Transcription factors regulating blood oxygen linked to melanoma metastases

Apr. 16, 2013 ? Researchers at the University of North Carolina have discovered that transcription factors regulating the levels of oxygen in the blood also play a role in the spread of the skin cancer melanoma.

In research published April 8 in the Journal of Clinical Investigation, a research team led by William Kim, MD, member of the UNC Lineberger Comprehensive Cancer Center, and graduate student and first author Sara Hanna, linked melanoma metastases to a pair of transcription factors known as HIF1 and HIF2.

Researchers found that HIF1 and HIF2 are overexpressed in melanoma tumors. In healthy cells, HIF1 and HIF2 assist in regulating hypoxia, the state caused by low levels of oxygen in the blood. Hypoxia has been linked to metastases in several sold tumors, and the UNC team has found that it promotes the spread of melanoma from the skin to other sites in the body through the lymphatic system.

Patients who are diagnosed with early stage melanomas have a high rate of survival, but the prognosis worsens significantly once the tumors spread to other sites throughout the body. Using in vitro systems and mouse models, researchers suppressed the expression of HIF1 and HIF2 in the melanoma tumors. While the inactivation of the transcription factors did not reduce the growth of the initial tumors, it did reduce the rate at which the melanoma spread to other sites in the body.

Both HIF1 and HIF2 independently activate the protein kinase SRC using different signaling pathways. The SRC protein has been linked to several different cancers, and the identification of its role in melanoma suggests that existing therapies targeting SRC may prove to be a viable target for therapies aimed at reducing the spread and ultimate lethality of the cancer.

"What we are trying to do now is inhibit these pathways with drugs in the mice to see if we see a decrease of metastasis," said Hanna.

UNC researchers who contributed to this article include Bhavani Krishnan, PhD; Sean Bailey; Stergios Moschos, MD; Pei-Fen Kuan, PhD; Marni Siegel and C. Ryan Miller, MD, PhD, of the Lineberger Cancer Center; and Lukas Osborne, E. Tim O'Brien III and Richard Superfine, PhD, of the UNC Department of Physics and Astronomy.

This research was supported by the National Institutes of Health (P30-DK-034987), the National Cancer Institute (3P30CA016086), the Department of Defense (W81XWH-09-2-0042) and the University Cancer Research Fund.

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The above story is reprinted from materials provided by University of North Carolina School of Medicine.

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Journal Reference:

1. Sara C. Hanna, Bhavani Krishnan, Sean T. Bailey, Stergios J. Moschos, Pei-Fen Kuan, Takeshi Shimamura, Lukas D. Osborne, Marni B. Siegel, Lyn M. Duncan, E. Tim O?Brien, Richard Superfine, C. Ryan Miller, M. Celeste Simon, Kwok-Kin Wong, William Y. Kim. HIF1? and HIF2? independently activate SRC to promote melanoma metastases. Journal of Clinical Investigation, 2013; DOI: 10.1172/JCI66715

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/~3/RqPeuRc4VtI/130416102125.htm

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Gene-expression signature may signify risk for recurrence, metastasis in prostate cancer

Apr. 15, 2013 ? A team led by Massachusetts General Hospital (MGH) researchers has identified a genetic signature that appears to reflect the risk of tumor recurrence or spread in men surgically treated for prostate cancer. If confirmed in future studies, this finding not only may help determine which patients require additional treatment after the cancerous gland has been removed, it also may help address the most challenging problem in prostate cancer treatment -- distinguishing tumors that require aggressive treatment from those that can safely be monitored.

The report has been issued online in PNAS Early Edition.

"Radical prostatectomy is the standard of care for men whose cancer is advanced but confined to the prostate gland, but we know that the factors we use to determine which patients need radiation therapy after surgery are inadequate," says W. Scott McDougal, MD, of the MGH Department of Urology, corresponding author of the report. "The treatments available to our patients can have significant impact on their quality of life, so a better way to know which patients with localized cancer need additional therapy after surgery and which require no additional treatment is a significant unmet need."

Gene expression signatures indicating patient prognosis and sometimes the most appropriate treatment have been incorporated into care for breast cancer and other tumors. Studies looking for such markers in prostate cancer have had variable results, and their potential usefulness to guide treatment has not been determined. For the current study the research team -- led by Chin-Lee Wu, MD, PhD, of the MGH Department of Pathology -- examined samples of malignant tissue from around 200 prostate cancer patients who had radical prostatectomies at the MGH between 1993 and 1995, analyzing the expression patterns of more than 1,500 genes associated with prostate cancer in earlier studies. With the results of that analysis, they developed a 32-gene index to reflect the likelihood that a patient's tumor would recur, signified by detectable levels of prostate-specific antigen (PSA) after the gland had been remove, or spread.

To validate the usefulness of the index, they used it to analyze tissue samples from a different group of almost 300 patients who had their prostates removed in 1996 and 1997, comparing the index with currently used prognostic factors -- such as PSA levels, physical examination, and a tumor's microscopic appearance -- to see how accurately each predicted the actual incidence of tumor recurrence or metastasis during the 10 years after surgery. The expression-based index proved to be the most accurate method. Among those it designated as high-risk, the actual incidence of tumor recurrence was 47 percent and of metastasis, 14 percent. Among those classified as intermediate risk, actual recurrence was 22 percent, and metastasis occurred in 2 percent. No recurrence or metastasis were seen in patients classified as low-risk by the gene-expression index.

To get a sense of whether the index could help determine risk at the time of diagnosis, the researchers used it to assess presurgical needle biopsy samples from 79 patients in the validation group. The risk assignment based on biopsy results closely matched the assessment based on surgically removed tissue, and the prognostic ability of the index was better than that of other pathological information available at the time a biopsy was taken. Because the current report is based on study of patients treated at a single institution, the authors note, it requires confirmation in larger, multi-institutional studies.

"A more accurate prognosis at the time of diagnosis could give patients and their physicians much more confidence in choosing a definitive therapy or pursuing active surveillance for those at low risk, which could reduce over-treatment, a critical issue in disease management," says lead author Wu, an associate professor of Pathology at Harvard Medical School. McDougal is the the Kerr Professor of Urology, at HMS.

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The above story is reprinted from materials provided by Massachusetts General Hospital.

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Journal Reference:

1. C.-L. Wu, B. E. Schroeder, X.-J. Ma, C. J. Cutie, S. Wu, R. Salunga, Y. Zhang, M. W. Kattan, C. A. Schnabel, M. G. Erlander, W. S. McDougal. Development and validation of a 32-gene prognostic index for prostate cancer progression. Proceedings of the National Academy of Sciences, 2013; 110 (15): 6121 DOI: 10.1073/pnas.1215870110

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/health_medicine/genes/~3/yqTbvnhFdUw/130415151442.htm

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Not Your Ordinary Home for Birds - Hancock Wildlife Foundation

Friday, April 12 2013 @ 06:24 PM EDT

Contributed by: MaryF

Jay Wexler of Boston University School of Law on April 11, 2013

A Resident of the Iowa Tribe's Aviary Relaxes Photo by Jay Wexler

Gracie was having a good day.? This was unusual.? Much of the time, she hangs out alone in a corner of the football-field length shelter she shares with a dozen or so other birds, enjoying looking at herself in a little mirror perhaps, but not doing much else.? Not that anyone can really blame her.? Since being hit by a car, she?s been blind in one eye and has such shoulder pain that she often keeps her head almost upside down to get some relief.? But on the day we met, Gracie was out of her corner, hopping sideways like a crab, staring me down with her one good eye as I crooned, ?Hello, Gracie,? to her over and over like a goofball.

?

Read the rest of the story here:

?

Source: http://www.hancockwildlife.org/article.php/NorYourOrdinaryHomeForBirds

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Can Emma Watson Top Abs And A Cappella At MTV Movie Awards?

The year's best singers (and dancers!) face off at Sunday's MTV Movie Awards in the new Best Musical Moment category.
By Kevin P. Sullivan

Logan Lerman, Ezra Miller and Emma Watson in "The Perks of Being A Wallflower"
Photo: Summit Entertainment

Source: http://www.mtv.com/news/articles/1705471/movie-awards-best-musical-moment.jhtml

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Blocking immune response protein helps body clear chronic infection; Potential therapy for HIV, other viral infections?

Apr. 11, 2013 ? UCLA scientists have shown that temporarily blocking a protein critical to immune response actually helps the body clear itself of chronic infection. Published in the April 12 edition of Science, the finding suggests new approaches to treating persistent viral infections like HIV and hepatitis C.

The research team studied type-1 interferons (IFN-1), proteins released by cells in response to disease-causing organisms that enable cells to talk to each other and orchestrate an immune response against infection. Constant IFN-1 signaling is also a trademark of chronic viral infection and disease progression, particularly in HIV.

"When cells confront viruses, they produce type-1 interferons, which trigger the immune system's protective defenses and sets off an alarm to notify surrounding cells," explained principal investigator David Brooks, assistant professor of microbiology, immunology and molecular genetics at UCLA's David Geffen School of Medicine and College of Letters and Sciences. "Type-1 interferon is like the guy in the watch tower yelling, 'red alert,' when the marauders try to raid the castle."

Scientists have long viewed IDF-1 as beneficial, because it stimulates antiviral immunity and helps control acute infection. Blocking IDF-1 activity, they reasoned, would allow infection to run rampant through the immune system.

On the other hand, prolonged IFN-1 signaling is linked to many chronic immune problems. The research team wondered whether obstructing the signaling pathway would enable the immune system to recover enough to fight off chronic infection.

To test this theory, Brooks and his colleagues injected mice suffering from chronic viral infection with an antibody that temporarily blocked IFN-1 activity.

Much to their surprise, they discovered that giving the immune system a holiday from IFN-1 boosted the body's ability to fight the virus. Stunningly, the respite also reversed many of the immune problems that result from chronic infection, such as a rise in proteins that suppress immune response, continuous activation of the immune system and disruption of lymph tissue.

The findings fly in the face of past studies that suggest eliminating IFN-1 activity in mice leads to severe, life-long infection.

"What we saw was entirely illogical," admitted Brooks. "We'd blocked something critical for infection control and expected the immune system to lose the fight against infection. Instead, the temporary break in IFN-1 signaling improved the immune system's ability to control infection. Our next task will be to figure out why and how to harness it for therapies to treat humans."

"We suspect that halting IFN-1 activity is like pushing the refresh button," said first author Elizabeth Wilson, a UCLA postdoctoral researcher. "It gives the immune system time to reprogram itself and control the infection."

Uncovering this mechanism could offer potential for new therapies to tackle viruses like HIV and hepatitis C, according to Brooks. The team's next step will be to pinpoint how to sustain IFN-1's control of the virus while blocking the negative impact that chronic IFN-1 activity wreaks on the immune system.

The National Institute of Allergy and Infectious Diseases and the UCLA Center for AIDS Research supported the research.

Brooks' coauthors included first author Elizabeth Wilson, Douglas Yamada, Heidi Elsaesser, Jonathan Herskovitz, Jane Deng and Genhong Cheng, all of UCLA; Bruce Aronow of the University of Cincinnati, and Christopher Karp of the University of Cincinnati and Bill and Melinda Gates Foundation.

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The above story is reprinted from materials provided by University of California, Los Angeles (UCLA), Health Sciences, via Newswise.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. E. B. Wilson, D. H. Yamada, H. Elsaesser, J. Herskovitz, J. Deng, G. Cheng, B. J. Aronow, C. L. Karp, D. G. Brooks. Blockade of Chronic Type I Interferon Signaling to Control Persistent LCMV Infection. Science, 2013; 340 (6129): 202 DOI: 10.1126/science.1235208

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/KziwAhoigYM/130411142712.htm

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Man slices arms to the bone with saws at California Home Depot

By John Simerson and Robert Kovacik, NBC Los Angeles

A man cut his arms to the bone with handsaws at a California home improvement store and was found in a pool of blood, authorities said.

Pasadena fire Capt. Art Hurtado was among horrified shoppers in the aisle Wednesday. He was shopping with his wife on his day off and jumped in to help.

Hurtado and his wife, Isabelle, saw West Covina police officers rush to the man, and he joined them.

"The officers had already found a man face down," Hurtado said, "and the whole store is in chaos."

More from NBCLosAngeles.com

"People just couldn?t believe it," added West Covina police Cpl. Rudy Lopez. ?He walked into the saw area, picked up a couple of saws in the saw area and started cutting both of his arms.?

Hurtado said that as soon as he noticed the first saw, he "thought it was just going to be a crime scene and a fatality."

Without gloves or any equipment, the 21-year fire department veteran began working on the victim.

"He was just barely breathing," Hurtado said.

But Hurtado kept trying, using what was on the store shelves around him.

"I can save this guy, if I engage, that?s what we do," he said.

"I started asking for a lot of towels," Hurtado added. "They finally showed up with a large packet of quarter-inch rope, nylon rope. And I ripped it open and just stretched it out, and I told the police officer I want 24-inch sections. Just start cutting."

Lopez said the man used several handsaws ? including one that is used to cut drywall ? to cut "all the way down to the bone."

"It was a godsend," Lopez said. "He happened to be at the right place at the right time, probably saved his life."

It was all in a day?s work, to Hurtado.

"Were we in a good place for it? No, but you improvise," he said. "You make things do. Like I said, if I didn?t have rope, I would have used my shoelaces. We would have made it work."

Home Depot told NBC Los Angeles in a statement that it will cooperate with law enforcement's investigation. The victim remained in surgery late Wednesday.

This story was originally published on Thu Apr 11, 2013 8:12 AM EDT

Source: http://feeds.nbcnews.com/c/35002/f/653381/s/2a9921a2/l/0Lusnews0Bnbcnews0N0C0Inews0C20A130C0A40C110C1770A36260Eman0Eslices0Earms0Eto0Ethe0Ebone0Ewith0Esaws0Eat0Ecalifornia0Ehome0Edepot0Dlite/story01.htm

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'G.I. Joe' commands No. 1 at box office with $41M

LOS ANGELES (AP) ? After a nine-month delay, "G.I. Joe: Retaliation" deployed to the top spot at the box office.

The action film starring Dwayne "The Rock" Johnson, Bruce Willis and Channing Tatum as the gun-toting military toys brought to life marched into the No. 1 position at the weekend box office, earning $41.2 million, according to studio estimates Sunday. "Retaliation" opened Wednesday at midnight, which helped bring its domestic total to $51.7 million.

Paramount postponed the sequel to 2009's "G.I. Joe: Rise of Cobra" last May from its original June opening date to convert the film to 3-D. The last-minute switcheroo came just weeks after "Battleship," another movie based on a Hasbro toy, sank at the box office. At that time, Paramount already began its advertising campaign for "Retaliation."

"It certainly vindicates the decision," said Don Harris, the studio's head of distribution. "Any time you make those sorts of moves, people always assume the worst. The truth is I'd seen this movie a long time ago in 2-D, and the movie worked in 2-D. It's not trying to be 'Schindler's List.' This movie is intended to be enjoyed as a big, action spectacle."

Internationally, Harris said "Retaliation" earned $80.3 million, making it the biggest international opening of the year. The film opened in 53 markets outside of the U.S. and Canada, including Russia, South Korea and Mexico.

After debuting in the top spot last weekend, the 3-D animated prehistoric comedy "The Croods" from DreamWorks Animation and 20th Century Fox slipped to the No. 2 spot with $26.5 million in its second weekend. The film features the voices of Nicolas Cage, Emma Stone and Catherine Keener as a cave family on the hunt for a new home.

Among the other new films this weekend, "Tyler Perry's Temptation" starring Jurnee Smollett-Bell and Lance Gross opened above expectations at No. 3 with $22.3 million, while the sci-fi adaptation "The Host" featuring Saoirse Ronan, Max Irons, and Jake Abel as characters from the Stephenie Meyer novel landed at No. 6 in its debut weekend with a modest $11 million.

Overall, the weekend box office was on par with last year when "The Hunger Games" continued to dominate in its second weekend of release with $58.5 million. After a slow start, Hollywood's year-to-date revenues are still 12 percent behind last year, heading into next month when summer movie season unofficially kicks off with "Iron Man 3" on May 3.

"It's getting us back on track after many weekends of down trending box office," said Paul Dergarabedian, box office analyst for Hollywood.com. "Last weekend was a turning point with the strength of 'The Croods' and 'Olympus Has Fallen' doing better than expected. We're heading toward the summer movie season on solid footing. It's been a tough year so far."

Estimated ticket sales for Friday through Sunday at U.S. and Canadian theaters, according to Hollywood.com. Where available, latest international numbers are included. Final domestic figures will be released Monday.

1. "G.I. Joe: Retaliation," $41.2 million ($80.3 million international).

2. "The Croods," $26.5 million ($52.5 million international).

3. "Tyler Perry's Temptation," $22.3 million.

4. "Olympus Has Fallen," $14 million.

5. "Oz the Great and Powerful," $11.6 million ($22.2 million international).

6. "The Host," $11 million ($6 million international).

7. "The Call," $4.8 million.

8. "Admission," $3.2 million.

9. "Spring Breakers," $2.7 million.

10. "The Incredible Burt Wonderstone," $1.3 million.

___

Estimated weekend ticket sales at international theaters (excluding the U.S. and Canada) for films distributed overseas by Hollywood studios, according to Rentrak:

1. "G.I. Joe: Retaliation," $80.3 million.

2. "The Croods," $52.5 million.

3. "Jack the Giant Slayer," $25.2 million.

4. "Oz the Great and Powerful," $22.2 million.

5. "Dragon Ball Z: Kami to Kami," $7 million.

6. "The Host," $6 million.

7. "Identity Thief," $5.5 million.

8. "Wreck-It Ralph," $4 million.

9. "A Good Day to Die Hard," $3.6 million.

10. "Hansel and Gretel: Witch Hunters," $3.3 million.

___

Online:

http://www.hollywood.com

http://www.rentrak.com

___

Universal and Focus are owned by NBC Universal, a unit of Comcast Corp.; Sony, Columbia, Sony Screen Gems and Sony Pictures Classics are units of Sony Corp.; Paramount is owned by Viacom Inc.; Disney, Pixar and Marvel are owned by The Walt Disney Co.; Miramax is owned by Filmyard Holdings LLC; 20th Century Fox and Fox Searchlight are owned by News Corp.; Warner Bros. and New Line are units of Time Warner Inc.; MGM is owned by a group of former creditors including Highland Capital, Anchorage Advisors and Carl Icahn; Lionsgate is owned by Lions Gate Entertainment Corp.; IFC is owned by AMC Networks Inc.; Rogue is owned by Relativity Media LLC.

___

Follow AP Entertainment Writer Derrik J. Lang on Twitter at http://www.twitter.com/derrikjlang.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/386c25518f464186bf7a2ac026580ce7/Article_2013-03-31-Box%20Office/id-fe8c399e2af8425a97b849fb01c8c934

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