Tag Archives: Prostate cancer

Fusion makes a difference – also in the prostate!

ansattebilde.may-britt.tessemailin falkmo hansenBloggers:  Ailin Falkmo Hansen (PhD candidate) and May-Britt Tessem (Research Scientist), MR Cancer group

 

Movember is around with a “trøndersk” spirit on Facebook, Instagram, and the city is filled with mustaches in different shapes and varieties. The goal is increased awareness of men’s health and prostate cancer – a disease we in the MR cancer group want to understand better.

vevsbit og MR

Prostate tissue samples are stored in liquid nitrogen prior to MR spectroscopy analyses (photo: Geir Mogen/NTNU)

How can cancer metabolism provide important information about prostate cancer?

Scientists around the world have shown that changes in metabolism are important characteristics of cancer. We have studied how metabolism is altered due to cancer and how metabolism is changed owing to cancer aggressiveness. Previously, we have found that the two molecules citrate and spermine may be markers for prostate cancer and also can reveal information about aggressiveness.

Prostate cancer is a heterogeneous type of cancer, and this is of importance for treatment and prognosis of patients. However, today there are no reliable methods for assessment of type of prostate cancer. Researchers world-wide are therefore searching for new methods that may provide diagnostic and/or prognostic information. Presence of the fusion gene TMPRSS2-ERG have been suggested to be a candidate method for risk stratification, and in a recently published study we investigated the link between prostate cancer metabolism and TMPRSS2-ERG.

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How to outsmart a prostate cancer cell

Siver MoestueBlogger: Siver Moestue, Associate Professor
MR Cancer Group, Department of circulation and medical imaging, NTNU

 

 

Cancer cells are notoriously difficult to deal with – partly because they have the ability to dodge the bullets we aim at them. They are inherently resistant to a lot of hostile conditions and therapies, but they can also activate compensatory mechanisms that rescue them when they are exposed to anticancer drugs. We have therefore tried to find a way to responsibly kill cancer cells (killing cancer cells without harming the normal cells in the body, that is) by identifying the crucial compensation mechanisms, and then applying a second drug that strikes the cancer cells where it hurts the most.

Essentially all the work that is performed inside our cells is carried out by proteins. Not all proteins work at the same time – most of them are responsive to cues from their surroundings that tell them when to work and when to take a break. One such cue is OGlcNacylation. Sounds difficult, but basically the cells put tiny “flags” consisting of amino sugars on proteins, thereby giving them new work orders (Figure 1).

Illustration of O-GlcNac Transferase (OGT)

Figure 1 Proteins can be activated, deactivated or otherwise change function when they are labelled with the amino sugar N-acetylglucosamine on specific amino acid residues. This process is called O-GlcNacylation, and may play an important role in cancer.

In cancer, it has been seen that an enzyme responsible for putting these amino sugar flags on proteins (OGT) is frequently over-activated. In a collaboration with Prof. Ian Mills (Norwegian Centre for Molecular Medicine) and Suzanne Walker (Harvard Medical School), we wanted to find out if a novel drug targeting OGT could be used to kill prostate cancer cells. To cut a long story short, they could – but only to a certain extent. The cells found a way to survive and continue to divide, just a little slower than before. To understand how the cancer cells escaped death, we took a deep dive into their metabolism using magnetic resonance spectroscopy.

Interestingly, we found that OGT inhibition made the cells reprogram metabolism. They stopped consuming glucose, instead turning to the common amino acid alanine as a new source of energy. Since OGlcNacylation is a process that normally allows cells to respond to starvation or altered supply of nutrients, this sort of makes sense. It also raised the question “What if we block the metabolism of the cells so they cannot use alanine anymore?”. Luckily, the well-known drug cycloserine (used to treat tuberculosis), does just that – by blocking the alanine-converting enzyme GPT2.

When we treated the prostate cancer cells with both the OGT inhibitor and cycloserine, the prostate cancer cells activated a self-destruct mechanism and died. Luckily, normal prostate cells tolerated the treatment very well.

MR spectrum of cells treated with an OGT inhibitor.

Figure 2 Left: MR spectrum showing how cells treated with an OGT inhibitor (black line) have low levels of glutamate and are virtually depleted of alanine. Right: Diagram demonstrating how LNCaP prostate cancer cells treated with a combination of an OGT inhibitor + cycloserine (blue bar) are far less viable than untreated control cells or cells treated with each of the drugs alone (grey bars).

What did we learn from all this? First, we demonstrated an important principle: Cancer cells may display metabolic ”soft spots” leaving them in a vulnerable position once they are under attack from anticancer drugs. Finding these – and attacking them with a second drug – could be a way of improving cancer therapy in the future. Second, we proved that it is possible to learn an old dog new tricks: cycloserine was developed to make it hard for tuberculosis bacteria to make their cell wall. However, as a side effect it also blocks the ability of mammalian cells to use alanine as an energy source. This does not seem to be a problem for normal cells, because they don´t depend on this mechanism at all. But under given conditions (such as when they are under attack from drugs blocking OGT), prostate cancer cells are addicted to it – and we can take advantage of that when we try to kill them.

The project was carried out with financial support from the Norwegian Cancer Society and the Research Council of Norway.

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Furry and fit: get moving this Movember!

Debbie Hill og Leslie WoodBloggers: Researcher Debbie Hill og PhD Candidate Leslie Euceda Wood
MR Cancer group, Department for ciruclation and medical imaging

 

 

 

It’s that time of year again! And this year, the Movember Foundation is challenging YOU to move every day this month to tackle physical inactivity. In keeping with the Movember spirit, the MR Cancer group (and friends!) donned their best training gear, and ventured out into the crisp breeze of a lovely November morning. Not only to raise a few smiles, but also to raise awareness for men’s health and prostate cancer.

MR Cancer-gruppen i treningstøy og barter.

According to the Movember Foundation a lack of physical activity is the fourth leading risk factor for global mortality, causing 3.2 million deaths worldwide per year. There is a push to combat physical inactivity by:

  1. Getting people moving (check out the MOVE campaign)
  2. Raising awareness on the dangers of physical inactivity & benefits of activity for both physical and mental health
  3. Finding new ways to encourage physical activity
  4. Investing in projects that increase understanding of what motivates men to move. Continue reading

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How moustaches, mice and magnets contribute to prostate cancer research

Debbie HillBlogger: Debbie Hill,
Post doctoral fellow at MR Cancer group

 

As winter approaches us here in Trondheim, the art of keeping warm becomes more important; after all, the well-known Norwegian saying is ‘there is no bad weather, only bad clothes’. So, it is quite convenient that the shortening and cooling of days coincides with the month of November, or Movember as it is affectionately known, where people all around the world insulate their upper lips from the onset of winter to increase awareness of prostate cancer (and to raise some money too!).

Here in the MR Cancer group at NTNU, the ‘prostate team’ are no exception; roughly half way through the month we have cultivated some impressive moustaches.

MR Cancer-gruppa med bart

The MR-Cancer Group Prostate Team.

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To treat or not to treat? The role of PET/MRI in prostate cancer

Mattijs ElschotBlog by: Mattijs Elschot
Postdoctoral Fellow at MR Cancer Group

Some prostate cancer patients need radical surgery to survive, whereas others can do without any form of treatment. The urologist determines to which group a patient belongs. Researchers at NTNU/St. Olavs Hospital investigate whether a PET/MRI scan can help making the correct decision.

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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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Your moustache makes a difference

Blogger: Siver Moestue532136_10151252982417512_69966992_n

 

 

 

 

During last years “Movember” – an annual month-long event involving the growing of moustaches during the month of November to raise awareness of prostate cancer – the Movember Foundation and associated charities raised 839 million NOK worldwide.

As a result, the Norwegian Cancer Society (Movember’s collaborator in Norway) distributed NOK 3.6 mill to research on prostate cancer in Norway. One of the two projects receiving support is a project led by Prof. Tone Frost Bathen (MR Cancer Group, ISB) and Prof. Anders Angelsen (Dept. of Surgery, St. Olavs Hospital and NTNU). The project is entitled “PET/MR imaging for improved diagnosis and personalized treatment in prostate cancer”.

.. we are highly grateful for the support from the Movember Foundation and all those who contribute by growing a moustache or make a donation to somebody who did.

This funding (NOK 1.2 mill) will be used to conduct a clinical trial in patients with suspected recurrence after prostate cancer surgery. This is a MO13-Download-Styleguide-I-patient group where rapid and accurate diagnostic procedures are needed to improve the outcome of the disease.

In collaboration with the Dept. of Radiology at St. Olavs Hospital, we will compare the diagnostic performance of PET/MR imaging with that of the current diagnostic procedures (CT + bone scintigraphy). A novel radiotracer, 18FACBC, will be used as its pharmacokinetic profile is suitable for imaging of the pelvic area.

Using PET/MR as a “one-stop-shop” can potentially simplify patient logistics, thereby shortening the time needed for re-staging the disease.

In addition, this tracer can also detect skeletal metastases, and we can therefore compare the sensitivity of PET/MR imaging to that of bone scintigraphy. Our hypothesis is that PET/MR imaging both can provide more accurate clinical information and reduce the number of different examinations the patients need to go through. Using PET/MR as a “one-stop-shop” can potentially simplify patient logistics, thereby shortening the time needed for re-staging the disease.

The project team believes that the multidisciplinary approach and the use of new technology will contribute to improved health services for prostate cancer patients, and we are highly grateful for the support from the Movember Foundation and all those who contribute by growing a moustache or make a donation to somebody who did. For more information on the study, contact Prof. Tone F. Bathen or Prof.  Anders Angelsen.

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NOK 14 million for more personalised prostate cancer treatment

Blogger: Tone Frost BathenTone Frost Bathen

 

 

 

The MR Cancer Group has a close collaboration with the clinical environments at the Department of Urology and Clinic for Medical Imaging at St. Olavs Hospital. The long-term goals of the projects are to optimise and personalise the diagnostics and treatment of prostate cancer, and thereby increase chances of survival and quality-of-life for this patient group.

We recently received funding of NOK 14 million through a special announcement from the Norwegian Cancer Society for personalised cancer treatment. This presents a unique opportunity to continue our research at a larger scale. The collaboration between clinicians and researchers at NTNU and St. Olavs Hospital, through the integrated university hospital, is key to the execution of the research project. It also enables swifter changes in clinical practice based on research outcomes.

MR undersøkelse av prostata

Photo: Kirsten Selnæs

 

MR-bilder av prostatakreft

By combining different MR methods, the diagnostic accuracy increases. Photo: Kirsten Selnæs

With this project we wish to solve important clinical challenges through the use of advanced medical imaging. Today’s diagnostic tools cannot differentiate between lethal and less dangerous forms of prostate cancer, something which complicates personalised treatment. Improved methods for detection and risk assessment will be of great importance to the treatment options for these patients in the future.

During this project we wish to develop and standardise new methods for MR imaging (MRI), including PET-MRI, for the detection and classification of prostate cancer. Unlike in other types of cancer, medical imaging only plays a limited role in the diagnosis of prostate cancer. For more accurate diagnostics we wish to study the clinical value of MR-guided biopsies, and multimodal MRI will be used to evaluate aggressiveness. The PET-MR scanner donated to St. Olavs Hospital by Trond Mohn is the only of its kind in Norway, and it presents unique opportunities for new approaches to medical imaging.

We will also make use of established research biobanks to describe molecular characteristics of both low and high risk prostate cancer. By connecting these findings with MR images, we hope the project will contribute to improved methods for personalised treatment of prostate cancer.

 

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MR and MRS give better prostate cancer diagnosis

Prostate cancer is one of the most common forms of cancer in Norway, but so far the clinical diagnostic tools have not been able to say much about where in the prostate gland the cancer is, or its aggressiveness in individual patients. A new method developed at the MR Centre may give a clearer answer.

By combining magnetic resonance imaging (MRI) with MR spectroscopy (MRS), PhD candidate Kirsten Margrete Selnæs has developed a method which helps localise cancer in the prostate gland, and how far the cancer has developed. The method can also give a clearer idea of how aggressive the cancer is, which is important with regards to treatment.

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MRI and MRS results from prostate cancer

Measuring aggressiveness

“One of the problems in prostate cancer is to know who has an aggressive form and needs immediate treatment, and who can wait,” Selnæs explains.

She used two different MR methods to answer the question of aggressiveness. First tissue samples from the prostate gland are studied outside the body (ex vivo).

The sample is run through an MR spectrometer which results in a spectrum – or metabolic profile. The researchers then look for values that are prominent in the aggressive cancer forms.

In the ex vivo tests the researchers found two possible biomarkers for prostate cancer aggressiveness: the metabolites citrate and spermin.

Then the same test is done on patients in the body (in vivo), although this gives fewer details. Nonetheless, Selnæs found that the results from the ex vivo tests correlate to those done in vivo. This could lead to a more detailed diagnosis before a potential removal of the prostate gland.

“Until now we have not been able to differentiate the aggressive from the less dangerous cancer in the clinic. But we now hope to be closer to a method for differentiating between the two without having to operate,” Selnæs says.

“With the screening programme for prostate cancer, many cases are discovered which will never develop into actual illness. But so far there has not been a method to confidently determine who will die from the cancer, and who do not even need treatment.”

A detailed map

Selnæs has also compared the MRS results with MR images to get a detailed overview over where the tissue samples come from.

Normally when collecting tissue from the prostate gland, one takes a biopsy, and although it is known whether the sample comes from for example the right or left side of the prostate gland, one does not know any more details.

By combining MRI with MRS in vivo in the patient, it is possible to give the urologist more precise data for where the biopsy should be taken – the difference is akin to trying to navigate from a photograph compared with a map with precise GPS coordinates.

The way it is done is to use the MR images to identify suspicious-looking areas and then run MRS tests on these. If the MRS results also show a typical ‘cancer-result’, it is more certain that it is actually cancer – there are more proofs.

To arrive at this result, Selnæs made us of a new method developed at the Institute for Laboratory medicine, Children’s and Women’s Health (LBK), where one can determine exactly where in the prostate gland the samples are gathered from. This enables the comparison of visual images from MR with the MRS results.

Further research

The research is in no way over although Selnæs has completed her PhD. The bio-marker results will be validated through larger patient studies, and an active monitoring study is planned with patients who according to clinical evaluation can wait with treatment.

“We will do an MR scan when they start the study, and after a year when they are back for their routine control. And we will look at whether there is something in the MR images or MR spectres that can tell us something about who should continue with monitoring,” Selnæs explains.

Thesis defence

Kirsten Margrete Selnæs will defend her thesis on 25. September 2012 at 12.15 in the Auditorium at MTFS, St. Olavs Hospital.

In connection with the defence, there will be a pre-defence seminar on prostate cancer and MR the day before, on the 24. September.

Related publications

 

Magnetic resonance imaging (MRI) is a method for imaging ‘slices’ of the body through the use of radio waves and magnetic fields, which have no known harmful biological effects.

Magnetic resonance spectroscopy (MRS) is a method for looking at the metabolism in cells and gives information about the cells’ biological reactions.

Metabolites are molecules that take part in, or are made from, the metabolism in the cells.

Prostate cancer is a malign tumour in the prostate gland and is the most common form of cancer among men in Norway.

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Closer to an understanding of prostate cancer

A new method for gathering tissue samples from patients having undergone prostate cancer surgery is giving researchers better tools for understanding the mechanisms behind the disease, which affects more than 4000 Norwegian men annually. With time, it could lead to better diagnosis and more targeted treatment.

Prostate biopsies.“Today there is no common consensus on how best to gather fresh tissue samples to understand the disease progression in individual prostate cancer patients,” says urologist Helena Bertilsson at the Department of Laboratory Medicine Children’s and Women’s Health (LBK), NTNU, and the Department of Urology at St. Olavs Hospital.

Bertilsson and her colleagues have found a new method for handling fresh tissue from prostate glands to study the genetics, proteins and metabolites. The goal is to understand the tumour’s biology and what makes cancer aggressive or not.

Magnetic resonance spectroscopy (MRS) is a method for looking at the metabolism in cells, which gives information about the cells’ biochemical reactions.

Metabolites are molecules that participate in, or are made as a result of the metabolism in the cell.

Prostate cancer is a malignant tumour in the prostate gland and is the most common form of cancer among Norwegian men.

“We have developed a quick and simple method which preserves the tissue through quick freezing, at the same time as the fresh tissue is kept in a form that enables researchers to answer many research questions of high current interest. One should be able to easily adopt it in the laboratory and know exactly what types of cells are present in the sample – and one should be able to analyze not only genes, but also proteins and metabolites.”

Bertilsson adds that when analyzing tissue at a molecular level, it is important that the quality of the genetic materials is as high as possible to obtain reliable results – and the make-up of the tissue is an important factor in the quality of the genetic material.

Better understanding

The new method could also hold a key to a better understanding of prostate cancer. Through the use of magnetic resonance spectroscopy (MRS), the researchers have looked at the cancer cells’ metabolism and compared this with the cells’ DNA profile (gene expression).

We already know that the level of the metabolite citrate is lower in prostate cancer cells, whereas the level of choline is higher. What we do not know so much about is why. Bertilsson has therefore studied these variations together with genetic data to see if and how they correlate.

One of the findings is that although some genes may seem very important in isolation, it is not given that they are the genes that actually impact the cancer cells’ ability to grow and spread. By comparing metabolic differences with genetic variation, different genes can emerge as important – genes that otherwise might have been dismissed as unimportant.

This is something Bertilsson wants to study further:

“This is what makes research fun – new ideas are formed all the time! It is something I would like to look more into in an animal model. What if we blocked this gene? The hypothesis is that the tumour would decrease and that we would see this as a reaction in the metabolite citrate.

“We will also look more at the genetic data, as we have only scratched the surface,” Bertilsson says.

This is something that could lead to more targeted treatment in the future.

More forms of cancer

The method developed at LBK also applies to other forms of cancer, such as kidney cancer, testicle cancer and breast cancer. There is also an on-going pilot study for intestinal cancer.

Related publications

Thesis defence

Helena Bertilsson will defend her thesis: “Prostate Cancer – translational research optimizing tissue sampling suitable for histopathologic, transcriptomic and metabolic profiling” at the Auditorium, Medisinsk teknisk forskningssenter, NTNU, Friday 21. September at 12.15.

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