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April 10th, 2018

Double-Drug Strategy Blocks Escape Route for Most Lung Cancers—"Finding Has Possibility of Dramatically Altering How We Treat Lung Cancer”

A one-two combo punch using two currently available drugs could be an effective treatment for the majority of lung cancers, a study by scientists with the University of Texas (UT) Southwestern’s Simmons Cancer Center shows. Researchers found that a combination of drugs – one targeting epidermal growth factor receptor (EGFR) and one targeting tumor necrosis factor (TNF) – effectively blocks the cancer from using TNF as an escape route. Using a mouse model, the researchers showed that when TNF is also blocked, the cancer becomes sensitive to EGFR treatment. “There has been a tremendous effort over the past several years to block EGFR as a treatment for lung cancer, but this therapy only works in a small subset of patients. The cancer fights back with a bypass pathway,” said senior author Dr. Amyn Habib (photo) with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern and a staff physician at the Dallas Veterans Affairs Medical Center. “Blocking both of these proteins could be a treatment that is beneficial for the majority of lung cancer patients,” said Dr. Habib, Associate Professor of Neurology and Neurotherapeutics with UT Southwestern’s Peter O’Donnell Jr. Brain Institute. Lung cancer is the most common cause of cancer deaths in the U.S. for both men and women, according to the National Cancer Institute and, in 2017, lung cancer caused 26 percent of all cancer deaths. Non-small cell lung cancer (NSCLC), the type of lung cancer for which the EGFR/TNF inhibitor combination would be effective, comprises approximately 85 percent of all lung cancers. The latest findings build on previous work by Dr. Habib’s lab showing that the same combination of drugs was successful in a mouse model of glioblastoma, a deadly type of brain cancer.

World First--Drug to Treat Skin Lesions in Tuberous Sclerosis Complex Approved

Scientists at Osaka University in Japan have developed a new drug treating skin lesions in tuberous sclerosis complex (TSC), a rare intractable disease, a world first. Following the physician-led clinical studies I and II by Osaka University, and Phase III clinical trials by a pharmaceutical company, the drug was approved within 6 months of the drug application by the SAKIGAKE Designation System, an early approval system led by the Japanese government, on March 23, 2018 and was then commercialized. This drug is the first drug designated by the SAKIGAKE system. The details of physician-led clinical studies I and II were published in JAMA Dermatology on January 1, 2017. The open-access article is titled: “Efficacy and Safety of Topical Sirolimus Therapy for Facial Angiofibromas in the Tuberous Sclerosis Complex A Randomized Clinical Trial.” TSC is an inherited autosomal dominant disease caused by mutations in TSC1 (hamartin) and TSC2 (tuberin) genes. Mutations in the TSC1 and TSC2 tumor suppressor genes cause hyperactivation of the mTORC1 (mammalian target of rapamycin complex 1), developing neoplastic lesions called hamartomas in numerous organs, such as the brain, skin, kidneys, and lungs. The symptoms of TSC include epilepsy, learning disabilities, developmental delays, and autism spectrum disorder in addition to hamartoma. Of the various symptoms, skin problems, such as facial angiofibromas, develop in more than 90 percent of patients with TSC. Hemorrhage, secondary bacterial infection, pain, and functional disorder associated with lesions inflict suffering on patients, severely compromising their quality of life for cosmetic reasons.

April 1st

Link Between Eating Red Meat & Distal Colon Cancer Seen inn UK Women

A new study suggests that a diet free from red meat significantly reduces the risk of a type of colon cancer in women living in the United Kingdom. University of Leeds researchers were part of an international team that assessed whether red meat, poultry, fish, or vegetarian diets are associated with risk of colon and rectal cancer. When comparing the effects of these diets to cancer development in specific subsites of the colon, they found that those regularly eating red meat compared to a red meat-free diet had higher rates of distal colon cancer -- cancer found on the descending section of the colon, where feces are stored. Lead author Dr. Diego Rada Fernandez de Jauregui is part of the Nutritional Epidemiology Group (NEG) at Leeds, and the University of the Basque Country in Spain. He said: "The impact of different types of red meat and dietary patterns on cancer locations is one of the biggest challenges in the study of diet and colorectal cancer. Our research is one of the few studies looking at this relationship and while further analysis in a larger study is needed, it could provide valuable information for those with family history of colorectal cancer and those working on prevention." More than 2.2 million new cases of colorectal cancer, also known as bowel cancer, are expected worldwide by 2030. It is the third most commonly diagnosed cancer in UK women. Previous studies have suggested that eating lots of red and processed meat increases the risk of colorectal cancer and it is estimated that around 1 in 5 bowel cancers in the UK are linked to eating these meats. However, there is limited available information about specific dietary patterns and the site of cancer occurrence in the bowel.

Cat-Like “Hearing” Achieved with Device Tens of Trillions Times Smaller Than Human Eardrum

Case Western Reserve University researchers have achieved cat-like “hearing” with a device 10,000,000,000,000 times smaller than human eardrum. The researchers are developing atomically thin "drumheads" able to receive and transmit signals across a radio frequency range far greater than what we can hear with the human ear. But the drumhead is tens of trillions times smaller in volume and 100,000 times thinner than the human eardrum. The advances will likely contribute to making the next generation of ultralow-power communications and sensory devices smaller and with greater detection and tuning ranges. "Sensing and communication are key to a connected world," said Philip Feng, PhD, an Associate Professor of Electrical Engineering and Computer Science and corresponding author on a paper about the work published in the March 30, 2018 issue of Science Advances. The article is titled “Electrically Tunable Single- and Few-Layer Mos2 Nanoelectromechanical Systems With Broad Dynamic Range.” "In recent decades, we have been connected with highly miniaturized devices and systems, and we have been pursuing ever-shrinking sizes for those devices." The challenge with miniaturization: Also achieving a broader dynamic range of detection, for small signals, such as sound, vibration, and radio waves. "In the end, we need transducers that can handle signals without losing or compromising information at both the 'signal ceiling' (the highest level of an undistorted signal) and the 'noise floor' (the lowest detectable level)," Dr. Feng said. While this work was not geared toward specific devices currently on the market, researchers said, it was focused on measurements, limits, and scaling which would be important for essentially all transducers. Those transducers may be developed over the next decade, but for now, Dr.

March 31st

Researchers Find New “Organ” Missed by Gold Standard Methods for Visualizing Anatomy & Disease; Newfound Network Is Source of Lymph; Stunning “Finding Has Potential to Drive Dramatic Advances In Medicine”

Researchers have identified a previously unknown feature of human anatomy with implications for the function of all organs, most tissues, and the mechanisms of most major diseases. Published online on March 27, 2018 in Scientific Reports, a new study co-led by an New York University (NYU) School of Medicine pathologist reveals that layers of the body long thought to be dense, connective tissues—below the skin’s surface, lining the digestive tract, lungs, and urinary systems, and surrounding arteries, veins, and the fascia between muscles—are instead interconnected, fluid-filled compartments. This series of spaces, supported by a meshwork of strong (collagen) and flexible (elastin) connective tissue proteins, may act like shock absorbers that keep tissues from tearing as organs, muscles, and vessels squeeze, pump, and pulse as part of daily function. Tbe open-access article is titled “Structure and Distribution of an Unrecognized Interstitium in Human Tissues.” Importantly, the finding that this layer is a highway of moving fluid may explain why cancer that invades it becomes much more likely to spread. Draining into the lymphatic system, the newfound network is the source of lymph, the fluid vital to the functioning of immune cells that generate inflammation. Furthermore, the cells that reside in the space, and collagen bundles they line, change with age, and may contribute to the wrinkling of skin, the stiffening of limbs, and the progression of fibrotic, sclerotic, and inflammatory diseases.The field has long known that more than half the fluid in the body resides within cells, and about a seventh inside the heart, blood vessels, lymph nodes, and lymph vessels. The remaining fluid is “interstitial,” and the current study is the first to define the interstitium as an organ in its own right, and as one of the largest of the body, say the authors.

"Butterflies of the Soul"--New Study Sheds Light on Developmental Origins of Interneurons

Modern neuroscience, for all its complexity, can trace its roots directly to a series of pen-and-paper sketches rendered by Nobel laureate Santiago Ramón y Cajal in the late 19th and early 20th centuries. His observations and drawings exposed the previously hidden composition of the brain, revealing neuronal cell bodies and delicate projections that connect individual neurons together into intricate networks. As he explored the nervous systems of various organisms under his microscope, a natural question arose: What makes a human brain different from the brain of any other species? At least part of the answer, Ramón y Cajal hypothesized, lay in a specific class of neuron--one found in a dazzling variety of shapes and patterns of connectivity, and present in higher proportions in the human brain than in the brains of other species. He dubbed them the "butterflies of the soul." Known as interneurons, these cells play critical roles in transmitting information between sensory and motor neurons, and, when defective, have been linked to diseases such as schizophrenia, autism, and intellectual disability. Despite more than a century of study, however, it remains unclear why interneurons are so diverse and what specific functions the different subtypes carry out. Now, in a study published in the March 22, 2018 issue of Nature, researchers from Harvard Medical School (HMS), the New York Genome Center, New York University, and the Broad Institute of MIT and Harvard have detailed for the first time how interneurons emerge and diversify in the brain.

March 29th

Pediatric Cancer Drug Shows 93 Percent Response Rate--“Nearly Universal Response Rate Seen with Larotrectinib Is Unprecedented,” Oncologist Says

A first-of-its-kind drug targeting a fused gene found in many types of cancer was effective in 93 percent of pediatric patients tested, researchers at the University of Texas (UT) Southwestern’s Simmons Cancer Center announced. Most cancer drugs are targeted to specific organs or locations in the body. Larotrectinib is the first cancer drug to receive FDA breakthrough therapy designation for patients with a specific fusion of two genes in the cancer cell, no matter what cancer type. The research was published online on March 29, 2018 in The Lancet Oncology. The article is titled “An Active Drug for TRK-Positive Paediatric Solid Tumours.” “In some cancers, a part of the TRK gene has become attached to another gene, which is called a fusion. When this occurs, it leads to the TRK gene being turned on when it’s not supposed to be and that causes the cells to grow uncontrollably. What’s unique about the drug is it is very selective; it only blocks TRK receptors,” said lead author Dr. Ted Laetsch, Assistant Professor of Pediatrics and with the Harold C. Simmons Comprehensive Cancer Center. Larotrectinib targets TRK fusions, which can occur in many types of cancer. While the TRK fusions occur in only a small percentage of common adult cancers, they occur frequently in some rare pediatric cancers, such as infantile fibrosarcoma, cellular congenital mesoblastic nephroma, and papillary thyroid cancer, said Dr. Laetsch, who leads the Experimental Therapeutics Program (ETP) in the Pauline Allen Gill Center for Cancer and Blood Disorders at Children’s Health in Dallas.

March 28th

Cockroach Genome Sequence Analysis Reveals Why These Insects Are Virtually Indestructible

They can regrow lost legs. They make their own antibiotics. And they have an almost supernatural sense of smell. Now, Chinese researchers have sequenced the genome of the American cockroach and discovered these abilities are all in the DNA. They report on this in an article published online on March 20, 2018 in Nature Communications. The open-access article is titled “The Genomic and Functional Landscapes of Developmental Plasticity In The American Cockroach.” The American cockroach, known scientifically as Periplanta Americana, has an enormous genome, Dr. Shuai Zhan and colleagues at the Chinese Academy of Sciences in Shanghai, found. And it’s more closely related to termites than it is to German cockroaches, despite their shared unsanitary habits and ability to horrify homeowners and terrorize tenants. Cockroaches spread germs and can aggravate asthma and allergies. "The harm of American cockroaches is becoming more serious with the threat of global warming," Dr. Zhan's team wrote. “Our study may shed light on both controlling and making use of this insect.” And the DNA explains why they are so prolific. When under stress, females can lay unfertilized eggs that will hatch in a process called parthenogenesis or “virgin” reproduction. The team found genes that explain how this can happen. Cockroaches can also survive terrible injuries. "The American cockroach has a strong capability of limb regeneration during the nymph stages, which is the main reason to call it ‘Xiao Qiang’ in China,” the researchers wrote. The name translates as “little mighty one," and the team found genetic pathways that underlie the process. DNA can also explain cockroaches’ noxious habits.

March 27th

Chinese Scientists Find Key Transcription Factor (Oct-4) Activating Genome Expression in Human Embryos; Ancient Genes Are Expressed First; Transposons Very Active in Early Embryos

Chinese scientists have identified the crucial factor that activates gene expression in human embryos, bringing them one step closer to explaining the mystery of human development at a very early embryonic stage, according to a paper published in the March 22, 2018 issue of Cell. The article is titled “Chromatin Accessibility Landscape in Human Early Embryos and Its Association with Evolution.” Human life begins from a fertilized egg. However, in the first two days after fertilization, almost no genes are expressed in human embryos. Previously scientists did not know how genomes become active and start gene expression in early embryos. "What activates gene expression? The puzzle has been troubling scientists around the world for a long time. We were the first to find it," said Dr. Liu Jiang, senior author of the paper. During human growth, different genes must be expressed at the right time and right place. The genetic code stored in DNA is "interpreted" by gene expression, which gives rise to all the particular features of an individual. A team from Beijing Institute of Genomics, Chinese Academy of Sciences (CAS), led by Dr. Liu, together with a group from the Center for Reproductive Medicine, Shandong University, under Dr. Chen Zijiang, and a group from Guangzhou Medical University under Dr. Liu Jianqiao, found that Oct-4, a transcriptional factor, plays a crucial role in activating zygotic genome expression. In the first two days, a human zygote will grow into eight cells after three cell divisions. Once the embryo has eight cells, it will generate a sufficient amount of Oct-4, which will directly bind with DNA and switch on the gene expression, Dr. Liu said. The research also found that genome activation follows a particular sequence.

March 26th

Girl (8 Years Old) Speaks for First Time in Four Years Thanks to Cutting-Edge Genomic Research; Case Highlights Enormous Potential in Genomics for Precision Medical Diagnostics & Treatments: Analysis Reveals Novel Treatment at Critical Moment

On March 27, 2018, Irish life sciences company Genomics Medicine Ireland (GMI) announced that pioneering genetic analysis has led to the successful diagnosis and treatment of a young girl with progressive dystonia, a very rare disease in children. The condition causes painful seizing of the muscles, which in the case of the patient, Mary-Ann Cleary, progressed so severely that she was unable to move or speak, eventually resulting in her being admitted to the Intensive Care Unit. GMI, in conjunction with the University College Dublin Academic Centre on Rare Diseases (ACoRD), worked with Professor Mary King, Consultant Paediatric Neurologist, and Research Fellow Dr. Eva Forman at Temple Street Children’s Hospital, and, following genomic sequencing, they identified a mutation in gene KMT2B, a histone demethylase gene. This was shown to respond to a treatment called deep brain stimulation (DBS), a procedure not traditionally performed on young children. In September 2017, Mary-Ann underwent DBS, and in November she spoke for the first time in four years. Her first word was “Mama.” This case highlights the enormous potential in genomics for precision medical diagnostics and treatments. Doctors in the UK, where the family now lives, were unable to identify a successful treatment for the patient over the course of her condition, despite a battery of tests over a number of years, which all eventually proved inconclusive. The genomic analysis of the patient’s blood sample by GMI, however, took only weeks to process, a fraction of the time and cost relative to what was undertaken previously.