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Archive - 2016

December 19th

Light Therapy Employing Light-Sensitive Drug Effectively Treats Early Prostate Cancer

A new non-surgical treatment for low-risk prostate cancer can effectively kill cancer cells while preserving healthy tissue, according to results of a new University College London (UCL)-led phase III clinical trial in 413 patients. The trial was funded by STEBA Biotech which holds the commercial license for the treatment. The new treatment, “vascular-targeted photodynamic therapy” (VTP), involves injecting a light-sensitive drug into the bloodstream and then activating it with a laser to destroy tumor tissue in the prostate. The research, published online on December 19, 2016 in The Lancet Oncology, found that approximately half (49%) of patients treated with VTP went into complete remission compared with 13.5% in the control group. The open-access article is titled “Padeliporfin Vascular-Targeted Photodynamic Therapy Versus Active Surveillance in Men with Low-Risk Prostate Cancer (CLIN1001 PCM301): an Open-Label, Phase 3, Randomised Controlled Trial.” An editorial entitled “Low-Risk Prostate Cancer: To Treat or Not to Treat,” accompanied the article. "These results are excellent news for men with early localized prostate cancer, offering a treatment that can kill cancer without removing or destroying the prostate," says lead investigator Professor Mark Emberton, Dean of UCL Medical Sciences and Consultant Urologist at UCLH. "This is truly a huge leap forward for prostate cancer treatment, which has previously lagged decades behind other solid cancers such as breast cancer. In 1975, almost everyone with breast cancer was given a radical mastectomy, but since then treatments have steady improved and we now rarely need to remove the whole breast.

Strong Prognostic Value of Circulating Tumor DNA and Its Level in Advanced Pancreatic Cancer

In a recent study, the presence of circulating tumor DNA (ctDNA) isolated from blood samples of patients with pancreatic adenocarcinoma was associated with poor outcomes. The article was published online on December 19, 2016 in Clinical Cancer Research, a journal of the American Association for Cancer Research. The article is titled “Plasma Circulating Tumor DNA in Pancreatic Cancer Patients Is a Prognostic Marker.” The senior author was Jean-Baptiste Bachet, M.D., Ph.D., from the Gastroenterology and Digestive Oncology Department at the Sorbonne University, and the Centre Universitaire des Saints-Pères, both in Paris, France. The incidence of pancreatic adenocarcinoma is on the rise in Western countries, and prognosis remains very poor. Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2030, behind lung cancer, and is therefore considered a public health problem, Dr. Bachet noted. There are several challenges to conducting translational research on pancreatic cancer, including the difficulty in obtaining tumor samples from patients, because of which, most studies have been limited to patients with resectable disease until now, Dr. Bachet explained. However, only 10 to15 percent of patients with pancreatic adenocarcinoma have resectable disease at diagnosis. Identification of robust prognostic or predictive biomarkers is urgently needed for all patients with pancreatic adenocarcinoma, whatever the stage of the disease, he said. Dr.

Tuberculosis Virulence Factor Identified, May Be New Drug Target

Scientists have discovered the mechanism that hijacks the immune system's response to tuberculosis, revealing an important new drug target for the disease that kills more than 1 million people each year. Herman Sintim, Ph.D., Purdue University's Drug Discovery Professor of Chemistry, collaborated with scientists at Johns Hopkins University to determine how tuberculosis turns off a human cell's signal to mount an immune response to the bacteria. Their findings were published online on December 12, 2016 in the journal Nature Chemical Biology. The article is titled “Inhibition of Innate Immune Cytosolic Surveillance by an M. tuberculosis Phosphodiesterase.” Tuberculosis is a bacterial disease that results in coughing, fever, night sweats, weight loss, and sometimes death. When Mycobacterium tuberculosis enters a human cell, the presence of its DNA and a molecule that it makes called c-di-AMP alert the cell to the bacteria's presence. The human cell responds by creating a messenger molecule, cGAMP, which signals nearby cells to mount an immune response to kill the tuberculosis bacteria. The human cell also produces another molecule, ENPP1, which degrades the cGAMP. That key step turns off the call for an immune response. "Immune response can involve reactive oxygen and nitrogen species, which can kill the bacteria, but at the same time cause collateral damage and also damage or kill the host cells as well," Dr. Sintim said. "There is a very delicate response to bacteria and stopping that response once bacteria have been taken care of." But the tuberculosis bacterium has found a way to turn off the call for help. By producing a protein called cyclic dinucleotide phosphodiesterase (CdnP), the bacterium reduces the concentration of the cell's messenger molecule, cGAMP, a nucleic acid.

Effective Chikungunya Fever Vaccine Utilizes Insect-Specific Virus Platform

Researchers from The University of Texas Medical Branch (UTMB) at Galveston have developed the first vaccine for chikungunya fever made from an insect-specific virus that doesn't have any effect on people, making the vaccine safe and effective. The newly developed vaccine quickly produces a strong immune defense and completely protects mice and non-human primates from disease when exposed to the chikungunya virus. The findings were published online on December 19, 2016 in Nature Medicine. The article is titled: A Chikungunya Fever Vaccine Utilizing an Insect-Specific Virus Platform.” "This vaccine offers efficient, safe, and affordable protection against chikungunya and builds the foundation for using viruses that only infect insects to develop vaccines against other insect-borne diseases," said UTMB Professor Scott Weaver, senior author of this paper. Chikungunya is a mosquito-borne virus that causes a disease characterized by fever and severe joint pain, often in hands and feet, and may include headache, muscle pain, joint swelling, or rash. Some patients will feel better within a week but many develop longer-term joint pain that can last up to years. Death is rare, but can occur. Traditionally, vaccine development involves tradeoffs between how quickly the vaccine works and safety. Live-attenuated vaccines that are made from weakened versions of a live pathogen typically offer rapid and durable immunity but reduced safety. On the other hand, the inability of inactivated vaccines to replicate enhances safety at the expense of effectiveness, often requiring several doses and boosters to work properly.

Gut Bacteria May Hold Key to Treating Autoimmune Disease

Defects in the body's regulatory T cells (T reg cells) cause inflammation and autoimmune disease by altering the type of bacteria living in the gut, researchers from The University of Texas (UT) Health Science Center at Houston have discovered. The study, entitled "Resetting Microbiota by Lactobacillus Reuteri Inhibits T reg Deficiency-Induced Autoimmunity via Adenosine A2A Receptors," was published online on December 19, 2016 in The Journal of Experimental Medicine, and suggests that replacing the missing gut bacteria, or restoring a key metabolite called inosine, could help treat children with a rare and often fatal autoimmune disease called IPEX syndrome. T reg cells suppress the immune system and prevent it from attacking the body's own tissues by mistake. Defects in T reg cells therefore lead to various types of autoimmune disease. Mutations in the transcription factor Foxp3, for example, disrupt T reg function and cause IPEX syndrome. This inherited autoimmune disorder is characterized by a variety of inflammatory conditions including eczema, type I diabetes, and severe enteropathy. Without a stem cell transplant from a suitable donor, IPEX syndrome patients usually die before the age of two. Autoimmune diseases can also be caused by changes in the gut microbiome, the population of bacteria that reside within the gastrointestinal tract. In the study, the team led by Dr. Yuying Liu and Dr. J.

December 18th

Identify of Human Dendritic Cells Dictated Largely by Ontogeny, Not Tissue Microenvironment

Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response. Scientists of the University Hospital Erlangen of the Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and the LIMES (Life and Medical Sciences) Institute of the University of Bonn have recently gained substantial knowledge of human dendritic cells, which might contribute to the development of immune therapies in the future. The results were published in the December 16, 2016 issue of Science Immunology. The article is titled “Human Lymphoid Organ Dendritic Cell Identity Is Predominantly Dictated by Ontogeny, not Tissue Microenvironment.” Dendritic cells - their name is derived from the large numbers of dendrites (branched projections) on their cell surface - populate most parts of the human body. There, they act as guards by recognizing, engulfing, and processing foreign pathogens. Finally, those dendritic cells migrate to nearby lymph nodes, where they interact with other immune cells to trigger a pathogen-specific immune response. Consequently, dendritic cells play an important role within the complex immune system. In recent years, it became evident that, in the mouse, dendritic cells are composed of different subtypes, which differ in function and distribution across the body. In contrast, less was known about the corresponding situation in humans. Recently, Dr. Gordon Heidkamp and Professor Dr. Diana Dudziak from the University Hospital Erlangen performed a global study, which, for the first time, systematically characterized dendritic cells in different human organs such as blood, spleen, thymus, tonsils, bone marrow, and cord blood.

Inspired by Camel and Llama Antibody Design, Scientists Develop Inside-Out Monoclonal Antibodies to Target Cancer-Associated Matrix Metalloproteinases (MMPs)

Researchers at the University of California, Riverside (UCR) have camels and llamas to thank for their development of a new cancer treatment that is highly selective in blocking the action of faulty matrix metalloproteinases (MMPs). MMPs are a group of 26 closely related proteinases (enzymes that break down other proteins) that are essential in tissue regeneration and other normal cellular processes. However, when a tumor grows, certain MMPs are over-produced, allowing cancer cells to spread to other parts of the body. In research published online on December 13, 2016 in PNAS, Xin Ge, Ph.D., an Assistant Professor of Chemical and Environmental Engineering in UCR's Bourns College of Engineering, and his colleagues describe the development of therapeutic monoclonal antibodies that are highly selective for MMPs, meaning they can bind to a specific MMP and block its activity without affecting other MMP family members. The creation of these human antibodies was inspired by antibodies found naturally in the camelid family of animals, which includes camels and llamas. The results could lead to new treatments--not only for a variety of cancers--but also for other diseases that arise from faulty proteinases, such as Alzheimer's, asthma, multiple sclerosis, and arthritis. For more than 20 years, scientists have been developing drugs that block faulty MMPs in order to stop cancers from starting and spreading. But clinical trials on a variety of promising small molecules have failed--largely because they lack the specificity needed to target faulty MMPs while still allowing "good" MMPs to perform their regular cellular duties.

December 16th

Study of Urinary Epidermal Growth Factor As Biomarker for Lupus Progression

Lupus, a chronic autoimmune disease, can wreak havoc on an affected individual's body through inflammation, pain, and even damage of the skin, joints, and organs. To try to better understand how the disease begins and progresses, researchers at the University of Michigan investigated whether kidney biomarkers would signal lupus progression and signs of complications. "Lupus patients have a high risk of kidney involvement, which can lead to end-stage renal disease requiring dialysis or transplant," says Emily Somers, Ph.D., Sc.M., an Associate Professor of Internal Medicine (Rheumatology), Environmental Health Sciences and Obstetrics and Gynecology at U-M and a member of the U-M Institute for Healthcare Policy and Innovation. "In addition, there is a great need for biomarkers to detect early kidney involvement and to monitor progression." Dr. Somers studies lupus outcomes and directs the Michigan Lupus Epidemiology and Surveillance (MILES) Program, which includes a cohort and biorepository registry of more than 650 lupus patients and controls from southeast Michigan. "Lupus is a disease that predominantly affects women, often striking at the prime of life," Dr. Somers says. "Through the MILES Program, we previously showed that for black women, who are disproportionately affected by lupus, their risk of lupus is highest in their 20s. Forty percent of black females with lupus have kidney involvement, and 15 percent have end-stage renal disease." In a new study, presented at the American Society of Nephrology's Kidney Week 2016 meeting in November, Dr. Somers teamed up with U-M colleagues Wenjun Ju, Ph.D., Associate Research Scientist, and Matthias Kretzler, M.D., Professor of Nephrology, to measure the urinary epidermal growth factor in patients with lupus. Dr. Ju and Dr.

Advance in Understanding of Inclusion Body Disease in Large Snakes

Inclusion body disease is a serious, chronic viral infection of snakes and can be devastating in captive reptile populations. Now, a new study published in the December 2016 issue of The Veterinary Journal sheds light on the disease, and may help veterinary care teams better protect the health of their populations of large snakes. The new article is titled “Detection and Prevalence of Boid Inclusion Body Disease in Collections of Boas and Pythons Using Immunological Assays.” The study was funded in part by a grant from the Morris Animal Foundation. Found in both boa constrictor and python species, inclusion body disease (IBD) signs may include periodic or chronic regurgitation, head tremors, abnormal shedding, anorexia, clogged nostrils, and pneumonia. The disease can rapidly progress to nervous system signs, such as disorientation, corkscrewing of the head and neck, holding the head in abnormal and unnatural positions, and rolling onto the back or stargazing. Current strategies for IBD control include identification and isolation of affected snakes, but making a definitive diagnosis of IBD in a living animal can be challenging. Infected snakes may continue to feed and otherwise behave normally, and may infect other snakes prior to developing clinical signs of illness and chronic disease. The prevalence of sub-clinical, infectious IBD disease in snakes prior to this study was not well understood. "In addition to developing diagnostic tests for IBD, a major finding in this study is the subclinical nature of IBD," said Dr. Elliott Jacobson, one of the papers' authors and faculty member at the College of Veterinary Medicine, University of Florida. "Many apparently healthy boa constrictors have not only the reptarenavirus, that is considered the causative agent, but also have subclinical IBD."

Progress Toward Understanding X-Chromosome Silencing in Humans

Researchers have discovered new insights into how one of the two X-chromosomes is silenced during the development of female human embryos and also in lab-grown stem cells. X-chromosome silencing is essential for proper development and these new findings are important for understanding how the activity of the X-chromosome is regulated to ensure the healthy development of human embryos. Female cells have two X-chromosomes. One X-chromosome is shut down in the earliest stages of development preventing the duplicated expression of genes from both X-chromosomes. Previous work using mouse embryos showed that a long RNA molecule called Xist coats regions of the silenced X-chromosome. By latching on to the DNA, Xist recruits proteins that shut down the chromosome. However, although XIST is expressed in human embryos, X-chromosome silencing isn't triggered until a few days later. The different observation in mouse and human embryos suggests that XIST is unable to fulfil the same role in humans as in mouse development. Until now, it was unclear why XIST does not inactivate the X-chromosome in human embryos, or what triggers X-chromosome silencing. Researchers at the Paris Diderot University, Institut Curie, and the Babraham Institute reported on December 15, 2016 in Cell Stem Cell that a second long RNA molecule, XACT, which exists in humans but not in mice, accumulates with XIST on active X-chromosomes in human embryos. The two RNAs do not overlap; instead XACT and XIST occupy large and distinct territories on the X-chromosome. Strikingly, unspecialized “naïve” human embryonic stem cells show the same pattern of XACT and XIST accumulation on active X-chromosomes, which suggests that this important epigenetic feature of embryo development is conserved in stem cells cultured in the laboratory.