The technique involves the creation in a lab of sperm grown from embryonic cells taken from the would-be parent. Although the science is in its infancy, it could ultimately help people rendered infertile by cancer treatment, or fortysomething women who can no longer produce their own eggs, to have children who are genetically related to them.

Currently, gametes derived from stem cells are used for medical research, but British law imposes a blanket ban on their use in assisted reproduction. Following pressure from Members of Parliment to relax the ban, the Department of Health has agreed it will "look further into this matter," according to the Associated Press.

The technique could allow infertile people to have children who are genetically related to them, although so far pregnancies have been successful only in mice. In 2006, Karim Nayernia of Newcastle University created seven mice using sperm grown from embryonic stem cells. And last year, Nayernia also made immature human sperm cells from bone marrow stem cells.

Dawn Primarolo, the Public Health Minister, confirmed last night that she was considering pleas from MPs and scientists to relax the ban. There was a 'powerful argument' that the new technique could help solve a shortage of sperm donors, she said, but she was sympathetic to arguments that a decision should not be rushed.

So far pregnancies have been successfully created only in mice: of seven born alive, all died prematurely. Experts believe it could be 10 years before a human pregnancy could be safely attempted. But scientists have cultured human sperm using stem cells - immature building blocks containing DNA - taken from bone marrow.

Unlike Britain, there are currently no legal restrictions on using stem cell derived gametes for research or in the clinic in the United States, either at the federal or state level. "It's way too speculative to be worthy of policy makers," Sean Tipton, director of public affairs at the American Society for Reproductive Medicine, told The Scientist.

The latest development is likely to anger many Catholic Labour MPs, who oppose the government's Human Fertilisation and Embryology bill — legislation currently being debated controlling the use of embryos in research and fertility treatment — because it includes new measures that ease regulations on the creation of animal-human hybrid embryos. But other MPs don't feel the bill goes far enough. "The government needs to recognize a few improvements are still needed, such as allowing the use of artificial gametes," Liberal Democrat MP Evan Harris, who is leading the charge for relaxed restrictions, told The Observer yesterday.

Article based on work published May 1, 2006 in the journal Nature:Laboratory Investigation

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Specialized Care for Ovarian Cancer Improves Outcomes

Treatment at semi-specialized or specialized hospitals improved survival time for ovarian cancer patients, a Dutch study found.

For the study, the researchers examined data on 8,621 ovarian cancer patients treated in the Netherlands between 1996 and 2003. Of those women, 40 percent were treated in general hospitals, 41 percent in semi-specialized hospitals, and 18 percent in specialized hospitals. Five-year survival was 38 percent, 39.4 percent, and 40.3 percent, respectively.

The University Medical Center Utrecht researchers said the difference was statistically significant for women ages 50 to 75 who were diagnosed with early ovarian cancer. Their risk of death decreased by 30 percent (semi-specialized hospital) and 42 percent (specialized hospital), compared to those treated at a general hospital.

"This result indicates that the level of collaboration during the study period did not suffice to deliver optimal care to all Dutch ovarian cancer patients, and regionalization of the care for such patients thus seems necessary," the researchers wrote.

While this and other studies that correlate patterns of care and clinical outcomes are important, they need to be interpreted with caution, Dr. Deborah Schrag, of the Dana-Farber Cancer Institute in Boston, wrote in an accompanying editorial. Confounding variables and information that isn't tracked in such studies can lead to inaccurate conclusions, she warned.

For example, in the Dutch study, the ages and types of treatment received by ovarian cancer patients at general hospitals appeared to be different than those of patients treated at semi-specialized and specialized hospitals. In addition, there was no information about other health issues that may have affected patient results.

"Therefore, this analysis, in and of itself, does not justify regionalization of ovarian cancer surgery in the Netherlands to specialty centers," Schrag wrote.

In order to achieve more accurate analyses, cancer registries need to collect a wider range of information, she suggested.

"As the number of cancer therapies increases, and as the need to systematically evaluate their real-world clinical effectiveness grows, there is a need to optimize the data that can be gleaned from observational data sources," Schrag wrote. "A compelling case can be made for expanding the scope of data that tumor registries collect."

Published March 11, 2008 in the Journal of the National Cancer Institute

related articles: How Is Ovarian Cancer Treated?
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Thyroid Hormone Could One Day Treat Osteoporosis

In experiments with rats and mice, scientists have found that thyroid stimulating hormone can prevent the bone loss associated with osteoporosis and may even restore lost bone.

"We found that [thyroid stimulating hormone] TSH, which is a hormone that was thought to be exclusively involved in the release of thyroid hormones, which are essential for the homeostasis of the body, can directly affect bone remodeling," said lead researcher Dr. Mone Zaidi, a professor of medicine and physiology and director of the Mount Sinai Bone Program at Mount Sinai School of Medicine in New York City.

TSH inhibits the process of bone reabsorption by the body, Zaidi said. "This is a process that is fundamental for the renewal of the skeleton. Throughout life, old bone is replaced by new bone. Osteoporosis occurs when this process is exaggerated, and bone removal outpaces bone replacement." In earlier research with mice, Zaidi's group found that TSH could actually suppress bone reabsorption. For the new study, the researchers wanted to see if TSH could stop bone reabsorption when the rates were as high as they are in osteoporosis.

Zaidi's team studied rats whose ovaries had been removed, which induced menopause-related osteoporosis. The researchers then gave the rats injections of TSH often as far apart as two weeks. Injections of TSH prevented bone loss and actually increased bone strength. "In addition, in rats, TSH actually restored the lost bone," Zaidi said.

There had been a fear that injections of TSH would release thyroid hormones, which could have unwanted effects. However, Zaidi and his colleagues found that this was not the case. Zaidi said TSH is already used in humans to treat thyroid disorders. "We might be able to use the same drug for different purposes, a much larger purpose than it has ever been employed for," he said.

Dr. Stephen Honig, director of the Osteoporosis Center at the Hospital for Joint Diseases in New York City, said the idea of treating the bone disease with TSH is intriguing. But, it's far from certain that the beneficial effects seen in rodents would apply to humans. And other problems related to the use of TSH would need to be solved, he said. He noted that TSH can cause hyperthyroidism - an overactive thyroid gland - that can unleash serious problems with the body's metabolism."This is a very interesting animal study that strongly suggests that thyroid stimulating hormone may have anti-reabsorption effects on bone," Honig said. However, h

"One question for TSH will be how often will it induce hyperthyroidism and can dose adjustments minimize this without impacting its bone-strengthening effects," Honig said. "The [study] authors suggest that, so far, hyperthyroidism has not been a problem, at least in a group of postmenopausal women being treated with TSH for thyroid cancer."

Published March 10, 2008 in the journal Proceedings of the National Academy of Sciences
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TUESDAY - March 11, 2008----------------------------------------------------News Archive/Return to Today's News Alerts

Letrozole (Femara) Prevents Late Recurrence of Breast Cancer

The aromatase inhibitor letrozole (Femara) can prevent late recurrence of breast cancer, even when patients start on the drug long after stopping adjuvant tamoxifen, researchers here said. Rates of overall and distant recurrence were cut more than 50% in women who began letrozole up to seven years after completing the standard five years of adjuvant tamoxifen - compared with those receiving no active therapy, reported Paul E. Goss, M.D., of Massachusetts General Hospital, and colleagues online in the Journal of Clinical Oncology.

Women who had surgery and completed adjuvant therapy years ago should consider starting on letrozole now, Dr. Goss said in an interview.

Dr. Goss said many patients and clinicians mistakenly believe that if breast cancer does not recur within five years of surgery, the risk of later recurrence declines. In fact, he said, the yearly risk of recurrence with hormone receptor-positive disease never declines. More than half of all breast cancer recurrences and deaths occur after five years of adjuvant tamoxifen, but longer treatment with the drug has not shown additional benefit, he and his colleagues wrote.

The new findings were a follow-up to the major study of letrozole as extended adjuvant therapy in breast cancer known as MA17 - a randomized trial in which 5,187 women who had estrogen receptor-positive breast cancer were assigned to receive placebo or letrozole beginning three months after ending the adjuvant tamoxifen regimen and continuing for a planned five years. In 2003, midway through the MA17 trial, an interim analysis showed that letrozole was clearly providing a survival benefit. The trial was unblinded and letrozole was offered to the 2,383 women in the placebo group.

At that time, it had been 1.1 to 7.1 years (median 31 months) since these women ended tamoxifen treatment.

Letrozole is approved for extended adjuvant treatment of early-stage breast cancer in postmenopausal women who are within three months of completion of five years of tamoxifen therapy. It is also approved for standard adjuvant treatment and as therapy for active metastatic breast cancer with positive or unknown estrogen receptor status.

Published March 12, 2008 in the Journal of Clinical Oncology
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Poor Prenatal Nutrition Permanently Damages Insulin-Producing Cells in the Pancreas

Scientists at Joslin Diabetes Center have discovered one reason why infants with low birth weight have a high potential of developing type 2 diabetes later in life.

In studies of mice, the researchers found that poor prenatal nutrition impairs the pancreas's ability to later secrete enough insulin in response to blood glucose.

"The effect doesn't show up until later on - usually not until adolescence or adulthood said principal investigator Mary-Elizabeth Patti, M.D., Assistant Investigator in Joslin's Research Section on Cellular and Molecular Physiology and Assistant Professor of Medicine at Harvard Medical School.

"Many people believe we don't have much of a prenatal nourishment problem in the United States," she added. "But poor nutrition of a developing baby can occur in many ways other than inadequate nutrition of the mother. It also can occur with abnormal development of the placenta and its blood vessels, or high blood pressure, which damages vessels." In addition, many other factors can result in intrauterine growth restriction and low birth weight.

The Joslin study, published in the March edition of Diabetes, reinforces what scientists have known from previous studies in humans: Infants with low birth weight - typically defined as under five and one-half pounds - have a higher risk for developing type 2 diabetes.

To understand the reason, the researchers designed a series of experiments. Using ordinary mice that were not inbred or genetically altered in any way, they mated females with males, dating the day of their pregnancy, which lasts three weeks. They separated the mothers into two groups. The control group ate as much chow as they wanted during the entire pregnancy. The other group also was fully nourished during the first two weeks but undernourished during.

Published March, 2008 in the journal Diabetes
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Injection Of Human Umbilical Cord Blood Helps The Aging Brain

When human umbilical cord blood cells (UCBC) were injected into aged laboratory animals, researchers at the University of South Florida (USF) found improvements in the microenvironment of the hippocampus region of the animals’ brains and a subsequent rejuvenation of neural stem/progenitor cells. The research presented the possibility of a cell therapy aimed at rejuvenating the aged brain.

Prior to this study, the research team led by Paula C. Bickford, Ph.D., of the VA and USF found that reducing neuroinflammation in aged rats by blocking the synthesis of the pro-inflammatory cytokine IL1? rescued some of the age-related decrease in neurogenesis and improved cognitive function. The number of proliferative cells increased within 24 hours following the UCBC injections into the aged laboratory rats and that the increased cell proliferation continued for at least 15 days following a single treatment.

“We think that UCBCs may have a similar potential to reduce inflammation and to restore some of the lost capacity of stem/progenitor cells to proliferate and differentiate into neurons,” said Dr. Bickford. “Brain cell neurogenesis decreases dramatically with increasing age, mostly because of a growing impoverishment in the brain’s microenvironment,” said co-author Alison Willing, PhD, of the USF Center of Excellence for Aging and Brain Repair. “The increase in neurogenesis we saw after injecting UCBCs seemed to be due to a decrease in inflammation.”

According to lead author Carmelina Gemma, Ph.D., of the James A. Haley Veterans Administration Medical Center (VA) and USF, the decrease in neurogenesis that accompanies aging is a result of the decrease in proliferation of stem cells, not the loss of cells. “In the brain, there are two stem cell pools, one of which resides in the hippocampus,” explained graduate student and first author Adam Bachstetter. “As in other stem cell pools, the stem cells in the brain lose their capacity to generate new cells. A potent stressor of stem cell proliferation is inflammation.”

“We have shown that injections of UCBCs can reduce neuroinflammation,” concluded co-author Paul R. Sanberg, Ph.D. D.Sc. director of the Center of Excellence for Aging and Brain Repair. “Our results raise the possibility that a cell therapy could be an effective approach to improving the microenvironment of the aged brain and restoring some lost capacity.”

Published February 14, 2008 in the journal BMC Neuroscience
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MONDAY - March 10, 2008-----------------------------------------------------News Archive/Return to Today's News Alerts

New Stem Cell Technique Improves Genetic Alteration

University of California at Irvine (UCI) researchers have discovered a dramatically improved method for genetically manipulating human embryonic stem cells, making it easier for scientists to study and potentially treat thousands of disorders ranging from Huntington’s disease to muscular dystrophy and diabetes. For the first time, this technique blends two existing cell-handling methods to improve cell survival rates and increase the efficiency of inserting DNA into cells. This approach is up to 100 times more efficient than current methods at producing human embryonic stem cells with desired genetic alterations.

Peter Donovan, professor of biological chemistry and developmental and cell biology at UCI, and co-director of the UCI Sue and Bill Gross Stem Cell Research Center and Leslie Lock, assistant adjunct professor of biological chemistry and developmental and cell biology at UCI, previously identified proteins called growth factors that help keep cells alive. Growth factors are like switches that tell cells how to behave, for example to stay alive, divide or remain a stem cell. Without a signal to stay alive, the cells die.

Donovan, Lock and Kristi Hohenstein, a stem cell scientist in Donovan’s lab – used those growth factors in the current study to keep cells alive, then they used a technique called nucleofection to insert DNA into the cells. Nucleofection uses electrical pulses to punch tiny holes in the outer layer of a cell through which DNA can enter the cell. Scientists can introduce DNA into cells that makes proteins glow green under a special light. The green color allows them to track cell movement when the cells are transplanted into an animal model, making it easier for researchers to identify the cells during safety studies of potential stem cell therapies.

Scientists can use the technique to develop populations of cells with abnormalities that lead to disease. They can then study those cells to learn more about the disorder and how it is caused. Scientists also possibly could use the technique to correct the disorder in stem cells, then use the healthy cells in a treatment.

The method potentially could help treat monogenic diseases, which include Huntington’s disease, sickle cell anemia, cystic fibrosis and hemophilia, that result from modifications in a single gene occurring in all cells of the body. These diseases affect millions of people worldwide. Scientists currently estimate that more 10,000 human diseases are monogenic, according to the World Health Organization.

Published March 6, 2008 in the journal Stem Cells
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The Protective Role of MicroRNA

Snippets of genetic material that have been linked to cancer also play a critical role in normal embryonic development in mice, according to a new paper from MIT cancer biologists.

The work, reported in the March 7 issue of Cell, shows that a family of microRNAs - short strands of genetic material - protect mouse cells during development and allow them to grow normally. But that protective role could backfire: The researchers theorize that when these microRNAs become overactive, they can help keep alive cancer cells that should otherwise die--providing another reason to target microRNAs as a treatment for cancer.

Discovered only a decade ago, microRNAs bind to messenger RNAs (mRNAs), preventing them from delivering protein assembly instructions, thereby inhibiting gene expression. The details of how microRNAs act are not yet fully understood.

"The scientific community is busy trying to understand what specific biological functions these microRNAs affect," said Andrea Ventura, lead author of the paper and postdoctoral associate in the Koch Institute for Integrative Cancer Research at MIT (formerly known as the Center for Cancer Research).

Ventura--who works in the laboratory of Tyler Jacks, director of the Koch Institute--and her colleagues studied the function of a family of microRNAs known as the miR-17~92 cluster.

Previous research has shown that the miR-17~92 cluster is overactive in some cancers, especially those of the lungs and B cells.

To better understand these microRNAs' role in cancer, the researchers decided to study their normal function. Knocking out microRNA genes and observing the effects can offer clues into how microRNA helps promote cancer when overexpressed.

They found that when miR-17~92 was knocked out in mice, the animals died soon after birth, apparently because their lungs were too small. Also, their B cells, a type of immune cell, died in an early stage of cell development.

This suggests that miR-17~92 is critical to the normal development of lung cells and B cells. In B cells, these microRNAs are likely acting to promote cell survival by suppressing a gene that induces cell death, said Ventura.

"Understanding why these things are happening provides important insight into how microRNAs affect tumorigenesis," he said.

The researchers theorize that when miR-17~92 becomes overactive in cancer cells, it allows cells that should undergo programmed cell death to survive.

Blocking microRNAs that have become overactive holds promise as a potential cancer treatment. Research is now being done on molecules that prevent microRNAs from binding to their target mRNA.

More work needs to be done to make these inhibitors into stable and deliverable drugs, but Ventura said it's possible it could be done in the near future.

The exact genes targeted by miR-17~92 are not known, but one strong suspect is a gene called Bim, which promotes cell death. However, a single microRNA can have many targets, so it's likely there are other genes involved.

The researchers also studied the effects of knocking out two other microRNA clusters that are closely related to miR-17~92 but located elsewhere in the genome.

They found that if the other two microRNA clusters are knocked out but miR-17~92 remains intact, the mice develop normally. However, if miR-17~92 and one of these similar clusters are removed, the mice die before birth, suggesting there is some kind of synergistic effect between these microRNA families.

Published March 7, 2008 in the journal Cell
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Mutant Fly Hints at Evolution of Carbon Dioxide Sensing

For us, carbon dioxide (CO2) is odorless and tasteless gas. But for insects, CO2 is an important mode of communication. Mosquitoes sense the CO2 that seeps from the skin of animals, homing in on it to find the source of their blood meals. Fruit flies secrete it themselves as part of an odor that warns other flies to flee in the face of danger. Now, Howard Hughes Medical Institute (HHMI) researchers have discovered a mutant fruit fly whose misguided nerve cells are providing a fascinating look at the evolution of systems that detect this ubiquitous gas.

According to S. Lawrence Zipursky, an HHMI investigator at the University of California, Los Angeles, his group didn't set out to tease apart the evolution of the CO2 sensory system; their hybrid fly was a serendipitous find that postdoctoral fellows Pelin Cayirlioglu, Ilona Grunwald Kadow, and Xiaoli Zhan made while looking for mutants that might help them understand how the olfactory system is wired in flies. When they found this mutant regulating the type of neurons that formed in the maxillary palp rather then olfactory receptor neurons - Zipursky discouraged his postdocs from investigating further. “I was skeptical. I said, `We're interested in wiring…and this is clearly not a wiring mutant,'” he said. “But they were much more imaginative than me. They came to me and said, `It really is an interesting issue from an evolutionary perspective'… and they pushed very hard to pursue it,” he chuckled. “I'm glad they did; it came to be a beautiful paper and a beautiful understanding.”

Insects detect CO2 using specialized neurons located in their olfactory system. Fruit flies normally have the CO2-sensing neurons only in their antennae, while blood suckers like mosquitoes and tsetse flies house them in the other half of their “noses”—a structure near their mouthparts called the maxillary palp. The CO2-sensing neurons in the antennae of the new found mutant flies were normal, said Zipursky. As expected, they expressed only CO2 receptors and made connections with the area of the fly's brain that is known to be associated with CO2 sensing. However, the strange neurons in the maxillary palp “weren't actually kosher.” According to Zipursky, “... they weren't CO2 neurons, and they weren't typical maxillary palp neurons. They were something in between,” he said.

The hybrid neurons were the result of a genetic mutation the team tracked to a short stretch of DNA that encoded not a protein, but a molecule known as a micro RNA. Zipursky's team found a specific microRNA, miR-279, which normally interferes with production of a protein called nerfin-1. When miR-279 malfunctioned, nerfin-1 became activated in the maxillary palp cells, and the fly developed CO2 receptors in an area it wasn't supposed to. Presumably these receptors developed only in this one errant region because of similarities in the genetic programs between maxillary palp olfactory neurons and CO2 neurons in the antennae.

This simple genetic mutation turned a very specialized neuron with only one type of receptor into a more generalized neuron with two types of receptors. Was this evolution in reverse? The evolution of insects' CO2 sensory apparatus, Zipursky said, might have looked just like the one they found: one that expressed both a CO2 receptor and another type of maxillary palp receptor, connecting two different regions of the fly's brain, said Zipursky. Over time, this neuron evolved to become more specialized. Depending on whether it was in the antennae or in the maxillary palp, it would have lost either its CO2 or olfactory receptors, and would have restricted its connections to one area of the brain. These changes could well have helped determine whether the modern fly's ancestor was attracted to the scent of CO2 or repelled by it.

According to Zipursky, the microRNA that was turned off in their mutant may have evolved as part of this process. However, he stressed, other genes must specify that CO2 receptors form in the fruit fly's antennae - their normal location. No one has yet looked at whether the odd way these neurons connect to the brain is enough to change a fly's behavior - attracting them to CO2 like a mosquito or whether other changes are required. “It's a great question,” he said.

Published February 29, 2008 in the journal Science

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