A recent analysis of clinical trial results performed by the Radiation Therapy Oncology Group (RTOG) demonstrate that a chromosomal abnormality—specifically, the absence (co-deletion) of chromosomes 1p and 19q—have definitive prognostic and predictive value for managing the treatment of adult patients with pure and mixed anaplastic oligodendrogliomas. The presence of the chromosomal abnormality was associated with a substantially better prognosis and near-doubling of median survival time when treatment with combined chemotherapy and radiation therapy was compared to treatment with radiation therapy alone.
Oligodendrogliomas are uncommon tumours that represent approximately 4.0% of all brain tumours. Mixed oliogdendrogliomas (those also containing astrocytic elements) account for 1.0% of all brain tumours. Pure and mixed oligodendrogliomas that contain anaplastic (malignant) cells typically grow more rapidly than non-anaplastic tumours.

The RTOG 9402 trial A Phase III Intergroup Randomized Comparison of Radiation Alone vs. Pre-Radiation Chemotherapy for Pure and Mixed Anaplastic Oligodendrogliomas was conducted with four other National Cancer Institute (NCI)-supported co-operative groups. Trial participants had a pathologically confirmed pure or mixed anaplastic oligodendroglioma and were randomly assigned into one of two treatment arms. The 148 participants randomised to Arm 1 were treated with PCV (procarbazine, CCNU [lomustine] and vincristine) chemotherapy and radiation therapy (RT), and the 143 participants randomised to Arm 2 were treated with RT alone.

RTOG 9402 study results showed no survival benefit for patients treated with early PVC chemotherapy plus RT over RT alone. Although a significant impact on median progression-free survival time was realised (2.6 years versus 1.7 years for RT alone), the regimen was associated with significantly more adverse side effects. The study authors also reported that study participants in both arms whose tumour lacked chromosomes 1p and 19q had longer median survival times as compared with participants without these deletions (> 7 vs. 2.8 years, respectively). This led the study authors to conclude that ‘tumours with 1p and 19q co-deletion are less aggressive or more responsive to PCV chemotherapy or both.’

A recent analysis undertaken of the RTOG 9402 data (at a median study participant follow-up time of 11 years) is planned for submission to the 2012 American Society of Clinical Oncology Annual Meeting. However, due to the finding’s significance for patient care, results are reported here in advance of submission. Radiation Therapy Oncology Group

Scientists based at the Cancer Research UK Cambridge Research Institute have discovered how receptors for the female sex hormone oestrogen attach to a different part of the DNA in breast cancer patients who are more likely to relapse, according to a study.
Crucially, they also found that within these more aggressive breast cancers, the oestrogen receptor (ER) was being ‘redirected’ to a different part of the genome by a protein called FOXA1. So drugs that specifically block FOXA1 could help treat patients who do not respond to conventional hormone treatments, such as tamoxifen.
The researchers used state of the art technology, called ChIP sequencing, to analyse ER-genome interactions in frozen breast tumour samples and create a map of all of the sites in the human genome where ER attaches itself to the DNA and switches on particular genes.
This map was used to compare where in the genome ER attached in tumours from people that responded well to treatment, versus those that went on to relapse or were resistant to treatment from the start.
This revealed almost 500 contact points that were common across all the samples analysed, but also a distinct set of contact points specific to patients with different clinical outcomes – of which 599 were associated with good response to treatment and 1,192 with poor response.
Studying patterns of gene activity in these two areas of the genome allowed the researchers to identify a subset of genes that are more active in tumours that return and spread.
Carlos Caldas, Professor of Cancer Medicine at the Department of Oncology at the University of Cambridge and the Cancer Research UK Cambridge Research Institute said: ‘Some breast cancers are treated with hormone treatments, such as tamoxifen, which work by blocking oestrogen receptors. But we know that about a third of patients either fail to respond to this type of treatment or go on to relapse at a later date.
‘Understanding the genetic differences that determine who will or won’t respond to a given treatment is a vital step in being able to choose the right drugs for individual patients. The next step will be to see if these findings can be repeated in larger groups of patients.’
Cancer Research UK’s Dr Jason Carroll, who jointly led the study with Professor Caldas, said: ‘These findings suggest that ER binds to different regions of the genome DNA in breast cancer patients that respond to treatment, compared to those that relapse and whose cancer spreads.
‘We know from previous studies involving breast cancer cells growing in the lab that a protein called FOXA1 is needed for oestrogen receptors to interact with the DNA and switch on genes that fuel cancer growth. But this is the first time we’ve examined frozen tumour samples and shown that FOXA1 redirects ER to different locations within the DNA in patients with different outcomes. This switches on different sets of genes, which in turn affect the outcome of the patient. We now hope to develop ways of blocking FOXA1 to help treat patients who no longer respond to standard treatments.’ University of Cambridge

As well as announcing the launch of a new global diagnostics business unit at Medica last month, Avantor Performance Materials also announced the creation of a new diagnostics product brand: BeneSpheradiagnostics solutions, which will include a broad and expanding range of reliable, affordable diagnostic technologies and easy-to-use products, focused on three segments: in vitro reagents and instruments for clinical chemistry, immunology, haematology, microbiology, histology and cytology and genetic testing; instruments for in vivo diagnostics, currently sold under the Diagnova name in India; and consumables and instruments for life sciences research in academia, government and pharmaceutical labs, also currently sold under the Diagnova name in India.
At the moment Avantor’s performance diagnostics solutions include J.T.Baker clinical reagents, which have provided world-class solutions for haematology and histology applications for over 30 years, and BeneSphera diagnostics solutions built on Diagnova, the company’s Indian-based diagnostics business with a 25-year legacy offering products, engineering and application support for immunology, clinical chemistry, haematology, microbiology, endoscopy and life science needs.
Avantor’s plans are to grow the new global diagnostics business through organic development and the strategic acquisition of R&D-backed manufacturing and distribution companies in targeted locations to support a strong global brand and supply chain.

The discovery of a gene that causes a form of hereditary spastic paraplegia may provide scientists with an important insight into what causes axons, the stems of our nerve cells, to degenerate in conditions such as multiple sclerosis.An international team of scientists led by Dr Evan Reid at the University of Cambridge and Dr Stephan Zuchner from the University of Miami reports that mutations in the gene known as reticulon 2 on chromosome 19 cause a form of hereditary spastic paraplegia (HSP). HSP is characterised by progressive stiffness and contraction (spasticity) of the legs, caused by selective and specific degeneration of axons.
The team identified three mutations in the reticulon 2 gene as causing a type of HSP – in one case, this mutation included an entire deletion of the gene. In addition, the researchers showed that reticulon 2 interacts with another gene, spastin. Mutations in this gene cause the most common form of hereditary spastic paraplegia.
Reticulon 2 provides the genetic code for a reticulon protein that is a member of a family of proteins recently shown to have a key role in shaping the endoplasmic reticulum. The endoplasmic reticulum is a network of interconnected sheets and tubules that extends throughout the cytoplasm in nearly all cells.
The endoplasmic reticulum has several functions, including protein synthesis, calcium signalling and the regulation of other components of the cell. Recent data suggest the sheets are involved in protein synthesis, whereas the tubules are specialised to carry out the other functions.
This new study provides the most direct evidence to date that defects in how the endoplasmic reticulum is shaped and formed could underlie axon degeneration. When axons degenerate, signals are unable to pass through the nerve cells, leading to a breakdown of communication within the central nervous system. This is common in degenerative diseases of the nervous system, such as multiple sclerosis.
‘Our work highlights important new disease mechanisms, which may provide a platform for us to study how axons are damaged in devastating illnesses such as HSP, and perhaps even in multiple sclerosis, which in some cases is very similar to HSP,’ explains Dr Reid, a Wellcome Trust Senior Research Fellow in Clinical Science. ‘But we must not forget how this work may immediately directly benefit families affected by HSP, for whom the discovery now opens up the possibility of genetic counselling and testing.’ Wellcome Trust

Roche Accu-Chek^® Inform II test strips chosen by CEGA Air Ambulance requirements for accuracy and ease-of-use

CEGA Air Ambulance has recently upgraded its blood glucose monitoring system to use the advanced Accu-Chek Inform II test strips from Roche.  Ensuring accurate and reliable results across a wide range of glucose levels, these easy to use blood glucose test strips provide the performance criteria necessary for monitoring critically ill patients prior to, during and after emergency flight transfers.

“We require a reliable, easy to use, professional tool for blood glucose measurement,” comments CEGA Senior Flight Nurse, Stuart Cox.  “After reviewing all the kits that are available on the market, we felt that the Roche Accu-Chek Inform II test strips best met our requirements for high quality patient care in the air ambulance environment.  The user interface is very simple and straightforward to use anywhere and by any of our trained staff.  In addition, the strips have a very good range compared to other systems, giving accurate results at both high and low glucose levels, which is essential for patient safety.”

Stress-induced insulin resistance and hyperglycaemia is common in critically ill patients [1,2,3] and so close monitoring of blood glucose levels is an important part of their care.  Studies have shown that maintenance of appropriate glycaemic control in such patients improves morbidity and mortality [1,4,5].

“Providing international medical assistance, including the transportation of critical care patients around Europe, we use the Accu-Chek Inform II glucose strips to assess patients prior to the flight to make sure they are stable; during the transfer to monitor them and guide any necessary treatment; and then after the flight to assess their status before handing them over to the next medical team.  The accuracy of the Accu-Chek Inform II strips ensures that patients get the right care at the right time, and we can have confidence in the results.”

The Accu-Chek Inform II test strips have undergone extensive evaluation, including studies at over 30 external sites as well as thorough internal testing [6]. The results of these evaluations demonstrate that the Accu‑Chek Inform II strips provide accurate and reliable blood glucose measurements under a variety conditions, including wide haematocrit and environmental ranges and in presence of maltose. Furthermore, the strips require a minimal sample volume of just 0.6µl and deliver accurate results from alternative sampling sites, such as the palm and forearm.

“The Accu-Chek Inform II strips mirror our needs for air ambulance work,” concludes Stuart.  “They are well researched, with evidence-based performance.  We also value the after sales and technical support we have received from Roche, which has been invaluable in the training of our staff.” www.roche.co.ukwww.cega-air-ambulance.com.

<sup>1.  Van den Berghe, G., Wouters, P., Weekers, F. et al (2001) N Engl. J. Med. 345: 1359-67
2. Van den Berghe, G. (2004) J. Clin. Invest. 114: 1187-1195
3. Mizock, B.A. Best Pract. Res. Clin. Endocrinol. Metab. 2001,15(4): 533 – 551.
4. Krinsley, J.S. (2004) Mayo Clin. Proc. 79:992-1000 
5.  Insulin in Intensive Care – The Leuven Protocol.  Intensive Care Society website: http://www.ics.ac.uk/icmprof/pubsother.asp?menuid=86. Information available on request, Roche Diagnostics, Burgess Hill, UK.</sup>