Minggu, 29 Maret 2009

Cancer drug 'fuels tumour growth'


Tumour blood vessels (in red), surrounded by cancer cells (in blue)
Tumour blood vessels (in red), surrounded by cancer cells (in blue)


UK scientists were investigating a kind of drug called an anti-angiogenesis, still under development, which hampers the growth of tumour blood vessels.

Avastin and Sutent, which act in a similar way, have been proven to work and were not covered in this research.

But cancer experts say the study in Nature Medicine could help make those drugs more effective.

The researchers focused on a drug called Cilengitide which is designed to prevent blood vessel cells sticking together and moving - an important part of angiogenesis.

Previous tests on people have found that a few patients with brain tumours benefited from high doses of the drug, but that it failed to work for most.

In this research, tests carried out on mice showed that low doses of Cilengitide actually stimulated the growth of cancers.

Further investigation showed it did this by switching on a molecule called VEGFR2, which triggers the angiogenesis process.

That is significant because although when a patient is initially given a drug, its level in the blood rises quickly ensuring a big dose goes to the tumour, after a while levels start to fall as the body begins to deal with the drug.

This is likely to be why trials of the drug have shown such poor results.

Caveat

Dr Kairbaan Hodivala-Dilke of the Institute of Cancer, who led the study, said it was important that the trials looking at this drug continued.

"We've got evidence now that low doses can enhance tumour growth. So there is no benefit of giving a high dose, which then drops, and then a high dose again.

"But that's not to say it can't work at all. It can, but there is this caveat."

She said it may be more effective to give the drug via an infusion pump, which would allow the dosage to remain topped up at an effective level.

Dr Andy Reynolds, from the Breakthrough Breast Cancer Research Centre at the Institute of Cancer Research, who also worked on the study, said: "Knowledge of this mechanism will help us develop new ways to make these drugs as effective as possible.

"In the future, we may be able to combine these inhibitors with other drugs to maximise their effectiveness for patients."

Dr Lesley Walker, director of cancer information at Cancer Research UK, which helped fund the research, said: "This study is important because it may help to explain the mixed results previously seen in patients and turn around disappointing results so people may still benefit from the drug without the potential harm."

Mechanisms

The research also has implications for the existing drugs Sutent, used to treat kidney cancer, and Avastin, for colorectal cancer.

They work by the same process, but on different targets.

At the moment, they can extend a patient's life by several months. Experts hope that this research could lead to a better understanding of the drugs' mechanisms and so to ways of making them more effective.

Dr Walker said: "Sutent and Avastin have proven effective enough for use in the NHS but there is still need to understand why they can sometime fail.

"It may be that there are similar mechanisms at work."

Last month, the National Institute for Health and Clinical Excellence - the NHS's drugs appraisal body - said Sutent could be considered for people with advanced kidney cancer. However, it decided against recommending Avastin for advanced colorectal cancer.

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World's cheapest car is launched


Annotated image of Tata car

The Tata Nano, the world's cheapest car, has been launched in India.

Costing just 100,000 rupees ($1,979; £1,366), the Nano will now go on sale across India next month, with deliveries starting in July.

Tata hopes the 10-foot (3-metre) long, five-seater car will be cheap enough to encourage millions of Indians to trade up from their motorcycles.

Tata owner Ratan Tata has described the Nano as a "milestone". Analysts say it will not make a profit for six years.

Tata's managing director Ravi Kant said that from the first orders, a ballot would then select the initial 100,000 people to get their Nano.

"I think we are at the gates of offering a new form of transport to the people of India and later, I hope, other markets elsewhere in the world," Mr Tata added.

"I hope it will provide safe, affordable four-wheel transportation to families who till now have not been able to own a car."

Environmentalists are warning that the Nano will add to India's already clogged up roads, and pollution levels will soar. Tata says the Nano will be the least polluting car in India.

Factory row

The four-door Nano has a 33bhp, 624cc engine at the rear.

The basic model has no airbags, air conditioning, radio, or power steering. However, more luxurious versions will be available.

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Inside the tiny Tata Nano (first broadcast 2008)

A slightly bigger European version, the Nano Europa is due to follow in 2011, and is expected to cost nearer to £4,000.

Analysts said that if the car proves an immediate hit in its home market, Tata may struggle to meet demand.

This is because the main Nano factory in the western state of Gujarat, which will be able to build 250,000 cars a year, is not due to open until next year.

In the meantime, Tata will only be able to build about 50,000 Nanos at its existing plants.

The delay happened when Tata had to abandon plans to build the Nano in a new plant in the eastern state of West Bengal due to a row over land acquired from farmers.

This caused the launch of the Nano to be put back by six months.

Global slowdown

Even if Tata can sell 250,000 models a year, it will add only 3% to the firm's revenues, says Vaishali Jajoo, auto analyst at Mumbai's Angel Broking.

"That doesn't make a significant difference to the top line," he said.

"And for the bottom line, it will take five to six years to break even."

Yet with seven million motorcycles sold last year in India, Tata is eyeing a huge marketplace for the Nano.

Like almost all global carmakers, Tata has seen sales fall as the global economic downturn has continued.

The firm made a 2.63bn rupees loss for three months between October and December.

In addition, Tata is struggling to refinance the remaining £2bn of its £3bn loan it took out to buy the Jaguar and Land Rover brands from Ford in June of last year.

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