Friday, 26 March 2010

Cancer genes switched off in humans

For the first time, researchers have used short sequences of RNA that can effectively treat skin cancer in people by silencing specific genes behind tumour production.

Mark Davis from the California Institute of Technology in Pasadena and his colleagues have used the technique, called RNA interference (RNAi), to deliver particles containing such sequences to patients with the skin cancer melanoma.

When analysing biopsies of the tumours after treatment, they found that the particles had inhibited expression of a key gene, called RRM2, needed for the cancer cells to multiply.

The researchers created the particles from two polymers plus a protein that binds to receptors on the surface of cancer cells and pieces of RNA called small-interfering RNA, or siRNA, designed to stop the RRM2 gene from being translated into protein.

The siRNA works by sticking to the messenger RNA (mRNA) that carries the gene's code to the cell's protein-making machinery and ensuring that enzymes cut the mRNA at a specific spot.

When the components are mixed together in water, they assemble into particles about 70 nanometres in diameter. The researchers can then administer the nanoparticles into the bloodstream of patients, where the particles circulate until they encounter 'leaky' blood vessels that supply the tumours with blood.

The particles then pass through the vessels to the tumour, where they bind to the cell and are then absorbed. Once inside the cell, the nanoparticles fall apart, releasing the siRNA. The other parts of the nanoparticle are so small, they pass out of the body in urine.

"It sneaks in, evades the immune system, delivers the siRNA, and the disassembled components exit out," Nature quoted Davis as saying.

When researchers analysed tumour samples from three of the patients who volunteered samples, they found fragments of the mRNA in exactly the length and sequence they would expect from the design of their siRNA.

And in at least one patient, the levels of the protein were lower than they were in samples of the tumours taken before treatment.

They also found that patients who were given higher doses had higher levels of siRNA in their tumours. "The more we put in, the more ends up where they are supposed to be, in tumour cells," said Davis.

Davis says that by targeting specific genes he hopes these treatments will not have major side effects. "My hope is to make tumours melt away while maintaining a high quality of life for the patients. We're moving another step closer to being able to do that now," he said.

The study has been published in Nature.

Saturday, 6 March 2010

Mesothelioma: Burn pits contained asbestos

The US military's largest contractor, KBR, has testified in court that it burned hazardous materials (including asbestos) in so-called "burn pits" in Iraq and Afghanistan at the behest of military officials. The company is hoping to avoid being held accountable for the burn pits, which may have exposed US military personnel overseas to toxic materials that could ultimately cause cancer later in life.

For example, asbestos burned in the pits could have become airborne. If inhaled or ingested, these airborne asbestos particles can lead to the development of mesothelioma, a rare cancer of the lungs and other major organs and tissues.

A class action suit was filed in October of last year against KBR and other companies. Combining 22 lawsuits from 43 states, the class action case was filed in US District Court in Maryland against KBR, Halliburton, and other military contractors. The plaintiffs are seeking damages after developing health issues that were allegedly caused by being in close proximity to these burn pits overseas, which were used for trash disposal.

KBR is not denying that the burn pits they operated did contain hazardous materials such as batteries, petroleum, asbestos, and medical waste. Instead the company hopes to challenge the idea that they should be held accountable for the items burned in the pits, as KBR was allegedly just following orders from high-ranking military officials.

According to one military reporter: "Though military officials say there are no known long-term effects from exposure to burn pits in Iraq and Afghanistan, more than 100 service members have come forward to Military Times [a newspaper] and Disabled American Veterans with strikingly similar symptoms: chronic bronchitis, asthma, sleep apnea, chronic coughs and allergy-like symptoms. Several also have cited heart problems, lymphoma and leukemia."

KBR is also being sued by a group of veterans who were exposed to hexavalent chromium while protecting KBR employees at the Qarmat Ali water treatment plant. The men have since suffered from a variety of symptoms, including difficulty breathing. A recent blog post on our Veterans Blog highlights the issue of hexavalent chromium and veteran exposure.