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New method for characterizing brain tumors

Blogger: Morteza EsmaeiliMortezaE
Postdoctoral Fellow at MR Cancer Group, NTNU

 

A new non-invasive method can identify a special mutation in a type of brain tumor called gliomas. This unique test can assist in research towards new treatments that target cancer cells in glioma patients carrying this mutation. The new method is developed by my colleagues and me at MR Cancer Group at NTNU and researchers at the Departments of Radiology and Pathology of Radboud University Medical Center in Nijmegen. We believe it is an important step towards improved tools for the diagnosis and treatment evaluation of brain tumor patients.

Gliomas are common subtypes of primary brain tumors that originate from glial cells in the brain. There are different grades of gliomas, indicating their degree of aggressiveness; however, they are most often classified as “low-grade” or “high-grade” gliomas. Glioblastomas are the most aggressive type of gliomas. Various types of gliomas have been identified, and they have different clinical behavior and response to treatment. This means there is an urgent need for more accurate and precise diagnosis, prognosis, and therapy monitoring tools.

MR-bilde av en hjerne

Gliomas are common subtypes of primary brain tumors that originate from glial cells in the brain. A new non-invasive method can identify a special mutation in gliomas. (Photo: Geir Mogen/NTNU)

Conventional anatomical imaging methods, such as magnetic resonance imaging (MRI) (Figure 1), provide limited information on tumor characterization and prognosis. Advances in personalized patient management and new drug treatments for brain tumors have generated increasing demand for reproducible, non-invasive, quantitative imaging biomarkers.

Recent developments have concentrated on the role of physiological and metabolic MRI, such as magnetic resonance spectroscopy (MRS, see an example in Figure 2), and other molecular imaging methods in understanding the metabolic processes associated with tumor growth and progression. These studies have indicated that cancer cell metabolism, contrary to the metabolism in normal cells, is modulated and reprogrammed to facilitate additional/excessive demands for biomass generation and rapid cellular growth and proliferation. This particular characteristic of cancer cells can be targeted as a “weak point” to kill these cells.

This particular characteristic of cancer cells can be targeted as a “weak point” to kill these cells.

Furthermore, the utility of various techniques in distinguishing between aggressive and benign tumors, tumor grading, and treatment response evaluation and monitoring are also of interest.

Conventional MR imaging of glioblastoma

Figure 1: Conventional MR imaging of glioblastoma. Tumor regions can be identified by different MR contrasts; For example, (A) T1-weighted pre-contrast exhibit a low-intensity lesion in the left frontal lobe region (yellow arrow), (B) post-contrast MR image demonstrates a focus of enhancement in that area, (C) and T2-weighted MR image shows increased-intensity at the same region. These MR techniques enable non-invasive imaging and diagnosis of tumor lesions in the brain. Illustration is adapted from Ahmed R. et al. Cancer Manag Res, 2014 (with permission).

During our study, we uncovered a new imaging biomarker to identify glioma subtypes with different prognosis and therefore this biomarker may be used for a better clinical management, avoiding extra cost for patients and communities. More specifically the biomarker concerns metabolite levels associated with a mutated IDH gene found in more than 70% of the brain tumors classified as low-grade gliomas and secondary gliomas. Glioma patients with this mutation actually have a better prognosis.

In particular, with our MRS technique we observe the indirect effect of the mutation in the IDH1 gene on the level of some phospholipid metabolites, which can be considered a molecular “finger print” for this mutation. These metabolites are major components of phospholipid metabolism in the synthesis of cancer cell membranes.

MR spectroscopy provides information additional to conventional MRI

Figure 2: MR spectroscopy provides information additional to conventional MRI. T2-weighted MR images of a mouse brain with glioma tumor (top, A) and a healthy mouse brain (bottom, B), and corresponding MRS data from area of interest (blue circles, C and D). MRS detects signals for different metabolites in normal brain and tumor tissue. In particular phospholipid metabolites are of interest to characterize brain tumors. (from left to right); PE, phosphoethanolamine; PC, phosphocholine; GPE, glycerophosphoethanolamine; GPC, glycerophosphocholine. Adapted from Esmaeili M. et al. Cancer Res. 2014 (with permission).

To be a bit technical: IDH1 acts in an energy-generating pathway known as the citric-acid cycle, and the IDH1 mutations associated with cancer causes a metabolite called 2-hydroxyglutarate to accumulate. IDH1 catalyzes the conversion of isocitrate into α-ketoglutarate, a reaction that takes place in energy-generating metabolic pathways. Most remarkable is that the mutated IDH1 enzyme has acquired the capacity to produce 2-hydroxyglutarate, which can accumulate in high concentrations in gliomas with the mutation. 2-hydroxyglutarate is commonly called an oncometabolite. Our finding shows that the mutation also alters lipogenesis in brain cancer cells. Phospholipid metabolism is a major network supporting cellular lipogenesis and cell membrane turnover.

The discovery of the IDH1 mutation has generated such intense interest that pharmaceutical companies are keen to find drugs that target mutant IDH1 gliomas

The discovery of the IDH1 mutation has generated such intense interest that pharmaceutical companies are keen to find drugs that target mutant IDH1 gliomas, with some companies focusing exclusively on targeting cancer metabolism. The findings of this study and those published recently on IDH related metabolism could be used in the development of drugs for cancers with these mutations. In addition, these findings enable the detection through non-invasive imaging of the direct metabolic consequence of a genetic mutation in a cancer cell. This offers a potential new tool in the management of brain tumor patients.

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Spectacular images of tumor blood vessels

Jana CebullaBlogger: Jana Cebulla
PhD Candidate at MR Cancer group

 

Angiogenesis is the formation of new blood vessels from pre-existing vessels. This process takes place during wound healing, but is also essential during the development of certain diseases, such as cancer.

In order to grow beyond a size of 1-2mm, tumors send out chemical signals telling nearby blood vessels to send new vessels in the direction of the tumor. This way, the cancer cells can get sufficient supplies of oxygen and nutrients. Angiogenesis has also been found to help cancer spread to other parts of the body (i.e. metastasize).

Blood vessels that are recruited by a tumor

Blood vessels (orange) that are recruited by a tumor (white) which was grown on the leg of a mouse (surrounding “healthy” tissue in blue). Photo: Jana Cebulla

Hopefully, in the future the worldwide research on angiogenesis can help put together all the pieces in the puzzle and describe how angiogenesis in cancer is regulated and how we can influence it with drugs in order to treat cancer patients more effectively.

Continue reading

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Copenhagen next!

We’re off to Copenhagen! You can meet us at the Science in The City festival from tomorrow until Thursday 26. July.

This is what we are doing there: http://scienceinthecity.dk/en/event/6-can-u-hear-u-sound

On Saturday at 17:00 our researcher Garrett Newton Andersen will demonstrate a hand-held ultrasound machine (Vscan) on stage: http://scienceinthecity.dk/en/event/103-scan-your-heart-stage-can-u-hear-u-sound

ScienceintheCity

 

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Applied Human Physiology in Extreme Environments

Blogger: Andreas Møllerløkken Andreas Møllerløkken

 

 

 

The NTNU Barophysiology Group aims to promote safety and minimize the acute and long-term harmful effects of diving and other extreme environmental exposures. Our work covers the topics of both basic and applied research. Through a translational approach, we study animal models to provide novel and comprehensive knowledge of pathophysiological mechanisms. We also use human field and laboratory studies to obtain physiologically relevant data.

This week we arrange a course, “Enjoy the Cold – Health, Protection and Survival in the Cold – Adaptation and risk assessment of human activities in cold environments” in Ny-Ålesund, Svalbard. This course aims at giving people who are working and participating in activities related to cold environments proper training and insights on different equipment that exists which can be used to manage the different challenges one faces in the cold environment. Through a combination of lectures, discussions, practical work and use of equipment, the participants will gain an intimate knowledge on how to handle work situations as well as accidents.

Measuring oxygen consumption during field work

Measuring oxygen consumption during field work

The Arctic areas have become regions of global importance because of their enormous natural resources and their strategic position. These northern areas are cold, harsh and hostile to man. Working in them is difficult, expensive and demands high levels of technical, scientific, and physiological expertise. Cold weather exposure can cause immediate health problems. For people with ailments, cold exposure can lead to new symptoms, or aggravate those existing. Cold exposure may also cause pain and disease in healthy subjects.

A number of climatic factors are known to increase challenges related to work in the northern areas, such as temperature, wind, icing, the polar low, uncertain weather forecasts and polar night. In addition to climatic factors, regulation of body temperature is affected by activity, technical protective actions/systems and clothing. The climatic problems connected with activity in the arctic areas are not only limited to equipment and equipment function. Cold is one of the most dangerous environmental risk factors for man. Not only does the cold challenge day to day function in those prepared for such an environment, but if conditions become more extreme, then it may also challenge survival. Although the human body has a physiological control mechanism, homeostasis, to maintain a stable and optimal internal environment independent of a changing external environment, this mechanism is not protection enough in the sub-arctic areas. Man is totally dependent on personal protective equipment, established working procedures and training to perform the work within specified safety and efficiency limits.

 Man is totally dependent on personal protective equipment, established working procedures and training

Increasing development and human activity in the Arctic environment calls for increased research focus on the appropriate applied human physiology in order to increase our knowledge on how the organism adapts to extreme environments.

It is well recognized that cold environments have negative health effects on the human body, but an important question is are there any increased health risks due to the physiological stress and decreased performance associated with survival requirements, for example having to wear heavy protective clothing constantly?

The course participants gets to experience field testing of immersion suits

The course participants gets to experience field testing of immersion suits

As diving is likely to be an important activity in these regions, the long-term health effects for divers who undertake the majority of their work in cold water should also be considered. More knowledge is needed to understand which processes come into play when the body’s ability to adaptation is exceeded, why one human reacts differently to another when exposed to the same environments and stressors, and how we can prepare ourselves to be protected against adverse health effects of exposures to extreme environments both in the short and long term.

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In 1990 the course “Health, Protection and Survival in the Cold” was arranged at Svea, and this was the first course in a series of courses that have been held throughout the years since then. All in all, some 250 persons have participated the course since its beginning in 1990, to get a better understanding of the different elements one meets in extreme environments and how they influence our own physiology.

With the increasing activity in the arctic regions, research within the human physiology and its response in the cold environment is necessary and give bases for our course.

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Are you at PhD student or Supervisor within Cardiovascular Disease in Norway?

Blogger: Øivind RognmoØivind Rognmo2

Are you at PhD student or Supervisor within Cardiovascular Disease in Norway?

I will recommend you to be members of the Norwegian PhD School of Cardiovascular Research (NORHEART) as it may offer you a lot of benefits.

 Foto: Geir Mogen, Istockphoto.com

NORHEART members comprise PhD students in Norwegian cardiovascular research, their supervisors, as well as lecturers from Norway and abroad. Sign up today to be a part of the number one education network for cardiovascular scientists in Norway!

Who can become member of NORHEART? All students from PhD programs or Medical Students Research programs at Norwegian Universities with projects focused on cardiovascular research. Supervisors, postdocs and other researchers within the field of cardiovascular research are also encouraged to register as members. Previous student members are listed as NORHEART alumnis.

What are the benefits for NORHEART members?

  • Priority at NORHEART events
  • Opportunities for travel and exchange grants
  • Automatic e-mail updates on key NORHEART events

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Improving nanoparticles for battling cancer

Blogger: Sjoerd Haksjoerd hak

 

The Research Council of Norway has recently awarded grants under the funding scheme Independent Basic Research Projects – Medicine, Health Sciences and Biology (FRIMEDBIO). There is tough competition for this funding nationally, and only the best projects get through. The Faculty of Medicine, NTNU, has been awarded funding for three talented young researchers, three research projects and two post docs. You can read about all these projects on the blog over the coming weeks. Sjoerd Hak received FRIMEDBIO-funding for his post doc project: “Multimodal in vivo study of nanoparticle decomposition and targeting dynamics”

In the field of nanomedicine, the use of drug loaded nanoparticles to deliver drugs to tumours is now well established (see Figure 1).

Tumour bloodvessels are very leaky as compared to healthy vasculature. When drug loaded nanoparticles are injected into the bloodstream, they can leak from the leaky tumour bloodvessels into the tumour tissue; whereas leakage from the blood vessels in healthy tissue is limited.

Exciting developments in nanotechnology have allowed for the production of a wide variety of advanced nanoparticles.

As compared to conventional therapy without nanoparticles, this results in a larger part of the injected drugs ending up in the tumour and a reduction in side effects (Figure 1B).

Figure 1. A: General design of a nanoparticle loaded with drug. The core/shell/surface coating can be composed of a variety of different materials, which has resulted in an enormous diversity in the design, and hence properties, of different nanoparticles. B: When a drug loaded nanoparticle is injected into the blood, it can leak into the tumour tissue due to the leaky tumour blood vessels. C: General design of a targeted nanoparticle loaded with drug. D: Nanoparticles can be specifically targeted to the cells making up the tumour vasculature. When these are injected into the blood, they accumulate in the tumor vasculature. The targeting and subsequent disrupting of tumour blood vessels is a promising therapeutic strategy. E: Nanoparticles can also be specifically targeted to cancer cells. When these targeted nanoparticles are injected into the blood, they accumulate in the tumor and bind to tumor cells, increasing the amount of drug delivered to individual cancer cells.

Figure 1. A: General design of a nanoparticle loaded with drug. The core/shell/surface coating can be composed of a variety of different materials, which has resulted in an enormous diversity in the design, and hence properties, of different nanoparticles. B: When a drug loaded nanoparticle is injected into the blood, it can leak into the tumour tissue due to the leaky tumour blood vessels. C: General design of a targeted nanoparticle loaded with drug. D: Nanoparticles can be specifically targeted to the cells making up the tumour vasculature. When these are injected into the blood, they accumulate in the tumour vasculature. The targeting and subsequent disrupting of tumour blood vessels is a promising therapeutic strategy. E: Nanoparticles can also be specifically targeted to cancer cells. When these targeted nanoparticles are injected into the blood, they accumulate in the tumour and bind to tumour cells, increasing the amount of drug delivered to individual cancer cells.

Although this has improved therapy for a group of cancer patients, the full potential of nanoparticles in cancer therapy remains to be explored. Exciting developments in nanotechnology have allowed for the production of a wide variety of advanced nanoparticles.

One highly interesting development is the synthesis of so-called targeted nanoparticles: Nanoparticles equipped with molecules on their surface making them specifically recognise and accumulate in tumour tissue (Figure 1C). This is a very promising approach to deliver drugs specifically to tumours and to spare healthy tissue (Figure 1 D-E).

For the development and successful application of such targeted nanoparticles, detailed studies to learn about and understand the in vivo behaviour of these novel targeted nanoparticles are essential.

For example, it is not well known how fast targeted nanoparticles accumulate in tumour tissue after injection. Moreover, it is now becoming clear that certain nanoparticles readily disintegrate upon injection into the blood, resulting in drug release in the blood. As such, the drug may be released before the tumour is reached. Hence, knowledge of nanoparticle degradation and tumour targeting rates and dynamics are crucial for successful development and application of targeted nanoparticles. However, these dynamics remain largely unstudied, which may be compounded by the fact that suitable experimental in vivo tools to do so are lacking

Ultimately, we anticipate to fine-tune our nanoparticle design and increase their value in the battle against­­­ cancer.

Over the last four years, during my recently completed PhD project, we have established the synthesis of innovative nanoparticles of which such dynamics can be quantitatively monitored. Furthermore, combining in vivo microscopy and magnetic resonance imaging, we have developed a unique experimental set-up which is highly suitable to study in vivo nanoparticle dynamics.

Over the next years, this novel experimental approach will be exploited to study degradation and targeting dynamics of our nanoparticles at an unprecedented level of detail. Importantly, this will provide general knowledge applicable to a variety of targeted therapies. Ultimately, we anticipate to fine-tune our nanoparticle design and increase their value in the battle against­­­ cancer.

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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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Breast cancer research beyond borders

Blogger: Maria Dung CaoMaria Dung

 

 

 

 

I have just spent 6 months away from home and worked at one of the well-known and respected breast cancer research groups in the field of magnetic resonance (MR) at Johns Hopkins University School of Medicine, Baltimore, USA.

Baltimore is an interesting city famous for its National history, good university, and high crime rate. To ensure the safety of the people, the city offers free shuttles and buses between campuses and also downtown.

Fotokollasje3brystkreft

Pictures from Baltimore and my colleagues Asif Rizwan, me, Samata Kakkad and Lu Jiang.

Baltimore is a big contrast to the small town of Trondheim where I have my regular job as a postdoctoral fellow at the research group The MR Cancer Group at NTNU headed by Tone Frost Bathen. Our group has established a solid competence in the field of MR and cancer, being internationally recognized as one of the most experienced groups in large-scale cancer tissue analyses. So even though Trondheim and Baltimore are quite different, we are joined by our interest for breast cancer research.

So, what did I do in Baltimore?  The research project includes biopsies from Norwegian breast cancer patients. The samples were collected for more than 10 years ago. They have been stored in liquid nitrogen (-190 Celsius) to minimized tissue degradation. The quality of the samples is well preserved even with long-time storage. This enables us to perform modern medical analyses that were not available at the time of sample inclusion.

We aimed to identify metabolites (small chemical compounds utilized and produced by the cells) and genes that can be used as new targets for breast cancer treatment. The studies of metabolites and genes are complementary and are important to improve the understanding of cancer biology and how cancer cells react to different treatment. We have performed the metabolite analysis here at NTNU and the gene analysis at Johns Hopkins.

BC1

We found that the metabolite profile (a spectrum of detectable metabolites in a sample) of breast cancer can be used to give information about breast cancer survival. Based on the metabolite profiles we were able to discriminate between patients that experienced cancer recurrence and died before 5 years and patients that survived more than 5 years. We identified a gene called GDPD5 that can be associated with tumor aggressiveness by regulating the choline phospholipid metabolism that is known to change in breast cancer.

At present, we are investigating the biological effects of targeting the GDPD5 gene in breast cancer cells. Also, we are developing system to deliver this treatment in animal models to investigate the effect of treatment in a living organism.

Findings from this project can be useful for developing new targeted therapies, especially for patients that have a more aggressive tumor and does not response well to currently available treatments.

BC2

A research stay abroad is not just about work, but also a chance to experience a new country, new friends, and colleagues. I have had a great time during my stay and have enjoyed working with people with diverse expertise in breast cancer research. I do think that a research stay abroad is a good opportunity to experience and learn something new.

It is also a good way to establish international collaboration between NTNU and other Universities around the world. However, from my experience, you do need to work hard and have a good and achievable project plan. The preparation beforehand can be time-consuming and tedious, which could make you lose interest, but we do have a good support system at NTNU and the people at the administration have been very helpful. So I would like to thank them, and a special thanks to the patients participating in this research project and Helse Midt-Norge for funding.

 

 

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What does the metabolite say? Can we predict cancer and heart disease?

Riyas_Vettukattil

Blogger: Riyas M. Vettukattil

 

 

 

 

When working as a doctor out in the clinic, I was always puzzled by a set of questions which are beyond the routine diagnostic challenges: I always wondered what makes people with similar build, age, ethnic background with a common diet and lifestyle habits end up with such different destinies? Some would die of a heart attack or perhaps a brain tumour within a few months, while others would live for years with no heart disease or cancer. How does a clinician know which person in his or her waiting room is at an immediate risk?

Unpredictable killers?

Cancer and heart disease are the leading causes of mortality in the developed world, and in many developing countries. It is a widely accepted fact that these diseases have “multifactorial” origin in most patients, meaning that these diseases cannot be explained by genetics alone and that the causative elements vary in an unpredictable fashion from patient to patient.

But what would happen if we had a lab test which could say something about risks and best treatments?

We have several laboratory tests, but so far no test can reliably identify who will get these illnesses and who won’t. The existing clinical and pathological tools for both these diseases are insufficient for accurate response prediction and for an individualised treatment.

But what would happen if we had a lab test which could say something about risks and best treatments?

Metabolites

What the metabolites say

Metabolomics, or the study of small molecular metabolites which are chemical substances produced as a result of the cells’ metabolism, could provide some answers. The identification of metabolic biomarkers for cardiac disease and cancer risk prediction, diagnosis and treatment response, could have the power to increase overall survival and the patients’ quality of life, as well as saving huge expenses for society.

As a part of my recently completed PhD research at the MR Cancer Group in Trondheim, we found aerobic fitness dependent differences in serum levels of free choline and phosphatidylcholine in a group of healthy volunteers from the Nord-Trøndelag health study (HUNT). Maximal oxygen uptake (VO2max) is the maximum capacity of an individual’s body to transport and use oxygen during incremental exercise, which reflects the physical fitness of the individual. In healthy people, VO2max is the best predictor of future cardiovascular disease (CVD) mortality. Hence, it is interesting to identify new biomarkers for low aerobic fitness that may also have a potential as early biomarkers of cardiovascular disease risk.

As we saw an association between aerobic fitness and serum levels of choline-containing metabolites (choline is an essential nutrient and its metabolites are needed for maintaining structural integrity and signalling roles for cell membranes). These metabolites could be early markers of heart disease risk, although this needs further validation studies. Detecting early warning signs of cardiovascular risks in a healthy population may further help in intervention programmes, such as lifestyle modifications, and thereby improve community health.

MR metabolomics er studien av små molekylære metabolitter. (Foto: Geir Mogen)

MR metabolomics the study of small molecular metabolites. (Photo: Geir Mogen)

In another study, the possibility of differentiating diffuse World Health Organization (WHO) Grade II and IV astrocytoma (a type of brain tumour) based on their metabolic profiles were shown. This is one of the common primary brain tumours in humans, which have very poor prognoses at higher grades. High and low grade astrocytomas are managed differently, and therefore it is essential to identify molecular and metabolic factors that may classify these patients with regards to optimal treatment and prognostication. Identifying new biological indicators using metabolomics offers a new objective diagnostic approach, which depends solely on biomarkers that can improve the accuracy of tumour grading and patient stratification.

These metabolic markers are still a long way from reaching routine clinical use. Still, I strongly believe that these are the first steps in that direction.

In a third study, metabolic markers of chemotherapy-related changes in ovarian serous carcinoma effusions were identified. The collection of fluid in the abdominal cavity and around the lungs (known as malignant effusions in serosal cavities) is seen in advanced stages of ovarian, breast and gastrointestinal cancers. Studying metabolites in theses fluids can provide important information about the exposure to chemotherapy, and metabolic characterisation could be a promising technique to further understand the mechanisms of abnormal fluid collections (effusion) development in malignant tumours, and to target clinical intervention.

These studies show that metabolomics techniques are useful in capturing molecular signatures of cancers and aerobic fitness, and may contribute further to the scientific understanding of the underlying biology.

However, these metabolic markers are still a long way from reaching routine clinical use. Still, I strongly believe that these are the first steps in that direction.

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Breast cancer, nanoparticles and superglue

Blogger: Siver A. MoestuePortrettbilde Siver

 

 

 

One of the best things about being a researcher is that you can work on completely new ideas and concepts without giving much thought to what is actually possible or not. Often it turns out that what you thought was impossible is possible after all if you a) develop a new technology, b) let enough researchers work on it for long enough, or c) have a bit of luck. Preferably all three.

One of the areas where we are still at the starting line is nanomedicine. Even though we are capable of making particles at nanoscale today, we know little about what role they will play in tomorrow’s medicine. In the meantime we can enjoy ourselves with hatching clever, and less clever, ideas and evaluate how far they could contribute to improved treatments in the future.

Elektronmikroskopbilde av nanopartikler (foto: YRR Mørch/SINTEF)

Electron microscope image of nanoparticles. (Photo: Yrr Mørch/SINTEF)

This is the status at NTNU today: In cooperation with SINTEF, we can under controlled conditions produce particles with a diameter of a few hundred nanometres (which is about as much as your fingernails grow while you read this…). These particles are made from the same plastic materials that are used in superglue. But at SINTEF they let the glue “dry” in such a way that we maintain a whole different level of control over shape, size and characteristics, than if you glue a broken cup together. In this way they produce tiny little plastic particles. They can also put things inside them or decorate them with all sorts on the outside. If you place them in water together with some proteins and give them a shake, they can even join up and produce air-filled bubbles.

You can read more about nanotechnology at SINTEF here.

Gassbobler laget av nanopartikler sett gjennom konfokalmikroskopet. (Foto: Yrr Mørch/SINTEF)

Gas bubbles made from nanoparticles seen through a confocal microscope. (Photo: Yrr Mørch/SINTEF)

Nanoparticles can be used for many things. At NTNU there are now about 20 researchers looking into how these tiny superglue particles can be used to improve cancer treatment. And so some of us privileged researchers are allowed to be creative.

Could we use these particles to detect cancer? Perhaps by placing a contrast agent inside and decorating the outside with something that recognises cancer cells? Or could it perhaps be smarter to use them to treat cancer? One of the problems with breast cancer treatment is that patients have to stop chemotherapy due to side effects. But if we could make sure that more chemo ends up in the tumour and less ends up in places where it causes side effects, this problem could largely be solved.

Researchers at NTNU, for example, work on filling the superglue droplets with chemo, making them into ‘large’ bubbles (about as much as a fingernail grows in an hour…), so that the superglue-droplet chemo can safely be transported around in the blood stream. And here comes the great trick: By targeting the superglue-droplet chemo-bubbles with ultrasound waves, we could make them burst where we want them to (for example in a tumour) so that the chemotherapy is released just there and nowhere else. This sounds difficult, but NTNU has for many years been a world leader in ultrasound technology. If we gain control over the behaviour of the nanoparticles, this should absolutely be possible.

superlim (foto: iStock)

Superglue, nanoparticles and breast cancer. (Illustration: iStock)

Finally, my own personal dream for the future: Nanoparticles containing chemo which are decorated with 1) structures that recognise cancer cells, and 2) structures making them ‘invisible’ to the body. Such particles could circulate in the blood over longer periods of time, acting as secret agents. When they find a unsuspecting cancer cell in the blood stream, they can attach themselves and deliver a suitable dose of chemo. The application? Well, you could imagine that such particles could help prevent a relapse in breast cancer patients after surgery, because often there will remain a few cancerous cells in the body that could cause a relapse several years after an operation.

Is any of this possible? 10 years ago many would have said a resounding “NO”, but now we can stretch to a “perhaps” or “why not”. The research area is growing, both at NTNU and in other places, thanks to research funding from, for example, the Norwegian Cancer Society and the Research Council of Norway. There is a steep learning curve, and we learn something new about these particles literally every day – a dream existence for a researcher.

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