and increased AXIN2 expression, suggesting activation of WNT signaling. The report also suggests that other mechanisms that constitutively activate the WNT pathway may be important in APA formation.
http://www.ncbi.nlm.nih.gov/pubmed/26815163

Sci Rep. 2016 Jan 27;6:19546. doi: 10.1038/srep19546.

12/01/2016

Do not miss our article in PNAS where we in collaboration with Yale University revealed that mutations in YY1 is a common event in insulinomas. In 14 out of 43 insulinomas T372R mutations were found leading to disrupted signalling in the cAMP and Ca2+-pathways, and increased insulin secretion as well as proliferation. http://www.ncbi.nlm.nih.gov/pubmed/25787250

Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):4062-7. doi: 10.1073/pnas.1503696112. Epub 2015 Mar 18. Research Support, Non-U.S. Gov't

26/12/2015

We have evaluated the outcome of surgery for hyperparathyroidism in multiple endocrine neoplasia type 1, and found that after long-term (median 20,6 years) subtotal parathyroidectomy remains our first choice in most patients. This method is associated with higher risk for recurrence, while total parathyroidectomy increases the risk for hypoparathyroidism, also after long-term follow-up. Improved methods for autotransplantation as well as more evidence around the cardiovascular or psychological risks of expressing a mild hypercalcemia after subtotal parathyroidectomy may change the recommendations.
http://link.springer.com/article/10.1007%2Fs00268-015-3297-9

Primary hyperparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1) is surgically treated with either a subtotal parathyroidectomy removing 3 or 3,5 glands (SPX), less than 3 glands (LSPX), or a total parathyroidectomy with autotransplantation (TPX). Previous studies with shorter follow-…

18/12/2015

In a recent article, published in Endocrine-Related cancer, we demonstrate that ATP1A1/ATP2B3-mutated adrenocortical adenomas giving primary aldosteronism i s associated with significant transcriptional upregulation of CYP11B2, compared to KCNJ5-mutated tumors. In our cohort of 165 tumors, 54,5% had KCNJ5-mutation, 6,1% ATP1A1, 3,0 % ATP2B3 and 3,0 % CACNA1D-mutations. Thus, 33,3% are still wildtype in all these genes. Read more:
http://erc.endocrinology-journals.org/content/22/5/735.full.pdf

18/12/2015

God Jul!