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Rethinking Cancer Research Through ‘Exceptional Responder’ Patients

Grace Silva and her oncologist, Jochen Lorch (Photo: Sam Ogden, Dana-Farber Cancer Institute.)

Grace Silva and her oncologist, Jochen Lorch (Photo: Sam Ogden, Dana-Farber Cancer Institute.)

By Richard Knox

By all odds, Grace Silva should have died more than three years ago. Instead, this 58-year-old grandmother is helping scientists rethink cancer treatment and research.

Silva’s case, detailed in this week’s New England Journal of Medicine, is one of only three recently published accounts of what cancer doctors call “exceptional responses” to a drug called everolimus (brand name Afinitor).

It was approved two years ago to treat certain breast cancers and is also used against some kidney and pancreas tumors. A couple of months after Silva started taking the drug, her thyroid tumors, which had spread to her lungs, melted away to nearly nothing. That basically never happens with this aggressive tumor, known as anaplastic thyroid cancer. “It was a near-complete response,” says her oncologist at Dana-Farber Cancer Institute, Dr. Jochen Lorch. “That in itself is exceptional. When we saw it, it was one of the better days around here.”

Studying The Exceptions

More remarkable still, Silva’s tumor stopped growing for 18 months. We’ll come back to what happened after that. But first, you should understand this story isn’t about everolimus or any particular cancer drug. It’s about how cancer specialists are learning how cancer works at the most basic level — by studying exceptional responders like Grace Silva.

And to appreciate why her case is important, you need to know how researchers figured out why she was an exceptional responder. It’s partly due to a five-year-old technology called next generation sequencing. It’s a cheap and rapid way of spelling out the genetic code of, in this case, individual patients’ tumors. Researchers can then look for gene mutations that are driving the uncontrolled growth that is cancer.

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When Muscular Dystrophy Is Personal — And Global

Chris Chege (courtesy Romana Vysatova)

Chris Chege (courtesy Romana Vysatova)

By Fred Thys
Guest Contributor

Every once in a while, I’m grateful I live in such a medically-minded town, with many deep thinkers trying to figure out treatments and cures for some very tough diseases.

I felt this way over the summer, at a conference in Boston on Facioscapulohumeral Muscular Dystrophy, a genetic disorder that affects 1 in 8,333 people and has no treatment. I did not attend the meeting due to some theoretical interest in the topic; for me, it’s personal.

My mother and grandmother suffered from the condition, and so does my brother. It causes gradual loss of muscle function, notably in the face, and in the muscles that mobilize the shoulder blades and the upper arm, but also in the legs.

My brother first developed symptoms when he was 15, and found that he could no longer run as fast as his high school soccer teammates. Since the age of 43, he has been confined to a wheelchair or scooter, unable to walk or stand.

But at the conference in August, I also realized that this illness with such a profound impact on my family, also has a global reach. Indeed, in regions like Africa, the condition is only just beginning to be acknowledged.

Enter: Chris Chege

I first saw Chege sitting on a tall stool at the back of the room with his wife. Their presence proved that the condition affects Africans, too, something that isn’t widely acknowledged. Chege and his wife had traveled to Boston from their home in Thika, in central Kenya, 30 miles Northeast of Nairobi.

An interview with Chege pointed to one possible reason that conference room was full, mainly, of white people: most people with the condition in Africa may not have been diagnosed with it yet.

But Chege said he sees others with FSHD in Kenya. He said he can tell.”By the way they walk,” he said. “I see them on national television when journalists go to their homes to interview them.” Continue reading

Tackling Autism In Babies? Small Study An ‘Absolute Miracle,’ Says Mom

Megan says the experimental trial she participated in with her daughter Isabel was "an absolute miracle," transforming the child from a troubled baby who looked headed for autism to a typical, happy preschooler.

Megan says the experimental trial she participated in with her daughter Isabel was “an absolute miracle,” transforming the child from a troubled baby who looked headed for autism to a typical, happy preschooler.

Research out this week suggests that it’s never too early to begin therapy to treat some of the defining symptoms of autism. Karen Weintraub reports on the promising new findings in USA Today under the headline, “Study: Autism Signs In Babies Can Be Erased.”

Karen expands on her report here:

In a small pilot study — the first to look at starting therapy in babies this young — researchers at the University of California Davis’ MIND Institute, began treating 7 babies who showed symptoms likely to turn into autism later. By their third birthdays, five of the children no longer exhibited any symptoms of autism, and a sixth was diagnosed with mild autism.

Because the study was so small, and autism cannot reliably be diagnosed in infancy, the researchers stopped short of calling the treatment a breakthrough. But they said they will be following up with a larger study, which they hoped would confirm the results.

One mother involved in the trial described the treatment as “an absolute miracle” for her daughter, Isabel. The mother, Megan, asked not to be fully identified, but talked openly about the trial and its benefits for her family.

At nine months old, Isabel wouldn’t turn her head when someone walked into a room calling her name. She never babbled, Megan said. She was physically delayed in fine and gross motor skills, and didn’t seem to know how to play with toys. All those are signs commonly seen in children who go on to be diagnosed with autism.

Megan heard about the trial through her pediatrician and the family – including Isabel’s dad and her older brother – moved from the Seattle area to Sacramento, so they could participate in the study.

In 12 weekly sessions, lead researcher Sally Rogers coached Megan and her husband John as they played with baby Isabel. Where most children will smile or giggle when happy, Isabel’s facial expressions didn’t change much; where others might cry if scared by a loud sound, Isabel rarely reacted to anything in her environment. But Rogers showed them that Isabel might glance over quickly when she was interested or look at her hands when something was too loud or overwhelming – cues that Megan and John could take to do more or less of whatever they were doing.

Once they learned to “speak” Isabel’s language, Megan said she and John were able to react to her and engage with their baby for the first time. Eventually, through this interaction, Isabel learned that she could communicate – and have fun doing it. That primed her to learn even more, Megan said.

Megan said she and her husband would never have figured out what to do without the coaching. Continue reading

One Shot, Two Shot: Study Finds One Dose of HPV Vaccine Could Be Enough

A teenager bares her band-aid after getting the HPV vaccine.

A teenager bares her band-aid after getting the HPV vaccine.

You’ve heard about the importance of getting an HPV vaccine and the surprisingly low percentage of young women who do so in the U.S.  For various reasons — accessibility, cost, bad information — many who start the 3-part vaccination series do not complete it.

But what if a single dose could protect women from HPV around the globe? The results of a new study suggest it very well could. Researchers found HPV antibodies in the blood of Costa Rican women who had received one dose of an HPV vaccine four years prior, indicating that one shot might be enough to equip the immune system to recognize and fight HPV infection. While antibody levels were higher in women who had received two doses compared to just one, antibody levels were similar between two- and three-dose recipients.

Public health officials have made the case that getting all 3 doses of the HPV vaccine is necessary for full protection.  And they’re not eating their words yet: the vaccine used in the recent study, Cervarix, only guards against two strains of HPV. It remains untested whether Gardasil, which protects against two additional strains of HPV and is the predominant HPV vaccine in the U.S., is effective after a single dose. That being said, the study’s findings are promising for the global fight against HPV.

Take a look at the news release from the American Association for Cancer Research website:

Women vaccinated with one dose of a human papillomavirus (HPV) vaccine had antibodies against the viruses that remained stable in their blood for four years, suggesting that a single dose of vaccine may be sufficient to generate long-term immune responses and protection against new HPV infections, and ultimately cervical cancer, according to a study published in Cancer Prevention Research, a journal of the American Association for Cancer Research.

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Autistic Kids Can Outgrow Critical Sensory Disconnect, Study Finds

By Karen Weintraub
Guest Contributor

For many people, the “read-my-lips” phenomenon happens almost unconsciously: in a crowded or noisy room, most of us can hear better by watching the person’s lips form the sounds.

That’s not true for many people with autism. They have long reported being unable to pay attention to words and visuals at the same time — which may explain why some on the spectrum avoid looking others in the eye. They have to limit their visual information so they can hear what the person is saying.

In the last few years, researchers have finally begun to take these reports seriously and to investigate them.

In a paper out this week in the journal Cerebral Cortex,  researchers at Albert Einstein College of Medicine in the Bronx showed that children with autism struggle to integrate information from multiple senses. High functioning children with autism, ages 5-12, didn’t get the benefit most people do from watching a person’s lips moving while speaking over background noise, according to research led by professor of pediatrics John Foxe. Continue reading

Study Suggests Cell Damage As Potential Danger Of Antibiotic Use

Cipro (Wikimedia Commons)

Cipro (Wikimedia Commons)

By Karen Weintraub
Guest Contributor

Might antibiotics be causing harm at a cellular level? That’s one possible conclusion from a new study by researchers at Boston University.

We’ve long known about the dangers of antibiotic resistance – that one day, the drugs will stop working – and scientists have learned in recent years that antibiotics also kill off “good” bacteria with the “bad.” But now, James J. Collins, a B.U. biomedical engineer, says his research in mice suggests that certain antibiotics, taken long-term, could be damaging our own cells.

In a study published today in Science Translational Medicine, Collins’ team showed that widely used antibiotics like ciprofloxacin and ampicillin can damage the cells’ fuel supply and cause oxidative stress, which has been linked to cancer, heart disease, Alzheimer’s and other ailments.

The research is still early and far from conclusive, but Collins says he thinks it’s convincing enough to at least merit more study.

When he and his colleagues exposed cells in a dish and then mice to these antibiotics over several weeks, they saw signs of serious cellular damage. The doses were similar to those given patients taking long-term therapy. The damage may explain why antibiotics have long been associated with side effects such as tendon, kidney and liver problems, says Collins, also a founding faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard. Continue reading

MGH Braces For Millions In Research Cuts

WBUR’s Curt Nickisch reports that Massachusetts General Hospital is budgeting for a $19 million cut next year due to decreases in federal research funding: 

MGH President Peter Slavin says the projected loss of $19 million is only part of it — that’s the amount that goes to the hospital to help pay overhead. Slavin says the National Institutes of Health has also been telling researchers to lower their maximum salaries, and warning that fewer grants will get the green light.

“Some young people who might have considered careers in biomedical research are just going to see this incredibly steep hill, and decide to do other things,” Slavin said. “That is tragic.”

mgh

Mass General’s annual research budget is about $800 million.

Last week WBUR reported on further sequester-related research cuts and how they might undermine basic science — and, specifically, Boston’s biomedical edge — in the future: Continue reading

Study Finds ‘Significant’ Weight Loss Among Seriously Mentally Ill

It’s widely known that people with serious mental illness have a lower life expectancy — around 25 years less — compared to the general population. One reason is that these folks are more likely to smoke and be overweight or obese which, of course, can lead to all sorts of critical health problems — heart disease, diabetes, respiratory troubles and a whole host of chronic illnesses. The challenges facing this population are great: the very medications they take to function through the day can lead to weight gain, and studies have shown that they often have poor diets and sedentary lives.

(Tobyotter/flickr)

(Tobyotter/flickr)

A number of efforts are currently underway to try to reverse this trend by focusing directly on the physical health of the mentally ill.

The latest study in this arena, published in The New England Journal of Medicine today, found that a so-called “behavioral weight-loss intervention” including weight-management counseling and group exercise “significantly” reduced weight “in overweight and obese adults with serious mental illness” (including those with major depression, schizophrenia and bi-polar disorder).

The mean weight loss, after 18 months, was 7 pounds, researchers from Johns Hopkins report. Not so much, you may think. But researchers note: “This extent of weight loss, albeit modest, has been shown to have beneficial effects, such as a reduced risk of cardiovascular disease among persons with an initially elevated risk.” Also noteworthy is that people in this study, called ACHIEVE, lost weight gradually over time.

“Participants in the intervention group in ACHIEVE continued to lose weight after 6 months and did not regain weight, Continue reading

Could Stressed-Out Rats Hold Clues To How Acupuncture Works?

Could rats subjected to chronic stress — their paws dunked in icy water — hold the key to how acupuncture works? And could all those needles, traditionally thought to unblock the flow of life energy, in fact be calming the body’s stress response?

That’s what Ladan Eshkevari, a licensed acupuncturist, physiologist and associate professor of nursing at Georgetown University School of Nursing theorizes after treating a group of stressed-out rats with acupuncture. In a study published recently in the Journal of Endocrinology, she found that the treatment actually lowered levels of the rat-equivalent of cortisol, a stress hormone, as well as other proteins and hormones secreted by biologic pathways involved in the stress response.

(SMercury98/flickr)

(SMercury98/flickr)

“Our study is one of the first…to show how acupuncture works on chronic stress,” she said. Understanding the ancient Chinese practice on a molecular level, she adds, might make it more acceptable in a mainstream Western medicine context.

Rats, of course, are rats; they’re mammals, sure, but they don’t always behave like people. Still, Eshkevari’s hypothesis is that rats and humans may be comparable when it comes to their response to chronic stress. She posits that acupuncture works by quieting a key pathway — the hypothalamus-pituitary-adrenal axis — that drives the production of critical stress hormones in the body. Cortisol in high levels has been linked to depression, anxiety, cardiovascular disease, insomnia and other conditions.

More than 3 million adults in the U.S. use acupuncture each year, according to the National Institutes of Health, yet “there has been considerable controversy surrounding its value as a therapy and whether it is anything more than placebo.” Despite numerous studies reporting its benefits for chronic pain, stress and other conditions (and the fact that it’s been used for over 2,500 years across Asia) experts says there’s no clear understanding of how, exactly, it works. Continue reading

News Flash: Sex With A Condom Still Fun, Study Finds

peachy92/flickr

peachy92/flickr

News Flash: Sex is fun — even with a condom.

That’s the takeaway from a nationwide online sex survey of men and women ages 18-59, just out in the Journal of Sexual Medicine. When asked to quantify their pleasure quotient, both men and women rated their most recent sexual experience as quite high, in general, with few differences based on condom and lubricant use.

Notably, the new study, which included 1,645 respondents, didn’t ask whether people preferred sex with or without a condom. It simply asked for a detailed accounting of a recent sexual encounter. So, among those who chose to use condoms (27.5% of men and 22.3% of women in the survey) the self-reported arousal rating and other key pleasure indicators appeared to be essentially comparable to non-condom users.

“Not everyone wants to or has to use a condom, or lubricant, when they have sex,” the study’s lead author, Debby Herbenick, Ph.D., MPH, with the Center for Sexual Health Promotion at Indiana University told me via email. “But if they want to use a condom or lubricant – to make sex safer or more comfortable – it’s unlikely to have a significant impact on overall pleasure for many (but not all) people.”

(I should say here that the study was funded by condom and vibrator maker Church & Dwight. This set off my skeptic’s alarm bells; I asked Herbenick whether the company played any role in analyzing the data. She said that Church & Dwight “did not intervene in that way. Our team at Indiana University analyzed the data on our own, we wrote the papers, and we managed the review process directly with the Journal of Sexual Medicine where the study was published.”)

Of course, conventional wisdom holds that sex is far hotter without a condom. See: Christian Grey on condom-free sex in “Fifty Shades Of Grey,” p. 271:

“I scoot out of bed, too, and grab my sweatpants and a cami top, then sit back on the bed, cross-legged, watching him. I don’t want him to go. What can I do?
“When is your period due?” He interrupts my thoughts.
What?
“I hate wearing these things,” he grumbles. He holds up the condom, then puts it on the floor and slips on his jeans.
“Well?” he prompts when I don’t reply, and he looks at me expectantly as if he’s waiting for my opinion on the weather. Holy crap…this is personal stuff.
“Next week.” I stare down at my hands.
“You need to sort out some contraception.”

(Also, read this single guy’s lament in which the author blames condoms for triggering “deflationary” erectile events.) Continue reading