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Responding to accusations of improper procedures, $ 3 billion research fund cancer Texas agreed to re -consider marketing a controversial $ 20 million award made in March for two institutions Houston. But it is unclear whether the plan will satisfy the critics, who ask a rigorous scientific review.

Meanwhile, according to emails obtained by a newspaper in Texas, a Nobel scientist who resigned in part to its price on concerns about the grant was forced to leave after he complained that the exams had become politicized.

The grant of the Institute of Prevention and Cancer Research of Texas (CPRIT) provides $ 20 million in one year to be split between Rice University and the University of Texas MD Anderson Cancer Center, who split-up of the lion to $ 18 million of his Institute of applied science Cancer (IACS). CPRIT Scientific Director, Alfred Gilman, announced earlier this month that he resign in part because he believes IACS, which plans to discover and develop drugs, is a research program "disguise [d]" the marketing to avoid scientific scrutiny. Scientific Review Board CPRIT shared these concerns.

Other questions about the allocation process have since come: Some members of the review of the marketing of CPRIT Council, which approved the granting of the incubator, have links with the rice or MD Anderson, for example. And from MD Anderson does not go through the office of the Provost of the University, which looks at potential conflicts of interest and have identified one in this case, because the lead researcher Lynda Chin is married to MD Anderson President Ronald DePinho. Critics allege that CPRIT and MD Anderson bypassed normal procedures.

Yesterday DePinho CPRIT sent a letter calling the allegations "inaccurate" and "false," but said it is "understandable" why scientists would be involved "in the absence of all the facts." The letter says MD Anderson is ready to submit its proposal for a "reconsideration." But the letter denies that the grant must go through the provost MD Anderson. Because it is a business plan, the proposal will be considered by "business affairs" department of MD Anderson, said the letter.

CPRIT Executive Director William Gimson wrote back the same day DePinho that CPRIT accepts the offer to re-examine the IACS part of the proposal of the incubator. (He refused the offer of MD Anderson to delay funding for a year, because it would be incompatible with CPRIT policies.) The letter also indicates that, in accordance with the incubator Request for Applications (RFA) has approved the last year by the Board CPRIT, the proposal will be considered by the review of the marketing CPRIT board. At the same time, Gimson wrote, "the incubator RFA is designed for commercial and any proposal must comply with this criterion."

What is not clear is whether the marketing examiners see the IACS project in the same way the scientific critics. They argue that because IACS objectives such as the study of "target biology" and did not identify the products or business, it is about marketing, not on science. Depending on how soon MD Anderson resubmits its proposal, the board exam marketing could make a decision before the next meeting of CPRIT board in July.

The Gilman concerns about the review process CPRIT led to pressure from, according to an online report today The Dallas Morning News . The article cites April 1 Gilman email to colleagues in which he said Gimson told him to resign because the board CPRIT "has no faith in your ability to do your job." Gilman wrote that he replied that "I will not resign, they would need to fire me."

More from the article:

The resignation request by Bill Gimson, executive director of the Institute of Prevention and Cancer Research of Texas, or CPRIT is came after Gilman wrote four pages letter in which he warned that "political considerations" should not be held to decide how public dollars should CPRIT award.

E-mail and letters Gilman were among hundreds of pages of documents published by CPRIT in response to a public records request by The Dallas Morning News. Reached for comment this morning, Gilman declined to answer questions.

Dozens of emails focus on Gilman position that the system of CPRIT "peer review" in which out-of-state scientific review applications to avoid potential conflicts of interest, is attacked by enemies, including some members of the monitoring committee agency that Gilman called "people really badly."

The researchers reacted with mixed feelings to the National Institutes of Health (NIH) plans to reorganize its great clinical prices to fit the mission its new center of translational science.

The program translational scientific and clinical Price (CSTC), a budget of $ 461 million in 2012, grant funds of several million dollars that support clinical research in 60 major academic medical centers. NIH has created a lot of anxiety in the CSTC community when he decided in late 2010 to move this flagship program of another center proposed at the National Center for the Advancement of Translational Sciences (NCATS), which aims to eliminate bottlenecks, throttling drug development.

A big concern was that the new supervisors to NCATS have no interest in continuing the CSEC support for community engagement and other aspects of medicine that do not concern the therapeutic development. They are not reassured when NCATS Acting Director Thomas Insel said that the centers would "evolve".

Anxious got some relief Friday when NIH issued a Request for Applications (RFA) for CTSAs renewal. search categories such as research and community epidemiology are still listed as potential activities CSEC. "The full spectrum of translational research is clearly included," says Lloyd Michener, who heads a community research center that is part of the CSTC from Duke University in Durham, North Carolina. At the same time, the proposals should not include as much specific activities as before, suggesting that this CTSAs person can focus on their strengths, said Henry Ginsberg, director of CSTC Columbia University and co-Chair of the Executive Committee CTSA Consortium.

in another indication that the agency does not grow drastically change NIH says it will seek the advice of a report from the Institute of medicine requested by Congress, due out next summer .

However, the FRG has budgetary implications: He says that the awards will now be adjusted to correspond to 3% of the overall NIH funding of an institution It will probably mean reductions for some and larger budgets. for the others. (Minimum $ 4 million A budget should protect small institutions have eviscerated programs.) NIH plans to withhold funds for a later competition, which will support the roles of CTSAs in a national network. "We do not know if all NCATS wants to achieve can be accomplished in the same total budget of the bottom line we have now," says Ginsberg.

Letters of Intent for the RFA are due on 10 December.

A seemingly small mistake in an article The New England Journal of Medicine ( NEJM ) landed a Danish physician and researcher in hot water last month after a German company threatened to sue for potential losses that could run into the millions of dollars. The exchange prompted consternation media in Denmark about whether academic freedom was censored, but the researcher Anders Perner of Copenhagen University Hospital has corrected the error, which occurred in the publication of a study of a drug widely used to prevent shock and avoided a lawsuit. Still, the episode has shone a light on a therapy that some researchers say may do more harm than good, despite its widespread use.

The question is hydroxyethyl starch (HES), a synthetic derivative of ordinary starch that has been used worldwide for decades to avoid shock in patients who have lost large amounts of blood. It is also used to treat patients with sepsis, the blood leaking out of their hair. "HES binds liquid, and the idea is that it continues the volume of blood," says Tobias Welte, a pulmonologist at the Hannover Medical School in Germany, who studied the compound.

27 June Perner
published a randomized clinical trial in NEJM who compared HES effects was in septic patients to treatment with an alternative called acetate Ringer. the results are not good for HES: After 0 days, 201 of the 398 patients in the HES group were dead, against 172 of the 400 patients in the group treated with acetate Ringer patients treated with HES were also more likely to need therapy. renal replacement and suffer a severe hemorrhage. the study was "well designed and well conducted," said Greg Martin, an expert in critical care medicine at Emory University school of medicine in Atlanta. = "# t = articletop">

On July 9, however, Perner received an email from the German pharmaceutical company Fresenius Kabi, one of the largest manufacturers of HES, saying that in NEJM article he had misidentified the compound used in the study. Perner had used Tetraspan, produced by B. Braun Melsungen, Germany, and often described as HES 130 / 0.42. (The first number gives the molecular weight of the chemical, the second is an indication of the number of hydroxyethyl starch in.) While section names methods of society and drugs, it is called HES 130 / 0.4 in the original article and its title. These are the specifications of the product HES Fresenius, Voluven.

The e-mail, Perner says, included a threat by Fresenius to take legal action to recover the financial losses of the company would suffer because of misinformation. In a market worth billions which could be a lot of money, says Welte. Perner says Fresenius also demanded an explicit declaration that the first version of the document was incorrect.

Perner and NEJM changed the online version accordingly and Fresenius said it's the end of the story. "Our goal was to have the scientific misinformation in the title and text of the article in NEJM corrected," wrote a company spokesperson in an email. "This is . happened if we see no need for action "

Fresenius said his product is different from that used Perner not only in the report hydroxyethyl, but in other ways as well; for example, contrasted with the test compound in the test, it was not produced using potato starch.

But Perner maintains it was not a error, claiming that the differences are inconsequential, and the data of the study are likely to apply to Voluven well. the change is minimal compared hydroxyethyl and unlikely to affect the drug action he argued. "We rounded up to 0.4 because the product lines HES is less relevant details," he said, stressing that the hydroxyethyl ratio is 0.4 to 0.44 in Tetraspan and 0.38 to 0.45 Voluven. "Paper is more accurate now," he admits, "but from a scientific point of view, I think it makes no difference." Welte agrees. "For all practical purposes, these compounds are identical. If you do a test with aspirin, you should not write if you used the drug produced by Bayer or anyone else either," he said.

The debate on security and the effectiveness of various forms of HES has been ongoing for some time. Welte was involved in a 08 study, also published in NEJM , which concluded that HES solutions should be avoided "until the end of the long-term studies with a sufficient number of patients show that HES solution is particularly safe in critically ill patients. "this study unused another compound (HES 0 / 0.5)," but you can take the data from the new study on top of ours and they are almost identical, "says Welte.

HES compounds were first developed by Fresenius in 1974, and others soon followed. Although the compounds have received regulatory approval in the United States and throughout Europe, Perner argues that their safety has not been assessed adequately by modern standards. "When side effects occurred, companies have made new smaller molecules, but launched on the back of products older, "he said. Others share his concern. "For me, there is sufficient evidence of adverse effects with starch solutions in sepsis to restrict the use of all starches until additional safety and efficacy data are available" said Martin. regulators ignored evidence of potential side effects and failed to act, says Welte.

Although there has been concern about the compounds since 01, benefit analysis risk years remained positive, the regulatory body of the German BfArM medicine said in a statement to science Insider. the new study results from Perner are being evaluated, a spokesman the agency said, but no decision will likely be made until the results of another clinical trial, expected in August, are presented. the study, led by John Myburgh at the George Institute for global Health in Sydney in Australia, the compound of Fresenius

Most experimental cancer drugs never make it to market because they do not contribute enough people in early clinical trials. But even in the "failure" of drug trials, researchers may find that some patients saw their tumors shrink dramatically. As it is not known why some react, but most do not, researchers generally shake head and move on. But researchers now report that by sequencing the entire genome of the tumor of a patient outliers, they learned why her cancer disappeared when she took an experimental drug that did not help others. This drug has a new lease on life with this cancer, and these tests can help revive other drugs against cancer that have shown promise in laboratory studies, but first failed in clinical trials.

Researchers at Memorial Sloan Kettering Cancer Center (MSKCC) in New York have been intrigued by the case of a woman with metastatic bladder cancer whose tumors disappeared after she received a drug, called everolimus, which targets a protein involved in cell growth known as the mTORC1. Most patients in the trial are not helped by drugs and it was abandoned as a single agent for bladder cancer. But this patient has been cancer-free for 2.5 years, a "result quite unprecedented" for this cancer that is resistant to chemotherapy, says doctor-researcher David Solit of MSKCC and Weill Cornell Medical College in New York.

The group Solit tested the women's tumors for mutations in a few genes in the mTORC1 pathway that could explain the sensitivity of the tumor, but found nothing. So, in collaboration with bioinformatics Barry Taylor's lab at the University of California, San Francisco, the group Solit sent a sample of the woman's tumor to a commercial laboratory for whole genome sequencing.

By comparing the genome of the tumor to normal DNA of women, the researchers found mutations in two genes, NF2 and TSC1 , the laboratory studies have also suggested are in the path of mTORC1. Mutations in TSC1 but not NF2 , also turned in several other samples of bladder cancer. Although TSC1 ( tuberous sclerosis 1 ) has not been on the radar of scientists, it was logical that this gene could be involved: People born with TSC1 mutation later develop benign tumors. The researchers then looked TSC1 mutations in 13 other patients in the same drug trials failed. Four whose tumors had shrunk mutations in TSC1 , but only one of the nine who did not respond had the change, the researchers report online today in Science .

Solit and others plan to screen patients with bladder cancer who have TSC1 mutation in their tumors so they can continue the trial everolimus and other mTORC1 drugs targeted in these patients. "Now we have a clear path forward," said Solit. And he thinks that the same approach can be used in other clinical trials. "This will change the way we view these outliers" said Solit . While researchers already knew that some drugs against cancer work only on patients with specific mutations in their tumors, whole genome sequencing could help identify more such genetic changes, he said.

"This is a great story," says cancer researcher José Baselga from the Massachusetts General Hospital in Boston. Baselga, who conducted a clinical trial of everolimus in breast cancer, now expected to test for patients TSC1 mutations to see if they explain why some responded better than others. the study also shows that the search for gene sensitivity to drugs will require more than testing for a tumor only a few candidates, Baselga said. "We probably go further" and sequence whole genomes, he said.

The discovery that the cell development is not a one way street won the Nobel Prize this year in physiology or medicine. John B. Gurdon, a developmental biologist at the Wellcome Trust / Cancer Research UK Gurdon Institute at the University of Cambridge in the UK and Shinya Yamanaka, a researcher on stem cells at Kyoto University in Japan and the Gladstone Institute at the University of California, San Francisco, won the prize for their discovery that mature cells can be reprogrammed to resemble versatile cells of a very early embryo. These so-called pluripotent cells have the ability to become any of the body's tissues. The work of the pair that connects two eras of modern biology, "revolutionized our understanding of how cells and organisms develop," the Nobel Committee in its announcement attribution.

The ability to reprogram adult cells allowed the researchers to study certain diseases in new ways and raises the possibility of one day becoming replacement tissue or even organs in the laboratory. "I think everyone who works on developmental biology and on the understanding of disease mechanisms will applaud these excellent choices and clear to the Nobel Prize," said John Hardy, a neuroscientist at University College London. "The work countless laboratories build on the breakthroughs they have pioneered. "

In normal development, the mature cells their pluripotent state in various specialized cell type-a neuron, muscle cell or a skin cell, for example. For many years, development biologists thought that the cellular maturation process was irreversible. In 1962, however, John Gurdon, working at Oxford University, has shown that under the right conditions, an adult cell nucleus could become young again development. He replaced the nucleus of a frog's egg with a nucleus taken from a cell in the intestine of a tadpole. In some cases, the egg cell was able to "reprogram" the DNA in the nucleus and the tadpole egg cell developed into an adult frog the first animal cloned from mature cells ^* . Other researchers built on the findings of Gurdon, the most famous of the team that cloned Dolly the sheep using a similar feat of nuclear transplantation. This breakthrough has shown that mammalian cells may undergo the same transformation of immature to mature.

More than four decades later, Shinya Yamanaka showed that an egg cell is not necessary to reprogram the DNA of a cell pluripotency. Working with mouse cells, Yamanaka and his colleagues found that adding extra copies of four genes to skin cells growing in a lab dish, they could induce the cells to act like embryonic stem (ES ) cells, pluripotent cells from early embryos. A few years later, Yamanaka and other teams have shown that a similar technique could work on human cells. This allowed scientists to establish stable growth of cell populations from patients with diseases such as amyotrophic lateral sclerosis (ALS). Researchers can study these cells, called induced pluripotent stem (iPS), for an overview of the disease. In the case of ALS, they can encourage them to become muscle and nerve cells that mimic the problems seen in people with the condition. Yamanaka, who originally trained as an orthopedic surgeon, welcomed the Nobel honor with a note of caution about the speed, it could provide medical benefits. "I feel a great joy, but at the same time a great responsibility. The iPS technology is new and actually we have not been able to apply these findings to develop new therapies or medication. I think we need further research to make a contribution to society as soon as possible. "

Yamanaka was also welcomed because it gives researchers a potential alternative to human ES cells, which were ethically and politically controversial given their source. scientists are still working to understand exactly how the reprogrammed cells by adding genes differ from pluripotent cells found in embryos, and how these differences may affect how cells . can be used

Gurdon issued a statement outlining how the research of two scientists had left the basic science in medicine: "I am extremely honored to have achieved this spectacular recognition, and very happy to be due to receive with Shinya Yamanaka, whose work has brought the whole field within the realistic expectation of therapeutic benefits. ... It is particularly nice to see how pure basic research, originally aimed at testing the genetic identity of different cell types in the body, found have clear human health prospects. "

At the press conference at Kyoto University today, Yamanaka said he could not have accomplished his work without the financial support it received from the country." I really feel that Japan is receiving the award. "in 09, he and Gurdon shared the prize Albert Lasker Basic Medical Research

More background information of Science and science :. Now

• Rewrite the cells their own destiny (one of science [1945024InsightsdelaDécenniedel'])
• Yamanaka initial meeting announcement in 06, covered by science NOW
• First publications in 07 describing ways to create induced pluripotent stem cells using mouse cells, as covered by science NOW profile
• 08 science Yamanaka
• First demonstration that induced pluripotent stem cells can be created using human cells, as covered by science NOW
• science [1945024s'] 08 Breakthrough of the year: reprogramming cells
• (Related video Discovery of the year and reference web links associated with the reprogramming of cells)
• 2010 article on how reprogrammed cells help researchers study various diseases ( science podcast on the same subject)