Saturday, 11 July 2015

‘Jumping genes’ may drive oesophageal cancer

Cancer Research UK scientists have found that ‘jumping genes’ may add to the genetic chaos behind more than three-quarters of oesophageal cancer cases, according to research published in BMC Genomics(link is external) today.
The scientists, from the University of Cambridge(link is external), used cutting-edge technology that can read DNA to study the genes of 43 oesophageal tumour and blood samples to discover how much these mobile genetic sequences travel.
“These jumping genes play hopscotch across our genetic code in cancer cells more than in normal cells." - Dr Paul Edwards
‘Jumping genes’, called L1 elements, can uproot themselves and move to new areas in the DNA, sometimes accidentally moving into genes that control the cell’s growth.
They found evidence that this happened around 100 times in each tumour sample, and in some tumours it happened 700 times.
If a jumping gene lands in or near an important gene that controls cell growth, it can wreak havoc, changing how the gene works so that it inadvertently tells the cell to grow and divide out of control – which could lead to cancer.
Study author Dr Paul Edwards, at the Cancer Research UK Cambridge Institute(link is external), said: “These jumping genes play hopscotch across our genetic code in cancer cells more than in normal cells. When one of these mobile genetic sequences plants itself in the middle of a gene that controls the cell’s growth it radically alters how the cell behaves, which can sometimes cause cancer.
“Research has shown that this might also happen in lung and bowel cancers. So it’s vital we find out more about how the cells do this in a bid to find ways to treat these cancers.”
The research is part of the International Cancer Genome Consortium (ICGC)(link is external) – a global project using the latest gene sequencing technology to reveal the genetic changes behind cancer. The oesophageal cancer project is funded by Cancer Research UK’s Catalyst Club*.
Dr Kat Arney, Cancer Research UK’s science information manager, said: “Oesophageal cancer is one of the hardest cancers to treat, and we are committed to funding more research to find out its underlying causes. These new findings reveal more about the genetic chaos that underpins oesophageal tumours, and could one day help us develop better ways to diagnose, treat and monitor the disease.”
Paterson et al. Mobile element insertions are frequent in oesophageal adenocarcinomas and can mislead paired end sequencing analysis. BMC Genomics. DOI: 10.1186/s12864-015-1685-z.

Wednesday, 20 May 2015

Data Disclosure Leads Researchers to End Study of Obesity Drug

A study of an obesity drug has ended after the manufacturer released early and ultimately misleading data, researchers said on Tuesday.
The company, Orexigen Therapeutics, disclosed in March that early results from a clinical trial of its drug Contrave had shown a 41 percent reduction in the risk of heart attacks, strokes and death from cardiovascular causes. Orexigen’s stock shot up, and the information no doubt helped lift sales of Contrave.
But the academic researchers who oversaw the study said on Tuesday that Orexigen had violated an agreement that the early results were not going to be shared widely, even within the company.
Moreover, as participants in the trial were followed for a longer period of time, the benefit of the drug in reducing cardiovascular risks vanished.
The researchers, in a news release issued by the Cleveland Clinic, said they took the unusual step of terminating the study and releasing the more updated results.
“We felt it was unacceptable to allow misleading interim data to be in the public domain and be acted upon by patients and providers,” Dr. Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic and head of the trial’s steering committee, said in an interview.
He said Orexigen had “acted improperly and unethically in violating the data access agreement” and the premature release of data had made it difficult to continue the study.
It’s unlikley that patients would want to stay in the trial and risk getting a placebo if they thought the drug, which is already available on the market, could reduce their risk of heart attacks.
The Food and Drug Administration, citing similar reasons, has already ordered Orexigen to conduct another large study of the drug to rule out an increase in cardiovascular risk.
Orexigen said in a statement on Tuesday that it had wanted to shut down the older study in December. It also denied misleading anyone, saying that it had stated “plainly and clearly” that the data it released was preliminary and that the cardiovascular benefits of Contrave had not been established.
Contrave, which was approved in September, is one of four new prescription weight-loss drugs that have come to market since 2012, following more than a decade in which there were no new medicines.
Despite the fact that one-third of American adults are obese, the drugs have not sold well for a variety of reasons, including lack of coverage byMedicare and some insurers, modest weight loss, a history of safety problems with diet drugs, and a feeling among doctors and patients that obesity is not a disease.
Still, Contrave is off to a stronger start than the others, with United States sales of $11.5 million in the first quarter. The drug is closing in on Belviq, which has been on the market longer, for the lead in prescriptions, according to Simos Simeonidis, an analyst at RBC Capital Markets. Belviq was developed by Arena Pharmaceuticals and Eisai.
The F.D.A. declined to approve Contrave in 2011 because the drug slightly raised blood pressure and pulse rates, a sign that it might increase the risk of heart attacks and strokes. The agency told Orexigen to conduct a large study to rule out that risk.
Under agreement with the F.D.A., Orexigen looked at the data after 94 cases of heart attack, stroke or death from cardiovascular causes had occurred — about 25 percent of the expected total in the trial. Those early results effectively ruled out that Contrave doubled the risk of cardiovascular problems, clearing the way for the drug to be approved.
But in an agreement with the academic steering committee, the data was supposed to be known only by a small group within Orexigen charged with filing the application for F.D.A. approval.
Dr. Nissen said many more people were told. And when the company found out that those getting Contrave actually had a 41 percent lower risk of a heart attack, stroke or death from cardiovascular death, the company filed a patent application covering use of the drug to prevent cardiovascular problems.
When the patent was granted in early March, Orexigen disclosed this in a filing to the Securities and Exchange Commission, apparently viewing it as material to the company. The filing contained the preliminary trial results.
The company’s action drew an unusual rebuke from a senior F.D.A. official, who said in interviews that data from so early in a trial was very unreliable.
The steering committee said on Tuesday that as the trial continued, more patients getting the drug began having heart attacks and strokes, or died. After 192 adverse cardiovascular events the trail was halfway completed, and the earlier reported benefit was no longer statistically significant. There were 102 events in the placebo group compared with 90 among those who received Contrave.
Orexigen also said it was fighting with its marketing partner, Takeda Pharmaceutical in part over which company will have to pay for the new cardiovascular trial. Orexigen said Takeda had initiated a formal dispute process claiming a material breach of the agreement between the companies.

Scientists capture video of 'killer' T-Cells fighting cancer cells inside the body

Researchers used state-of-the-art imaging techniques to capture the ruthless 'killer' T-cells at work.
Killer, or cytotoxic, T-cells are white blood cells with the specialised role of destroying tumour cells or cells that have been invaded by viruses.


Cytotoxic T-cells are white blood cells with the specialised role of destroying tumour cells or cells that have been invaded by viruses.
One teaspoon full of blood might contain around five million T-cells, each measuring around 10 micrometres in length, or about a tenth of the width of a human hair. 

Professor Gillian Griffiths, director of Cambridge University's Institute for Medical Research, who led the study, said: 'Inside all of us lurks an army of serial killers whose primary function is to kill again and again.
'These cells patrol our bodies, identifying and destroying virally infected and cancer cells and they do so with remarkable precision and efficiency.'
One teaspoon full of blood might contain around five million T-cells, each measuring around 10 micrometres in length, or about a tenth of the width of a human hair.
In the video, the T-cells appear as orange or green amorphous blobs that move around rapidly, constantly investigating their environment.
When a killer T-cell finds a cancer cell (blue in the video), membrane 'fingers' explore its surface to confirm its identity. 
The T-cell then binds to the cancer cell and injects toxic proteins (red) down special pathways called microtubules to the interface where the two cells meet

The T-cell then punctures the surface of the cancer cell and delivers its deadly cargo. 
'In our bodies, where cells are packed together, it's essential that the T-cell focuses the lethal hit on its target, otherwise it will cause collateral damage to neighbouring, healthy cells,' said Prof Griffiths.
'Once the cytotoxins are injected into the cancer cells, its fate is sealed and we can watch as it withers and dies. 
'The T-cell then moves on, hungry to find another victim.' 
The researchers captured the footage through high-resolution 3D time-lapse multi-colour imaging, making use of both spinning disk confocal microscopy and lattice light sheet microscopy. 
These techniques involves capturing slices through an object and ‘stitching’ them together to provide the final 3D images across the whole cell. 
Using these approaches the researchers have managed to elucidate the order the events leading to delivery of the lethal hit from these serial killers.
The study by a joint team of British and US scientists is described in the journal Immunity.

Friday, 8 May 2015

19 brilliant people

1.    Thomas Edison
An inventor known for his many failures long before his successes, Thomas Edison was even told that he was "too stupid to learn anything" by one of his teachers early on in life. Yet everyone knows the name of the man responsible for inventing the lightbulb -- even if it took him 1,001 attempts to get it right. His perseverance with this particular invention clearly embodies his positive saying, “I have not failed 10,000 times -- I’ve successfully found 10,000 ways that will not work.” 

2.       Walt Disney
Even the head of the world's largest animation empire hit a rough patch. In 1919 he was fired from the Kansas City Star because he "lacked imagination and had no good ideas," according to his editor. 

3.       The Beatles
When The Beatles auditioned for Decca Records in 1962, Dick Rowe told their manager Brian Epstein, "Guitar groups are on their way out." Despite that dismissal, the English rock band went on to become one of the most influential groups of all time.

4.       Herman Melville
In the author's lifetime, Moby Dick was not considered a masterpiece. After publishing the novel, Melville struggled financially for the rest of his life. He used much of his savings to publish his subsequent novel Pierre, which also was not well-received. At the time of his death in 1891, he was a customs inspector at a ship dock in New York. 

5.       Soichiro Honda
When Honda, an engineer for whom the popular car company is named, first failed to get a job with now-competitor Toyota, he took to making scooters in his own garage. Little did the world know that this time of unemployment would lead him to create the billion-dollar business we recognize today. 

6.       Vincent van Gogh
His paintings may be worth millions today, but no one really gave them a second thought during van Gogh's lifetime. In fact, he managed to create almost 900 paintings in a span of 10 years, yet he only lived to see a single one sold (which went to a friend at a very low price)

7.       Taylor Swift
She may have only been 11 years old at the time, but the young and driven TSwift struggled at first to find a record label in Nashville, Tennessee, that would sign her. During a middle school spring break, she took a demo CD of her singing karaoke covers of country stars Dolly Parton, the Dixie Chicks and LeAnn Rimes to Music Row and handed copies to as many music label receptionists as she could, but said she wasn't signed because "everyone in that town wanted to do what I wanted to do." She clearly found her niche, though -- this musical princess has since learned how to play quite a few instruments, taken over the country and pop-rock scene, and openly defied one the most popular music streaming companies.

8.       Stephen King
This wildly successful American author of all things horror and suspense almost didn't get his big break -- 30 times! It was with his wife Tabby's help that he was finally able to convince Doubleday to publish Carrie. He has since become the 19th best-selling author of all time.

9.       Harland david sanders
Our favorite colonel from Kentucky Fried Chicken sure had to fight the good fight to get his secret recipe into the restaurant world. He was rejected a whopping 1,009 times before he finally got that fried chicken to taste just right. Talk about perseverance.

10.   Charles Schultz
The famous cartoonist who brought the world the "Peanuts" comic strip experienced quite a bit of rejection early in his career. None of the cartoon drawings he designed for his high school yearbook were ever selected to be published, and later Walt Disney turned him down for a job. It looks like it's a good thing he believed that "you can't create humor out of happiness."

11.   Elvis Presley
Before the King of Rock 'n' Roll hit it big, he was told by the Grand Ole Opry manager in Nashville that he would be better off going back to his job as a truck driver than pursuing a career in music. Elvis many have never returned to that venue for another concert, but it's obvious he didn't have to go back to prove Jim Denny wrong.

12.   J. K. Rowling
Before J.K. Rowling hit it big with Harry Potter, she was a broke, divorced single mother struggling to get by on welfare. In a matter of five years, the series took off, leading her to become the first billionaire author. 

13.   Akio morita
The founder of Sony was considered a major flop at first, manufacturing a rice cooker that burned way more food than it cooked. But despite poor early sales that brought the mockery of Sony as a new company by the business community, Akio Morita found a way to turn the brand into the multi-billion dollar company the world knows today. 

14.   Stephen spielberg
He may now be one of the most successful filmmakers in the world, but the University of Southern California refused to give Steven Spielberg a shot in the School of Theater, Film and Television -- three times. He clearly didn't take no for an answer as he went on to pursue directing, and the school awarded him an honorary degree in 1994.

15.  Lady Gaga
This New York-native, electro-pop diva proved just how badly she wanted to be in the spotlight throughout the early years of her career. After dropping out of New York University's Tisch School of the Arts to pursue her music and joining with major label Def Jam Recordings, she was let go only three months after being signed, forcing her to start all over again.-
16. F.Scott Fitzgerald
F. Scott Fitzgerald had extremely high hopes for his 1925 novel The Great Gatsby, hoping for "something new—something extraordinary and beautiful and simple and intricately patterned." Unfortunately, the book received mixed reviews upon its release, and sales proved even worse. It wasn't until after he died in 1940, considering himself a forgotten failure, that the book struck a chord with the country to the point of becoming a classic component of every high schooler's literature education.

17.  Albert Einestein

Einstein was a late bloomer, not speaking until age 4 or reading until age 7. These challenges did not prevent him from winning the Nobel prize in physics for discovering the photoelectric effect and developing the relativity theory. There's no doubt that the folks at Zurich Polytechnic School regret their initial rejection of the man whose name is now synonymous with "genius."
18. Claude Monet
One of the most well-known artists of the impressionist movement, Claude Monet was not quite praised for his work when he was alive. In fact, it was quite the opposite, with the Paris Salon endlessly mocking and rejecting his art. Yet, today Monet is considered the “prince of Impressionists.”
19. Emily Dickinson
The now-beloved letters and poetry of Emily Dickinson failed to resonate with their audience at first. While the author ultimately shared approximately 1,800 complete works with the world, fewer than a dozen of them were published in her lifetime.