Genome of Mysterious Extinct Human Reveals Brown-Eyed Girl.


The genome of a recently discovered branch of extinct humans known as the Denisovans that once interbred with us has been sequenced, scientists said .

Genetic analysis of the fossil revealed it apparently belonged to a little girl with dark skin, brown hair and brown eyes, researchers said. All in all, the scientists discovered about 100,000 recent changes in our genome that occurred after the split from the Denisovans. A number of these changes influence genes linked with brain function and nervous system development, leading to speculation that we may think differently from the Denisovans. Other changes are linked with the skin, eyes and teeth.

“This research will help [in] determining how it was that modern human populations came to expand dramatically in size as well as cultural complexity, while archaic humans eventually dwindled in numbers and became physically extinct,” said researcher Svante Pääbo at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

Future research may turn up other groups of extinct humans in Asia “in addition to Neanderthals and Denisovans,” Pääbo told LiveScience.

Although our species comprises the only humans left alive, our planet was once home to a variety of other human species. The Neanderthals were apparently our closest relatives, and the last of the other human lineages to vanish. [10 Mysteries of the First Humans]

However, scientists recently revealed another group of extinct humans once lived at the same time as ours. DNA from fossils unearthed in Denisova Cave in southern Siberia in 2008 revealed a lineage unlike us and closely related to Neanderthals. The precise age of the Denisovan material remains uncertain — anywhere from 30,000 to 80,000 years of age.

“The Denisovan genome is particularly close to my heart, because it was the first time that a new group of extinct humans was discovered and defined just from DNA sequence evidence and not from the morphology of bones,” Pääbo said.

Denisovan genes unzipped

Now, based on only a tiny sample of genetic material from a finger bone, scientists have sequenced the complete genome of the Denisovans (pronounced deh-NEESE-so-vans), as they are now called.

To make the most of what little genetic material they had, the researchers developed a technique that unzipped the double strands of DNA in the bone, doubling the amount of DNA they could analyze. This enabled them to sequence each position in the genome about 30 times over, generating an extremely thorough genome sequence. [See Photos of Denisovan Fossils]

“We have very few errors in the sequences, even less errors than we often have when you sequence a person today,” Pääbo said. “With just a few technical reservations, there is actually today then no difference in what we can learn genetically about a person that lived 50,000 years ago and from a person today, provided that we have well-enough preserved bones.”

Comparing the Denisovan genome with ours confirmed past research suggesting the extinct lineage once interbred with ours and lived in a vast range from Siberia to Southeast Asia. The Denisovans share more genes with people from Papua New Guinea than any other modern population studied.

In addition, more Denisovan genetic variants were found in Asia and South America than in European populations. However, this likely reflects interbreeding between modern humans and the Denisovans’ close relatives, the Neanderthals, rather than direct interbreeding with the Denisovans, researchers said.

Denisovans began to diverge from modern humans in terms of DNA sequences about 800,000 years ago. Among the genetic differences between Denisovans and modern humans are likely changes that “are essential for what made modern human history possible, the very rapid development of human technology and culture that allowed our species to become so numerous, spread around the whole world, and actually dominate large parts of the biosphere,” Pääbo said.

Eight of these genetic changes have to do with brain function and brain development, “the connectivity in the brain of synapses between nerve cells function, and some of them have to do with genes that, for example, can cause autism when these genes are mutated,” Pääbo added.

What makes humans special?

It makes a lot of sense to speculate that what makes us special in the world relative to the Denisovans and Neanderthals “is about connectivity in the brain,” Pääbo said. “Neanderthals had just as large brains as modern humans had — relative to body size, they even had a bit larger brains. Yet there is, of course, something special in my mind that happens with modern humans. It’s sort of this extremely rapid technological cultural development that comes, large societal systems, and so on. So it makes sense that, well, what pops up is sort of connectivity in the brain.”

The fact that differences are seen between modern humans and Denisovans in terms of autism-linked genes is especially interesting, because whole books have been written “suggesting that autism may affect sort of a trait in human cognition that is also crucial for modern humans, for how we put ourselves in the shoes of others, manipulate others, lie, develop politics and big societies and so on,” Pääbo said.

The genetic diversity suggested by this Denisovan sample was apparently quite low. This was probably not due to inbreeding, the researchers say — rather, their vast range suggests their population was initially quite small but grew quickly, without time for genetic diversity to increase as well.

“If future research of the Neanderthal genome shows that their population size changed over time in similar ways, it may well be that a single population expanding out of Africa gave rise to both the Denisovans and the Neanderthals,” Pääbo said.

Intriguingly, comparing the X chromosome, which is passed down by females, to the rest of the genome, which is passed down equally in males and females, revealed “there is substantially less Denisovan genetic material in New Guinea on the X chromosome than there is on the rest of the genome,”researcher David Reich at Harvard Medical School in Boston told LiveScience.

One possible explanation “is that the Denisovan gene flow into modern humans was mediated primarily by male Denisovans mixing with female modern humans,” Reich said. “Another possible explanation is that actually there was natural selection to remove genetic material on the X chromosome that came from Denisovans once that entered the modern human population, perhaps because it caused problems for the people who carried it.”

These current Denisovan findings have allowed the researchers to re-evaluate past analysis of the Neanderthal genome. They discovered modern humans in the eastern parts of Eurasia and Native Americans actually carry more Neanderthal genetic material than people in Europe, “even though the Neanderthals mostly lived in Europe, which is really, really interesting,” Reich said.

The researchers would now like to upgrade the Neanderthal genome to the quality seen with the Denisovan genome. The genetic techniques they used could also be employed in forensic investigations, and in analyzing other fossil DNA, said researcher Matthias Meyer, also at the Max Planck Institute for Evolutionary Anthropology.

Source:  Science.

 

Supersonic Flying Wing Nabs $100,000 from NASA.


An aircraft that resembles a four-point ninja star could go into supersonic mode by simply turning 90 degrees in midair. The unusual “flying wing” concept has won $100,000 in NASA funding to trying becoming a reality for future passenger jet travel.

The supersonic, bidirectional flying wing idea comes from a team headed by Ge-Chen Zha, an aerospace engineer at Florida State University. He said the fuel-efficient aircraft could reach supersonic speeds without the thunderclap sound produced by a sonic boom — a major factor that previously limited where the supersonic Concorde passenger jet could fly over populated land masses.

“I am hoping to develop an environmentally friendly and economically viable airplane for supersonic civil transport in the next 20 to 30 years,” Zha said. “Imagine flying from New York to Tokyo in four hours instead of 15 hours.”

The U.S. military’s B-2 Spirit stealth bomber that debuted in 1989 represents the only previously successful flying wing aircraft, even though experimental flying wings flew before then. Zha’s bidirectional flying wing kicks the general concept up a notch by essentially laying two flying wings on top of one another at a 90 degree angle, so that the aircraft faces one way for subsonic flight and rotates another way for supersonic flight. [Supersonic Biplane Design Stops Sonic Booms]

The midair transformation allows the aircraft to fly in its most fuel-efficient modes at both subsonic and supersonic speeds, Zha explained. Jet engines located on top of the aircraft in concept illustrations appear to rotate independently of the aircraft so that they can always point forward in flight.

Such midair spinning might sound unpleasant for people riding the aircraft. But a five-second rotation would only cause pilots and passengers to experience a “g-force” just one-tenth the force of gravity — less than what airline passengers experience during takeoff.

NASA liked the idea enough to give Zha and his colleagues a $100,000 grant from the Innovative Advanced Concepts program. But the U.S. space agency does not expect such funded concepts to fly for at least another 20 years or so.

“We are inventing the ways in which next-generation aircraft and spacecraft will change the world and inspiring Americans to take bold steps,” said Michael Gazarik, director of NASA’s Space Technology Program.

The bidirectional flying wing aircraft could also lead to the first supersonic drones soaring over the U.S. homeland or distant battlefields. Zha previously pitched the robotic military version to the U.S. Air Force at an unmanned aerial systems conference in 2009.

Both the U.S. government and aircraft manufacturers also have begun pushing for hypersonic aircraft capable of flying more than five times the speed of sound (Mach 5). Aerospace giant EADS displayed one passenger jet concept at the Paris Air Show in 2011, but aviation experts suggested a ticket to board the flight would cost at least $10,000.

The U.S. has already begun carrying out tests of unmanned hypersonic aircraft, but with mixed results. A U.S. Air Force test of the unmanned X-51A WaveRider ended prematurely when the aircraft plunged into the Pacific Ocean on Aug. 14.

Source: NASA

Genome Brings Ancient Girl to Life


In a stunning technical feat, an international team of scientists has sequenced the genome of an archaic Siberian girl 31 times over, using a new method that amplifies single strands of DNA. The sequencing is so complete that researchers have as sharp a picture of this ancient genome as they would of a living person’s, revealing, for example that the girl had brown eyes, hair, and skin. “No one thought we would have an archaic human genome of such quality,” says Matthias Meyer, a postdoc at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “Everyone was shocked by the counts. That includes me.”

That precision allows the team to compare the nuclear genome of this girl, who lived in Siberia’s Denisova Cave more than 50,000 years ago, directly to the genomes of living people, producing a “near-complete” catalog of the small number of genetic changes that make us different from the Denisovans, who were close relatives of Neandertals. “This is the genetic recipe for being a modern human,” says team leader Svante Pääbo, a paleogeneticist at the institute.

Ironically, this high-resolution genome means that the Denisovans, who are represented in the fossil record by only one tiny finger bone and two teeth, are much better known genetically than any other ancient human—including Neandertals, of which there are hundreds of specimens. The team confirms that the Denisovans interbred with the ancestors of some living humans and found that Denisovans had little genetic diversity, suggesting that their small population waned further as populations of modern humans expanded. “Meyer and the consortium have set up the field of ancient DNA to be revolutionized—again,” says Beth Shapiro, an evolutionary biologist at the University of California, Santa Cruz, who was not part of the team. Evolutionary geneticist Sarah Tishkoff of the University of Pennsylvania agrees: “It’s really going to move the field forward.”

Pääbo’s group first gave the field a jolt in May 2010 by reporting a low-coverage sequence (1.3 copies on average) of the composite nuclear genome from three Neandertals. They found that 1% to 4% of the DNA of Europeans and Asians, but not of Africans, was shared with Neandertals and concluded that modern humans interbred with Neandertals at low levels.

Just 7 months later, the same group published 1.9 copies on average of a nuclear genome from a girl’s pinky finger bone from Denisova Cave. They found she was neither a Neandertal nor a modern human—although bones of both species had been found in the cave—but a new lineage that they called Denisovan. The team found “Denisovan DNA” in some island Southeast Asians and concluded that their ancestors also interbred with the ancestors of Denisovans, probably in Asia.

But these genomes were too low quality to produce a reliable catalog of differences. Part of the problem was that ancient DNA is fragmentary, and most of it breaks down into single strands after it is extracted from bone.

Meyer’s breakthrough came in developing a method to start the sequencing process with single strands of DNA instead of double strands, as is usually done. By binding special molecules to the ends of a single strand, the ancient DNA was held in place while enzymes copied its sequence. The result was a sixfold to 22-fold increase in the amount of Denisovan DNA sequenced from a meager 10-milligram sample from the girl’s finger. The team was able to cover 99.9% of the mappable nucleotide positions in the genome at least once, and more than 92% of the sites at least 20 times, which is considered a benchmark for identifying sites reliably. About half of the 31 copies came from the girl’s mother and half from her father, producing a genome “of equivalent quality to a recent human genome,” says paleoanthropologist John Hawks of the University of Wisconsin, Madison, who was not part of the team.

Now, the view of the ancient genome is so clear that Meyer and his colleagues were able to detect for the first time that Denisovans, like modern humans, had 23 pairs of chromosomes, rather than 24 pairs, as in chimpanzees. By aligning the Denisovan genome with that of the reference human genome and counting mutations, the team calculated that the Denisovan and modern human populations finally split between 170,000 and 700,000 years ago.

The researchers also estimated ancient Denisovan population sizes by using methods to estimate the age of various gene lineages and the amount of difference between the chromosomes the girl inherited from her mother and father. They found that Denisovan genetic diversity, already low, shrank even more 400,000 years ago, reflecting small populations at that time. By contrast, our ancestors’ population apparently doubled before their exodus from Africa.

The team also counted the differences between Denisovans and chimps, and found that they have fewer differences than do modern people and chimps. The girl’s lineage had less time to accumulate mutations, and the “missing evolution” suggests she died about 80,000 years ago, although the date is tentative, says co-author David Reich, a population geneticist at Harvard University. If this date—the first proof that a fossil can be directly dated from its genome—holds up, it is considerably older than the very rough dates of 30,000 to more than 50,000 years for the layer of sediment where the fossils of Denisovans, Neandertals, and modern humans all were found.

The team says the new genome confirms their previous findings, showing that about 3% of the genomes of living people in Papua New Guinea come from Denisovans, while the Han and Dai on mainland China have only a trace of Denisovan DNA. Furthermore, the team determined that Papuans have more Denisovan DNA on their autosomes, inherited equally often from both parents, than on their X chromosomes, inherited twice as often from the mother. This curious pattern suggests several possible scenarios, including that male Denisovans interbred with female modern humans, or that these unions were genetically incompatible, with natural selection weeding out some of the X chromosomes, Reich says.

The new genome also suggests one odd result. By using the detailed Denisovan genome to sharpen the view of their close cousins the Neandertals, the team concludes that living East Asians have more Neandertal DNA than Europeans have. But most Neandertal fossils are from Europe; paleoanthropologist Richard Klein of Stanford University in Palo Alto, California, calls the result “peculiar.”

Most exciting to Pääbo is the “nearly complete catalog” of differences in genes between the groups. This includes 111,812 single nucleotides that changed in modern humans in the past 100,000 years or so. Of those, eight were in genes associated with the wiring of the nervous system, including those involved in the growth of axons and dendrites and a gene implicated in autism. Pääbo is intrigued in particular by a change in a gene that is regulated by the so-called FOXP2 gene, implicated in speech disorders. It is “tempting to speculate that crucial aspects of synaptic transmission may have changed in modern humans,” the team wrote. Thirty-four genes are associated with disease in humans. The list suggests some obvious candidates for gene-expression studies. “The cool thing is that it isn’t an astronomically large list,” Pääbo says. “Our group and others will probably be able to analyze most of them in the next decade or two.”

Back in Leipzig, the mood is upbeat, as researchers pull fossil samples off the shelf to test anew with “Matthias’s method.” First on Pääbo’s list: Neandertal bone samples, to try to produce a Neandertal genome to rival that of the little Denisovan girl.

Source: Scientific American.

 

 

Compounds activate key cancer enzyme to interfere with tumor formation.


NIH-supported research may provide tool to study cancer metabolism

Scientists have known for decades that cancer cells use more glucose than healthy cells, feeding the growth of some types of tumors. Now, a team that includes researchers from the National Institutes of Health’s new National Center for Advancing Translational Sciences (NCATS) has identified compounds that delay the formation of tumors in mice, by targeting a key enzyme that governs how cancer cells use glucose and its metabolites.

The study, published August 26 in the advance online publication of Nature Chemical Biology, was led by researchers from the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT), Cambridge. Researchers from the Structural Genomics Consortium at the University of Toronto and Harvard Medical School, Boston, also joined NCATS scientists to author the paper.

All cells use an enzyme called pyruvate kinase to derive energy from glucose. Recent studies have shown that cancer cells preferentially use one form of pyruvate kinase, called PKM2, which uses glucose to make additional cancer cells instead of energy. This altered metabolic state appears to be a fundamental aspect of many cancers, and reversing the process represents a new opportunity for cancer treatment.

In the study report, the researchers describe the identification of molecular compounds that activate PKM2, correct the way human cancer cells use glucose, and delay tumor development and decrease tumor size in mice. The results support PKM2 activation as a potential therapeutic strategy for cancer. However, the researchers emphasized there is much more work needed to understand the implications of their findings for humans, such as determining what types of tumors might be sensitive to PKM2 activation.

“The last several years have brought an avalanche of new discoveries that have begun to explain a phenomenon of altered cancer cell metabolism first described almost 90 years ago,” said Christopher P. Austin, M.D., NCATS Division of Pre-Clinical Innovation director and one of the paper’s authors. “This work provides a wonderful example of how molecular compounds can be used as tools to probe and understand biological processes, and at the same time explore new drug targets in the fight against cancer.”

NIH Common Fund’s Molecular Libraries Program supported this research, as well as the prior development of the PKM2 activators. Additional support was provided by NCATS.

“It is gratifying to see such important scientific discoveries made possible in part by the Molecular Libraries Program,” said James M. Anderson, M.D., Ph.D., director of the Division of Program Coordination, Planning, and Strategic Initiatives that guides the NIH Common Fund’s programs. “This collaboration paired experts from two different scientific disciplines and transformed our understanding of cancer cell metabolism.”

The study of cancer cell metabolism, pioneered by Nobel Laureate Otto Warburg in the early part of the 20th century, has witnessed a resurgence in research activity in recent years. New compound tools will be critical to dissecting the complex pathways that govern how cancer cells utilize nutrients such as glucose that provide the molecular building blocks to support rampant cell growth. The PKM2 activators detailed in the paper are among the first pharmacological compounds identified that will enable researchers to dig deeper into this key problem.

MIT researcher Matthew Vander Heiden, M.D., Ph.D., senior author of the paper and a medical oncologist whose lab studies cancer metabolism, has been a leading advocate of the idea that metabolic reprogramming provides cancer cells with an ability to prosper and grow. Previous work pioneered by Vander Heiden with Dimitrios Anastasiou and Lewis Cantley, both of Harvard Medical School, suggested that activating PKM2 might restore cancer cell metabolism to a normal state.

To test that theory, MIT researchers and the NIH formed a collaboration in 2008 to identify PKM2 activators, laying the foundation for the current study. NCATS researchers discovered the compounds, using a high-throughput screening robotic system. Researchers optimized the compounds in order to yield molecules with the needed pharmacological activity and the required physical properties for experimentation.

In the new study, the researchers focused their attention on how the compounds activate PKM2 and the effect this activation has on the formation of tumors. Hints as to the consequences of PKM2 activation were derived from experiments involving PKM1, a highly related enzyme of PKM2 that is found in healthy cells in an active state.

The unique mechanism of PKM2 activators prompted the research team to dig deeper into the metabolic consequences of activating PKM2. The researchers looked at the ability of the activators to mimic the results associating PKM1 expression with delayed tumor development. Aided by researchers at Agios Pharmaceuticals, Cambridge, Mass., they determined that one PKM2 activator, TEPP-46, could be used in a mouse study. The mice were given the compound, and it hindered tumor development and reduced tumor size.

“All cancers have PKM2, and learning about the basics of cancer cell metabolism and proliferation is essential to targeting human tumors,” Vander Heiden said. “I am cautiously optimistic that as we learn more about cancer cell metabolism, we may be able to identify drugs that act on PKM2 or other metabolic enzymes that could be tested against human cancers.”

The National Center for Advancing Translational Sciences (NCATS) aims to catalyze the generation of innovative methods and technologies that will enhance the development, testing and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. For more information about NCATS, visit http://www.ncats.nih.gov.

The NIH Common Fund supports a series of exceptionally high-impact research programs that are broadly relevant to health and disease. Common Fund programs are designed to overcome major research barriers and pursue emerging opportunities for the benefit of the biomedical research community at large. The research products of Common Fund programs are expected to catalyze disease-specific research supported by the NIH Institutes and Centers. Additional information about the NIH Common Fund can be found at http://commonfund.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.

For more information about NIH and its programs, visit www.nih.gov.

Source: NIH.gov

 

FDA Approves Four-in-One HIV Pill .


The FDA has approved the single-treatment regimen formerly known as “Quad” for treatment-naive adults with HIV-1 infection. The once-daily pill, marketed as Stribild, combines two previously approved antiretrovirals (emtricitabine and tenofovir) with the new integrase inhibitor elvitegravir and cobicistat, an elvitegravir booster.

In two double-blind trials involving some 1400 treatment-naive adults, 88% to 90% of patients who received Stribild had undetectable amounts of HIV in their blood at 48 weeks, compared with 84% to 87% of patients treated with other regimens. In HIV and ID Observations, Paul Sax writes that further studies are planned in women and in patients with renal insufficiency. “The bottom line,” though, is that the new drug “is an effective, very convenient option for initial HIV treatment.” (Editors’ note: Sax was an investigator in one of the phase III trials leading to approval.)

Source: FDA news

 

Researchers Find Early-Onset Testicular Cancer May Occur from Spontaneous Genetic Mutations.


Although it is clear that genetic mutations contribute to cancer risk, researchers have been unable to pinpoint the genetic cause of most cancers arising at a young age in people without a family history of the disease. Now Memorial Sloan-Kettering researchers have found that some early-onset testicular cancers may result from spontaneous, or de novo, genetic changes. These de novo mutations are not inherited from either parent, but arise in either the egg or sperm cell or sometime during embryonic development.

The mutations occur in the form of copy number variations (CNVs), in which one or more DNA segments are duplicated or deleted. Though previous research has demonstrated an association between de novo CNVs and autism, the new study, published in the August 10 issue of the American Journal of Human Genetics, is the first to suggest that these types of DNA changes may also be linked to cancer susceptibility.

“We now have the first evidence that de novo CNVs could be linked to cancer predisposition,” says medical oncologist Zsofia K. Stadler, who led the study. In addition to improving understanding of the genetic origins of testicular cancer, the authors indicate that similar spontaneous changes may be critical to understanding the origin of other pediatric cancers.

CNVs and Testicular Cancer

Because de novo CNVs have been found in higher rates in children with certain disorders, including autism and schizophrenia, the Memorial Sloan-Kettering team suspected that these types of genetic changes might also play a role in cancers that occur in younger people.

The researchers looked for CNVs in 116 people with early-onset testicular cancers (diagnosed at or before age 35), breast cancers (diagnosed at or before age 45), and colorectal cancers (diagnosed at or before age 50). Comparing the DNA of these people with the DNA of their unaffected parents, scientists found that 7 percent of the men with testicular cancer had de novo CNVs. None of the patients with breast or colorectal cancer had these DNA changes.

“We have always known that even in cancer-prone families, the mutations had to start somewhere,” says Kenneth Offit, Chief of the Clinical Genetics Service and the study’s senior author. “In this study, we appear to have pinpointed the spontaneous origin of genetic changes in the most common cancer occurring in young men.”

The researchers propose that de novo changes might be more relevant to cancers that affect people before their reproductive years, as in many men with testicular cancer. In these cases, genetic abnormalities have rarely been passed between generations, and instead develop anew for each person. In contrast, breast and colorectal cancers, even if they affect a person early in life, usually arise after the age of reproduction, which could partly explain the lower frequency of de novo mutations in these cancers.

Future Research

For the next stage of research, Memorial Sloan-Kettering investigators will focus on the DNA regions where CNVs were found in order to understand how these changes are affecting the function of genes and proteins.

In addition, they are using advanced genetic sequencing technology to look for additional de novo changes — apart from CNVs — in survivors of childhood malignancies. This approach, called next-generation sequencing, can scan the entire genome to detect the tiniest of mutations, where a single DNA base (the commonly known T, C, G, and A that make up the “letters” of DNA) differs between child and parent.

“I think we’re going to find these kinds of genetic changes in several early-onset cancers,” Dr. Stadler says. “With newer sequencing technology, we will be able to identify other rare alterations affecting cancer risk that were previously impossible to detect.”

This research was supported in part by funding from the Starr Cancer Consortium, The Society of MSKCC, and the Damon Runyon Cancer Research Foundation.

Source: MSKCC.

Two Dead from Hantavirus Exposure in Yosemite, 1700 at Risk .


Hantavirus pulmonary syndrome has been confirmed in three people in the U.S. — likely acquired at Yosemite National Park in June — the National Park Service announced this week. The syndrome is caused by exposure to urine, feces, or saliva from rodents, particularly deer mice, infected with hantavirus.

Two of the three confirmed cases have died, and a probable fourth case has also been identified.

The national park service is contacting 1700 people who stayed at the Curry Village “Signature Tent Cabins” since mid-June to warn them to seek medical care immediately if they experience early symptoms of hantavirus infection. Early signs include fever, headache, and muscle ache, which can appear 1 to 6 weeks after exposure. These can quickly progress to severe respiratory problems and death.

Source: National Park Service news

Aspirin Linked to Reduced Mortality in Prostate Cancer.


In men who’ve undergone treatment for localized prostate cancer with radical prostatectomy or radiotherapy, aspirin use is associated with reduced prostate cancer mortality, researchers report in the Journal of Clinical Oncology.

Nearly 6000 men treated for localized prostate cancer were identified from a U.S. cancer registry. About one third took anticoagulants (aspirin, clopidogrel, enoxaparin, or warfarin) at some point during roughly 6 years’ follow-up, with aspirin being most commonly used.

Overall, prostate cancer mortality was significantly lower among anticoagulant users than nonusers (actuarial 10-year risk estimate, 3% vs. 8%). Patients with high-risk disease derived the greatest benefit. In subanalyses according to anticoagulant type, a significant risk reduction was seen only with aspirin (adjusted hazard ratio, 0.43).

The researchers note that coagulation plays a role in metastasis. They hypothesize, then, that aspirin’s effects on platelet aggregation may offer protection against metastasis.

Source: Journal of Clinical Oncology

 

Cannabis Use Associated with Neuropsychological Decline, Drop in IQ .


Persistent cannabis use, especially when begun during adolescence, leads to measurable neuropsychological decline by midlife, according to a study in the Proceedings of the National Academy of Sciences.

Researchers followed a birth cohort of some 1000 New Zealanders. The subjects’ cannabis use was periodically measured, starting at age 18 and continuing through age 38. Intelligence testing was done during childhood and again at age 38.

Use of cannabis at least 4 days per week was associated with neuropsychological decline by age 38. The decline was especially notable among adolescents who were cannabis dependent (8-point loss in IQ by adulthood). The overall effect persisted after controlling for education and use of other drugs and tobacco.

Asked to comment, Barbara Geller of Journal Watch Psychiatry said: “The belief that cannabis represents a more benign recreational drug than alcohol is belied by this research and by reports of increased vulnerability to psychosis in adolescent-onset users.”

Source: PNAS

Stem Cell Transplant Experts Discuss the Procedure and How to Become a Stem Cell Donor.


This morning, Good Morning America co-host Robin Roberts announced that she will undergo a bone marrow transplant at Memorial Sloan-Kettering Cancer Center. Learn about the treatment and recovery process from Memorial Sloan-Kettering experts.

Over the course of three decades, Memorial Sloan-Kettering physicians have performed more than 4,000 bone marrow transplants – nearly 400 annually in recent years. This procedure, also known as a stem cell transplant, is used to replenish bone marrow and hematopoietic stem cells that have been destroyed due to a variety of reasons, such as certain types of cancer, cancer treatments, blood diseases, or immune disorders. Hematopoietic, or blood-forming, stem cells are produced in the bone marrow.

Our investigators have also been at the forefront of research in stem cell transplantation since 1973, when our doctors performed the world’s first successful transplant between a patient and an unrelated donor. Many of the transplant approaches and supportive care regimens widely used today were pioneered at Memorial Sloan-Kettering.

In a recent interview, experts on our Adult Bone Marrow Transplantation Service talked about the procedure, the recovery process, and how to become a bone marrow or stem cell donor.

What does a stem cell transplant involve?

There are two main types of transplants. In an autologous transplant, a patient’s own stem cells are collected and then transplanted back. In an allogeneic transplant, the stem cells are obtained from another person or from donated umbilical cord blood and then given to the patient.

Before either type of transplant, the patient receives high doses of chemotherapy or a combination of chemotherapy and radiation therapy to kill any cancerous cells and hematopoietic stem cells in the bone marrow. Healthy blood stem cells are then transplanted into the bloodstream through an intravenous catheter, in a process similar to a blood transfusion.

The stem cells migrate to the bone marrow, where after several weeks they usually begin to develop into new infection-fighting white blood cells, oxygen-rich red blood cells, and blood-clot-forming platelets.

How do doctors decide that a person should receive a transplant?

We carefully select patients for this procedure because transplantation can be extremely challenging for a patient and his or her family. This is both because of the toxicity of the high-dose regimens before the transplant and because the patient’s immune system must be suppressed for an extended period of time after the procedure to prevent a rejection of the transplanted cells.

Despite the risks, outcomes have dramatically improved over the past decades, and stem cell transplants can often cure a person’s disease. In fact, a recent study conducted by the National Marrow Donor Program found that Memorial Sloan-Kettering significantly exceeded its predicted one-year survival rate for patients undergoing an allogeneic transplant.

What is the recovery process like for a patient?

Most patients remain in the hospital for several weeks to receive medical support. To protect against infection, everyone who enters the patient’s room is required to wear gloves, masks, and sometimes disposable gowns, and to wash their hands with antiseptic soap. Patients can’t have any fresh fruit, flowers, or plants in their rooms, as these can carry disease-causing molds and bacteria.

The first year after the transplant is critically important because it’s the period when complications – such as infection or rejection – are most likely to happen. Patients are typically able to get back to their regular activities after a year, with a lower risk of developing an infection.

How do you identify donors for patients who need an allogeneic transplant?

Finding an appropriate donor is critical to the success of an allogeneic transplant. Because the immune system can identify and destroy any cells perceived as foreign, a donor’s tissue type should match the patient’s as closely as possible. The process of tissue typing is based on analyzing proteins called human leukocyte antigens (HLA), which are found on the surface of white blood cells and tissues.

We work closely with our patients to find a bone marrow match. Often, the ideal donor is a sibling who has inherited the same HLA. The majority of patients do not have a brother or sister who is a match, so we can look for other family members who may be a partial match. But because family size is getting smaller in North America, it is becoming more challenging to find appropriate family member donors.

We often look to volunteer donor registries, such as the National Marrow Donor Program, and in some cases we consider using umbilical cord blood stored in public banks, such as through National Cord Blood Program. It can also be difficult to find stem cells from people of mixed ethnic or minority backgrounds through these registries, so we encourage more people to consider becoming a donor.

How can I register to become a bone marrow or stem cell donor?

You can join the Be The Match Registry or DKMS Americas. Everyone who is medically able should consider becoming part of a marrow registry. Learn more about who can donate, donor requirements, and medical guidelines from the National Marrow Donor Program.

Source: MSKCC.