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Archive - May 1, 2017


Birinapant & Carboplatin Combination Could Offer New Treatment Option for Ovarian Cancer, Animal Studies & Human Disease-in-a-Dish Models Suggest; Clinical Trial Contemplated; Effectiveness in Other Cancers Also Suggested

Researchers have been trying to understand why up to 85 percent of women experience recurrence of high-grade serous ovarian cancer -- the most common subtype of ovarian cancer -- after standard treatment with the chemotherapy drug carboplatin. Preclinical research from Sanaz Memarzadeh (photo), MD, PhD, who is a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, has potentially solved this mystery and pinpointed a combination therapy that may be effective for up to 50 percent of women with ovarian cancer. Dr. Memarzadeh's research, published online on April 3, 2017 in Precision Oncology, shows a new combination therapy of carboplatin and an experimental drug called birinapant can improve survival in mice with ovarian cancer tumors. Additional findings reveal that testing for a specific protein could identify ovarian tumors for which the treatment could be effective. Importantly, the treatment could also target cancers that affect other parts of the body, including the bladder, cervix, colon, and lung cancer. The open-access article is titled “Birinapant sensitizes platinum-resistant carcinomas with high levels of cIAP to carboplatin therapy.” In 2015, Dr. Memarzadeh and her team uncovered and isolated carboplatin-resistant ovarian cancer stem cells. These cells have high levels of proteins called cIAPs, which prevent cell death after chemotherapy. Because the cancer stem cells survive carboplatin treatment, they regenerate the tumor; with each recurrence of ovarian cancer, treatment options become more limited. Dr. Memarzadeh showed that birinapant, which degrades cIAPs, can make carboplatin more effective against some ovarian cancer tumors.

Tea Tree Genome Sequenced; Insights into Tea Flavor & Independent Evolution of Caffeine Biosynthesis

The most popular varieties of tea -- including black tea, green tea, Oolong tea, white tea, and chai -- all come from the leaves of the evergreen shrub Camellia sinensis, otherwise known as the tea tree. Despite tea's immense cultural and economic significance, relatively little is known about the shrub behind the tea leaves. However, the first draft of the tea tree genome published online on May 1, 2017 in Molecular Plant may help explain why tea leaves are so rich in antioxidants and caffeine. The open-access article is titled “The Tea Tree Genome Provides Insights into Tea Flavor and Independent Evolution of Caffeine Biosynthesis.” Understanding how the tea tree differs genetically from its close relatives may help tea growers figure out what makes Camellia sinensis leaves so special. The genus Camellia contains over 100 species--including several popular decorative garden plants and C. oleifera, which produces "tea tree" oil--but only two major varieties (C. sinensis. var. assamica and C. sinensis var. sinensis) are grown commercially for making tea. "There are many diverse flavors, but the mystery is what determines or what is the genetic basis of tea flavors?" says plant geneticist Li-Zhi Gao, PhD, of Kunming Institute of Botany in China. Previous studies have suggested that tea owes much of its flavor to a group of antioxidants called flavonoids, molecules that are thought to help plants survive in their environments. One, a bitter-tasting flavonoid called catechin, is particularly associated with tea flavor. Levels of catechin and other flavonoids vary among Camellia species, as does caffeine. Gao and his colleagues found that C. sinensis leaves not only contain high levels of catechins, caffeine, and flavonoids, but also have multiple copies of the genes that produce caffeine and flavonoids.

ISEV Announces Junior Member Scholarship Winners for Annual Meeting in Toronto May 18-21

The International Society for Extracellular Vesicles (ISEV) has announced the 25 Junior Member Scholarship winners for the ISEV 2017 annual meeting in Toronto, Canada (May 18-21). The scholarships are intended to support young researchers (students and postdocs) in pursuing their studies in the area of extracellular vesicles through attendance at the ISEV 2017 annual meeting. Among the 25 winners are junior ISEV members from Austria, Brazil, Germany, Canada, USA, The Netherlands, Ireland, Japan, China, Korea, UK, France, Australia, and Portugal. Among the winning abstracts are ones entitled “Molecular Subtypes of Glioma Stem Cells As Determinants of Tumor Vesiculome and Extracellular Vesicle Mediated Intercellular Communication,” “Real-Time Quantification of Multivesicular Body-Plasma Membrane Fusion Reveals Modulation of Exosome Release by G Protein-Coupled Receptor Signaling,” and “Picornavirus Infection Induces the Release of Distinct EV Populations Containing Infectious Virus and Altered Host-Derived Contents.” You may hear the scholarship winners’ presentations at the ISEV 2017 meeting in Toronto. You may view the entire list of scholarship winners and their abstract titles at the link provided below. Further information on the ISEV 2017 annual meeting May 18-21 can be found at:

[ISEV Junior Member Scholarship Winners] [ISEV 2017 Annual Meeting May 18-21]

DUX-Family Proteins Trigger Zygote Genome Activation; Discovery Is Landmark in Developmental Biology

The formation of a human embryo begins with the fertilization of the oocyte by the sperm cell. This yields the zygote, the primordial cell that carries one copy each of the maternal and the paternal genomes. However, this genetic information starts being expressed only after the zygote divides a couple of times. But what triggers this process, called "zygotic genome activation," was unknown until now. EPFL (Ecole Polytechnique Fédérale de Lausanne) scientists in Switrzerland have just found that members of the DUX family of proteins are responsible for igniting the gene expression program of the nascent embryo. Published online on May 1, 2017 in Nature Genetics, this discovery is a milestone for developmental biology. The article is titled “DUX-Family Transcription Factors Regulate Zygotic Genome Activation In Placental Mammals.” Lead author Dr. Alberto de Iaco, a postdoc in the lab of Dr. Didier Trono at EPFL, drew upon a seemingly irrelevant study of patients suffering from a form of muscular dystrophy where mutations lead to the production in muscle cells of a protein called DUX4, which is normally detected only at the earliest stage of human embryonic development. Dr. De Iaco also found that when DUX4 is forcibly produced in muscle cells, it turns on a whole set of genes that are expressed during zygotic genome activation. This was what first suggested that DUX4 could be the key regulator of this seminal event. To confirm this, the researchers analyzed publicly available data to determine what components of the human genome are expressed during the first few days of embryonic development. They found that DUX4 is one of the very first genes expressed at this stage, releasing a high concentration of its protein product just before zygotic genome activation.

Novel Antibacterial Wound Cover, Made in Part from Crustacean Shell Extract, Could Prevent Thousands of Infections Each Year

A new type of wound dressing could improve thousands of people's lives, by preventing them from developing infections. he dressing, a type of compression held in place by a bandage, uses an antibacterial substance formed from the shells of crustaceans like shrimps. It is described in a paper published in the May 2017 issue of Radiation Physics and Chemistry. The open-access article is titled “Chitosan-Containing Hydrogel Wound Dressings Prepared by Radiation Technique.” Antimicrobial resistance is becoming a worldwide health threat. A recent report by the Review on Antimicrobial Resistance, commissioned in 2014 by then UK Prime Minister David Cameron and led by economist Jim O'Neill, warns that antimicrobial resistance could kill 10 million people each year by 2050, dwarfing even the number of estimated deaths from cancer. Because of this, preventing infection has never been more important. The protective dressing was developed by Dr. Radoslaw Wach and his colleagues from Lodz University of Technology in Poland. Their innovation builds on a type of dressing that has been around for centuries. By providing moisture to a wound, hydrogel dressings can speed up aspects of healing and cool the wound down. The dressings are durable and elastic, meaning they can easily adapt to the shape of the affected body part. Dr. Wach and his colleagues adapted the hydrogel dressing manufacturing technique to make a version of the classic dressing with an added benefit. The team did this by incorporating an antibacterial and biodegradable substance called chitosan, extracted from the shells of crustaceans, within the dressing itself.

New Imaging Method May Predict Immunotherapy Response Early in Anti-Cancer Treatment

A noninvasive PET imaging method that measures granzyme B (image), a protein released by immune cells to kill cancer cells, was able to distinguish mouse and human tumors that responded to immune checkpoint inhibitors from those tumors that did not respond early in the course of treatment. The results were published in the May 2017 issue of Cancer Research. The article is titled “Granzyme B PET Imaging as a Predictive Biomarker of Immunotherapy Response.” The senior author was Umar Mahmood, MD, PhD, Professor of Radiology at Harvard Medical School and Director of the Division of Precision Medicine at the Athinoula A. Martinos Center for Biomedical Imaging in Massachusetts General Hospital (MGH), Boston. Although immunotherapies, such as checkpoint inhibitors, have revolutionized cancer treatment, they only work in a minority of patients, which means that most patients receiving this treatment will not benefit but still have the increased risk of side effects, besides losing time that they could spend on other therapies, Dr. Mahmood explained. Response to immunotherapy often cannot be measured effectively at early time points by traditional imaging techniques that measure tumor size, such as CT and MRI scans, or those that measure tumor glucose uptake, such as FDG PET, because these techniques cannot distinguish a nonresponding tumor from a tumor that is responding to immunotherapy but appears to grow in size because it is filled with immune cells and accompanied by increased glucose uptake, Dr. Mahmood noted. Tissue biopsies can be unreliable because of tumor heterogeneity and constant changes in the levels of the biomarker proteins measured.

Serial Analysis of Circulating Tumor Cells (CTCs) May Provide Biomarker Predictive of NSCLC Response to Crizotinib

Among patients with non-small cell lung cancer (NSCLC) fueled by ALK (anaplastic lymphoma kinase) gene alterations who were being treated with crizotinib (Xalkori), a decrease in the number of circulating tumor cells (CTCs) harboring increased numbers of copies of the ALK gene over the first two months of treatment was associated with increased progression-free survival. These results were published in the May 2017 issue of Cancer Research. The open-access article is titled “Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival During Crizotinib Treatment in ALK-Rearranged Non–Small Cell Lung Cancer Patients.” The research group was led by Françoise Farace, PhD, leader of the circulating cells team at Gustave Roussy, INSERM, Université Paris-Saclay, Villejuif, France. Approximately 4 percent of NSCLCs are driven by genetic aberrations called ALK gene rearrangements, according to Dr. Farace. "The approval of the ALK-targeted therapeutic crizotinib has improved outcomes for patients with ALK-rearranged NSCLC, but the duration of responses varies widely, from a few months to several years," she said. Dr. Farace and colleagues prospectively recruited 39 patients with ALK-rearranged NSCLC to the study. All patients had a blood sample taken before starting crizotinib treatment. Blood samples were taken about two months later for 29 of these patients; 10 patients received follow-up care at a different center and no serial blood samples were available for analysis. After enriching for CTCs, the researchers analyzed the samples for ALK rearrangements and for an increase in the number of copies of the ALK gene. All patients had both CTCs with ALK rearrangements and CTCs with ALK copy number gain before treatment and at two months.