Eliminating the 'good cholesterol' receptor may fight breast cancer

Public release date: 3-Apr-2012
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Contact: Steve Graff
stephen.graff@jefferson.edu
215-955-5291
Thomas Jefferson University

Study suggests SR-BI plays a role in breast cancer tumor growth, say Jeffersons Kimmel Cancer Center researchers

CHICAGO Removing a lipoprotein receptor known as SR-BI may help protect against breast cancer, as suggested by new findings presented at the American Association for Cancer Research Annual Meeting 2012 by Jefferson's Kimmel Cancer Center researchers.

In vitro and mouse studies revealed that depletion of the SR-BI resulted in a decrease in breast cancer cell growth.

SR-BI is a receptor for high-density lipoproteins (HDL) that are commonly referred to as "good cholesterol" because they help transport cholesterol out of the arteries and back to the liver for excretion.

The team, including Christiane Danilo, of the Department Stem Cell Biology and Regenerative Medicine at Thomas Jefferson University, and Philippe G. Frank, Ph.D., an assistant professor in the Department of Stem Cell Biology and Regenerative Medicine at Jefferson, had good reason to believe that SR-BI played a role in breast cancer growth: Previous lab research had revealed that mice fed a high cholesterol diet develop more advanced tumors and their tumors produce more SR-BI.

To further investigate SR-BI's role in breast cancer tumors, the team manipulated levels of the receptor in human breast cancer cell lines and examined its effect on tumor formation in a mouse model.

In vitro, they found that ablation of the receptor protein in breast cancer cells led to a decrease in cancer cell proliferation, migration and invasion. Mouse models also showed that depletion of the receptor could confer protection against tumor growth.

Environmental factors, such as diet and obesity, have long been considered risk factors for the high breast cancer incidence in the Western world, and epidemiologic evidence indicates that cancer patients display abnormal levels of cholesterol carrying lipoproteins. However, the role of cholesterol in breast cancer had not yet been specifically examined.

"The results of this novel study show that depletion of SR-BI reduces cancer cell and tumor growth, suggesting that it could play an important role in breast cancer," said Dr. Frank. "More studies are warranted to further characterize the role of SR-BI in tumor progression."

###

Other researchers include Michael P. Lisanti, M.D., Ph.D., Chairman of the Department of Stem Cell Biology and Regenerative Medicine at Jefferson, and Maria Antonietta Mainieri of the University of Calabria, Rende, in Italy.

The study was funded by the Susan G. Komen Foundation.

---

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?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Public release date: 3-Apr-2012
[ | E-mail | Share ]

Contact: Steve Graff
stephen.graff@jefferson.edu
215-955-5291
Thomas Jefferson University

Study suggests SR-BI plays a role in breast cancer tumor growth, say Jeffersons Kimmel Cancer Center researchers

CHICAGO Removing a lipoprotein receptor known as SR-BI may help protect against breast cancer, as suggested by new findings presented at the American Association for Cancer Research Annual Meeting 2012 by Jefferson's Kimmel Cancer Center researchers.

In vitro and mouse studies revealed that depletion of the SR-BI resulted in a decrease in breast cancer cell growth.

SR-BI is a receptor for high-density lipoproteins (HDL) that are commonly referred to as "good cholesterol" because they help transport cholesterol out of the arteries and back to the liver for excretion.

The team, including Christiane Danilo, of the Department Stem Cell Biology and Regenerative Medicine at Thomas Jefferson University, and Philippe G. Frank, Ph.D., an assistant professor in the Department of Stem Cell Biology and Regenerative Medicine at Jefferson, had good reason to believe that SR-BI played a role in breast cancer growth: Previous lab research had revealed that mice fed a high cholesterol diet develop more advanced tumors and their tumors produce more SR-BI.

To further investigate SR-BI's role in breast cancer tumors, the team manipulated levels of the receptor in human breast cancer cell lines and examined its effect on tumor formation in a mouse model.

In vitro, they found that ablation of the receptor protein in breast cancer cells led to a decrease in cancer cell proliferation, migration and invasion. Mouse models also showed that depletion of the receptor could confer protection against tumor growth.

Environmental factors, such as diet and obesity, have long been considered risk factors for the high breast cancer incidence in the Western world, and epidemiologic evidence indicates that cancer patients display abnormal levels of cholesterol carrying lipoproteins. However, the role of cholesterol in breast cancer had not yet been specifically examined.

"The results of this novel study show that depletion of SR-BI reduces cancer cell and tumor growth, suggesting that it could play an important role in breast cancer," said Dr. Frank. "More studies are warranted to further characterize the role of SR-BI in tumor progression."

###

Other researchers include Michael P. Lisanti, M.D., Ph.D., Chairman of the Department of Stem Cell Biology and Regenerative Medicine at Jefferson, and Maria Antonietta Mainieri of the University of Calabria, Rende, in Italy.

The study was funded by the Susan G. Komen Foundation.

---

[ | E-mail | Share ]

?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

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Why Some Pain Relievers Cause Intense Itching

Head Lines | Health See Inside

A frustrating side effect of some painkillers is finally explained

By Erica Westly ?| April 3, 2012

Image: Getty Images

Millions of patients benefit from opioids such as morphine and codeine, but the pain relief they provide often comes with intense itching. In some cases, the irritation is so bad that patients will opt to cut back on painkillers. Now a study in the October 14 issue of Cell has found a possible explanation?the first step to creating drugs that will not make patients choose between experiencing itchiness and pain.

Until recently, many experts had assumed that itching from opioids was unavoidable because it is a common side effect of drugs that interact with the nervous system. The brain has four main types of receptors that respond to opioids, and every type has many structural variants, called isoforms. Most opioids are nonspecific, which means they bind to all the isoforms. This leads to powerful pain relief, although scientists do not know exactly why.

In the new research, a team led by itch researcher Zhou-Feng Chen of Washington University in St. Louis showed that only one opioid receptor isoform is responsible for itching?and it is not involved in pain. Mice bred to have fewer of these particular receptors did not scratch themselves when given an opioid, but they did exhibit the telltale mouse signs of pain relief, such as less flinching when researchers flicked their tails.

Now that scientists know that pain relief and itching can be decoupled, they will try to make itch-free opioid drugs a reality.

This article was published in print as "Defeating Pain without the Itch."

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Study: Our ancestors used fire a million years ago

In an undated photo provided by Michael Chazen, Paul Goldberg takes samples in Excavation 1 at Wonderwerk Cave in South Africa. Scientists said Monday, April 2, 2012 that they've found the earliest firm evidence of human ancestors using fire: material about 1 million years old in in Wonderwerk cave. Burned bones and microscopic ash in the dirt suggests fire frequently burned there, apparently under the control of our ancestor Homo erectus, researchers said. (AP Photo/courtesy of Michael Chazan)

In an undated photo provided by Michael Chazen, Paul Goldberg takes samples in Excavation 1 at Wonderwerk Cave in South Africa. Scientists said Monday, April 2, 2012 that they've found the earliest firm evidence of human ancestors using fire: material about 1 million years old in in Wonderwerk cave. Burned bones and microscopic ash in the dirt suggests fire frequently burned there, apparently under the control of our ancestor Homo erectus, researchers said. (AP Photo/courtesy of Michael Chazan)

An undated photo provided by Paul Goldberg shows a micrograph of burned bone found at Wonderwerk Cave in South Africa. Scientists said Monday, April 2, 2012 that they've found the earliest firm evidence of human ancestors using fire: material about 1 million years old in in Wonderwerk cave. Burned bones and microscopic ash in the dirt suggests fire frequently burned there, apparently under the control of our ancestor Homo erectus, researchers said. (AP Photo/courtesy of Paul Goldberg)

An undated photo provided by Michael Chazen shows the inside of Wonderwerk cave in South Africa. Scientists said Monday, April 2, 2012 that they've found the earliest firm evidence of human ancestors using fire: material about 1 million years old in in Wonderwerk cave. Burned bones and microscopic ash in the dirt suggests fire frequently burned there, apparently under the control of our ancestor Homo erectus, researchers said. (AP Photo/courtesy of Michael Chazen)

EMBARGOED UNTIL 3 P.M. EDT ON MONDAY, APRIL 2, 2012 - In an undated photo provided by Michael Chazen, an unidentified worker takes samples at Wonderwerk cave in South Africa. Scientists said Monday, April 2, 2012 that they've found the earliest firm evidence of human ancestors using fire: material about 1 million years old in Wonderwerk cave. Burned bones and microscopic ash in the dirt suggests fire frequently burned there, apparently under the control of our ancestor Homo erectus, researchers said. (AP Photo/courtesy of Michael Chazan)

NEW YORK (AP) ? When did our ancestors first use fire? That's been a long-running debate, and now a new study concludes the earliest firm evidence comes from about 1 million years ago in a South African cave.

The ash and burnt bone samples found there suggest fires frequently burned in that spot, researchers said Monday.

Over the years, some experts have cited evidence of fire from as long as 1.5 million years ago, and some have argued it was used even earlier, a key step toward evolution of a larger brain. It's a tricky issue. Even if you find evidence of an ancient blaze, how do you know it wasn't just a wildfire?

The new research makes "a pretty strong case" for the site in South Africa's Wonderwerk Cave, said Francesco Berna of Boston University, who presents the work with colleagues in the Proceedings of the National Academy of Sciences.

One expert said the new finding should be considered together with a previous discovery nearby, of about the same age. Burnt bones also have been found in the Swartkrans cave, not far from the new site, and the combination makes a stronger case than either one alone, said Anne Skinner of Williams College in Williamstown, Mass., who was not involved in the new study.

Another expert unconnected with the work, Wil Roebroeks of Leiden University in The Netherlands, said by email that while the new research does not provide "rock solid" evidence, it suggests our ancestors probably did use fire there at that time.

The ancestors probably brought burning material from natural blazes into the cave to establish the fires, said Michael Chazan of the University of Toronto, a study author. Stone tools at the site suggest the ancestors were Homo erectus, a species known from as early as about 2 million years ago.

The scientists didn't find signs of fire preparation, like a hearth or a deep pit. But Berna said it's unlikely the fires were simply natural blazes, such as from lightning strikes.

That's because the evidence shows repeated fires burned deep inside the cave, he said. The cave entrance is almost 100 feet away, and because of changes in the cave over the past 1 million years, the entrance was apparently even farther away when the fires burned, he said. In contrast, he said, the bones at Swartkrans could have been burned by a natural fire in the open before winding up in that cave.

The scientists also found no sign that the Wonderwerk cave fires were ignited by spontaneous combustion of bat guano, which they called a rare but documented event.

Berna and colleagues describe animal bones that show discoloring and a chemical signature of being heated. They also report microscopic bits of ash in excavated dirt from the cave, indicating burning of light material like leaves, grasses and twigs. And they found evidence of heating in samples of fractured stone.

Several lines of evidence suggest the material was heated within the cave rather than blown or washed in from outside.

It's not clear what the fires were used for. While the burnt bones suggest cooking, the ancestors might have eaten the meat raw and tossed the bones into the fire, Berna noted. Other possible uses might be warmth, light and protection from wild animals, he said.

In a statement to The Associated Press, Roebroeks and Paola Villa of the University of the Witwatersrand in Johannesburg, South Africa, and the University of Colorado Museum in Boulder, said that while the new study probably demonstrates use of fire, they'd like to see signs of preparations like a hearth to be sure.

In any case, they said, the work does not show that human ancestors were using fire regularly throughout their range that long ago. In a paper published last year, they traced such habitual use of fire to about 400,000 years ago.

Berna said researchers will return to the Wonderwerk cave this summer and pursue hints that fires were used there even earlier than their paper suggests.

___

Online:

Journal website: http://www.pnas.org

Wonderwerk Cave information: http://bit.ly/H4sDS4

___

Malcolm Ritter can be followed at http://www.twitter.com/malcolmritter

Associated Press

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Long-Term Estrogen Therapy Does Up Breast Cancer Risk: Study

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Samsung throws in free extended battery with VZW Galaxy Nexus, applies to new purchases only

Samsung must be keenly aware that the Galaxy Nexus' battery life takes a hit on Verizon's LTE network: for a limited time, the outfit's throwing in a free 2,100mAh extended battery for first-time buyers (sorry, current Nexus owners are out of luck). To take advantage of the promotion, you'll have to purchase it through Samsung Direct (link below), which means you'll be paying $300 for the device and agreeing to a two-year contract. As Android and Me notes, though, you'd save quite a bit of money picking up the VZW Nexus and accompanying battery pack at Amazon for a combined $134. Suffice to say, then, this isn't a stellar deal, but those of you who disagree can avail yourselves through May 10, or while supplies last.

Samsung throws in free extended battery with VZW Galaxy Nexus, applies to new purchases only originally appeared on Engadget on Mon, 02 Apr 2012 11:21:00 EDT. Please see our terms for use of feeds.

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Niners Nation :: 2012 NFL Mock Draft: Should The 49ers Trade Up?

We all know NFL Mock Drafts have a relatively limited value when it comes to projecting the future. In reality, mock drafts are meant more as simply tools for generating discussion. When you talk about a team like the 49ers that is down at the 30th pick of the first round, it makes them even less valuable for predictive purposes.

At the same time, we can still use them to get a better handle on what we think the 49ers might do. A lot of people try and project out how the front office will handle the draft, but as we have seen just in free agency, the 49ers are rather unpredictable. When we think they are going to zig, they zag. I have to think it will play out the same way in the draft, which means I have no idea how it will play out.

Mocking the Draft has a variety of writers put together mock drafts, and Brad Wells from Stampede Blue put together this one, which features a 49ers trade up. Brad has the 49ers trading their first and second round picks to the Steelers to move up in the first round and draft highly touted offensive lineman Cordy Glenn.

I spoke with Brad a few days ago and the 49ers draft came up. In discussing the 49ers options, I told him my gut was telling me the 49ers would deal from their first round pick. I didn't provide specifics on where they might trade, but I discussed needs with him and he responded accordingly. While I think a deal down to get a future pick is more likely, a trade up would not surprise me either if the 49ers think there is a guy worthing making such a move.

At the same time, the 49ers have made it very clear they will not overpay beyond their pre-determined value of an asset. They were able to make some moves last year (making separate trades to net Colin Kaepernick and Daniel Kilgore), so they can get deals done even with such a firm handle on value.

We can't really predict a trade, but how high could the 49ers potentially move if they had an eye on somebody in the first round? In a perfect world I would love to see the 49ers land Stanford guard David DeCastro, but this is far from a perfect world. He struggled a bit trying to show some center skills at his Pro Day, but as a guard he has been lights out throughout the draft process. But that doesn't mean the 49ers can't land another solid guard a little lower down if they feel so compelled.

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