Retinoic acid (vitamin A) and steroids are hormones found in our body that protect against oxidative stress, reduce inflammation and are involved in cellular differentiation processes. One of the characteristics of tumours is that their cells have lost the ability to differentiate; therefore these hormones have useful properties to prevent cancer. Currently, retinoic acid and steroids are being used to treat some types of leukemia.
A study led by the research group on Genes and Cancer of the Bellvitge Biomedical Research Institute (IDIBELL) has shown that loss of BRG1 gene implies a lack of response of cells to these hormones, and therefore the tumour may continue growing.
The IDIBELL research group on Genes and Cancer led by Montse Sanchez-Cespedes discovered some years ago that the BRG1 gene, a tumour suppressor, is inactivated in non-small cell lung cancer by genetic mutations. ‘The BRG1 protein is part of a chromatin remodelling complex that regulates the expression of several genes,’ said the researcher, ‘and is related to the differentiation of lung cells, allowing cells response to certain hormones and environment vitamins like vitamin A or steroids.’
When BRG1 is mutated and therefore inactive, tumour cells do not respond to the presence of these hormones and they continue growing and spreading. For this reason, these types of tumours are refractory to treatment with these substances.
‘At the moment,’ says Montse Sanchez-Cespedes, ‘we are not able to restore the functionality of a tumour suppressor gene as BRG1 in patients. Therefore, we are still far from a therapeutic application but the discovery enables us to better understand the biology of tumours. What we will try to do in the immediate future is to look for agents that specifically destroy the cells with mutated BRG1, following the strategy of lethal synthetics’.
In any case, this finding it can be useful in advancing personalised medicine, because ‘it explains why lung cancer patients are resistant to these treatments and may serve to rule out therapies with lipid-derived hormones in patients with BRG1 mutations, not just in lung cancer but also in breast and prostate, among others. ‘ IDIBELL

Researchers from the Perelman School of Medicine at the University of Pennsylvania have identified an abnormal amount a protein called Prostaglandin D2 in the bald scalp of men with male pattern baldness, a discovery that may lead directly to new treatments for the most common cause of hair loss in men. In both human and animal models, researchers found that a prostaglandin known as PGD2 and its derivative, 15-dPGJ2, inhibit hair growth. The PGD2-related inhibition occurred through a receptor called GPR44, which is a promising therapeutic target for androgenetic alopecia in both men and women with hair loss and thinning.
Male pattern baldness strikes 8 of 10 men under 70 years old, and causes hair follicles to shrink and produce microscopic hairs, which grow for a shorter duration of time than normal follicles.
Researchers took an unbiased approach when scanning for potential biological causes of baldness, looking in scalp tissue from balding and non-bald spots from men with male pattern baldness and then corroborating findings in mouse models. They found that levels of PGD2 were elevated in bald scalp tissue at levels 3 times greater than what was found in comparative haired scalp of men with androgenetic alopecia. When PGD2 was added to cultured hair follicles, PGD2-treated hair was significantly shortened, while PGD2’s derivative, 15-dPGJ2, completely inhibited hair growth.
‘Although a different prostaglandin was known to increase hair growth, our findings were unexpected, as prostaglandins haven’t been thought about in relation to hair loss, yet it made sense that there was an inhibitor of hair growth, based on our earlier work looking at hair follicle stem cells,’ said George Cotsarelis, MD, chair and professor of Dermatology, and senior author on the studies. In a Penn study published in the Journal of Clinical Investigation last year, underlying hair follicle stem cells were found intact, suggesting that the scalp was lacking an activator or something was inhibiting hair follicle growth.
Prostaglandins are well characterised for their role in many bodily functions — controlling cell growth, constricting and dilating smooth muscle tissue — and a different prostaglandin (F2alpha) is known to increase hair growth. Researchers found that as PGD2 inhibits hair growth, other prostaglandins work in opposition, enhancing and regulating the speed of hair growth.
While these studies looked at AGA in men, the researchers noted that prostaglandins may represent a common pathway shared by both men and women with AGA. Future studies, potentially testing topical treatments that may target GPR44, can determine whether targeting prostaglandins will benefit woman with AGA as well. Penn University

An international team of researchers have developed a new method for measurement of aggregated beta-amyloid – a protein complex believed to cause major nerve cell damage and dysfunction in Alzheimer’s disease. The new method might facilitate diagnosis and detection as well as development of drugs directed against aggregated beta-amyloid.
Alzheimer’s disease (AD) is the most common cause of memory decline and dementia. According to the Alzheimer World Report 2011, today around 36 million people suffer from Dementia (around 20 – 25 million are Alzheimer’s patients). These numbers will dramatically increase with the ageing populations over the next few decades. For the year 2050 the expected number of dementia patients will be 115 – 200 million (70 – 150 million Alzheimer’s cases). It is therefore important to develop new therapies and diagnostic methods to detect and treat this complex chronic neurodegenerative brain disease.
Alzheimer’s disease is characterised by aggregates in the brain, containing a protein called beta-amyloid. The neuropathology of Alzheimer’s disease has recently been linked to the neurotoxic amyloid-β (Aβ) oligomers. The crucial role of Aβ oligomers in the early events of AD is experimentally underlined. Several recent results suggest that those oligomers may cause the death of neurons and neurological dysfunctions relevant to memory. Furthermore Aβ oligomers levels are increased in brain and cerebrospinal fluid samples from people with Alzheimer’s disease. This reflects the potential of Aβ oligomers as a marker for the early diagnosis of the disease.
An international team of scien
He analysed the cerebrospinal fluid of 30 neurological patients, including 14 Alzheimer’s patients. ‘These samples provided from leading expert academic memory clinics in Germany and Sweden are of the best quality and are highly characterised in order to provide robust and reliable results on promising novel biomarker candidates’, Professor Harald Hampel of Frankfurt University, a lead investigator comments.
‘Because of the limited number of samples, however, further study is needed to confirm the results,’ said Dr. Oskar Hansson of Lund University. The study was an international co-operation with the University of California in the U.S., the Goteborg and Malmö Universities from Sweden and the University of Frankfurt in Germany.
The test might not only be used fo
tists from Germany, Sweden and the U.S. have used a new method to quantify soluble variants of aggregated beta-amyloid (Aβ oligomers) in cerebrospinal fluid by flow cytometry. "We found that patients with a greater number of Aβ oligomers in the cerebrospinal fluid had a more pronounced disease," says Dr. Alexander Navarrete Santos (the developer of this method and now employee of the Research Laboratory of the University of Halle, Department of Cardiothoracic Surgery), and first author of the study.r the early detection of AD but can also be used when developing new and effective therapies for AD. A decline in the number of Aβ oligomers in cerebrospinal fluids could be a hint for the effectiveness of new drug therapies. EurekAlert

An important step towards developing a rapid, inexpensive diagnostic method for autism has been take by Uppsala University, among other universities. Through advanced mass spectrometry the researchers managed to capture promising biomarkers from a tiny blood sample.
There are no acknowledged biomarkers for autism today. Researchers at Berzelii Centre and the Science for Life Laboratory in Uppsala who, in collaboration with colleagues at Linnaeus University in Sweden and the Faculty of Medicine in Tehran, Iran, who have discovered some promising biomarkers.
Many diseases are caused by protein alterations inside and outside the body’s cells. By studying protein patterns in tissue and body fluids, these alterations can be mapped to provide important information about underlying causes of disease. Sometimes protein patterns can also be used as biomarkers to enable diagnosis or as a prognosticating tool to monitor the development of a disease. In the current study disruptions of the nervous system were in focus when the scientists studied protein patterns in autism spectrum disorder (ASD).
To identify potential biomarkers (peptides or proteins), the researchers performed a detailed protein analysis of blood plasma from children with ASD compared with a control group. Using advanced mass spectrometric methods, they succeeded in identifying peptides consisting of fragments of a protein whose natural function is in the immune system, the complement factor C3 protein.
The study is based on blood samples from a relatively limited group of children, but the results indicate the potential of our methodological strategy. There is already a known connection between this protein and ASD, which further reinforces the findings, says Jonas Bergquist, professor of analytical chemistry and neurochemistry at the Department of Chemistry – BMC (Biomedical Centre) in Uppsala.
The hope is that this new set of biomarkers ultimately will lead to a reliable blood-based diagnostic tool. Uppsala University

Why do some people experience post-traumatic stress disorder (PTSD) while others who suffered the same ordeal do not? A new UCLA study may shed light on the answer.

UCLA scientists have linked two genes involved in serotonin production to a higher risk of developing PTSD. The findings suggest that susceptibility to PTSD is inherited, pointing to new ways of screening for and treating the disorder.

‘People can develop post-traumatic stress disorder after surviving a life-threatening ordeal like war, rape or a natural disaster,’ said lead author Dr. Armen Goenjian, a research professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA. ‘If confirmed, our findings could eventually lead to new ways to screen people at risk for PTSD and target specific medicines for preventing and treating the disorder.’

PTSD can arise following child abuse, terrorist attacks, sexual or physical assault, major accidents, natural disasters or exposure to war or combat. Symptoms include flashbacks, feeling emotionally numb or hyper-alert to danger, and avoiding situations that remind one of the original trauma.

Goenjian and his colleagues extracted the DNA of 200 adults from several generations of 12 extended families who suffered PTSD symptoms after surviving the devastating 1988 earthquake in Armenia.

In studying the families’ genes, the researchers found that persons who possessed specific variants of two genes were more likely to develop PTSD symptoms. Called TPH1 and TPH2, these genes control the production of serotonin, a brain chemical that regulates mood, sleep and alertness — all of which are disrupted in PTSD.

‘We suspect that the gene variants produce less serotonin, predisposing these family members to PTSD after exposure to violence or disaster,’ Goenjian said. ‘Our next step will be to try and replicate the findings in a larger, more heterogeneous population.’

PTSD affects about 7 percent of Americans and has become a pressing health issue for a large percentage of war veterans returning from Iraq and Afghanistan. The UCLA team’s discovery could be used to help screen people who may be at risk for developing PTSD.

‘A diagnostic tool based upon TPH1 and TPH2 could enable military leaders to identify soldiers who are at higher risk of developing PTSD and reassign their combat duties accordingly,’ Goenjian said. ‘Our findings may also help scientists uncover alternative treatments for the disorder, such as gene therapy or new drugs that regulate the chemicals responsible for PTSD symptoms.’

According to Goenjian, pinpointing genes connected with PTSD symptoms will help neuroscientists classify the disorder based on brain biology instead of clinical observation. Psychiatrists currently rely on a trial-and-error approach to identify the best medication for controlling an individual patient’s symptoms. UCLA