Trojan Horses: Nanoparticles sneak drugs into brain to battle cancer

Photo by dierk schaefer
Photo by dierk schaefer

I just read an interesting article in the Berkeley Science Review about using nanoparticles to make chemotherapy more effective against a type of brain cancer called glioblastoma. I was then surprised and proud when I realized one my former science-writing students, Dharsi Devendran, wrote it.

Although rare, glioblastoma is an invasive and deadly brain cancer with octopus-like tentacles that are difficult to completely remove with surgery. Even the standard combined treatment of surgery, radiation and chemotherapy isn’t very effective — people typically die within months of diagnosis. So researchers are actively searching for better treatments.

Devendran explains:

Although it is difficult to fight, glioblastoma also has a weakness. In its rush to feed itself, it accelerates the blood vessel formation process and creates hole-riddled blood vessels around the tumor. Because cancer drugs are small enough to slip through these holes, they can exploit this defect—but they also need a strategy to cross the blood-brain barrier in order to reach the tumor.

Acting like a security system for the brain, the blood-brain barrier is a network of blood vessels that allow essential nutrients to enter while blocking harmful molecules. Unfortunately, it also blocks life-saving chemotherapy drugs, unless researchers can find clever ways to sneak them through the barrier.

Ting Xu, PhD, professor of materials science at UC Berkeley, and her collaborators are developing tiny nanocarriers that can envelop and protect chemotherapy drugs as they move through the blood, across the blood-brain barrier, and into the brain to the glioblastoma tumor tissue.

The researchers designed a new nanocarrier, called a 3-helix micelle (3HM), out of proteins with molecules on the surface that fit into specific proteins found only on the surface of the tumor cells — like fitting a key into a lock. Once the 3HM nanocarriers access the tumor cells, they release their chemotherapy drugs to help destroy the glioblastoma.

Xu’s team has shown that their 3HM nanocarrier is twice as effective at reaching glioblastoma cells as liposomes, a nanocarrier made of fatty acids that is a standard in nanotechnology drug delivery. This is in part because the 3HM is five times smaller than liposomes.

“We still don’t understand the mechanism completely,” said JooChuan Ang, a graduate student in Xu’s group, in the article. “Size is definitely a factor, but there could be other factors that contribute…”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Tattoo ink may mimic cancer on PET-CT images

19824000898_7611622d67_o_Flickr_PauloGuereta
Photograph by Paulo Guereta

The hit new crime thriller Blindspot is about a mysterious woman, Jane Doe, who is covered in extensive full-body tattoos. If Jane Doe were a real woman who ever needed medical imaging, she might need to be concerned.

In a case report published recently in the journal Obstetrics & Gynecology, researchers found that extensive tattoos can mimic metastases on images from positron emission tomography (PET) fused with computed tomography (CT). PET-CT imaging is commonly used to detect cancer, determine whether the cancer has spread and guide treatment decisions. A false-positive finding can result in unnecessary or incorrect treatment.

Ramez N. Eskander, MD, assistant professor of obstetrics and gynecology at UC Irvine, and his colleagues describe the case study of a 32-year-old woman with cervical cancer and extensive tattoos. The pre-operative PET-CT scan using fluorine-18-deoxyglucose confirmed that there was a large cervical cancer mass, but the scan also identified two ileac lymph nodes as suspicious for metastatic disease. However, final pathology showed extensive deposition of tattoo ink and no malignant cells in those ileac lymph nodes.

It is believed that carbon particles in the tattoo pigment migrate to the nearby lymph nodes through macrophages, using mechanisms similar to those seen in malignant melanoma. The researchers explain in their case report:

Our literature search yielded case reports describing the migration of tattoo ink to regional lymph nodes in patients with breast cancer, melanoma, testicular seminoma, and vulvar squamous cell carcinoma, making it difficult to differentiate grossly between the pigment and the metastatic disease, resulting in unnecessary treatment.

The authors warn other physicians to be aware of the possible effects of tattoo ink on PET-CT findings when formulating treatment plans, particularly for patients with extensive tattoos.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

How Damaged Is Your DNA?

Summary of the factors that cause DNA damage and the associated diseases. (Courtesy of Sylvain Costes)
Summary of the factors that cause DNA damage and the associated diseases. (Courtesy of Sylvain Costes)

DNA stores the genetic information in each living cell, so its integrity and stability is essential to life.

DNA is constantly being damaged by environmental factors like exposure to ionizing radiation, ultraviolet light and toxins. DNA replication is also prone to error during normal cell division. So your body is busy constantly repairing damaged DNA. However, sometimes this normal DNA repair process fails, causing DNA damage and genetic mutations to accumulate which leads to serious health problems like cancer, immunological disorders and neurological disorders.

If your annual checkup included a simple blood test to determine how much DNA damage you have in your body, you may be able to optimize your long-term health by taking action to minimize DNA damage due to your diet, exercise and environment.

A start-up company called Exogen Biotechnology wants to provide the public with a way to monitor their DNA health, so they can act to reduce their DNA damage. Exogen has developed technology that can rapidly quantify a type of DNA damage called double-strand breaks.

“DNA double-strand breaks are when the two strands of the DNA are cut, so they can move apart,” explained Sylvain Costes, a Staff Scientist at Lawrence Berkeley National Laboratory and co-founder of Exogen.  “This is linked to mutation and chromosome rearrangement, so it’s a big deal – it’s the dangerous type of DNA damage. That’s what we look at.”

Exogen’s DNA damage measurement is based on technology developed over 15 years ago called immunocytochemistry – a technique that uses a primary antibody that recognizes the protein that is repairing the DNA break, along with a secondary fluorescent antibody that binds to the primary antibody. This creates bright spots in the microscope image where there are double-strand DNA breaks, so scientists can take a picture and count the breaks.

Exogen is moving this technique out of the laboratory to make it publicly available. They have significantly improved the technology, so that it’s feasible to rapidly test small blood samples for the level of DNA double-strand breaks. A customer collects tiny blood samples using an in-home kit, combines the blood samples with a fixative solution to preserve them, logs on to the Exogen website to register the samples and complete the questionnaire, and mails the samples to Exogen for analysis.

Exogen tested their new technology in two pilot studies with a total of 97 people. They observed a significant increase in the level of DNA damage with age, where 70 year olds had double the number of DNA double-strand breaks compared to 20 year olds. The four people who had suffered from cancer also had a higher level of DNA damage compared to others in their age group.

“When we did the first pilot study, we saw the excitement of the people,” said Costes. “They realized that this is something totally new; something we know in the research field, but that’s never been given to the people.”

Inspired by the initial pilot studies, Exogen wants to build a large database of DNA damage levels for research purposes so they can better understand the meaning of an elevated level of DNA damage and how certain factors affect DNA health. Of course, their data collection process and database are secure, encrypted and fully HIPAA compliant.

In order to get the necessary blood samples, they are currently running a crowdfunding campaign on Indiegogo. People that donate $99 receive a kit to safely collect three blood samples at home, and then they receive a report on their current level of DNA damage. Exogen is calling the campaign a “citizen science project” since volunteers also fill out questionnaires about their medical history and lifestyle. They’ve already collected $76,000 and the crowdfunding campaign runs through March 26. They plan to spend the money on a microscope and liquid handler, which will allow them to fully automate their system so they can analyze up to 400 blood samples per day.

Currently, Exogen can’t interpret the results or give people advice about how to lower their DNA damage, because the Food and Drug Administration (FDA) hasn’t approved them as a diagnostic test. The goal of the crowdfunding campaign is to collect blood samples from 1000 people so they can go to the FDA.

“Once we have FDA approval, we can start counseling,” said Costes. “Primary care doctors can start engaging and testing it further with their patients, because we’ll provide a guideline to help them understand what it means.”

Costes stressed that their test is very different from genetic testing provided by companies like 23andme. Exogen isn’t looking at the genetic makeup. Instead, they are looking at a physiological response, so they compare it to a cholesterol test.

“To me this is identical to cholesterol,” clarified Costes. “Your genetics places you in a certain range, but your lifestyle can change where you are within that range. In contrast to genetic testing, we feel like this test can bring hope because you have a way to act.”

One of their applications is to determine how DNA damage is affected by lifestyle factors like diet.  Exogen plans to study a group of people for a long time to better understand how DNA damage correlates with specific diseases and with health improvements due to people’s actions. They want to evaluate whether people can improve their DNA health by changing their lifestyle or environment, instead of their fate being driven entirely by genetics.

However, none of the exciting applications can happen until Exogen collects data from a larger number of people. “We need your help to make it happen,” Costes concludes. “We can’t do it alone.”

This is a repost of my KQED Science blog.

Screenings Sunscreens

photograph of someone applying sunscreen
Photograph courtesy of Hacklock via Creative Commons.

I’m one of those grocery shoppers who turns the package around to check the ingredients, before I buy it for the first time. Checking food packages is relatively easy, because I expect only recognizable simple ingredients. As they say, would my Great Grandmother recognize this as food? What about sunscreen? How can you tell if it’s safe?

The Environmental Working Group (EWG) has done extensive research to evaluate the effectiveness and safety of over 1800 sunscreens on the market, so you don’t have to. Their sixth annual 2012 Sunscreen Guide lists the best and worst sunscreens. It’s worth a look to make sure your sunscreen isn’t on their “Hall of Shame.” The EWG also provides detailed information about potentially harmful sunscreen ingredients.

For more information about sunscreen safety, check out my KQED Quest blog.

Is Your Dentist Giving You A Brain Tumor?

dental x-ray
Courtesy of TheKarenD via Creative Commons.

In the United States, it is common to have dental X-rays as part of your regular checkup or when you have tooth pain. These X-rays use a small amount of ionizing radiation to take a picture of your teeth, bones and gums in order to show tooth decay, impacted teeth, bone loss, and other mouth problems.  Since ionizing radiation exposure is known to increase the risk of certain kinds of cancer, scientists have recently studied whether dental X-rays increase your risk of brain tumors.

An article was just published in the peer-reviewed medical journal, Cancer. It reported the results of a large study that examined the association between dental X-rays and the risk of the most common type of brain tumor (meningioma). The study was headed by researcher Elizabeth Claus, M.D., Ph.D. at the Yale University School of Medicine, in collaboration with the University of California at San Francisco School of Medicine, Brigham and Women’s Hospital, University of Texas M.D. Anderson Cancer Center, and Duke University of Medicine.

Recent news coverage sensationalized the results of this study, possibly alarming people and dissuading them from having dental X-rays. So here are the basics of the report. This research was a case-control study that compared the histories of 1433 people who had a confirmed meningioma brain tumor (the “cases”) with 1350 people without a brain tumor (the “controls”) who were matched to have the same age, sex and state of residence as the brain tumor cases. All participants were 20 to 79 years old, lived in the United States, and were enrolled in the study between May 2006 and April 2011. Both groups were contacted by telephone and interviewed for about an hour. This phone interview included questions about the onset, frequency and type of dental care they had received over their lifetime.

The researchers were interested in three types of dental X-rays:

  • Bitewingsa small X-ray view that shows the upper and lower back teeth simultaneously, where the patient bites down on a small holder filled with the X-ray film. Bitewings are frequently used during regular checkups to look for cavities.
  • Full-mouth – a series of about 14-21 X-ray films that are used to view the entire mouth for dental problems, usually performed during a person’s first visit to the dentist.
  • Panoramic – a single X-ray that shows a broad view of the entire mouth to provide information about the teeth, jawbones, sinuses, and other tissues of the head and neck. Panoramic X-rays are taken occasionally, often to evaluate wisdom teeth, using a machine that moves around the patient’s head.

This large case-control study showed that people with a brain tumor reported having dental X-rays significantly more frequently over their lifetime than the controls without a brain tumor. However, the differences were only significant for bitewing and panoramic type dental X-rays, and not for full-mouth X-rays which actually expose the mouth to a greater dose of radiation. This inconsistency demonstrates that further research is needed to prove any link between dental X-rays and brain tumors.

The biggest issue with this study is that participants were asked to recall their own history of dental X-rays throughout their lifetime, which makes the results less reliable. In particular, there is a fear of “recall bias” – the people with brain tumors may have been focusing on the potential causes of their cancer and therefore may have been more likely to recall dental X-rays than the control group, potentially biasing the results. Although more work, the researchers should have acquired the participants’ dental histories directly from medical records.

While this study does suggest that regular dental X-rays may be linked to an increased risk of developing a brain tumor, it does not prove an actual link. There could be other factors that contributed to this association. In order to establish a causal link, the researchers should consider performing a different kind of study that follows a group of people over time to see who develops a brain tumor.

More importantly, the recent sensationalized news headlines ignored the important fact that brain tumors are rare. Men and women in the United States have a 0.61% lifetime risk of being diagnosed with any type of primary malignant brain or central nervous system tumor, implying a 0.21% lifetime risk of developing meningioma. For instance, this is much smaller than the 12.2% lifetime risk of a woman developing breast cancer.

So this research study should not scare people away from having dental X-rays when recommended by their dentist. The American Dental Association recommends that dentists now evaluate the benefit of X-ray exposure for each patient, reducing the frequency of routine X-rays for healthy patients. In addition, dental X-rays now expose patients to less radiation than in the past.