Researchers from the University of Leeds, UK, the Charité University Medical School and the Max Delbrück Centre for Molecular Medicine (MDC) in Berlin, Germany, have discovered a new driving force behind cancer growth.
Their studies have identified how 'junk' DNA promotes the growth of cancer cells in patients with Hodgkin's lymphoma. Professor Constanze Bonifer (University of Leeds) and Dr Stephan Mathas (Charité, MDC) who co-led the study suspect that these pieces of 'junk' DNA, called 'long terminal repeats', can play a role in other forms of cancer as well. The work is published in Nature Medicine.*
The researchers uncovered the process by which this 'junk DNA' is made active, promoting cancer growth.
"We have shown this is the case in Hodgkin's lymphoma, but the exact same mechanism could be involved in the development of other forms of blood cancer," said Prof. Bonifer. "This would have implications for diagnosis, prognosis, and therapy of these diseases."
'Long terminal repeats' (LTRs) are a form of 'junk DNA' - genetic material that has accumulated in the human genome over millions of years. Although LTRs originate from viruses and are potentially harmful, they are usually made inactive when embryos are developing in the womb.
If this process of inactivation doesn't work, then the LTRs could activate cancer genes, a possibility that was suggested in previous animal studies. This latest research has now demonstrated for the first time that these 'rogue' active LTRs can drive the growth of cancer in humans.
The work focused on cancerous cells of Hodgkin's lymphoma (the Hodgkin-/Reed Sternberg cells) that originate from white blood cells (antibody-producing B cells). Unusually, this type of lymphoma cell does not contain a so-called 'growth factor receptor' that normally controls the growth of other B-cells.
They found that the lymphoma cells' growth was dependent on a receptor that normally regulates the growth of other immune cells, but it is not usually found in B-cells. However in this case, the Hodgkin-/Reed Sternberg cells 'hijacked' this receptor for their own purposes by activating some of the 'junk DNA'. In fact the lymphoma cells activated hundreds, if not thousands, of LTRs all over the genome, not just one.
Hodgkin-/Reed Sternberg cells may not be the only cells that use this method to subvert normal controls of cell growth. The researchers found evidence of the same LTRs activating the same growth receptor in anaplastic large cell lymphoma, another blood cancer.
The consequences of such widespread LTR activation are currently still unclear, according to the study's authors. Such processes could potentially activate other genes involved in tumour development. It could also affect the stability of chromosomes of lymphoma cells, a factor that may explain why Hodgkin-/Reed Sternberg cells gain many chromosomal abnormalities over time and become more and more malignant.
The Institute of Food Research has collaborated in the development of a new method for detecting spores of non-proteolytic Clostridium botulinum. This bacterium is the major health hazard associated with refrigerated convenience foods, and these developments give the food industry and regulators more quantitative information on which to base the procedures that ensure food safety.
Botulism is a rare but deadly form of food poisoning that can be caused by consuming tiny quantities of botulinum neurotoxin. The botulinum neurotoxin is the most potent toxin known (just 30ng of neurotoxin is sufficient to cause illness and even death), and the consumption of as little as 0.01g of food in which C. botulinum has grown can result in botulism.
The majority of cases of foodborne botulism are caused by two bacteria known as non-proteolytic C. botulinum and proteolytic C. botulinum. A major difference between these two bacteria is that non-proteolytic C. botulinum is able to grow and produce toxin at 3°C, whilst proteolytic C. botulinum will not grow at temperatures less than 12°C.This ability to grow at form toxin at refrigeration temperatures makes non-proteolytic C. botulinum a major hazard in minimally heated refrigerated foods, such as chilled ready meals.
The production incorporates practices and risk assessments based on the latest scientific information, such as spore heat resistance, growth properties of non-proteolytic C. botulinum, and the incidence of these spores in food. The new method of detecting non-proteolytic C. botulinum is providing high quality information on the incidence of spores in food. An important feature of the new method is that it is specific, and enumerates only non-proteolytic C. botulinum spores. Some previous techniques were not optimised to distinguish between non-proteolytic C. botulinum and proteolytic C. botulinum. The new method is verysensitive with a low detection limit that has been achieved by the use of a selective enrichment and large test samples, and importantly this has been confirmed using carefully structured control samples.
The robust method was developed as a collaboration between the Nestlé Research Centre, Switzerland and IFR, an institute of the Biotechnology and Biological Sciences Research Council (BBSRC) and is designed to provide the data the food industry needs for quantitative microbial risk analysis and the implementation of food safety objectives. This allows the total risk from spores of non-proteolytic C. botulinum in the final meal to be calculated. Modelling the risk of this total spore count rising above safe levels and the frequency that this event occurs will allow the management and control of the process more accountably.
