Scientists at the Wellcome Trust Sanger Institute and their international collaborators have shown that acute myeloid leukemia (AML) is not a single disorder, but at least 11 different diseases, and that genetic changes explain differences in survival among young AML patients. Published in June 9, 2016 issue of the New England Journal of Medicine, the ground-breaking study on the genetics of AML could improve clinical trials and the way patients are diagnosed and treated in the future. The open-access NEJM article is titled “Genomic Classification and Prognosis in Acute Myeloid Leukemia.” In the largest study of its kind, researchers studied 1,540 patients with AML who were enrolled in clinical trials. They analyzed more than 100 genes known to cause leukemia, in order to identify common genetic themes behind the development of the disease. The researchers found that the patients could be divided into at least 11 major groups, each with different constellations of genetic changes and distinctive clinical features. Despite finding common themes however, the study also showed that most patients had a unique combination of genetic changes driving their leukemia. This genetic complexity helps explain why AML shows such variability in survival rates among patients. Full knowledge of the genetic make-up of a patient's leukemia substantially improved the ability to predict whether that patient would be cured with current treatments. This information could be used to design new clinical trials to develop the best treatments for each AML subtype, with the ultimate goal of bringing more extensive genetic testing into routine clinical practice. Dr.
A species of tropical fish has been shown to be able to distinguish between human faces. It is the first time fish have been shown to have this ability. The research, carried out by a team of scientists from the University of Oxford (UK) and the University of Queensland (Australia), found that archerfish (photo) were able to learn and recognize faces with a high degree of accuracy -- an impressive feat, given this task requires sophisticated visual recognition capabilities. The study was published online on June 7, 2016 in the journal Scientific Reports. The open-access article is titled “Discrimination of Human Faces by Archerfish (Toxotes chatareus).” First author Dr Cait Newport, Marie Curie Research Fellow in the Department of Zoology at Oxford University, said: “Being able to distinguish between a large number of human faces is a surprisingly difficult task, mainly due to the fact that all human faces share the same basic features. All faces have two eyes above a nose and mouth, therefore to tell people apart we must be able to identify subtle differences in their features. If you consider the similarities in appearance between some family members, this task can be very difficult indeed. It has been hypothesized that this task is so difficult that it can only be accomplished by primates, which have a large and complex brain. The fact that the human brain has a specialized region used for recognizing human faces suggests that there may be something special about faces themselves. To test this idea, we wanted to determine if another animal with a smaller and simpler brain, and with no evolutionary need to recognize human faces, was still able to do so.” The researchers found that fish, which lack the sophisticated visual cortex of primates, are nevertheless capable of discriminating one face from up to 44 new faces.
When gardeners look at a petunia, they see the vibrant and versatile blooms of the most popular bedding plant in the U.S. But when plant scientists look at a petunia, they see an important model plant species--one that just became more useful with the release of its parents' genomes. An international consortium of researchers has sequenced the two wild parent species of the domesticated petunia. The study, which was published online on May 27, 2016 in the journal Nature Plants, reveals that the petunia has a complicated genetic history, having undergone one whole genome triplication shared with all the Solanaceae, and identifies an especially dynamic portion of the genome containing genes for color and scent. The published genomes will be a valuable resource for the many scientists who use the petunia to explore biological questions relating to symbiosis, self-fertilization, and circadian rhythms. The open-access Nature Plants article is titled “Insight into the Evolution of the Solanaceae from the Parental Genomes of Petunia hybrid.” "Petunia is the most important bedding plant in the U.S.," said first author Aureliano Bombarely, Ph.D., an Assistant Professor of Horticulture at Virginia Polytechnic Institute and formerly a postdoctoral scientist at the Boyce Thompson Institute (BTI) in New York, while working on the petunia genome. But besides its use in landscaping, the petunia has been used to study transposable elements--bits of DNA that can move independently around the genome--and has also been used as a model for flower development, scent production, and interactions with pollinators. Domesticated petunias (Petunia hybrida) are a hybrid of two wild species; one with a small, purple flower called Petunia inflata and one with a larger white flower called Petunia axillaris.
A Washington State University biologist has found what he calls "very strong support" for an 86-year-old hypothesis about how nutrients move through plants. His two-decade analysis of the phenomenon has resulted in a suite of techniques that may ultimately be used to fight plant diseases and make crops more efficient. Some 90 percent of the food we consume at one time went through a plant's phloem, the vascular system that carries sugars and other nutrients from leaves, where they are produced by photosynthesis, to roots and fruits. But scientists know so little about how this works, said Michael Knoblauch, Ph.D., professor in the WSU School of Biological Sciences, that they're like cardiologists who haven't learned about the heart. "If you have a little-supported hypothesis that is central to plant function, it's a problem," he said. "For example, take plant-insect interactions. Aphids feed on the system. If we don't understand how the system works in detail, we cannot find new strategies to kill aphids. Plant viruses also move through the system." The fundamental principle of phloem transport was published by Ernst Münch in 1930. While his hypothesis is intuitive and elegant, it does not appear to account for the extreme pressure needed to move fluid in something as large as a tree. Münch left that to others to figure out. "He came up with the hypothesis because he knew how solute-driven flow could work," said Dr. Knoblauch. "But he was not into measuring all these things or finding evidence for his hypothesis." To make his findings, published online on June 2, 2016 in the journal eLife, Knoblauch spent more than 20 years devising ways to look inside a living plant without disrupting the processes he was trying to measure and describe.
A Web-mediated follow-up application (Moovcare™) improves advanced lung cancer survival, according to a French multicenter randomized phase III study. Researchers analyzed the association and evolution of self-reported clinical symptoms over time. The median overall survival of patients who used the application was 19 months, compared to 12 months for those who received standard follow-up care. Patient quality of life was also better among patients who used the application. The study was featured in a press briefing June 6, 2016 and presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting (June 3-7) in Chicago, Illinois. “Through personalized follow-up using this convenient and simple online application, we can detect complications and signs of relapse and offer appropriate care earlier,” said lead study author Dr. Fabrice Denis, M.D., Ph.D., a researcher at the Institut Inter-regional de Cancérologie Jean Bernard in Le Mans, France. “This approach introduces a new era of follow-up in which patients can give and receive continuous feedback between visits to their oncologist.” After completing initial chemotherapy, radiation therapy, or surgery, 133 patients with stage III/IV lung cancer were randomly assigned to Web-mediated follow-up or standard follow-up. The standard follow-up included doctor visits and CT scans every 3-6 months (or more often at the researcher’s discretion). Patients in the Web-application group had the same schedule of planned doctor visits, but three times fewer scheduled scans. They used the Web application to self-assess symptoms weekly. Caregivers could also enter data on behalf of the patients. The application analyzed twelve symptoms and reported results to the oncologist.
An international team of researchers has discovered unexpected functions of small nucleolar RNAs (snoRNAs) that may explain the cause of some human diseases. The research, led by Professor Stefan Stamm from the University of Kentucky and Professor Ruth Sperling from the Hebrew University of Jerusalem, appears in the March 22, 2016 issue PNAS. The article is titled “Dual Function of C/D Box Small Nucleolar RNAs in rRNA Modification and Alternative Pre-mRNA Splicing.” The loss of snoRNAs is associated with a number of diseases, including Prader-Willi syndrome, which characterized by an insatiable appetite, and several forms of cancer: smoldering multiple myeloma, breast cancer, and prostate cancer. Also, genetic duplications of some snoRNAs could play a role in autism. However, it has not previously been clear how changes in snoRNA expression could lead to these diseases. Using RNA sequencing and molecular biology techniques, the researchers have now found that often snoRNAs not only modify ribosomes, but actually perform a dual function: they can also regulate alternative splicing, resulting in regulating the alternative inclusion of small pieces in proteins, which regulates protein function, thus inhibiting the generation of aberrant protein variants. These new functions can explain the role of snoRNAs in human diseases, as upon their loss the formation of aberrant protein variants may no longer be prevented. In mechanistic studies, the researchers also showed that short synthetic RNAs could be used as a substitute for the missing snoRNAs. This could point to a possible therapy for genetic hyperphagia (a condition that causes extreme hunger or appetite) and some forms of cancer. “This research helps us to understand the unexpected dual role of snoRNAs in gene regulation.
Historically, less than 50% of children with high-risk neuroblastoma live five or more years after diagnosis. A National Cancer Institute (NCI)-funded phase III trial performed by the Children’s Oncology Group found that adding a second autologous stem-cell transplant (ASCT, a transplant that uses the patient’s own stem cells) to standard therapy improves outcomes for these patients. At 3 years, 61.4% of patients who received a double transplant were alive and cancer-free, compared to 48.4% of those who received a single transplant. Side effects were similar between single and double transplant. These data were presented at ASCO’s Sunday, June 5, 2016 Plenary Session, which featured four abstracts deemed to have the greatest potential to impact patient care, out of the more than 5,000 abstracts featured as part of the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting (June 3-7) in Chicago, Illinois. “This finding will change the way we treat children with high-risk neuroblastoma in North America, which still claims many young lives and is in urgent need of better treatments,” said lead study author Julie R. Park, M.D., an attending physician at Seattle Children’s Hospital and Professor in Pediatrics at the University of Washington School of Medicine in Seattle, Washington. “However, the regimen we use for high-risk neuroblastoma is also the most aggressive and toxic regimen we give to children with cancer. For that reason, future research needs to focus on both exploring possible late effects of current therapy and developing newer less toxic therapies.” The trial enrolled children newly diagnosed with high-risk neuroblastoma, who were a median age of 3.1 years. The majority of patients (88%) had Stage 4 disease and 38.2% had a tumor high-risk genetic abnormality called MYCN amplification.
A large-scale genomic analysis finds that patterns of genetic changes detected in blood samples (liquid biopsy) closely mirror those identified in traditional tumor biopsy. With blood samples from more than 15,000 patients and 50 different tumor types, this is one of the largest cancer genomics studies ever conducted. The study was featured in a press briefing on June 4, 2016 and presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting (June 3-7) in Chicago, Illinois. “These findings suggest that analysis of shed tumor DNA in patient blood, also known as a liquid biopsy, can be a highly informative, minimally-invasive alternative when a tissue biopsy is insufficient for genotyping or cannot be obtained safely,” said study presenter Philip Mack, Ph.D., Professor and Director of Molecular Pharmacology at the University of California Davis Comprehensive Cancer Center. “Moreover, this test, known as Guardant360, provides an unparalleled opportunity to monitor changes in the cancer as it evolves over time, which can be critical when patients and physicians are discussing treatment options for continued tumor control.” Currently, doctors largely rely on tumor biopsies to assess whether tumors have certain genetic mutations that can be targeted by available cancer drugs. Tumor biopsy involves a surgical procedure, however, and patients are not always healthy enough to undergo it, and frequent repeated tests are not always feasible.Tumor cells also sh ed small pieces of their genetic material or DNA into the bloodstream. This so-called circulating tumor DNA (ctDNA) can be collected from the blood and analyzed in the lab to help inform treatment decisions for individual patients, similar to tumor biopsy.
A randomized phase III clinical trial, MA.17R found that postmenopausal women with early breast cancer benefit from extending aromatase inhibitor (AI) therapy with letrozole (Femara) from 5 to 10 years. Following five years of an AI and any duration of prior tamoxifen, women who received letrozole for five additional years had a 34% lower risk of recurrence than those who received placebo. The trial was led by the Canadian Cancer Trials Group, with participation from the National Clinical Trials Network. These results were discussed in ASCO’s Sunday, June 5, 2016 Plenary Session, which featured four abstracts deemed to have the greatest potential to impact patient care, out of the more than 5,000 abstracts featured at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting (June 3-7) in Chicago, Illinois. “Women with early-stage hormone-receptor-positive breast cancer face an indefinite risk of relapse,” said lead study author Paul Goss, M.D., F.R.C.P., Ph.D., director of Breast Cancer Research at Massachusetts General Hospital in Boston, Massachusetts and Professor of Medicine at Harvard Medical School. “The study provides direction for many patients and their doctors, confirming that prolonging aromatase inhibitor therapy can further reduce the risk of breast cancer recurrences. Longer AI therapy also showed a substantial breast cancer preventative effect in the opposite, healthy breast.” Overall survival was not significantly different in MA.17R between the two groups, but Dr. Goss notes that because of the slow chronic relapsing nature of hormone-receptor positive breast cancer, overall survival has proved difficult to demonstrate in clinical trials. Because of this, most endocrine therapies for breast cancer have gained regulatory approval based solely on improvement of disease-free survival.
A European phase III trial, one of the largest ever conducted in pancreatic cancer, showed that adding the oral drug capecitabine chemotherapy to gemcitabine prolongs survival without increased toxicity. Adjuvant gemcitabine chemotherapy is currently the standard of care worldwide after surgical removal of pancreatic cancer. The study was featured in a press briefing on June 3, 2016 and presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting (June 3-7) in Chicago, Illinois. “Unfortunately, most patients are not candidates for surgery when they are diagnosed with pancreatic cancer,” said lead study author John P. Neoptolemos, M.A., M.B., B.Chir., M.D., F.Med.Sci., the Chair of Surgery in the Department of Molecular and Clinical Cancer Medicine at the University of Liverpool in Liverpool, United Kingdom. “These findings are significant because they show that those patients who can undergo surgery have a fighting chance of surviving this cancer with the combination of two commonly used chemotherapies.” With 732 patients, the European Study Group for Pancreatic Cancer (ESPAC) 4 trial is the second-¬largest clinical trial ever conducted in patients with pancreatic cancer who had undergone surgery. Within 12 weeks of surgery, patients with early-¬stage pancreatic ductal adenocarcinoma were randomly assigned to receive either gemcitabine alone or gemcitabine with capecitabine for 24 weeks. The median overall survival was 28.0 months with the combination regimen vs. 25.5 months with gemcitabine alone. The estimated 5-¬year survival rates were 28.8% vs. 16.3% in the two groups. “The difference in median survival may seem modest, but the improvement in long-¬term survival is substantial for this cancer,” said Dr. Neoptolemos.