Study unveils a blueprint for treating a deadly brain tumor

NIH-funded, preclinical study suggests a common form of brain cancer may be treated with combination radio- and chemotherapy

In a study of mice and human brain tumors researchers at the University of the Michigan, Ann Arbor, searched for new treatments by exploring the reasons why some patients with gliomas live remarkably longer than others. The results suggested that certain patients' tumor cells are less aggressive and much better at repairing DNA than others but are difficult to kill with radiation. The researchers then showed that combining radiation therapy with cancer drugs designed to block DNA repair may be an effective treatment strategy. The study was funded by the National Institutes of Health.

The researchers focused on low-grade gliomas that carry a disease-causing mutation in a gene called isocitrate dehydrogenase 1 (IDH1), which encodes a protein known to help cells produce energy. This mutation is found in about 50 percent of cases of primary low-grade gliomas, a common and lethal form of brain tumor. Glioma patients whose tumors have mutations in IDH1 are typically younger and live longer than those whose tumors have the normal gene.  These tumors also often have mutations in genes called TP53 (a tumor suppressor gene) and ATRX (a DNA-protein complex remodeling gene).

"Every year thousands of people are diagnosed with brain cancer and have little hope for long-term survival," said Maria G. Castro, Ph.D., professor of neurosurgery at Michigan Medicine and a senior author of the paper published in Science Translational Medicine. "Our team's mission is to find life-saving treatments for these patients. The results from this study could be a blueprint for extending, if not saving, the lives of many patients."

The researchers recreated the patients' tumors by genetically engineering mice to grow brain cancer cells that have the disease-causing mutations in IDH1 along with mutations in TP53 and ATRX. Like the patients, these mice lived longer than control mice whose tumors were programmed to have normal IDH1 while still harboring the mutations in TP53 and ATRX. 

When the research team examined the tumors, they found that the IDH1 mutation made the glioma cells less aggressive. The cells divided at a lower rate than the controls and were much less likely   to trigger tumor growth when implanted into mouse brains.

They also discovered that the IDH1 mutation, in the presence of mutations in TP53 and ATRX, made the tumors resistant to ionizing radiation, a treatment that kills cells often by damaging DNA. For instance, radiation exposure extended the lives of mice that were implanted with control tumors but had no effect on mice implanted with IDH1 mutant cells.

Further experiments provided a possible explanation for this resistance. The results suggested the disease-causing mutation changed the activity of IDH1 which, in turn, triggered a cascade of chemical reactions that modified the cancer cells' genes in a way that increased the manufacture of proteins known to repair damaged DNA.

"Our results demonstrate that the metabolic changes caused by the IDH1 mutation reprograms brain cancer cells," said Dr. Castro.

These results led the researchers to formulate and test a new combination therapy. They found that they could extend the lives of mice with mutant IDH1 tumors by exposing them to radiation while also injecting them with anti-cancer drugs designed to block DNA repair. In contrast, treating these mice with either radiation or one of the drugs alone had no effect. Several of the findings seen in mice were also seen in human gliomas grown in petri dishes.

"These findings have the potential to impact many younger glioma patients with low grade tumors by either 'curing' them or extending their lives," said Jane Fountain, Ph.D., program director, NIH's National Institute of Neurological Disorders and Stroke. "The preclinical model Dr Castro's team developed will be extremely valuable to cancer researchers. It closely mirrors the human disease."  

Dr. Castro's team has started planning a Phase 1 clinical trial which will test the safety and efficacy of the combination therapy strategy outlined in this study.

This study was supported by grants from the NIH (NS094804, NS105556, NS076991, NS096756, NS099427, NS103500, NS106887, EB022563, CA224160, CA009676, CA151022, DK097153).

NINDS <http://www.ninds.nih.gov> is the nation's leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

How to have safe Delivery of pregnancy

FAMILY PLANNING WITH ERANGA ISAAC
+2348059233001, srhealthadvocate@gmail.com

How to have safe Delivery of pregnancy

FINDINGS according to the World Health Organisation, show that about 287,000 women worldwide die from pregnancy-related causes each year, and approximately three million newborns do not survive past the first 28 days of life. The majority of these deaths occur in developing countries at or around the time of delivery, and result from treatable conditions that could be prevented with adequate care.

At this juncture, it is imperative for us to make haste to point that more than a third of women in developing world do not give birth in a health facility that has properly trained staff and adequate equipment. The majority of these women with an unmet need for delivery care – 36 million out of the 44 million – live in sub-Saharan Africa and South Asia. These findings come from a new Guttmacher Institute Study, Adding it up: The Need for and Cost Maternal and Newborn Care-Estimates for 2012, by Susheela singh, Jacqueline E. Darroch and Lori S. Ashford.

In a release by the Guttmacher Institute in May 28, 2013, between 2008 and 2012, the proportion of women in the developing world who delivered in health facilities increased from 55% to 64%. However, the proportion varied widely across sub-regions. In 2012, roads rates were lowest in Eastern Africa (44%), Western Africa (47%) and South Asia (51%) and highest in South America (94%), Central Asia (95%) and Eastern Asia (99%). Despite the substantial improvements in recent years, 44 million women in the developing world, as well as their newborns, lacked facility-based delivery care in 2012. the unmet need for delivery care was many times higher in the 69 poorest countries (49%) than in the rest of the developing world (6%).

“Delivering in a health facility with the assistance of trained health professionals and having access to emergency care should complications arise are absolutely critical to saving lives,” said susheela Singh.

“But making sure women receive adequate antenatal care is no less important to protecting the health of pregnant women and their newborns, and improvements in this area are happening much too slowly.”

Overall, in 2012, only about half (55%) of women who gave birth in the developing world had at least four antenatal visits, the minimum number recommended by the World Health Organization (WHO). Because access to care largely depends on the strength of a country’s health system, there is a significant disparity between the proportion of women receiving adequate antenatal care (the WHO – recommended 4+ visits) in the 69 poorest countries (44%) and the proportion receiving such care in developing countries with higher per capita incomes (81%). In sub-Sahara Africa, progress in providing antenatal care has been minimal; the number of women lacking appropriate care actually increased between 2008 and 2012, because increases in service provision did not keep pace with the rising number of births each year.
The study also found that obtaining antenatal care does not necessarily mean that a woman receives all of the essential services needed to ensure a healthy pregnancy. For example, in the developing world, about one-third of women with some professional antenatal care did not have at least one urine test, and a similar proportion did not have blood tests are recommended to screen for hypertensive disease and to assess anemia status and the need for iron supplementation. Among women who gave birth in 2012, 41% of those in sub-Sahara Africa and 37% of those in the 69 poorest countries did not take any iron supplements.

Providing the current level of pregnancy care to women and newborns costs about US$11 billion per year; providing the WHO-recommended level of antenatal, delivery, newborn and postnatal care to all women – both those currently receiving services and those who have unmet need for care – would require doubling expenditure levels to US $24 billion. Like current spending, the additional US $13 billion in costs could be shared among national governments, donor agencies and households.
“Extensive efforts have been made in recent years to improve reproductive health services and reduce maternal and child mortality, and although we are beginning to see the impact of that investment, the level of unmet need for essential care for mothers and newborns remains very high,” said Jacqueline E, Darrock. “The tremendous gains that would result from providing quality pregnancy and delivery services to all women and families would far outweigh the cost of providing these services to all who need them.”

Edo Refs set for a mock fitness test exercise

By Our Correspondent

In a bid to improving the fitness of Edo referees, the Edo State Football Referees Coumcil said all was set for a mock fitness test exercise to usher in new training programs designed by both the national and state training departments of referees.

Speaking at the end of a training section at the UNIBEN Sports Complex in Benin, the Chairman of the Council, Mr. Johnbull Okundolor said the training program was in line with the one designed by the National Training Officer of the Nigeria Football Referee Association (NRA), Olori Sarah Jumoke Adeniran FIFA (Rtd.). He said the Council will not compromise on training standard, and urged all to cooperate with the training department. Mr. Okundolor emphasised that attendance to the training programs, is what guarantees match placement.

"The National Training Officer of the NRA has designed a training program that will be beneficial to all active Referees, we of the Edo State Council will consolidate and improve on it, though, our training department led by FIFA Efosa Igudia has also drew out training programs that are of international standard.

"Better times are ahead of Edo Referees as modality is on ground to increase the number of FIFA badged referees in the State. With these training programs, I believed it will be achieved", Mr. Okundolor said.

Also speaking, the Edo State Training Officer, FIFA Efosa Celestine Igudia said the training program became necessary especially as the Confederation Cup is fast approaching. FIFA Efosa also said the training will go a long way in preparing Edo Referees for the National Cooper Test Exercise. He said he was very hopeful that more referees from Edo State will pass the quarterly fitness test coming up soon.

"We are going to have a mock fitness test soon in Edo State Council and it will be a test of the first set of training programs. 

"With these training programs, the hurdles of passing national fitness test, will be taken away", the FIFA badged referee said.