Posts Tagged ‘professor’

One-two punch for brain tumors? New clinical trial opens

The experimental approach, based on U-M research, delivers two different genes directly into the brains of patients following the operation to remove the bulk of their tumors.

The idea: trigger immune activity within the brain itself to kill remaining tumor cells — the ones neurosurgeons can’t take out, which make this type of tumor so dangerous.

It’s the first time this gene therapy approach is being tried in humans, after more than a decade of research in experimental models.

One of the genes is designed to kill tumor cells directly, and is turned on when the patient takes a certain drug. The other gene spurs the body’s own immune system to attack remaining cancer cells. Both are delivered into brain cells via a harmless virus.

The Phase I clinical trial has already enrolled two patients who have tolerated the gene delivery without complications. All patients in the study must have a presumptive diagnosis of WHO grade 3 or 4 malignant primary glioma, such as glioblastoma multiforme; patients must not have been treated yet by any therapy. They must also meet other criteria for inclusion in the trial.

More patients will be able to enroll at a pace of about one every three weeks, through a careful selection process. In addition to surgery and gene therapy at U-M, each will receive standard chemotherapy and radiation therapy as well as follow-up assessments for up to two years.

“We’re very pleased to see our years of research lead to a clinical trial, because based on our prior work we believe this combination of cell-killing and immune-stimulating approaches holds important promise,” says principal investigator Pedro Lowenstein, M.D., Ph.D., the U-M Medical School Department of Neurosurgery professor who has co-led the basic research effort to develop and test the strategy.

Co-leader Maria Castro, Ph.D., notes that the patients who agree to take part in the Phase I trial will be the first in the world to help establish the safety of the approach in humans. “Without them, and without our partners on the U-M Neurosurgery team, and donors to the Phase One Foundation that support our work, we wouldn’t be able to take this important step in testing this novel therapeutic approach.”

For more about the trial, visit http://umhealth.me/gliomatrial or call 1-800-865-1125.

source : http://www.sciencedaily.com/releases/2014/09/140902143230.htm

Is the HPV vaccine necessary?

“I often have parents ask me if their child should get the HPV vaccine and what are my thoughts about giving it. Some parents are concerned it will promote sexual activity, others think it is unnecessary and others think their child is too young. If the child falls between the recommended ages given by the American Academy of Pediatrics I strongly recommend the vaccination. It really could be the difference between life and death,” said Hannah Chow-Johnson, MD, pediatrician at Loyola University Health System and assistant professor in the Department of Pediatrics at Loyola University Chicago Stritch School of Medicine.

According to Chow there are only two shots that can prevent cancer. One is hepatitis B and the other is the Human Papilloma Virus (HPV) vaccine. HPV is the most common sexually transmitted disease and is known to cause several different types of cancer, including cervical cancer, which is the second leading cancer-cause of death in women.

“Parents need to take into consideration the anti-cancer benefits when considering if they want their child to receive the HPV vaccine,” said Chow.

According to the Centers for Disease Control and Prevention there are more than 20 million people in the U.S. infected with HPV and at least half of these are between the ages of 15-25.

HPV is transmitted through intercourse and genital contact. Both men and women can harbor the virus, which can remain in a person for years after the initial infection.

“One of the scary aspects of HPV is that a person can be infected and not even know it. He or she may have no symptoms at all and still be spreading the virus,” Chow said. “This is why I strong believe in vaccinating males and females early, well before any exposure takes place.”

Prevention is critical when it comes to HPV. According to Chow the vaccine’s protection rate is 93 percent when given before any exposure. After exposure the vaccine doesn’t treat pre-exiting viruses but will help protect against future exposure.

“HPV is a very dangerous virus that can lead to death. Since there is no cure, prevention is all the more important. This vaccine could save the life of your child,” Chow said.

source : http://www.sciencedaily.com/releases/2014/08/140828135242.htm

How premalignant cells can sense oncogenesis, halt growth

Since the 1980s, scientists have known that mutations in a human gene called RAS are capable of setting cells on a path to cancer. Today, a team at Cold Spring Harbor Laboratory (CSHL) publishes experiments showing how cells can respond to an activated RAS gene by entering a quiescent state, called senescence.

CSHL Professor Nicholas Tonks and Benoit Boivin, now a University of Montreal Assistant Professor, co-led a team that traced the process in exquisite detail. They began by confirming that activation of mutant, oncogenic H-RAS, one of the human RAS oncogene variants, spurs cells to generate hydrogen peroxide (H2O2), a form of reactive oxygen species, or ROS. “Most people, when they think about ROS, think about the great damage they can do at high concentrations,” says Tonks. “But this research exemplifies how the controlled production of ROS in cells can play a beneficial role.”

The team showed how the production of ROS in response to oncogenic H-RAS enables cells to fine-tune signaling pathways, leading them to enter a senescent state. A key part of this process is the impact of ROS on a protein called PTP1B. Tonks discovered PTP1B some 25 years ago. It is an enzyme — one in a family of protein tyrosine phosphatases (PTPs), of which there are 105 in humans — that performs the essential biochemical task of removing phosphate groups from amino acids called tyrosines in other proteins. Adding and removing phosphates is one of the principal means by which signals are sent among proteins.

In cells with oncogenic H-RAS, ROS is produced in small quantities, sufficient to render PTP1B inactive. The team found that with the phosphate-removing enzyme unable to do its usual job, a key protein called AGO2 remains phosphorylated — with the consequence that it can no longer do what it normally does, which is engage the cell’s RNA interference machinery. In normal cells, the RNAi machinery represses a gene called p21. But in this specific condition — with H-RAS oncogenically activated, PTP1B inactivated by ROS, and RNAi disabled — p21 proteins begin to accumulate unnaturally, the team discovered.

“This is the key step — accumulation of p21 proteins effectively halts the cell cycle and enables the cell to enter the senescent state,” explains Ming Yang, a doctoral student in the Tonks lab. She and Astrid Haase, Ph.D., a postdoctoral investigator in the laboratory of CSHL Professor Greg Hannon, are the first two authors, respectively, on the team’s paper, published in Molecular Cell.

“This is confirmation of a hypothesis we presented five years ago,” Tonks says. “We knew that oncogenic RAS induced the production of ROS. We proposed that this would lead to regulation of PTPs, and using the example of PTP1B this is precisely what the team discovered in this work — showing also how inactivation of this PTP is part of a complex signaling cascade that can culminate in the induction of senescence.”

ROS have been linked to the pathogenesis of several diseases including Alzheimer’s, diabetes and heart failure. “By showing that PTP1B inactivation by oxidation prevents AGO2 from doing its job, we make a clear link between ROS and gene silencing which could also be observed in other pathologies” says Boivin. Hence, the role of PTP1B in keeping the RNAi machinery active could have important ramifications.

Entering senescence is not enough to arrest oncogenesis completely. Oncogenic mutations typically multiply as cancers evolve to promote their survival and proliferation. But the current work does show the potential importance of knowing the genetic background of a cancer patient, for there are windows of time — narrow though they may be — in which naturally occurring processes induce pauses in growth.

source : http://www.sciencedaily.com/releases/2014/08/140828135521.htm