Posts Tagged ‘scientific’

Sabotage as therapy: Aiming lupus antibodies at vulnerable cancer cells

The findings were published recently in Nature‘s journal Scientific Reports.

The study, led by James E. Hansen, M.D., assistant professor of therapeutic radiology at Yale School of Medicine, found that cancer cells with deficient DNA repair mechanisms (or the inability to repair their own genetic damage) were significantly more vulnerable to attack by lupus antibodies.

“Patients with lupus make a wide range of autoantibodies that attack their own cells and contribute to the signs and symptoms associated with lupus. Some of these antibodies actually penetrate into cell nuclei and damage DNA, and we suspected that we may be able to harness the power of these antibodies for use in targeted cancer therapy,” Hansen said.

The genetic code that determines how a cell develops is written in DNA. Damage to this code can cause a cell to malfunction, die, or transform into a cancer cell. Normal cells are equipped to repair damaged DNA and preserve the genetic code, but many cancer cells have defective DNA repair machinery and accumulate genetic mutations.

This difference between normal cells and certain cancer cells creates an opportunity to develop therapies that damage DNA and only kill cancer cells that cannot repair the damage. However, DNA is sequestered inside cell nuclei, where delivery of therapies can be challenging. Yale Cancer Center researchers are finding that naturally occurring lupus antibodies just may be a solution to this problem.

“Lupus antibody-based cancer therapy is an emerging new concept, and I believe we are just seeing the tip of the iceberg in terms of the potential of this approach,” said Hansen.

The researchers previously found that a lupus antibody called 3E10 inhibits DNA repair and sensitizes cancer cells to DNA damage, and they have now found that the DNA-damaging lupus antibody 5C6 is toxic to DNA repair-deficient cancer cells.

“Now that we know that more than one lupus antibody has a selective effect on cancer cells, I am confident that additional lupus autoantibodies with even greater therapeutic potential await discovery,” Hansen said.

source : http://www.sciencedaily.com/releases/2014/09/140902151302.htm

Brain tumors fly under body’s radar like stealth jets, new research suggests

Like a stealth fighter jet, the coating means the cells evade detection by the early-warning immune system that should detect and kill them. The stealth approach lets the tumors hide until it’s too late for the body to defeat them.

The findings, made in mice and rats, show the key role of a protein called galectin-1 in some of the most dangerous brain tumors, called high grade malignant gliomas. A research team from the University of Michigan Medical School made the discovery and has published it online in the journal Cancer Research.

In a stunning example of scientific serendipity, the team uncovered galectin-1’s role by pursuing a chance finding. They had actually been trying to study how the extra production of galectin-1 by tumor cells affects cancer’s ability to grow and spread in the brain.

Instead, they found that when they blocked cancer cells from making galectin-1, the tumors were eradicated; they did not grow at all. That’s because the “first responders” of the body’s immune system – called natural killer or NK cells – spotted the tumor cells almost immediately and killed them.

But when the tumor cells made their usual amounts of galectin-1, the immune cells couldn’t recognize the cancerous cells as dangerous. That meant that the immune system couldn’t trigger the body’s “second line of defense”, called T cells – until the tumors had grown too large for the body to beat.

Team leader Pedro Lowenstein, M.D., Ph.D, of the U-M Department of Neurosurgery, says the findings open the door to research on the effect of blocking galectin-1 in patients with gliomas.

“This is an incredibly novel and exciting development, and shows that in science we must always be open-minded and go where the science takes us; no matter where we thought we wanted to go,” says Lowenstein, whose graduate student Gregory J. Baker is the first author of the paper.

“In this case, we found that over-expression of galectin-1 inhibits the innate immune system, and this allows the tumor to grow enough to evade any possible effective T cell response,” he explains. “By the time it’s detected, the battle is already lost.”

The NK-evading “stealth” function of the extra-thick coating of galectin-1 came as a surprise, because glioma researchers everywhere had assumed the extra protein had more to do with the insidious ability of gliomas to invade the brain, and to evade the attacks of T cells.

Gliomas, which make up about 80 percent of all malignant brain tumors, include anaplastic oligodendrogliomas, anaplastic astrocytomas, and glioblastoma multiforme. More than 24,000 people in the U.S. are diagnosed with a primary malignant brain tumor each year.

The tiny tendrils of tumor that extend into brain tissue from a glioma are what make them so dangerous. Even when a neurosurgeon removes the bulk of the tumor, small invasive areas escape detection and keep growing, unchecked by the body.

Helping the innate immune system to recognize early stages of cancer growth, and sound the alarm for the body’s defense system to act while the remaining cancer is still small enough for them to kill, could potentially help patients.

While the new discovery opens the door to that kind of approach, much work needs to be done before the mouse-based research could help human patients, says Lowenstein, who is the Richard Schneider Collegiate Professor in Neurosurgery and also holds an appointment in the U-M Department of Cell and Developmental Biology. Galectin-1 may help other types of tumor evade the innate NK cells, too

The new research suggests that in the brain’s unique environment, galectin-1 creates an immunosuppressive effect immediately around tumor cells. The brain cancer cells seem to have evolved the ability to express their galectin-1 genes far more than normal, to allow the tumor to keep growing.

Lowenstein and co-team leader Maria Castro, Ph.D., have long studied the immune system’s interactions with brain cancer, using funding from the National Institutes of Health, and are co-leading a new clinical trial for malignant glioma (NCT01811992), that aims to translate prior research achievements into new trials for patients with brain tumors.

Most brain tumor immune research has focused on triggering the action of the adaptive immune system – whose cells control the process that allows the body to kill invaders from outside or within.

But that system take days or even weeks to reach full force – enough time for incipient tumors to grow too large for immune cells to eliminate solid tumor growth. The new research suggests the importance of enhancing the ability of the innate immune system’s “early warning” sentinels to spot glioma cells as early as possible.

source : http://www.sciencedaily.com/releases/2014/08/140806153927.htm

Three-in-one optical skin cancer probe

Researchers from the University of Texas at Austin’s Cockrell School of Engineering have now developed a probe that combines into one device three unique ways of using light to measure the properties of skin tissue and detect cancer. The researchers have begun testing their 3-in-1 device in pilot clinical trials and are partnering with funding agencies and start-up companies to help bring the device to dermatologists’ offices.

The researchers describe the skin cancer probe in a new paper published in the journal Review of Scientific Instruments, from AIP Publishing.

Skin cancers of all types are the most common forms of cancer in North America, and melanoma, the most deadly form of skin cancer, is one of the leading causes of cancer death, killing nearly 10,000 people every year in the United States.

Currently, the only definitive way to diagnose skin cancer is to perform a biopsy, in which doctors remove a suspect skin lesion and then examine the stained tissue under a microscope to look for cancerous cells. Determining which lesions to biopsy is an imprecise art, however, and for every case of skin cancer detected there are roughly 25 negative biopsies performed, translating to a cost of $6 billion to the U.S. health care system, according to estimations performed by the researchers.

James Tunnell, an associate professor in the biomedical engineering department at UT, believes the new probe developed by his team could eventually help reduce the high number and cost of negative biopsies by giving a clear picture of which skin lesions are most likely cancerous. He and his colleagues combined three common spectroscopic techniques — Raman spectroscopy, diffuse reflectance spectroscopy, and laser-induced fluorescence spectroscopy — into one probe to create a more complete picture of a skin lesion. By revealing information invisible to the human eye, the probe could offer a better screening tool for cancer and eliminate many negative biopsies.

As normal skin becomes cancerous, cell nuclei enlarge, the top layers of skin can thicken and the skin cells can increase their consumption of oxygen and become disorganized, Tunnell said. The changes alter the way light interacts with the tissue.

To detect all these changes requires multiple spectroscopic techniques. For example, diffuse optical spectroscopy is sensitive to absorption by proteins such as hemoglobin while Raman spectroscopy is sensitive to vibrational modes of chemical bonds, such as those found in connective tissues, lipids, and cell nuclei, Tunnell noted.

Previous research efforts have tried combining spectroscopic techniques to aid in skin cancer detection, but the University of Texas team is the first to combine three techniques in a single probe that would be inexpensive enough to be used widely in clinics and doctors’ offices. The probe itself is about the size of a pen and the spectroscopic and computer equipment that supports it fits neatly onto a portable utility cart that can be wheeled between rooms. Each reading takes about 4.5 seconds to perform. The 3-in-1 nature of the probe saves time and money while still giving a comprehensive examination of the skin properties.

“Skin is a natural organ to apply imaging and spectroscopy devices to because of its easy access,” Tunnell said. Most devices have been at the research stage for the last 10 years or so, but several are now undergoing clinical development, he noted. “This probe that is able to combine all three spectral modalities is the next critical step to translating spectroscopic technology to the clinic.”

source : http://www.sciencedaily.com/releases/2014/08/140805131714.htm