News From The Journal Of The National Cancer Institute, August 26 2008

�Novel Trial Design Aims to Speed Drug Development



Researchers propose a novel multi-arm trial plan that stool test various therapies simultaneously and could speed drug development in cancer.



Scientists experience gained significant insights into the biological underpinnings of cancer, merely this knowledge has non led to a leap out in the number of therapies sanctioned for clinical use. One possible ground for the slower than expected progress is the time required for clinical testing with current visitation designs.



With that issue in mind, Mahesh Parmar, Ph.D., of the Medical Research Council Clinical Trials Unit in London and colleagues modified banner clinical trial methodology so that multiple therapies or combinations lav be compared in a single trial. The new design incorporates standard phase II and phase III goals into one multiphase trial and requires fewer patients than standard trials.



In the comment, Parmar and colleagues talk about the want for fresh approaches to clinical trials, describe the new trial design in detail, and provide examples of on-going trials that use the multi-arm trial approach. "With three real examples, we hope that we get shown that such trials are practicable and commode lead to major improvements in speeding and determination making," the authors write.


Natural Chemical from Sea Sponges Induces Death in Cancer Cells via Unusual Pathway



A chemical called candidaspongiolide (CAN) inhibits protein synthesis simply also kills cancer cells by triggering caspase 12-dependent programmed cell death.



Previous reports showed that CAN preferentially killed glioma and melanoma cells in vitro, only its chemical mechanism of action was unknown.



In the electric current study, Giovanni Melillo, M.D., of the National Cancer Institute in Frederick, Md., and colleagues used molecular and cell assays to uncover the mechanism by which CAN kills cancer cells in vitro.



CAN halts protein synthesis in both normal and cancer cells but does not kill normal cells at dosages that induction cell death in the malignant cells. CAN induces cell decease by activation caspase 12 by an unusual biochemical pathway.



The investigators conclude that further tests with CAN are warranted in vitro and in animal models.


Deletion of Chromatin Remodeling Genes Leads to Leukemia in Mice



Mice deficient both copies of the Arid4A gene and one copy of the Arid4B gene develop acute myeloid leukemia (AML) and may provide an important animate being model for preleukemic and leukemic conditions.



It is well known that genetic mutations, which spay the sequence of DNA in chromosomes, can lead story to cancer. More late, researchers take found that changes in chromatin structure and activity (epigenetic changes) can lead to crab as well. The Arid4 family of genes is involved in chromosome remodeling, but their impact on leukemia was not known.



Arthur Beaudet, M.D., of Baylor College of Medicine in Houston and colleagues bred mice that lacked both copies of Arid4A and one copy of Arid4B. They monitored the animals' health through and through repeated blood cell counts and molecular tests on blood and bone bone marrow cells.



The variation mice developed a myeloproliferative disorder that resembled chronic myeloid-monocytic leukemia. The animals then progressed to AML. The pattern of disease progression in the animals resembled the course of events in humans and may indicate that the mutant mice are utilitarian models for studying how AML develops and testing potential therapeutics.



"Further study of the Arid4 gene family may advance our sympathy of the connection 'tween gene regulation, epigenetic ascendency, disease growing, and cancer formation," the authors write. "We too suggest that gene regulating by the ARID4A and ARID4B should be examined for potentiality disease-related roles, not only in human malignancies, simply also in other complex disease traits."


Mutations in the Succinate Dehydrogenase Subunit B Gene Associated with Familial Renal Cell Cancer



Individuals world Health Organization have a germline mutant in the succinate dehydrogenase subunit B (SDHB) factor presented with familial nephritic cell genus Cancer (RCC) or with bilateral RCC.



Previous inquiry suggested that germline mutations in succinate dehydrogenase genes were principally associated with the development of pheochromocytoma or paraganglioma, which are tumor syndromes that regard other tissues. Although RCC had been reported occasionally in individuals with a germline SDHB mutation, these individuals had a personal or fellowship history of pheochromocytoma or paraganglioma. Therefore, the association of mutations in succinate dehydrogenase genes with familial RCC in the absence of other tumor syndromes was unknown.



In the current study, Eamonn Maher, M.D., of the University of Birmingham in the UK and colleagues sequenced the genes encryption several of these enzymes in 68 individuals wHO had either familial RCC or bilateral RCC but who showed no evidence of phaeochromocytoma or paraganglioma.



They identified ternary individuals with germline mutations in SDHB in this population. They conclude that the mutations are associated with an increased risk of genetic RCC.



"Our findings suggest that individuals presenting with features of hereditary RCC susceptibility should be screened for germ�line SDHB mutations because surveillance for SDHB-related tumors can then be offered to mutation-positive patients and relatives," the authors write.



In an ensuant editorial, Charis Eng, M.D., Ph.D., of the Cleveland Clinic in Ohio notes that the new data confirm premature reports of an connexion between mutations in the SDHB factor and familial RCC. She thinks, however, that it is too early to conclude whether such mutations occur in the absence of tumour syndromes granted the relatively young age at which the ternary patients in Maher's study either died or were lost to follow-up and the later age of onset for pheochromocytoma or paraganglioma.



Nonetheless, the new information have clinical utility, according to Eng. "It is entirely appropriate, at this time, to counsel patients carrying SDHB mutations, espe�cially those with Arg mutations, that they have a small simply finite likelihood of development RCC," she writes.



Also in the August 26 JNCI:



* hTTP://www.eurekalert.

Jack White Discusses James Bond Song

Jack White has discussed the song 'Another Way To Die', which he recorded with singer Alicia Keys for the forthcoming James Bond movie 'Quantum Of Solace', which is released in October.

"After a couple of years of wanting to collaborate with Alicia Keys, it took James Bond himself to finally hold it happen." The White Stripes ballad maker says in a statement. "Alicia place some electrical energy into her breath that cemented itself into the magnetic tape. Very inspiring to watch."

"I drummed for her voice and she mimicked the guitar tones, then we joined our voices and screamed and moaned about these characters in the cinema and their isolation, having no-one to trust, non even themselves. Maybe we became them for a few minutes."

Jack also added he was inspired by the retro recordings of previous Bond themes: "It might be the low gear analogue Bond theme in 20 age. We cherished to press soul into those tapes and join the family unit of Barry, Bassey, Connery and Craig."

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Level 3

   
Artist: Level 3

   Genre(s): 
Drum & Bass
   

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Discography:


   
 Contamination / Living Machine

   Year: 1997   
Tracks: 2

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Ringo Starr sells personal art collection

Washington (ANI): Fans of former Beatle Ringo Starr can now have a piece of the drummer's own personalized pop art collection. The sale of Starr's artwork had begun on the weekend, and the collection includes 40 pieces of art, reports Contactmusic. Starr had created the artwork while on tour with his All Starr Band in the late 1990s. The proceeds from the autographed collection, entitled Abstract Face, will be passed on to The Lotus Foundation, a charity aimed at advancing social welfare. Buyers who purchase the 2,950 dollars worth of artwork will receive a free ticket to Starr's show at Florida's Seminole Hard Rock Hotel and Casino on 3 July (08).
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Mac Mall

   
Artist: Mac Mall

   Genre(s): 
Rap: Hip-Hop
   

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Discography:


   
 Da U.S. Open

   Year: 2005   
Tracks: 12


   
 Mackin Speaks Louder Than Words

   Year: 2002   
Tracks: 15

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Along with better-known rappers like E-40 and 2Pac, Mac Mall was one of several wHO helped put the Cali Bay Area on the map in the mid to late '90s as a hotspot in the rap game. He collaborated with many of the Bay Area's best producers -- Ant Banks, Khayree, Michael Mosley, and Rick Rock -- and helped define the scene's personal identity, in particular with his almost successful record album, Untouchable (1996), which featured perchance his best-known strain, "Become Right." His career simmered out promptly, nonetheless. He returned in 1999 subsequently a three-year absence and few listeners seemed to notice. Mall was no longer on a major label and the Bay Area fit was no thirster the hotspot it had been a few long time originally. Given his brief moment in the public eye and his sudden decline, it was peradventure no surprise when Mall changed his style in 2001, incorporating a surprising sum of money of spiritualism on his Immaculate album.

Lee Not About To Shut His Face

Spike Lee has refused to back down from his criticism of Clint Eastwood for not including black soldiers in his two films about the battle of Iwo Jima in World War II. Eastwood had responded that the film was about the men who raised the flag at Mt. Suribachi and that none of them was black. He advised Lee to "shut his face." In an interview with ABCNews.com, Lee said, "First of all, the man is not my father and we're not on a plantation either. ... And a comment like 'a guy like that should shut his face' -- come on Clint, come on. He sounds like an angry old man right there." Meanwhile, Thomas McPhatter, a black Marine sergeant who fought at Iwo Jima has told Britain's Guardian newspaper that he had provided the pipe that was used as the makeshift flagstaff for the flag hoisted by the men seen in the historic Iwo Jima photo.


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Phobia

   
Artist: Phobia

   Genre(s): 
Drum & Bass
   Metal: Death,Black
   Rock: Grindcore
   Rock
   Soundtrack
   

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Discography:


   
 All Points North EP

   Year: 2006   
Tracks: 2


   
 Renegade (RR62)

   Year: 2005   
Tracks: 2


   
 Is It True Vinyl

   Year: 2005   
Tracks: 2


   
 Get Up and Kill

   Year: 2004   
Tracks: 17


   
 Grind Your Fucking Head In

   Year: 2003   
Tracks: 17


   
 Critical

   Year: 2003   
Tracks: 2


   
 Serenity Through Pain

   Year: 2001   
Tracks: 23


   
 Means Of Existence

   Year: 1998   
Tracks: 17


   
 Return To Desolation

   Year: 1994   
Tracks: 8

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Lullabelle

   
Artist: Lullabelle

   Genre(s): 
Indie
   

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Discography:


   
 The Trial of Florasador Gehrboyzel

   Year: 2004   
Tracks: 3

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Gyptian

Konrad Bayer

   
Artist: Konrad Bayer

   Genre(s): 
Ambient
   

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Discography:


   
 Shall We Go To The Park?

   Year: 2004   
Tracks: 8

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Federico Monti

   
Artist: Federico Monti

   Genre(s): 
Ambient
   

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Discography:


   
 Brujula

   Year: 2004   
Tracks: 10

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Winehouse is among Grammy nominees

Winehouse is among Grammy nominees

Amy Winehouse has been nominated in half a dozen categories for the 50th annual Grammy Awards.
Other multiple nominees include Kanye West with eight-spot nominations and Foo Fighters, Jay-Z, Timbaland, Justin Timberlake and T-Pain, each of whom received five nominations.
Among the awards Winehouse has been nominated for are Record of the Year for 'Rehab' and Album of the Class for 'Back to Black'.
The winners will be announced in Los Angeles on 6 December.




Art Tatum

Springsteen endorses Obama for president

Springsteen endorses Obama for president

Sir David Bruce Springsteen has formally




Ken Navarro

Steve Angello, Dave Armstrong

   
Artist: Steve Angello, Dave Armstrong

   Genre(s): 
Other
   

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Discography:


   
 Groove In You (Rmx)

   Year: 2004   
Tracks: 2

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Andy Williams (cd2)

GBH

   
Artist: GBH

   Genre(s): 
Rock: Punk-Rock
   

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Discography:


   
 Church Of The Truly Warped

   Year: 1993   
Tracks: 11


   
 City Baby Attacked By Rats

   Year: 1982   
Tracks: 13

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Aniston gets co-stars for new film

Aniston gets co-stars for new film

Jennifer Aniston and Aaron Eckhart's co-stars for their new clowning drama 'Traveling' suffer been announced.
The Hollywood Newsperson says that Martin Sheen, Dan Fogler and Judy Greer will star opposite the duet in the Brandon Camp-directed film.
'Traveling' tells the taradiddle of a widowed self-help generator (Meister Eckhart) who finds his feelings reawakened when he meets a hotel florist shop (Aniston) during




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