Jail death of Delhi rape suspect sparks criticism

The mother of Ram Singh, the man accused of driving the bus on which a 23-year-old student was gang raped in December 2012, cries as she speaks to journalists outside the family's home in New Delhi, India, Monday, March 11, 2013. Indian police confirmed that Ram Singh, one of the men on trial for his alleged involvement in the gang rape and fatal beating of a woman aboard a New Delhi bus committed suicide in an Indian jail Monday, but his lawyer and family allege he was killed. (AP Photo/Manish Swarup) INDIA OUT

The mother of Ram Singh, the man accused of driving the bus on which a 23-year-old student was gang raped in December 2012, cries as she speaks to journalists outside the family's home in New Delhi, India, Monday, March 11, 2013. Indian police confirmed that Ram Singh, one of the men on trial for his alleged involvement in the gang rape and fatal beating of a woman aboard a New Delhi bus committed suicide in an Indian jail Monday, but his lawyer and family allege he was killed. (AP Photo/Manish Swarup) INDIA OUT

Mangelal Singh, the father of Ram Singh, the man accused of driving the bus on which a 23-year-old student was gang raped in December 2012, speaks to journalists as his mother weeps at the family's home in New Delhi, India, Monday, March 11, 2013. Indian police confirmed that Ram Singh, one of the men on trial for his alleged involvement in the gang rape and fatal beating of a woman aboard a New Delhi bus committed suicide in an Indian jail Monday, but his lawyer and family allege he was killed. (AP Photo/Manish Swarup) INDIA OUT

The mother of Ram Singh, the man accused of driving the bus on which a 23-year-old student was gang raped in December 2012, cries as she speaks to journalists inside the family's home in New Delhi, India, Monday, March 11, 2013. Indian police confirmed that Ram Singh, one of the men on trial for his alleged involvement in the gang rape and fatal beating of a woman aboard a New Delhi bus committed suicide in an Indian jail Monday, but his lawyer and family allege he was killed.(AP Photo/Manish Swarup) INDIA OUT

Unidentified relatives of Ram Singh, the man accused of driving the bus on which the 23-year-old student was gang raped in December 2012, walk with Singh's mother outside the family's home in New Delhi, India, Monday, March 11, 2013. Indian police confirmed that Ram Singh, one of the men on trial for his alleged involvement in the gang rape and fatal beating of a woman aboard a New Delhi bus committed suicide in an Indian jail Monday, but his lawyer and family allege he was killed.(AP Photo/Manish Swarup) INDIA OUT

V.K. Anand, lawyer of Ram Singh, a man on trial for the gang rape and fatal beating of a 23-year-old student aboard a New Delhi bus addresses the media outside a hospital in New Delhi, India, Monday, March 11, 2013. Singh committed suicide in an Indian jail Monday, police said, but his lawyer and family allege he was killed. (AP Photo/Saurabh Das)

NEW DELHI (AP) ? Whether he was killed or committed suicide, the jailhouse death Monday of a man on trial for the gang rape and fatal beating of a woman on a New Delhi bus has triggered shock at the enormous security failure at one of India's best-known prisons.

Authorities said Ram Singh, who was accused of driving the bus during the December attack, was in a cell with three other inmates at Tihar Jail in New Delhi when he hanged himself either with his own clothes or a bedsheet about 5:30 a.m.

"This is suicide," Home Minister Sushilkumar Shinde said.

His family and lawyer alleged foul play.

"There were no circumstances which could have led to Ram Singh committing suicide. There was no mental stress. He was very happy (about the trial's course)," his lawyer V.K. Anand said.

Singh, 33, had been among five defendants facing the death penalty if convicted of the rape attack, which horrified Indians and set off national protests. A sixth accused is being tried and jailed separately because he is a juvenile.

Singh's death in custody raised further questions about a criminal justice system already under attack for failing to protect the nation's women.

"It's a grave incident," said Shinde, the nation's top law enforcement official. "It's a major lapse."

The government had ordered a magistrate's inquiry and would take action after it received the report, he said.

Kiran Bedi, the former director of the jail and now an activist, said prison officials had a moral and legal obligation to ensure Singh's safety, and she expressed surprise that authorities had not been monitoring him with cameras.

"You are duty bound to protect the lives of the prisoners," she said.

Mamta Sharma, chair of India's National Commission for Women, said jail authorities had to explain Singh's death "despite so much protection, so much precaution, so much security."

"This means that even though he was accused of such a heinous crime, the jail administration did not keep a watchful eye on him," she said.

In 2011, 68 inmates in India killed themselves and another eight were killed by fellow inmates, according to India's National Crime Records Bureau. Tihar Jail is badly overcrowded and its 12,000 prisoners are nearly twice as many as it was designed to hold. Bedi said that despite that, the treatment of inmates has improved over the past two decades as the jail became more transparent, with volunteers constantly coming in and prisoners better educated about their rights.

Lawyers for the defendants had previously accused police of beating confessions out of the men.

Ram Singh's father, Mangelal Singh, said his son had been raped in prison by other inmates and had been repeatedly threatened by inmates and guards. Nevertheless, he said he visited his son four days ago and the man appeared fine and gave no hint of any despair that could drive him to take his own life.

Ram Singh also had a badly injured hand and would have been unable to hang himself, his father said, speaking from outside his small home in a New Delhi slum.

"Somebody has killed him," he said, saying he would push for a top-level investigation from India's Central Bureau of Investigation into the death.

Mangelal Singh said he feared for the safety of another son who is also on trial in the rape case.

Vivek Sharma, a lawyer representing another defendant, said he planned to ask the court to provide greater protection for his client.

"In a high-security jail, an occurrence of this kind is highly condemnable. It raises the serious issue of security of the accused persons in the jail," he said.

"My clients don't feel safe in Tihar Jail," said another defense lawyer, A.P. Singh.

Vimla Mehra, the director general of the jail, declined to say how Ram Singh could have managed to kill himself without alerting the other inmates in his small cell or the guards.

"The inquiry is being conducted and it would be premature to make any statement about the details of the incident," she said. Previous reports that Singh was under suicide watch were incorrect a police official said, speaking on condition of anonymity because he was not authorized to release details to the media.

The rape victim and a male friend were attacked after boarding the bus Dec. 16 as they tried to return home after watching a movie, police say. The six men, the only occupants of the private bus, beat the man with a metal bar, raped the woman and used the bar to inflict massive internal injuries to her, police say. The victims were dumped naked on the roadside, and the woman died from her injuries two weeks later in a Singapore hospital.

The attack set off nationwide protests about India's treatment of women and spurred the government to hurry through a package of laws to protect them.

The rape victim's family said that with such a strong case for the prosecution, they had expected Singh to be convicted and executed anyway.

"He knew he was going to get the death penalty, and so he took his life," the victim's brother told the Times Now TV.

Singh's death comes as the trial was deep underway. The four surviving defendants were briefly produced in court Monday.

K.T.S. Tulsi, a former top lawyer in the office of the solicitor general of India, said the suicide should have no impact on the trial, which is being held in a closed courtroom under a gag order that prevents news organizations from publishing details of the proceedings.

He said the death highlighted how important it is for society not to demonize people who have been accused but not convicted of crimes.

"It is so unfortunate that the media goes on to presume that they are guilty and goes on to condemn them and demonize them to an extent that it makes the life of these people not worth living," he said.

__

Associated Press reporters Manish Swarup and Ashok Sharma contributed to this report.

__

Follow Ravi Nessman on Twitter at www.twitter.com/ravinessman

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/3d281c11a96b4ad082fe88aa0db04305/Article_2013-03-11-India-Gang%20Rape/id-47c064d5e71c49a9a2cd374a94d04efc

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Venezuela's Hugo Chavez dies from cancer

CARACAS (Reuters) - Venezuelan President Hugo Chavez died on Tuesday after a two-year battle with cancer, ending 14 years of tumultuous rule that made the socialist leader a hero for the poor but a hate figure to his opponents.

The flamboyant 58-year-old had undergone four operations in Cuba for a cancer that was first detected in his pelvic region in mid-2011. His last surgery was on December 11 and he had not been seen in public since.

"We have just received the most tragic and awful information. At 4.25 p.m. (03.55 p.m. EST) today March the 5th, President Hugo Chavez Frias died," Vice President Nicolas Maduro announced in a televised address, his voice choking.

"It's a moment of deep pain," he said in the address, in which he appeared with senior ministers.

Chavez easily won a new six-year term at an election in October and his death will devastate millions of supporters who adored his charismatic style, anti-U.S. rhetoric and oil-financed policies that brought subsidized food and free health clinics to long-neglected slums.

Detractors, however, saw his one-man style, gleeful nationalizations and often harsh treatment of opponents as traits of an egotistical dictator whose misplaced statist economics wasted a historic bonanza of oil revenues.

Chavez's death opens the way for a new election that will test whether his socialist "revolution" can live on without his dominant personality at the helm.

VICE PRESIDENT MADURO FAVORITE TO WIN ELECTION

The vote should be held within 30 days and will likely pit Maduro against Henrique Capriles, the centrist opposition leader and state governor who lost to Chavez in the October election.

One recent opinion poll gave Maduro a strong lead.

Maduro is Chavez's preferred successor, enjoys support among many of the working class and could benefit from an inevitable surge of emotion in the coming days.

But the president's death could also trigger in-fighting in a leftist coalition that ranges from hard-left intellectuals to army officers and businessmen.

Venezuela has the world's largest oil reserves and some of the most heavily traded bonds, so investors will be highly sensitive to any signs of political instability.

A defeat for Maduro would bring major changes to Venezuela and could also upend its alliances with Latin American countries that have relied on Chavez's oil-funded largesse - most notably with communist-led Cuba, which recovered from financial ruin in the 1990s thanks largely to Chavez's aid.

Chavez was a garrulous figurehead for a global "anti-imperialist" alliance stretching as far as Belarus and Iran, and he will be sorely missed by anti-U.S. agitators.

Maduro said he would ensure the future of Chavez's work.

"We call on all compatriots to guarantee the peace. We, his civil and military compatriots, assume the legacy of Hugo Chavez," Maduro said.

"His project, his flags will be raised with honor and dignity. Commander, thank you, thank you so much, on behalf of these people whom you protected."

After the cancer was diagnosed in June 2011, Chavez went through several cycles of disappearing from the public eye for weeks at a time for treatment in Havana, only to return just as his adversaries were predicting his demise.

His health weakened severely just after his re-election on October 7, possibly due to his decision to campaign for a third term instead of stepping aside to focus on his recovery.

HUMBLE ROOTS

Chavez was raised by his grandmother in a house with a mud floor in rural Venezuela and evoked almost religious passion among poor supporters who loved his folksy charm, common touch and determination to put the nation's oil wealth at their service.

He burst onto the national scene by leading an attempted coup in 1992. It failed and he was imprisoned, but he then formed a political party on his release two years later and swept to power in a 1998 election.

It was the first of four presidential election victories, built on widespread support among the poor.

But Chavez alienated investors with waves of takeovers and strict currency controls, often bullied his rivals, and disappointed some followers who say he focused too much on ideological issues at the expense of day-to-day problems such power cuts, high inflation and crime.

Chavez built a highly centralized political system around his larger-than-life image and his tireless, micro-managing style created something close to a personality cult. He was particularly adept at exploiting divisions within a fractious opposition.

Chavez was briefly toppled in a coup in 2002, but returned triumphantly after his supporters took to the streets.

Apparently realizing the end was nigh, Chavez named Maduro his successor in December, just before his fourth operation, which followed months of grueling chemotherapy and radiation treatment.

MADURO'S PROSPECTS

On February 18, Chavez made a surprise pre-dawn return from Cuba and was taken to a ninth-floor suite of a military hospital in Caracas, surrounded by tight security.

The government published a handful of pictures of Chavez lying in a hospital bed while he was still in Havana - the only time he was seen since the latest surgery. Supporters held tearful vigils around the country to pray for his recovery.

Maduro, 50, will now focus on marshalling support from Chavez's diverse coalition, which includes leftist ideologues, businessmen, and radical armed groups called "colectivos".

Seeking to knock down rumors of tensions at the top of the ruling Socialist Party (PSUV), Maduro has stressed the unity between him and Diosdado Cabello, a powerful former army buddy of Chavez who heads the National Assembly.

Maduro is a former bus driver who rose from union activist to foreign minister and then to president-in-waiting. He won Chavez's confidence by meticulously echoing his vitriolic rhetoric and never airing a dissenting opinion.

Maduro has mimicked Chavez's rabble-rousing style in appearances in recent weeks, peppering speeches with insults aimed at adversaries.

Capriles, Maduro's likely opponent, is a 40-year-old governor of Miranda state who led a hard-fought campaign against Chavez in the October election.

There are clear ideological differences between the 20 or so groups in the opposition's Democratic Unity coalition and without their enmity to Chavez to bind them, the alliance could splinter.

Until recently, polls had shown Capriles would beat any of Chavez's proteges. But the naming of Maduro as Chavez's heir, and the outpouring of emotion that will accompany Chavez's death, have changed the picture.

A survey carried out by local pollster Hinterlaces between January 30 and February 9 gave Maduro 50-percent support, compared to 36 percent for Capriles.

Wall Street investors, who would like to see a more pro-business government in Caracas but have been keen buyers of high-yielding Venezuelan bonds, will be watching closely.

Tributes began pouring in from abroad.

U.N. Secretary-General Ban Ki-moon offered his "deepest condolences" to the people of Venezuela, while Russia's U.N. ambassador Vitaly Churkin told reporters:

"It's a tragedy. He was a great politician."

(Additional reporting by Girish Gupta, Mario Naranjo, Marianna Parraga and Patricia Velez in Caracas, David Adams in Miami, Louis Charbonneau and Daniel Bases in New York; Editing by Kieran Murray, Sandra Maler and David Brunnstrom)

Source: http://news.yahoo.com/venezuela-says-chavezs-breathing-problems-worsened-024327679.html

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Microsoft lapse cause outages in Azure service

REDMOND, Wash. Microsoft unwittingly let an online security certificate expire Friday, triggering a worldwide outage in an online service that stores data for a wide range of business customers.

The sloppy housekeeping represents an embarrassing lapse for Microsoft Corp. as the software maker tries to bring in more revenue from the storage service, which is called Azure.

The expired certificate is needed to properly run online services such as Azure which use an "https" protocol to block unauthorized users from accessing information.

Microsoft's failure to renew the security certificate apparently caused the Azure service to go down shortly before 4 p.m. EST Friday. The breakdown prevented Azure customers from accessing files kept in Microsoft's data centers.

The service still hadn't been fully restored more than four hours later, according to a post on Microsoft's website.

"We apologize for any inconvenience this causes our customers," Microsoft said.

Azure's failure illuminates the pitfalls of storing important information in remote data centers. Online storage, often called "cloud computing," is growing in appeal because it allows workers to pull up data, wherever they are, to an Internet-connected device.

Cloud computing's convenience can turn into a major aggravation when a problem crops up like the one that tripped up Microsoft Friday.

Source: http://feeds.cbsnews.com/~r/CBSNewsWebMD/~3/locm2BdnuPY/

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LG will debut Optimus F5 & Optimus F7 Android-powered LTE phones at Mobile World Congress

Mobile World Congress will be upon us next week and?LG has announced they will debut the Optimus F5 and Optimus F7 Android-powered LTE phones at the global venue. Both will have Android 4.1.2 (Jelly Bean) and be 4G LTE capable. Though the Optimus F5 will have a?1.2 GHz dual-core processor,?4.3-inch IPS screen (256 ppi resolution), 5-megapixel rear-facing camera plus 1.3-megapixel front-facing camera, with 8 GB internal storage plus supports up to 32 GB SD card storage. The?Optimus F7 will have a?1.5 GHz dual-core processor,?4.7-inch True IPS screen (312 ppi resolution- comparable to Apple?s Retina Display), 8-megapixel rear-facing camera plus 1.3-megapixel front-facing camera, with 8 GB internal storage plus supports up to 32 GB SD card storage.

We should have more info on the phones next week so try back. Check out the specs in the meantime?

Optimus F5 Key Specifications:

• Operating System: Android Jelly Bean 4.1.2
• Processor: 1.2 GHz Dual-Core
• Display: 4.3-inch IPS (256 ppi)
• Size: 126.0 x 64.5 x 9.3mm
• Memory: 8 GB / 1 GB RAM / microSD (up to 32GB)
• Camera: 5.0 MP AF / 1.3 MP
• Battery: 2,150mAh

Optimus F7 Key Specifications:

• Operating System: Android Jelly Bean 4.1.2
• Processor: 1.5 GHz Dual-Core
• Display: 4.7-inch True HD IPS (312 ppi)
• Size: 131.7 x 68.2 x 9.6mm
• Memory: 8 GB / 2 GB RAM /microSD (up to 32GB)
• Camera: 8.0 MP AF / 1.3 MP
• Battery: 2,540mAh

Source: http://www.androidtapp.com/lg-will-debut-optimus-f5-optimus-f7-android-powered-lte-phones-at-mobile-world-congress/

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[VIDEO]: NCAA & Olympic Wrestling Legend @DannyGable On Olympic Wrestling Decree

NCAA and Olympic Wrestling Legend Danny Gable weighed in on the decree that came out last week that wrestling will no longer be in the Olympics starting in 2020. ?I cried right away,? Gable said. ?I am a guy where wrestling was my best sport.? I?ve influenced a lot of people over the world and I?ve been able to help a lot of people over the world.? And because of that, the opportunity needs to be out there,? he explained.

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Source: http://radio.foxnews.com/2013/02/20/video-ncaa-olympic-wrestling-legend-dannygable-on-olympic-wrestling-decree/

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Hopkins scientists create method to personalize chemotherapy drug selection

Public release date: 14-Feb-2013
[ | E-mail | Share ]

Contact: Vanessa Wasta
wasta@jhmi.edu
410-614-2916
Johns Hopkins Medicine

Patient-specific cancer cell lines designed to predict chemotherapy sensitivity

In laboratory studies, scientists at the Johns Hopkins Kimmel Cancer Center have developed a way to personalize chemotherapy drug selection for cancer patients by using cell lines created from their own tumors.

If the technique is successful in further studies, it could replace current laboratory tests to optimize drug selection that have proven technically challenging, of limited use, and slow, the researchers say.

Oncologists typically choose anticancer drugs based on the affected organs' location and/or the appearance and activity of cancer cells when viewed under a microscope. Some companies offer commercial tests on surgically removed tumors using a small number of anticancer drugs. But Anirban Maitra, MBBS, professor of pathology and oncology at the Johns Hopkins University School of Medicine, says the tissue samples used in such tests may have been injured by anesthetic drugs or shipping to a lab, compromising test results.

By contrast, he says "our cell lines better and more accurately represent the tumors, and can be tested against any drug library in the world to see if the cancer is responsive."

The Johns Hopkins scientists developed their test-worthy cell lines by injecting human pancreatic and ovarian tumor cells into mice genetically engineered to favor tumor growth. Once tumors grew to one centimeter in diameter in the mice, the scientists transferred the tumors to culture flasks for additional studies and tests with anticancer drugs.

In one experiment, they successfully pinpointed the two anticancer drugs from among more than 3,000 that were the most effective in killing cells in one of the pancreatic cancer cell lines. A report on the success was published online Jan. 22 in the journal Clinical Cancer Research.

The new method was designed to overcome one of the central problems of growing human tumor cell lines in a laboratory dish -- namely the tendency of noncancerous cells in a tumor to overgrow cancerous ones, says James Eshleman, M.D., Ph.D., professor of pathology and oncology and associate director of the Molecular Diagnostics Laboratory at Johns Hopkins. As a consequence, it has not been possible to conventionally grow cell lines for some cancers. Still other cell lines, Eshleman says, don't reflect the full spectrum of disease.

To solve the problem of overcrowding by noncancerous cells, Maitra and Eshleman bred genetically engineered mice that replace the noncancerous cells with mouse cells that can be destroyed by chemicals, leaving pure human tumor cells for study.

"Our technique allows us to produce cell lines where they don't now exist, where more lines are needed, or where there is a particularly rare or biologically distinctive patient we want to study," says Eshleman.

In its proof of concept research, the Johns Hopkins team created three pancreatic ductal adenocarcinoma cell lines and one ovarian cancer cell line. They then tested one of the pancreatic cancer cell lines (called Panc502) against the Johns Hopkins Drug Library of 3,131 drugs, identifying tumor cells most responsive to the anticancer drugs digitoxin and nogalamycin.

For 30 days, they watched the effects in living mice of the two drugs and a control medicine on tumors grown from implanted cells derived from Panc502 and an additional pancreatic cell line, Panc410. They measured the size of tumors twice a week. Both drugs demonstrated more activity in reducing the tumor appearance and size in Panc502 than in Panc410, supporting the notion that the cell line technology may better predict sensitivity to the two drugs.

The investigators have given one type of their genetically engineered mice to The Jackson Laboratory in Bar Harbor, ME, a mouse genetics research facility, for breeding and distribution to other laboratories and are looking to partner with a company to distribute two other types.

###

Study co-authors were Hirohiko Kamiyama, Sherri Rauenzahn, Joong Sup Shim, Collins A. Karikari, Georg Feldmann, Li Hua, Mihoko Kamiyama, F. William Schuler, Ming-Tseh Lin, Robert M. Beaty, Balasubramanyam Karanam, Hong Liang, Michael E. Mullendore, Guanglan Mo, Manuel Hidalgo, Elizabeth Jaffee, Ralph H. Hruban, Richard B. S. Roden, Antonio Jimeno, and Jun O. Liu, of Hopkins; and H. A. Jinnah of Emory University School of Medicine in Atlanta.

The work was supported by the National Institutes of Health, National Cancer Institute (CA130938, CA62924 and CA122581), the Sol Goldman Pancreatic Cancer Research Center, the Stewart Trust Fund, the Lustgarten Foundation, the Mary Lou Wootton Pancreatic Pancreatic Cancer Research Fund, the Michael Rolfe Pancreatic Cancer Foundation and the HERA Foundation.

Rauenzahn, Maitra and Eshleman may receive royalty payments if the mice are licensed, and Eshleman is an advisory board member for Roche Molecular Diagnostics. These relationships have been disclosed and are under the management of the Johns Hopkins University School of Medicine Conflict of Interest Committee.

On the Web:

www.hopkinskimmelcancercenter.org

Photo of cell lines available upon request.

Johns Hopkins Kimmel Cancer Center
Office of Public Affairs Media Contacts:

Vanessa Wasta
410-614-2916; wasta@jhmi.edu

Amy Mone
410-614-2915, amone@jhmi.edu
February 14, 2013

---

[ | E-mail | Share ]

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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: 14-Feb-2013
[ | E-mail | Share ]

Contact: Vanessa Wasta
wasta@jhmi.edu
410-614-2916
Johns Hopkins Medicine

Patient-specific cancer cell lines designed to predict chemotherapy sensitivity

In laboratory studies, scientists at the Johns Hopkins Kimmel Cancer Center have developed a way to personalize chemotherapy drug selection for cancer patients by using cell lines created from their own tumors.

If the technique is successful in further studies, it could replace current laboratory tests to optimize drug selection that have proven technically challenging, of limited use, and slow, the researchers say.

Oncologists typically choose anticancer drugs based on the affected organs' location and/or the appearance and activity of cancer cells when viewed under a microscope. Some companies offer commercial tests on surgically removed tumors using a small number of anticancer drugs. But Anirban Maitra, MBBS, professor of pathology and oncology at the Johns Hopkins University School of Medicine, says the tissue samples used in such tests may have been injured by anesthetic drugs or shipping to a lab, compromising test results.

By contrast, he says "our cell lines better and more accurately represent the tumors, and can be tested against any drug library in the world to see if the cancer is responsive."

The Johns Hopkins scientists developed their test-worthy cell lines by injecting human pancreatic and ovarian tumor cells into mice genetically engineered to favor tumor growth. Once tumors grew to one centimeter in diameter in the mice, the scientists transferred the tumors to culture flasks for additional studies and tests with anticancer drugs.

In one experiment, they successfully pinpointed the two anticancer drugs from among more than 3,000 that were the most effective in killing cells in one of the pancreatic cancer cell lines. A report on the success was published online Jan. 22 in the journal Clinical Cancer Research.

The new method was designed to overcome one of the central problems of growing human tumor cell lines in a laboratory dish -- namely the tendency of noncancerous cells in a tumor to overgrow cancerous ones, says James Eshleman, M.D., Ph.D., professor of pathology and oncology and associate director of the Molecular Diagnostics Laboratory at Johns Hopkins. As a consequence, it has not been possible to conventionally grow cell lines for some cancers. Still other cell lines, Eshleman says, don't reflect the full spectrum of disease.

To solve the problem of overcrowding by noncancerous cells, Maitra and Eshleman bred genetically engineered mice that replace the noncancerous cells with mouse cells that can be destroyed by chemicals, leaving pure human tumor cells for study.

"Our technique allows us to produce cell lines where they don't now exist, where more lines are needed, or where there is a particularly rare or biologically distinctive patient we want to study," says Eshleman.

In its proof of concept research, the Johns Hopkins team created three pancreatic ductal adenocarcinoma cell lines and one ovarian cancer cell line. They then tested one of the pancreatic cancer cell lines (called Panc502) against the Johns Hopkins Drug Library of 3,131 drugs, identifying tumor cells most responsive to the anticancer drugs digitoxin and nogalamycin.

For 30 days, they watched the effects in living mice of the two drugs and a control medicine on tumors grown from implanted cells derived from Panc502 and an additional pancreatic cell line, Panc410. They measured the size of tumors twice a week. Both drugs demonstrated more activity in reducing the tumor appearance and size in Panc502 than in Panc410, supporting the notion that the cell line technology may better predict sensitivity to the two drugs.

The investigators have given one type of their genetically engineered mice to The Jackson Laboratory in Bar Harbor, ME, a mouse genetics research facility, for breeding and distribution to other laboratories and are looking to partner with a company to distribute two other types.

###

Study co-authors were Hirohiko Kamiyama, Sherri Rauenzahn, Joong Sup Shim, Collins A. Karikari, Georg Feldmann, Li Hua, Mihoko Kamiyama, F. William Schuler, Ming-Tseh Lin, Robert M. Beaty, Balasubramanyam Karanam, Hong Liang, Michael E. Mullendore, Guanglan Mo, Manuel Hidalgo, Elizabeth Jaffee, Ralph H. Hruban, Richard B. S. Roden, Antonio Jimeno, and Jun O. Liu, of Hopkins; and H. A. Jinnah of Emory University School of Medicine in Atlanta.

The work was supported by the National Institutes of Health, National Cancer Institute (CA130938, CA62924 and CA122581), the Sol Goldman Pancreatic Cancer Research Center, the Stewart Trust Fund, the Lustgarten Foundation, the Mary Lou Wootton Pancreatic Pancreatic Cancer Research Fund, the Michael Rolfe Pancreatic Cancer Foundation and the HERA Foundation.

Rauenzahn, Maitra and Eshleman may receive royalty payments if the mice are licensed, and Eshleman is an advisory board member for Roche Molecular Diagnostics. These relationships have been disclosed and are under the management of the Johns Hopkins University School of Medicine Conflict of Interest Committee.

On the Web:

www.hopkinskimmelcancercenter.org

Photo of cell lines available upon request.

Johns Hopkins Kimmel Cancer Center
Office of Public Affairs Media Contacts:

Vanessa Wasta
410-614-2916; wasta@jhmi.edu

Amy Mone
410-614-2915, amone@jhmi.edu
February 14, 2013

---

[ | E-mail | Share ]

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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.

Source: http://www.eurekalert.org/pub_releases/2013-02/jhm-hsc021413.php

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Evaluating evolutionary rates could shed light into functions of uncharacterized genes

Feb. 8, 2013 ? Genes that have roles in the same biological pathways change their rate of evolution in parallel, a finding that could be used to discover their functions, said a researcher at the University of Pittsburgh School of Medicine in the February issue of Genetics.

Humans have nearly 21,000 genes that make as many proteins, but the functions of most of those genes have not been fully determined, said lead investigator Nathan Clark, Ph.D., assistant professor of computational and systems biology at the Pitt School of Medicine. Knowing what a particular gene does could help unravel the workings of the body, foster understanding of disease processes and identify targets for new drugs.

"For our study, we took a close look at the way genes evolved between species and we found an interesting signature," he said. "Genes that perform biological functions together have similar evolutionary histories in that the rates at which they change parallel each other. This could allow us to identify partner genes that we might never have suspected to work together in biochemical pathways."

The researchers studied the evolving genomes of 18 yeast species and 22 mammalian species, looking particularly at genes that are involved in meiosis, a cell division process, and in DNA repair. They found parallel changes, such as acceleration or deceleration, in evolutionary rates among not only genes encoding proteins that physically interact with each other, but also among those that had no direct contact but still participated in meiosis or DNA repair pathways.

All genes mutate over time, which can be beneficial, harmful or meaningless. Some yeast species evolved a different method of reproduction and meiosis stopped as it was no longer essential for survival, Dr. Clark said. Through subsequent generations, the rate of change in the genes involved in making meiosis proteins accelerated, leading to deterioration of the unnecessary DNA sequences.

"A key question is: How important is that gene at that time?" he said. "If a species encounters a new challenge in its environment, the genes associated with it might have to evolve through subsequent generations in order to adapt that important pathway and ensure species survival."

By tracking those complementary rate changes, it could be possible to identify which genes participate in the same important pathways, providing clues to their function.

"In the future, a researcher studying a particular disease process might be able to plug in a couple of known genes in a database of evolutionary rate changes to find others that have a parallel history," Dr. Clark said. "That could provide new insight into the workings of the biological pathway of interest."

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The above story is reprinted from materials provided by University of Pittsburgh Schools of the Health Sciences.

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Journal Reference:

1. N. L. Clark, E. Alani, C. F. Aquadro. Evolutionary Rate Covariation in Meiotic Proteins Results from Fluctuating Evolutionary Pressure in Yeasts and Mammals. Genetics, 2012; 193 (2): 529 DOI: 10.1534/genetics.112.145979

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/top_environment/~3/rpQyH73T8hE/130208124747.htm

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