BUSM in vitro study identifies potential combination therapy for breast cancer

Public release date: 2-Jul-2012
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Contact: Jenny Eriksen Leary
jenny.eriksen@bmc.org
617-638-6841
Boston University Medical Center

(Boston) A study conducted at Boston University School of Medicine (BUSM) demonstrates an effective combination therapy for breast cancer cells in vitro. The findings, published in the July 2012 issue of Anticancer Research, raise the possibility of using this type of combination therapy for different forms of breast cancer, including those that develop resistance to chemotherapy and other treatments.

The study was led by researchers at the Boston University Cancer Center. Sibaji Sarkar, PhD, adjunct instructor of medicine at BUSM, is the study's corresponding author.

According to the Centers for Disease Control and Prevention, breast cancer is the most common cancer among women in the United States aside from non-melanoma skin cancer. Breast cancer also is one of the leading causes of cancer death among women of all races and Hispanic origin populations.

Triple negative breast cancer, which accounts for approximately 14 to 20 percent of all breast cancer cases, is a type of the disease that occurs when the cancer cells lack hormone receptors, including the receptor called HER-2, and typically will not respond to hormone and herceptin-based therapies. Triple negative breast cancer occurs more often in African-American women and is considered to be a more aggressive form of the disease with higher rates of recurrence and mortality than other forms of breast cancer.

"Cancer is like a car without brakes. Cell growth speeds up and it doesn't stop," said Sarkar. "When expressed, tumor suppressor genes, which work in a protective way to limit tumor growth, function as the brakes. They are not expressed in most cancers, causing the cancer to grow and potentially metastasize."

A major focus in the area of anti-cancer drug development is to find a way to re-express tumor suppressor genes so that they can help inhibit cancer cell growth. Some tumor suppressor genes are imprinted, meaning that from the two genes inherited from the mother and father, only one of the genes is functional. In cancer, both imprinted tumor suppressor genes may become non-functional and unable to stop tumor growth.

The researchers tested, in vitro, a combination therapy of an epigenetic drug with a protease inhibitor on breast cancer cell lines that are hormone responsive and breast cancer lines, like triple negative, that are not hormone responsive. They utilized histone deacetylases inhibitors (HDACi) and calpeptin, which inhibits calpain, a protein involved in the regulation of signaling proteins. Calpain inhibition is being studied as a potential treatment model for blood clots and other neurological diseases.

In this study, they found that the combination therapy both inhibited cell growth and increased cell death in both cancer cell lines by inducing cell cycle arrest and cell death. However, the mechanism of how the combination therapy stops the cells from growing was different. Cells in the hormone responsive line stopped the cell cycle in an earlier phase compared to the non-hormone responsive cells. In the triple negative breast cancer cell line, the inhibitors allowed an imprinted tumor suppressing gene, ARHI, to re-express, which helped stop the growth of the cancer cells and led to cancer cell death.

"The study data demonstrates that HDACi's bring back the brakes of the car, halting cell growth and promoting cell death," added Sarkar, who also is a faculty member at the Genome Science Institute at Boston University. "These results provide a model to investigate the re-expression of tumor suppressor genes, including imprinted genes, in many forms of breast cancer."

This study needs further investigation but raises the possibility of using this type of combination therapy for diverse types of breast cancers including those that are hormone refractory and develop drug resistance to conventional chemotherapy.

###

This study was funded by the American Cancer Society.

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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: 2-Jul-2012
[ | E-mail | Share ]

Contact: Jenny Eriksen Leary
jenny.eriksen@bmc.org
617-638-6841
Boston University Medical Center

(Boston) A study conducted at Boston University School of Medicine (BUSM) demonstrates an effective combination therapy for breast cancer cells in vitro. The findings, published in the July 2012 issue of Anticancer Research, raise the possibility of using this type of combination therapy for different forms of breast cancer, including those that develop resistance to chemotherapy and other treatments.

The study was led by researchers at the Boston University Cancer Center. Sibaji Sarkar, PhD, adjunct instructor of medicine at BUSM, is the study's corresponding author.

According to the Centers for Disease Control and Prevention, breast cancer is the most common cancer among women in the United States aside from non-melanoma skin cancer. Breast cancer also is one of the leading causes of cancer death among women of all races and Hispanic origin populations.

Triple negative breast cancer, which accounts for approximately 14 to 20 percent of all breast cancer cases, is a type of the disease that occurs when the cancer cells lack hormone receptors, including the receptor called HER-2, and typically will not respond to hormone and herceptin-based therapies. Triple negative breast cancer occurs more often in African-American women and is considered to be a more aggressive form of the disease with higher rates of recurrence and mortality than other forms of breast cancer.

"Cancer is like a car without brakes. Cell growth speeds up and it doesn't stop," said Sarkar. "When expressed, tumor suppressor genes, which work in a protective way to limit tumor growth, function as the brakes. They are not expressed in most cancers, causing the cancer to grow and potentially metastasize."

A major focus in the area of anti-cancer drug development is to find a way to re-express tumor suppressor genes so that they can help inhibit cancer cell growth. Some tumor suppressor genes are imprinted, meaning that from the two genes inherited from the mother and father, only one of the genes is functional. In cancer, both imprinted tumor suppressor genes may become non-functional and unable to stop tumor growth.

The researchers tested, in vitro, a combination therapy of an epigenetic drug with a protease inhibitor on breast cancer cell lines that are hormone responsive and breast cancer lines, like triple negative, that are not hormone responsive. They utilized histone deacetylases inhibitors (HDACi) and calpeptin, which inhibits calpain, a protein involved in the regulation of signaling proteins. Calpain inhibition is being studied as a potential treatment model for blood clots and other neurological diseases.

In this study, they found that the combination therapy both inhibited cell growth and increased cell death in both cancer cell lines by inducing cell cycle arrest and cell death. However, the mechanism of how the combination therapy stops the cells from growing was different. Cells in the hormone responsive line stopped the cell cycle in an earlier phase compared to the non-hormone responsive cells. In the triple negative breast cancer cell line, the inhibitors allowed an imprinted tumor suppressing gene, ARHI, to re-express, which helped stop the growth of the cancer cells and led to cancer cell death.

"The study data demonstrates that HDACi's bring back the brakes of the car, halting cell growth and promoting cell death," added Sarkar, who also is a faculty member at the Genome Science Institute at Boston University. "These results provide a model to investigate the re-expression of tumor suppressor genes, including imprinted genes, in many forms of breast cancer."

This study needs further investigation but raises the possibility of using this type of combination therapy for diverse types of breast cancers including those that are hormone refractory and develop drug resistance to conventional chemotherapy.

###

This study was funded by the American Cancer Society.

---

[ | 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.

Source: http://www.eurekalert.org/pub_releases/2012-07/bumc-biv070212.php

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Hyped plan to end Syria crisis falls flat

WASHINGTON (AP) ? The much-hyped plan to end Syria's misery and guide its transition to democracy appears to have fallen flat despite the endorsement of Western powers.

Russia's objections gutted the most stringent conditions on a potential interim leader in Damascus. The Syrian opposition quickly dismissed the proposal as a waste of time and with "no value on the ground."

The U.S. and its allies insist the plan will force Syrian President Bashar Assad from power. Russia disagrees and Assad is unlikely to acquiesce.

It all leaves U.N. envoy Kofi Annan's efforts to end 15 months of bloodshed no better off than before.

Western nations needed to win Russia's backing for the plan at an international conference Saturday in Geneva, so they dropped the demand that "those whose continued presence and participation would undermine the credibility of the transition and jeopardize stability and reconciliation" would be excluded from the process.

That was widely understood to mean Assad and much of his inner circle, and while the West insisted, Assad's main allies in Moscow resisted intensely.

As a result, the plan contains no criteria for excluding anyone from the transitional government and leaves its composition entirely up to the "mutual consent" of Assad administration and the fractured opposition. Both sides presumably have unlimited veto power over members of the interim government, which could prolong the stalemate and keep Assad in charge.

U.S. and Western officials acknowledge the possibility of that scenario. But they insist that the "mutual consent" language puts the opposition on equal footing with Assad in determining who will be part of the governing body.

Annan said he could not imagine that the Syrian people would choose anyone with blood on their hands to lead them.

Secretary of State Hillary Rodham Clinton, going further, said the plan requires Assad to leave because there is no chance he can meet the "mutual consent" standard.

"What we have done here is to strip away the fiction that he and those with blood on their hands can stay in power," she said.

Yet as Russian Foreign Minister Sergey Lavrov pointed out, the plan excludes no one. Nor does it give anyone without a vested interest any authority to suggest who might or might not be acceptable.

That's why Assad's foes are skeptical, at the very least.

"The country has been destroyed and they want us then to sit with the killer?" asked opposition figure Haitham Maleh.

Bassma Kodmani, a Paris-based spokeswoman for the main opposition group, the Syrian National Council (SNC), said the agreement was "ambiguous" and lacks a mechanism or timetable for implementation.

Western officials say they expect Russia and China, which have blocked U.N. action on Syria, to make the case to Assad that he needs to step down for the good of his country. They hope, as Clinton said Saturday, that Assad will "see the writing on the wall" and remove himself from the equation.

So far, though, neither has shown any inclination to back away from defending Assad.

Clinton and her Western counterparts will take the Annan plan to a meeting of the "Friends of Syria" group in Paris on Friday to get a broader endorsement of the deal. This, they hope, will raise the pressure on Russia and China to convince Assad of the need to get the transition started.

Should that fail and the process remain stalled, they intended to return to the U.N. Security Council for a resolution that would compel compliance.

The SNC said nearly 800 people have been killed in violence across the country in the past week and that more than 14,000 people have died in the 15-month-old uprising against Assad's rule.

There's an urgent need for a solution because the conflict is threatening to spill across borders after Syria shot down a warplane from neighboring Turkey, which responded by setting up anti-aircraft guns along the frontier.

___

EDITOR'S NOTE ? Matthew Lee covers international affairs and U.S. foreign policy for The Associated Press.

___

Online:

Clinton statement: http://tinyurl.com/7fjpj54

An AP News Analysis

Source: http://news.yahoo.com/analysis-plan-end-syria-crisis-falls-flat-174529569.html

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Pakistan: US drone strike kills 8 militants

DERA ISMAIL KHAN, Pakistan (AP) ? Pakistani intelligence officials say a U.S. drone strike has killed eight suspected militants in the North Waziristan tribal region near the Afghan border.

They say missiles fired from an unmanned drone struck a house in Dre Nishter village early Sunday. They spoke on condition of anonymity because they were not authorized to talk to the media.

The officials said the house was being used by militants loyal to commander Hafiz Gul Bahadur, and some foreigners were also among the dead.

The U.S. has criticized Pakistan for failing to crack down on fighters who stage attacks in Afghanistan and has stepped up drone attacks in the tribal region to combat them.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2012-07-01-AS-Pakistan/id-946f28bba58c46d7b88832a34db08b5c

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Syria conference leaves open Assad question

GENEVA (AP) ? An international conference on Saturday accepted a U.N.-brokered peace plan that calls for the creation of a transitional government in Syria, but at Russia's insistence the compromise agreement left the door open to Syria's president being part of it.

The U.S. backed away from insisting that the plan should explicitly call for President Bashar Assad to have no role in a new Syrian government, hoping the concession would encourage Russia to put greater pressure on its longtime ally to end the violent crackdown that the opposition says has claimed more than 14,000 lives.

But even with Russia's most explicit statement of support yet for a political transition in Syria, it is far from certain that the plan will have any real effect in curbing the violence. A key phrase in the agreement requires that the transitional governing body "shall be formed on the basis of mutual consent," effectively giving the present government and the opposition veto power over each other.

Syrian opposition figures immediately rejected any notion of sharing in a transition with Assad, though the agreement also requires security force chiefs and services to have the confidence of the people. Assad's government had no immediate reaction, but he has repeatedly said his government has a responsibility to eliminate terrorists and will not accept any non-Syrian model of governance.

U.S. Secretary of State Hillary Clinton insisted on Saturday that Assad would still have to go, saying it is now "incumbent on Russia and China to show Assad the writing on the wall" and help force his departure."

"There is a credible alternative to the Assad regime," she said. "What we have done here is to strip away the fiction that he and those with blood on their hands can stay in power."

Kofi Annan was appointed the special envoy in February, and in March he submitted a six-point peace plan that he said the Assad regime accepted. It led to the April 12 cease-fire agreement that failed to hold.

Moscow had refused to back a provision that would call for Assad to step aside, insisting that outsiders cannot order a political solution for Syria and accusing the West of ignoring the darker side of the Syrian opposition. The opposition has made clear it would not take part in a government in which Assad still held power.

Russian Foreign Minister Sergey Lavrov underlined that the plan does not require Assad's ouster, saying there is "no attempt in the document to impose on the Syrian people any type of transitional process."

Lavrov accused armed opposition groups in Syria of provoking the government to use force disproportionately. "We cannot say that the regime should simply withdraw its heavy artillery that it is shooting at armed citizens," he said, referring to one of the conditions that the U.N. had set for sending truce monitors to Syria. "Certain armed groups and those who sponsor them are always trying to provoke the spiraling violence."

Chinese Foreign Minister Yang Jiechi called for all sides to end to the violence "without attaching any conditions," but said that no one from the outside can make any legitimate decisions for the Syrian people.

More than a year into the uprising, Syria's opposition is still struggling to overcome infighting and inexperience, preventing the movement from gaining the traction it needs to instill confidence in its ability to govern.

The U.N. plan calls for establishing a transitional government of national unity, with full executive powers, that could include members of Assad's government and the opposition and other groups. It would oversee the drafting of a new constitution and elections.

Annan said following the Geneva talks that "it is for the people of Syria to come to a political agreement."

"I will doubt that the Syrians who have fought so hard to have independence ... will select people with blood on their hands to lead them," he said.

The envoy had earlier warned the permanent members of the U.N. Security Council ? Britain, China, France, Russia and the United States ? that if they fail to act at the talks hosted by the United Nations at its European headquarters in Geneva, they face an international crisis of "grave severity" that could spark violence across the region and provide a new front for terrorism.

"History is a somber judge and it will judge us all harshly, if we prove incapable of taking the right path today," he said.

Syria, verging on a full-blown civil war, has endured a particularly bloody week, with up to 125 people reported killed nationwide on Thursday alone.

The opposition's divisions are tied to issues at the heart of the revolution: Whether to seek dialogue with the regime and what ideology should guide a post-Assad Syria.

Rami Abdul-Rahman, director of the Britain-based Syrian Observatory for Human Rights, said following the agreement that "no member of the Syrian opposition will accept to be part of a transitional government while Assad is still in power."

"Assad's staying in power will mean the continuation of the bloodshed in Syria," he said.

Unlike Libya's National Transitional Council, which brought together most factions fighting Moammar Gadhafi's regime and was quickly recognized by much of the international community, Syria's opposition has no leadership on the ground.

Regime opponents in Syria are a diverse group, representing the country's ideological, sectarian and generational divide. They include dissidents who spent years in prison, tech-savvy activists in their 20s, former Marxists, Islamists and Paris-based intellectuals.

Communication among those abroad and those in the country is extremely difficult. Political activists in Syria are routinely rounded up and imprisoned. Many have gone into hiding, communicating only through Skype using fake names, and the country is largely sealed off to exiled dissidents and foreign journalists.

International tensions also heightened last week after Syria shot down a Turkish warplane, leading to Turkey setting up anti-aircraft guns on its border with its neighbor.

British Foreign Secretary William Hague noted on Saturday that U.N. Secretary-General Ban Ki-moon told diplomats a U.N. monitoring mission in Syria would have to be pulled back if no diplomatic solution was found.

The head of the struggling U.N. observer mission, Norwegian Maj. Gen. Robert Mood, has described the 300 monitors approved by the U.N. Security Council to enforce a failed April cease-fire as being largely confined to bureaucratic tasks and calling Syrians by phone because of the dangers on the ground. Their mandate expires on July 20.

"Ultimately, we want to stop the bloodshed in Syria. If that comes through political dialogue, we are willing to do that," said Khalid Saleh, a spokesman for the Syrian National Council, a coalition of Syrian opposition groups based in Istanbul, Turkey. "We are not willing to negotiate (with) Mr. Assad and those who have murdered Syrians. We are not going to negotiate unless they leave Syria."

Clinton said Thursday in Riga, Latvia, that all participants in the Geneva meeting, including Russia, were on board with the transition plan. She told reporters that the invitations made clear that representatives "were coming on the basis of (Annan's) transition plan."

The United Nations says violence in the country has worsened since a cease-fire deal in April, and the bloodshed appears to be taking on dangerous sectarian overtones, with growing numbers of Syrians targeted on account of their religion. The increasing militarization of both sides in the conflict has Syria heading toward civil war.

Source: http://news.yahoo.com/syria-conference-leaves-open-assad-173505185.html

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Video: Jindal discusses journalism?s future

A Second Take on Meeting the Press: From an up-close look at Rachel Maddow's sneakers to an in-depth look at Jon Krakauer's latest book ? it's all fair game in our "Meet the Press: Take Two" web extra. Log on Sundays to see David Gregory's post-show conversations with leading newsmakers, authors and roundtable guests. Videos are available on-demand by 12 p.m. ET on Sundays.

Source: http://www.msnbc.msn.com/id/3032608/vp/48032237#48032237

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Nikon J1 w/10-30mm & 16GB iPad 3 for $850 together [updated]

UPDATE (6/29/12 at 3pm ET): The price dropped by $50 since the original post: Adorama has a creative combined purchase promotion. You pay $850 $900 and you get both the Nikon J1 w/10-30mm & 16GB Apple iPad (3rd generation). Simply add the bundle to cart and proceed to checkout. There is no coupon code to enter. Each item goes for $500 individually, but if you buy them together, you save $150 $100. The iPad model is MC531ZM/A and the bundle also includes the iPad Camera Connection kit.

Source: http://cameradeals.1001noisycameras.com/2012/06/nikon-j1-w10-30mm-16gb-ipad-3-for-900-together.html

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Apple wins again: Court orders ban on US sales of Samsung Galaxy Nexus smartphone

For the second time in a matter of days, Apple was granted a temporary injunction by a US court banning sales of a Samsung mobile device - this time the Galaxy Nexus smartphone.

On Friday US judge Lucy Koh granted Apple a preliminary injunction against the sale of Samsung?s Galaxy Nexus smartphone. Last week the same judge handed down a ban on sales of Samsung?s Galaxy 10.1 Tab inside the US.

Apple and Samsung have been at each other?s throats since April last year, battling it out over alleged patent infringements in courts around the world. Apple claims that the Korean electronics maker ?slavishly? copied a number of features of its iPhone and iPad mobile devices in the design of its own products, such as the Galaxy tablet and Nexus smartphone. Samsung has hit back at Apple with patent-related accusations of its own.

Friday?s ruling in a California court centered on a lawsuit filed by Apple in February claiming Samsung infringed a patent relating to the Siri voice-activated virtual assistant found on the iPhone, specifically US Patent No. 8,086,604, for a ?universal interface for retrieval of information in a computer system.?

The Android-powered Galaxy Nexus, which was developed by Samsung and Google, hit the market late last year and is the search giant?s flagship smartphone.

Speaking during Friday?s ruling, Judge Koh said, ?Apple has made a clear showing that, in the absence of a preliminary injunction, it is likely to lose substantial market share in the smartphone market and to lose substantial downstream sales of future smartphone purchases and tag-along products.?

Friday?s injunction is subject to Apple paying a $96 million bond, substantially more than last week?s $2.6 million bond, but still peanuts to one of the world?s biggest companies. The purpose of the bond is to protect against damages suffered by Samsung if the ruling is later found to have been wrong.

The temporary injunction will at some point be the subject of a court trial, where it will either be made permanent or thrown out. As things stand today, Apple will be more than happy with the way things are progressing, while lawyers at Samsung will be looking at whether they have any chance of overturning Friday?s decision.

The road to smartphone dominance in a fast-growing market now worth billions of dollars is clearly a long, as well as costly, one.

[Source: Reuters]

Source: http://www.digitaltrends.com/mobile/apple-wins-again-court-orders-ban-on-us-sales-of-samsung-galaxy-nexus-smartphone/

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