One of the biggest challenges facing cancer researchers — and lots of other medical researchers, in fact — is that experimental models cannot perfectly replicate human diseases in the laboratory.
That’s why human Organs-on-Chips, small devices that mimic human organ environments in an affordable and lifelike manner, have quickly been taken up into use by scientists in academic and industry labs and are being tested by the U.S. Food and Drug Administration.
Now, the chips have helped discover an important link between breathing mechanics and lung cancer behavior. …
On average, one in four people who have a heart attack sustain long-lasting damage to the mitral valve, which has the important job of making sure blood pumps through the heart’s ventricles in the right direction. If the valve is damaged, the heart’s pumping efficiency is reduced and blood can flow backward, which can lead to heart failure and death.
Now, a team of collaborators from Boston Children’s Hospital, Massachusetts General Hospital and Brigham and Women’s Hospital has shown, for the first time, that it’s possible to treat and even prevent mitral valve damage after heart attack with an FDA-approved, anti-hypertension drug called losartan. Their findings are published in the Journal of the American College of Cardiology. …
The average human has 60,000 miles of blood vessels coursing through their body. There are a number of mechanisms the body uses to keep that vast vascular network healthy, including a tiny fat molecule, a lipid called S1P, that plays a particularly important role.
S1P receptors dot the surface of the endothelium, a layer of cells that line the inside of all the body’s blood cells. Together, these so-called endothelial cells form a barrier between the body’s circulating blood and surrounding tissue. When S1P molecules activate their receptors, it suppresses endothelial inflammation and generally helps regulate cardiovascular health.
Now, researchers led by Timothy Hla, PhD, from the Boston Children’s Hospital Vascular Biology Program, report a novel therapeutic fusion that could trigger increased S1P receptor activity and recover blood vessel health following the onset of hypertension, atherosclerosis, stroke, heart attack and other cardiovascular diseases. …
The blood-brain barrier was designed by nature to protect the brain and central nervous system (CNS) from toxins and other would-be invaders in the body’s circulating blood. Made up of tightly-packed cells, the barrier allows nutrients to pass into the CNS and waste products from the brain to be flushed out, while blocking entry of harmful substances.
A dysfunctional blood-brain barrier can contribute to CNS diseases including Alzheimer’s and multiple sclerosis (MS). But, ironically, the same blood-brain barrier can keep out drugs intended to treat CNS disease. Scientists have long been seeking ways to overcome this obstacle.
Now, Timothy Hla, PhD, and members of his laboratory in the Boston Children’s Hospital Vascular Biology Program have found a way to selectively control openings in the blood brain barrier to allow passage of small drug molecules. …
Without a blood supply, a tumor can remain dormant and harmless. But new blood vessel growth from an existing vessel, a process called angiogenesis, is a hallmark of both benign and malignant tumors. During angiogenesis, blood vessels invade tumors and activate them, fueling their growth.
Now, Marsha A. Moses, PhD, who directs the Vascular Biology Program at Boston Children’s Hospital, and members of her laboratory have revealed that a specialized imaging system can detect changes in cell behaviors. These changes predict when tumors are leaving a state of dormancy and becoming more likely to grow. …
Sometimes a scientific idea takes a long time to make its way forward. Angiogenesis is a case in point. As surgeon-in-chief at Boston Children’s Hospital, Judah Folkman, MD, noted that malignant tumors often had a bloody appearance. In The New England Journal of Medicine in 1971, he hypothesized that tumors cannot grow beyond a certain size without a dedicated blood supply, and that “successful” tumors secrete an unknown substance that encourages blood vessel growth, or angiogenesis.
If angiogenesis could be blocked, he argued, tumors might not grow or spread. Rather than waging a toxic chemical and radiation battle with a tumor, one could starve it into submission by shutting down its blood supply.
A person born with a port-wine birthmark on his or her face and eyelid(s) has an 8 to 15 percent chance of being diagnosed with Sturge-Weber syndrome. The rare disorder causes malformations in certain regions of the body’s capillaries (small blood vessels). Port-wine birthmarks appear on areas of the face affected by these capillary malformations.
Aside from the visible symptoms of Sturge-Weber, there are also some more subtle and worrisome ones. Sturge-Weber syndrome can be detected by magnetic resonance imaging (MRI). Such images can reveal a telltale series of malformed capillaries in regions of the brain. Brain capillary malformations can have potentially devastating neurological consequences, including epileptic seizures.
Frustratingly, since doctors first described Sturge-Weber syndrome over 100 years ago, the relationship between brain capillary malformations and seizures has remained somewhat unexplained. In 2013, a Johns Hopkins University team found a GNAQ R183Q gene mutation in about 90 percent of sampled Sturge-Weber patients. However, the mutation’s effect on particular cells and its relationship to seizures still remained unknown.
But recently, some new light has been shed on the mystery. At Boston Children’s Hospital, Sturge-Weber patients donated their brain tissue to research after it was removed during a drastic surgery to treat severe epilepsy. An analysis of their tissue, funded by Boston Children’s Translational Neuroscience Center (TNC), has revealed the cellular location of the Sturge-Weber mutation. The discovery brings new hope of finding ways to improve the lives of those with the disorder. …
Oral squamous cell carcinoma (OSCC), a kind of oral cancer, affects some 30,000 Americans annually. It spreads through the lymphatic system and often has already metastasized by the time it’s diagnosed. The top image here, from a recent study in the American Journal of Pathology, is a healthy mouse tongue; the bottom is the swollen tongue of a mouse with OSCC. The cancerous tongue is overloaded with lymphatic vessels, appearing in blue and white, which help the tumor spread to the regional lymph nodes. The Bielenberg lab in Boston Children’s Hospital’s Vascular Biology Program is studying ways of blocking the progression of this and other cancers by inhibiting their spread through the lymphatic system. (Image: Bielenberg laboratory/Kristin Johnson)
Painful, tissue-damaging vaso-occlusive crises (a.k.a. pain crises) are one of the key clinical concerns in sickle cell disease (SCD). The characteristic C-shaped red blood cells of SCD become jammed in capillaries, starving tissues of oxygen and triggering searing pain. Over a patient’s life, these repeated rounds of oxygen deprivation (ischemia) can take a heavy toll on multiple organs.
There’s some debate as to why these crises take place—is the sickled cell’s shape and rigidity at fault, or are the blood vessels chronically inflamed and more prone to blockage? Either way, doctors can currently do little to treat vaso-occlusive crises, and nothing to prevent them.
You are what you eat, the saying goes. For some conditions (think cardiovascular disease or type 2 diabetes), there are clear connections between diet, health and illness.
For breast cancer, the picture is less clear. Many epidemiologic and laboratory studies have examined the Western diet (in particular, cholesterol) and its relation to breast cancer, with conflicting results.
“There’s been a raging debate in the field,” says Christine Coticchia, PhD, who works in the laboratory of Boston Children’s Hospital’s Vascular Biology Program director, Marsha Moses, PhD. “The biology of cancer and of cholesterol are so complex, and there are many subsets of breast cancer. In order to find any connections, you have to ask very specific questions.”
Banding together with Keith Solomon, PhD, in Boston Children’s Urology Department, Coticchia and Moses asked whether dietary cholesterol might encourage progression of the most aggressive, so-called “triple-negative” breast tumors. As they report in the American Journal of Pathology, they found a big impact, at least in mice. But it’s too early to say just yet that cutting back on cholesterol will help women avoid breast cancer. …