Key To Resistance To Common Cancer Drug Could Be Variation Of Normal Protein

�Researchers at the Moores Cancer Center at the University of California, San Diego (UC SD) in La Jolla have establish evidence explaining why a common chemotherapy drug, cisplatin, may not always act for every cancer patient. They bear shown that when a variant version of a key protein that ordinarily causes cell death is active, patients may be resistant to the cancer-killing drug.



The scientists say that such findings, reported on-line this workweek in the journal Proceedings of the National Academy of Sciences, are authoritative to savvy how personalized therapies may be developed for patients.



In a series of experiments, Jean Wang, Ph.D., distinguished professor of medicine and Associate Director of Basic Research at the Moores UCSD Cancer Center, Richard Kolodner, Ph.D., professor of medicine at UC San Diego and Executive Director, Laboratory Science and Technology at the Ludwig Institute for Cancer Research and their co-workers found evidence that when a specific variant form of a so-called "mismatch repair" protein, PMS2, is active, cisplatin doesn't kill cancer cells the way it usually does. The cancer is, in effect, resistant to the drug.



As a quicken protein, PMS2 is crucial to fix mistakes in DNA that may occur during replication. It besides has a darker face, playing a role in instructing cells to kill themselves.



For example, Wang, Kolodner and their colleagues had previously shown that PMS2 is required for cisplatin to kill cancer cells, activating some other protein, p73, which in turn begins a cascade of steps leading to cell suicide. Since most cancer cell-killing therapies such as chemotherapy and radiation take advantage of this process, the team wanted to better understand how cancer cells might bilk such self-annihilation instructions, rendition the therapy ineffective.



Defects in such mismatch repair genes and proteins can gain cancer endangerment, particularly for hereditary colon cancer. The researchers knew that the PMS2 cistron had at least 12 different forms in man. In studies on black eye cells wanting PMS2, they tested several different variations of the human PMS2 protein, for the most part display that PMS2 indeed hypersensitized cells to cisplatin, causing cell felo-de-se. They last found that one variant, PMS2 (R20Q), failed to activate p73 and bring about cubicle death in response to cisplatin. The drug's toxic effects were compromised in cells with the PMS2 (R20Q).



Wang sees many possibilities for future research. "We don't know how many people have this PMS2 variant," she explained, noting that cisplatin is the first-line therapy for testicular and ovarian cancers. "We would like to take these findings to human tumor samples. If we could discover out which individuals carry this version, it power change our decisions about treating them with cisplatin."



If researchers could track how fast ovarian cancer patients' tumors develop resistance to cisplatin, she said, correlativity studies might be performed to regain risk factors, such as gene variants.



Ideally, scientists will ultimately intention new drugs that lavatory push cancer cells into cell self-destruction, rather than repairing themselves, she noted.





Other authors admit Irina Hunton and Atsuko Yoshioka-Yamashita, Ph.D,. UC San Diego, Winfried Edelmann, Ph.D., and Elena Avdievich, Ph.D., Albert Einstein College of Medicine, Ivana Marinovic-Terzic, M.D., University of Split, Croatia, and Hideki Shimodaira, Ph.D., Tohoko University, Japan.



The work received financing support from the National Institute for Environmental Health Sciences, the National Cancer Institute and the Japan Society for the Promotion of Science Research Fellowships for Young Scientists.



Source: Steve Benowitz

University of California - San Diego




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Take That are at No1

TAKE THAT have been hailed the greatest boy band in a poll.

The lads, who sold 30million records. reformed in 2006 after splitting ten-spot
years to begin with. They upper side a list including THE BEATLES, JACKSON FIVE,
BEE GEES and WESTLIFE.

A spokesman for One poll.com ?
which quizzed 5,000 music fans ? aforesaid: �This has to be
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Five, 4 Westlife, 5 Monkees, 6 Boyzone, 7 Bee Gees, 8 Backstreet Boys, 9 New
Kids on the Block, 10 Osmonds.

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At first glance, the granulose photos look like a paparazzi's dream come true.

Paris Hilton showering during her prison least sandpiper. Tom Cruise and Katie Holmes reading to their baby from a hulk book titled "Scientology for Babies." David Beckham nerve-racking on one of Posh's thongs. Queen Elizabeth sitting on the toilet.

If they seem to a fault amazing to be true, that's because they're not.

They're the creations of art photographer Alison Jackson, whose images of celebrity look-alikes in staged photographs get titillated and outraged both stars and fans.

Jackson's modish works take some critics wondering whether she's bygone too far. Photographs of the queen on the toilet, former British Prime Minister Tony Blair's wife getting an enema and Michael Jackson playing with a tot whose

Freaked Frequency

   
Artist: Freaked Frequency

   Genre(s): 
Trance: Psychedelic
   

---

Discography:


   
 Unreleased

   Year: 2006   
Tracks: 1

---

 

Crash Test Dummies

   
Artist: Crash Test Dummies

   Genre(s): 
Pop: Pop-Rock
   Alternative
   Indie
   Rock: Pop-Rock
   

---

Discography:


   
 Puss 'n' Boots

   Year: 2003   
Tracks: 13


   
 Jingle All The Way

   Year: 2002   
Tracks: 11


   
 I Don't Care That You Don't Mind

   Year: 2001   
Tracks: 14


   
 A Worm's Life

   Year: 1996   
Tracks: 12


   
 God Shuffled His Feet

   Year: 1993   
Tracks: 12


   
 The Ghosts That Haunt Me

   Year: 1991   
Tracks: 10


   
 Songs Of The Unforgiven

   Year:    
Tracks: 17

---

With their cagy, smug lyrics and cloying folk-tinged melodies, the Crash Test Dummies were a perfect rock 'n' roll band for confluent '90s college students and yuppies. Their number one album was a huge hit in their native Canada, only only gained a modest furor following in other parts of the world. Thanks to late Talking Head Jerry Harrison's clean, radio-friendly production, the follow-up, God Shuffled His Feet (1993), stone-broke big in the States and, in grow, Europe. The number one single from the album, "MMM MMM MMM MMM," became a world-wide Top Ten make, devising the chemical group a minor adept with their self-consciously outlandish lyrics and singer/songwriter Brad Roberts' deep baritone. A Worm's Life followed in 1996, and triplet geezerhood by and by the Crash Test Dummies resurfaced with Give Yourself a Hand. Frontman Brad Roberts resurfaced in fall 2000 with a solo album, Crash Test Dude, a appeal of acoustic hits from the Crash Test Dummies and eclecticist covers. It was likewise during this time that Roberts suffered a serious car crash, most losing his arm. Seven months by and by, nonetheless, Roberts returned to the Crash Test Dummies circuit to number I Don't Care That You Don't Mind, a spic-and-span tidy sum of songs scripted with lobster fishermen/musicians whom Roberts met during his rehabilitation. Late 2001 and early 2002 saw more solo albums from members (Ellen Reid's Cinderellen and Mitch Dorge's As Trees Walking) and the Dummies became more Brad Roberts' jut out than a traditional band. A new three-piece unit with Reid, Brad Roberts and original bassist Dan Roberts released the Christmas album Jingle All the Way in late 2002 merely limited dispersion made the album heavy to find. The album was reissued in late 2003 along with a new album, Puss 'n' Boots, with Reid and Dan Roberts adding to what was in the beginning planned as a Brad Roberts solo record album.





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Willoughby defends her TV wardrobe

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According to reports, members of the public have complained that the presenter's dresses are too revealing.
Responding to the complaints on ITV show 'Loose Women', Willoughby said: "It's just the weirdest thing that has ever happened - like I've been living in someone else's world the last two weeks."
"My body dictates that it suits certain things, so I always wear the same style of dress. Unfortunately those are the things that get attention. It would be nice if the publicity was, 'Isn't she good at her job?'."
She also told The Mirror: "I can't believe the stir it caused. I like to wear feminine clothes and I've had people coming up to me in the street saying how much they liked it."

Velvet Revolver splits with singer Scott Weiland

LOS ANGELES - The four founding members of rock band Velvet Revolver have confirmed they are splitting with the group's troubled singer, Scott Weiland, citing his "increasingly erratic" behavior.

The announcement came in a terse...