A newborn’s first stool can signal the child may struggle with persistent cognitive problems, according to Case Western Reserve University Project Newborn researchers. 
In particular, high levels of fatty acid ethyl esters (FAEE) found in the meconium (a newborn’s first stool) from a mother’s alcohol use during pregnancy can alert doctors that a child is at risk for problems with intelligence and reasoning.
Left untreated, such problems persist into the teen years, the research team from the Jack, Joseph and Morton Mandel School of Applied Social Sciences found.
“We wanted to see if there was a connection between FAEE level and their cognitive development during childhood and adolescence—and there was,” said Meeyoung O. Min, PhD, research assistant professor at the Mandel School and the study’s lead researcher. “FAEE can serve as a marker for foetal alcohol exposure and developmental issues ahead.”

Detecting prenatal exposure to alcohol at birth could lead to early interventions that help reduce the effects later, Min said.

For this study, researchers analysed the meconium of 216 subjects for levels of FAEE. (FAEE are composed of a group of products from metabolizing alcohol; this study examined ethyl myristate, ethyl oleate ethyl linoleate and ethyl linolenate.) They then gave intelligence tests at ages 9, 11 and 15.
The conclusion: There was a link between those with high levels of FAEE at birth and lower IQ scores. 

“Although we already knew a mother’s alcohol use during her pregnancy may cause cognitive deficits, what is significant is that the early marker, not previously available, predicted this, establishing the predictive validity of FAEEs for determining alcohol exposure in utero” Min said. Case Western Reserve University

A new study from Lund University in Sweden shows that women with low levels of an anti-stress hormone have an increased risk of getting breast cancer. The study is the first of its kind on humans and confirms previous similar observations from animal experiments.
The recent findings on a potential new marker for the risk of developing breast cancer. The study focused on a hormone which circulates freely in the blood, enkephalin, with pain- and anxiety-reducing properties. Enkephalin also reinforces the immune system by directly affecting immune cells.

“This is the first time the role of enkephalin in breast cancer has been studied in humans, and the results were surprisingly clear. Among women with the lowest levels of the hormone, the risk of breast cancer was more than three times that of the women with the highest levels of the hormone. This is one of the strongest correlations between cancer risk and a freely circulating biomarker ever described”, said Olle Melander and Mattias Belting, both professors at Lund University and consultant physicians at Skåne University Hospital.

The findings were possible thanks to a broad approach combining the latest knowledge within cancer and cardiovascular research at Lund University; the study was based on blood samples taken from just over 1 900 women in Malmö.  The women were followed up with regard to breast cancer for an average period of 15 years.

The results were adjusted for age, menopause, hormonal treatment, smoking and other factors which can affect the risk of getting breast cancer.

The current study confirms a statistical correlation between low enkephalin concentrations in the blood and increased risk of breast cancer, and it remains to be seen whether there is a causal relation showing that a low level of the hormone directly affects tumour development. The researchers also point out that geographical location and age, in spite of the adjustments in the study, may be significant. The average age of the women studied was 57.

On the other hand, the study’s results are backed up by a subsequent control study of a group of 1 500 women with a marginally higher average age. In this group, the link between low levels of the hormone and breast cancer was even stronger. Animal studies by other researchers also gave similar indications. These studies established that enkephalin can reinforce the activity of the immune system against cancer cells, as well as having a direct tumour-inhibiting effect.

The researchers at Lund University hope that, after further studies, the results will facilitate prevention and early detection of breast cancer.  For those with an increased risk of breast cancer, potential preventive treatments could take the form of lifestyle interventions to reduce stress and new drugs. The findings fit well with the development towards individualised risk assessment and treatment, on the basis of each woman’s needs. Lund University

The term intellectual disability covers a large number of clinical entities, some with known cause and others of uncertain origin. For example Down syndrome is due to an extra copy of chromosome 21 and Rett syndrome is in part caused by a mutation in the control switch gene called MeCP2.

In other cases the mechanisms by which they are produced are not clearly identified. It is the case of most of those disorders classified under the large umbrella of autism. An study by Manel Esteller, director of the Program Epigenetics and Cancer Biology (PEBC) of the Bellvitge Biomedical Research Institute (IDIBELL), ICREA researcher and Professor of Genetics at the University of Barcelona , has discovered a mechanism that identifies a cause of intellectual disabilities in these puzzling cases.

‘We have analysed the genome of 215 patients with mental retardation, autism or Rett syndrome, in which they had not found any genetic alteration in the genes classically associated with these clinical conditions, to see if we could find a molecular cause. And this process has allowed us to detect a new mutated gene that could be causing these disorders. ‘He explained Manel Esteller.

‘Specifically, the identified gene is called JMJD1C (Jumonji Domain Containing 1C) and is an epigenetic gene which its normal function is to control the activity of other genes. Only a small percentage of mental retardation of unknown origin is due to mutation of this gene. This finding suggests that many genes with low frequency disturbance are responsible for cases with unknown cause. They have demonstrated that this gene joins the MeCP2 gene so it could also contribute to cases of atypical Rett Syndrome ‘says Esteller. IDIBELL

A database compiled by Ash Alizadeh and his team provides broad patterns that correlate with poor or good survival rates for a variety of cancers.

Physicians have long sought a way to accurately predict cancer patients’ survival outcomes by looking at biological details of the specific cancers they have. But despite concerted efforts, no such clinical crystal ball exists for the majority of cancers.

Now, researchers at the Stanford University School of Medicine have compiled a database that integrates gene expression patterns of 39 types of cancer from nearly 18,000 patients with data about how long those patients lived.

Combining the data from so many people and cancers allowed the researchers to overcome reproducibility issues inherent in smaller studies. As a result, the researchers were able to clearly see broad patterns that correlate with poor or good survival outcomes. This information could help them pinpoint potential therapeutic targets.

“We were able to identify key pathways that can dramatically stratify survival across diverse cancer types,” said Ash Alizadeh, MD, PhD, an assistant professor of medicine and a member of the Stanford Cancer Institute. “The patterns were very striking, especially because few such examples are currently available for the use of genes or immune cells for cancer prognosis.”

In particular, the researchers found that high expression of a gene called FOXM1, which is involved in cell growth, was associated with a poor prognosis across multiple cancers, while the expression of the KLRB1 gene, which modulates the body’s immune response to cancer, seemed to confer a protective effect.

The new database, which will be available to physicians and researchers, is called PRECOG, an abbreviation for “prediction of cancer outcomes from genomic profiles.” Stanford’s Department of Medicine

A multidisciplinary team at Yale, led by Yale Cancer Center members, has defined a subgroup of genetic mutations that are present in a significant number of melanoma skin cancer cases. Their findings shed light on an important mutation in this deadly disease, and may lead to more targeted anti-cancer therapies.

The role of mutations in numerous genes and genomic changes in the development of melanoma — a skin cancer with over 70,000 new cases reported in the United States each year — is well established and continues to be the focus of intense research. Yet in approximately 30% of melanoma cases the genetic abnormalities are unclear. To deepen understanding of melanoma mutations, the Yale team conducted a comprehensive analysis using whole-exome sequencing of more than 200 melanoma samples from patients with the disease.

The multidisciplinary team — drawing on their expertise in genetics, cancer, computational biology, pharmacology, and other disciplines — also tested the response of tumour cells with specific mutations to anti-cancer drugs.

The researchers confirmed that a gene known as NF1 is a “major player” in the development of skin cancer. “The key finding is that roughly 45% of melanomas that do not harbour the known BRAF or NRAS mutations display loss of NF1 function, which leads to activation of the same cancer-causing pathway,” said Dr. Michael Krauthammer, associate professor of pathology and the study’s corresponding author.

Additionally, researchers observed that melanoma patients with the NF1 mutation were older and had a greater number of mutations in the tumours. These include mutations in the same pathway, collectively known as RASopathy genes.

Yet mutations in NF1 are not sufficient to cause skin cancer, said Ruth Halaban, senior research scientist in dermatology, a member of Yale Cancer Center, and lead author of the study. “Loss of NF1 requires more accompanying changes to make a tumour,” she explained. “Our study identified changes in about 100 genes that are present only in the malignant cells and are likely to be causative. This panel of genes can now be used in precision medicine to diagnose malignant lesions and can be applied to personalized cancer treatment.”

By testing the response of the melanoma samples to two cancer drugs, the researchers also determined that, in addition to loss of NF1, multiple factors need to be tested to predict the response to the drugs. “It opens the door to more research,” said Halaban, who is also principal investigator at Yale SPORE in Skin Cancer.
Yale University

Study identifies ‘major player’ in skin cancer genes
A multidisciplinary team at Yale, led by Yale Cancer Center members, has defined a subgroup of genetic mutations that are present in a significant number of melanoma skin cancer cases. Their findings shed light on an important mutation in this deadly disease, and may lead to more targeted anti-cancer therapies.

The role of mutations in numerous genes and genomic changes in the development of melanoma — a skin cancer with over 70,000 new cases reported in the United States each year — is well established and continues to be the focus of intense research. Yet in approximately 30% of melanoma cases the genetic abnormalities are unclear. To deepen understanding of melanoma mutations, the Yale team conducted a comprehensive analysis using whole-exome sequencing of more than 200 melanoma samples from patients with the disease.

The multidisciplinary team — drawing on their expertise in genetics, cancer, computational biology, pharmacology, and other disciplines — also tested the response of tumour cells with specific mutations to anti-cancer drugs.

The researchers confirmed that a gene known as NF1 is a “major player” in the development of skin cancer. “The key finding is that roughly 45% of melanomas that do not harbour the known BRAF or NRAS mutations display loss of NF1 function, which leads to activation of the same cancer-causing pathway,” said Dr. Michael Krauthammer, associate professor of pathology and the study’s corresponding author.

Additionally, researchers observed that melanoma patients with the NF1 mutation were older and had a greater number of mutations in the tumours. These include mutations in the same pathway, collectively known as RASopathy genes.

Yet mutations in NF1 are not sufficient to cause skin cancer, said Ruth Halaban, senior research scientist in dermatology, a member of Yale Cancer Center, and lead author of the study. “Loss of NF1 requires more accompanying changes to make a tumour,” she explained. “Our study identified changes in about 100 genes that are present only in the malignant cells and are likely to be causative. This panel of genes can now be used in precision medicine to diagnose malignant lesions and can be applied to personalized cancer treatment.”

By testing the response of the melanoma samples to two cancer drugs, the researchers also determined that, in addition to loss of NF1, multiple factors need to be tested to predict the response to the drugs. “It opens the door to more research,” said Halaban, who is also principal investigator at Yale SPORE in Skin Cancer. Yale University