Silibinin has an outstanding safety profile in humans and is currently used for the treatment of liver disease and poisoning. Scientists at the Max Planck Institute of Psychiatry in Munich discovered in collaboration with scientists from the Helmholtz Zentrum München in cell cultures, animal models and human tumor tissue that silibinin can be applied to treat Cushing Disease, a rare hormone condition caused by a tumor in the pituitary gland in the brain. The researchers have filed a patent and now plan clinical trials using silibinin as a non-invasive treatment strategy. Thus, in future, patients might not have to undergo brain surgery anymore.
Cushing Disease, not to be confused with Cushing’s Syndrome, is caused by a tumor in the pituitary gland in the brain. The tumor secrets increased amounts of the stress hormone adrenocorticotropin (ACTH) followed by cortisol release from the adrenal glands leading to rapid weight gain, elevated blood pressure and muscular weakness. Patients are prone to osteoporosis, infections and may show cognitive dysfunction or even depression. In 80 to 85 % of the patients the tumor can be removed by uncomfortable brain surgery. For inoperable cases, there is currently only one targeted therapy approved which unfortunately causes intense side effects such as hyperglycemia in more than 20 % of the patients.
Scientists around Günter Stalla, endocrinologist at the Max Planck Institute of Psychiatry in Munich, now discovered in cell cultures, animal models and human tumor tissue that a harmless plant extract can be applied to treat Cushing Disease. “Silibinin is the major active constituent of milk thistle seeds. It has an outstanding safety profile in humans and is already used for the treatment of liver disease and poisoning,” explains Marcelo Paez-Pereda, leading scientist of the current study published in the renowned scientific journal Nature Medicine. After silibinin treatment, tumor cells resumed normal ACTH production, tumor growth slowed down and symptoms of Cushing Disease disappeared in mice.
In 2013, the Max Planck scientists filed a patent on a broad family of chemical and natural compounds, including silibinin, to treat pituitary tumors. Compared to humans, of which only 5.5 in 100,000 people worldwide develop Cushing Disease, this condition is very common in several pets. For example, 4 % of dogs and even 7 % of horses suffer from Cushing Disease. Thus, the researchers now plan to test special formulations with a very pure substance and slow release of the active component silibinin in clinical trials.
Silibinin: Mode of action
“We knew that Cushing Disease is caused by the release of too much ACTH. So we asked ourselves what causes this over production and how to stop it,” says Paez-Pereda. In their first experiments the researchers found tremendously high amounts of the heat shock protein 90 (HSP90) in tumor tissue from patients with Cushing Disease. In normal amounts HSP90 helps to correctly fold another protein, the glucocorticoid receptor which in turn inhibits the production of ACTH. “As there are too many HSP90 molecules in the tumor tissue, they stick to the glucocorticoid receptor,” explains Paez-Pereda. “We found that silibinin binds to HSP90 thus allowing glucocorticoid receptor molecules to dissolve from HSP90. With silibinin we might have discovered a non-invasive treatment strategy not only for the rare Cushing Disease but also for other conditions with the involvement of glucocorticoid receptors such as lung tumors, acute lymphoblastic leukemia or multiple myeloma,” concludes Paez-Pereda.
The above story is based on materials provided by Max-Planck-Gesellschaft. Note: Materials may be edited for content and length.
RESEARCHERS FROM TAU AND PARTNER INSTITUTIONS DEVELOP GROUNDBREAKING DEVICE THAT SPOTS LUNG CANCER – TO STOP IT IN ITS TRACKS
Lung cancer causes more deaths in the U.S. than the next three most common cancers combined (colon, breast, and pancreatic). The reason for the striking mortality rate is simple: poor detection. Lung cancer attacks without leaving any fingerprints, quietly afflicting its victims and metastasizing uncontrollably — to the point of no return.
Now a new device developed by a team of Israeli, American, and British cancer researchers may turn the tide by both accurately detecting lung cancer and identifying its stage of progression. The breathalyzer test, embedded with a “NaNose” nanotech chip to literally “sniff out” cancer tumors, was developed by Prof. Nir Peled of Tel Aviv University‘sSackler Faculty of Medicine, Prof. Hossam Haick (inventor) of the Technion — Israel Institute of Technology, and Prof. Fred Hirsch of the University of Colorado School of Medicine in Denver.
The study, presented at a recent American Society of Clinical Oncology conference in Chicago, was conducted on 358 patients who were either diagnosed with or at risk for lung cancer. The participants enrolled at UC Denver, Tel Aviv University, University of Liverpool, and a Jacksonville, Florida, radiation center. Other researchers included Prof. Paul Bunn of UC Denver; Prof. Douglas Johnson, Dr. Stuart Milestone, and Dr. John Wells in Jacksonville; Prof. John Field of the University of Liverpool; and Dr. Maya Ilouze and Tali Feinberg of TAU.
The smell of cancer
“Lung cancer is a devastating disease, responsible for almost 2,000 deaths in Israel annually — a third of all cancer-related deaths,” said Dr. Peled. “Lung cancer diagnoses require invasive procedures such as bronchoscopies, computer-guided biopsies, or surgery. Our new device combines several novel technologies with a new concept — using exhaled breath as a medium of diagnosing cancer.
“Our NaNose was able to detect lung cancer with 90 percent accuracy even when the lung nodule was tiny and hard to sample. It was even able to discriminate between subtypes of cancer, which was unexpected,” said Dr. Peled.
Lung cancer tumors produce chemicals called volatile organic compounds (VOCs), which easily evaporate into the air and produce a discernible scent profile. Prof. Haick harnessed nanotechnology to develop the highly sensitive NaNose chip, which detects the unique “signature” of VOCs in exhaled breath. In four out of five cases, the device differentiated between benign and malignant lung lesions and even different cancer subtypes.
The bigger the tumor …
“Cancer cells not only have a different and unique smell or signature, you can even discriminate between subtypes and advancement of the disease,” said Dr. Peled. “The bigger the tumor, the more robust the signature.”
The device and subsequent analysis accurately sorted healthy people from people with early-stage lung cancer 85 percent of the time, and healthy people from those with advanced lung cancer 82 percent of the time. The test also accurately distinguished between early and advanced lung cancer 79 percent of the time.
“The device could prove valuable in helping determine patients who need more intensive screening for lung cancer,” said Dr. Peled. “We’re hoping to have a device that would be able to give you a go/no-go result — something’s wrong, go get an X-ray.”
The Boston-based company Alpha Szenszor has licensed the technology and hopes to introduce it to the market within the next few years. Meanwhile, a new, smaller version of the device has since been developed that can plug into a computer’s USB port.
The above story is based on materials provided by American Friends of Tel Aviv University. Note: Materials may be edited for content and length.