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Sábado, 25.07.15

First malaria vaccine takes a key step forward


First malaria vaccine takes a key step forward

 By Leslie Roberts 24 July 2015 2:45 pm

You’d think that the first-ever vaccine candidate to protect against malaria would be cause for jubilation. But instead, as data on the candidate, known as RTS,S or Mosquirix, have dribbled out over the past couple of years, it has been greeted with considerable head-scratching and some consternation about whether and how to use it.

The problem is that the vaccine, developed by pharmaceutical giant GlaxoSmithKline (GSK) in partnership with the PATH Malaria Vaccine Initiative, doesn’t work all that well. In a large phase III trial, it reduced episodes of malaria by about one-third in young children in sub-Saharan Africa. That’s well under the 50% efficacy expected at the beginning of the trial, and a far cry from the 95% efficacy vaccine makers dream of, leaving scientists and policymakers asking: How good is good enough?


Part of that answer came today, as the European Medicines Agency (EMA) endorsed the vaccine for use in African children 6 weeks to 17 months old. The move is a key first step on the complicated path to potentially rolling out the vaccine in sub-Saharan Africa. Under the fastest scenario, however, introduction will not begin until 2017.

“We are very much thrilled with the outcome, says Moncef Slaoui, the chair of GSK vaccines who for the past 30 years has been working alongside Joe Cohen and others to develop the vaccine. “Child health in Africa will be transformed,” he predicts.

But ask any malaria expert about what to do with RTS,S and they will tell you, “it’s complicated.” There’s no question that the vaccine candidate is a huge achievement: No one has ever developed a vaccine against a parasite, especially one as wily as Plasmodium falciparum, the major cause of malaria in Africa. And malaria is an enormous problem, claiming nearly 600,000 lives a year, mostly children in sub-Saharan Africa. New tools to reduce malaria’s toll are desperately needed.

But at the same time, everyone, including GSK scientists, wants something better from a vaccine. At the end of the multistage RTS,S trial, which overall involved 16,000 children in eight African countries, the vaccine reduced malaria cases 39% in toddlers aged 5 to 17 months and 27% in infants 6 to 12 weeks old. Because the vaccine’s efficacy wanes with time, the trial tested three doses delivered 1 month apart, followed by a booster 18 months later.

The EMA’s “positive scientific opinion,” as it is awkwardly called, essentially concludes that the benefits outweigh the risks of using the vaccine in both age groups. The opinion is not a recommendation for use or a formal approval—that is for countries to decide—but it paves the way for the World Health Organization (WHO) to make a global recommendation on whether and how to use the vaccine. The WHO is expected to issue that recommendation by the end of the year.

The EMA review is part of an arcane regulatory process known as article 58. As a service to poor countries that might not have the scientific expertise, the agency’s Committee for Medicinal Products for Human Use reviewed the scientific evidence—in this case hundreds of thousands of pages—with same rigor as it would in reviewing a drug to be marketed in the European Union.

Next, in its review, WHO will look at such real-world questions as cost-effectiveness, feasibility, and the public-health value of the vaccine compared with other interventions. The outcome could go many ways. For instance, WHO could recommend the vaccine’s use in all African countries affected by malaria or only in areas where transmission is high. It might recommend its use just in toddlers, in which efficacy was higher, or in infants as well.

A second WHO committee will rule on whether the vaccine meets international standards of quality and safety and efficacy.

As with the EMA, WHO’s recommendations are not binding, but resource-poor countries usually follow them. And donors like GAVI, the vaccine alliance, will not pay for the vaccine in poor countries without this recommendation.

Ultimately, it will be up to regulatory agencies in individual countries to decide whether to approve RTS,S. Assuming WHO recommends the vaccine’s use, it will be a “tough decision” for countries with limited resources, says Mary Hamel, an epidemiologist at the U.S. Centers for Disease Control and Prevention and one of the principal investigators. David Kaslow, vice president of product development for PATH, agrees. “It is a bit unusual since the vaccine would be introduced in context of other interventions, which also have costs associated with them,” he says.

If the vaccine does move forward, scientists and policymakers agree, it should be used only as a complement to other tools to fight malaria, such as bed nets and antimalarial drugs, not as a replacement. Nor should financing of the vaccine divert resources from other effective interventions or research, WHO said today in a statement.

The EMA’s opinion is sure to fuel an ongoing debate over whether it is better to wait for a near-perfect malaria vaccine or make the best with what you’ve got. In a BBC commentary, GAVI head Seth Berkley and Mark Dybul, head of The Global Fund, explore the dilemma.“Mosquirix is about 5 to 10 years ahead of any other candidate vaccines,” they write,  “and there’s no guarantee any of them will be better.”

“With every vaccine of course you hope for 100% protection,” Slaoui says, and GSK is already working on a second-generation vaccine. But he calls the current vaccine’s protection “substantial.” “If your child has three cases of severe malaria a year instead of six, it will change their lives.” 


Posted in Europe, Health

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por cyto às 12:36

Sábado, 25.07.15

sophisticated new probe that detects HIV’s hiding places inside and outside of cells



A DNAscope of tissue from a monkey infected with the simian AIDS virus precisely shows the distribution of viral DNA (red) in T cells (blue) and myeloid cells (green).


A DNAscope of tissue from a monkey infected with the simian AIDS virus precisely shows the distribution of viral DNA (red) in T cells (blue) and myeloid cells (green).

'Molecular microscrope' finds hidden AIDS virus in the body

By Jon Cohen 24 July 2015 12:45 pm

Researchers have developed a sophisticated new probe that detects HIV’s hiding places inside and outside of cells. “It’s a fantastic new technique that’s going to allow us to visualize the virus in tissues like we’ve never been able to before,” says immunologist Richard Koup, deputy director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, who was not involved in the research. Insights from this high-powered molecular microscope, revealed at an international AIDS conference last week, may clarify critical questions about HIV persistence and, ultimately, about how to rid the body of the virus.

To date, assessments of HIV in tissue—known as in situ analysis—have been hampered by one major difficulty. The most common probes, which use fluorescent markers or radioactive labels to pinpoint the virus’s location in a tissue sample, sometimes have difficulty distinguishing the target—HIV RNA and DNA—from surrounding cellular components. In essence, a marker can mislabel cell tissue as the virus, creating background noise that throws off the analysis. The new technique has “very little noise,” says immunologist Jake Estes of the Frederick National Laboratory of the National Cancer Institute (a sister of NIAID) in Frederick, Maryland, who used it to produce highly detailed images of the AIDS virus in various monkey tissues (above) that he presented at the conference.

Estes developed the technique in collaboration with Advanced Cell Diagnostics of Hayward, California, by modifying the company’s already existing RNAscope product to detect HIV RNA, DNA or both at the same time. RNA and DNA are made of nucleotides that pair with a complement—guanine, for example, binds to cytosine. Traditional methods for mapping HIV genetic material use long strings of these nucleotides, called oligomers, to find and bind to complimentary strands of DNA or RNA in sample tissues. These oligomers are labeled with a marker so they send a signal when they hit their target, allowing researchers to create an image of precisely where the viral genetic material is dispersed throughout the tissue sample. But oligomers are large and somewhat clumsy molecules, and they occasionally bind to cellular components other than the target sequence.

Estes’s new technique, in contrast, uses a more complex probe system that all but eliminates those kinds of errors. In essence, the approach chops an oligomer in two and sends both halves out to find the target sequence. Their markers light up if an additional oligomer that bridges the two halves binds to both, which only occurs when they park next door to each other on the target. The probability is extremely low that the two probes would land next to each other on anything other than HIV.

HIV is an RNA virus, but it also converts to a DNA form that allows it to weave its genes into a human chromosome. Estes, who works with virologist Jeffrey Lifson, has also developed a DNAscope to visualize this HIV DNA—called the provirus—which becomes integrated into human cells and can persist for decades without being attacked by the immune system or antiretroviral (ARV) drugs. “Reservoirs” of infected cells that hold latent provirus are a key reason why powerful combinations of ARVs cannot eliminate infections and cure people.

Estes, Lifson, and co-workers infected monkeys with the simian version of the AIDS virus and then analyzed tissues from many parts of their bodies. Their RNAscope and DNAscope were able to distinguish cells that harbor the provirus, viral RNA, or even viruses outside of cells much more clearly than any previous in situ technique. “We’re convinced that we can see individual virions and that this has exquisite sensitivity and specificity,” Estes says. To double check their work, they counted HIV virions by eye in one of their new images, and then compared their count to a validated measure of viral levels. “We see a beautiful correlation,” Estes says.

HIV/AIDS researchers working to cure the infection face several obstacles that these new scopes could help overcome. One is the lack of detectable virus in the blood plasma of patients on effective ARV therapy, which makes it difficult for researchers to assess whether an intervention aimed at curing the infection is working. Several techniques exist to measure changes in reservoirs, but each has shortcomings that the new scopes might be able to supplement. Another obstacle is not knowing precisely where in the body the provirus prefers to hide. If the new probes can help solve this longstanding riddle, they could refine attempts to shrink viral reservoirs. “If we can go in and see what happens to the virus in these different tissues with this sort of sensitivity and specificity, it’s going to answer a lot of questions,” NIAID’s Koup says.


Posted in Health

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por cyto às 12:25

Sábado, 25.07.15

Multigene Panel Testing in Oncology Practice


Multigene Panel Testing in Oncology Practice: How Should We Respond? 

Allison W. Kurian, MD, MSc1,2; James M. Ford, MD1,3
JAMA Oncol. 2015;1(3):277-278. doi:10.1001/jamaoncol.2015.28.
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A great success of modern human genetics is the identification of specific genes that, when altered, confer clinically recognized traits, such as cancer susceptibility, and enable predictive genetic testing. In past decades, cost and turn-around time limited cancer genetic risk assessment, and it was rarely feasible to test a patient for more than 1 well-defined condition (eg, hereditary breast ovarian cancer [HBOC] or Lynch syndrome). Transformative sequencing advances now permit massively parallel, rapid analysis of many genes, making the “$1000 genome” an imminent reality. In June 2013, long-term barriers to cancer genetic testing were breached by a remarkable convergence of events: the disclosure of her BRCA1 mutation by the actress Angelina Jolie, which dramatically increased public awareness and demand for genetic testing1; and the US Supreme Court decision against gene patenting, which allowed competition to reduce the price ofBRCA1 and BRCA2 (BRCA1/2) testing.2 Incentives quickly shifted toward sequencing more genes as laboratories competed to offer panels of increasing numbers of genes (from 6 to >100) at decreasing prices. Perhaps because testing costs have fallen so greatly, insurers rarely object to multigene panels as a means of diagnosing recognized syndromes (eg, HBOC) when relevant guidelines are met. However, most payers will not cover more than 1 cancer risk assessment test, creating an incentive to sequence any genes of interest concurrently rather than sequentially. In short, multigene panels have entered the clinic,3 and there seems little chance of forcing the genie back into the bottle.

Fortunately, multigene panels offer significant benefits over sequential single-gene testing. They are cheaper, faster, and more efficient for differential diagnosis. Most important, they may identify deleterious mutations that the pedigree would not suggest, particularly for families with cancer patterns that deviate from recognized syndromes. These advances come with drawbacks, however, related to the lack of a testing track record for many genes on commercially available panels.4 Panel testing is complicated by 3 levels of uncertainty about mutations in less widely tested genes, regarding (1) the magnitude of cancer risk (penetrance), (2) the anatomical and age-specific scope of cancer risk, and (3) the clinical relevance of missense variants in genes for which the spectrum of normalcy is poorly defined. Variants of uncertain significance (VUS) increase in frequency with the number of genes sequenced,5 and, if skilled genetic counseling is not provided, this may cause anxiety and unwarranted interventions. Recently, concerns have arisen that technical advances in genomics have outpaced our ability to provide safe, ethical care. When guided by appropriate expertise and in conjunction with clinical research, however, multigene panels offer substantial opportunities to improve cancer risk assessment, early detection, and prevention.

Ideally, a new test would enter patient care only after all essential questions about its interpretation were answered. Instead, we must now evaluate multigene panel testing in medias res. Our recommendations for next steps include research, referral, and training.

Well-designed studies are crucial to determine the clinical and societal value of multigene panel testing. Studies must evaluate cancer causation associated with mutations in unfamiliar genes (eg, BRIP1, RAD51D), particularly among families not meeting traditional syndromic criteria; must elucidate mutation prevalence and penetrance, and the anatomic, pathologic, and prognostic characteristics of associated cancers; and must evaluate panel testing’s impact on the uptake and outcomes of screening and prophylactic procedures. High-priority topics include the effectiveness of clinician-patient communication and the health care delivery systems required for panel testing, with consideration of access and ethics; and the cost-effectiveness of a multigene panel vs sequential single-gene testing strategy. We urgently need a bioinformatics infrastructure for data sharing, rapid VUS reclassification, and active case-finding of mutation carriers’ at-risk relatives: such infrastructure will be mandatory for consideration of whole-genome sequencing in routine practice. The Table presents a proposed research agenda.

Table.  Proposed Research Agenda for Multiple-Gene Panel Testing
Image not available.

The exponential growth in data volume and complexity strains existing counseling models,6 which entail discussion of gene-specific cancer risks and evidence-based interventions for well-studied syndromes. Clinicians face new and difficult questions:


  • For which patients is a multigene panel indicated instead of a single-gene test?

  • For which patients will insurance cover a multigene panel?

  • Which panel should be used: high-penetrance (5-6 genes), tumor site-specific (15-20), or broader (25-100)?

  • Should patients be counseled about the specific risks of each gene before testing?

  • How to manage mutations inconsistent with family history (eg, CDH1, no gastric cancer)?

  • Should relatives be offered testing for mutations of uncertain penetrance (eg, CHEK2)?

  • How should patients be counseled about VUS, given their high rate with multigene panels?

  • Should less familiar mutations be managed similarly to recognized syndromes (eg, screening breast magnetic resonance imaging for PALB2 as for BRCA1/2 mutation carriers)?


Proposed modifications to the clinician-patient encounter, including a streamlined counseling approach guided by clinical relevance, are being tested in important clinical trials.7

Amid this uncertainty, a point of clarity emerges: that expertise in cancer genetics, always endorsed by the American Society of Clinical Oncology, National Comprehensive Cancer Network, and others,4 is more critical now than ever before. We recommend referral to expert clinicians for test selection, pretest and posttest counseling whenever possible. The existing workforce is insufficient, and thus we urge a societal investment in training for genomics and precision medicine, both of genetic counselors and of interested physicians in oncology and other specialties.

The growing accessibility of genomic sequencing has a dazzling potential to transform oncology and medicine. However, the imperative to do no harm mandates that we exercise careful judgment in (1) the patients we select for multigene panel testing; (2) the number and identity of genes we sequence, with custom gene selection a rational alternative to prefabricated panels; and (3) the cancer screening and prevention strategies we advise.

Practice guidelines are evolving with emerging evidence, but it is important to maintain a clear separation between routine care and research,4 particularly for comprehensive strategies such as whole-genome sequencing. Patient care should be guided by the family cancer history when a less-studied mutation is detected, and participation in well-designed trials of testing, communication, and intervention strategies (Table) should be strongly encouraged.


Corresponding Author: Allison W. Kurian, MD, MSc, Division of Oncology, Stanford University School of Medicine, HRP Redwood Building, Room T254A, 150 Governor’s Lane, Stanford, CA 94305-5405 (

Published Online: March 5, 2015. doi:10.1001/jamaoncol.2015.28.

Conflict of Interest Disclosures: Drs Kurian and Ford have received research funding from Invitae and from Myriad Genetics.

Correction: This article was corrected on March 25, 2015, to fix reference 3.


Borzekowski  DL, Guan  Y, Smith  KC, Erby  LH, Roter  DL.  The Angelina effect. Genet Med. 2014;16(7):516-521.
PubMed   |  Link to Article
Offit  K, Bradbury  A, Storm  C, Merz  JF, Noonan  KE, Spence  R.  Gene patents and personalized cancer care. J Clin Oncol. 2013;31(21):2743-2748.
PubMed   |  Link to Article
Hooker  GW, Nagy  R, Buchanan  A,  et al. Cancer genetic counseling and testing in an era of rapid change. Abstract presented at the American College of Medical Genetics Annual Meeting; March 25, 2014; Nashville, Tennessee.
Hall  MJ, Forman  AD, Pilarski  R, Wiesner  G, Giri  VN.  Gene panel testing for inherited cancer risk. J Natl Compr Canc Netw. 2014;12(9):1339-1346.
Kurian  AW, Hare  EE, Mills  MA,  et al.  Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment. J Clin Oncol. 2014;32(19):2001-2009.
PubMed   |  Link to Article
Stadler  ZK, Schrader  KA, Vijai  J, Robson  ME, Offit  K.  Cancer genomics and inherited risk. J Clin Oncol. 2014;32(7):687-698.
PubMed   |  Link to Article
Bradbury  AR, Patrick-Miller  L, Long  J,  et al.  Development of a tiered and binned genetic counseling model for informed consent in the era of multiplex testing for cancer susceptibility [published online October 9, 2014]. Genet Med. doi:10.1038/gim.2014.134.

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por cyto às 12:14

Sábado, 25.07.15

Model shows how cancerous tumors manipulate blood-vessel growth


Model shows how cancerous tumors manipulate blood-vessel growth

A simulation has been built to show how cancerous tumors manipulate blood-vessel growth for their own benefit. Since the ability to stop tumors through anti-angiogenesis is one goal of cancer therapy, this new work should help researchers quickly test strategies with sophisticated computer models.

Like all cells, those in tumors need access to the body's fine network of blood vessels to bring them oxygen and carry away waste. Tumors have learned to game the process called angiogenesis in which new vessels sprout from existing ones, like branches from a tree.

The research team created a detailed model of how proteins involved in angiogenesis communicate with each other and how tumors take charge of the protein signaling chain that controls vessel growth. They were led by theoretical physicists José Onuchic, PhD, and Eshel Ben-Jacob, PhD, both at Rice University in Houston, Texas.

A key finding in the work, published in the Proceedings of the National Academy of Sciences (2015; doi: 10.1073/pnas.1511814112), showed that ligands known as "jagged" play a major role in the chaotic vessel growth observed around tumors.

In normal growth, an endothelial cell sprouts from an existing vessel as a tip, while others that follow the tip cell become the stalk cells that ultimately form vessel walls. The cell-to-cell notch signaling pathway directs the endothelial cell's decision to become a tip or stalk.

Notch receptors are proteins that bind with delta ligand or jagged ligand molecules produced by cells. How they interact determines the cell's fate. When notch and delta bind, they prompt a few cells to be tips and adjacent ones to be stalks; how this happens was the subject of an earlier study.

The new model has uncovered the role of jagged ligands. Because jagged is overexpressed in the tumor environment, notch-jagged binding overpowers notch-delta and results in a new kind of cell, a tip/stalk hybrid. While such cells can still form new vessels, these vessels rarely mature.

"You get blood vessels that send out many branches, but very few of them are as well-developed as seen during normal angiogenesis," said coauthor Mohit Kumar Jolly, a Rice University bioengineering graduate student.

"High levels of jagged in the environment can trigger the formation of blood vessels that are useful to the tumor: fast-developing, leaky, and spread chaotically all over the tumor mass," added lead author Marcelo Boareto, a postdoctoral fellow at the Swiss Federal Institute of Technology in Zurich, Switzerland.

"Tumors don't have to wait for the vessels to develop," Onuchic said. "They take advantage of the leakiness of the structure."

The notch-delta pathway has been heavily studied and is the target of many anti-angiogenesis drugs now in use, according to the researchers. "We wondered exactly what notch-jagged signaling does that is not done in notch-delta signaling," Boareto said. "We find that when the cells communicate mostly via jagged, we see a new kind of cell that is not exactly tip and not exactly stalk, but somewhere in between.

"This compromised cell is the major difference between normal and tumor angiogenesis and suggests that if notch-jagged signaling can be somehow suppressed without affecting notch-delta, we can probably disrupt tumor angiogenesis," he said.

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por cyto às 12:06

Sábado, 25.07.15

Cancers caught during screening colonoscopy are more survivable


Cancers caught during screening colonoscopy are more survivable

July 13, 2015

Patients whose colorectal cancer (CRC) is detected during a screening colonoscopy are likely to survive longer than those who wait until they have symptoms before having the test, according to a study in the July issue of GIE: Gastrointestinal Endoscopy, the monthly peer-reviewed scientific journal of the American Society for Gastrointestinal Endoscopy (ASGE).

The study, "Survival in patients with diagnosed by screening ," looked at 312 patients in 10 gastroenterology practices in Germany, all aged 55 or older, who were diagnosed with CRC in 2003-2005. Of those, 60 patients were diagnosed during a , meaning they had no symptoms and/or only a negative test (FOBT). The other 252 patients had their cancers detected during a diagnostic colonoscopy, following a positive FOBT and/or symptoms including abdominal pain, , weight loss, changes in bowel habits, or rectal bleeding.

None of the patients had had a previous colonoscopy, and all received endoscopic follow-up care. The patients were followed for as long as 10 years after diagnosis.

Patients whose cancer was detected during screening colonoscopy lived 20.2 months longer, on average, than those who had the test after noticing symptoms or having a positive FOBT (diagnostic colonoscopy). The latter group tended to have more advanced stage tumors; as expected, those whose cancer was in a more advanced stage had shorter survival times.

About 55 percent of the patients with diagnostic colonoscopy, and about 77 percent of the screening colonoscopy patients, survived beyond the time period of the study.

According to the lead author, Kilian Friedrich, MD, "We know that screening colonoscopy can prevent cancer by detecting and removing precancerous polyps. Independent of that, this study shows that screening colonoscopy also can contribute to reduced mortality from colorectal cancer by catching tumors at earlier and more treatable stages."

The researchers concluded that, although screening approaches differ between nations, this finding of increased survival among recipients of screening colonoscopy likely applies to other countries.

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por cyto às 12:00

Sábado, 25.07.15

Low-grade brain tumor diagnosis redefined


Low-grade brain tumor diagnosis redefined


A tumor's DNA, and not just the tumor stage and what the affected cells look like under a microscope, is key to determining if a lower-grade malignant brain tumor (glioma) may rapidly progress to glioblastoma, the most common and deadliest form of malignant brain cancer. This multicenter, national study, and its proposed changes in how some brain tumors are classified and ultimately treated, were published in the New England Journal of Medicine (2015; doi:10.1056/NEJMoa1402121).

The findings, according to researchers from the Hermelin Brain Tumor Center at Henry Ford Hospital in Detroit, MI, could result in earlier and more aggressive treatment for those tumors projected to be on the fast path. Looking at DNA changes may also open treatment options in a move toward precision medicine.

Glioma is the most common type of malignant brain tumor with 6,500 expected cases of grade 2 and grade 3, and 12,500 expected cases of grade 4 (glioblastoma) each year.

Though glioblastoma has notably poor prognosis, the lower grades have survival that is harder to predict. Some patients may progress and succumb by 6 months, while others may survive 15 years. In this study, diagnosis criteria using changes in tumor DNA was found to improve the prediction.

Glioma is very difficult to treat successfully because, rather than being a clearly defined mass, the tumor blends with healthy brain tissue and sends out tentacles of microscopic cancer cells. This makes complete neurosurgical resection impossible and leaves the chance for tumor recurrence and progression.

"This new study holds a great deal of promise for our patients because we will no longer have to wait the months or years after surgery to determine if a particular glioma will progress to a glioblastoma," said Steven N. Kalkanis, MD, co-director of the Hermelin Brain Tumor Center.

"Now genes in the tumor can be quickly analyzed to look for any changes, deletions or other mutations, allowing us the opportunity to treat gliomas that may become glioblastomas more aggressively at the start, potentially leading to longer survival."

For more than 100 years, clinicians have been diagnosing and determining treatment for gliomas based on histologic classes developed in the early 1900s. Using this method, gliomas were classified microscopically on the basis of their similarity to a specific cell of origin (astrocyte, oligodendrocyte or a mixture of these cells), often making diagnosis subjective.

But diagnosis based on the molecular make up of a tumor takes away a great deal of uncertainty and offers a more concrete diagnosis. The study analyzed 293 lower-grade gliomas (grade 2 and grade 3) from adults. The samples were integrated with patient clinical data to test for associations.

For the study, gliomas were clustered into classes based on their genetic similarity. These clusters were then compared against tumor grade, histologic class, and molecular subtype.

When the researchers grouped gliomas according to IDH gene mutation and chromosome deletion status, they found three distinct molecular classes emerge that were more consistent with IDH gene mutation and 1p/19q chromosome deletion than with histologic class.

These findings suggest that lower-grade gliomas with wild-type IDH gene mutations are likely to behave like tumors diagnosed as glioblastoma with wild-type IDH.

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por cyto às 11:54

Sábado, 25.07.15

Study finds state regulations linked to late cancer diagnoses


Study finds state regulations linked to late cancer diagnoses

July 20, 2015

States' regulations of health insurance and practitioners significantly influence when patients receive colorectal or breast cancer diagnoses, especially among people younger than the Medicare-eligible age of 65, according to a new study by researchers at Georgia State University's School of Public Health and the University of North Carolina at Chapel Hill.

The study suggests that where people live is a strong predictor of whether they will receive potentially life-saving screenings.

Dr. Lee Rivers Mobley, associate professor of spatial science and health economics at Georgia State's School of Public Health, was the principal author of "United States Health Policies and Late-Stage Breast and Colorectal Cancer Diagnosis: Why Such Disparities by Age?" recently published in Health Economics Review.

"Progress has been made in the war against cancer, yet the high proportions of late-stage diagnoses remain a concern," the researchers noted in their study.

Late-stage diagnoses range from 54 to 60 percent of newly diagnosed cases across the states, while late-stage diagnoses range from 24 to 36 percent, the study found.

Colorectal cancer is the second leading cause of cancer deaths in the United States and the risk of developing it rises after age 40. Despite overall declining rates of colorectal cancer—largely because of endoscopic screenings and polyp removal—rates have been increasing steadily since 1998 among those younger than 50 "for whom screening is not routinely recommended," the authors said. Breast cancer is the second leading cause of cancer deaths among women and its rates have remained steady since about 2003.

The researchers concluded that a state's regulatory climate is "an important predictor" of late-stage colorectal and breast cancer diagnoses.

The study examined individual states' regulatory policies and analyzed cancer cases in 40 states from the United States Cancer Statistics (USCS) database reported between 2004 and 2009 to determine whether area cancer screening use or accessibility to health care providers affected odds of late-stage diagnosis. The study excluded 10 states, including Illinois and Ohio, because of incomplete or incompatible data sets.

Mobley and the study's co-author, Dr. Tzy-Mey Kuo, a researcher at North Carolina's Lineberger Comprehensive Cancer Center, are the first team to use the newly available USCS database, which is housed in the National Center for Health Statistics Research Data Center at the Centers for Disease Control and Prevention.

The researchers also noted they designed the study to end in 2009 so that future research may evaluate the effects of recent insurance regulations, notably the Affordable Care Act of 2010.

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por cyto às 11:50

Sábado, 25.07.15

Simulation tool teaches clinical breast examination

Simulation tool teaches clinical breast examination


Despite the use of ever-increasingly advanced technology to diagnose breast cancer, the role of the clinical breast examination is as important as ever. To further advance the hands-on technique, a new sensor-based tool has been designed to improve the technique.

Carla Pugh, MD, PhD, and her group at the University of Wisconsin (UW) Health Clinical Simulation Program are known for innovating the use of simulation-based tools for teaching and evaluating surgical and examination techniques. They have explored sensor-based techniques for cast placement and removal, for learning ultrasound examination of the thyroid, and for teaching pelvic examinations in the developing world.1-3 Recently, Pugh's team focused on refining the clinical breast examination. Pugh, a surgeon, is clinical director of the UW Health Clinical Simulation Program and director of patient safety and education at the University of Wisconsin Hospital and Clinics. She is a proponent of using haptic skills in medicine, and to that end she has created a variety of simulative models for teaching clinicians effective manual examination techniques.


In a talk at TedMed 2014, Pugh described haptics as “the art and science of touch. Knowing how to touch something. Knowing how things are supposed to feel.” It is the ability to discern the difference between what is normal and what is not normal. The tricky thing about haptics is that we do not have a sure-fire way of teaching it; nor do we have a way of measuring it. Therefore, we have no way of measuring an operator's competency in the technique, Pugh explained.4

“How could clinicians learn the technique? How can a body of knowledge be mastered when some of its most important aspects cannot be taught in a lecture, read in a book, or even be experienced—such as in an emergency, when situation can change so quickly?”4


The current method for training a clinician to perform a clinical breast examination is to have an experienced practitioner observe the trainee palpate the breast. Visual observation, however, does not convey the degree of pressure the trainee is using to palpate the breast and whether it is enough to detect a mass, which is the crucial point of the examination. To this end, Pugh and her team devised a sensor system that registers the amount of force applied. The device creates a map of the trainee's palpation that shows blue where the least pressure was applied and red where the most pressure was applied.

The UW group conducted a study in 2013 and 2014 to see how much more accurate the haptic sensor-equipped training device is compared with an examination conducted by an experienced clinician.5 For the project, practicing physicians performed simulated clinical breast examinations exactly the way they would on a symptomatic patient who presents in an office visit. The fictional patient claims to have felt a mass on self-examination but is currently unable to locate the lesion.


The researchers recruited a total of 553 physician attendees from three annual clinical meetings: the American Society of Breast Surgeons (136 doctors), the American Academy of Family Physicians (236 doctors), and the American College of Obstetricians and Gynecologists (181 doctors). The participants used the Pugh devices specifically developed to teach breast examination techniques. There were four models.

  • Model A had a soft, superficial mass measuring 2 cm by 2 cm.
  • Model B was the same as model A, except the mass was smaller (2 cm by 1 cm).
  • Model C had a hard, 2-cm mass located near the chest wall.
  • Model D was the same as model C, except the mass was molded from a soft silicone derivative.

The videos, combined with sensor-map recordings, show successful and unsuccessful techniques for clinical breast examinations. The least successful technique was associated with a light palpation; that technique placed the physicians at significant risk for missing deep-tissue lesions near the chest wall.

This study underscores the potential that sensor technology has for teaching proper technique and thereby extending the lives of patients who might otherwise be lost to breast cancer.


Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey. 


1.  Maag AL, Laufer S, Kwan C, Cohen ER, Lenhart RL, Stork NC, Halanski MA, Pugh CM. Sensor-based assessment of cast placement and removal. Stud Health Technol Inform. 2014;196:259-61.

2: Kwan C, Cohen E, Pugh C. Application of a new adaptable thyroid model for ultrasound and hands-on skill assessment. Stud Health Technol Inform. 2014;196:230-2.

3: Kwan C, Cohen E, Salud L, Pugh C. Modification of the pelvic examination simulator for the developing world. Stud Health Technol Inform. 2014;196:222-4.

4. TedMed 2014: Carla Pugh. Available at: Accessed April 12, 2015

5: Laufer S, Cohen ER, Kwan C, D'Angelo AL, Yudkowsky R, Boulet JR, McGaghie WC, Pugh CM. Sensor technology in assessments of clinical skill. N Engl J Med. 2015 Feb 19;372(8):784-6.. 

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por cyto às 11:47

Sábado, 25.07.15

Clear Connection between Wireless Devices and Cancer


Study Suggests Clear Connection between Wireless Devices and Cancer

24 July 2015 Taylor & Francis


A metabolic imbalance caused by radiation from your wireless devices could be the link to a number of health risks, such as various neurodegenerative diseases and cancer, a recent study suggests.

“Oxidative Mechanisms of Biological Activity of Low-intensity Radiofrequency Radiation,” a review article published in Electromagnetic Biology & Medicine, explores experimental data on the metabolic effects of low-intensity radiofrequency radiation in living cells.

This imbalance, also known as oxidative stress, is defined by co-author Dr. Igor Yakymenko as, “an imbalance between the production of reactive oxygen species (ROS) and antioxidant defence.”

Yakymenko explains the oxidative stress due to RFR exposure could explain not only cancer, but also other minor disorders such as headache, fatigue, and skin irritation, which could develop after long-term RFR exposure.

“These data are a clear sign of the real risks this kind of radiation poses for human health,” Yakymenko said. 

The article explains that ROS are often produced in cells due to aggressive environments, and can also be provoked by “ordinary wireless radiation.”

Up-to-date research demonstrates possible carcinogenic effects of radiofrequency (RFR)/microwave radiation. In 2011, the International Agency for Research on Cancer classified RFR as a possible carcinogen for humans. But clear molecular mechanisms of such effects of RFR were a bottleneck in acceptance of a reality of risk.

The article demonstrates that the hazardous effects of RFR could be realized through the “classical mechanisms” of oxidative impairments in living cells.

Yakymenko and his colleagues call for a precautionary approach in using wireless technologies, such as cell phones and wireless Internet.

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por cyto às 02:01

Quinta-feira, 23.07.15

Dartmouth researchers perform first total syntheses of compounds involved in rapid cell death in leukemia


Dartmouth researchers perform first total syntheses of compounds involved in rapid cell death in leukemia

Published on July 22, 2015 at 5:18 AM 

Dartmouth researchers and their colleagues have carried out the first total syntheses of certain compounds involved in excessive cell death in leukemia.

The findings appear in the journal Angewandte Chemie International Edition. A PDF is available on request.

"We anticipate that these compounds will serve as useful tools for dissecting an important but as yet undefined step in the regulation of apoptosis," says senior author Jimmy Wu, an associate professor of chemistry at Dartmouth. "Studies to clarify the biological mechanism by which they operate are ongoing."

The researchers completed the total syntheses of several members of the family of dimeric nuphar alkaloids, which are compounds previously isolated from the yellow pond lily. These are structurally complex molecules that are capable of including apoptosis, or programmed cell death, in certain human leukemia cell lines faster than any other small molecule. The researchers also were able to synthesize some related structures that they predict might exist in nature but have not yet been found.

There have been only two reports that attempt to explain the biological mechanism of action of these molecules. But these are incomplete and more research is required to fully reveal how these compounds work. The Dartmouth-led team's synthetic efforts now provide a means to a steady supply of the active compounds for further study. Preliminary biological tests conducted by co-author Alan Eastman, a professor of pharmacology and toxicology at Dartmouth's Geisel School of Medicine, indicate that all the compounds, both naturally occurring and ones predicted to be exist in nature, are capable of inducing extremely rapid apoptosis in leukemia cells. The researchers are in the process of studying their biological mechanism of action.

"Insufficient apoptosis is strongly linked to cancer and autoimmune disorders," Wu says. "There are also numerous diseases associated with excessive cell death, such as AIDS, Alzheimer's, Huntington's, Parkingson's and ALS. A better understanding of the biological basis of how the dimeric nuphar alkaloids can so rapidly induce cell death may lead to novel points of intervention for the design of prospective therapeutics and other diseases attributed to abnormal apoptosis."


Dartmouth College

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por cyto às 22:57

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Julho 2015