Posts Tagged ‘body’

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

Family conflicts, other non-physical worries before cancer surgery raise patients’ complication risk

The findings are published in the Journal of Gastrointestinal Surgery.

“We know that quality of life is a very complex thing, but we can now measure it and work with it almost like blood pressure,” says lead author Juliane Bingener, M.D., a gastroenterologic surgeon at Mayo Clinic in Rochester. “We can say, ‘This is good, this is in the normal range, but this one here, that is not good, and maybe we should do something.'”

Quality of life as measured in the study is about more than happiness and how well people feel physically, Dr. Bingener says. It also includes the financial, spiritual, emotional, mental and social aspects of their lives and whether their needs are being met.

Researchers studied 431 colon cancer surgery patients and found that before surgery, 13 percent had a quality of life deficit, defined as an overall quality of life score of less than 50 on a 100-point scale.

Nearly three times as many patients who entered surgery with a quality of life deficit experienced serious post-surgery complications as those with a normal or good quality of life score. Patients with a postoperative complication spent 3.5 days longer in the hospital on average than those who didn’t.

“The question I’m exploring is whether, if we understand before surgery that someone is in the red zone for quality of life, can we do something to help them cope with the new stress that’s going to come, so they’re better equipped to go through surgery?” Dr. Bingener says.

Preventing complications by intervening with behavioral therapy or other assistance would likely cost much less than an ICU stay for an infection after major surgery, Dr. Bingener notes.

Stress can weaken patients’ immune response, putting them at higher risk of infection. A patient’s outlook on life can also influence how active they are in working to recover.

“You have a surgery, you’re lying there in pain, now you wonder, ‘Why should I even get up and walk around? Why do I have to do these deep-breathing exercises? I don’t feel like it.’ You might get pneumonia much faster than somebody who says, ‘Oh, I have to get up. There’s something worth living for, my quality of life is good and I need to get back to that,'” Dr. Bingener says.

The study is part of ongoing work by Mayo to identify and address factors that can influence patients’ recovery from cancer surgery, to help improve their outcomes. Years ago, physicians were just concerned with whether patients survived cancer, because survival was so hard to achieve, Dr. Bingener says. Now, there is growing awareness of the mind’s influence on the body’s health.

“We’re understanding much better now that patients are not just a body with a disease: There’s a whole person with that, and everything plays together,” Dr. Bingener says. “Now that survival is possible, we want to achieve it in a way that preserves normal life for patients as much as possible. And we think that’s probably also the most economical way to go.”

source : http://www.sciencedaily.com/releases/2014/09/140902114416.htm

Introducing the multi-tasking nanoparticle

“These are amazingly useful particles,” noted co-first author Yuanpei Li, a research faculty member in the Lam laboratory. “As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors; apply light to make the nanoparticles release singlet oxygen (photodynamic therapy) or use a laser to heat them (photothermal therapy) — all proven ways to destroy tumors.”

Jessica Tucker, program director of Drug and Gene Delivery and Devices at the National Institute of Biomedical Imaging and Bioengineering, which is part of the National Institutes of Health, said the approach outlined in the study has the ability to combine both imaging and therapeutic applications in a single platform, which has been difficult to achieve, especially in an organic, and therefore biocompatible, vehicle.

“This is especially valuable in cancer treatment, where targeted treatment to tumor cells, and the reduction of lethal effects in normal cells, is so critical,” she added.

Though not the first nanoparticles, these may be the most versatile. Other particles are good at some tasks but not others. Non-organic particles, such as quantum dots or gold-based materials, work well as diagnostic tools but have safety issues. Organic probes are biocompatible and can deliver drugs but lack imaging or phototherapy applications.

Built on a porphyrin/cholic acid polymer, the nanoparticles are simple to make and perform well in the body. Porphyrins are common organic compounds. Cholic acid is produced by the liver. The basic nanoparticles are 21 nanometers wide (a nanometer is one-billionth of a meter).

To further stabilize the particles, the researchers added the amino acid cysteine (creating CNPs), which prevents them from prematurely releasing their therapeutic payload when exposed to blood proteins and other barriers. At 32 nanometers, CNPs are ideally sized to penetrate tumors, accumulating among cancer cells while sparing healthy tissue.

In the study, the team tested the nanoparticles, both in vitro and in vivo, for a wide range of tasks. On the therapeutic side, CNPs effectively transported anti-cancer drugs, such as doxorubicin. Even when kept in blood for many hours, CNPs only released small amounts of the drug; however, when exposed to light or agents such as glutathione, they readily released their payloads. The ability to precisely control chemotherapy release inside tumors could greatly reduce toxicity. CNPs carrying doxorubicin provided excellent cancer control in animals, with minimal side effects.

CNPs also can be configured to respond to light, producing singlet oxygen, reactive molecules that destroy tumor cells. They can also generate heat when hit with laser light. Significantly, CNPs can perform either task when exposed to a single wavelength of light.

CNPs offer a number of advantages to enhance imaging. They readily chelate imaging agents and can remain in the body for long periods. In animal studies, CNPs congregated in tumors, making them easier to read on an MRI. Because CNPs accumulated in tumors, and not so much in normal tissue, they dramatically enhanced tumor contrast for MRI and may also be promising for PET-MRI scans.

This versatility provides multiple options for clinicians, as they mix and match applications.

“These particles can combine imaging and therapeutics,” said Li. “We could potentially use them to simultaneously deliver treatment and monitor treatment efficacy.”

“These particles can also be used as optical probes for image-guided surgery,” said Lam. “In addition, they can be used as highly potent photosensitizing agents for intraoperative phototherapy.”

While early results are promising, there is still a long way to go before CNPs can enter the clinic. The Lam lab and its collaborators will pursue preclinical studies and, if all goes well, proceed to human trials. In the meantime, the team is excited about these capabilities.

“This is the first nanoparticle to perform so many different jobs,” said Li. “From delivering chemo, photodynamic and photothermal therapies to enhancing diagnostic imaging, it’s the complete package.”

source : http://www.sciencedaily.com/releases/2014/08/140826112648.htm