Tag Archives: IKM

The Black Death bacteria continues to kill

Egil Lien med verneutstyr

Egil Lien wearing safety gear at the lab.

It took almost six months for Egil Lien to get permission from the Federal Bureau of Investigation in the US to study the plague bacteria that, in its time, killed half of Norway’s population. Now, an antibiotic-resistant strain of the bacteria has been found.

As the bacteria responsible for killing a large part of Europe’s population during the Black Death, the plague bacteria Yersinia pestis has a long kill list on its conscience.

Read more at Gemini.no

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Filed under Inflammatory and Immune System, NTNUmedicine, Research

Early markers of a potentially dangerous type of prostate cancer

Morten Beck RyeBloggers: May-Britt Tessemansattebilde.may-britt.tessem and Morten Beck Rye

As we speak there are no accurate methods to diagnose potentially dangerous prostate cancer in an early stage of cancer.

From a pathologist’s point of view, aggressive cancers look totally similar to harmless subtypes in the beginning of development. As a consequence, the patients will be at high risk of overtreatment in the majority of cases where prostate cancer is detected. We urgently need new tools and markers to sort out the potentially dangerous types of prostate cancer from the non-dangerous in early disease. Most importantly, this will save the patients from reduced quality of life due to unnecessary surgical interventions, and also be economically beneficial for society.

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Filed under Cancer, Research

The Integrated University Hospital improves patient care

Blogger: Bjørn GustafssonBjørn_Gustafsson_blid_Foto_GeirMogen
Dean of Research, The Faculty of Medicine, NTNU

Last week one of our research groups, led by Professor Duan Chen, published a comprehensive scientific study showing promising results in treating gastric cancer, by blocking the tumor nerve supply. The article was published in the prestigious journal Science Translational Medicine.

From left: The Knowledge Center, Chun-Mei Zhao, Gøran T. Andersen (in the background), Duan Chen bottom right

From left: The Knowledge Center, Chun-Mei Zhao, Gøran T. Andersen (in the background), Duan Chen bottom right (Photo: Helsebygg/Geir Mogen)

The term “translational medicine” involves transferring new knowledge from basic research on for instance cell culture or animal models to practical use in patient care; also coined with the term “from bench-to-bedside”.

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Filed under Cancer, NTNUmedicine, Opinions, Oral and Gastrointestinal, Research

CEMIR seminar in Trondheim, September 4, 2014

The Centre of Molecular Inflammation Research, CEMIR, will hold the annual scientific seminar on inflammation research on September 4, 2014.

Speakers include the renowned professors

Cemir collage seminar

Clockwise from top left: Alan Aderem, Göran Hansson, Stefanie Vogel and Douglas Golenbock

The invited speakers will relate to the inflammation research area in different ways.

The seminar is open for all and you do not need to register in avance to participate.

CEMIR was established in 2013 as a Centre of Excellence appointed by the Research Council of Norway. The vision of CEMIR is to lay the foundation for identifying new therapeutic targets and developing new diagnostic tools for inflammatory diseases through an integrated 10-year programme of research and research training in molecular innate immune responses. CEMIR is hosted by the Faculty of Medicine at the Norwegian University of Science and Technology (NTNU).

Please find the full seminar program and see the titles of the talks here: CEMIR seminar 2014 programme (pdf)

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Treating cancer with botox

Gøran Andersen og Duan Chen.

Gøran Andersen and Duan Chen. (Foto: Geir Mogen)

In laboratory tests at The Faculty of medicine, NTNU, Botox proved highly effective at suppressing gastric cancer in mice.

The promising results have led to the launch of an early clinical trial involving human patients with stomach cancer in Norway and St. Olavs Hospital.

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Filed under Cancer, NTNUmedicine, Research

Cortisone does not relieve cancer pain

Blogger: Ørnulf PaulsenØrnulf-Paulsen-WEB

Ørnulf Paulsen is a PhD student at European Palliative Care Research Centre, NTNU, and Senior Consultant in palliative medicine at Telemark Hospital

Until now, clinicians have assumed that corticosteroids effectively relieve pain in cancer patients. A new study shows that this is not the case.

The results from our study have recently been published in the acknowledged Journal of Clinical Oncology.

Placebo shows same effect

Corticosteroids are widely used for the most advanced cancer patients, and pain treatment is one of the indications. The pain relieving effect, however, has never been documented in research results. Our study showed that the drug had no pain relieving effect for the cancer patients who participated in the study.

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Filed under Cancer, NTNUmedicine, Research

Ask a researcher: Is the 5:2 diet healthy for women?

Question

Is the 5:2 diet healthy for women?

 

Answer from Catia Martins Catia Martins. Photo: Geir Mogen

 

 

 

5:2 diet is a type of intermittent fasting, which involves a “feed day”, where food is consumed ad libitum over a 24-hours period, alternated with a “fast day” where food intake is completely or partially restricted over 24 hours. The fasting days usually vary between 2-4 days/week.

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Filed under Metabolic and Endocrine, NTNUmedicine, Spør en forsker

Taking care of knowledge

Kuiper_TrondheimAstrid Lægreid. Foto: Geir MogenBloggers: Astrid Lægreid, professor, Department of Cancer Research and Molecular Medicine and Martin Kuiper professor, Department of Biology

 

 

 

It is often overlooked that after you publish your research results you have not necessarily provided your new knowledge to your colleagues in the best possible way. Today’s biomedical science is very much dependent on the use of computers, to analyse and integrate the various types of data and facts that you and your fellow scientists have produced.  And whereas a computer can do many things, it has difficulty in understanding what is so easily understood by us when we read a scientific publication.

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Filed under NTNUmedicine, Research

How plague bacteria kill immune cells

PNAS cover

The article has the cover image for the current issue of PNAS. (May 20, 2014)

Many bacteria kill considerable numbers of host cells upon infection. However, the mechanisms behind the cell death are in many cases unclear. A recent article in PNAS by the the CEMIR-affiliated researcher professor Egil Lien,  describes how the bacteria Yersinia pestis, the causative agent of plague, kills key immune cells called macrophages by apoptosis mediated by kinase RIP1 and caspase-8 together with RIP3.

Apoptosis is often considered to be a “silent” type of cell death. However, we found that the death was accompanied by inflammatory processes via IL-18 and IL-1b generating inflammasomes and transcription factor NF-kB, also via RIP kinases and caspase-8. Importantly, mice deficient in caspase-8 and RIP3 were highly susceptible to bacterial infection, suggesting a key pathway for anti-bacterial defenses.

The article made it to the cover in the current issue of PNAS. Learn more about the image here.

Egil Lien. Foto: NTNU

Professor Egil Lien. Foto: NTNU

Reference

Wenga, D. , Marty-Roixa, R., Ganesana, S., Proulxb, M.K., Vladimera, G.I., Kaiserc, W.J., Mocarskic, E.S., Pouliota, K., Chand, F.K., Mellihere, M.A., Harrisf, P.A., Bertinf, J.,  Goughf, P. J., Shayakhmetovg, D.M., Goguenb, J.D., Fitzgeralda, K.A., Silvermana, N., Lien, E. Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death. PNAS (published online).

 

 

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Filed under Infection, NTNUmedicine, Research

A new mechanism explaining the anti-inflammatory effect of HDL is revealed

 

espevik_fotografGeirMogen-(Nathalie_Niz_fotograGeirMog

Bloggers: Nathalie Niyonzima and Eivind Samstad

 

 

 

Atherosclerosis is a progressive disease that was once believed to be a disease of cholesterol storage. Today, it is well acknowledged that atherosclerosis is an inflammatory disease, and that cells and signalling molecules from the innate immune system shape the course of the disease in various ways. The defence of the normal artery depends on innate immune responses provided by endothelial cells. When challenged by inflammation, macrophages and other cells of the immune responses are recruited to the artery wall. The macrophage is an integral component to the pathogenesis of atherosclerosis, functioning at the intersection of inflammation and cholesterol homeostasis. Atherosclerotic plaque formation is driven by the persistence of lipid-laden macrophages in the artery wall. The mechanisms by which these cells become trapped, and thereby establishing chronic inflammation, remain unknown (Peter Libby, Nature 2011).

Atherosclerosis

Atherosclerosis. Illustration: iStock

There has long been a focus on finding therapeutic methods to reduce the levels of cholesterol in the arterial wall. Studies have shown that high HDL levels are associated with reduced cardiovascular risk. This is mainly due to HDL’s ability to transport excess cholesterol in arterial macrophages to the liver for excretion (i.e., reverse cholesterol transport). Despite considerable understanding of HDL and its metabolism, therapies that aim to increase HDL levels have not been successful. Because of the heterogeneity in HDL particles, just increasing HDL levels has not been beneficial, reflecting the qualitative changes in the particles. HDL has also been shown to have other functions beyond cholesterol transport – several studies have shown that HDL is anti-inflammatory, but the mechanisms behind this are not well understood (Xuewei Zhu, Ann.Rev.Nutr 2012).

In a recent study published in the prestigious journal Nature Immunology, our research partners have taken a closer look at the anti-inflammatory effects of HDL (De Nardo, et.al, Nature 2013). They identified that HDL’s anti-inflammatory effects are mediated through the induction of ATF3. ATF3 is a key transcriptional regulator of innate immune response genes, which is induced by TLR stimulation and other stimuli, and acts as negative regulator of proinflammatory cytokines (Elisabeth S.Gold, JEM 2012).

Using mouse model and human bone marrow dendritic cells (BMDMs) treated with native HDL or reconstituted HDL prior to TLR stimuli; they showed that HDL regulates inflammation in macrophages by inhibiting transcription of proinflammatory genes such as IL-1β, IL-6 and IL-12.

In order to confirm that the anti-inflammatory effects of HDL were mediated through an inflammatory repressor, they performed microarray analysis on resting BMDMs and HDL-pretreated BMDMs subsequently stimulated with TLR ligand. ATF3 was the most induced transcription factor in the presence of HDL, and it was shown to bind to the promoters of several proinflammatory genes, thereby regulating inflammation.

They demonstrated the relevance of these findings by using Apoe-deficient mice fed a high-fat diet and injected with HDL. They observed that mice treated with HDL had lesser inflammation than the untreated ones, and that the induction of ATF3 correlated with the downregulation of proinflammatory cytokines.

Besides promoting cholesterol efflux from macrophages, HDL has been shown to protect endothelial integrity by promoting endothelial repair mechanisms. Using a model of vascular repair, they showed that the protective effects of HDL on endothelial repair are for the most part driven by ATF3.

These results provide us a link between HDL and its anti-inflammatory properties that has been a puzzle over long time. The fact that ATF3 is required for the anti-inflammatory effects of HDL shows that ATF3 is a key point for endothelial damage and inflammation. The current study has laid the foundation for understanding the regulatory mechanisms that control inflammation in atherosclerosis and other chronic inflammatory diseases.

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