A Henry Ford Hospital research team has identified specific genes that may lead to improved survival of glioblastoma, the most common and deadly form of cancerous brain tumour.

The molecular data is expected to aid further research into genes that either help or impede the survival of patients diagnosed with the tumour, which can invade and rapidly grow in any part of the human brain.

‘Studies such as ours that help define molecular alterations associated with short-term survival likely will help define the reasons why our current treatments don’t succeed in these patients,’ says Dr. Steven Kalkanis, M.D., a neurosurgeon and surgical oncologist at Henry Ford’s Hermelin Brain Tumor Center, and lead author of the study.

‘As new mechanisms of resistance are revealed and targeted agents are developed to address these mechanisms, the number of long-term survivors should increase.’
The study focused on 476 patients at Henry Ford Hospital who were diagnosed with glioblastoma from 1995 to 2008. Each was randomly chosen from the Hermelin Center’s brain tumour tissue bank, which holds more than 4,100 unique patient brain tumour specimens.

The patients were evaluated as part of the international Cancer Genome Atlas, to which the Hermelin Brain Tumor Center at Henry Ford Hospital was a major contributor.

Besides noting a steady rise in survival rates over the 14 years examined in the study, researchers found that the median survival time among this group rose from 11.8 months in patients diagnosed from 1995 to 1999 to 15.9 months in those diagnosed from 2005 to 2008.

After categorising each patient as a short (less than nine months), medium (nine to 24 months) or long-term (at least 24 months) survivor, the researchers looked for relationships between survival time and patient age, gender, functional impairment, increases in tumour size, surgery and chemotherapy.

They then performed a molecular analysis of each tumour specimen and explored its relationship to short- and long-term survival.

Besides confirming earlier studies that showed improved survival of glioblastoma as new techniques and medications were introduced, the new study found:
•Survival times among Henry Ford patients were ahead of national glioblastoma survival trends.
•Those age 70 and older included more short-term survivors that the younger age groups.
•Gender differences were only detected when comparing the short- and medium-term survivors, with females more likely to be short-term survivors.
•The tumor’s location within the brain was not a significant factor in survival time.
•Specific genes identified by the researchers may independently improve patient survival. The Henry Ford team concluded that more and ongoing research in this area is vital to understanding how to fight the usually fatal cancer tumour.

‘Among the factors which are associated with increased survival of glioblastoma patients during the time period we studied,’ says Tom Mikkelsen, M.D., a neuro-oncologist and co-director of the Henry Ford’s Hermelin Brain Tumor Center, ‘is the multidisciplinary care co-ordinated by a dedicated tumour board as common practice for managing brain tumour patients. New expertise in neurosurgery, molecular pathology and experimental therapeutics are critical and must be personalised for each patient.’ Henry Ford Health System

The discovery of a new therapeutic target for certain kinds of myeloproliferative disease is, without doubt, good news. This is precisely the discovery made by the Stem Cell Physiopathology group at the CNIC (the Spanish National Cardiovascular Research Center), led by Dr. Simón Méndez–Ferrer. The team has shown that the microenvironment that controls hematopoietic stem cells can be targeted for the treatment of a set of disorders called myeloproliferative neoplasias, the most prominent of which are chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and atypical chronic myelogenous leukemia (CML).

The findings, published today in Nature, demonstrate that these myeloproliferative neoplasias only appear after damage to the microenvironment that sustains and controls the hematopoietic stem cells—the cells that produce the cells of the blood and the immune system. Protecting this microenvironment, or niche, has thus emerged as a new route for the treatment of these diseases, for which there is currently no fully effective treatment.

‘In normal conditions, the microenvironment is able to control the proliferation, differentiation and migration of the hematopoietic stem cell. A specific genetic mutation in these cells results in inflammatory injury to the microenvironment and this control breaks down. What our work shows is that this damage can be prevented or reversed by treatments that target the niche,’ explained Dr. Méndez-Ferrer.

Indeed, the same team of researchers has demonstrated the efficacy of a possible new treatment, which has been patented through the CNIC. The treatment involves an innovative use of clinically approved treatments for other diseases, so that, according to the authors, ‘it shouldn’t be associated with adverse side effects’. The new treatment route has been tested in animals and has received financial backing for a multicenter phase II clinical trial. ‘This study has a very strong translational and clinical potential’, emphasized study first author Dr. Lorena Arranz, who added that ‘current treatment for myeloproliferative neoplasias is largely symptomatic and directed at preventing thrombosis and fatal cardiovascular events’.

The only real cure available today is a bone marrow transplant, which is not advisable in patients over 50 years old. ‘This makes it important to identify new therapeutic targets for the development of effective treatments,’ the investigators conclude.
EurekAlert
www.eurekalert.org/pub_releases/2014-06/cndi-moh062014.php

Researchers from Oregon State Public Health Lab have modified the protocol for a relatively new test for a dangerous form of antibiotic resistance, increasing its specificity to 100 percent. Their research, confirming the reliability of a test that can provide results in hours and is simple and inexpensive enough to be conducted in practically any clinical laboratory.

The test, called Carba NP, originally developed by Patrice Nordmann and Laurent Poirel at the University of Fribourg, Switzerland, and Laurent Dortet of the University Hospital of the South-Paris Medical School, France, allows for rapid identification of carbapenem-resistant Enterobacteriaceae (CRE), often referred to in the media as ‘super bugs’ for their ability to resist most major antibiotics. Carbapenems are an important class of powerful antibiotics for treating severe infections caused by multidrug-resistant Gram negative bacteria. Carbapenemases are enzymes produced by some bacteria which inactivate these antibiotics.

‘Over the past decade carbapenemase-producing CRE (CP-CRE) have rapidly spread around the globe and are currently considered an urgent public health threat by the Centers for Disease Control and Prevention (CDC),’ says Karim Morey of the Oregon State Public Health Lab, an author on the study. ‘Timely detection of CP-CRE is critical to patient care and infection control.’

Polymerase chain reaction (PCR), a DNA-based test, is currently the gold standard for detecting CRE, but it is expensive and requires equipment that many labs just do not have, especially in low-income countries that are large reservoirs for CRE. Carba NP is a much less expensive test that most labs should be able to afford.

In the study Morey and her colleagues evaluated the ability of the Carba NP test to properly identify 59 of the 201 clinical isolates as carbapenemase producers. Using a previously published Mayo Clinic protocol, they correctly identified 92% as being carbapenemase producers, including all strains of NDM-1 and KPC, two important types of CRE. When they adjusted the protocol to increase the inoculum size and tested again they achieved 100% sensitivity. The average time to complete a test was 2.5 hours.

‘We conclude that the Carba NP test is highly sensitive, specific and reproducible for the detection of carbapenemase production in a diverse group of organisms,’ says Morey.

This work was done as part of the Drug Resistant Organism Coordinated Regional Epidemiology Network, a statewide initiative to prevent the emergence and spread of CRE in the state of Oregon and Funded by the CDC. EurekAlert

Improved diagnosis and management of one of the most common cancers in men – prostate cancer – could result from research at the University of Adelaide, which has discovered that seminal fluid (semen) contains biomarkers for the disease.
Results of a study have shown that the presence of certain molecules in seminal fluid indicates not only whether a man has prostate cancer, but also the severity of the cancer.
Speaking in the lead-up to Men’s Health Week (9-15 June), University of Adelaide research fellow and lead author Dr Luke Selth says the commonly used PSA (prostate specific antigen) test is by itself not ideal to test for the cancer.
‘While the PSA test is very sensitive, it is not highly specific for prostate cancer,’ Dr Selth says. ‘This results in many unnecessary biopsies of non-malignant disease. More problematically, PSA testing has resulted in substantial over-diagnosis and over-treatment of slow growing, non-lethal prostate cancers that could have been safely left alone.
‘Biomarkers that can accurately detect prostate cancer at an early stage and identify aggressive tumours are urgently needed to improve patient care. Identification of such biomarkers is a major focus of our research,’ he says.
Dr Selth, a Young Investigator of the Prostate Cancer Foundation (USA), is a member of the Freemasons Foundation Centre for Men’s Health at the University of Adelaide and is based in the University’s Dame Roma Mitchell Cancer Research Laboratories.
Using samples from 60 men, Dr Selth and colleagues discovered a number of small ribonucleic acid (RNA) molecules called microRNAs in seminal fluid that are known to be increased in prostate tumours. The study showed that some of these microRNAs were surprisingly accurate in detecting cancer.
‘The presence of these microRNAs enabled us to more accurately discriminate between patients who had cancer and those who didn’t, compared with a standard PSA test,’ Dr Selth says. ‘We also found that the one specific microRNA, miR-200b, could distinguish between men with low grade and higher grade tumours. This is important because, as a potential prognostic tool, it will help to indicate the urgency and type of treatment required.’ University of Adelaide

In many patients it is not easy to differentiate between the chronic inflammatory skin diseases psoriasis and eczema. Researchers at the Helmholtz Zentrum München and the Technical University of Munich (TUM) have now developed a procedure based on a skin analysis that enables an exact diagnosis to be made.

In some patients, the chronic inflammatory skin diseases psoriasis and eczema are similar in appearance. Up to now, dermatologists have therefore had to base their decision on which treatment should be selected on their own experience and an examination of tissue samples. A team of researchers at the Helmholtz Zentrum München and the Technical University of Munich (TUM) have now analysed the molecular processes that occur in both diseases and discovered crucial differences. This has enabled them for the first time to gain a detailed understanding of the ways in which the respective disease process occurs. Building on this knowledge, the scientists, led by Dr. Stefanie Eyerich and Prof. Dr. Kilian Eyerich as well as Prof. Dr. Fabian Theis, have developed a diagnostic procedure which in practice enables psoriasis and eczema to be reliably differentiated from one another on the basis of only two genes.

“Both diseases have a highly complex appearance, which often varies widely from one patient to another,” says Dr. Stefanie Eyerich, who heads the Specific Immunology working group at the Institute of Allergy Research (IAF) at the Helmholtz Zentrum München. “This has led previous attempts to compare their molecular signature to fail.” In this study, the researchers identified 24 patients who were suffering simultaneously from psoriasis and eczema and in each analyzed at the molecular level the characteristic differences they demonstrated between psoriasis and eczema compared to clinically unremarkable skin.

“We were thus able to drastically reduce random genetic or environmental influences and gain a detailed picture of the development of these two diseases,” explains Prof. Fabian Theis of the Institute of Computational Biology (ICB) at the Helmholtz Zentrum München.

In recent years, many new specific treatments have been developed for psoriasis and eczema. However, in each case, these are only effective for one or other of the two diseases. And they are very expensive: one such treatment generally costs several tens of thousands of euros per year, per patient. The ability to make an exact diagnosis therefore has a considerable economic impact.

If it cannot be clearly determined on presentation which of the two diseases is involved, the newly developed diagnostic tool will help to differentiate them. It involves a test which compares samples of diseased and healthy skin and is concluded within one day. The researchers have now filed a patent application for it.