Archive for January, 2009
Grant To Improve Targeting In Parkinson’s Surgery
A $51,000 grant will enable University of Cincinnati (UC) researchers to determine whether sophisticated new imaging technologies can help them achieve pinpoint placement of deep-brain stimulation electrodes in patients with Parkinson’s disease. George Mandybur, MD, a neurosurgeon with the Mayfield Clinic and the UC Neuroscience Institute, is leading the pilot study, which will take place at University Hospital.
Mandybur and his team will use a 3-Tesla MRI scanner with high-resolution sequences, along with diffusion tensor imaging fiber tracking, in an attempt to quickly and accurately predict the size and position of the subthalamic nucleus, a small area deep within the brain. The size and location of the subthalamic nucleus can vary significantly from patient to patient.
Physicians have long known that by stimulating the subthalamic nucleus they can alleviate symptoms and improve the lives of some patients with Parkinson’s disease. Traditionally, surgeons have located the target by using standard medical atlases and multiple preoperative and intraoperative imaging techniques, including 1.5-Tesla MRI. “But current methods have drawbacks,” Mandybur says. “The borders of the subthalamic nucleus can be indistinct, to the extent that sometimes we cannot visualize the nucleus well.”
To be certain that the electrodes are in the right place, surgeons have relied on electrophysiological confirmation, stimulating the target while the patient is awake and often making multiple passes through brain tissue. When surgery is prolonged in an effort to define the target, the risk of complications can increase.
In their study, Mandybur and his co-investigators will use new imaging modalities, including the more powerful 3-Tesla MRI and diffusion tensor imaging, which provides a map of critical white-matter tracts in the brain. White-matter tracts are electrical connections that should not be surgically disrupted.
The study will involve 20 patients at the James J. and Joan A. Gardner Center for Parkinson’s Disease and Movement Disorders at the UC Neuroscience Institute. Funding comes from the Sunflower Revolution, an annual fundraiser and bike ride held in Cincinnati. The Sunflower event is a collaboration among the UC Neuroscience Institute, the University Hospital Foundation and the Davis Phinney Foundation of Boulder, Colo.
—————————-
Article adapted by Medical News Today from original press release.
—————————-
Mandybur’s co-investigators are Gregory Toczyl, MD, a neurosurgeon and the 2008-2009 Davis Phinney-Donald Krumme Fellow in Parkinson’s Disease and Movement Disorders; Jim Eliassen, PhD, and Jing-huei Chang, PhD, of the UC Department of Psychiatry; Fredy J. Revilla, MD, of the UC Department of Neurology; and James Leach, MD, of the Department of Radiology at Cincinnati Children’s Hospital Medical Center.
The UC Neuroscience Institute, a regional center of excellence at UC and University Hospital, is dedicated to patient care, research, education, and the development of new treatments for stroke, brain and spinal tumors, epilepsy, traumatic brain and spinal injury, Alzheimer’s disease, Parkinson’s disease, disorders of the nerves and muscles, disorders of the senses (swallowing, voice, hearing, pain, taste and smell) and psychiatric conditions (bipolar disorder, schizophrenia and depression).
The Mayfield Clinic is recognized as one of the nation’s leading physician organizations for clinical care, education and research of the spine and brain. Supported by 20 neurosurgeons, three neurointensivists, an interventional radiologist and a pain specialist, the clinic treats 20,000 patients from 35 states and 13 countries in a typical year.
Source: Cindy Starr
University of Cincinnati
CDC Recognizes UCSF’s Research As Critical To HIV Prevention
Two HIV prevention interventions developed by UCSF researchers have been selected as additions to the Centers for Disease Control and Prevention’s 2008 Compendium of Evidence-based HIV Prevention Interventions.
The UCSF interventions – Positive Choice: Interactive Video Doctor and the Healthy Living Project – comprise two of the eight added to the list of 57 rigorously evaluated highly effective HIV prevention programs recommended by the CDC for implementation.
“Both of these interventions meet the CDC’s very highest standard and reflect UCSF’s leadership in developing efficacious behavioral HIV prevention programs. The release of the CDC’s 2008 Compendium is particularly timely as a new administration with a preference for evidence based approaches and a desire to better fund domestic HIV prevention programs takes charge,” said Healthy Living senior investigator, Stephen F. Morin, director of UCSF’s Center for AIDS Prevention Studies and UCSF professor of medicine.
In addition, these UCSF research programs are among the first interventions to establish a reduction in the risk of transmission acts among people living with HIV, commonly called “prevention with positives.” This has emerged as a top priority in CDC prevention planning because the approach can efficiently concentrate resources on reducing the number of new infections by engaging people living with HIV as partners in prevention.
Positive Choice: Interactive Video Doctor uses a video doctor to simulate the ideal doctor-patient risk counseling conversation. Interactive video clips using an actor-portrayed doctor are matched to patients’ answers from assessment questions allowing the omission of any non-relevant counseling. The counseling sessions, which last an average of 24 minutes, end with a prompt to patients to discuss the risky behaviors with their healthcare provider during their regular appointment following the video counseling session. The program sharply reduced sexual and drug risk behaviors by the HIV-positive patients and in some cases, eliminated risky behaviors all together.
“Positive Choice does not replace a patient’s healthcare provider, but facilitates and supports an important dialogue. Key features of the program are that it was developed so anyone can easily use it – even those with low literacy skills – and it can target multiple risk behaviors. Importantly, the program was evaluated with a diverse group of patients of both genders. In fact, we have already been contacted by providers who want to implement the program,” said the program’s principal investigator, Barbara Gerbert, PhD, professor in the Division of Behavioral Sciences, Professionalism, and Ethics and director of the Center for Health Improvement and Prevention Studies (CHIPS) at UCSF.
Healthy Living addresses three crucial interrelated aspects of living with HIV: stress and coping, transmission risk behaviors, and adherence to anti-HIV medication regimens. The three aspects are addressed in a series of individually tailored client centered 90 minute counseling sessions. Starting with stress and coping and building on the framework and skills developed in those sessions, counselors then guide their clients through risk reduction sessions that allow clients to identify their own risk behaviors. Clients then identify boundaries for their risk behaviors that they are able to stay within. In one sub-group of men who have sex with men, researchers found that many clients chose to engage in risky sexual behaviors solely with known HIV positive partners – a strategy termed serosorting.
Clients address the third aspect, medication adherence, in sessions that focus on the development of a personal health plan. Using the same client based problem solving approach, counselors help clients identify barriers to taking their pills as directed and assist them in distilling solutions to overcome those barriers.
“Healthy Living was rigorously tested in a diverse group of men and women in cities across the country and was shown to reduce risk behaviors. The program equips clients with skills to self identify and reduce HIV transmission risk behaviors and develop strategies to ensure that they take their vital anti-HIV medications as directed. By reducing risky behavior and lowering levels of virus in the blood through enhanced treatment adherence, the intervention provides two mechanisms for lowering HIV transmission,” said program investigator, Mallory O. Johnson, PhD, associate professor of medicine at UCSF’s Center for AIDS Prevention Studies (CAPS).
The National Institute on Drug Abuse provided funding for the development of Positive Choice: Interactive Video Doctor. The National Institute of Mental Health provided funding for the development of Healthy Living. Both NIDA and NIMH are part of the National Institutes of Health.
Co-investigators for Positive Choice: Interactive Video Doctor include Daniel Ciccarone, Stuart Gansky, Stephen McPhee, Sophia Calderón, and Alyssa Bogetz from UCSF; and Katherine Clanon, from the East Bay AIDS Education and Training Center, Oakland, CA; David R. Bangsberg, from Harvard; and Elizabeth Robertson, Richard Jenkins, and Eve Reider from the National Institute on Drug Abuse.
Co-investigators for Healthy Living include Willo Pequegnat from the National Institute of Mental Health; Cheryl Gore-Felton, Lance S. Weinhardt, Jeffrey A. Kelly, and Sheryl L. Catz from the Center for AIDS Intervention Research at the Medical College of Wisconsin, Milwaukee; Mary Jane Rotheram-Borus from UCLA; Sheri B. Kirshenbaum, Anke A. Ehrhardt and Robert Remien from Columbia University; Margaret Chesney from the University of Maryland; and Margarita Lightfoot, Edwin Charlebois, and Wayne Steward from UCSF CAPS.
UCSF’s CAPS and CHIPS are affiliated with the AIDS Research Institute (ARI) at UCSF. UCSF ARI houses hundreds of scientists and dozens of programs throughout UCSF and affiliated labs and institutions, making ARI one of the largest AIDS research entities in the world.
UCSF is a leading university dedicated to defining health worldwide through advanced biomedical research, graduate level education in the life sciences and health professions and excellence in patient care.
—————————-
Article adapted by Medical News Today from original press release.
—————————-
Source: Jeff Sheehy
University of California – San Francisco
Potential Lung Cancer Drug Tested By Translational Genomics Research Insitute Affiliates
TGen Clinical Research Services (TCRS) at Scottsdale Healthcare and Mayo Clinic are testing a new drug that may offer broad potential to treat solid tumors.
Clinical trials of the drug TH-302 are being conducted at TGen Clinical Research Services at Scottsdale Healthcare, a partnership of the Phoenix-based Translational Genomics Research Institute (TGen) and Scottsdale-based Scottsdale Healthcare Corp., and at Mayo Clinic in Arizona.
Dr. Glen Weiss, Director of Thoracic Oncology at TCRS at Scottsdale Healthcare, said the new drug appears promising and may be more effective and less toxic to healthy tissues than conventional drugs.
“TH-302 is a new, novel, small molecule that is activated under a metabolic condition characteristic of cancer cells – hypoxia (lack of oxygen). The drug candidate may provide an opportunity to treat slowly dividing tumor cells within hypoxic regions that generally evade traditional chemotherapeutic agents and ultimately contribute to relapse,” Dr. Weiss said.
Phase 1 and Phase 1/2 trials are underway to investigate the safety and activity of TH-302 in patients with advanced solid tumors. After evidence of tumor activity was observed in the Phase 1 trial in patients with advanced melanoma – both non-small cell lung cancer and small cell lung cancer – the study was expanded to further investigate TH-302 anti-tumor activity in these tumors. Both Phase 1 and 1/2 trials continue to enroll patients with other solid tumors. If successful, Phase 2 and 3 clinical trials will confirm the drug’s effectiveness on solid tumors.
In cancer, as a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. This condition is called tumor hypoxia. Several studies have shown that higher levels of tumor hypoxia correlate with poor treatment outcomes for a variety of solid tumors. It is believed that hypoxia may severely limit the curability of tumors.
TH-302 is converted selectively in the presence of hypoxia to the drug’s active form, bromo-isophosphoramide mustard, a potent DNA alkylator. TH-302 targets levels of hypoxia that are common in tumors but are rare in normal tissues – this is how selective targeting of the tumor occurs. After conversion to the active form of the drug, the more resistant hypoxic cells are exposed to high concentrations of released cytotoxic agent, which can also diffuse into the oxygenated regions of a tumor cell.
The Phase 1/2 trials are investigating the safety and activity of TH-302 in combination with a number of conventional chemotherapies that are believed to be effective in the non-hypoxic regions of solid tumors.
—————————-
Article adapted by Medical News Today from original press release.
—————————-
The clinical trial at TCRS at Scottsdale Healthcare will investigate the safety and pharmacology of multiple doses of TH-302 in patients with late-stage cancer.
About TGen
The Translational Genomics Research Institute (TGen) is a non-profit organization dedicated to conducting groundbreaking research with life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process. For more information, visit: http://www.tgen.org.
About Scottsdale Healthcare
Scottsdale Healthcare is a primary clinical research site for TGen. TGen Clinical Research Services (TCRS) at Scottsdale Healthcare is housed in the Virginia G. Piper Cancer Center at Scottsdale Healthcare, located on the Scottsdale Healthcare Shea medical campus. Scottsdale Healthcare is the not-for-profit parent organization of the Scottsdale Healthcare Shea, Scottsdale Healthcare Osborn and Scottsdale Healthcare Thompson Peak hospitals, Virginia G. Piper Cancer Center, Scottsdale Clinical Research Institute, TGen Clinical Research Services at Scottsdale Healthcare, Scottsdale Healthcare Home Health Services, Scottsdale Healthcare Community Health Services, and Scottsdale Healthcare Foundation. For additional information, visit http://www.shc.org.
About Mayo Clinic
Mayo Clinic Cancer Center is one of only 39 U.S. medical centers that have been named as a National Cancer Institute (NCI) Comprehensive Cancer Center. To receive this designation, an institution must meet rigorous standards demonstrating scientific excellence and the ability to integrate diverse research approaches to address the problem of cancer. Mayo Clinic Cancer Center is the only national, multi-site center with the NCI’s Comprehensive Cancer Center designation. In Arizona, Mayo’s clinical and research experts work together to address the complex needs of cancer patients, with a dedication to understanding the biology of cancer; discovering new ways to predict, prevent, diagnose and treat cancer; and transforming the quality of life for cancer patients today and in the future.
About Threshold Pharmaceuticals
Threshold is a biotechnology company focused on the discovery and development of drugs targeting Tumor Hypoxia, the low oxygen condition found in microenvironments of most solid tumors. This approach offers broad potential to treat most solid tumors. By selectively targeting tumor cells, we are building a pipeline of drugs that hold promise to be more effective and less toxic to healthy tissues than conventional anticancer drugs. For additional information, please visit our website (http://www.thresholdpharm.com).
Source: Steve Yozwiak
The Translational Genomics Research Institute
Early-Stage Multiple Sclerosis Reversed By Stem Cell Transplant
Researchers from Northwestern University’s Feinberg School of Medicine appear to have reversed the neurological dysfunction of early-stage multiple sclerosis patients by transplanting their own immune stem cells into their bodies and thereby “resetting” their immune systems.
“This is the first time we have turned the tide on this disease,” said principal investigator Richard Burt, M.D. chief of immunotherapy for autoimmune diseases at the Feinberg School. The clinical trial was performed at Northwestern Memorial Hospital where Burt holds the same title.
The patients in the small phase I/II trial continued to improve for up to 24 months after the transplantation procedure and then stabilized. They experienced improvements in areas in which they had been affected by multiple sclerosis including walking, ataxia, limb strength, vision and incontinence. The study will be published online January 30 and in the March issue of The Lancet Neurology.
Multiple sclerosis (MS) is an autoimmune disease in which the immune system attacks the central nervous system. In its early stages, the disease is characterized by intermittent neurological symptoms, called relapsing-remitting MS. During this time, the person will either fully or partially recover from the symptoms experienced during the attacks. Common symptoms are visual problems, fatigue, sensory changes, weakness or paralysis of limbs, tremors, lack of coordination, poor balance, bladder or bowel changes and psychological changes.
Within 10 to 15 years after onset of the disease, most patients with this relapsing-remitting MS progress to a later stage called secondary progressive multiple sclerosis. In this stage, they experience a steady worsening of irreversible neurological damage.
The 21 patients in the trial, ages 20 to 53, had relapsing-remitting multiple sclerosis that had not responded to at least six months of treatment with interferon beta. The patients had had MS for an average of five years. After an average follow-up of three years after transplantation, 17 patients (81 percent) improved by at least one point on a disability scale. The disease also stabilized in all patients.
In the procedure, Burt and colleagues treated patients with chemotherapy to destroy their immune system. They then injected the patients with their own immune stem cells, obtained from the patients’ blood before the chemotherapy, to create a new immune system. The procedure is called autologous non-myeloablative haematopoietic stem-cell transplantion.
“We focus on destroying only the immune component of the bone marrow and then regenerate the immune component, which makes the procedure much safer and less toxic than traditional chemotherapy for cancer,” Burt said. After the transplantation, the patient’s new lymphocytes or immune cells are self-tolerant and do not attack the immune system.
“In MS the immune system is attacking your brain,” Burt said. “After the procedure, it doesn’t do that anymore.”
In previous studies, Burt had transplanted immune stem cells into late-stage MS patients. “It didn’t help in the late stages, but when we treat them in the early stage, they get better and continue to get better,” he said.
“What we did is promising and exiting, but we need to prove it in a randomized trial,” Burt noted. He has launched a randomized national trial.
—————————-
Article adapted by Medical News Today from original press release.
—————————-
For more information visit : http://clinicaltrials.gov/ct2/show/NCT00273364
Source: Marla Paul
Northwestern University
Improved Understanding Of Circadian Clocks
Scientists from Queen Mary, University of London have discovered a new part of the mechanism which allows our bodyclocks to reset themselves on a molecular level.
Circadian clocks regulate the daily fluctuations of many physiological and behavioural aspects in life, and are synchronised with our surrounding environment via light or temperature cycles. Natural changes in the length of the day mean that an animal’s circadian clock often has to reset itself on a molecular level, to avoid getting out of sync with the changing calendar.
Professor Ralf Stanewsky and his team from Queen Mary’s School of Biological and Chemical Sciences study the circadian clocks of Drosophila, a type of fruit fly. Writing in the journal Current Biology, they report that the resetting process is governed by three factors, called Cryptochrome, Jetlag and Timeless.
The team’s findings suggest that the light responses of circadian clocks are fine tuned on a molecular, by small differences in the binding affinities of clock proteins.
Professor Stanewsky explains: “A circadian photoreceptor called Cry is activated by light in the blue spectrum. Once active, Cry then becomes able to bind to a protein called Jetlag. The Jetlag protein then helps to destroy another protein called Timeless, which is used to reset the bodyclock.
“Crucially though, we found that Jetlag also helps to destroy the original photoreceptor Cry itself. This allows the Timeless protein to reaccumulate during the next day, making sure that the clock mechanism continues to tick.”
—————————-
Article adapted by Medical News Today from original press release.
—————————-
Source: Sian Halkyard
Queen Mary, University of London
Key Component In Cell Replication Identified By Stanford Scientists
Last week, a presidential limousine shuttled Barack Obama to the most important job in his life. Scientists at the Stanford University School of Medicine have now identified a protein that does much the same for the telomerase enzyme – ferrying the critically important clump of proteins around to repair the ends of chromosomes that are lost during normal replication. Without such ongoing maintenance, stem cells would soon cease dividing and embryos would fail to develop.
“This is the first new protein component of telomerase that has been identified in 10 years,” said Steven Artandi, MD, PhD, associate professor of hematology. “And it’s likely to be a valuable target for anti-cancer therapies.”
Artandi is the senior author of the research, which will be published in the Jan. 30 issue of Science. Graduate student Andrew Venteicher is the first author. The two collaborated with scientists at the National Cancer Institute-Frederick and the University of Georgia to conduct the research.
Telomerase is normally expressed in adult stem cells and immune cells, as well as in cells of the developing embryo. In these cells, the enzyme caps off the ends of newly replicated chromosomes, allowing unfettered cell division. Without telomerase, cells stop dividing or die within a limited number of generations. Unfortunately, the enzyme is also active in many cancer cells. Artandi and his collaborators found that blocking the inappropriate expression of the protein, called TCAB1, in human cancer cells keeps telomerase from reaching its DNA targets, called telomeres, and may limit the cell’s life span.
“There are currently no effective telomerase inhibitors,” said Artandi. “We’ve never really understood before how the enzyme gets to the telomeres; it’s been a complete black box. Now we’re starting to piece together how it happens, and that gives us more opportunities to interfere with its function.”
Telomerase has been subject of intense research for years, but scientists have been stymied by the enzyme’s large size and extreme rarity. Few cells in the adult body make the huge protein complex, and even they make only tiny amounts. As a result, only some members have been identified.
“It’s been incredibly challenging to figure out all the protein components of telomerase,” said Artandi, who refers to the unknown members of the complex as “dark matter.” “We know how big the enzyme is, and it’s clear that the known components don’t add up to the total. Now we’ve identified one more member.”
The researchers used a highly sensitive protein identification technique called mass spectrometry to ferret out TCAB1′s presence in telomerase based on its ability to bind to another, known component of the enzyme. Early last year, Artandi’s lab used the same technique to identify for the first time two other proteins – pontin and reptin – that are important for assembling the massive complex. This time around they identified TCAB1, a protein of previously unknown function.
Unlike pontin and reptin, TCAB1 is a true component of telomerase. But it’s not required for the enzyme’s activity. Rather, it recruits the telomerase complex to processing and holding areas in the nucleus of the cell called Cajal (pronounced “cuh-hall”) bodies. Like a high-end garage, Cajal bodies apply the finishing touches to a variety of proteins that use small molecules of RNA to conduct their activities (telomerase, for example, uses an RNA molecule as a template for the DNA chain it tacks onto the ends of chromosomes). When appropriate, TCAB1 then chauffeurs the telomerase complex to the waiting end of a newly replicated chromosome.
“TCAB1 is absolutely necessary for the telomerase to make this jump from Cajal bodies to telomeres,” said Artandi. “When we inhibited its activity in human cancer cells, the telomeres grew shorter,” implying the cancer cells would die more quickly.
Prior to this study, TCAB1 had no known function. “Andy [Venteicher] found that TCAB1 binds not only telomerase, but also a specific class of small, non-coding RNA molecules that also end up in the Cajal bodies,” said Artandi. He added that the protein may be a common biological shuttle responsible for delivering a variety of molecules to their destinations. He and his collaborators plan to continue their study of TCAB1 and also to identify other telomerase components.
“This is a story that’s been unfolding over decades,” said Artandi. “Telomerase is such a high-priority target for many diseases, but it’s hard to attack when you know very little about it. But that’s changing now.”
—————————-
Article adapted by Medical News Today from original press release.
—————————-
The research was funded by the National Cancer Institute and the Leukemia and Lymphoma Society. Stanford graduate student Kelly McCann also participated in the research.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions – Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital at Stanford.
Source: Krista Conger
Stanford University Medical Center
Periodontal Treatment Not Found To Reduce Preterm Birth Risk
The study, involving researchers from Duke University Medical Center and the University of North Carolina at Chapel Hill, is one of the largest randomized trials to date to look at the link between the two conditions.
Previous research had suggested that gum disease was associated with very preterm deliveries (defined as less than 32 weeks gestation). That led insurance policies and healthcare providers to recommend scaling and root planing, sometimes referred to as “deep cleaning,” in pregnant women. It was thought that such care had the potential to reduce preterm delivery risk.
These new findings, based on a randomized trial of 1,800 pregnant women with periodontal disease, indicate that routine gum treatments do not reduce the risk of early delivery.
“I’m always asked whether we should mandate dental treatment for all pregnant women,” said Amy Murtha, MD, director of obstetrics research at Duke University Medical Center in Durham, NC, who presented the findings at the annual meeting of the Society for Maternal-Fetal Medicine in San Diego. “The biggest implication of this study is that this level of standard periodontal care will not affect the birth outcome.”
That’s not to say pregnant women should not get dental exams and treatment as needed; they should, Murtha added. “Our study emphasizes that treating periodontal disease during pregnancy is safe, but that standard periodontal care is not enough.”
Progression, or worsening of periodontal disease occurs in about 25 percent of pregnancies, said Steven Offenbacher, DDS, PhD, the study’s lead investigator and director of the UNC-Chapel Hill School of Dentistry-based Center for Oral and Systemic Diseases. The bacterial infection attacks the teeth-supporting tissues below the gum line. Left untreated, it can lead to tooth loss as well as a host of other problems.
This study, conducted at Duke, the University of Alabama at Birmingham and the University of Texas at San Antonio, was overseen by the UNC-Chapel Hill School of Dentistry. Pregnant women with periodontal disease were randomly assigned to two groups: one received periodontal treatment before 23 weeks gestation; the other did not. Overall, no significant differences were reported regarding obstetric or neonatal outcomes when the two groups were compared.
Despite the findings, Murtha said much remains unknown about the relationship between the two conditions. “Periodontal disease and poor pregnancy outcomes travel together, but we don’t know why.”
Nor do researchers understand how or why pregnancy appears to jumpstart the onset and progression of the disease. Murtha said it may be that preterm birth and periodontal disease share a common underlying trait, such as an exaggerated inflammatory response, but more studies are needed to fully explain the connection.
Additional research is also needed to determine whether more intensive periodontal care during pregnancy might make a difference. “Although we did not reduce the risk of preterm births, the level of periodontal care provided in this study was not as effective as compared to earlier studies,” Offenbacher said. It may be that a more aggressive approach to periodontal disease management could have a different outcome, he added.
—————————-
Article adapted by Medical News Today from original press release.
—————————-
The study was funded by the National Institute of Dental and Craniofacial Research. James D. Beck, PhD, associate dean for research and a Kenan professor within the UNC-Chapel Hill School of Dentistry, was the study’s co-principal investigator. Other UNC-Chapel Hill School of Dentistry researchers include: Luisito Mendoza, DDM and Sally Mauriello, EdD. UNC-Chapel Hill Gillings School of Global Public Health researchers include David Couper, PhD; and Dawn Stewart, MS. Researchers David Cochran, DDS, PhD, and Donald Dudley, MD, are with the University of Texas Health Science Center at San Antonio. Researchers Michael Reddy, DMD, DMSc; Nicolaas Geurs, DDS, and John Hauth, MD, are with the University of Alabama at Birmingham. Heather Jared, MS, formerly with the UNC-Chapel Hill School of Dentistry, also contributed to this research.
Source: Debbe Geiger
Duke University Medical Center
Skin Color Studies On Tadpoles Lead To Cancer Advance
The humble tadpole could provide the key to developing effective anti-skin cancer drugs, thanks to a groundbreaking discovery by researchers at the University of East Anglia (UEA).
The scientists have identified a compound which, when introduced into Xenopus Laevis tadpoles, blocks the movement of the pigment cells that give the tadpoles their distinctive markings and which develop into the familiar greenish-brown of the adult frog.
It is the uncontrolled movement and growth of pigment cells (melanophore) in both tadpoles and humans that causes a particularly dangerous form of skin cancer. By blocking the migration of these cells, the development and spread of cancerous tumours can potentially be prevented.
Published in the Cell Press journal Chemistry & Biology, the findings are the culmination of several years’ work by the UEA team. This unconventional study, which was initiated with funding from the UK Medical Research Council, identifies for the first time an effective new man-made MMP (metalloproteinase) inhibitor, known as ‘NSC 84093′.
The work was led by the University of East Anglia, in partnership with the John Innes Centre (JIC) and Pfizer.
“This is an exciting advance with implications in the fight against cancer,” said lead author Dr Grant Wheeler of UEA’s School of Biological Sciences.
“The next step is to test the compound in other species and, in the longer term, embark on the development of new drugs to fight skin cancer in humans.”
The species Xenopus Laevis (South African clawed frog) is more closely related to humans than one might expect. It only diverged from man 360 million years ago and has the same organs, molecules and physiology. This means that the same mechanisms are involved in causing cancer in both Xenopus tadpoles and humans.
Until the 1960s, Xenopus Laevis frogs were used as the main human pregnancy test. A woman’s urine sample was injected into a live frog. If the urine contained the hCG (human chrionic gonadotropin) hormone, the frog would lay eggs within 24 hours, indicating that the woman was pregnant.
—————————-
Article adapted by Medical News Today from original press release.
—————————-
‘A chemical genomic approach identifies matrix metallaoproteinases as playing an essential and specific role in Xenopus melanophore migration’ by Grant Wheeler (UEA), Matthew Tomlinson (UEA), Carla Garcia-Morales (UEA), Robert Field (JIC), Pingping Guan ( JIC), Richard Morris (JIC), Martin Rejzek (JIC) and Mark Fidock (Pfizer) is published online on January 29 and in print on January 30.
Source: Simon Dunford, Press Officer
University of East Anglia
Oncogene Inhibits Tumor Suppressor To Promote Cancer: Study Links B-RAF And LKB1
Scientists have uncovered an interesting connection between two important protein kinase signaling pathways that are associated with cancer. The research, published by Cell Press in the January 30th issue of the journal Molecular Cell, may direct new therapeutic strategies for multiple types of cancer.
The protein kinase LKB1 is a known tumor suppressor and the LKB1-AMPK signaling pathway couples energy metabolism with cell growth, proliferation and survival. “Mutations in LKB1 are not frequent in human cancers and it is not clear how tumor cells suppress the signaling pathway to gain growth advantage under conditions of energy stress (common in cancer cells),” explains senior study author Dr. Lewis C. Cantley from Beth Israel Deaconess Medical Center and Harvard Medical School.
Dr. Cantley and colleagues, including Dr. Bin Zheng, designed a study to investigate the molecular mechanisms associated with suppression of the LKB1-AMPK pathway in tumor cells. The researchers used malignant melanoma cells that often have a mutation called “V600E” in the RAF protein B-RAF. The RAF-MEK-ERK pathway is well established as a key regulator of cell growth, proliferation, differentiation and survival.
Mutations in the RAF kinase B-RAF have been found in many types of human cancer but, while oncogenic B-RAF V600E has been linked with tumor induction, growth, maintenance and progression, the specific molecular mechanisms have not been identified. Dr. Cantley’s group found that melanoma cells with the B-RAF V600E mutation had impaired AMPK activation and that inhibition of B-RAF signaling activated AMPK.
The researchers went on to show that LKB1 was phosphorylated by two kinases that are downstream of B-RAF, ERK and Rsk. The phosphorylation of LKB1 interfered with the ability of LKB1 to bind and activate AMPK. Importantly, expression of mutant LKB1 that could not be phosphorylated resulted in activation of AMPK and an inhibition of melanoma cell proliferation.
“Taken together, our results provide a molecular linkage between the LKLB1-AMPK and the RAF-MEK-ERK pathways and suggest that suppression of LKB1 function by B-RAF V600E plays an important role in B-RAF V600E-driven tumorigenesis,” says Dr. Zheng. “It’s conceivable that tumor cells must turn off the LKB1-AMPK signaling pathway to gain a growth advantage under conditions of energy stress.”
Given that B-RAF mutation and loss of LKB1 are associated with multiple types of cancer, the work is likely to have a significant clinical impact. “Further understanding of how the intriguing molecular linkage between LKB1-AMPK and RAF-MEK-ERK functions in tumorigenesis could potentially provide great therapeutic opportunities for cancer treatment,” offers Dr. Cantley.
—————————-
Article adapted by Medical News Today from original press release.
—————————-
The researchers include Bin Zheng, Harvard Medical School, Boston, MA; Joseph H. Jeong, Dana-Farber Cancer Institute, Boston, MA; John M. Asara, Harvard Medical School, Boston, MA; Yuan-Ying Yuan, Harvard Medical School, Boston, MA; Scott R. Granter, Brigham and Women’s Hospital, Boston, MA; Lynda Chin, Dana-Farber Cancer Institute; and Lewis C. Cantley, Harvard Medical School, Boston, MA.
Source: Cathleen Genova
Cell Press
With Medical School Enrollment Expanding For The First Time In 30 Years, Medical Leaders Urge Educators To Institute Curricula Reform Now
Calling this period “an unparalleled opportunity” for change, an influential group of medical leaders today urged the nation’s medical schools to reform their educational model because it too often fails to give new physicians the right mix of competencies and experiences to practice medicine effectively. The call to action for education reform comes as medical schools are expanding their enrollments for the first time in 30 years to address a shortage of physicians in the United States. In a new report, sponsored by the Josiah Macy, Jr. Foundation, the panel of experts says “medical education has not kept pace with the growing public expectations of physicians or with the novel demands of an increasingly complex healthcare system.”
According to the report “Revisiting the Medical School Educational Mission at a Time of Great Expansion,” medical schools are experiencing an historic growth spurt. By 2020, allopathic medical schools are expected to graduate an additional 5,000 doctors each year. There are nine new allopathic medical schools underway or in the planning stages, and 108 of the nation’s 126 medical schools are increasing class size, some by adding new branches. The number of osteopathic schools is growing as well. Today, there are 28 such schools in the United States, nine more than in 2000, with more planned.
“If we are going to open new schools and expand existing schools, we want to be sure we’re doing it in the most socially responsible way,” says George Thibault, MD, president of the New York-based Josiah Macy, Jr. Foundation. Thibault says this is even more important given the renewed prospects of health reform under the new Obama Administration. If more people have health insurance, there will be a much greater demand for physicians to deliver care. “What we’re saying to medical educators is let’s seize this opportunity to address the mismatch between the kinds of physicians we’re producing and what people want and need,” he says.
The 36-member panel is chaired by Jordan Cohen, MD, the former president of the Association of American Medical Colleges, and composed of medical and institutional leaders from around the country. The group was convened by the Macy Foundation in 2008 to assess ways in which expansion of enrollment could be harnessed to advance the effectiveness of medical education.
“What medical education needs to recognize is that it has a fundamental social mission to train future physicians for a rapidly changing health care system that seeks different competencies than in the past,” says Cohen. “The leaders of medical education institutions need to seize the opportunity that expansion affords to ensure that their institutions are responsive to their public purpose.”
Highlights of what areas schools should focus on:
- Giving student more opportunities to learn the principles of quality improvement, patient safety and patient-centered care;
- Preparing students to work effectively and collaborative as members of health care teams and as part of a system of care;
- Using community-based settings more as classrooms, and hospital settings less, to expose students to a more realistic practice environment;
- Ensuring that physicians have more background in public health education and the role that social factors play in affecting patient health; and
- Emphasizing the importance of problem solving and self-directed learning as a way to keep up with the fast-paced health care environment.
Expanding Diversity and Instilling Professionalism
Increasing the diversity of the applicant pool should be a top priority, the group says. One way to do this would be to relieve the burden of medical student debt. More than 80 percent of medical students today graduate with educational debt that averages $160,000.
The group suggests several ways schools can ease that burden including making additional funds available from endowments or other sources; organizing the curriculum to allow students the option of meeting graduation requirements in three rather than four years; capping tuition at current or reduced levels; and advocating the creation or support of more government programs that provide debt forgiveness in return for limited public service such as the National Health Service Corps.
The high price tag of medical schools discourages too many college students of high potential but modest means from even considering medical careers, the panel adds. The high debt also affects the kinds of physician’s medical students choose to become, which is helping to fuel a shortage of lower paid primary care doctors, such as family physicians and geriatricians.
There also is strong support for re-examining the medical school admissions process to make it more flexible, which would be an important step to attract and produce a more diverse workforce that is more culturally competent and reflective of society. The panel says schools should reduce their reliance on standardized tests, college grade point averages, and traditional undergraduate course requirements as part of the admissions process, and instead employ a more balanced, comprehensive set of admissions criteria to attract, matriculate and support students.
When it comes to professionalism, the group says there is a “conspicuous gap” between what educators say about their commitment to high professional standards and the actual behavior on display in many student learning environments. The panel says schools need to more aggressively commit to professionalism during training and expose students to positive role models that espouse the ethic of putting patients first.
What Barriers Stand in the Way?
Despite the possibility of reform, the panel admits there are substantive barriers to overcome, including:
- The need to capture the attention and active participation of institutional leaders, without which meaningful change won’t happen.
- The perception that current accreditation standards for both undergraduate and graduate medical education are overly rigid. The panel acknowledges that this perceived rigidity may keep educators from considering changes that would shift away from traditional training experiences they have grown comfortable with.
Barriers aside, the panel says schools should not let this opportunity pass them by – especially those medical schools that are just opening their doors or still in the planning stages. “They are in an optimal position to think freshly about how they are constructing their programs so they can be better aligned with societal needs,” says Cohen.
—————————-
Article adapted by Medical News Today from original press release.
—————————-
Copies of the report “Revisiting the Medical School Educational Mission at a Time of Expansion” can be obtained by visiting http://www.macyfoundation.org
The Josiah Macy, Jr. Foundation is a privately endowed philanthropy located in the borough of Manhattan, New York City. The Foundation supports programs designed to improve the education of health professionals in the interest of the health of the public.
Source: Janet Firshein
Burness Communications
