Wireless Implant Could Help Remove Deadly Brain Tumors

Brain tumors are among the most deadly and difficult-to-treat cancers. Glioblastoma, a particularly aggressive form, kills more than 10,000 Americans a year and has a median survival time of less than 15 months. For patients with brain tumors, treatment typically includes open-skull surgery to remove as much of the tumor as possible followed by chemotherapy or radiation, which come with serious side effects and numerous hospital visits.

What if a patient’s brain tumor could be treated painlessly, without anesthesia, in the comfort of their home? Researchers at Stanford Medicine have developed, and tested in mice, a small wireless device that one day could do just that. The device is a remotely activated implant that can heat up nanoparticles injected into the tumor, gradually killing cancerous cells. In mice with brain tumors, 15 minutes of daily treatment over 15 days, as the animals went about their normal activities, was enough to significantly increase survival times. The researchers published their work in August in Nature Nanotechnology.

The nanoparticles help us target the treatment to only the tumor, so the side effects will be relatively less compared with chemotherapy and radiation,” said Hamed Arami, PhD, co-lead  author of the paper, a former postdoctoral fellow at Stanford Medicine who is now at Arizona State University.

Arami, trained as a bioengineer, came to focus on brain cancer as a postdoctoral fellow in the lab of the late Sam Gambhir, MD, former chair of radiology at Stanford Medicine and a pioneer in molecular imaging and cancer diagnostics who died of cancer in 2020 . Five years prior, Gambhir’s teenage son, Milan, died of a glioblastoma.

Source: https://scopeblog.stanford.edu/

How To Detect Very Small Tumors

Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis, (UC Davis) offers a significant advance in using magnetic resonance imaging (MRI) to pick out even very small tumors from normal tissue.

Chemical probes that produce a signal on magnetic resonance imaging, or MRI, can be used to target and image tumors. The new research is based on a phenomenon called magnetic resonance tuning that occurs between two nanoscale magnetic elements. One acts to enhance the signal, and the other quenches it. Previous studies have shown that quenching depends on the distance between the magnetic elements. This opens new possibilities for noninvasive and sensitive investigation of a variety of biological processes by MRI.

The UC Davis team created a probe that generates two magnetic resonance signals that suppress each other until they reach the target, at which point they both increase contrast between the tumor and surrounding tissue. They call this two-way magnetic resonance tuning, or TMRET. Combined with specially developed imaging analysis software, the double signal enabled researchers to pick out brain tumors in a mouse model with greatly increased sensitivity.

It’s a significant advance,” said senior author Yuanpei Li, associate professor of biochemistry and molecular medicine at the UC Davis School of Medicine and Comprehensive Cancer Center. “This could help detect very small early-stage tumors.”

The probe developed by the UC Davis team contains two components: nanoparticles of superparamagnetic iron oxide, or SPIO, and pheophorbide a–paramagnetic manganese, or P-Mn, packaged together in a lipid envelope. SPIO and P-Mn both give strong, separate signals on MRI, but as long as they are physically close together those signals tend to cancel each other out, or quench. When the particles enter tumor tissue, the fatty envelope breaks down, SPIO and P-Mn separate, and both signals appear.

Li’s laboratory focuses on the chemistry of MRI probes and developed a method to process the data and reconstruct images, which they call double-contrast enhanced subtraction imaging, or DESI. But for expertise in the physical mechanisms, they reached out to professors Kai Liu and Nicholas Curro at the UC Davis Department of Physics (Liu is now at Georgetown University). The physicists helped elucidate the mechanism of the TMRET method and refine the technique.

The researchers tested the method in cultures of brain and prostate cancer cells and in mice. For most MRI probes, the signal from the tumor is up to twice as strong as from normal tissue – a “tumor to normal ratio” of 2 or less. Using the new dual-contrast nanoprobe, Li and colleagues could get a tumor-to-normal ratio as high as 10.

The findings are published in the journal Nature Nanotechnology.

Source: https://www.ucdavis.edu/

Modified Polio Vaccine Helps Fight Deadly Brain Tumors

A modified version of the polio vaccine, infused straight into aggressive brain tumors, helped some patients live for years longer than they normally would have, doctors reported. It’s no miracle cure — only about 20 percent of patients with gliomas were helped — but some are alive six years later, the team reported in the New England Journal of Medicine. 


“It’s a hopeful enough finding to move forward and test the vaccine in more people”, the team at the Duke University School of Medicine said.  “It’s very unusual, almost unprecedented to get this kind of long-term survival,” adds neurologist Dr. Darell Bigner, who led the study team.

The Duke team tested 61 glioma patients over five years. They all had grade IV gliomas, a group of brain tumors that includes glioblastoma. These patients have a “dismal” prognosis, the Duke team wrote in the New England Journal of Medicine. “There is currently no effective therapy.” Standard treatment of brain tumors includes surgery if the tumor is somewhere reachable; chemotherapy; and radiation. But if the tumor is aggressive, it’s usually fatal.

These are people who failed everything,” Bigner said. “Virtually all patients, no matter what you treat them with, are dead within in two years.” About a third of all brain tumors are gliomas, according to the National Brain Tumor Society. About 80,000 people a year are diagnosed with a brain tumor, and about 24,000 of those are malignant. “The average survival rate for all malignant brain tumor patients is only 34.7 percent,” the group says. But there’s evidence that some viruses can home in on tumors and kill them. It’s not clear why, but viruses can also make tumors more visible to the immune system. 

The team at Duke worked with the National Cancer Institute to design and manufacture a modified version of polio vaccine virusPolio viruses are attracted to nerve cells — that’s why they cause paralysis. The medical team used polio viruses already weakened and altered for use in polio vaccines, and genetically engineered them to carry parts of a common cold virus, called a rhinovirus, known to be attracted to glioma cells.

Source: https://www.nejm.org/