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Archive - 2019

November 12th

Anthrax Toxin May Be Effective Weapon in Fighting Bladder Cancer

Anthrax may soon help more people win the fight against bladder cancer, which the Centers for Disease Control and Prevention (CDC) says strikes approximately 72,000 Americans each year and kills about 16,000, and is one of the most expensive cancers to treat. The current treatments for bladder cancer are invasive for patients - who often must sit for hours at a time with a bladder full of an agent designed to kill cancer cells and tumors. Bladder cancer also is one of the most reoccurring for people diagnosed with the disease. Now, researchers at Purdue University have come up with a way to combine the anthrax toxin (image) with a growth factor to kill bladder cancer cells and tumors. The research was published online on October 4, 2019 in the International Journal of Cancer. "We have effectively come up with a promising method to kill the cancer cells without harming the normal cells in the bladder," said R. Claudio Aguilar, PhD, an Associate Professor and the Assistant Head of Biological Sciences in Purdue's College of Science. "It is basically like creating a special solution that targets cancer cells, while leaving healthy cells alone." Dr. Aguilar said the bladder has its own protective layer, which saves the good cells from the anthrax mixture but offers no protection for the cancer cells and tumors. He said the Purdue system works within minutes - instead of the usual hours for bladder cancer treatment - to target the cancer cells in the bladder. "We have seen outstanding results with our treatment," said Dr. Aguilar, who works as part of a team focused on cell identity and signaling at the Purdue University Center for Cancer Research. "It is fast and effective, both of which are critical for people dealing with this devastating disease." Dr. Aguilar and his group worked with the Purdue teams led by Dr.

Frequent Technical Bias Occurs in RNA-Seq Expression Studies, Leading to Widespread Misinterpretation of Gene Expression Data; Authors Present Approach to Removing This Bias

Reproducibility is a major challenge in experimental biology, and with the increasing complexity of data generated by genomic-scale, this concern is immensely amplified. RNA-seq, one of the most widely used methods in modern molecular biology, allows in a single test the simultaneous measurement of the expression level of all the genes in a given sample. New research, published online on November 12, 2019 in the open-access journal PLOS Biology by Shir Mandelbaum, Zohar Manber, Orna Elroy-Stein, and Ran Elkon from Tel Aviv University, identifies a frequent technical bias in data generated by RNA-seq technology, which recurrently leads to false results. The article is titled “Recurrent Functional Misinterpretation of RNA-Seq Data Caused By Sample-Specific Gene Length Bias.” Analyzing dozens of publicly available RNA-seq datasets, which profiled the cellular responses to numerous different stresses, Dr. Mandelbaum and colleagues noticed that sets of particularly short or long genes repeatedly showed changes in expression level (as shown by the apparent number of RNA transcripts from a given gene). Puzzled by this recurring pattern, the authors then asked whether it reflects some universal biological response common to many different triggers or if it, rather, stems from some experimental artefact. To tackle this question, they compared replicate samples from the same biological condition. Differences in gene expression between replicates can reflect technical effects that are not related to the experiment's biological factor of interest. Unexpectedly, the same pattern of particularly short or long genes showing changes in expression level was observed in these comparisons between replicates, demonstrating that this pattern is the result of a technical bias that seemed to be coupled with gene length.

November 11th

Biomarker Blood Test Could Reveal High-Risk Heart Patients in Need of Treatment

Without occasionally looking under the hood, it’s difficult topredict whether expensive car repairs lie ahead. In a similar way, preventive cardiologists are looking for ways to detect early-stage heart disease in people who aren’t currently in treatment. Preventive cardiology researchers at the University of Texas (UT) Southwestern Medical Center believe that a new blood test for protein biomarkers could identify these individuals. Their new study, published online on November 11, 2019 in Circulation, pooled patient data from three major patient populations including multiple ethnicities and totaling nearly 13,000 people. The team asked whether measuring levels of two biomarkers – proteins in the blood – would identify people in need of treatment. The researchers found that approximately one-third of adults with mild hypertension who are not currently recommended for treatment have slight elevations of one of these two biomarkers; these individuals were more likely to have heart attacks, strokes, or congestive heart failure over the next 10 years. In other words, these patients are “flying under the radar” and do not know that they are at greater risk of cardiovascular events. The Circulation article is titled “Incorporation of Biomarkers Into Risk Assessment for Allocation of Antihypertensive Medication According to the 2017 ACC/AHA High Blood Pressure Guideline: A Pooled Cohort Analysis.” Dr. Ambarish Pandey (left in photo) and Dr. Parag Joshi (right in photo) believe some patients at risk of heart disease could be helped by a biomarker blood test.“We think this type of test can help in the shared decision-making process for patients who need more information about their risk,” said preventive cardiologist Dr. Parag Joshi, Assistant Professor of Internal Medicine.

Study Reveals How Two Strains of One Bacterium Combine to Cause Flesh-Eating Infection

In recent years, scientists have found that serious infections that progress rapidly and resist treatment are often caused by multiple microbes interacting with one another. Very little is known about these so-called “polymicrobial infections,” but traditional diagnostic methods often misidentify them as monomicrobial, or single-microbe, infections. A new study by a team of scientists that included researchers from the University of Maryland, the University of Texas Medical Branch, and CosmosID, Inc., used genetic analysis to reveal how two different strains of a single species of flesh-eating bacteria worked in concert to become more dangerous than either one strain alone. The study was published online in the Proceedings of the National Academy of Sciences on November 11, 2019. The article is titled “T6SS and ExoA of Flesh-Eating Aeromonas Hydrophila In Peritonitis And Necrotizing Fasciitis During Mono- And Polymicrobial Infections.” "This research provides clear evidence that a very severe infection considered to be caused by a single species of a naturally occurring bacterium actually had two strains," said Rita Colwell (photo), PhD, a Distinguished University Professor in the University of Maryland Institute for Advanced Computer Studies and a co-author of the study. "One of the strains produces a toxin that breaks down muscle tissue and allows the other strain to migrate into the blood system and infect the organs." The original infection--cultured from a patient who developed the severe flesh-eating disease known as necrotizing fasciitis--was diagnosed as a monomicrobial disease. Traditional diagnostics could only determine that the infection was caused by a single species of bacteria called Aeromonas hydrophila.

Penn Scientists Uncover Dose of Medication More Likely to Put Patients with Pemphigus (Chronic, Sometimes Fatal Skin Disease) into Remission; Findings May Inform Use of Recent FDA Approved Drug Rituximab to Better Treat Patients with Pemphigus

Pemphigus, an autoimmune disease mediated by B cells and which causes painful blisters and sores on the skin and mucous membranes, is a rare chronic autoimmune condition that can be fatal if not treated. Treatment for pemphigus, most commonly through an oral medication, was often slow and would not result in complete remission. Now, new research from a team in the Perelman School of Medicine at the University of Pennsylvania shows that a lymphoma-dose regimen of rituximab, a medication regularly used to treat lymphoma and rheumatoid arthritis, is more likely to put patients with pemphigus into complete remission as compared to a rheumatoid arthritis (RA) regimen of the same medication. The findings--which were published online on October 23, 2019 in JAMA Dermatology -- have direct implications for patient care. The article is titled " Factors Associated with Complete Remission After Rituximab Therapy for Pemphigus.” When rituximab, an antibody which was first used to treat B cell lymphoma, became a treatment for pemphigus vulgaris, clinicians could choose to prescribe either a "lymphoma dose" or an "RA dose." A lymphoma-dose regimen of rituximab is a more aggressive approach to treatment compared to the dosing method for patients with rheumatoid arthritis. What's more, the U.S. Food and Drug Administration (FDA) now has an approved dosing regimen for pemphigus vulgaris, but it closely resembles the often less-effective RA dose. While both lymphoma and RA dosing approaches deplete B cells that cause disease, the lymphoma regimen takes into account a person's height and weight to determine a dose and is given weekly for four weeks. A rheumatoid arthritis dose is a fixed dose of two 1000 mg infusions given two weeks apart.

Computer Analysis Reveals Over 1 Million Nucleic Acid Polymer Molecules That Are Possible Alternatives to DNA & RNA

Biology encodes information in DNA and RNA, which are complex molecules finely tuned to their functions. But are they the only way to store hereditary molecular information? Some scientists believe life as we know it could not have existed before there were nucleic acids, thus understanding how they came to exist on the primitive Earth is a fundamental goal of basic research. The central role of nucleic acids in biological information flow also makes them key targets for pharmaceutical research, and synthetic molecules mimicking nucleic acids form the basis of many treatments for viral diseases, including HIV. Other nucleic acid-like polymers are known, yet much remains unknown regarding possible alternatives for hereditary information storage. Using sophisticated computational methods, scientists from the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology, the German Aerospace Center (DLR), and Emory University explored the "chemical neighborhood" of nucleic acid analogues. Surprisingly, they found well over a million variants, suggesting a vast unexplored universe of chemistry relevant to pharmacology, biochemistry and efforts to understand the origins of life. The molecules revealed by this study could be further modified to gives hundreds of millions of potential pharmaceutical drug leads. The study results were published on September 9, 2019, in the Journal of Chemical Information and Modeling.

Genetic Diversity Facilitates Effectiveness of Cancer Therapy; Cancer Patients with Broader Diversity of HLA Genes Respond Better to Treatment with Checkpoint Inhibitors

The constant battle against infectious pathogens has had a decisive influence on the human immune system over the course of our evolution. A key role in our adaptation to pathogens is played by HLA molecules. These proteins activate the immune system by presenting it with fragments of pathogens that have entered the body. People with a wide variety of different HLA proteins are thus better armed against a large number of pathogens. Researchers at the Max Planck Institute for Evolutionary Biology in Plön, Germany, together with colleagues in New York, have been investigating the diversity of HLA genes in cancer patients being treated with immune checkpoint inhibitors. This form of immunotherapy activates the body's own immune cells to enable them to identify and eliminate tumor cells. The researchers discovered that patients with a wide variety of HLA molecules derive more benefit from this type of therapy. This means that in future, doctors may be able to offer improved individual treatment based on a patient's HLA gene profile. In the evolution of an organism, the characteristics which often prevail are those which increase the chances of survival and reproduction of their carrier. In contrast, for a robust immune system it could be advantageous for it to be variable, keeping as many options open as possible - a hypothesis which has been tested and confirmed in an early study carried out specifically on HLA molecules by Fr. Federica Pierini and Dr. Tobias Lenz at the Max Planck Institute for Evolutionary Biology. It is therefore essential for the effectiveness of an immune system to have many different variants of HLA molecules, Because each variant can bind to several different pathogen or cancer cell protein fragments.

November 7th

For First Time, Potential Treatment Path Becomes Clear for Subtype of Charcot-Marie-Tooth Disease

An unexpected finding from the Scripps Research laboratory of Xiang-Lei Yang (photo), PhD, has illuminated a potential strategy for treating the inherited neurological disease Charcot-Marie-Tooth (CMT), for which there is no approved medicine today. CMT is a progressive disease that typically develops early in life, affecting roughly 1 in 2,500 people. Over time, the disease inflicts damage on patients' peripheral nervous system--which extends from the spinal cord into the hands and feet--often resulting in difficulties with balance, walking, and fine motor skills such as writing or buttoning a shirt. In a study that was published online on November 6, 2019 in Nature Communications, Dr. Yang and her team show that a drug may be able to prevent the disease-causing mechanisms from occurring within cells, quelling many key symptoms, Including Motor Deficits. The open-access article is titled “Transcriptional Dysregulation by a Nucleus-Localized Aminoacyl-tRNA Synthetase Associated With Charcot-Marie-Tooth Neuropathy.” The approach centers on enzymes known as aminoacyl-tRNA synthetases (aaRSs), which are pervasive throughout the body. They are the largest protein family linked to CMT disease, and also the long-running research specialty of Dr. Yang's lab. These enzymes are essential to life because they kick off the first step of making new proteins, which are the building blocks of everything from blood and hormones to skin and bones. But in patients with CMT, some of the aaRS enzymes don't function as they should. As a result, peripheral neurons aren't made properly and become toxic to the peripheral nervous system. In her search for a potential treatment approach, Dr. Yang wanted to find out why the mutated enzymes only seem to affect peripheral neurons.

Researchers Seek to Attack Leukemia Stem Cells in Effort to Cure Chronic Myeloid Leukemia

Why do some cancers come back? Sometimes, a treatment can effectively eliminate cancer cells to undetectable levels, but, if the treatment stops, cancer may return. This is the case with chronic myeloid leukemia treated with drugs known as tyrosine kinase inhibitors. These drugs have dramatically improved clinical outcomes and generated unprecedented rates of complete responses and long-term survival. To achieve these results, patients have to take the drug for the rest of their lives. "Clinical trials testing the effect of discontinuing the drug have shown that at least half of the patients achieve treatment-free remission, but in the other half the cancer returns," said Daniel Lacorazza (photo), PhD, Associate Professor of Pathology & Immunology at Baylor College of Medicine and Principal Investigator in the Experimental Immunology & Hematology Laboratory at Texas Children's Hospital. "We think that relapse occurs because tyrosine kinase inhibitors affect most chronic myeloid leukemia cells, but not leukemia stem cells. It's like removing the tree, but leaving the roots that can sprout new shoots." Leukemia stem cells are an elusive, small cell population that initiates and sustains leukemia. Stem cells can regenerate via a poorly understood mechanism of self-renewal and enter a path of development that gives rise to new leukemia cells. Dr. Lacorazza and his colleagues think that clues to treatment-free remission might be found in this little known, self-renewal mechanism. "The results of the drug discontinuation trials suggest that a cure may not be possible with tyrosine kinase inhibitors alone.

November 6th

Early Results from First-In-U.S. Trial of CRISPR-Edited Immune Cells for Cancer Patients Suggest Safety of Approach

On November 6, 2019, it was announced that genetically editing a cancer patient’s immune cells using CRISPR/Cas9 technology, then infusing those cells back into the patient appears safe and feasible, based on early data from the first-ever clinical trial to test the approach in humans in the United States. Researchers from the Abramson Cancer Center of the University of Pennsylvania ( have infused three participants in the trial thus far – two with multiple myeloma and one with sarcoma – and have observed that the edited T cells expand and bind to their tumor target with no serious side effects related to the investigational approach. Penn is conducting the ongoing study in cooperation with the Parker Institute for Cancer Immunotherapy (PICI) ( and Tmunity Therapeutics ( “This trial is primarily concerned with three questions: can we edit T cells in this specific way? Are the resulting T cells functional? And are these cells safe to infuse into a patient? This early data suggests that the answer to all three questions may be yes,” said the study’s principal investigator Edward A. Stadtmauer, MD, Section Chief of Hematologic Malignancies at Penn. Dr. Stadtmauer will present the findings on December 7, 2019 at the 61st American Society of Hematology Annual Meeting and Exposition in Orlando (Abstract #49)( 7-10).