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Archive - Apr 2015

April 20th

AACR ANNUAL MEETING: Oral Milk Thistle Extract (Silibinin) Stops Colorectal Cancer Stem Cells from Growing Tumors; University of Colorado Cancer Group Sees Future Human Clinical Trial As Likely

In results presented at the American Association for Cancer Research (AACR) Annual Meeting 2015 (April 18-22, 2015, in Philadelphia), a University of Colorado (CU) Cancer Center study shows that orally administering the chemical silibinin, purified from milk thistle, slows the ability of colorectal cancer stem cells to grow the disease. When stem cells from tumors grown in silibinin-fed conditions were re-injected into new models, the cells failed to develop equally aggressive tumors even in the absence of silibinin. "It's very simple: tumors from mice that were initially fed silibinin had fewer cancer stem cells, were smaller, had lower metabolisms and showed decreased growth of new blood vessels. Importantly, when these cancer stem cells from tumors in mice fed silibinin were re-injected into new mice, we found these stem cells had lost their potential to repopulate even in the absence of silibinin exposure," says Rajesh Agarwal, Ph.D., Co-Program Leader of Cancer Prevention and Control at the CU Cancer Center and Professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences. Silibinin is a non-toxic, potentially chemopreventive agent derived from milk thistle seeds. Results presented by Dr. Agarwal and colleagues at last year's AACR Annual Meeting showed that, in cell cultures, silibinin affects cell signaling associated with the formation and survival of colorectal cancer stem cells. The current study extends this promising line of research into mouse models. Specifically, the group used sorted colorectal cancer stem cells to grow tumors in mice that were either fed or not fed with silibinin. Tumor growth was measured by visible size, MRI scan, and measurement of tumor metabolism (glucose use).

April 19th

Knuckle-Cracking Riddle Finally Solved

"Pull my finger," a phrase embraced by school-aged kids and embarrassing uncles the world over, is now being used to settle a decades-long debate about what happens when you crack your knuckles. In a new study published online on April 15, 2015 in an open-access article in PLOS ONE, an international team of researchers led by the University of Alberta (U of A) used MRI video to determine what happens inside finger joints to cause the distinctive popping sounds heard when cracking knuckles. The article is titled “Real-Time Visualization of Joint Cavitation.” For the first time, they observed that the cause is a cavity forming rapidly inside the joint, not the collapse of that cavity. In the work, the scientists present direct evidence from real-time MRI that the mechanism of joint cracking is related to cavity formation rather than cavity collapse. "We call it the 'pull my finger study'--and actually pulled on someone's finger and filmed what happens in the MRI. When you do that, you can actually see very clearly what is happening inside the joints," explained lead author Dr. Greg Kawchuk, a Professor in the Faculty of Rehabilitation Medicine. Scientists have debated the cause of joint cracking for decades, dating back to 1947 when U.K. researchers first theorized vapor bubble formation as the cause. That was put in doubt in the 1970s when another team of scientists instead fingered collapsing bubbles as the cause. The idea for the project was born when Nanaimo, British Columbia chiropractor Jerome Fryer approached Dr. Kawchuk about a new knuckle-cracking theory. They decided to skip the theories and, with University of Alberta colleagues Jacob Jaremko, Hongbo Zeng, Richard Thompson, and Australian Lindsay Rowe, decided to actually look inside the joint.

Gene Mutation Increases Artemesin Resistance of Malaria Parasite (Plasmodium falciparum) in Africa

Early indicators of the malaria parasite in Africa developing resistance to the most effective drug available have been confirmed, according to new research published in an open-access article in the May 2015 issue of Antimicrobial Agents and Chemotherapy. The article is titled “The Mu Subunit of Plasmodium falciparum Clathrin-Associated Adaptor Protein 2 Modulates in vitro Parasite Response to Artemisinin and Quinine.” Researchers at the London School of Hygiene & Tropical Medicine found Plasmodium falciparum malaria parasites with a mutation to the gene Ap2mu were less sensitive to the anti-malarial drug artemisinin. A study in 2013, also led by the School, suggested an initial link between a mutation in the ap2mu gene and low levels of malaria parasites remaining in the blood of Kenyan children after they had been treated. However, further research was needed to confirm if these genetic characteristics represented an early step towards resistance. In the new study, researchers genetically altered the malaria parasite in the laboratory to mutate ap2mu in the same way that had been observed in Kenya. They found the altered parasite was significantly less susceptible, requiring 32% more drug to be killed by artemisinin. The genetically altered parasite was also 42.4% less susceptible to the traditional antimalarial drug, quinine. Earlier this year, a different research group discovered mutations in the gene kelch13 that were linked to reduced susceptibility to artemisinin combination treatment in South East Asia. Historically, resistance to antimalarial medicines has emerged in South East Asia and then spread to Africa. But these new findings suggest a different route to drug resistance may be developing independently in Africa. Lead researcher Dr.

April 18th

Aethlon Subsidiary Exosome Sciences Collaborates with Boston University School of Medicine in Study Quantitating Exosomes That Can Carry Tau Protein Across the Blood-Brain Barrier; Part of DETECT Study of Biomarkers for CTE Looks at 78 Former NFL Players

In an April 16, 2015 press release, Aethlon Medical, Inc. (OTCQB:AEMD, AEMDD) (http://www.aethlonmedical.com/), a pioneer in developing targeted therapeutic devices to address infectious diseases and cancer, announced that Dr. Robert Stern, Professor of Neurology, Neurosurgery, and Anatomy and Neurobiology at Boston University School of Medicine (BUSM) has presented preliminary, unpublished findings related to research being conducted by Aethlon Medical's majority-owned subsidiary, Exosome Sciences, Inc. (http://www.exosomesciences.com/) . The presentation was given on Apriol 16, 2015, at the 5th Annual Traumatic Brain Injury Conference that was held in Washington, D.C. The findings are part of the Diagnosing and Evaluating Traumatic Encephalopathy Using Clinical Tests (DETECT) study, a research project funded by the National Institutes of Health (NIH), being conducted at BUSM's CTE Program. The DETECT study examines potential biomarkers for CTE (chronic traumatic encephalopathy) by studying a sample of former professional American football players and a control group of same-age men without any history of brain trauma from contact sport involvement. In connection with the DETECT study, researchers at Exosome Sciences have been applying proprietary techniques to isolate microscopic exosomes that transport CTE-associated tau protein (tausomes) across the blood-brain barrier. As part of the DETECT project at BUSM, blood samples from 78 former NFL players and 16 control subjects were analyzed by Exosome Sciences researchers. In the study, researchers were able to isolate and quantify the presence of tausomes in the blood. During his presentation, Dr. Stern reported that former NFL players' tausome levels were measured to be significantly higher than those of the control subjects.

Aethlon Announces Cancer Clinical Trial Agreement with UC Irvine to Assess Plasma Exosome Concentration in Cancer Patients Undergoing Treatment; Company Has Candidate Device to Reduce Presence of Circulating Tumor-Derived Exosomes

In an April 15, 2015 press release, Aethlon Medical, Inc. (OTCQB:AEMD) (http://www.aethlonmedical.com/), a pioneer in developing targeted therapeutic devices to address infectious diseases and cancer, announced today that it has entered into an investigator-initiated clinical trial agreement with the University of California, Irvine (UCI). Under the agreement, a clinical study protocol entitled, "Plasma Exosome Concentration in Cancer Patients Undergoing Treatment," will seek to enroll five individuals in each of nine defined tumor types for a total study population of up to 45 subjects. The tumor types include the following forms of cancer; breast adenocarcinoma, colorectal, gastric & gastroesophageal, pancreatic, cholangiocarcinoma, lung (NSCLC), head & neck (SCC), melanoma, and ovarian adenocarcinoma. The principal investigator of the study is Edward Nelson, M.D. The study endpoints include establishing baseline exosome levels and monitoring changes in circulating exosome concentration associated with tumor treatment and the association of longitudinal changes in circulating exosome concentrations with response to treatment. The clinical study will also provide data to help direct future clinical investigations of the Aethlon Hemopurifier® as a therapeutic candidate to reduce the presence of circulating tumor-derived exosomes, which are known to suppress the immune system of cancer patients and contribute to the spread of metastasis. Aethlon Medical believes that the Hemopurifier is a first-in-class bio-filtration device that targets the single-use removal of viruses and tumor-derived exosomes from the circulatory system. Recruitment of participants in the study will be through the use of internal and outside referrals to the University of California, Irvine Medical Center (UCIMC).

Achelios to Announce Results of Phase IIa Drug Trial of NSAID for Topical Treatment of Migraines

In an April 18, 2015 press release, Achelios Therapeutics (http://achelios.com/) announced that it will present, on April 22, 2015, results from a Phase IIa placebo-controlled clinical trial in moderate and severe migraine sufferers treated with TOPOFEN™, the company's proprietary topical anti-migraine therapy. The data to be presented demonstrate that the simple application of a well-known non-steroidal anti-inflammatory drug (NSAID), using the company's proprietary formulation, on the skin, over the trigeminal nerve branches, can be a safe and effective alternative treatment for patients suffering from acute migraine. William R. Bauer, M.D., Ph.D., FAAN, a neurologist and migraine headache specialist and advisor to Achelios, said, "Migraine remains a significant global cause of disability and disruption of activities of daily living. TOPOFEN results show promise to provide a safe and effective treatment that will positively impact the disabling effects of such a condition." The results of the clinical trial will be presented at the Emerging Science session of the American Academy of Neurology annual meeting in Washington, D.C., on Wednesday, April 22, 2015. The study was conducted by scientists from Achelios and the Michigan Headache & Neurological Institute in Ann Arbor, Michigan. Wolfgang Liedtke, M.D., Ph.D., from Duke University will present the results as a member of the team that conducted the research and a paid advisor to Achelios. Dr. Liedtke, an Associate Professor of Neurology and Attending Physician in the Duke Pain Medicine clinics, said, "The results of the study are encouraging, and those of us who treat migraine think it may lead to a meaningful alternative treatment for a substantial number of migraineurs.

Inflammation Plays Causal Role in Serious Nervous System Involvement Seen in 15% of Lyme Disease Patients; Anti-Inflammatory Steroid Dexamethasone Largely Effective Against Many of These NS Complications

About 15% of patients with Lyme disease develop peripheral and central nervous system involvement, often accompanied by debilitating and painful symptoms. New research indicates that inflammation plays a causal role in the array of neurologic changes associated with Lyme disease, according to a study published online on April 16, 2015 in The American Journal of Pathology. The investigators at the Tulane National Primate Research Center and Louisiana State University Health Sciences Center also showed that the anti-inflammatory drug dexamethasone prevents many of these reactions. "These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis," explained Mario T. Philipp, Ph.D., Professor of Microbiology and Immunology and Chair of the Division of Bacteriology and Parasitology at Tulane National Primate Research Center (Covington, Louisiana). Lyme disease in humans results from the bite of a tick infected with the spirochete Borrelia burgdorferi (Bb). As Bb disseminates throughout the body, it can cause arthritis, carditis, and neurologic deficits. When the nervous system is involved, it is called Lyme neuroborreliosis (LNB). Clinical symptoms of LNB of the peripheral nervous system may include facial nerve palsy, neurogenic pain radiating along the back into the legs and feet, limb pain, sensory loss, or muscle weakness. Central nervous system involvement can manifest as headache, fatigue, memory loss, learning disability, depression, meningitis, and encephalopathy. To understand further the neuropathologic effects of Bb infection, researchers infected 12 rhesus macaques with live B. burgdorferi; two animals were left uninfected as controls.

Unique Combination of Single Molecule Fluorescence Microscopy and Optical Trapping Reveals Structure & Function of Certain DNA Repair Proteins

By combining two highly innovative experimental techniques, scientists at the University of Illinois at Urbana-Champaign have, for the first time, simultaneously observed the structure and the correlated function of specific proteins critical in the repair of DNA, providing definitive answers to some highly debated questions, and opening up new avenues of inquiry and exciting new possibilities for biological engineering. Scientists who study biological systems at the molecular level have over the years looked to the structure of protein molecules--how the atoms are organized--to shed light on the diverse functions each protein performs in the cell. The inverse is also true: observing the specific work particular protein molecules perform has provided important clues as to the conformation of the respective molecules. But, until recently, our most advanced laboratory experiments could only investigate one at a time--static form or dynamic function--and from the results, deduce the other. This indirect method often doesn't provide definitive answers. Now, Illinois biological physicists Dr. Taekjip Ha and Dr. Yann Chemla have combined two cutting-edge laboratory techniques that, when used together, directly get at the structure-function relationship in proteins. Dr. Ha is well recognized for his innovative single molecule fluorescence microscopy and spectroscopy techniques. Dr. Chemla is a top expert in optical trapping techniques. Their combined method--simultaneous fluorescence microscopy and optical trapping--yields far more definitive answers to questions relating structure to function than either technique could independently. Working in collaboration, Dr. Ha and Dr. Chemla each applied the above techniques in their laboratories, with conclusive results.

April 17th

Mutual Gaze Between Dogs & Humans Drives Neural Feedback Loop Based on Oxytocin, Same Hormone That Strengthens Human Mother-Child Bonding Through Mutual Gaze

A new study suggests that dogs and humans may have tapped into an instinctual bonding mechanism that originally evolved to reinforce the strongest biological bonds -- those between parent and offspring. In work reported in an open-access article published in the April 17, 2015 issue of Science, Dr. Miho Nagasawa from both Azabu University (Kanagawa, Japan) and Jichi Medical University (Tochigi, Japan) and colleagues from those institutions, as well as from the University of Tokyo, demonstrated that the hormone oxytocin, which spikes in both human and canine brains when the species interact, operates in a neural feedback loop that likely strengthened the bonds between man and his “best friend” for millennia. The researchers show that mutual gaze between the two -- an oxytocin-driven bonding mechanism known to strengthen emotional ties between human mothers and their infants -- helps to regulate the bonds between dogs and their owners as well. Because wolves don’t have this same response, even when they’ve been raised by humans, Dr. Nagasawa and colleagues suggest that this particular social bonding mechanism co-evolved in both dogs and humans over the course of the animals’ domestication. The researchers put dogs into a room with their owners, documenting every interaction between the two species, such as talking, touching, and gazing, for 30 minutes. They then measured oxytocin levels in the dogs’ and owners’ urine and discovered that increased eye contact between dogs and their owners had driven up levels of oxytocin in the brains of both species. In a second experiment, the researchers sprayed oxytocin directly into the noses of certain dogs and placed them in a room with their owners and some strangers. Female dogs responded to the treatment by increasing the amount of time they gazed at their owners.

Microbiome of Remote Amazonian Indians 40 Percent More Diverse Than That of Those in Industrialized Countries

A multicenter team of U.S. and Venezuelan scientists, led by researchers from the New York University (NYU) Langone Medical Center, has discovered the most diverse collection of bodily bacteria yet in humans among an isolated tribe of Yanomami Indians in the remote Amazonian jungles of southern Venezuela. By comparison, the microbiome of people living in industrialized countries is about 40 percent less diverse, the scientists estimate. The team reports its findings online on April 17, 2015 in an open-access article in Science Advances. The results, the researchers say, suggest a link between modern antibiotics and industrialized diets, and greatly reduced diversity of the human microbiome--the trillions of bacteria that live in and on the body and are increasingly seen as vital to our health. The Yanomami villagers of this study, who have subsisted by hunting and gathering for hundreds of generations, are believed to have lived in total seclusion from the outside world until 2009 when they were first contacted by a medical expedition. Among a rare population of people unexposed to modern antibiotics, the villagers offer a unique window onto the human microbiome. "We have found unprecedented diversity in fecal, skin, and oral samples collected from the Yanomami villagers," says Maria Dominguez-Bello, Ph.D., Associate Professor of Medicine at NYU Langone Medical Center and the senior author of the study. "Our results bolster a growing body of data suggesting a link between, on the one hand, decreased bacterial diversity, industrialized diets, and modern antibiotics, and on the other, immunological and metabolic diseases--such as obesity, asthma, allergies, and diabetes, which have dramatically increased since the 1970s," notes Dr. Dominguez-Bello.