Researchers discover atomic bomb effect results in adult-onset thyroid cancer

Public release date: 29-Aug-2008

Contact: Jeremy Moore
Jeremy.moore@aacr.org
267-646-0557
American Association for Cancer Research
Researchers discover atomic bomb effect results in adult-onset thyroid cancer

PHILADELPHIA – Radiation from the atomic bomb blasts in Hiroshima and Nagasaki, Japan, in 1945, likely rearranged chromosomes in some survivors who later developed papillary thyroid cancer as adults, according to Japanese researchers.

In the September 1, 2008, issue of Cancer Research, a journal of the American Association for Cancer Research, the scientists report that subjects who lived close to the blast sites, were comparably young at the time, and developed the cancer quickly once they reached adulthood, were likely to have a chromosomal rearrangement known as RET/PTC that is not very frequent in adults who develop the disease.

"Recent in vitro and in vivo studies suggest that a single genetic event in the MAP kinase-signaling pathway may be sufficient for thyroid cell transformation and tumor development," said the study's lead author, Kiyohiro Hamatani, Ph.D., laboratory chief, Department of Radiobiology and Molecular Epidemiology at the Radiation Effects Research Foundation (RERF) in Hiroshima.

"Thyroid cancer is associated with exposure to external or internal ionizing radiation.Elucidation of mechanisms of radiation-induced cancer in humans, especially early steps and pathways, has potential implications for epidemiological risk analyses, early clinical diagnosis, and chemopreventive interventions," Hamatani said.

He adds that there are several irradiated populations worldwide that have been shown to have an increase in thyroid cancer, and that children exposed to radioactive fallout from the 1986 Chernobyl nuclear power plant accident who develop papillary thyroid cancer have also been found to have RET/PTC rearrangements, although they are slightly different.

This study is part of the foundation's long running follow-up research on 120,000 atomic bomb survivors. During 1958 to 1998, the study found about 470 thyroid cancer cases of which the estimated number of excess cases attributable to radiation is 63. About 90 percent of thyroid cancer among the survivors is of the papillary type.

Hamatani and colleagues from across Japan made a comparison between adult-onset papillary thyroid cancers with RET/PTC rearrangements and those with a BRAF mutation. More than 70 percent of adult onset papillary thyroid cancer in non-exposed patients is associated with mutations in the BRAF gene.

The researchers looked at the genetic profile of cancer patients in the RERF's follow-up study--50 patients who were exposed to atomic bomb radiation and 21 patients who were not. Three factors were found to be independently associated with the development of adult-onset papillary thyroid cancer with RET/PTC rearrangements. They were greater radiation dose, shorter time elapsed since radiation exposure, and younger age at the time of the bombings, Hamatani says.

"That means that a younger person living close to the bombing site would be more likely to have adult onset thyroid cancer having RET/PTC rearrangements," he said. "This is the first time this has been shown."

The findings also suggest that in childhood papillary thyroid cancer RET/PTC rearrangements may be much less clearly associated with radiation exposure, compared with adult-onset cancer, because RET/PTC rearrangements are frequent in childhood papillary thyroid cancer patients regardless of history of radiation exposure.

The researchers do not know exactly how radiation is involved in the occurrence of RET/PTC rearrangements. "It could be either by direct DNA damage or by other pathways such as a result of radiation-induced genomic instability," Hamatani said.

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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and 80 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Researchers find high levels of toxic metals in herbal medicine products sold online

This paper is similar to the one published by the lead author and his colleagues in JAMA in 2005.I have followed it up with a feature article in the PTIFEATURE published by the Press Trust of India, the premier news agency of India

K.S.Parthasarathy





Public release date: 26-Aug-2008


Contact: Michelle Roberts
michelle.roberts@bmc.org
617-638-8491
Boston University
Researchers find high levels of toxic metals in herbal medicine products sold online

Boston, MA--Researchers at Boston University School of Medicine (BUSM) have found that one fifth of both U.S.-manufactured and Indian-manufactured Ayurvedic medicines purchased via the Internet contain lead, mercury or arsenic. These findings appear in the August 27th issue of the Journal of the American Medical Association (JAMA).

Ayurveda is a form of medicine that originated in India more than 2,000 years ago and relies heavily on herbal products. In India, an estimated 80 percent of the population practices Ayurveda. In the United States, Ayurvedic remedies have increased in popularity and are available from South Asian markets, health food stores, and on the Internet. Ayurvedic medicines are divided into two major types: herbal only and rasa shastra. Rasa shastra is an ancient practice of deliberately combining herbs with metals, minerals and gems. Ayurvedic experts in India believe that if Rasa Shastra medicines made with metals such as lead and mercury are properly prepared and administered, they will be safe and therapeutic.

Using an Internet search, the researchers identified 25 Web sites featuring 673 Ayurvedic medicines. They randomly selected and purchased 193 products made by 37 different manufacturers for analyses. Overall, 20.7 percent of Ayurvedic medicines contained detectable lead, mercury and/or arsenic. U.S. and Indian manufactured products were equally likely to contain toxic metals. Rasa shastra compared with non-rasa shastra medicines were more than twice as likely to contain metals and had higher concentrations of lead and mercury. Among products containing metals, 95 percent were sold by U.S. Web sites and 75 percent claimed Good Manufacturing Practices or testing for heavy metals. All metal-containing products exceeded one or more standards for acceptable daily intake of toxic metals.

"This study highlights the need for Congress to revisit the way dietary supplements are regulated in the U.S.," said lead author Robert Saper, MD, MPH, Director of Integrative Medicine in the Family Medicine Department at BUSM. Saper first published on this topic in December, 2004 (JAMA). In that study he and his colleagues found 20% of Ayurvedic medicines produced in South Asia only and available in Boston area stores contained potentially harmful levels of lead, mercury, and/or arsenic. "Our first priority must be the safety of the public. Herbs and supplements with high levels of lead, mercury, and arsenic should not be available for sale on the Internet or elsewhere," he said.

Saper adds, "We suggest strictly enforced, government mandated daily dose limits for toxic metals in all dietary supplements and requirements that all manufacturers demonstrate compliance through independent third-party testing."

"The medicines which are supposed to cure sickness should not promote another illness due to the presence of toxic materials such as lead," said co-author Venkatesh Thuppil, PhD, Director of the National Referral Centre for Lead Poisoning in India, as well as a Professor at St. John's Medical College in India.

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Biochemists manipulate fruit flavor enzymes

Public release date: 20-Aug-2008
Contact: Robert Cahill
Robert.Cahill@uth.tmc.edu
713-500-3042
University of Texas Health Science Center at Houston
Biochemists manipulate fruit flavor enzymes

Would you like a lemony watermelon? How about a strawberry-flavored banana? Biochemists at The University of Texas Medical School at Houston say the day may be coming when scientists will be able to fine tune enzymes responsible for flavors in fruits and vegetables. In addition, it could lead to environmentally-friendly pest control.

In the advance online publication of Nature on Aug. 20, UT Medical School Assistant Professor C.S. Raman, Ph.D., and his colleagues report that they were able to manipulate flavor enzymes found in a popular plant model, Arabidopsis thaliana, by genetic means. The enzymes—allene oxide synthase (AOS) and hydroperoxide lyase (HPL)—produce jasmonate (responsible for the unique scent of jasmine flowers) and green leaf volatiles (GLV) respectively. GLVs confer characteristic aromas to fruits and vegetables.

Green leaf volatiles and jasmonates emitted by plants also serve to ward off predators. "Mind you plants can't run away from bugs and other pests. They need to deal with them. One of the things they do is to release volatile substances into the air so as to attract predators of the bugs," Raman said.

"Genetic engineering/modification (GM) of green leaf volatile production holds significant potential towards formulating environmentally friendly pest-control strategies. It also has important implications for manipulating food flavor," said Raman, the senior author. "For example, the aroma of virgin olive oil stems from the volatiles synthesized by olives. By modifying the activity of enzymes that generate these substances, it may be possible to alter the flavor of the resulting oils."

According to Raman, "Our work shows how you can convert one enzyme to another and, more importantly, provides the needed information for modifying the GLV production in plants." The scientists made 3-D images of the enzymes, which allowed them to make a small, but specific, genetic change in AOS, leading to the generation of HPL.

AOS and HPL are part of a super family of enzymes called cytochrome P450. P450 family enzymes are found in most bacteria and all known plants and animals. Although AOS or HPL are not found in humans, there are related P450 family members that help metabolize nearly half of the pharmaceuticals currently in use. In plants, AOS and HPL break down naturally-occurring, organic peroxides into GLV and jasmonate molecules. "Each flavor has a different chemical profile," Raman said.

"A notable strength of this manuscript is the combined use of structural and evolutionary biology to draw new insights regarding enzyme function. These insights led to the striking demonstration that a single amino acid substitution converts one enzyme into another, thereby showing how a single point mutation can contribute to the evolution of different biosynthetic pathways. This begins to answer the long-standing question as to how the same starting molecule can be converted into different products by enzymes that look strikingly similar," said Rodney E. Kellems, Ph.D., professor and chairman of the Department of Biochemistry & Molecular Biology at the UT Medical School at Houston.

The study dispels the earlier view that these flavor-producing enzymes are only found in plants, Raman said. "We have discovered that they are also present in marine animals, such as sea anemone and corals. However, we do not know what they do in these organisms."

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The study is titled "Structural insights into the evolutionary paths of oxylipin biosynthetic enzymes." The lead authors were Dong-Sun Lee, Ph.D., an assistant professor in the Department of Biochemistry & Molecular Biology at the UT Medical School at Houston, and Pierre Nioche, Ph.D., an assistant professor at the Université Paris Descartes. Mats Hamberg, M.D., Ph.D., professor of medical chemistry in the Division of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden, collaborated on the research.

The research is supported by Pew Charitable Trusts through a Pew Scholar Award, The Robert A. Welch Foundation, The National Institutes of Health, a Beginning Grant in Aid from the American Heart Association, and an INSERM Avenir Grant sponsored by La Fondation pour la Recherche Medicale.

Water refineries

Public release date: 31-Jul-2008
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Contact: Josh Chamot
jchamot@nsf.gov
703-292-7730
National Science Foundation
Water refineries?
New method extracts oxygen from water with minimal energy, potentially boosting efforts to develop solar as a 24-hour energy source
A snapshot showing the new, efficient oxygen catalyst in action in Dan Nocera's laboratory at MIT.
Click here for more information.

Using a surprisingly simple, inexpensive technique, chemists have found a way to pull pure oxygen from water using relatively small amounts of electricity, common chemicals and a room-temperature glass of water.

Because oxygen and hydrogen are energy-rich fuels, many researchers have proposed using solar electricity to split water into those elements--a stored energy source for when the sun goes down. One of the chief obstacles to that green-energy scenario has been the difficulty of producing oxygen without large amounts of energy or a high-maintenance environment.

Now, Massachusetts Institute of Technology chemist Daniel Nocera and his postdoctoral student Matthew Kanan have discovered an efficient way to solve the oxygen problem. They announced their findings July 31, 2008, online in the journal Science.

"The discovery has enormous implications for the large scale deployment of solar since it puts us on the doorstep of a cheap and easily manufactured storage mechanism," said Nocera. "The ease of implementation means that this discovery will have legs. I have great faith in my chemistry, materials science and engineering colleagues in the community to drive this discovery hard and hopefully their work, along with our continued studies will yield viable technologies within 10 years."

While a home-based energy source using this technique could be a decade away, the breakthrough is a major step forward.

"This study demonstrates how research is critical for driving American competitiveness in the global energy marketplace. By funding fundamental research in water and renewable energy, we are investing in both our economic and environmental futures," said Arden L. Bement, Jr., director of the National Science Foundation (NSF).

To produce oxygen, Nocera and Kanan added cobalt and phosphates to neutral water and then inserted a conductive-glass electrode. As soon as the researchers applied a current, a dark film began to form on the electrode from which tiny pockets of oxygen began to appear, eventually building into a stream of bubbles.

After analyzing the electrode, the researchers concluded that a cobalt-phosphate mixture, possibly combined with phosphate, had deposited as a film.

Nocera and Kanan believe the film is the catalyst that helps break apart the water molecules to create oxygen gas. The protons (hydrogen nuclei) released from the process pick up electrons and convert back into hydrogen at a partner electrode.

Nocera and Kanan also found evidence that the catalyst seems to refresh itself, a mechanism that would make maintenance of such oxygen-extracting systems far simpler than alternatives, although that finding needs confirmation from additional experiments.

"The simplicity of this process is amazing," said Luis Echegoyen, director of NSF's Chemistry Division. "Using common and affordable elements, and a glass of water, these chemists may have given us a future way to efficiently obtain oxygen by splitting water."

Despite the straightforward experimental setup, the exact mechanism driving the reactions is still unknown. For direct conversion of solar energy into hydrogen and oxygen, researchers will need to study the new research results and incorporate the mechanisms into a larger system that also cleanly produces hydrogen.

Nocera is a member of NSF's Powering the Planet, a partnership that NSF forged between MIT, Caltech and several other institutions as an NSF Chemical Bonding Center in 2005. In his role as a co-investigator with the center, Nocera has been pursuing sustainable energy technology through a broader effort to learn from, and apply, the lessons of photosynthesis and other natural processes.

"When we support fundamental research we never know where that investment will lead. In this instance, it may lead to new opportunities for sustainable energy," said Tony Chan, assistant director for NSF's Mathematics and Physical Sciences Directorate.

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