Posts Tagged ‘first’

Newest precision medicine tool: Prostate cancer organoids

The researchers, whose results were published today in Cell, successfully grew six prostate cancer organoids from biopsies of patients with metastatic prostate cancer and a seventh organoid from a patient’s circulating tumor cells. Organoids are three-dimensional structures composed of cells that are grouped together and spatially organized like an organ. The histology, or tissue structure, of the prostate cancer organoids is highly similar to the metastasis sample from which they came. Sequencing of the metastasis samples and the matched organoids showed that each organoid is genetically identical to the patient’s cancer from which it originated.

“Identifying the molecular biomarkers that indicate whether a drug will work or why a drug stops working is paramount for the precision treatment of cancer,” said Yu Chen, MD, PhD, Assistant Attending Physician in the Genitourinary Oncology Service and Human Oncology and Pathogenesis Program at MSK. “But we are limited in our capacity to test drugs — especially in the prostate cancer setting, where only a handful of prostate cancer cell lines are available to researchers.”

With the addition of the seven prostate cancer organoids described in the Cell paper, Dr. Chen’s team has effectively doubled the number of existing prostate cancer cell lines.

“We now have a new resource at our disposal that captures the molecular diversity of prostate cancer. This will be an invaluable tool we can use to test drug sensitivity,” he added.

The use of organoids in studying cancer is relatively new, but the field is exploding quickly according to Dr. Chen. In 2009, Hans Clevers, MD, PhD, of the Hubrecht Institute in the Netherlands demonstrated that intestinal stem cells could form organoids. Dr. Clevers is the lead author on a companion piece also published in Cell today that describes how to create healthy prostate organoids. Dr. Chen’s paper is the first to demonstrate that organoids can be grown from prostate cancer samples.

The prostate cancer organoids can be used to test multiple drugs simultaneously, and Dr. Chen’s team is already retrospectively comparing the drugs given to each patient against the organoids for clues about why the patient did or didn’t respond to therapy. In the future, it’s possible that drugs could be tested on a patient’s organoid before being given to the patient to truly personalize treatment.

After skin cancer, prostate cancer is the most common cancer in American men — about 233,000 new cases will be diagnosed in 2014. It is also the second leading cause of cancer death in men; 1 in 36 men will die of the disease.

Despite its prevalence, prostate cancer has been difficult to replicate in the lab. Many mutations that play a role in its growth are not represented in the cell lines currently available. Cell lines can also differ from their original source, and because they are composed of single cells, they do not offer the robust information that an organoid — which more closely resembles a living organ — can provide.

source : http://www.sciencedaily.com/releases/2014/09/140904131142.htm

Prostate cancer: Pioneering new imaging method

Severely ill prostate cancer patients are helping researchers test a diagnostic tool that involves injecting a radioactive substance into their bodies. Norway has the fifth highest mortality rate for prostate cancer in Europe.

Four doses of a radioactive tracer called 18F- FACBC are on their way from Oslo to Trondheim in a private jet. Three NTNU researchers, one doctor, two radiographers and a bioengineer fidget nervously as they wait. They check the time.

The plane cannot be delayed. Today is a bad day for fog to descend around Oslo’s main airport, Gardermoen, or for there to be a traffic jam between the Trondheim airport and the city hospital, St. Olavs. Everything has to be on time.

Radioactive decay

From the second that 18F- FACBC is injected into its container, it begins to degrade. In 110 minutes, half of the radioactive substance is gone. If the plane is delayed too much, there won’t be any radioactivity left for the last patient. Then more doses have to be flown up from Oslo.

Now the plane is 20 minutes late. Time really is money when it comes to this radioactive substance. One dose costs NOK 30 000 (3700 Euros). The first patient is already on the table, ready for the procedure. He has an aggressive form of prostate cancer. Doctors fear that it has spread to his lymph nodes.

Now he is waiting to be examined with the most advanced imaging technology that can be found in Norway, a combined PET MRI scan with a price tag of NOK 50 million. He will have to lie still in what boils down to a tiny cave for over an hour while the machine scans and makes images of his blood, bones, and cancer cells.

Finding its way through the body

But this kind of advanced imaging requires a radioactive tracer. With its short half-life, 18F- FACBC (which is an abbreviation for 1-amino-3-fluorine 18-fluorocyclobutane-1-carboxylic acid) has just the right characteristics for the job.

The medical team works quickly when the doses finally arrive at the hospital.

Fortunately, the timing is perfect. First the patient is given an injection of the tracer in his arm, and then placed into the machine, where the tracer finds its way into his veins.

For the radioactive substance to find its way into cancer cells, it needs to have a carrier, a kind of pilot that is able to lead the way to the tumours. In this case, an amino acid acts as the carrier. This is because of cancer cells’ appetite for certain amino acids. A cancer cell is much more active than other cells. It needs more building blocks than other cells, more food. As a result, it attracts and absorbs the amino acid that has been injected into the body.

The radioactive tracer is picked up by detectors that are placed in a ring around the patient in the scanner, and the machine makes images of the cancer cells that light up from the tracer. At the same time, MRI photos of the area are taken, so that doctors get a unique package of information to help them determine which type of treatment is appropriate.

Eight private jets

After an hour, the scan is over and the patient is backed out of the PET MRI. A day later, all of the radioactivity will have left his body. In a few days, he will be in surgery. Hopefully, he has a number of healthy years left to live.

It will take a few years, however, before researchers will be able to conclude how PET MRI scans can be used to improve the diagnosis and treatment of prostate cancer. First, they need to conduct their study with 32 patients. Eight private jets of radioactive tracer will need to be flown to Trondheim, at a cost of NOK 960 000 for this substance.

Shorter, less surgery

This is the first research study in the world where amino acids and PET MRI are being used to try to improve the diagnosis of prostate cancer.[faktaboks=”1″ stillopp=”hoyre” storrelse=”liten”/]

Currently, doctors remove the lymph nodes found in the pelvis of patients with aggressive prostate cancer, without really knowing if it is necessary. Only by cutting into the lymph nodes after they have been removed can doctors determine if the cancer had actually spread.

The NTNU researchers’ goal is for PET MRI to be able to do this detective work before the patient has to undergo surgery, so that surgeons know whether or not removing a patient’s lymph nodes is actually necessary. As a result, some patients should be able to have shorter, less involved surgery, which means less side effects and potential complications.

Diagnoses and the answer key

Researcher will go through the images of all 32 study participants, and then compare these images to their “answer key,” which in this case are the lymph nodes that were removed and biopsied from the patients. Comparing the nodes with the PET MRI images will show whether or not the scans can be used to help in the diagnosis of prostate cancer.

source : http://www.sciencedaily.com/releases/2014/09/140904084500.htm

Fighting prostate cancer with tomato-rich diet

With 35,000 new cases every year in the UK, and around 10,000 deaths, prostate cancer is the second most common cancer in men worldwide.

Rates are higher in developed countries, which some experts believe is linked to a Westernised diet and lifestyle.

To assess if following dietary and lifestyle recommendations reduces risk of prostate cancer, researchers at the Universities of Bristol, Cambridge and Oxford looked at the diets and lifestyle of 1,806 men aged between 50 and 69 with prostate cancer and compared with 12,005 cancer-free men.

The NIHR-funded study, published in the medical journal Cancer Epidemiology, Biomarkers and Prevention, is the first study of its kind to develop a prostate cancer ‘dietary index’ which consists of dietary components — selenium, calcium and foods rich in lycopene — that have been linked to prostate cancer.

Men who had optimal intake of these three dietary components had a lower risk of prostate cancer.

Tomatoes and its products — such as tomato juice and baked beans — were shown to be most beneficial, with an 18 per cent reduction in risk found in men eating over 10 portions a week.

This is thought to be due to lycopene, an antioxidant which fights off toxins that can cause DNA and cell damage. Vanessa Er, from the School of Social and Community Medicine at the University of Bristol and Bristol Nutrition BRU, led the research.

She said: “Our findings suggest that tomatoes may be important in prostate cancer prevention. However, further studies need to be conducted to confirm our findings, especially through human trials. Men should still eat a wide variety of fruits and vegetables, maintain a healthy weight and stay active.”

The researchers also looked at the recommendations on physical activity, diet and body weight for cancer prevention published by the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR).

Only the recommendation on plant foods — high intake of fruits, vegetables and dietary fibre — was found to be associated with a reduced risk of prostate cancer. As these recommendations are not targeted at prostate cancer prevention, researchers concluded that adhering to these recommendations is not sufficient and that additional dietary recommendations should be developed.

source : http://www.sciencedaily.com/releases/2014/08/140827100218.htm