Posts Tagged ‘field’

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

Showcase of latest advances in medical imaging for revolutionary proton therapy cancer treatment

The University of Lincoln’s Professor Nigel Allinson MBE will deliver the keynote talk at the tenth International Conference on Position Sensitive Detectors. The conference, which takes place from 7th to 12th September 2014, features the latest developments in this field from leading researchers around the world.

Professor Allinson leads the pioneering PRaVDA (Proton Radiotherapy Verification and Dosimetry Applications) project. He and his multinational team are developing one of the most complex medical instruments ever imagined to improve the delivery of proton beam therapy in the treatment of cancer.

Proton beam therapy is a type of particle therapy that uses a beam of protons to irradiate diseased tissue. Proton beam therapy has the ability to deliver high doses of radiation directly to a tumour site with very little radiation being absorbed into healthy tissue.

PRaVDA, funded by a £1.6 million grant from the Wellcome Trust, will provide a unique instrument capable of producing real-time 3D images — a proton CT — of a patient, drawing data from the same protons used in the treatment itself.

The patent-pending technology, which uses detectors at the heart of the Large Hadron Collider at CERN alongside world-first radiation-hard CMOS imagers, will reduce dose uncertainties from several centimetres to just a few millimetres.

This promises to make proton therapy an option for thousands more cancer patients by reducing the risks of healthy tissue being damaged during treatment, particularly in vulnerable parts of the body such as the brain, eye and spinal cord.

Professor Allinson, who will also be talking about his research to prospective students at the University of Lincoln open day on Saturday, 20th September, said: “PRaVDA will ensure more difficult tumours will become treatable and more patients overall will be able to receive this revolutionary treatment.”

Other members of the PRaVDA team will also present their work at the conference, describing in more detail the high-speed tracking technology that can record the paths of individual protons as they enter and leave a patient. The team will also outline how they make and test the new detectors in PRaVDA to ensure they are resistant to the high levels of radiation present in proton therapy.

The researchers have just taken delivery of some of the technology which will lie at the heart of the system: two state-of-the-art custom integrated circuits (chips) which will underpin PRaVDA’s imaging capabilities.

One device is a radiation-hard CMOS imager, measuring 10cm x 6.5cm, and producing more than 1,500 images per second. The camera chip in a mainstream smartphone is a CMOS imager but PRaVDA’s chip is over 300 times larger and operates 50 times faster — the fastest large-area CMOS imager ever made. The completed PRaVDA instrument will contain 48 of these imagers, giving a total imaging area of nearly two-and-a-half square metres.

The second device is the read-out chip for the very high-speed strip detectors that track the passage of individual protons as they enter and exit a patient. This chip, called Rhea, converts the electric charge created by a passing proton into a digital signal with additional logic to provide accurate timing (to one hundredth of one millionth of a second) while preventing erroneous signals being recorded.

The strip detectors were designed at the University of Liverpool by the same team that developed detectors for the Large Hadron Collider at CERN, which led to the discovery of the Higgs Boson in 2013. Nearly 200 Rheas are used in the complete PRaVDA system.

PRaVDA’s industrial partner, ISDI LTD, designed both devices. Their testing was undertaken by the project’s second industrial partner, aSpect Systems GmbH, in Dresden, Germany.

source : http://www.sciencedaily.com/releases/2014/09/140904121147.htm

Keyhold surgery for cancer spread to liver

Each year, 3500 Norwegian develop colorectal cancer. Most of them undergo surgery. In half of them, the cancer spreads. Thirty per cent of those in whom the cancer has spread can now be operated on with a new surgical method.

“With our new surgical method we can transform an acute, terminal disease into a chronic disease,” says one of the world’s leading surgeons in the field of laparoscopy (keyhole surgery), Professor Bjørn Edwin at the Intervention Centre of UiO and Oslo University Hospital, Norway.

His solution is to preserve as much of the liver as possible.

“We try to take as little as possible. This is a completely new way of thinking.”

The most common surgical method is still to remove half of the liver if the cancer has spread to parts of it.

“By removing only a small piece at a time, we increase the chances that the patient can have repeat surgery. In other words, we try to preserve the liver to have some of it left if the cancer should return. Most of the patients have a recurrence within ten years. The idea is this: If we leave parts of the right side, we can later remove the left side of the liver. This is what we refer to as good liver housekeeping,” Bjørn Edwin explains. He notes that the method only works for patients in whom the cancer has spread from the intestine to the liver. For patients with a primary tumour in the liver, other treatment methods are used.

For the last twenty years, Edwin has remained one of the country’s leading pioneers in the field of laparoscopy.

“With laparoscopy, we can intervene and operate many times, since the method does not produce the same adhesions as open surgery does. The results are equally good, and there are fewer complications. In addition, laparoscopy has taught the surgeons to operate more neatly,” Bjørn Edwin states to the researchmagazine Apollon.

Four small holes

This way to perform surgery is far better for the patient than a classic operation. Instead of cutting open the abdomen, the surgeon makes four small holes. He can then use trocars, which are stiff tubes, to insert his instruments and a camera. One hole is for the video camera. Through the other holes, the surgeon can introduce a forceps, an instrument, a scalpel or other implements needed to cut the liver loose. Before starting the procedure, however, they must first inflate the abdomen to provide a large cavity where they can work.

A large amount of blood flows through the liver. To avoid haemorrhages, the blood flow to the part which is to be operated on must be halted by ligating the arteries. This can be done by tying a suture around the blood vessels.

“If the patient nevertheless should start haemorrhaging we must switch to a regular operation. This happens in only one of a hundred cases. Previously, we also opened the abdomen occasionally to be on the safe side.”

Many different techniques can be used to cut the liver. The surgeons can use a scalpel, ultrasound or electrosurgical forceps. To incise the large blood vessels they use a sewing machine. Before the blood vessel is cut, they block it by sewing three rows of clips on each side of the cut.

The excised section of liver must be withdrawn from the body intact.

If the excised section of liver were ground up, it could be brought out of the body in liquid form, but then the pathologists would be unable to analyse the tumours. The liver section must therefore be removed whole.

This is done by inserting a plastic bag through one of the stiff tubes. The bag has the shape of an angler’s hand net.

“We catch the liver, close the bag, pull it towards the skin and out through a small incision.”

A gentle procedure

Laparoscopy is not only less painful than classic surgery, but the patients recover more quickly and spend fewer days in hospital.

“The average hospitalization period after a laparoscopic intervention is three days, while patients spend five to seven days in hospital after open surgery.”

Edwin is currently investigating the correlation between surgical methods and survival rates.

“Based on the illness histories of patients who have been operated on for cancer that has spread to the liver, expected survival is higher with laparoscopy, but the responses are not statistically significant. We don’t know exactly why the survival rates increase, but it might be related to the immune response.”

The story behind

Gastric surgeons started to use keyhole surgery in the late eighties, initially on gall-bladder patients. This surgical method was described one hundred years ago, and was first used by gynaecologists during the forties.

“In those days, the surgeon looked through a telescope, but having video on a screen enabled us to perform laparoscopy in a far more sophisticated way.”

Bjørn Edwin is a pioneer in the field of keyhole surgery and was among the very first to use this method for liver surgery. Now, Bjørn Edwin has taught his method to surgeons in Norway as well as abroad.

“Laparoscopy will increasingly replace open surgery. Ten years after we started, other countries have followed. American hospitals are still opposed to the surgical method for preserving liver tissue. France is now using it, and Russia is following suit.”

When he attended a world conference on cancer of the liver and pancreas in 2008, hardly anyone used laparoscopy on these organs. Two years later, there were some. At this year’s conference in Seoul it became evident that many have now started to use this new surgical technique.

Interdisciplinary team

To perform modern laparoscopy, collaboration with the engineers is absolutely essential. Using a three-dimensional map of the liver, the surgical team can see where the blood vessels are located and plan where to make their incisions accordingly.

“We are now undertaking research to enable us to see the movements of the instruments interactively on the map of the liver during surgery,” Bjørn Edwin says. He emphasizes that the trials with modern laparoscopy would have been impossible without the strong interdisciplinary team at the Intervention Centre.

“There, we have close proximity to physicists, radiologists and other specialists. It’s a superb setting for undertaking a development stage,” Edwin points out.

source : http://www.sciencedaily.com/releases/2014/08/140825084628.htm