Posts Tagged ‘type’

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

RNA sequence could help doctors to tailor unique prostate cancer treatment programs

Colin Collins and Alexander Wyatt, and other researchers from the Vancouver Prostate Centre at the Vancouver Coastal Health Research Institute, matched 25 patients’ treatment outcomes with the RNA sequence of their prostate cancer tumors. They suggest that similarities between the RNA of some of the patients’ tumors could open up new avenues of treatment.

Prostate cancer is the fourth most common cancer worldwide, but can be effectively managed. Doctors normally recommend a combination of therapies, because patients’ reaction to treatment varies considerably. The side-effects of these treatments can be significant, so current research is focused around precision medicine — classifying patients on their tumor’s molecular changes, and only giving them the treatments that are expected to be most effective.

To investigate variations between the highest risk cases of prostate cancer, researchers conducted a range of genomic analyses, including sequencing the RNA in 25 patients’ prostate tumors. The RNA molecules direct which proteins the cell produces, so the RNA sequences show how tumor cells behave differently to normal cells.

Alexander Wyatt, Vancouver Prostate Centre, says: “Most genomic sequencing studies have focused on the DNA, which gives us important information about a tumor’s history. In our study we examined RNA, which tells us which genes are being used and are disrupted at the time the tumor was collected.”

They then matched up this data with the detailed follow-up information that they had for each of the patients. They were then able to see what sequence disruptions were associated with a positive reaction to different therapies, and they believe this could aid personalized medicine.

Alexander Wyatt says: “We were surprised by the sheer number of genomic differences between patients. This complexity may help explain why patients respond differently to treatment, and why some tumors grow faster than others. The more we understand tumor-to-tumor variability, the closer we come to accurately tailoring a patient’s management specifically for his own tumor. Overall, this is a very exciting time for cancer research, as global sequencing efforts mean we are advancing towards precision oncology.”

Another potential use of this information is that in certain groups, there was a similarity in the type of genes and pathways that were disrupted in the tumors. This might indicate an underlying cancer mechanism that could be exploited to create new cancer treatments.

Alexander Wyatt says: “Despite the enormous complexity between patients at the individual gene level, when we examined the functions of affected genes, clear commonalities between groups of patients emerged. Ultimately it may be possible to exploit this convergent biology.”

source : http://www.sciencedaily.com/releases/2014/08/140826091051.htm

Repurposing anti-depressant medication to target medulloblastoma

The multi-institutional group, led by scientists at Cancer and Blood Diseases Institute (CBDI) at Cincinnati Children’s Hospital Medical Center, publish their results in the journal’s online edition on Aug. 24. The researchers suggest their laboratory findings in mouse models of the disease could lead to a more targeted and effective molecular therapy that would also reduce the harmful side effects of current treatments, which include chemotherapy, radiation or surgery.

“Although current treatments improve survival rates, patients suffer severe side effects and relapse tumors carry mutations that resist treatment,” said lead investigator Q. Richard Lu, PhD, scientific director of the Brain Tumor Center, part of the CBDI at Cincinnati Children’s. “This underscores an urgent need for alternative targeted therapies, and we have identified a potent tumor suppressor that could help a subset of patients with an aggressive form of medulloblastoma.”

Using genetically-engineered mice to model human medulloblastoma, the authors identified a gene called GNAS that encodes a protein called Gsa. Gsa kicks off a signaling cascade that researchers found suppresses the initiation of an aggressive form of medulloblastoma driven by a protein called Sonic hedgehog — considered one of the most important molecules in tissue formation and development.

The scientists used an anti-depressant medication called Rolipram — approved for behavioral therapy for use in Europe and Japan — to treat mice that were engineered not to express the GNAS gene. Lack of GNAS allowed aggressive formation of medulloblastoma tumors in neural progenitor cells of the GNAS mutant mice.

Rolipram treatment in the mice elevated levels of a molecule called cAMP, which restored the GNAS-Gsa pathway’s tumor suppression function. This caused the tumors to shrink and subside. The study also suggests that elevating cAMP levels in cells enhances the potency of Sonic hedgehog inhibitors, currently being tested in clinical trials to fight tumor growth.

The scientists stressed that a significant amount of additional research is needed before their findings could become directly relevant to clinical treatment. The authors also caution that the effect of raising cAMP levels may depend on the type of cancer, and that laboratory results in mice do not always translate uniformly to humans.

source : http://www.sciencedaily.com/releases/2014/08/140824152337.htm